Improvement of pasture biomass modelling using high-resolution satellite imagery and machine learning.

Robust quantification of vegetative biomass using satellite imagery using one or more forms of machine learning (ML) has hitherto been hindered by the extent and quality of training data. Here, we showcase how ML predictive demonstrably improves when additional training data is used. We collated field datasets of pasture biomass obtained via destructive sampling, 'C-Dax' reflective measurements and rising plate meters (RPM) from ten livestock farms across four States in Australia. Remotely sensed data from the Sentinel-2 constellation was used to retrieve aboveground biomass using a novel machine learning paradigm hereafter termed "SPECTRA-FOR" (Spectral Pasture Estimation using Combined Techniques of Random-forest Algorithm for Features Optimisation and Retrieval). Using this framework, we show that the low temporal resolution of Sentinel-2 in high latitude regions with persistent cloud cover leads to extensive gaps between cloud-free images, hindering model performance and, thus, contemporaneous ability to forecast real-time pasture biomass. By leveraging the spectral consistency between Sentinel-2 and Planet Lab SuperDove to overcome this limitation, we used ten spectral bands of Sentinel-2, four bands of Sentinel-2 as a proxy for pre-2022 SuperDove (referred to as synthetic SuperDove or SSD), and the actual SuperDove (ASD), given that SuperDove imagery has a higher resolution and more frequent passage compared with Sentinel-2. Using their respective bands as input features to SPECRA-FOR, model performance for the ten bands of Sentinel-2 were R2 = 0.87, root mean squared error (RMSE) of 439 kg DM/ha and mean absolute error (MAE) of 255 kg DM/ha, while that for SSD increased to an R2 of 0.92, RMSE of 346 kg DM/ha and MAE = 208 kg DM/ha. The study revealed the importance of robust data mining, imagery harmonisation and model validation for accurate real-time modelling of pasture biomass with ML.

Relationship between floating marine debris accumulation and coastal fronts in the Northeast coast of the USA.

Floating marine debris (FMD) is one of the world's most concerning issues due to its potential impact on biodiversity, communities, and ecosystem services. FMD transport and concentrations are driven by fronts, generated by oceanographic processes, and the accumulation of FMD has been reported in gyres, eddies, tidal fronts, salinity fronts, and coastal fronts. This study explores the relationship between fronts and FMD accumulation in the Gulf of Maine (GoM) and the surrounding coastal areas (USA). Frontal edge detection algorithms were applied to sea surface temperature (SST) imagery from the Moderate-resolution Imaging Spectroradiometer (MODIS) between 2002 and 2012. Frontal location is spatially correlated with FMD concentrations collected by the Sea Education Association. Higher concentrations of FMD are associated with frontal frequencies (FF) of 5-10 %. FMD is trapped between fronts and the coastline in accumulation zones. These results highlight the need to consider coastal FMD hotspots, given these are areas of high biodiversity value.

Prevalence of Chlamydia infection detected by immunohistochemistry in patients with anorectal ulcer and granulation tissue.

Anorectal ulcer with granulation tissue is typically associated with left-sided inflammatory bowel disease or infection. Due to emerging cases of Chlamydia proctitis, we aim to investigate the prevalence of Chlamydia infection using immunohistochemistry (IHC) in anorectal biopsies showing ulcer and granulation tissue. Seventy-seven patients including 60 males and 17 females with mean age of 51 years old were retrospectively identified in surgical pathology archives. Chlamydia IHC was validated with a monoclonal antibody on an index who was positive for Chlamydia by rectal swab nucleic acid amplification test (NAAT), then performed on formalin fixed and paraffin embedded (FFPE) tissue sections. Confirmative molecular test using real-time PCR was performed on DNA extractions of 14 IHC-positive and 14 IHC-negative FFPEs, 18 NAAT-positive, and 5 NAAT-negative cytology specimens. Chlamydia IHC showed strong intracytoplasmic or extracellular sphere morphology in 14 of 77 (18.2 %) FFPEs, including 11 of 60 (18.3 %) males and 3 of 17 (17.6 %) females (age 11-84 years). Eight of 14 (57.1 %) Chlamydia-IHC positive patients had known history of STDs, high-risk behavior, or immunosuppressive conditions. One of 14 (7.1 %) IHC-positive FFEP and 15 of 18 (83.3 %) NAAT-positive cytology cases were confirmed by real-time PCR. Chlamydia inclusions were detected in all 4 randomly selected NAAT and PCR-positive cytology specimens by IHC. Our data suggested that Chlamydia infection is more prevalent than we thought in patients with active proctitis and ulceration. Chlamydia IHC may be performed as a screening test in biopsies to facilitate early detection of this treatable proctitis in high-risk population.

