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Floods are the most frequent, costliest natural disasters having devastating consequences on people, infrastructure, and the ecosystem. During flood events near real-time satellite imagery has proven to be an efficient management tool for disaster management authorities. However one of the challenges is accurate classification and segmentation of flooded water. The generalization ability of binary segmentation using threshold split-based method, is limited due to the effects of backscatter, geographical area, and time of image collection. Recent advancements in deep learning algorithms for image segmentation has demonstrated excellent potential for improving flood detection. However, there have been limited studies in this domain due to the lack of large scale labeled flood event dataset. In this paper, we present two deep learning approaches, first using a UNet and second, using a Feature Pyramid Network (FPN), both based on a backbone of EfficientNet-B7, by leveraging publicly available Sentinel-1 dataset provided jointly by NASA Interagency Implementation and Advanced Concepts Team, and IEEE GRSS Earth Science Informatics Technical Committee. The dataset covers flood events from Nebraska, North Alabama, Bangladesh, Red River North, and Florence. The performances of both networks were evaluated with multiple training, testing, and validation. During testing, the UNet model achieved the meanIOU score of 75.06% and the FPN model achieved the meanIOU score of 75.76%.

Hydroxychloroquine (HCQ) is the cornerstone of systemic lupus erythematous (SLE or lupus) treatment, yet, the optimal dosing of HCQ in SLE is unknown. Reducing HCQ dose to 5 mg/kg to limit toxicity, as suggested by the American Academy of Ophthalmologists (AAO),(1) also predicts increased flares.(2) One study showed six-fold higher risk of severe SLE flares in patients receiving AAO recommended HCQ dosing.(2) Therefore, establishing effective therapeutic ranges of HCQ blood levels may provide an opportunity to individualize HCQ dosing to maximize efficacy and limit toxicity. The objective of this study was to examine the association of HCQ blood levels with high lupus disease activity (HDA) in a prospective SLE cohort. This cross-sectional study measured HCQ blood levels in unique SLE visits using liquid chromatography-tandem mass spectrometry. HCQ blood levels and SLE disease activity index (SLEDAI) scores were measured on the day of the visit for each patient. High lupus disease activity (HDA) was defined as SLEDAI scores of ≥6.(3) To identify significant HCQ blood levels that determined lower odds of HDA, we examined associations between HDA and every 50-100 ng/ml increase in HCQ blood levels starting at 100 ng/ml through 1500 ng/ml. Other factors that can affect HCQ levels, such as patient-reported adherence, kidney function, and HCQ dose and timing, were included in multivariable models. Among 143 SLE patients in whom HCQ blood levels were measured, 92% were women and 32% were of non-White race or Hispanic ethnicity. HDA was noted in 18% of patients. We noted a 75% reduction in the odds of HDA first at HCQ blood levels of ≥750 ng/ml (Adjusted OR 0.25, 95% CIs 0.066-0.89, p-value = 0.035; Figure 1). This effect peaked with HCQ blood levels ≥1100 ng/ml with 93% lower odds of HDA at this level (Adjusted OR 0.07, 95% CIs 0.005-0.61, p-value = 0.038; Figure 1). Interestingly, levels of 1150 ng/ml or higher did not further reduce the odds of HDA (Figure 1). Additionally, we noted that female sex was associated with 88% lower odds of HDA (Table 1), while other factors including HCQ dose or timing were not associated with HDA (Table 1). We report an effective therapeutic range of HCQ blood levels, 750-1100 ng/ml, that significantly correlated with reduced risk of high lupus disease activity (HDA) by 75-93% in patients with SLE. These findings could guide clinicians to individualize HCQ doses to achieve target blood levels within this range to maximize efficacy, while balancing safety. [1]Marmor MF, Kellner U, Lai TYY, Melles RB, Mieler WF. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Ophthalmology 2016;123:1386–1394. [2)] Jorge AM, Mancini C, Zhou B, et al. Hydroxychloroquine Dose per Ophthalmology Guidelines and the Risk of Systemic Lupus Erythematosus Flares. JAMA. 2022;328(14):1458–1460. [3]Arora, S., Isenberg, D.A. and Castrejon, I. (2020), Measures of Adult Systemic Lupus Erythematosus: Disease Activity and Damage. Arthritis Care Res, 72: 27-46. The UW SLE Cohort is supported by the DOM and ICTR at UW-Madison. Shivani Garg: None declared, Betty Chewning: None declared, Shelby Gomez: None declared, Christie Bartels Grant/research support from: Received an independent learning grant from Pfizer for a different research project. [Display omitted] Table 1Factors Associated with High SLE Disease Activity (SLEDAI ≥6), Multivariable ModelVariablesAdjusted Odds Ratio (95% CIs)p-valueAge (per 10 years increase)0.99 (1.03, 9.6)0.89Female0.11 (0.013, 0.83)0.03Non-White race & Hispanic ethnicity0.75 (0.23, 2.3)0.61Weight (per 5 kg increase)0.97 (0.93-1.01)0.13CKD stage ≥21.077 (0.29, 3.9)0.91HCQ total dose200 mg dailyref300 mg/d1.8 (0.29, 22)0.43400 mg daily3.0 (0.49, 22)0.25AAO-Guideline based dose, ≤5 mg/kg/day1.4 (0.2, 12)0.73HCQ blood levels ≥1100 ng/ml0.07 (0.004, 0.45)0.02Patient-reported adherence ≥80%0.57 (0.16, 2.1)0.38Social Determinants of Health, Present3.2 (0.86, 12)0.99HCQ dose timing<4 hoursref4-6 hours3.3 (0.15, 153)0.486-8 hours2.03 (0.1, 81)0.66>8 hours0.15 (0.08, 60)0.80

