Development of ISB 1442, a CD38 and CD47 bispecific biparatopic antibody innate cell modulator for the treatment of multiple myeloma.

Antibody engineering can tailor the design and activities of therapeutic antibodies for better efficiency or other advantageous clinical properties. Here we report the development of ISB 1442, a fully human bispecific antibody designed to re-establish synthetic immunity in CD38+ hematological malignancies. ISB 1442 consists of two anti-CD38 arms targeting two distinct epitopes that preferentially drive binding to tumor cells and enable avidity-induced blocking of proximal CD47 receptors on the same cell while preventing on-target off-tumor binding on healthy cells. The Fc portion of ISB 1442 is engineered to enhance complement dependent cytotoxicity, antibody dependent cell cytotoxicity and antibody dependent cell phagocytosis. ISB 1442 thus represents a CD47-BsAb combining biparatopic targeting of a tumor associated antigen with engineered enhancement of antibody effector function to overcome potential resistance mechanisms that hamper treatment of myeloma with monospecific anti-CD38 antibodies. ISB 1442 is currently in a Phase I clinical trial in relapsed refractory multiple myeloma.

GrassGroTM simulation of pasture, animal performance and greenhouse emissions on low and high sheep productivity grazing systems: 1-year validation and 25-year analysis.

Globally, there is a focus on reducing the absolute methane (CH4) and nitrous oxide emissions, and the emissions intensity (EI, kg CO2e/kg animal product) of livestock production. Increasing the productivity of mixed pasture systems has the potential to increase food (e.g., lamb) and textile fibre (e.g., wool) production while reducing the EI of those products from grazing livestock. The objective of this study was to quantify the differences in greenhouse gas (GHG) emissions and EI between sheep on Low (i.e., low sustainable stocking rate) and High (i.e., high sustainable stocking rate) productivity grazing systems (PGSs). Therefore, a replicated breeding-ewe trial on 18 paddocks was established across 2 - years. Three flocks on Low (3 × 16 ewes/flock) and High PGSs (3 × 32 ewes/flock) rotated across three land-classes and three paddocks per PGS. In year 1, the observed on-farm pasture quantity, quality, and botanical composition, together with lamb BW (kg), and daily CH4 production (DMP, g CH4/head per day) using Open Path Fourier Transformed Infrared (OP-FTIR) spectrometers data were measured. Subsequently, two simulations using GrassGroTM were conducted: (1) a 1-year GrassGroTM simulation that used the observed on-farm data to adjust parameters: date of mating, paddock fertility, and weight of mature ewes to validate GrassGroTM predictions to achieve accuracy and precision targets; and (2) a 25-year (1986-2011) simulation to analyse the effects of Low and High PGSs on sheep production and GHG emissions across a variable climate. The 1-year validation predictions fitted well with the observed on-farm data for: pasture biomass (kg/ha), DM digestibility (%), botanical composition (kg/ha), lamb (kg) product, and DMP (g CH4/head per day). The subsequent predicted results from the 25-year GrassGroTM simulation showed minimal effect of PGS on the mean DM intake (kg DM/day) or DMP for Low and High PGSs, but this was thought to be due to the biomass in both PGSs exceeding 1 500 kg DM/ha. The EI, over the 25-year simulation, on the High PGS was 16.5% lower than the Low PGS. Additional calculations of DMP were conducted using a recent global equation, giving estimates of DMP that closely matched the observed on-farm OP-FTIR DMP measurements, but these were lower than the GrassGroTM predictions and improved the accuracy and precision. It is concluded that in some pasture situations, managing pastures and stock numbers to intensify grazing systems can allow increased livestock production, without increasing daily CH4 emissions/head while substantially decreasing the EI of the animal products generated.

Benchmarking non-attendance patterns in paediatric medical imaging: A retrospective cohort study spotlighting First Nations children.

