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The COVID-19 pandemic has had an enormous impact on the provision of behavioral health care services across the United States. This column examines this impact within the context of New York State's supported employment initiative, which involved 89 implementation sites before the start of the pandemic. The pandemic caused changes to the training and implementation supports provided, the number of sites providing these services, and the ways in which sites provided supported employment services. Although mean self-assessed implementation fidelity decreased modestly, employment outcomes that dipped early in the pandemic rebounded quickly to prepandemic levels.

Supplementary Figures S1-S2 from Evaluation of Lapatinib and Topotecan Combination Therapy: Tissue Culture, Murine Xenograft, and Phase I Clinical Trial Data

Purpose: Topotecan resistance can result from drug efflux by P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) as well as survival signals initiated by epidermal growth factor receptor family members. The present studies were done to determine the effect of combining topotecan and the dual epidermal growth factor receptor/HER2 inhibitor lapatinib in tissue culture, a murine xenograft model, and a phase I clinical trial.Experimental Design: The effects of lapatinib on topotecan accumulation and cytotoxicity in vitro were examined in paired cell lines lacking or expressing Pgp or BCRP. Antiproliferative effects of the combination were assessed in mice bearing HER2+ BT474 breast cancer xenografts. Based on tolerability in this preclinical model, 37 patients with advanced-stage cancers received escalating doses of lapatinib and topotecan in a phase I trial.Results: Lapatinib increased topotecan accumulation in BCRP- or Pgp-expressing cells in vitro, and the combination showed enhanced efficacy in HER2+ BT474 xenografts. In the phase I study, nausea, vomiting, diarrhea, and fatigue were dose limiting. The maximum tolerated doses were 1,250 mg/d lapatinib by mouth for 21 or 28 days with 3.2 mg/m2 topotecan i.v. on days 1, 8, and 15 of 28-day cycles. Pharmacokinetic analyses showed that combined drug administration resulted in decreased topotecan clearance consistent with transporter-mediated interactions. Seventeen (46%) patients had disease stabilization.Conclusions: The lapatinib/topotecan combination is well tolerated and warrants further study.

Belantamab mafodotin (belamaf) is an antibody-drug conjugate (ADC) targeting B-cell maturation antigen (BCMA). Nonlinear mixed-effects models were developed to characterize the population pharmacokinetics (PopPK) of ADC, total monoclonal antibody (mAb), and cysteine-maleimidocaproyl-MMAF (cys-mcMMAF) after 0.03-4.6 mg/kg dosing every 3 weeks in heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM) (DREAMM-1, n=73; DREAMM-2, n=218). Sequential modeling methodology was employed. Individual post hoc parameter estimates from the final ADC model were used to develop total mAb and cys-mcMMAF models. Formal covariate selection used a modified stepwise forward inclusion method with backward elimination. A linear, two-compartment PopPK model with a time-varying clearance (CL) described ADC PK. Initial ADC typical value (TV) for CL for a DREAMM-2 patient was 0.936 L/day with a half-life of 11.5 days, over time CL was reduced by 28% resulting in a half-life of 14.3 days. Time to 50% maximal CL change was approximately 50 days. Baseline soluble BCMA (sBCMA), immunoglobulin (IgG), albumin, and bodyweight impacted ADC CL. Cys-mcMMAF concentrations were described with a linear two-compartment model linked to ADC; input rate was governed by deconjugation/intracellular proteolytic degradation of ADC represented by an exponentially decreasing MMAF:mAb (drug antibody ratio; DAR) after each dose. Time to 50% DAR reduction was 10.3 days. Baseline sBCMA and IgG impacted cys-mcMMAF central volume of distribution. In conclusion, ADC, total mAb, and cys-mcMMAF concentration-time profiles in RRMM were well described by PopPK models, and exposure was most strongly impacted by disease-related characteristics.

BackgroundParent-only interventions for childhood anxiety may be an important alternative to resource and time intensive child-focused cognitive behavioural therapy (CBT). This systematic review and meta-analysis aimed to investigate the efficacy of parent-only interventions in reducing symptoms of anxiety disorders in school-aged children.MethodsA systematic search of five databases (inception to March 2021) identified 29 eligible studies. A range of study designs were captured, including randomised controlled trials (RCTs) and case series. A narrative synthesis was conducted. Random effects meta-analyses were performed on parent- and child-reported outcomes and pre-test post-test effect sizes were calculated for uncontrolled studies.ResultsFindings indicated a significant treatment effect for parent-only interventions compared to waitlist controls. No significant differences were found when comparing parent-only interventions with other active interventions; anxiety symptoms reduced in both conditions. No significant treatment effects were found for child-rated outcomes. Calculated effect sizes for uncontrolled studies were typically large, although sample sizes were small. No clear evidence was found for a superior type, duration or format of intervention.LimitationsThe methodological quality of many studies in this review (19/29) was rated ‘weak’. Only English language papers were included.ConclusionsTo date, this is the first systematic review and meta-analysis of the efficacy of parent-only interventions for reducing symptoms of child anxiety disorders. Our results suggest that parent-only interventions may be effective in reducing child anxiety. These findings are important for clinical practice because they suggest that efficient, low intensity interventions delivered to parents may lead to positive outcomes for children.

