cloneRate: fast estimation of single-cell clonal dynamics using coalescent theory.

MOTIVATION: While evolutionary approaches to medicine show promise, measuring evolution itself is difficult due to experimental constraints and the dynamic nature of body systems. In cancer evolution, continuous observation of clonal architecture is impossible, and longitudinal samples from multiple timepoints are rare. Increasingly available DNA sequencing datasets at single-cell resolution enable the reconstruction of past evolution using mutational history, allowing for a better understanding of dynamics prior to detectable disease. There is an unmet need for an accurate, fast, and easy-to-use method to quantify clone growth dynamics from these datasets. RESULTS: We derived methods based on coalescent theory for estimating the net growth rate of clones using either reconstructed phylogenies or the number of shared mutations. We applied and validated our analytical methods for estimating the net growth rate of clones, eliminating the need for complex simulations used in previous methods. When applied to hematopoietic data, we show that our estimates may have broad applications to improve mechanistic understanding and prognostic ability. Compared to clones with a single or unknown driver mutation, clones with multiple drivers have significantly increased growth rates (median 0.94 versus 0.25 per year; P = 1.6×10-6). Further, stratifying patients with a myeloproliferative neoplasm (MPN) by the growth rate of their fittest clone shows that higher growth rates are associated with shorter time to MPN diagnosis (median 13.9 versus 26.4 months; P = 0.0026). AVAILABILITY AND IMPLEMENTATION: We developed a publicly available R package, cloneRate, to implement our methods (Package website: https://bdj34.github.io/cloneRate/). Source code: https://github.com/bdj34/cloneRate/.

Delays in the diagnosis and surgical treatment of drug-resistant epilepsy: A cohort study.

OBJECTIVE: Delay in referral for epilepsy surgery of patients with drug-resistant epilepsy (DRE) is associated with decreased quality of life, worse surgical outcomes, and increased risk of sudden unexplained death in epilepsy (SUDEP). Understanding the potential causes of delays in referral and treatment is crucial for optimizing the referral and treatment process. We evaluated the treatment intervals, demographics, and clinical characteristics of patients referred for surgical evaluation at our level 4 epilepsy center in the U.S. Intermountain West. METHODS: We retrospectively reviewed the records of patients who underwent surgery for DRE between 2012 and 2022. Data collected included patient demographics, DRE diagnosis date, clinical characteristics, insurance status, distance from epilepsy center, date of surgical evaluation, surgical procedure, and intervals between different stages of evaluation. RESULTS: Within our cohort of 185 patients with epilepsy (99 female, 53.5%), the mean ± standard deviation (SD) age at surgery was 38.4 ± 11.9 years. In this cohort, 95.7% of patients had received definitive epilepsy surgery (most frequently neuromodulation procedures) and 4.3% had participated in phase 2 intracranial monitoring but had not yet received definitive surgery. The median (1st-3rd quartile) intervals observed were 10.1 (3.8-21.5) years from epilepsy diagnosis to DRE diagnosis, 16.7 (6.5-28.4) years from epilepsy diagnosis to surgery, and 1.4 (0.6-4.0) years from DRE diagnosis to surgery. We observed significantly shorter median times from epilepsy diagnosis to DRE diagnosis (p < .01) and epilepsy diagnosis to surgery (p < .05) in patients who traveled further for treatment. Patients with public health insurance had a significantly longer time from DRE diagnosis to surgery (p < .001). SIGNIFICANCE: Both shorter distance traveled to our epilepsy center and public health insurance were predictive of delays in diagnosis and treatment intervals. Timely referral of patients with DRE to specialized epilepsy centers for surgery evaluation is crucial, and identifying key factors that may delay referral is paramount to optimizing surgical outcomes.

Releasing incompatible males drives strong suppression across populations of wild and Wolbachia-carrying Aedes aegypti in Australia.