Abstract Context Variations in the prevalence and etiology of type 2 diabetes (T2D) across race and ethnicity may affect treatment responses. Semaglutide is a glucagon-like peptide-1 analog approved for once-weekly, subcutaneous treatment of T2D. Objective To compare semaglutide efficacy and safety in race and ethnicity subgroups across the SUSTAIN trials. Design Post hoc analysis of data from phase 3 randomized SUSTAIN 1–5 and 7 (pooled), and SUSTAIN 6 trials. Participants 3074 subjects (SUSTAIN 1–5 and 7) and 1648 subjects (SUSTAIN 6). Interventions Semaglutide 0.5 or 1.0 mg, placebo, or active comparator (sitagliptin 100 mg, exenatide extended release 2.0 mg, insulin glargine 100IU/ml and dulaglutide 0.75 or 1.5 mg). Main Outcome Measures Change in hemoglobin A1C (HbA1c) and body weight from baseline to weeks 30, 40 and 104, and other efficacy and safety endpoints. Results HbA1c was reduced from baseline by 1.0 to 1.5 percentage points and 1.3 to 2.0 percentage points, and body weight was reduced by 2.3 to 4.7 kg and 3.6 to 6.1 kg with semaglutide 0.5 and 1.0 mg, respectively, across race and ethnicity subgroups. Minor changes in blood pressure and lipid profiles were observed. Adverse events (AEs) were reported in similar proportions of subjects across trials. More Asian versus other race subgroups discontinued treatment prematurely due to AEs. The most commonly reported AEs were gastrointestinal disorders. Conclusions In this SUSTAIN trials post hoc analysis, semaglutide was associated with consistent and clinically relevant reductions in HbA1c and body weight in subjects with T2D, with minor variations in efficacy and safety outcomes associated with race or ethnicity.

Purpose: To evaluate the astigmatism correcting effect of penetrating arcuate keratotomy (AK) done during femtosecond laser-assisted cataract surgery (FLACS). Methods: In this nonrandomized prospective study, 80 eyes of 70 patients were studied. The study included patients who underwent combined FLACS and AK, with corneal astigmatism ranging from 0.4 to 1.5 diopters (D). Femtosecond laser-assisted penetrating arcuate keratotomies were created at 8 mm optical zone at 80% depth and were centered at the limbus. Keratometric astigmatism was measured prior to and 3 months post-surgery. Vector analysis was performed using Power vector analysis method. Results: The mean preoperative keratometric astigmatism without accounting for axis was 0.85 ± 0.27 D, which reduced significantly to 0.47 ± 0.27 D at 3-month follow-up. The mean astigmatism correction attained without accounting for axis was 0.38 ± 0.32 D. The vector corrected mean preoperative astigmatism was 0.85 ± 0.27 D which reduced significantly to 0.50 ± 0.31 D postoperatively (P < 0.001, 95% CI). Vector corrected mean astigmatism correction attained was 0.35 ± 0.38 D. There were no significant intraoperative or postoperative complications. Conclusion: Preexisting astigmatism can be tackled effectively with penetrating AK during FLACS although under correction is observed with present nomograms. Further refinements may achieve better correction.