This study examined the relationship between individual placement and support (IPS) employment specialists' time spent in the community and employment outcomes in the current digital age, featuring increased technology use and online hiring practices.The authors examined the relationship between employment outcomes and IPS employment specialists' time spent in the community at 78 sites in 2018 and 84 sites in 2019.The amount of time staff spent in the community was significantly and positively associated with better employment outcomes.These data support the continued importance of employment specialists' spending time in the community with employers and IPS recipients to achieve optimal outcomes for recipients.

GSK2838232 is a novel, potent HIV-1 maturation inhibitor for use in regimen-based combination antiretroviral therapy from a once-daily oral dose boosted with a pharmacoenhancer (ritonavir or cobicistat). This phase 1 study in healthy participants was conducted in 2 parts. Part 1 (n = 14) assessed the relative bioavailability of single doses of a 200-mg GSK2838232 tablet and capsule formulation boosted with 100 mg ritonavir in fed and fasted (tablet-only) subjects. Part 2 (n = 10) assessed the pharmacokinetics of repeated 500-mg once-daily doses of GSK2838232 without a pharmacoenhancing boosting agent. In part 1, GSK2838232 demonstrated comparable bioavailability following a single dose of 200 mg GSK2838232 as capsule and tablet formulations in combination with ritonavir (RTV) under fed conditions, with lower intrasubject variability observed for the tablet formulation. In part 2, following administration of 500 mg GSK2838232 once daily for 11 days under fed conditions, Cmax , AUC0-τ , and Cτ showed a small degree of accumulation (1.2- to 1.3-fold) of GSK2838232. The median tmax was approximately 4 hours on both day 1 and day 11 when given with food. The mean t½ was approximately 23 hours on day 11. Steady-state concentrations were achieved by day 3 with a geometric mean steady-state Cτ on day 11 of 28 ng/mL. The tablet formulation was generally well tolerated as a single 200-mg dose with RTV under fed and fasted conditions and following administration of multiple daily doses (11 days) of 500 mg unboosted.

Two sections of heat-treated (HT) and non-heat-treated (NHT) Cable-in-Conduit Conductor (CICC) of a design similar to the ITER tokomak have been imaged using very high energy X-ray tomography at the ESRF beamline ID19. The sample images were collected at four temperatures down to 77 K. These results showed a greater degree of movement, bundle distortion and touching strands in the NHT sample. The HT sample showed non-linear movements with temperature especially close to 77 K; increasing non-circularity of the superconducting fibre bundles towards the periphery of the CICC, and touching bundles throughout the CICC. The images have highlighted where future design might improve potential weakness, in particular at the outer perimeters of the conductor and the individual sub-cable, ‘petal’ wraps.

Assessing the numbers and distribution of at-risk megafauna such as the black rhino (Diceros bicornis) is key to effective conservation, yet such data are difficult to obtain. Many current monitoring technologies are invasive to the target animals and expensive. Satellite monitoring is emerging as a potential tool for very large animals (e.g., elephant) but detecting smaller species requires higher resolution imaging. Drones can deliver the required resolution and speed of monitoring, but challenges remain in delivering automated monitoring systems where internet connectivity is unreliable or absent. This study describes a model built to run on a drone to identify in situ images of megafauna. Compared with previously reported studies, this automated detection framework has a lower hardware cost and can function with a reduced internet bandwidth requirement for local network communication. It proposes the use of a Jetson Xavier NX, onboard a Parrot Anafi drone, connected to the internet throughout the flight to deliver a lightweight web-based notification system upon detection of the target species. The GPS location with the detected target species images is sent using MQ Telemetry Transport (MQTT), a lightweight messaging protocol using a publisher/subscriber architecture for IoT devices. It provides reliable message delivery when internet connection is sporadic. We used a YOLOv5l6 object detection architecture trained to identify a bounding box for one of five objects of interest in a frame of video. At an intersection over union (IoU) threshold of 0.5, our model achieved an average precision (AP) of 0.81 for black rhino (our primary target) and 0.83 for giraffe (Giraffa giraffa). The model was less successful at identifying the other smaller objects which were not our primary targets: 0.34, 0.25, and 0.42 for ostrich (Struthio camelus australis), springbok (Antidorcas marsupialis) and human respectively. We used several techniques to optimize performance and overcome the inherent challenge of small objects (animals) in the data. Although our primary focus for the development of the model was rhino, we included other species classes to emulate field conditions where many animal species are encountered, and thus reduce the false positive occurrence rate for rhino detections. To constrain model overfitting, we trained the model on a dataset with varied terrain, angle and lighting conditions and used data augmentation techniques (i.e., GANs). We used image tiling and a relatively larger (i.e., higher resolution) image input size to compensate for the difficulty faced in detecting small objects when using YOLO. In this study, we demonstrated the potential of a drone-based AI pipeline model to automate the detection of free-ranging megafauna detection in a remote setting and create alerts to a wildlife manager in a relatively poorly connected field environment.