Releasing sterile or incompatible male insects is a proven method of population management in agricultural systems with the potential to revolutionize mosquito control. Through a collaborative venture with the "Debug" Verily Life Sciences team, we assessed the incompatible insect technique (IIT) with the mosquito vector Aedes aegypti in northern Australia in a replicated treatment control field trial. Backcrossing a US strain of Ae. aegypti carrying Wolbachia wAlbB from Aedes albopictus with a local strain, we generated a wAlbB2-F4 strain incompatible with both the wild-type (no Wolbachia) and wMel-Wolbachia Ae. aegypti now extant in North Queensland. The wAlbB2-F4 strain was manually mass reared with males separated from females using Verily sex-sorting technologies to obtain no detectable female contamination in the field. With community consent, we delivered a total of three million IIT males into three isolated landscapes of over 200 houses each, releasing ∼50 males per house three times a week over 20 wk. Detecting initial overflooding ratios of between 5:1 and 10:1, strong population declines well beyond 80% were detected across all treatment landscapes when compared to controls. Monitoring through the following season to observe the ongoing effect saw one treatment landscape devoid of adult Ae. aegypti early in the season. A second landscape showed reduced adults, and the third recovered fully. These encouraging results in suppressing both wild-type and wMel-Ae. aegypti confirms the utility of bidirectional incompatibility in the field setting, show the IIT to be robust, and indicate that the removal of this arbovirus vector from human-occupied landscapes may be achievable.

The Asymmetry Within: A Renewed Look at Cupids Bow in Unilateral Cleft Lip.

The purpose of this study is to analyze the angular variations within Cupid's bow in patients with unoperated unilateral cleft lip (UCL). Angular features of Cupid's bow were quantified in standardized presurgical photographs of children with UCL by 5 medical professionals specializing in craniofacial anomalies. The peaks and valley of Cupid's bow were identified. A cleft side (CSA) and a noncleft side angle (NCSA) were delineated and measured by each expert. The data was pooled, and the angles were analyzed for symmetry. Cupid's bow asymmetry was defined as a difference between NCSA and CSA ≥3°. Of the 37 patients studied, 29 were found to have asymmetry of Cupid's bow with an average angle difference of 8.0° (95% CI: 6.6°-9.5°). Within this group,15 patients were found with acute asymmetry and 14 with obtuse asymmetry. Geometric analysis was performed on an example of a patient with acute asymmetry to demonstrate how correction of asymmetry can be considered during surgical repair. There is an asymmetry that exists in the Cupid's bow of a significant number of patients with unoperated UCL. This finding not only adds to our understanding of UCL but may also have important implications when selecting the method/technique of surgical repair.

Transformers for Remote Sensing: A Systematic Review and Analysis.

Research on transformers in remote sensing (RS), which started to increase after 2021, is facing the problem of a relative lack of review. To understand the trends of transformers in RS, we undertook a quantitative analysis of the major research on transformers over the past two years by dividing the application of transformers into eight domains: land use/land cover (LULC) classification, segmentation, fusion, change detection, object detection, object recognition, registration, and others. Quantitative results show that transformers achieve a higher accuracy in LULC classification and fusion, with more stable performance in segmentation and object detection. Combining the analysis results on LULC classification and segmentation, we have found that transformers need more parameters than convolutional neural networks (CNNs). Additionally, further research is also needed regarding inference speed to improve transformers' performance. It was determined that the most common application scenes for transformers in our database are urban, farmland, and water bodies. We also found that transformers are employed in the natural sciences such as agriculture and environmental protection rather than the humanities or economics. Finally, this work summarizes the analysis results of transformers in remote sensing obtained during the research process and provides a perspective on future directions of development.

Japanese Encephalitis Emergence in Australia: The Potential Population at Risk.

In Australia, Japanese encephalitis virus circulated in tropical north Queensland between 1995 and 2005. In 2022, a dramatic range expansion across the southern states has resulted in 30 confirmed human cases and 6 deaths. We discuss the outbreak drivers and estimate the potential size of the human population at risk.

Daily cannabis use may cause cannabis-induced hyperalgesia.

