Reliable e-nose for air toxicity monitoring by filter diagonalization method

This paper introduces a compact, affordable electronic nose (e-nose) device devoted to detect the presence of toxic compounds that could affect human health, such as carbon monoxide, combustible gas, hydrogen, methane, and smoke, among others. Such artificial olfaction device consists of an array of six metal oxide semiconductor (MOS) sensors and a computer-based information system for signal acquisition, processing, and visualization. This study further proposes the use of the filter diagonalization method (FDM) to extract the spectral contents of the signals obtained from the sensors. Preliminary results show that the prototype is functional and that the FDM approach is suitable for a later classification stage. Example deployment scenarios of the proposed e-nose include indoor facilities (buildings and warehouses), compromised air quality places (mines and sanitary landfills), public transportation, mobile robots, and wireless sensor networks.

Toxicity, Monitoring, and Biodegradation of Cypermethrin Insecticide: A Review

Cypermethrin insecticide is widely used to prevent and control pest and crop diseases though, its residues have caused significant damage to the environment and living organisms. Microbial remediation becomes a popular approach to counter the toxicity of cypermethrin in both aquatic as well as terrestrial life. Cypermethrin can be effectively degraded to nontoxic compounds by bacterial and fungal strains. Various bacterial and fungal strains such as Ochrobactrum lupini DG-S-01, Bacillus sp. strain SG2, Azoarcus indigens strain HZ5, Streptomyces aureus strain HP-S-01, and Aspergillus oryzae M-4 are used for the cypermethrin degradation. Extensive usage of cypermethrin has caused problems such as surface water contamination, reduced fertility of the soil, detrimental effects on soil microbiota and non-targeted species. Due to environmental concerns associated with the cypermethrin in groundwater and food products, there is a crucial need to develop economical, rapid, and reliable techniques that can be used for field applications. An in-depth understanding of cypermethrin is explored in this review paper and possible solutions to mitigate its environmental toxicity are suggested.

Feasibility of a Supportive Mobile Health App for Chimeric Antigen Receptor T-Cell Therapy

BACKGROUND: The operationalization of chimeric antigen receptor (CAR-T) therapy for hematologic malignancies can be complex for patients and their caregivers. In the weeks before CAR-T therapy, patients must process large amounts of information and coordinate logistics involving caregivers, lodging, and transportation. Immediately following CAR-T therapy, patients must be monitored closely for toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). In the months following CAR-T therapy, patients may be referred back to local oncologists without a clear plan for managing potential late effects such as hypogammaglobulinemia or neuropsychiatric complications (Chakraborty 2021). Mobile health (mHealth) apps may be able to improve the patient experience during CAR-T therapy by facilitating care coordination, home-based toxicity monitoring, and patient education (Banerjee 2021). By empowering patients and caregivers to better understand CAR-T therapy and actively participate in their care, mHealth tools may ultimately augment workflows for CAR-T clinics as well. However, the feasibility and acceptability of such supportive mHealth apps during CAR-T therapy have not been established. STUDY DESIGN: We have designed a "Companion for CAR-T" mHealth app to assist with care coordination, toxicity monitoring, and patient education during CAR-T therapy. Key components of the app are summarized in the Figure. In brief, pre-CAR-T components include educational videos and dynamic calendars to assist patients with coordinating logistics. Post-CAR-T components include app-based prompts to input body temperature daily, an electronic Immune Effector Cell-Associated Encephalopathy (eICE) screening tool for ICANS that can be administered by caregivers, and a patient-specific long-term survivorship care plan. Global app components include an 'Appointment Companion' to facilitate patient-provider discussions during appointments as well as a digital CAR-T wallet card to convey key health-related information to other healthcare providers. We plan to investigate the "Companion for CAR-T" app through a pilot study of 20 patients receiving commercially available CAR-T therapies for any hematologic malignancy at our institution. Co-primary endpoints include (1) app feasibility, defined as the percentage of patients who access all 5 core modules shown in the Figure at least once; and (2) app acceptability, defined as the percentage of patients who agree that the app was helpful during their experience with CAR-T therapy. Secondary endpoints include the incidence of fevers or eICE deficits recorded via the app. Exploratory endpoints include longitudinal trends in patient-reported outcomes such as emotional distress at each clinic visit. DISCUSSION: If feasibility and acceptability of the "Companion for CAR-T" app are demonstrated through this pilot study, we plan to launch a multicenter randomized Phase 2 study of this mHealth tool versus usual care to assess its effect on perceived stress and decisional conflict. Other important steps for our group include the translation of app content into different languages and the provision of tablet computing devices for patients who do not own smartphones. Once validated and expanded in these aforementioned ways, potential strengths of the "Companion for CAR-T" app include its ability to be personalized easily with information specific to individual CAR-T therapies, malignancies, and centers. Figure 1 Figure 1. Disclosures Banerjee: Sanofi: Consultancy; SparkCures: Consultancy; Pack Health: Research Funding. Sykes: Patient Discovery Solutions, Inc.: Current Employment. Shah: Amgen: Consultancy; Indapta Therapeutics: Consultancy; Sutro Biopharma: Research Funding; Sanofi: Consultancy; Teneobio: Research Funding; Precision Biosciences: Research Funding; Poseida: Research Funding; Karyopharm: Consultancy; Janssen: Research Funding; GSK: Consultancy; Kite: Consultancy; Nektar: Research Funding; Oncopeptides: Consultancy; CSL Behring: Consultancy; Bluebird Bio: Research Funding; BMS/Celgene: Research Funding; CareDx: Consultancy. Andreadis: Incyte: Honoraria; Roche: Current equity holder in publicly-traded company, Ended employment in the past 24 months; GenMAB: Research Funding; Merck: Research Funding; Novartis: Research Funding; Epizyme: Honoraria; Crispr Therapeutics: Research Funding; Atara: Consultancy, Honoraria; Karyopharm: Honoraria; TG Therapeutics: Honoraria; Kite: Honoraria; BMS/Celgene: Research Funding. Martin: Amgen: Research Funding; GlaxoSmithKline: Consultancy; Oncopeptides: Consultancy; Janssen: Research Funding; Sanofi: Research Funding. Shore: Patient Discovery Solutions, Inc.: Current Employment. Sodowick: Patient Discovery Solutions, Inc.: Current Employment. Wong: Amgen: Consultancy; Genentech: Research Funding; Fortis: Research Funding; Janssen: Research Funding; GloxoSmithKlein: Research Funding; Dren Biosciences: Consultancy; Caelum: Research Funding; BMS: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees.