Polystyrene matrix nanocomposites were formulated using a custom nano particle consisting of nanodiamond covalently bonded to graphene oxide. Dispersion and mechanical property results for the nano composite are compared to those results for the neat polymer as well as for a nanocomposite infused with graphene oxide only. Dynamic light scattering was performed to determine the size of particles and the results showed that the custom nanoparticle reduced agglomeration by about 50% as compared to the graphene oxide alone. Microscale Vickers hardness testing revealed that neat polymer as well as the two nanocomposite samples all have similar hardness while nanoscale atomic force microscopy revealed that the neat polymer samples have the highest stiffness on average and the custom nanoparticle composite samples have the lowest stiffness. This difference in mechanical behavior with scale is attributed to local defects at the particle/matrix interface.

Belantamab mafodotin is an antibody-drug conjugate comprising a humanized anti-B-cell maturation antigen (BCMA) monoclonal antibody conjugated to monomethyl auristatin F (MMAF) via a protease-resistant maleimidocaproyl linker. Single-agent belantamab mafodotin showed clinically meaningful activity and manageable safety in patients with heavily pretreated relapsed/refractory multiple myeloma (RRMM) in the phase I DREAMM-1 and phase II DREAMM-2 studies and is approved by the US Food and Drug Administration and European Medicines Agency for RRMM treatment. To support monotherapy dose selection, the relationship between Cycle 1 exposure (derived using a population pharmacokinetic model) and clinical response (for multiple efficacy and safety end points) was explored. In DREAMM-2, efficacy end points (probability of response (PoR) and progression-free survival (PFS)) were associated with exposure in univariate evaluation; however, once disease burden factors were included in the model (e.g., baseline soluble BCMA, s2 -microglobulin), exposure was no longer significant. Patients with higher disease burden had lower exposure. In DREAMM-1, belantamab mafodotin exposure was the only variable to correlate with PoR and PFS. Probability of corneal events (keratopathy), but not dry eye or blurred vision, was strongly associated with belantamab mafodotin exposure (DREAMM-2). Higher cys-mcMMAF maximum plasma drug concentration (Cmax ) and lower baseline platelet count were associated with increased probability of thrombocytopenia (DREAMM-1 and DREAMM -2). In general, safety end points were more strongly associated with belantamab mafodotin exposure than efficacy end points, particularly after disease factors and patient characteristics were taken into account. Overall, these findings supported the monotherapy dose recommendation of belantamab mafodotin as 2.5 mg/kg every 3 weeks in patients with RRMM who have received four or more prior therapies.

Little is known about clients' preferences for family involvement and subsequent family contact in naturalistic, community-based coordinated specialty care (CSC) settings. The study's primary goal was to characterize clients' preferences and longitudinal patterns of family contact with providers across the OnTrackNY network in New York.Clinical administrative data collected at 3-month intervals and spanning 21 OnTrackNY CSC sites were used to analyze the preferences of 761 clients at baseline (unconditional involvement, conditional involvement, or no involvement) and patterns of family contact with program staff (always, sometimes, never, or early discharge) and their correlates during the initial 12-month service period. Data from clients discharged before 12 months were included for comparison.At baseline, most clients requested some form of family involvement (unconditional, 59%; conditional, 35%; and none, 6%). Within each 3-month assessment period, rates of family contact ranged from 73% to 84%. Variables associated with both client preferences and contact patterns included baseline insurance status, housing status, race, frequency of family contact, and employment. Clients' preferences for no or conditional family involvement were associated with higher rates of early discharge (i.e., before 1 year).Structuring family involvement around clients' preferences did not appear to negatively affect family contact, and for some clients, it seemed to bolster such contact. Additional mixed-methods research is needed to deepen the understanding of the contexts and reasoning underlying both client preferences for family involvement and subsequent levels of family contact.

Background The EnSite Precision™ Cardiac Mapping System is a catheter navigation and mapping system capable of displaying the three-dimensional (3D) position of conventional and sensor enabled electrophysiology catheters, as well as displaying cardiac electrical activity as waveform traces and dynamic 3-D maps of cardiac chambers. Objective The EnSite Precision™ Observational Study was designed to quantify and characterize the use of the EnSite Precision™ Cardiac Mapping System for mapping and ablation of cardiac arrhythmias in a real-world environment and to evaluate procedural and subsequent clinical outcomes. Methods 1065 patients were enrolled at 38 centers in the U.S. and Canada between 2017–2018. Eligible subjects were adults undergoing a cardiac electrophysiology mapping and radiofrequency ablation procedures using the EnSite Precision™ System. Results Of 989 patients who completed the protocol, a geometry was created in 936 (94.7%). Most initial maps were created using Automap (n=545, 67.0%) or a combination of Automap and manually mapping (n=151, 18.6%). Median time to create an initial map was 9.0 min (IQR 5.0–15.0), with a median number of used mapping points per minute of 92.7 (IQR 30.0–192.0). During ablation, AutoMark was used in 817 (82.6%) of procedures. The most frequent metrics for lesion color were Impedance Drop or Impedance Drop Percent (45.5% combined), time (23.9%) and average force (14.2%). At Canadian sites where LSI was an option, it was used as the color metric in 87 (45.8%) of cases (10.6% overall). The EnSite System was stable throughout 79.7% (n=788 of 989) of procedures. Factors affecting stability were respiratory change (n=88 of 989, 8.9%), patient movement (n=73, 7.4%), CS Positional Reference dislodgement (n=32, 3.2%), and cardioversion (n=19, 1.9%). Conscious sedation was used in 189 (19.1%) of patients. Acute success was reached based on the pre-defined endpoints for the procedure in 97.4% (n=963) of cases. Conclusion In a real-world study analysis, the EnSite Precision™ mapping system was associated with a high prevalence of acute procedural success, low mapping times, and high system stability. Funding Acknowledgement Type of funding source: None