Assessing real-time positive subjective effects of alcohol using high-resolution ecological momentary assessment in risky versus light drinkers.

BACKGROUND: High-resolution ecological momentary assessment (HR-EMA) can assess acute alcohol responses during naturalistic heavy drinking episodes. The goal of this study was to use HR-EMA to examine drinking behavior and subjective responses to alcohol in risky drinkers (moderate-severe alcohol use disorder [MS-AUD], heavy social drinkers [HD]) and light drinkers (LD). We expected that risky drinkers would endorse greater alcohol stimulation and reward, with lower sedation, than LD, even when controlling for amount of alcohol consumed. METHODS: Participants (N = 112; 54% male, M ± SD age = 27.2 ± 4.2 years) completed smartphone-based HR-EMA during one typical alcohol drinking occasion and one non-alcohol-drinking occasion in their natural environment. Participants were prompted to complete next-day surveys that assessed drinking-related outcomes, study acceptability, and safety. RESULTS: HR-EMA prompt completion rates were excellent (92% and 89% for the alcohol and nonalcohol episodes, respectively). The MS-AUD group consumed the most alcohol with the highest estimated blood alcohol concentration (eBAC) by the end of the alcohol drinking episode (0.14 g/dL) versus LD (0.02 g/dL), with HD intermediate (0.10 g/dL). Relative to LD, MS-AUD and HD endorsed greater positive effects of alcohol (stimulation, liking, and wanting). CONCLUSIONS: This study is the first to use HR-EMA to measure and compare real-world acute alcohol responses across diverse drinker subgroups, including persons with MS-AUD. Results demonstrate that risky drinkers experience heightened pleasurable effects measured in real-time during natural-environment alcohol responses. Rather than drinking excessively to eventually achieve desirable subjective effects, risky drinkers show sensitivity to positive alcohol effects throughout a heavy drinking episode.

Integration of the Verbatim Exercise into a Hospice and Palliative Medicine Fellowship.

One of the more challenging aspects of specialty level training in any medical fellowship is learning to communicate mindfully and effectively with patients and families in the face of serious illness. For the past five years, our accredited Hospice and Palliative Medicine (HPM) fellowship program has been integrating the "verbatim"-an exercise with a long and integral history in the training of health care chaplains. Verbatims are word-for-word accounts of a clinician's encounter with a patient and/or the patient's family. The verbatim serves as a formative educational exercise offering a method to hone one's clinical skills and competencies, while providing a unique space to practice self-awareness and self-reflection. Although sometimes difficult and intense for the fellow, we have found this to be a helpful exercise in improving the fellow's ability to make meaningful connections with patients and leading to improved outcomes of communication episodes. This potential growth in self-awareness supports both resiliency and mindfulness, which are essential skills for longevity and reduction of burnout risk in the field of HPM. The verbatim invites all participants to reflect on their own participation in facilitating whole person care to patients and families. Out of the six HPM milestone metrics for fellowship training, the verbatim exercise supports achievement in at least three of the milestones. We present survey data over the past five years of our fellowship in support of the utility of this exercise and for consideration to include this exercise in a palliative medicine fellowship. We offer additional suggestions for further study of this formative tool. This article delineates the verbatim technique and its specific integration into our accredited ACGME Hospice and Palliative Medicine fellowship training program.

Assessing the effectiveness of MARPOL Annex V at reducing marine debris on Australian beaches.