INTRODUCTION: Non-attendance at Medical Imaging (MI) appointments can result in inefficiencies in healthcare resource allocation, increased financial burdens, and lead to potential barriers to effective healthcare delivery. We evaluated factors associated with non-attendance of MI appointments for children including variables: gender; age groups; residential postcodes; Indigenous status; appointment dates; appointment reminders and socio-economic status. METHOD: Retrospective cohort study of children with scheduled MI appointments at a Tertiary paediatric hospital in Australia, between January and December 2022. Data were extracted from the Radiology Information System and integrated with socio-economic census data through linking with postcode. Chi-squared, and logistic regression analysis were performed to identify significant predictors of non-attendance. RESULTS: Out of 17,962 scheduled outpatient appointments, 6.2 % did not attend. Males were less likely to attend than females (7.3 % vs. 5.8 %; p < 0.001). Older children had the highest frequency of non-attendance (p < 0.001). First Nations identified children had a higher likelihood of non-attendance at 14.5 % compared to non-First Nations at 5.8 %, and the odds ratio (OR) of First Nation children not attending was 2.54 (CI 2.13-3.03; p < 0.001) higher than non-First Nations children. Children from areas of disadvantage were less likely to attend (p < 0.001). Bone mineral densitometry had the highest odds of non-attendance (19.4 % of bookings) compared to other imaging modalities (p < 0.001). CONCLUSION: The following characteristics were associated with non-attendance: older male gender, residing in areas of socio-economic disadvantage, or identifying as First Nations Australians. By reviewing these findings with the cultural and professional experience of our Indigenous co-author, we have identified some strategies for improving attendance amongst First Nations children. IMPLICATIONS FOR PRACTICE: Factors associated with non-attendance, or "missed opportunities for care", provide opportunities for intervention to improve attendance for vulnerable groups of children who require medical imaging.

Common Peroneal Nerve Compression Neuropathy Due to a Large Synovial Cyst From the Proximal Tibiofibular Joint in a Teenager.

Ganglion cysts are very rare in the lower limb and when present, ganglion cysts rarely cause compression neuropathy at any site. Peripheral nerve sheath tumors as a whole, are also very rare and mostly presented as a painful lump along the nerve path. Ganglion cysts are non-neoplastic gelatinous cysts, which lack true synovial lining. They can be divided into intraneural cysts which can be found within the epineurium of a peripheral nerve and lead to signs and symptoms of peripheral neuropathy or extraneural cysts which can develop from surrounding joints or tendon sheaths causing gradual nerve compression. Intraneural tumors of common peroneal nerve (CPN) are widely reported in the literature with varying degrees of symptoms; however, there are only a few case reports describing CPN palsy due to extraneural cysts. We are reporting a rare case of atraumatic CPN palsy, which resulted in irreversible foot drop in a teenage boy who presented with right leg radiating calf and foot pain. We recommend prompt investigation and excision of the cyst to decompress the nerve to increase the chances of early recovery and favorable outcomes.

First MTP joint injuries: MR imaging findings in surgically managed patients.

OBJECTIVES: Determine whether MR imaging findings or demographics predict surgical management in patients with first MTP joint injuries. MATERIALS AND METHODS: Retrospective study of 161 forefoot MRs for traumatic first MTP injury (M:F 92:69, mean age 33 ± 13 yrs.). Two radiologists reviewed imaging for ligamentous, osseous, and tendinous injuries. Ligaments and tendons were graded as 0:normal, 1:sprain or strain, 2:partial tear, 3:complete tear. Osseous injuries were classified as edema, fracture, or cartilage injury. Clinical data obtained included sex, age, injury acuity, sport participation, level of sport, and treatment. Imaging findings and demographic data were assessed to determine predictive factors for surgical management. Statistics included kappa, chi-squared, Fisher's exact, and logistic regression. RESULTS: Logistic regression (odds ratio [95% CI], p-value) showed that grade 2 or 3 injuries of the plantar ligamentous complex (2.87, [1.10, 7.48], p = 0.031), grade 2 or 3 injuries of the medial collateral ligament (3.24, [1.16, 9.08], p = 0.025), and participation in collegiate or professional sports (4.34 [1.64, 11.52], p = 0.003) were associated with an increased rate of surgical intervention. k = ligamentous injury (0.71-0.83), osseous trauma (0.88-0.95), and tendon injury (0.78). All other imaging findings and demographic factors were not significant predictors of surgery (p > 0.05). CONCLUSION: Participation in collegiate or professional sports and tears of the plantar ligamentous complex or medial collateral ligament predicted surgical management in patients with first MTP trauma.