DREAMM-2 (NCT03525678) is an ongoing global, open-label, phase 2 study of single-agent belantamab mafodotin (belamaf; GSK2857916), a B-cell maturation antigen-targeting antibody-drug conjugate, in a frozen-liquid presentation in patients with relapsed/refractory multiple myeloma (RRMM). Alongside the main study, following identical inclusion/exclusion criteria, a separate patient cohort was enrolled to receive belamaf in a lyophilised presentation (3.4 mg/kg, every 3 weeks) until disease progression/unacceptable toxicity. Primary outcome was independent review committee-assessed overall response rate (ORR). Twenty-five patients were enrolled; 24 received ≥1 dose of belamaf. As of 31 January 2020, ORR was 52% (95% CI: 31.3–72.2); 24% of patients achieved very good partial response. Median duration of response was 9.0 months (2.8–not reached [NR]); median progression-free survival was 5.7 months (2.2–9.7); median overall survival was not reached (8.7 months–NR). Most common grade 3/4 adverse events were keratopathy (microcyst-like corneal epithelial changes, a pathological finding seen on eye examination [75%]), thrombocytopenia (21%), anaemia (17%), hypercalcaemia and hypophosphatemia (both 13%), neutropenia and blurred vision (both 8%). Pharmacokinetics supported comparability of frozen-liquid and lyophilised presentations. Single-agent belamaf in a lyophilised presentation (intended for future use) showed a deep and durable clinical response and acceptable safety profile in patients with heavily pre-treated RRMM.

Routinely censusing rhinoceros’ populations is central to their conservation and protection from illegal killing. In Namibia, both white (Ceratotherium simum) and black (Diceros bicornis) rhinoceros occur on private land, in the latter case under a custodianship program of the Namibian Ministry of Environment and Tourism (MET). Black rhinoceros custodian landowners are responsible for the protection of the rhinoceroses on their land and are required to report regularly to the MET. Monitoring imposes a financial burden on custodians yet many of the techniques used involve expensive monitoring techniques that include the need for aerial support and/or animal instrumentation. During May and June 2018, WildTrack undertook a pilot study to census black and white rhinoceros on three private custodianship properties in Namibia. We tested three footprint identification methods for obtaining estimates of rhinoceros populations in an effort to provide less costly alternative monitoring options to rhinoceros custodians. The first was a full monitoring protocol with two components: (a) tracking each individual animal and matching them to their footprints, (b) identifying those individuals from the heel lines on the prints. The second method used simple visual heel line identification ex-situ, and the third method used just an objective footprint identification technique. These methods offer different options of fieldwork labour and cost and were designed to offer monitoring options to custodians that provided information about rhinoceros movement and location, with minimal disturbance to the rhinoceros, and best matched their human and economic resources. In this study, we describe the three methods and report the results of the pilot study to compare and evaluate their utility for rhinoceros monitoring. The first method successfully matched each trail photographed to a known rhinoceros at each site. When the other two methods disagreed with the first, they did so by failing to match single trails to a known rhinoceros, thereby creating fictitious identities consisting of a single trail. This failure occurred twice in one application, but otherwise at most once. We expect this failure can be eliminated through more stringent criteria for collecting photographs of footprints. We also briefly compare the use of footprint monitoring with other commonly used monitoring techniques. On this basis, landowners hosting rhinoceros can evaluate which method best suits their needs and resources.