BACKGROUND AND OBJECTIVES: Public opinion about cannabis as a medical treatment is generally favorable. As many as 35% of primary care patients report medical use of cannabis, most commonly for pain treatment. We designed a way to test whether cannabis helps chronic pain. METHODS: A retrospective cohort study was conducted to explore whether daily long-term cannabis use was associated with increased pain sensitivity using the cold pressor test (CPT) to measure pain tolerance. Patients who used cannabis every day were compared to patients who inhaled tobacco and control patients who never used tobacco or cannabis. The effect of cannabis use on CPT was assessed using a generalized linear model. RESULTS: Patients using cannabis daily had a median CPT of 46 s, similar to those who did not use cannabis but who inhaled tobacco (median CPT 45 s). Patients who used both cannabis and tobacco had the lowest CPT (median 26 s). The control group had a median CPT of 105 s. Cannabis use was associated with a significantly decreased pain tolerance (χ²(1) = 8.0, p = .004). The effect of tobacco on CPT was only marginally significant (χ²(1) = 3.8, p = .052). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: This suggests a phenomenon similar to opioid-induced hyperalgesia; a drug that reduces pain short term, induces pain long term-opponent process. Daily cannabis use may make chronic pain worse over time by reducing pain tolerance. In terms of risk/benefit, daily cannabis users risk addiction without any long-term benefit for chronic pain.

A comparison of quantitative and qualitative shoulder range of motion with patient-reported outcomes.

BACKGROUND: The evaluation of shoulder function requires a combination of physical examination of shoulder range of motion and measures of functional outcome measures. Although efforts have been made to define range of motion for clinical evaluation with respect to functional outcomes, a disconnect still exists when defining a successful outcome. We aim to compare quantitative and qualitative measures of shoulder range of motion with patient-reported outcome measures. METHODS: Data from 100 patients who presented to the office of a single surgeon with a chief complaint of shoulder pain were evaluated for this study. Evaluation included American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form, Single Assessment Numeric Evaluation relative to the shoulder of interest, demographic information, and range of motion in the shoulder of interest. RESULTS: Internal rotation angle did not correlate with patient-reported outcomes, whereas external rotation and forward flexion angles did. Qualitative internal rotation as measured by hand-behind-back reach demonstrated a weak to moderate correlation with patient-reported outcomes, and a significant difference in global range of motion and functional outcome measures were identified in patients who can or cannot reach above the belt line or to the thoracic spine. Qualitative assessment of forward flexion demonstrated that patients who can reach specific anatomic landmarks have significantly improved functional outcome measures, and the same is true when comparing patients who can externally rotate past neutral. CONCLUSIONS: Hand-behind-back reach can be used as a clinical marker of global range of motion and functional outcome measures for patients with shoulder pain. Goniometer measurement of internal rotation has no relationship with patient-reported outcomes. Forward flexion and external rotation assessment with qualitative cutoffs can additionally be used clinically to determine functional outcome for patients with shoulder pain.

Clinical and radiological outcomes in lateralized versus nonlateralized and distalized glenospheres in reverse total shoulder arthroplasty: a randomized control trial.