A systematic review of breast milk microbiota composition and the evidence for transfer to and colonisation of the infant gut.

The intestinal microbiota plays a major role in infant health and development. However, the role of the breastmilk microbiota in infant gut colonisation remains unclear. A systematic review was performed to evaluate the composition of the breastmilk microbiota and evidence for transfer to/colonisation of the infant gut. Searches were performed using PUBMED, OVID, LILACS and PROQUEST from inception until 18th March 2020 with a PUBMED update to December 2021. 88 full texts were evaluated before final critique based on study power, sample contamination avoidance, storage, purification process, DNA extraction/analysis, and consideration of maternal health and other potential confounders. Risk of skin contamination was reduced mainly by breast cleaning and rejecting the first milk drops. Sample storage, DNA extraction and bioinformatics varied. Several studies stored samples under conditions that may selectively impact bacterial DNA preservation, others used preculture reducing reliability. Only 15 studies, with acceptable sample size, handling, extraction, and bacterial analysis, considered transfer of bacteria to the infant. Three reported bacterial transfer from infant to breastmilk. Despite consistent evidence for the breastmilk microbiota, and recent studies using improved methods to investigate factors affecting its composition, few studies adequately considered transfer to the infant gut providing very little evidence for effective impact on gut colonisation.

Monobody adapter for functional antibody display on nanoparticles for adaptable targeted delivery applications.

Vascular endothelial cells (ECs) play a central role in the pathophysiology of many diseases. The use of targeted nanoparticles (NPs) to deliver therapeutics to ECs could dramatically improve efficacy by providing elevated and sustained intracellular drug levels. However, achieving sufficient levels of NP targeting in human settings remains elusive. Here, we overcome this barrier by engineering a monobody adapter that presents antibodies on the NP surface in a manner that fully preserves their antigen-binding function. This system improves targeting efficacy in cultured ECs under flow by >1000-fold over conventional antibody immobilization using amine coupling and enables robust delivery of NPs to the ECs of human kidneys undergoing ex vivo perfusion, a clinical setting used for organ transplant. Our monobody adapter also enables a simple plug-and-play capacity that facilitates the evaluation of a diverse array of targeted NPs. This technology has the potential to simplify and possibly accelerate both the development and clinical translation of EC-targeted nanomedicines.

The Emirates Mars Mission.

The Emirates Mars Mission (EMM) was launched to Mars in the summer of 2020, and is the first interplanetary spacecraft mission undertaken by the United Arab Emirates (UAE). The mission has multiple programmatic and scientific objectives, including the return of scientifically useful information about Mars. Three science instruments on the mission's Hope Probe will make global remote sensing measurements of the Martian atmosphere from a large low-inclination orbit that will advance our understanding of atmospheric variability on daily and seasonal timescales, as well as vertical atmospheric transport and escape. The mission was conceived and developed rapidly starting in 2014, and had aggressive schedule and cost constraints that drove the design and implementation of a new spacecraft bus. A team of Emirati and American engineers worked across two continents to complete a fully functional and tested spacecraft and bring it to the launchpad in the middle of a global pandemic. EMM is being operated from the UAE and the United States (U.S.), and will make its data freely available.

Sampling implications of variation in daily activity of the sheep tick, Ixodes ricinus at a coastal grassland site in the U.K.