8018 Background: Belantamab mafodotin (belamaf; BLENREP), a B-cell maturation antigen (BCMA) targeted antibody–drug conjugate approved for adult patients with RRMM, has a multimodal mechanism that eliminates myeloma cells via direct cytotoxicity and a systemic anti-tumor immune response, which may be augmented by an immune checkpoint inhibitor. DREAMM-4 (NCT03848845) assessed safety and clinical activity of belamaf with pembrolizumab (pembro) in RRMM. Methods: This was a Phase I/II, single-arm, open-label study of adults with RRMM after ≥3 lines of therapy (LOT, including anti-CD38 monoclonal antibody, proteasome inhibitor, and immunomodulator). Part 1 established the dose of belamaf 2.5 mg/kg with pembro 200 mg, both IV Q3W up to 35 cycles, for the Part 2 expansion. Primary efficacy endpoint was investigator-assessed overall response rate (ORR, ≥partial response [PR] per IMWG criteria by investigator). Secondary endpoints included duration of response (DoR), progression-free survival (PFS), adverse events (AEs) per NCI-CTCAE v4.03, and pharmacokinetics (PK). Results: This primary analysis of all treated pts (as of Oct 18, 2021) included 34 pts (6 in Part 1 and 28 in Part 2). In both parts, median prior LOT was 5 (range 3–13); 10 pts (29%) had high-risk cytogenetics and 9 (26%) had extramedullary disease. ORR was 47%, with most responses (10/16 pts) ≥ very good PR (VGPR, Table). Median follow-up was 14.7 months (mo); median (95% CI) DoR was 8.0 (2.1–not reached) mo; median PFS was 3.4 (1.4–5.6) mo. Most pts had ≥1 AE (any grade [Gr]: 97%; Gr ≥3: 74%) and treatment-related AE (TRAE, any Gr: 97%; Gr ≥3: 65%). Most common (≥35%) AEs were keratopathy (any Gr: 76%; Gr ≥3: 38%), vision blurred (any Gr: 38%; Gr ≥3: 0%), and thrombocytopenia (any Gr: 35%; Gr ≥3: 29%). AEs led to dose delays (65%) and dose reductions (32%), but not discontinuation. Nine pts had a serious AE (SAE); 4 pts had ≥1 SAE related to study treatment. Two pts had immune-related AEs of Gr 1 (gout and autoimmune hypothyroidism). Preliminary PK and soluble BCMA data were consistent with single-agent belamaf therapy. Conclusions: Belamaf + pembro demonstrated a favorable ORR compared with single-agent belamaf in heavily pre-treated RRMM. No new TRAEs were identified; AE frequency and severity were similar to single-agent belamaf. Correlative biomarker studies are ongoing. Clinical trial information: NCT03848845. [Table: see text]

TPS8073 Background: Belantamab mafodotin (belamaf: BLENREP) is a first-in-class, monomethyl auristatin F (MMAF)-containing, B-cell maturation antigen (BCMA)-directed antibody–drug conjugate (ADC). In the DREAMM-2 study, belamaf showed deep responses with a manageable safety profile in patients with relapsed/refractory multiple myeloma (RRMM). At 13 months of follow-up, the median duration of response was 11 months and overall survival was 13.7 months at the 2.5 mg/kg Q3W dose. Corneal events are common and expected with belamaf and other MMAF-containing ADCs. In DREAMM-2, corneal events were managed with dose modifications. Clinical responses were observed even with prolonged dose holds, suggesting alternative dosing regimens may lower corneal event rates without compromising efficacy. The DREAMM-14 study (NCT05064358) will investigate if an improved benefit/risk profile of single-agent belamaf can be achieved by modifying the dose, schedule, or both, relative to the approved dosing regimen (2.5 mg/kg Q3W). Methods: This Phase II, randomized, open-label study will include adults with RRMM who had ≥3 prior lines of therapy (LOT), including an anti-CD38 monoclonal antibody, an immunomodulatory agent, and a proteasome inhibitor. Patients with corneal epithelial disease (except nonconfluent superficial punctate keratitis) or with prior exposure to BCMA-targeted therapies, or ADCs will be excluded. Patients will be randomized into Arms A–D (n=40 each) and Arm E (n=20) in parallel and stratified by the International Staging System (I vs II vs III) and prior LOT (3 vs ≥4). Belamaf will be administered as follows—Arm A: 2.5 mg/kg Q3W; Arm B: 1.9 mg/kg Q3W; Arm C: 2.5 mg/kg Q6W; Arm D: 1.9 mg/kg Q6W; Arm E: 1.9 mg/kg Q6W with ocular event-related dose modifications based on oncology staff assessment of ocular symptoms (patient-reported symptoms using the Ocular Surface Disease Index), and visual acuity (Snellen chart or equivalent) in addition to corneal findings assessed by an eye care specialist. Patients in all Arms will have response assessments, safety assessments, and ophthalmic exams performed by an eye care specialist Q3W regardless of dosing schedule. Ocular event-related dose modifications (except in Arm E) will be guided by a modified Keratopathy and Visual Acuity scale. The primary endpoint will be incidence of ocular events. Key secondary endpoints include ocular safety and tolerability, overall safety and tolerability, pharmacokinetics, and efficacy outcomes. Follow-up for progression-free survival will be Q3W until progressive disease, start of new anticancer therapy, withdrawal of consent, end of study, or death. Status: Recruitment is ongoing. Funding: GSK (Study 209628); drug linker technology licensed from Seagen Inc.; mAb produced using POTELLIGENT Technology licensed from BioWa. Clinical trial information: NCT05064358.