BACKGROUND: Lateralization in reverse total shoulder arthroplasty (RTSA) has been used to theoretically offer the potential benefits of reduced scapular notching rates and improved stability and range of motion (ROM), particularly external rotation. The aim of this study was to compare ROM and clinical and radiographic outcomes between patients who underwent RTSA with a lateralized vs. a nonlateralized and distalized glenosphere. METHODS: A single-surgeon randomized control trial was conducted comparing 27 patients with a lateralized glenosphere and 26 patients with a nonlateralized and distalized glenosphere. A total of 66 patients were enrolled, 2 patients died before 2-year follow-up, 4 patients withdrew from the study, and 7 patients were lost to follow-up. All patients in the lateralized group received 6 mm of lateralization through the glenosphere. Participants represented a population presenting to an orthopedics sports medicine clinic with any indication for RTSA including revision arthroplasty. Patients completed preoperative and routine postoperative functional outcome measures 3, 6, 12, and a minimum of 24 months postoperatively, including American Shoulder and Elbow Surgeons, Patient-Reported Outcomes Measurement Information System Physical Function Upper Extremity, and Activities of Daily Living Requiring Active External and Internal Rotation assessments. Patients were also evaluated with ROM and radiographic measurements. The primary outcome of interest in this study was ROM, particularly external rotation. RESULTS: At 2-year follow-up, both groups had significant improvement in their American Shoulder and Elbow Surgeons, Patient-Reported Outcomes Measurement Information System Physical Function Upper Extremity, and Activities of Daily Living Requiring Active External and Internal Rotation scores with no significant difference observed between the groups. There were no statistically significant differences in incidence of scapular notching or acromial stress fractures. ROM in both groups improved significantly at their 2-year assessment with the only exception to this being external rotation at 90° of abduction in the nonlateralized and distalized group (39° ± 31° vs. 48° ± 24°, P = .379). CONCLUSIONS: Regardless of glenosphere lateralization status, patients in both groups had significant improvement in functional outcome scores and ROM, and there were no significant differences observed between the groups at 2-year follow-up. Longer follow-up is needed to determine the effect of implant design on late complications, long-term outcomes, and implant retention.

Contributions of climate change and human activities to grassland degradation and improvement from 2001 to 2020 in Zhaosu County, China.

Grassland degradation poses a serious threat to biodiversity, ecosystem services, and human well-being. In this study, we investigated grassland degradation in Zhaosu County, China, between 2001 and 2020, and analyzed the impacts of climate change and human activities using the Miami model. The actual net primary productivity (ANPP) obtained with CASA (Carnegie-Ames-Stanford Approach) modeling, showed a decreasing trend, reflecting the significant degradation that the grasslands in Zhaosu County have experienced in the past 20 years. Grassland degradation was found to be highest in 2018, while the degraded area continuously decreased in the last 3 years (2018-2020). Climatic factors for found to be the dominant factor affecting grassland degradation, particularly the decrease in precipitation. On the other hand, human activities were found to be the main factor affecting improvement of grasslands, especially in recent years. This finding profoundly elucidates the underlying causes of grassland degradation and improvement and helps implement ecological conservation and restoration measures. From a practical perspective, the research results provide an important reference for the formulation of policies and management strategies for sustainable land use.

Exploring Indigenous and Local Knowledge and Practices (ILKPs) in Traditional Jhum Cultivation for Localizing Sustainable Development Goals (SDGs): A Case Study from Zunheboto District of Nagaland, India.

Globally, shifting cultivation is known to be an important driver of tropical deforestation. However, in this paper, we argue that it can be sustainably managed if the environmental boundary conditions, laid by the traditional customs and practices, are fully respected. We narrate an empirical study from the Zunheboto district of Nagaland, India, where we deployed a mixed research method to explore the Indigenous and Local Knowledge and Practices (ILKPs) associated with shifting cultivation (aka Jhum), particularly concerning farm-level practices, forest and biodiversity conservation, and disaster risk reduction measures. The research method included analysis of primary data obtained through Focus Group discussions (FGDs), key informant interviews (n = 21), and a questionnaire survey (n = 153) with Jhum farmers from two different age groups, i.e., below 50 years (middle-aged farmers) and above 50 years (older farmers). From the qualitative inquiry, we identified 15 ILKPs, which were then validated from survey responses. We used the Mann-Whitney U test to examine differences in agreement between two groups of framers. Based on this analysis, we conclude that upholding of the ILKPs holds strong potential for the local implementation of several Sustainable Development Goals (SDGs), particularly, SDG-1(No poverty), SDG-2 (Zero hunger), and SDG-15 (Life on land). However, eight of the identified ILKPs showed a statistically significant difference between older and middle-aged farmers, underlining a declining trend. Finally, we suggest suitable policy measures to mainstream ILKPs to balance the trade-offs in food production and biodiversity conservation, and to ensure the future sustainability of Jhum cultivation in the region and beyond.

Spatial-temporal pattern of change in production-living-ecological space of Nanchong City from 2000 to 2020 and underlying factors.