The sheep tick, Ixodes ricinus L. (Acari: Ixodidae), is an important vector of many pathogens of medical and veterinary significance. Determining vector abundance is a requisite of assessing potential vector-borne disease risk. Estimation of tick abundance is often conducted by blanket drag sampling a site, conducted at one time point during the day. The time of day chosen for sampling can vary, is not widely standardized and is often unreported by the investigator. This study investigated whether the time of day chosen for sampling had an effect on tick collection at an open grassland coastal site in North Devon, U.K., during May 2019 to July 2019. Tick abundance for both adults and nymphs in the evening period was more than twice that found in the mid-day sampling period. Overall abundance differed with site aspect, ground temperature and relative humidity. This study shows that for this open grassland recreational site, the time of day chosen for sampling has important implications for tick collection and the assessment of the relative risk of human exposure to ticks and tick-borne infections.

Management of well appearing infants born to afebrile mothers with inadequate GBS prophylaxis: A retrospective comparison of the three approaches recommended by the COFN.

BACKGROUND: There are three different approaches set forth by the Committee on the Fetus and Newborn (COFN) for managing asymptomatic neonates born to mothers with inadequate intrapartum antibiotic prophylaxis (IAP) for early-onset Group B Strep (GBS) infection. The first approach is that of categorical risk factor assessments, and recommends that asymptomatic infants born to afebrile mothers with inadequate IAP for GBS be monitored with clinical observation for 36-48 hours. The second approach recommends serial physical examinations and vital signs for 36-48 hours to closely monitor changes in clinical condition for all patients. The Kaiser Permanente EOS risk calculator (SRC) is an example of the third approach, a multivariate risk assessment, and it takes into consideration several perinatal risk factors. This multivariate risk assessment then provides recommendations for reassessment and management based on presume risk of the infant developing or having Early Onset Sepsis (EOS). The aim of our study was to compare these three recently published recommendations from the COFN for the management of asymptomatic neonates born to afebrile mothers with inadequate IAP for GBS. STUDY DESIGN: This is a retrospective study of asymptomatic neonates with gestational age ≥35 weeks born to afebrile mothers with indicated inadequate IAP for GBS between April 2017 and July 2020. Management recommendations of the SRC were compared to the recommendations of categorical risk assessment and risk assessment based on clinical condition. RESULTS: A total of 7,396 infants were born during the study period, 394 (5.3%. to mothers with inadequate IAP. Recommendations for these infants according to both the categorical risk factor guideline and the clinical condition guideline include extended, close observation. However, the SRC recommended routine newborn care for 99.7%.f these infants. None of the infants developed EOS. CONCLUSION: The SRC recommend routine neonatal care without enhanced and prolonged observation for nearly all asymptomatic infants born to afebrile mothers with inadequate IAP. As none of the infants in this cohort had EOS, further studies in a larger cohort are needed to establish the safety of SRC in neonates born to mothers with inadequate IAP.

Quantifying Sub-Meter Surface Heterogeneity on Mars Using Off-Axis Thermal Emission Imaging System (THEMIS) Data.

Surface heterogeneities below the spatial resolution of thermal infrared (TIR) instruments result in anisothermality and can produce emissivity spectra with negative slopes toward longer wavelengths. Sloped spectra arise from an incorrect assumption of either a uniform surface temperature or a maximum emissivity during the temperature-emissivity separation of radiance data. Surface roughness and lateral mixing of different sub-pixel surface units result in distinct spectral slopes with magnitudes proportional to the degree of temperature mixing. Routine Off-nadir Targeted Observations (ROTO) of the Thermal Emission Imaging Spectrometer (THEMIS) are used here for the first time to investigate anisothermality below the spatial resolution of THEMIS. The southern flank of Apollinaris Mons and regions within the Medusae Fossae Formation are studied using THEMIS ROTO data acquired just after local sunset. We observe a range of sloped TIR emission spectra dependent on the magnitude of temperature differences within a THEMIS pixel. Spectral slopes and wavelength-dependent brightness temperature differences are forward-modeled for a series of two-component surfaces of varying thermal inertia values. Our results imply that differing relative proportions of rocky and unconsolidated surface units are observed at each ROTO viewing geometry and suggest a local rock abundance six times greater than published results that rely on nadir data. High-resolution visible images of these regions indicate a mixture of surface units from boulders to dunes, providing credence to the model.