IntroductionAddiction has long been recognized as a disease that may have a dramatic influence on the addicted individual’s family members, manifesting as stress or trauma-related physical and psychological symptoms, resulting in increase in the usual family’s use of health-care services. There is little research available to identify and explore problems of families associated with such patients. In this study, we will evaluate stress among family members of substance abuse patients and try to focus on how these family members are dealing with these stress factors. The study will also compare different types of coping mechanisms among family members of patients taking licit and illicit substances.ObjectivesTo identify stress among families of patients abusing licit and illicit drugs and assess and compare their coping mechanisms.Methods175 family members of patients with licit substance abuse cases and 175 family members of patients with illicit substance abuse were taken for study after informed consent. Stress among participants was evaluated using Symptom Rating Test and The Depression Anxiety and Stress Scales (DASS). Coping Questionnaire (CQ) and Breif COPE was used to assess coping among them.ResultsThe study demonstrated that the total number and severity of symptoms, including psychological and physical symptoms, are found lesser in caregivers (participants) of patients abusing licit substances than in patients abusing illicit drugs. These symptoms among family members grow as the patient’s age rises. Symptoms in participants are more if their patient is female as compared to male. And also, total symptoms are more if they are living in nuclear family (Table 1). In our results, total coping and engaged coping mechanisms in family members are found to be not significant as per drug type and remains the same for both licit and illicit drugs abusing patients’ families. Avoidant coping mechanisms in family members are more if their patient is female and in nuclear family.Table 1symp1CoefficientsStd. Err.P Valueage0.005*0.0010.000drug_type-0.114*0.0270.000female_d0.230*0.0280.000nuclear_d0.124*0.0270.000ConclusionsIn our study, it was clearly noticed that the total symptoms, both physical and psychological, were found more in family members of patients abusing illicit drugs. Impact of substance abuse related problems is found more in female members compared to male members of family.Disclosure of InterestNone Declared

Imiquimod (IMQ) is an immunomodulating drug that is approved for the treatment of superficial basal cell carcinoma, actinic keratosis, external genital warts and perianal warts. However, IMQ cream (Aldara ) has several drawbacks including poor skin permeation, local toxicity, and compromised patient compliance as a topical pharmacological option. Our research aimed to develop and optimize nanostructured lipid carriers (NLCs) containing IMQ for the first time using a hybrid design of experiments approach. The optimized formulation was then incorporated into a matrix-type topical patch as an alternative dosage form for topical application and evaluated for IMQ deposition across different skin layers in comparison to the performance of the commercial product. Additionally, our work also attempted to highlight the possibility of implementing environment-friendly practices in our IMQ-NLCs formulation development by reviewing our analytical methods and experimental designs and reducing energy and solvent consumption where possible. In this study, stearyl alcohol, oleic acid, Tween 80 (polysorbate 80), and Gelucire 50/13 (Stearoyl polyoxyl-32 glycerides) were selected for formulation development. The formulation was optimized using a 2 factorial design and a central composite design. The optimized formulation achieved the average particle size, polydispersity index, and zeta potential of 75.6 nm, 0.235, and - 30.9 mV, respectively. Subsequently, a matrix-type patch containing IMQ-NLCs was developed and achieved a statistically significant improvement in IMQ deposition in the deeper skin layers. The IMQ deposition from the patch into the dermis layer and receptor chamber was 3.3 ± 0.9 µg/cm and 12.3 ± 2.2 µg/cm , while the commercial cream only deposited 1.0 ± 0.8 µg/cm and 1.5 ± 0.5 µg/cm of IMQ, respectively. In summary, IMQ-NLC-loaded patches represent great potential as a topical treatment option for skin cancer with improved patient compliance.