This study analyzed the spatial-temporal change pattern and underlying factors in production-living-ecological space (PLES) of Nanchong City, China, over the past 20 years using historical land use data (2000, 2010, 2020). A land use transfer matrix was calculated from the historical land use maps, and spatial analysis was conducted to analyze changes in the land use dynamics degree, standard deviation ellipse, and center of gravity. The results showed that there was a rapid spatial evolution of the PLES in Nanchong from 2000 to 2010, followed by a stabilization in the second decade. The transfer of ecological-production space occurred mainly in the Jialing and Yilong River basins, while the reduction of production space and the increase of living space were most prominent in the intersection of three districts (Shunqing, Jialing, and Gaoping districts). The return of production-ecological space was observed in the south and northeast of Yingshan, and there was little notable transfer of other types. The distribution of production space in Nanchong evolved in a north-south to east-west trend, with the center of gravity moving from Yilong to Peng'an County. The living space and production space expanded in a north-south direction, and the center of gravity position was in Nanbu, indicating a more balanced growth or decrease in the last 20 years. The changes in the spatial-temporal pattern of PLES in Nanchong were attributed to the intertwined factors of national policies, economic development, population growth, and the natural environment. This study introduced a novel approach towards rational planning of land resources in Nanchong, which may facilitate more sustainable urban planning and development.

Fresh tissue procurement and preparation for multicompartment and multimodal analysis of the prostate tumor microenvironment.

BACKGROUND: Prostatic cancers include a diverse microenvironment of tumor cells, cancer-associated fibroblasts, and immune components. This tumor microenvironment (TME) is a known driving force of tumor survival after treatment, but the standard-of-care tissue freezing or fixation in pathology practice limit the use of available approaches/tools to study the TME's functionality in tumor resistance. Thus, there is a need for approaches that satisfy both clinical and laboratory endpoints for TME study. Here we present methods for clinical case identification, tissue processing, and analytical workflow that are compatible with standard histopathology while enabling molecular and functional interrogation of prostate TME components. METHODS: We first performed a small retrospective review to identify cases where submission of alternate prostate tissue slices and a parallel live tissue processing protocol complement traditional histopathology and enable viable multicompartment analysis of the TME. Then, we tested its compatibility with commonly employed methods to study the microenvironment including quantification of components both in situ and after tissue dissociation. We also evaluated tissue digestion conditions and cell isolation techniques to aid various molecular and functional endpoints. RESULTS: We identified Gleason Grade Group 3+ clinical cases where tumor volume was sufficient to allow slicing of unfixed tissue and distribution of alternating tissue slices to standard-of-care histopathology and viable multi-modal TME analyses. No single method was found that preserved cellular sub-types for all downstream readouts; instead, tissues were further divided so techniques could be catered to each endpoint. For instance, we show that incorporating the protease dispase into tissue dissociation improves viability for culture and functional analyses but hinders immune cell analysis by flow cytometry. We also found that flow activated cell sorting provides highly pure cell populations for quantitative reverse-transcription polymerase chain reaction and RNA-seq while isolation using antibody-labeled paramagnetic particles facilitated functional coculture experiments. CONCLUSIONS: The identification of candidate cases and use of these techniques enable translational research and the development of molecular and functional assays to facilitate prostate TME study without compromising standard-of-care histopathological diagnosis. This allows bridging clinical histopathology and further interrogation of the prostate TME and promises to advance our understanding of tumor biology and unveil new predictive and prognostic markers of prostate cancer progression.

Comparison of multicenter MRI protocols for visualizing the spinal cord gray matter.