QOLP-15. FEASIBILITY OF AN ELECTRONIC PATIENT REPORTED STEROID TOXICITY MONITORING PROGRAM IN PATIENTS WITH MALIGNANT GLIOMAS

OBJECTIVE To determine the feasibility of a longitudinal, electronic, patient-reported survey of steroid toxicity in patients with malignant glioma (MG). BACKGROUND Corticosteroids are frequently used for management of cerebral edema in MG, with side effects resulting from prolonged use or high dosage. Corticosteroid use is common and may negatively impact quality of life (QOL) and survival in MG. DESIGN/METHODS We prospectively enrolled patients with MG receiving neuro-oncologic care at the University of Rochester with or without their caregivers on an IRB-approved study. Subjects received 12 weekly electronic questionnaires through a secure health portal focused on symptoms of corticosteroid toxicities, dosing and functional status. Weekly toxicity scores were calculated based on the number of reported toxicities (0-17). Completed questionnaires were reviewed by a care team member to inform clinical management. Corticosteroid dosing adjustments were documented in the medical record. Feasibility was defined as an overall questionnaire completion rate of 70%. RESULTS 11 patient/caregiver pairs were enrolled (11 patients, including 9 with caregivers). Median patient age was 58. Patient tumors were glioblastoma (82%), anaplastic astrocytoma (9%) and anaplastic oligodendroglioma (9%). Phase of treatment was concurrent (55%), adjuvant (36%) and recurrence (9%). Median dexamethasone does at study start and conclusion were 4mg/day and 3mg/day. Median weekly toxicity score was 5/17 (range: 0-14). The most common toxicities were muscle weakness, sleep disturbance and weight gain and were reported by 82% of participants. Overall questionnaire completion rate was 81%. Ten percent of questionnaires resulted in clinically significant symptoms requiring follow-up from a provider. CONCLUSION Patients with MG experience frequent corticosteroid toxicities. Electronic corticosteroid toxicity monitoring is feasible in patients with MG and may lead to changes in management. Future studies are needed to assess utility of this tool and impact on QOL and survival.

Simultaneous Cardiac and Neurological Monitoring to Assess Chemical Exposures and Drug Toxicity in Xenopus Laevis

Simultaneous monitoring of electrocardiogram (ECG) and electroencephalogram (EEG) under chemical exposure requires innovative engineering techniques that can capture minute physiological changes in studied animal models. However, this is often administered with a bulky system that may cause signal distortions and discomfort for animals. We develop an integrated bioelectronic sensing system to provide simultaneous ECG and EEG assessment in real-time under chemical exposure for Xenopus laevis. The microelectrode array (MEA) membrane with integrated ECG and EEG sensing offers an opportunity to achieve multichannel noninvasive electrophysiological monitoring with favorable dimensions and spatial resolution. To validate the performance of our system, we assessed the ECG and EEG of Xenopus under exposure of Pentylenetetrazol (PTZ), an epilepsy-inducing drug. Effects of PTZ were detected with clear ECG and EEG alterations, including frequent ictal and interictal EEG events, 30 dB average EEG amplitude elevations, abnormal ECG morphology, and heart rate changes. Overall, our Xenopus-based real-time electrophysiology monitoring system holds high potential for many applications in drug screening and remote environmental toxicity monitoring.