To mitigate marine debris and promote sustainable marine industries, legislation and regulations surrounding the management of marine debris have been adopted worldwide. One of the most well-known and important agreements is the International Convention for the Prevention of Pollution from Ships (MARPOL), which focuses on reducing all types of ship-sourced marine pollution. MARPOL Annex V, which deals with the disposal of solid waste, came into force on 31 December 1988. However, was only amended to include a complete ban on waste disposal as of 1 January 2013. Assessing the effectiveness of key regulations is fundamental for supporting evidence-based decisions regarding the management of our oceans. Here, we evaluated whether MARPOL Annex V translated into a decrease in the incidence of shipping- and commercial fishing-sourced debris on remote beaches in Australia using 14 years of standardised, community-driven data. From 2006 to 2020 there was a significant change over time in the density of fishing and shipping debris on Australian beaches; debris density increased up to 2013 followed by a decrease until mid-2017. Although the new regulation started in January 2013, the decrease in density was not recorded until one year later. The decline was only observed for 4 years, reinforcing the existence of lags between the implementation of international agreements and the corresponding potential reduction in debris in the environment. This provides compelling evidence that international agreements and policies by themselves are not enough to solve the debris problem, with improved implementation and enforcement also required. We discuss future perspectives and solutions to reduce ocean-sourced litter inputs into the ocean and highlight the urgent need for action.

Development and validation of an integrative pan-solid tumor predictor of PD-1/PD-L1 blockade benefit.

BACKGROUND: Anti-PD-1 and PD-L1 (collectively PD-[L]1) therapies are approved for many advanced solid tumors. Biomarkers beyond PD-L1 immunohistochemistry, microsatellite instability, and tumor mutation burden (TMB) may improve benefit prediction. METHODS: Using treatment data and genomic and transcriptomic tumor tissue profiling from an observational trial (NCT03061305), we developed Immunotherapy Response Score (IRS), a pan-tumor predictive model of PD-(L)1 benefit. IRS real-world progression free survival (rwPFS) and overall survival (OS) prediction was validated in an independent cohort of trial patients. RESULTS: Here, by Cox modeling, we develop IRS-which combines TMB with CD274, PDCD1, ADAM12 and TOP2A quantitative expression-to predict pembrolizumab rwPFS (648 patients; 26 tumor types; IRS-High or -Low groups). In the 248 patient validation cohort (248 patients; 24 tumor types; non-pembrolizumab PD-[L]1 monotherapy treatment), median rwPFS and OS are significantly longer in IRS-High vs. IRS-Low patients (rwPFS adjusted hazard ratio [aHR] 0.52, p = 0.003; OS aHR 0.49, p = 0.005); TMB alone does not significantly predict PD-(L)1 rwPFS nor OS. In 146 patients treated with systemic therapy prior to pembrolizumab monotherapy, pembrolizumab rwPFS is only significantly longer than immediately preceding therapy rwPFS in IRS-High patients (interaction test p = 0.001). In propensity matched lung cancer patients treated with first-line pembrolizumab monotherapy or pembrolizumab+chemotherapy, monotherapy rwPFS is significantly shorter in IRS-Low patients, but is not significantly different in IRS-High patients. Across 24,463 molecularly-evaluable trial patients, 7.6% of patients outside of monotherapy PD-(L)1 approved tumor types are IRS-High/TMB-Low. CONCLUSIONS: The validated, predictive, pan-tumor IRS model can expand PD-(L)1 monotherapy benefit outside currently approved indications.

Therapies activating the immune system (checkpoint inhibitors) have revolutionized the treatment of patients with advanced cancer, however new molecular tests may better identify patients who could benefit. Using treatment data and clinical molecular test results, we report the development and validation of Immunotherapy Response Score (IRS) to predict checkpoint inhibitor benefit. Across patients with more than 20 advanced cancer types, IRS better predicted checkpoint inhibitor benefit than currently available tests. Data from >20,000 patients showed that IRS identifies ~8% of patients with advanced cancer who may dramatically benefit from checkpoint inhibitors but would not receive them today based on currently available tests. Our approach may help clinicians to decide which patients should receive checkpoint inhibitors to treat their disease.

Ocular adverse events associated with chimeric antigen receptor T-cell therapy: a case series and review.