A growing body of literature demonstrates that high-fidelity implementation of the individual placement and support (IPS) model of supported employment increases the chances of achieving desired outcomes. This study examined the relationship between IPS fidelity, as self-reported by program sites, and employment outcomes and determined whether this relationship was maintained over time.A total of 78 outpatient programs in New York State provided data on self-reported IPS fidelity and employment outcomes. Pearson correlations were used to determine the relationship between fidelity scores and competitive employment rates. A mixed-effects model examined the relationship between repeated fidelity and employment measures over time.A significant positive relationship was found between better self-reported IPS fidelity and greater employment. The relationship between IPS fidelity and employment was sustained over time (up to one year).Higher-fidelity implementation of the IPS model, as self-assessed by program sites, was associated with higher employment rates, which were sustained over time.

Data on numbers and distribution of free-ranging giant panda are essential to the formulation of effective conservation strategies. There is still no ideal method to identify individuals and sex this species. The traditional bite-size method using bamboo fragments in their feces lacks accuracy. The modern DNA-based estimation is expensive and demands fresh samples. The lack of identifiable individual features on panda pelage and no apparent sexual dimorphism impede reliable estimation from camera trap images. Here, we propose an innovative and non-invasive technique to identify and sex this species using a footprint identification technique (FIT). It is based on a pairwise comparison of trails (unbroken series of footprints) using discriminant analysis, with a Ward's clustering method. We collected footprints from 30 captive animals to train our algorithm and used another 11 animals for model validation. The accuracy for individual identification was > 90% for individuals with more than six footprints and 89% with fewer footprints per trail. The accuracy for sex discrimination was about 84% using a single footprint and 91% using trails. This cost-effective method provides a promising future for monitoring wild panda populations and understanding their dynamics and especially useful for monitoring reintroduced animals after the detachment of GPS collars. The data collection protocol is straightforward and accessible to citizen scientists and conservation professionals alike.

Introduction: Belantamab mafodotin is a first-in-class, monomethyl auristatin F (MMAF)-containing, B-cell maturation antigen (BCMA)-directed antibody-drug conjugate (ADC) that is approved in the United States and European Union for adult patients with relapsed/refractory multiple myeloma (RRMM). In the pivotal Phase II DREAMM-2 study, single-agent belantamab mafodotin (2.5 mg/kg administered intravenously every 3 weeks [Q3W]) demonstrated an objective response rate of 32% with a manageable safety profile in triple-class refractory adult patients with RRMM (Lonial et al. Lancet Oncol. 2020). At 13 months of follow-up, responses were durable, with a median duration of response of 11 months and an overall survival of 13.7 months (Lonial et al. ASH 2020, Poster 1417). Corneal events are common and expected with belantamab mafodotin and other MMAF-containing ADCs. In DREAMM-2, keratopathy (a pathological eye exam finding) presented as superficial punctate keratopathy and/or microcyst-like epithelial changes. Ocular symptoms, such as decline in best-corrected visual acuity or patient-reported adverse events (eg, blurred vision or dry eye), were also common during treatment. Corneal events with or without symptoms were managed with dose modifications (delays and reductions), and clinically meaningful responses were observed even with prolonged treatment-free intervals; this suggests that alternative dosing regimens of belantamab mafodotin may lower rates of corneal events without compromising efficacy. The goal of the DREAMM-14 study is to investigate whether an improved overall benefit/risk profile of single-agent belantamab mafodotin can be achieved by modifying the belantamab mafodotin dose, schedule, or both relative to the approved dosing regimen (2.5 mg/kg Q3W). Methods: This Phase II, 5-arm, randomized, parallel, open-label multicenter study will include patients with RRMM who have received at least 3 prior lines of therapy including an anti-CD38 monoclonal antibody (mAb), an immunomodulatory agent, and a proteasome inhibitor. Patients aged ≥18 years with Eastern Cooperative Oncology Group Performance Status ≤2 and who provide informed consent will be eligible. Patients with corneal epithelial disease (except mild punctate keratopathy) or prior exposure to BCMA-targeted therapies or ADCs will be excluded. Patients will be randomized into Arms A to D (n=40 each) and arm E (n=20) in parallel and stratified by the International Staging System (ISS) for MM (I vs II vs III) and prior lines of therapy (3 vs ≥4). Single-agent belantamab mafodotin will be administered at doses and schedules as follows-Arm A: 2.5 mg/kg Q3W (control); Arm B: 1.9 mg/kg Q3W; Arm C: 2.5 mg/kg Q6W; Arm D: 1.9 mg/kg Q6W; Arm E: 1.9 mg/kg Q6W with dose modifications based on oncology staff assessment of ocular symptoms (patient-reported symptoms using the Ocular Surface Disease Index) and visual acuity. Participants in all arms will have Q3W response assessments and Q3W ophthalmic examinations and monitoring by qualified eye care specialists. Ocular event-related dose modifications for all arms except Arm E will be guided by the Keratopathy and Visual Acuity (KVA) scale. Participants in all arms will be treated until progressive disease, unacceptable toxicity, or death. The primary endpoint will be incidence of Grade ≥2 ocular adverse events according to the KVA scale. Key secondary endpoints include ocular safety and tolerability, pharmacokinetics, and efficacy outcomes of belantamab mafodotin in all arms. Follow-up for progression-free survival will be Q3W until progressive disease, start of new anticancer therapy, withdrawal of consent, end of study, or death. Follow-up for overall survival will be Q12W from treatment discontinuation. The duration of this study will be approximately 22 months. The study is planned to start in the first quarter of 2022. Funding: GSK (Study 209628); drug linker technology licensed from Seagen; mAb produced using POTELLIGENT Technology licensed from BioWa. Disclosures Hultcrantz: GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees, Research Funding; Curio Science LLC: Consultancy; Intellisphere LLC: Consultancy; Amgen: Research Funding; Daiichi Sankyo: Research Funding. Kleinman: Calm Water Therapeutics LLC: Current Employment; GlaxoSmithKline: Consultancy; Eyeon Therapeutics Inc.: Current holder of individual stocks in a privately-held company; ONL Therapeutics: Consultancy, Current holder of individual stocks in a privately-held company; Triphase Accelerator: Consultancy; Helixmith Co., Ltd: Consultancy; Aprea Therapeutics: Consultancy; Editas Medicine, Inc.: Consultancy; Olema Pharmaceuticals, Inc.: Consultancy. Ghataorhe: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. McKeown: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company; AstraZeneca: Current equity holder in publicly-traded company; Novartis: Current equity holder in publicly-traded company. He: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Ling: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Jewell: Alcon: Current equity holder in publicly-traded company; Novartis: Current equity holder in publicly-traded company; GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Brunner: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Byrne: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company; Adaptimmune: Current equity holder in publicly-traded company; Novartis: Current equity holder in publicly-traded company. Eliason: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Scott: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Opalinska: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company.