PURPOSE: Spinal cord gray-matter imaging is valuable for a number of applications, but remains challenging. The purpose of this work was to compare various MRI protocols at 1.5 T, 3 T, and 7 T for visualizing the gray matter. METHODS: In vivo data of the cervical spinal cord were collected from nine different imaging centers. Data processing consisted of automatically segmenting the spinal cord and its gray matter and co-registering back-to-back scans. We computed the SNR using two methods (SNR_single using a single scan and SNR_diff using the difference between back-to-back scans) and the white/gray matter contrast-to-noise ratio per unit time. Synthetic phantom data were generated to evaluate the metrics performance. Experienced radiologists qualitatively scored the images. We ran the same processing on an open-access multicenter data set of the spinal cord MRI (N = 267 participants). RESULTS: Qualitative assessments indicated comparable image quality for 3T and 7T scans. Spatial resolution was higher at higher field strength, and image quality at 1.5 T was found to be moderate to low. The proposed quantitative metrics were found to be robust to underlying changes to the SNR and contrast; however, the SNR_single method lacked accuracy when there were excessive partial-volume effects. CONCLUSION: We propose quality assessment criteria and metrics for gray-matter visualization and apply them to different protocols. The proposed criteria and metrics, the analyzed protocols, and our open-source code can serve as a benchmark for future optimization of spinal cord gray-matter imaging protocols.

Patterns of antimicrobial, multidrug and methicillin resistance among Staphylococcus spp. isolated from canine specimens submitted to a diagnostic laboratory in Tennessee, USA: a descriptive study.

BACKGROUND: Multidrug- and methicillin-resistant staphylococci are both veterinary and public health concerns due to their zoonotic potential. Therefore, the objective of this study was to investigate patterns of antimicrobial, multidrug, and methicillin resistance among four Staphylococcus spp. commonly isolated from canine clinical specimens submitted to the Clinical Bacteriology Laboratory at the University of Tennessee College of Veterinary Medicine (UTCVM). METHODS: Results of antimicrobial susceptibility testing and mecA polymerase chain reaction (PCR) for isolates of four common Staphylococcus spp. isolates were obtained from the Bacteriology Laboratory at the UTCVM between 01/01/2006 and 12/31/2017. Cochran-Armitage trend test was used to assess temporal trends of antimicrobial resistance (AMR), multidrug resistance (MDR), and methicillin resistance. Kappa test of agreement was used to assess agreement between the results of PCR and disk diffusion tests. RESULTS: Most of the 7805 isolates were S. pseudintermedius (6453 isolates), followed by S. coagulans (860), S. aureus (330), and S. schleiferi (162). Among S. pseudintermedius isolates, 45.5% were MDR, and 30.8% were methicillin-resistant (MRSP). There was a significant temporal increase in MRSP (p = 0.017). Chloramphenicol resistance increased among both MRSP and methicillin-susceptible (MSSP) isolates (p <  0.0001). Among S. aureus isolates, 40.9% were MDR, 37.4% were methicillin-resistant (MRSA), and the proportion of MRSA isolates increased significantly (p = 0.0480) over time. There was an increasing temporal trend in the proportion of MDR isolates among MSSP (p = 0.0022), but a decrease among MRSP (p <  0.0001) and MRSA (p = 0.0298). S. schleiferi had the highest percentage (56.9%) of methicillin-resistant isolates. Oxacillin disk diffusion was superior to cefoxitin for the detection of mecA-mediated resistance and had almost perfect agreement with mecA PCR assay for S. pseudintermedius (95.4% agreement, kappa (κ) = 0.904; p <  0.0001), S. coagulans (95.6%, κ = 0.913; p <  0.0001) and S. schleiferi (97.7%, κ = 0.945; p <  0.0001). However, cefoxitin disk diffusion was superior to oxacillin disk diffusion and had almost perfect agreement with mecA PCR assay for S. aureus (95.3%, κ = 0.834; p <  0.0001). CONCLUSIONS: The levels of resistance and increasing temporal trends are concerning. These findings have implications for treatment decisions and public health due to the zoonotic potential of staphylococci. Continued surveillance and use of antibiograms to guide clinical decisions will be critical.

The clinical course of comorbid substance use disorder and attention deficit/hyperactivity disorder: protocol and clinical characteristics of the INCAS study.