Management of bone metastasis and cancer treatment-induced bone loss during the COVID-19 pandemic: An international perspective and recommendations.

Optimum management of patients with cancer during the COVID-19 pandemic has proved extremely challenging. Patients, clinicians and hospital authorities have had to balance the risks to patients of attending hospital, many of whom are especially vulnerable, with the risks of delaying or modifying cancer treatment. Those whose care has been significantly impacted include patients suffering from the effects of cancer on bone, where delivering the usual standard of care for bone support has often not been possible and clinicians have been forced to seek alternative options for adequate management. At a virtual meeting of the Cancer and Bone Society in July 2020, an expert group shared experiences and solutions to this challenge, following which a questionnaire was sent internationally to the symposium's participants, to explore the issues faced and solutions offered. 70 respondents, from 9 countries (majority USA, 39%, followed by UK, 19%) included 50 clinicians, spread across a diverse range of specialties (but with a high proportion, 64%, of medical oncologists) and 20 who classified themselves as non-clinical (solely lab-based). Spread of clinician specialty across tumour types was breast (65%), prostate (27%), followed by renal, myeloma and melanoma. Analysis showed that management of metastatic bone disease in all solid tumour types and myeloma, adjuvant bisphosphonate breast cancer therapy and cancer treatment induced bone loss, was substantially impacted. Respondents reported delays to routine CT scans (58%), standard bone scans (48%) and MRI scans (46%), though emergency scans were less affected. Delays in palliative radiotherapy for bone pain were reported by 31% of respondents with treatments often involving only a single dose without fractionation. Delays to, or cancellation of, prophylactic surgery for bone pain were reported by 35% of respondents. Access to treatments with intravenous bisphosphonates and subcutaneous denosumab was a major problem, mitigated by provision of drug administration at home or in a local clinic, reduced frequency of administration or switching to oral bisphosphonates taken at home. The questionnaire also revealed damaging delays or complete stopping of both clinical and laboratory research. In addition to an analysis of the questionnaire, this paper presents a rationale and recommendations for adaptation of the normal guidelines for protection of bone health during the pandemic.

Management of infants born to mothers with chorioamnionitis: A retrospective comparison of the three approaches recommended by the committee on fetus and newborn.

BACKGROUND: Based on the most recently published recommendations from the Committee on the Fetus and Newborn (COFN), three approaches currently exist for the use of risk factors to identify infants who are at increased risk of early-onset sepsis (EOS). Categorical risk factor assessments recommend laboratory testing and empiric antibiotic therapy for all infants born to mothers with a clinical diagnosis of chorioamnionitis. Risk assessments based on clinical condition recommend frequent examinations and close vital sign monitoring for infants born to mothers with chorioamnionitis. The Kaiser Permanente EOS risk calculator (SRC) is an example of the third approach, multivariate risk assessments. The aim of our study was to compare the three risk stratification approaches recommended by the COFN for management of chorioamnionitis-exposed infants. METHODS: Retrospective study of 1,521 infants born ≥35 weeks to mothers with chorioamnionitis. Management recommendations of the SRC were compared to the recommendations of categorical risk assessment and risk assessment based on clinical condition (CCA). RESULTS: Hypothetical application of SRC and CCA resulted in 79.6% and 76.8-85.1% respectively fewer infants allocated empiric antibiotic therapy. While CCA recommended enhanced observation for all chorioamnionitis-exposed infants, SRC recommended routine care without enhanced observation in 44.3% infants. For the six infants (0.39%) with EOS, SRC and CCA recommended empiric antibiotics only for three symptomatic infants. CONCLUSION: The SRC and CCA can reduce antibiotic use but potentially delay antibiotic treatment. The SRC does not recommend enhanced observation with frequent and prolonged vital signs for >44% of chorioamnionitis-exposed infants.