Permissioned blockchain is the blockchain network that requires access to be part of the network. Participant’s actions are governed by the control layer that runs on top of the blockchain. This type of blockchains is preferred by individuals who need role description, identity, and security within the blockchain. Secure multi-party computation (MPC) is a part of cryptography that involves the modeling of procedures for two or more participants who want to work together. These participants involve sharing of input and required computational data for a particular function without sharing their confidential data actively to each other and achieving a common goal which is beneficial to both as the outcome achieved is only revealed to the participants and is highly required for their functional purpose. In this work, SPDZ (Speedz) implementation is explored leveraging additive secret sharing on the private blockchain (Hyperledger fabric). SPDZ protocol is chosen over any other computational protocol as it is highly secured from any active deceptive n-1 participant among the n participants. In this work, a backend is developed that uses a fabric SDK node.js library that interacts with the Hyperledger Fabric network. The proposed solution is shown through a demonstration. This paper concludes that for business-to-business scenarios, using SPDZ protocol on permissioned blockchain provides more security against adversaries as permissioned blockchain provides transparency over the participants of the network. As a result, permissioned blockchain is a more secure choice for enterprises to compute confidential data rather than permissionless blockchain.

Background:Up to 80% of patients with lupus (or SLE) are nonadherent to hydroxychloroquine (HCQ) associated with 45% higher acute care visits. HCQ nonadherence is even higher in patients of Black race or those with social barriers, potentially leading to higher acute care use and poor outcomes. Moreover, recent studies showed that the recommended HCQ dose (≤5 mg/kg/day) risk 6-fold higher SLE flares requiring hospitalization, due to subtherapeutic HCQ levels. Therefore, therapeutic drug level monitoring for HCQ in blood could guide clinicians to optimize HCQ dosing to maximize efficacy, adherence, and reduce acute care visits. Yet, HCQ blood level monitoring is not routinely done in North America due to concerns about cost and coverage. Establishing that HCQ blood level monitoring could reduce healthcare costs, acute care use, and improve outcomes in lupus would support payer approval to monitor HCQ levels during routine SLE visits.Objectives:The objective of this study was to examine the effectiveness of HCQ blood level monitoring in reducing the risk of acute care visits in patients with vs. without therapeutic HCQ blood levels.Methods:We measured HCQ blood levels during 223 consecutive patient-visits using liquid chromatography mass spectrometry. HCQ blood levels were categorized as: a) subtherapeutic (<750 ng/ml), b) therapeutic (750-1200 ng/ml), or c) supratherapeutic (>1200 ng/ml) per our prior findings [1]. All lupus-related acute care (hospital or ER) visits from the index patient visit through the next follow-up visit were manually abstracted. Covariates included socio-demographics, SLE disease activity score, SLE damage index, kidney function, steroid and HCQ doses, history of previous SLE related acute care visits, exposure to SLE triggers (e.g., infection), or immunosuppressive drugs. Using Proportional Means Hazards modelling, we examined associations between HCQ blood levels and acute care visits including recurrent visits. Using the results of our Proportional Means Hazards model, we calculated the predicted mean frequency of acute care visits with therapeutic HCQ levels stratified by race adjusting for covariates.Results:Across 223 patient-visits, a total of 39 SLE-related acute care visits were observed. We noted that patients of Black race or Hispanic ethnicity had 4-fold higher risk of acute care visits (Adjusted HR 3.8; Table 1). A recent exposure to SLE triggers, higher steroid doses, and previous SLE-related acute care visits were was associated with higher acute care visits (Table 1). Finally, a 78% lower risk of acute care visits was seen in patients with therapeutic HCQ blood levels, 750-1200 ng/ml, compared to those with subtherapeutic levels, <750 ng/ml (Table 1).The predicted mean frequency of SLE-related acute care visits with therapeutic HCQ levels for a 30-year-old person of Black race with social barriers, active lupus, no organ damage, 5mg/kg dosing, and no exposure to SLE triggers was 5x lower compared to a patient with similar characteristics but with subtherapeutic levels (0.8 vs. 4.2 at 20 months; Figure 1).Conclusion:Therapeutic HCQ blood levels (750-1200 ng/ml) were associated with 78% lower acute care visits, and predicted 5x lower acute care visits in patients of Black race or Hispanic ethnicity who historically face higher nonadherence and worse SLE outcomes. Therapeutic HCQ blood level monitoring could prevent unnecessary acute care visits and health disparities in lupus, thus warranting its use during SLE visits.REFERENCES:[1] Garg, S., Chewning, B., Hutson, P., Astor, B.C. and Bartels, C.M. (2024), Reference Range of Hydroxychloroquine Blood Levels That Can Reduce Odds of Active Lupus and Prevent Flares. Arthritis Care Res. https://doi.org/10.1002/acr.25228Figure 1.Predicted mean frequency of acute care visits with and without therapeutic HCQ blood levels for a 30-year-old patient of Black or White race with at least one social barrier, active lupus (SLEDAI ≥6), without organ damage (SDI 0), HCQ dose ≤5mg/kg/day, and without recent triggers that flare lupus.Acknowledgements:The UW SLE Cohort is supported by the Department of Medicine and the Institute for Clinical and Translational Research at the University of Wisconsin-Madison.Disclosure of Interests:None declared.