BACKGROUND/AIMS: Chimeric antigen receptor T-cell (CAR T) therapy has been shown to improve the remission rate and survival for patients with refractory haematological malignancies. The aim of this study is to describe ocular adverse effects associated with CAR T therapy in patients with haematological malignancies. METHODS: This is a retrospective, single-institution, case series. Patients aged 18 years or older who received standard of care CAR T therapy for relapsed/refractory large B-cell lymphoma with a documented ophthalmic evaluation were included. The primary outcome was clinician ophthalmic examination findings. RESULTS: A total of 66 patients received CAR T-cell therapy from February 2018 to October 2019 with 11 receiving an ophthalmic examination. Eleven patients (n=22 eyes) who received CAR T-cell therapy were included in review. The median time from CAR T-cell infusion date to ocular examination was 57.5 days. The median patient age at the time of examination was 60.5 years. Ten patients had subjective symptoms prompting ophthalmic examination. Two patients reported floaters and photopsias. One patient had worsening ocular graft-versus-host disease. Two patients were identified with possible reactivation of viral infections, including herpes zoster ophthalmicus and regressing acute retinal necrosis. CONCLUSIONS: The increasing use of CAR T therapy for malignancies underscores the importance of ophthalmologists and oncologists understanding the potential toxicities associated with its use, particularly ocular toxicities and when to refer for an ophthalmic examination.

Drinking context, alcohol use, and subjective responses during binge drinking episodes measured by high-resolution ecological momentary assessment (HR-EMA).

OBJECTIVE: Subjective responses to alcohol play a key role in the development and maintenance of risky drinking and alcohol use disorder (AUD). The social and environmental context where drinking occurs may moderate alcohol's subjective effects, but ecologically valid studies of these associations are limited. The present study used high-resolution ecological momentary assessment (HR-EMA) targeting real-world binge drinking episodes to examine associations among drinking context, alcohol consumption, and subjective responses to alcohol. METHOD: Young adult heavy drinkers (N = 61; 57% male) completed two smartphone-based, 3-hr HR-EMA of drinking context (social context and location), alcohol use, and subjective responses (alcohol stimulation, sedation, feeling, liking, and wanting more). Analyses examined the associations between drinking context and subjective alcohol responses, accounting for demographic characteristics and individual differences in alcohol consumption. RESULTS: Most (85%) participants reported binge drinking during real-world drinking events. Estimated blood alcohol concentration (eBAC) and alcohol stimulation and reward (liking, wanting) were greater when participants drank with others (vs. alone) and in a bar/restaurant (vs. other location). Sedation was higher when drinking alone versus with others. CONCLUSIONS: The present study extends prior laboratory-based research and shows that subjective responses during naturalistic binge drinking episodes may be influenced by drinking context. Drinking with others and in bars and restaurants may increase alcohol consumption, enhance alcohol's rewarding effects, and lead to more alcohol-related harm in at-risk drinkers. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Liquid-based rapid onsite evaluation of endobronchial ultrasound cytologies.

INTRODUCTION: Rapid onsite evaluation (ROSE) generally uses smears made at the site of the procedure ("smear-based ROSE"). It requires considerable time, generally 2 individuals, technical expertise, and it can be difficult to estimate material available for ancillary studies. We developed an alternative ROSE using liquid-based cytology ThinPrep with hematoxylin and eosin (H&E) stain ("liquid-based ROSE") and assessed its advantages. MATERIALS AND METHODS: Clinicians rinse the sample(s) into CytoRich Red and send to Pathology. A defined proportion of the needle rinse is removed for a ThinPrep stained with a rapid H&E. Adequacy and diagnosis were compared to final outcome. Total time was recorded. RESULTS: Among 52 liquid-based ROSE readings, 28 (53.8%) were interpreted as "adequate" with final as adequate; 17 (32.7%) were interpreted as "inadequate" with final as inadequate; 7 (13.5%) were interpreted as "inadequate" with final as adequate. Of 23 readings provided with onsite diagnosis, 15 (65.2%) were interpreted as definitive positive or negative diagnoses; 6 (26%) were interpreted as nondiagnostic; and 2 (8.7%) were interpreted as atypical. All definitive diagnoses were concordant with final diagnoses. The time for liquid ROSE performance ranges from 6 to 22 minutes (mean: 13 minutes) and required only 1 individual. CONCLUSIONS: Liquid-based ROSE allows accurate adequacy determination and diagnosis, takes about 15 minutes of cytologist time, and can be performed by just 1 person. The technique produces well-preserved and stained slides, it may allow a better estimation of the total amount of material in the specimen vial and may provide a better platform for telecytology.