Cutaneous toxicities in patients with melanoma receiving checkpoint inhibitor therapy: a retrospective review. The experience of a single large specialist institution.

Checkpoint inhibitor (CPI) therapy has significantly improved overall survival for metastatic melanoma, and is now approved for use in the adjuvant setting. Modulating the immune system is recognized to cause cutaneous immune-related adverse events (irAEs). We conducted a retrospective observational cohort study of adult patients with melanoma at our tertiary referral centre, who received CPI therapy from 2006 to March 2018. This is the single largest study of cutaneous irAEs occurring on CPI therapy in patients with melanoma to date and encompasses 12 years. The results showed that cutaneous toxicity occurs in 24% of patients but is generally manageable, with < 5% patients discontinuing treatment.

Introducing bedaquiline: experiences from the Challenge TB Project.

BACKGROUND: Drug-resistant tuberculosis (DR-TB) remains a global public health crisis. In 2013, the World Health Organization recommended the introduction of bedaquiline (BDQ) for eligible DR-TB patients.METHODS: We conducted a retrospective review and analyses of project reports from 2016 to mid-2019 on the processes, activities implemented, available results on enrolment and interim treatment outcomes, across the 23 Challenge TB (CTB) supported countries.RESULTS: Initial introduction of BDQ-containing regimens in the 23 CTB-supported countries took on average 2 years, with subsequent nation-wide scale-up achieved in Ethiopia and Kyrgyzstan within a short time period. Successful implementation required critical interventions including advocacy, revision of policies and guidelines, capacity building of health care workers, and strengthening of laboratory networks. The number of countries providing BDQ increased from 9 to 23; 9398 patients were enrolled on bedaquiline containing regimens; 71% were culture-negative after 6 months of treatment; and the number of countries reporting serious adverse events increased (from 5 to 18). Major challenges included limited in-country coordination with drug regulatory agencies, unrealistic quantification and drug ordering, weak laboratory networks and reporting systems for drug safety.CONCLUSION: BDQ introduction required a systematic and programmatic approach. The initial time investment helped achieve initial introduction and scale-up of coverage, ownership and sustainability by National TB Programmes.

Remembering the past to live better in the future: A feasibility randomised controlled trial of memory specificity training for motivation in psychosis.

BACKGROUND AND OBJECTIVES: People with a diagnosis of psychosis often experience low motivation and reduced activity levels. Autobiographical memory deficits have been identified in people with psychosis and this may limit the role of memory retrieval in supporting motivation. This pilot study adapted a recently developed protocol, Memflex, which aims to enhance autobiographical memory and has shown promise in depression. Our brief intervention targets experiential negative symptoms of psychosis using supported autobiographical memory retrieval. METHOD: A sample of 31 participants with psychosis were recruited from inpatient and community settings and randomised in a 2:1 ratio to either a basic recall control or an enhanced recall intervention group. Participants were asked to generate positive autobiographical memories linked to activities they wish to repeat in the future. The enhanced recall condition received additional prompts from the Memflex protocol, and the basic recall condition received no additional support. RESULTS: The intervention delivered was acceptable (rated >80%) and feasible (94% adherence) to those who took part. Participants were able to generate positive autobiographical memories linked to their goals and experienced appropriate emotions linked to these. The controlled preliminary effect sizes (0.2-0.34) showed encouraging signals for self-efficacy, motivation and a reduction in negative mood. LIMITATIONS: As this was a pilot study with a small sample size between-group tests of statistical significance were not conducted, and therefore findings should be interpreted with caution. CONCLUSIONS: These findings suggest that guided autobiographical memory retrieval may be an effective way tool for targeting motivation in people with psychosis.

Evidence for a Diagenetic Origin of Vera Rubin Ridge, Gale Crater, Mars: Summary and Synthesis of Curiosity's Exploration Campaign.