Futility and toxicity monitoring without halting for interim analyses.

e13579 Background: Many trial designs with futility or toxicity monitoring require that accrual halt to wait for currently enrolled patients to complete their assessment window. However, logistics often prevent this. In these cases, the performance of those designs might be compromised. This study examines the performance of 2 popular designs when enrollment is not halted at interim. Methods: Simulations were run to examine the effect of continuous enrollment on the operating characteristics (OCs) of a Simon’s 2-stage design for futility monitoring and a design using Bayesian posterior probabilities for toxicity monitoring. Both sets of 10,000 simulations examined the OCs when accrual rate was 0.5, 1.5, 3 and 5 patients/month with an assessment window of 30, 60 and 180 days. Results: The first scenario examined the OCs of a Simon design with 12 patients in the first stage and 21 at the end of the second stage. Regardless of accrual rate, the expected number of patients (EN0) increased and probability of early termination (PET0) decreased under the null hypothesis. Rate of change increased as assessment window increased. EN0 was 16 and PET0 was 54% when halting enrollment between stages. With continuous enrollment, EN0 ranged from 16-19, 17-21, and 18-21 patients for the 30-, 90- and 180-day assessment windows. PET0 ranged from 54%-50% with a 30-day assessment window. It halved to 24% with 3 patients/month enrolled and a 90-day window. PET0 was essentially 0 with a 180-day window and an enrollment of 3 patients/month. OCs for toxicity monitoring were examined for the early stopping rule Pr(toxicity rate > 0.3 | data) > 0.85 with toxicity rate ̃ beta(1, 1) with a maximum sample size of 20 and cohort size of 5. Expected number of patients (EN) increased and probability of early termination (PET) decreased as accrual rate increased, with rate of change increasing as assessment window increased. When the true probability of toxicity was 50% and enrollment halted between cohorts, EN was 10 patients and PET was 78%. EN was 17 and PET 54% with an assessment window of 30 days and 5 patients were enrolled per month. With a 90-day assessment window and 3 patients/month enrolled, EN was 16 and PET 59%. EN was 20 and PET was 12% with a 180-day assessment window and 3 patients were enrolled per month. Similar results were noted for cohorts of size 10 and a maximum number of 40 patients. Conclusions: The performance of designs that require halting enrollment while waiting for results of an interim analysis can be compromised by continuous accrual when assessment windows are lengthy and the accrual is fast. In these circumstances, consideration should be given to designs, such as Bayesian multiple imputation for delayed outcomes (Cai et al Stat Med 2014) and TOP2 (Lin et al JNCI 2019), that do not require accrual halt to make real-time interim analysis in the presence of pending patients, which protects patients from excessive toxicity or a futile intervention.

Telomere Length and Arsenic: Improving Animal Models of Toxicity by Choosing Mice With Shorter Telomeres

Arsenic is both a chemotherapeutic drug and an environmental toxicant that affects hundreds of millions of people each year. Arsenic exposure in drinking water has been called the worst poisoning in human history. How arsenic is handled in the body is frequently studied using rodent models to investigate how arsenic both causes and treats disease. These models, used in a variety of arsenic-related testing, from tumor formation to drug toxicity monitoring, have virtually always been developed from animals with telomeres that are unnaturally long, likely because of accidental artificial selective pressures. Mice that have been bred in captivity in laboratory conditions, often for over 100 years, are the standard in creating animal models for this research. Using these mice introduces challenges to any work that can be affected by the length of telomeres and the related capacities for tissue repair and cancer resistance. However, arsenic research is particularly susceptible to the misuse of such animal models due to the multiple and various interactions between arsenic and telomeres. Researchers in the field commonly find mouse models and humans behaving very differently upon exposure to acute and chronic arsenic, including drug therapies which seem safe in mice but are toxic in humans. Here, some complexities and apparent contradictions of the arsenic carcinogenicity and toxicity research are reconciled by an explanatory model that involves telomere length explained by the evolutionary pressures in laboratory mice. A low-risk hypothesis is proposed which has the power to determine whether researchers can easily develop more powerful and accurate mouse models by simply avoiding mouse lineages that are very old and have strangely long telomeres. Swapping in newer mouse lineages for the older, long-telomere mice may vastly improve our ability to research arsenic toxicity with virtually no increase in cost or difficulty of research.

Diclofenac Toxicity Abatement in Wastewater with Solar Disinfection: A Study in the Rural Area of Brazil’s Central−West Region

Domestic wastewater has been targeted for the presence of emerging contaminants such as antibiotics, of which diclofenac is one of the most frequently detected. Many studies have focused on the removal of these emerging pollutants. However, the legislation has focused on toxicity monitoring. In search of simplified solutions for rural areas, and to guarantee the safe reuse of effluent in agriculture, this study evaluated the efficiency of a decentralized solar disinfection (SODIS) system regarding the reduction of ecotoxicity, phytotoxicity, and pathogens in domestic wastewater after adding diclofenac potassium. For this purpose, the bioindicators Artemia sp., Allium cepa L. and Lactuca sativa were used, after 1, 2, and 3 h of exposure to solar radiation. After 3 h of exposure to solar radiation, toxicity was reduced and root growth inhibition was noted, which indicates low effluent toxicity after treatment by the SODIS system. It was achieved a reduction of 3 and 2 log units in the concentration of total coliforms and Escherichia coli, respectively.