Many sites in the densely populated Indo-Gangetic Plain (IGP) frequently exceed the national ambient air quality standard (NAAQS) of 100 μg m−3 for 24 h average PM10 and 60 μg m−3 for 24 h average PM2.5 mass loadings, exposing residents to hazardous levels of particulate matter (PM) throughout the year. We quantify the contribution of long-range transport to elevated PM levels and the number of exceedance events through a back-trajectory climatology analysis of air masses arriving at the IISER Mohali Atmospheric Chemistry facility (30.667° N, 76.729° E; 310 m a.m.s.l.) for the period August 2011–June 2013. Air masses arriving at the receptor site were classified into six clusters, which represent synoptic-scale air-mass transport patterns. Long-range transport from the west leads to significant enhancements in the average fine- and coarse-mode PM mass loadings during all seasons. The contribution of long-range transport from the west and south-west (source regions: Arabia, Thar Desert, Middle East and Afghanistan) to coarse-mode PM varied between 9 and 57 % of the total PM10–2.5 mass. Local pollution episodes (wind speed < 1 m s−1) contributed to enhanced PM2.5 mass loadings during both the winter and summer seasons and to enhanced coarse-mode PM only during the winter season. South-easterly air masses (source region: eastern IGP) were associated with significantly lower fine- and coarse-mode PM mass loadings during all seasons. The fraction of days in each season during which the PM mass loadings exceeded the national ambient air quality standard was controlled by long-range transport to a much lesser degree. For the local cluster, which represents regional air masses (source region: NW-IGP), the fraction of days during which the national ambient air quality standard (NAAQS) of 60 μg m−3 for 24 h average PM2.5 was exceeded varied between 36 % of the days associated with this synoptic-scale transport during the monsoon, and 95 % during post-monsoon and winter seasons; the fraction of days during which the NAAQS of 100 μg m−3 for the 24 h average PM10 was exceeded, varied between 48 % during the monsoon and 98 % during the post-monsoon season. Long-range transport was responsible for both, bringing air masses with a significantly lower fraction of exceedance days from the eastern IGP and air masses with a moderate increase in the fraction of exceedance days from the west (source regions: Arabia, Thar Desert, Middle East and Afghanistan). In order to bring PM mass loadings into compliance with the NAAQS and to reduce the number of exceedance days, mitigation of regional combustion sources in the NW-IGP needs to be given highest priority.

Abnormalities in the semantic and syntactic organization of speech have been reported in individuals at clinical high-risk (CHR) for psychosis. The current study seeks to examine whether such abnormalities are associated with changes in brain structure and functional connectivity in CHR individuals. Automated natural language processing analysis was applied to speech samples obtained from 46 CHR and 22 healthy individuals. Brain structural and resting-state functional imaging data were also acquired from all participants. Sparse canonical correlation analysis (sCCA) was used to ascertain patterns of covariation between linguistic features, clinical symptoms, and measures of brain morphometry and functional connectivity related to the language network. In CHR individuals, we found a significant mode of covariation between linguistic and clinical features (r = 0.73; p = 0.003), with negative symptoms and bizarre thinking covarying mostly with measures of syntactic complexity. In the entire sample, separate sCCAs identified a single mode of covariation linking linguistic features with brain morphometry (r = 0.65; p = 0.05) and resting-state network connectivity (r = 0.63; p = 0.01). In both models, semantic and syntactic features covaried with brain structural and functional connectivity measures of the language network. However, the contribution of diagnosis to both models was negligible. Syntactic complexity appeared sensitive to prodromal symptoms in CHR individuals while the patterns of brain-language covariation seemed preserved. Further studies in larger samples are required to establish the reproducibility of these findings.