This paper provides an overview of the Curiosity rover's exploration at Vera Rubin ridge (VRR) and summarizes the science results. VRR is a distinct geomorphic feature on lower Aeolis Mons (informally known as Mount Sharp) that was identified in orbital data based on its distinct texture, topographic expression, and association with a hematite spectral signature. Curiosity conducted extensive remote sensing observations, acquired data on dozens of contact science targets, and drilled three outcrop samples from the ridge, as well as one outcrop sample immediately below the ridge. Our observations indicate that strata composing VRR were deposited in a predominantly lacustrine setting and are part of the Murray formation. The rocks within the ridge are chemically in family with underlying Murray formation strata. Red hematite is dispersed throughout much of the VRR bedrock, and this is the source of the orbital spectral detection. Gray hematite is also present in isolated, gray-colored patches concentrated toward the upper elevations of VRR, and these gray patches also contain small, dark Fe-rich nodules. We propose that VRR formed when diagenetic event(s) preferentially hardened rocks, which were subsequently eroded into a ridge by wind. Diagenesis also led to enhanced crystallization and/or cementation that deepened the ferric-related spectral absorptions on the ridge, which helped make them readily distinguishable from orbit. Results add to existing evidence of protracted aqueous environments at Gale crater and give new insight into how diagenesis shaped Mars' rock record.

Digital health screening tool for identification of elder mistreatment.

PURPOSE: It is estimated that 15.7% of people aged 60 years and older were subjected to some form of Elder Mistreatment (EM) globally (Yon et al., 2017). In the USA, as many as 1 in 24 EM cases are left unidentified by professionals, with a 300% increased mortality risk for older adults who do not receive help (National Center on Elder Abuse, n.d.; Dong, 2009). Current methods of screening tend to miss less obvious signs of EM and may discourage older adults from disclosing EM, due to either a lack of understanding of what constitutes mistreatment or fear of retaliation from the perpetrator. METHOD: Our approach shifts the focus of EM identification to the older adults themselves through an automated tablet-based tool. The Virtual cOaching in making Informed Choices on Elder Mistreatment Self-Disclosure (VOICES) tool includes various multimedia components such as videos, audio, and animations designed to educate and enhance screening. Patients screened as positive are guided through a Brief Negotiated Interview (BNI) utilizing motivational interviewing to assist in self-identification (recognize that they are experiencing elder mistreatment) or self-disclosure (inform others about their elder mistreatment experiences). During tool development, we conducted a qualitative study to evaluate the perceived value and likelihood of adopting a tablet-based approach to facilitate screening and self-disclosure of EM in the ED. We held 3 focus groups with stakeholders, including 24 adults 60 years or over, 2 social workers, 2 caregivers, and 2 ED clinicians. We used the findings from the focus groups and User-Centered Design approach (UCD) to develop the tablet-based screening tool. Once the tool was ready, we tested its usability and acceptability with 14 older adults. RESULTS AND DISCUSSION: Focus group participants supported use of a tablet-based tool to screen for EM, indicating that digital screening benefits from feelings of privacy and anonymity. On a 7-point Likert scale ranging from "1=Very Comfortable" to "7=Very Uncomfortable", older adults scored 2.8 on average for whether they would feel comfortable using a tablet device to screen for EM. Prominent suggestions made by older adults included using a female voice for the tool narrator, larger font size, more multimedia, headphones for privacy; and having someone available during screening for assistance if needed. Participants indicated that it is difficult for older adults experiencing EM to ask for help and that any type of mistreatment screening would be helpful. They also highlighted the need to explain community resources available to older adults once EM is disclosed, especially resources offering help to the caregiver. Participants of the usability evaluation rated the tool a mean score of 86.6 (median= 88.8, iQR =18.1) on the System Usability Scale (SUS), far above the benchmark SUS score of 68, which indicates that the system is "good" or "acceptable" (Bangor et al., 2008). Shifting the focus from the provider to the older adult may encourage self-disclosure of EM by addressing major barriers to traditional screening processes. In summary, this study supported the use of self-administered automated tablet-based screening for EM. Participants generally believed that the use of digital health tools to facilitate the screening process would be beneficial in the ED setting.