Fluorescence Polarization Imaging of Methylene Blue Facilitates Quantitative Detection of Thyroid Cancer in Single Cells.

BACKGROUND: Diagnostic accuracy of the standard of care fine-needle aspiration cytology (FNAC) remains a significant problem in thyroid oncology. Therefore, a robust and accurate method for reducing uncertainty of cytopathological evaluation would be invaluable. METHODS: In this double-blind study, we employed fluorescence emission and quantitative fluorescence polarization (Fpol) confocal imaging for sorting thyroid cells into benign/malignant categories. Samples were collected from malignant tumors, benign nodules, and normal thyroid epithelial tissues. RESULTS: A total of 32 samples, including 12 from cytologically indeterminate categories, were stained using aqueous methylene blue (MB) solution, imaged, and analyzed. Fluorescence emission images yielded diagnostically relevant information on cytomorphology. Significantly higher MB Fpol was measured in thyroid cancer as compared to benign and normal cells. The results obtained from 12 indeterminate samples revealed that MB Fpol accurately differentiated benign and malignant thyroid nodules. CONCLUSIONS: The developed imaging approach holds the potential to provide an accurate and objective biomarker for thyroid cancer, improve diagnostic accuracy of cytopathology, and decrease the number of lobectomy and near-total thyroidectomy procedures.

Deconvolution microscopy: A platform for rapid on-site evaluation of fine needle aspiration specimens that enables recovery of the sample.

CONTEXT: Rapid on-site evaluation (ROSE) optimises the performance of cytology, but requires skilled handling, and smearing can make the material unavailable for some ancillary tests. There is a need to facilitate ROSE without sacrificing part of the sample. OBJECTIVE: We evaluated the image quality of inexpensive deconvolution fluorescence microscopy for optically sectioning non-smeared fine needle aspiration (FNA) tissue fragments. DESIGN: A portion of residual material from 14 FNA samples was stained for 3 min in Hoechst 33342 and Sypro™ Red to label DNA and protein respectively, transferred to an imaging chamber, and imaged at 200× or 400× magnification at 1 micron intervals using a GE DeltaVision inverted fluorescence microscope. A deconvolution algorithm was applied to remove out-of-plane signal, and the resulting images were inverted and pseudocoloured to resemble H&E sections. Five cytopathologists blindly diagnosed 2 to 4 representative image stacks per case (total 70 evaluations), and later compared them to conventional epifluorescent images. RESULTS: Accurate definitive diagnoses were rendered in 45 (64%) of 70 total evaluations; equivocal diagnoses (atypical or suspicious) were made in 21 (30%) of the 70. There were two false positive and two false negative "definite" diagnoses in three cases (4/70; 6%). Cytopathologists preferred deconvolved images compared to raw images (P < 0.01). The imaged fragments were recovered and prepared into a ThinPrep or cell block without discernible alteration. CONCLUSIONS: Deconvolution improves image quality of FNA fragments compared to epifluorescence, often allowing definitive diagnosis while enabling the ROSE material to be subsequently triaged.

Clinical, pathologic, and molecular analyses of superficial low-grade fibromyxoid sarcoma in two young patients: A rare and deceptive mimic of benignancy.

Low-grade fibromyxoid sarcoma (LGFMS) is a histopathologically deceptive soft tissue neoplasm with bland cytology, which is typically encountered in deep soft tissue of adults. We report two cases of superficial LGFMS in young patients (16 and 21 years old, respectively), which were difficult to diagnose on histopathologic and clinical findings alone. LGFMS commonly mimics benign neoplasms such as cellular neurothekeoma, fibromatosis, neurofibroma, and perineurioma. Malignancies included in the differential diagnosis are soft tissue neoplasms such as dermatofibrosarcoma protuberans and myxofibrosarcoma. A high degree of reported variation in pattern and cellularity among LGFMS further complicates the diagnosis. Careful examination and appropriate immunohistochemistry panels including MUC4 are essential for narrowing the differential diagnosis. Molecular studies for possible FUS translocation can confirm the diagnosis of LGFMS. Sufficient sampling and workup of these lesions are critical, especially in younger patients. Young age and superficial presentation can easily sway dermatopathologists/dermatologists toward an incorrect diagnosis of benignancy.