As parents age, well siblings are often asked to assume caregiving responsibilities for their brother or sister with mental illness. However, relatively little is known about how well siblings prioritize sibling caregiving responsibilities with other life demands. We examined well siblings’ attitudes toward self-care and caregiving for their sibling with mental illness (self- and sibling-care) using two cross-sectional samples. The first sample of well siblings (N = 242) was used to examine the psychometric properties of the self- and sibling-care measure (SSCM), designed to assess the degree to which siblings prioritize their own needs and the needs of their sibling with mental illness. A second sample (N = 103) was used to determine the relative contribution of self- and sibling-care attitudes in accounting for variation in well siblings’ reports of personal loss and stress-related personal growth. Results support the psychometric validity of the SSCM and suggest that self- and sibling-care attitudes account for greater variance in scores on perceived personal loss and stress-related growth than demographic or caregiving factors. Our findings support the need to address family care responsibilities and resource limitations through recovery-oriented mental health policies, services, and programs.

Objective:Fidelity assessments help ensure that evidence-based practices are implemented properly. Although assessments are typically conducted by independent raters, some programs have implemented self-assessments because of resource constraints. Self-assessments were compared with independent assessments of programs implementing individual placement and support supported employment.Methods:Eleven community-based outpatient programs in New York State completed both self- and independent assessments. Intraclass correlation coefficients and paired t tests were used to compare scores from self- and independent assessments.Results:For both assessment methods, mean scores for all programs were within the range of fair fidelity. Self- and independent assessment total scores were not significantly different; however, significant differences were found on some scale items in this small sample.Conclusions:Self-assessment may be valid for examining a program’s overall functioning and useful when resource constrain...