BACKGROUND: Substance use disorders (SUD) often co-occur with attention deficit hyperactivity disorder (ADHD). Although the short-term effects of some specific interventions have been investigated in randomized clinical trials, little is known about the long-term clinical course of treatment-seeking SUD patients with comorbid ADHD. AIMS: This paper presents the protocol and baseline clinical characteristics of the International Naturalistic Cohort Study of ADHD and SUD (INCAS) designed and conducted by the International Collaboration on ADHD and Substance Abuse (ICASA) foundation. The overall aim of INCAS is to investigate the treatment modalities provided to treatment-seeking SUD patients with comorbid ADHD, and to describe the clinical course and identify predictors for treatment outcomes. This ongoing study employs a multicentre observational prospective cohort design. Treatment-seeking adult SUD patients with comorbid ADHD are recruited, at 12 study sites in nine different countries. During the follow-up period of nine months, data is collected through patient files, interviews, and self-rating scales, targeting a broad range of cognitive and clinical symptom domains, at baseline, four weeks, three months and nine months. RESULTS: A clinically representative sample of 578 patients (137 females, 441 males) was enrolled during the recruitment period (June 2017-May 2021). At baseline, the sample had a mean age (SD) of 36.7 years (11.0); 47.5% were inpatients and 52.5% outpatients; The most prevalent SUDs were with alcohol 54.2%, stimulants 43.6%, cannabis 33.1%, and opioids 14.5%. Patients reported previous treatments for SUD in 71.1% and for ADHD in 56.9%. Other comorbid mental disorders were present in 61.4% of the sample: major depression 31.5%, post-traumatic stress disorder 12.1%, borderline personality disorder 10.2%. CONCLUSIONS: The first baseline results of this international cohort study speak to its feasibility. Data show that many SUD patients with comorbid ADHD had never received treatment for their ADHD prior to enrolment in the study. Future reports on this study will identify the course and potential predictors for successful pharmaceutical and psychological treatment outcomes. TRIAL REGISTRATION: ISRCTN15998989 20/12/2019.

Hyperspectral response of agronomic variables to background optical variability: Results of a numerical experiment.

Understanding how biophysical and biochemical variables contribute to the spectral characteristics of vegetation canopies is critical for their monitoring. Quantifying these contributions, however, remains difficult due to extraneous factors such as the spectral variability of canopy background materials, including soil/crop-residue moisture, soil-type, and non-photosynthetic vegetation (NPV). This study focused on exploring the spectral response of two important agronomic variables (1) leaf chlorophyll content (Cab ) and (2) leaf area index (LAI) under various canopy backgrounds through a global sensitivity analysis of wheat-like canopy spectra simulated using the physically-based PROSAIL radiative transfer model. Our results reveal the following general findings: (1) the contribution of each agronomic variable to the simulated canopy spectral signature varies considerably with respect to the background optical properties; (2) the influence of the soil-type and NPV on the spectral response of canopy to Cab and LAI is more significant than that caused by soil/crop-residue moisture; (3) spectral bands at 560 and 704 nm remain sensitive to Cab while being least affected by the impacts of variations in the NPV, soil-type and moisture; (4) the near-infrared (NIR) spectral bands exhibit higher sensitivity to LAI and lower background effects only in the cases of soil/crop-residue moisture but are relatively strongly affected by soil-type and NPV. Comparative analysis of the correlations of twelve widely used vegetation indices with agronomic variables indicates that LICI (LAI-insensitive chlorophyll index) and Macc01 (Maccioni index) are more effective in estimating Cab , while OSAVI (optimized soil adjusted vegetation index) and MCARI2 (modified chlorophyll absorption ratio index 2) are better LAI predictors under the simulated background variability. Overall, our results highlight that background reflectance variability introduces considerable differences in the agronomic variables' spectral response, leading to inconsistencies in the VI- Cab /-LAI relationship. Further studies should integrate these results of spectral responsivity to develop trait-specific hyperspectral inversion models.

Beliefs affecting concussion reporting among military cadets: advanced observations through machine learning.