Angiokeratoma-like purpuric palmar nodules following chemotherapy.

We describe a patient with leukemia undergoing chemotherapy who developed painful purpuric nodules of the digits. These findings were concerning for endocarditis (clinically) and angiokeratomas on gross histology. After extensive evaluation, we report the development of painful purpuric nodules as a likely side effect of the patient's therapeutic regimen (hydroxyurea, danorubicin, cytarabine, and methotrexate).

Real-World Performance of a Comprehensive Genomic Profiling Test Optimized for Small Tumor Samples.

PURPOSE: Tissue-based comprehensive genomic profiling (CGP) is increasingly used for treatment selection in patients with advanced cancer; however, tissue availability may limit widespread implementation. Here, we established real-world CGP tissue availability and assessed CGP performance on consecutively received samples. MATERIALS AND METHODS: We conducted a post hoc, nonprespecified analysis of 32,048 consecutive tumor tissue samples received for StrataNGS, a multiplex polymerase chain reaction (PCR)-based comprehensive genomic profiling (PCR-CGP) test, as part of an ongoing observational trial (NCT03061305). Sample characteristics and PCR-CGP performance were assessed across all tested samples, including exception samples not meeting minimum input quality control (QC) requirements (< 20% tumor content [TC], < 2 mm2 tumor surface area [TSA], DNA or RNA yield < 1 ng/µL, or specimen age > 5 years). Tests reporting ≥ 1 prioritized alteration or meeting TC and sequencing QC were considered successful. For prostate carcinoma and lung adenocarcinoma, tests reporting ≥ 1 actionable or informative alteration or meeting TC and sequencing QC were considered actionable. RESULTS: Among 31,165 (97.2%) samples where PCR-CGP was attempted, 10.7% had < 20% TC and 59.2% were small (< 25 mm2 tumor surface area). Of 31,101 samples evaluable for input requirements, 8,089 (26.0%) were exceptions not meeting requirements. However, 94.2% of the 31,101 tested samples were successfully reported, including 80.5% of exception samples. Positive predictive value of PCR-CGP for ERBB2 amplification in exceptions and/or sequencing QC-failure breast cancer samples was 96.7%. Importantly, 84.0% of tested prostate carcinomas and 87.9% of lung adenocarcinomas yielded results informing treatment selection. CONCLUSION: Most real-world tissue samples from patients with advanced cancer desiring CGP are limited, requiring optimized CGP approaches to produce meaningful results. An optimized PCR-CGP test, coupled with an inclusive exception testing policy, delivered reportable results for > 94% of samples, potentially expanding the proportion of CGP-testable patients and impact of biomarker-guided therapies.

Development and Validation of StrataNGS, a Multiplex PCR, Semiconductor Sequencing-Based Comprehensive Genomic Profiling Test.

Despite widespread use in targeted tumor testing, multiplex PCR/semiconductor (Ion Torrent) sequencing-based assessment of all comprehensive genomic profiling (CGP) variant classes has been limited. Herein, we describe the development and validation of StrataNGS, a 429-gene, multiplex PCR/semiconductor sequencing-based CGP laboratory-developed test performed on co-isolated DNA and RNA from formalin-fixed, paraffin-embedded tumor specimens with ≥2 mm2 tumor surface area. Validation was performed in accordance with MolDX CGP validation guidelines using 1986 clinical formalin-fixed, paraffin-embedded samples and an in-house developed optimized bioinformatics pipeline. Across CGP variant classes, accuracy ranged from 0.945 for tumor mutational burden (TMB) status to >0.999 for mutations and gene fusions, positive predictive value ranged from 0.915 for TMB status to 1.00 for gene fusions, and reproducibility ranged from 0.998 for copy number alterations to 1.00 for splice variants and insertions/deletions. StrataNGS TMB estimates were highly correlated to those from whole exome- or FoundationOne CDx-determined TMB (Pearson r = 0.998 and 0.960, respectively); TMB reproducibility was 0.996 (concordance correlation coefficient). Limit of detection for all variant classes was <20% tumor content. Together, we demonstrate that multiplex PCR/semiconductor sequencing-based tumor tissue CGP is feasible using optimized bioinformatic approaches described herein.