Introduction: Belamaf (GSK2857916) is a first-in-class BCMA-targeting antibody-drug conjugate (ADC) with a humanized afucosylated anti-BCMA mAb conjugated to a cytotoxic payload mafodotin (MMAF) by a protease-resistant maleimidocaproyl linker (mc). This ADC binds to BCMA and eliminates MM cells by a multimodal mechanism. It delivers MMAF to MM cells, which inhibits microtubule polymerization, resulting in apoptosis; enhances antibody-dependent cellular cytotoxicity and phagocytosis; and induces release of markers characteristic of immunogenic cell death. This analysis assessed the E-R relationships for ocular safety endpoints in the DREAMM-2 study (NCT03525678; Lonial et al. Lancet Oncol 2020). Methods: Heavily pretreated patients with RRMM were administered belamaf 2.5 or 3.4 mg/kg intravenously every 3 weeks in the pivotal Phase II study, DREAMM-2 (N=218; Lonial et al., Lancet Oncol 2020). Population pharmacokinetic (PK) models of belamaf and cys-mcMMAF were developed and used to predict individual Cycle 1 exposure measures (Ferron-Brady et al., AACR 2020; presentation CT196). Exposure-safety analyses evaluated the probability of Grade ≥2 or ≥3 corneal adverse event (CAE; based on ocular examination and graded using a study-specific keratopathy and visual acuity [KVA] scale), or ocular events including Grade ≥1 or ≥2 blurred vision or dry eye (graded with Common Terminology Criteria for Adverse Events [CTCAE] v4.03), definite worsening in best corrected visual acuity (BCVA) in the better-seeing eye, and unilateral or bilateral worsening in BCVA to 20/50 or worse (BCVA measured with Snellen scale). The time to first occurrence of these events was also evaluated. Generalized linear models were used to assess event probabilities, while Cox proportional hazard models were used to assess time to event endpoints. Baseline patient characteristics, including serum levels of free soluble BCMA (sBMCA), a marker of disease burden, and history of eye conditions (Popat et al., ASH 2020; presentation TBD), were also evaluated for association with these endpoints. Results: Higher belamaf Ctau (the predicted concentration on Day 21 at the end of the first cycle) was associated with greater probability of developing Grade ≥2 or ≥3 CAE as well as an earlier onset of these events. History of dry eye was associated with an increased probability of Grade ≥2 CAE; lower baseline sBCMA level was associated with higher probability of Grade ≥2 or ≥3 CAE. Higher belamaf Ctau was not found to be associated with probability of occurrence or timing of first occurrence of blurred vision, dry eye (Ferron-Brady et al. AACR 2020; presentation CT196), definite worsening in BCVA, and unilateral or bilateral worsening in BCVA to 20/50 or worse.Lower baseline sBCMA level was associated with higher probability of occurrence for most of these endpoints, with some showing an earlier occurrence. History of dry eye was associated with higher probability of any grade of blurred vision, while presence of keratopathy at baseline increased the probability of a Grade ≥2 blurred vision with an earlier occurrence of any grade and Grade ≥2 blurred vision. Conclusions: After accounting for patient and disease factors, higher belamaf exposure (Ctau) was associated with an increased probability of corneal AEs (KVA scale) but not with other ocular events (e.g., blurred vision, dry eye, or worsening in visual acuity) in integrated E-R safety analyses of DREAMM-2. Funding: GSK (Study 205678); drug linker technology licensed from Seattle Genetics; mAb produced using POTELLIGENT Technology licensed from BioWa. Disclosures Ferron-Brady: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Rathi:GSK: Current Employment, Current equity holder in publicly-traded company. Collins:GSK: Current Employment, Current equity holder in publicly-traded company. Struemper:GSK: Current Employment, Current equity holder in publicly-traded company. Opalinska:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Jewell:GSK: Current Employment, Current equity holder in publicly-traded company; Novartis: Current equity holder in publicly-traded company.

Context: Belamaf showed deep and durable single-agent activity in the pivotal DREAMM-2 study primary analysis ( NCT03525678 ) (1–7) in a patient population that historically has a poor prognosis (overall survival [OS] 6–9 months). Objective: To present longer-term efficacy/safety outcomes (13-month follow-up) with single-agent belamaf in DREAMM-2 in the overall patient population and patients with HR cytogenetics and RI, subgroups with poor outcomes. Methods: DREAMM-2 is an ongoing study of belamaf 2.5 mg/kg (n=97) or 3.4 mg/kg (n=99). Primary outcome: overall response rate (ORR; ≥partial response). In post-hoc analyses, HR-cytogenetics included t(4;14), t(14;16), 17p13del, or 1q21 + . RI was based on eGFR (mild: ≥60– Results: Overall population ORRs in the 2.5 mg/kg and 3.4 mg/kg groups were 32% (97.5% CI: 21.7–43.6) and 35% (97.5% CI: 24.8–47.0); 19% and 23% of patients (58% and 66% of responders) achieved very good partial response or better. Median duration of response was 11.0 (95% CI: 4.2–not reached [NR]) and 6.2 months (95% CI: 4.8–NR). Median progression-free survival was 2.8 (95% CI: 1.6–3.6) and 3.9 months (95% CI: 2.0–5.8); median estimated OS was 13.7 (95% CI: 9.9–NR) and 13.8 months (95% CI: 10.0–NR). Most common Grade ≥3 adverse events (AEs) were keratopathy (microcyst-like epithelial changes [MECs] observed on eye examination; 2.5 mg/kg: 46%; 3.4 mg/kg: 42%), thrombocytopenia (2.5 mg/kg: 22%; 3.4 mg/kg: 32%), and anemia (2.5 mg/kg: 21%; 3.4 mg/kg: 27%). AE-related permanent discontinuation occurred in 9% and 12%; discontinuation due to MECs was rare (2.5 mg/kg: 1%; 3.4 mg/kg: 3%). HR cytogenetics and RI subgroup analyses will be presented at the conference. Conclusions: Deep and durable responses to single-agent belamaf were sustained and no new safety signals identified with longer follow-up in this heavily pretreated RRMM population. Funding: GSK (205678). Drug linker technology licensed from Seattle Genetics; mAb produced using POTELLIGENT Technology licensed from BioWa. References: [1] Lonial et al. Lancet Oncol. 2020. [2] Lonial et al. ASCO 2020. EP436. [3] Lonial et al. EHA 2020. EP970. [4] Cohen et al. ASCO 2020. EP441. [5] Trudel et al. EHA 2020. EP1037. [6] Lee et al. ASCO 2020. EP419. [7] Lee et al. EHA 2020. EP1006.