BACKGROUND: Untreated concussions are an important health concern. The number of concussions sustained each year is difficult to pinpoint due to diverse reporting routes and many people not reporting. A growing body of literature investigates the motivations for concussion under-reporting, proposing ties with knowledge of concussion outcomes and concussion culture. The present work employs machine learning to identify trends in knowledge and willingness to self-report concussions. METHODS: 2,204 cadets completed a survey addressing athletic and pilot status, concussion symptoms and outcome beliefs, ethical beliefs, demographics, and reporting willingness. RESULTS: Clustering and non-negative matrix analysis identified connections to self-report willingness within: knowledge of symptoms, ethical beliefs, reporting requirements, and belief of long-term concussion outcomes. Support vector machine classification of cadet reporting likelihood reveals symptom and outcome knowledge may be inversely related to reporting among those rating ethics considerations as low, while heightened ethics may predict higher reporting likeliness overall. CONCLUSIONS: Machine-learning analysis bolsters prior theories on the importance of concussion culture in reporting and indicate more symptom knowledge may decrease willingness to report. Uniquely, our analysis indicated importance of ethical behavior may be associated with general concussion reporting willingness, inviting further consideration from healthcare practitioners seeking increased reporting.

Concussion reporting intentions for incoming military athletes and cadets.

Cultures of concussion reporting exist outside athletics; however, athlete-only studies dominate the literature. Comparing athletes and similar high-risk populations broadens our understanding of concussion reporting acculturation. We aimed to (1) describe and compare concussion self-report willingness as measured by anticipated concussion reporting (ACR), perceived costs, perceived rewards, brain health knowledge, and correct symptom identification for incoming cadets at the United States Air Force Academy (USAFA) (n = 1,136; female = 276, 24.43%) and (2) determine whether those variables predict ACR. Univariate analyses were performed to compare intercollegiate status, sex, and parental income for perceived costs and rewards, and brain health knowledge (α = 0.05) and multinomial logistic regressions to determine if those variables predicted ACR. A $40,000 parental increase in income resulted in one additional symptom identified (ß = 0.80, p = 0.026). Athletes demonstrated greater brain health knowledge by nearly one symptom correctly identified (ß = 0.98, p = 0.002); non-athletes reported significantly greater ACR (ß = 5.92; p < 0.001). Our model accounted for 37% of the variance in ACR (χ2 = 393.86, p < 0.001, Nagelkerke R2 = 0.37). Before military acculturation, athletes had less intention to seek medical care for concussion, likely from prior athletic experiences.

Land-Use and Land-Cover Classification in Semi-Arid Areas from Medium-Resolution Remote-Sensing Imagery: A Deep Learning Approach.

Detailed Land-Use and Land-Cover (LULC) information is of pivotal importance in, e.g., urban/rural planning, disaster management, and climate change adaptation. Recently, Deep Learning (DL) has emerged as a paradigm shift for LULC classification. To date, little research has focused on using DL methods for LULC mapping in semi-arid regions, and none that we are aware of have compared the use of different Sentinel-2 image band combinations for mapping LULC in semi-arid landscapes with deep Convolutional Neural Network (CNN) models. Sentinel-2 multispectral image bands have varying spatial resolutions, and there is often high spectral similarity of different LULC features in semi-arid regions; therefore, selection of suitable Sentinel-2 bands could be an important factor for LULC mapping in these areas. Our study contributes to the remote sensing literature by testing different Sentinel-2 bands, as well as the transferability of well-optimized CNNs, for semi-arid LULC classification in semi-arid regions. We first trained a CNN model in one semi-arid study site (Gujranwala city, Gujranwala Saddar and Wazirabadtownships, Pakistan), and then applied the pre-trained model to map LULC in two additional semi-arid study sites (Lahore and Faisalabad city, Pakistan). Two different composite images were compared: (i) a four-band composite with 10 m spatial resolution image bands (Near-Infrared (NIR), green, blue, and red bands), and (ii) a ten-band composite made by adding two Short Wave Infrared (SWIR) bands and four vegetation red-edge bands to the four-band composite. Experimental results corroborate the validity of the proposed CNN architecture. Notably, the four-band CNN model has shown robustness in semi-arid regions, where spatially and spectrally confusing land-covers are present.