Novel applications of Convolutional Neural Networks in the age of Transformers.

Convolutional Neural Networks (CNNs) have been central to the Deep Learning revolution and played a key role in initiating the new age of Artificial Intelligence. However, in recent years newer architectures such as Transformers have dominated both research and practical applications. While CNNs still play critical roles in many of the newer developments such as Generative AI, they are far from being thoroughly understood and utilised to their full potential. Here we show that CNNs can recognise patterns in images with scattered pixels and can be used to analyse complex datasets by transforming them into pseudo images with minimal processing for any high dimensional dataset, representing a more general approach to the application of CNNs to datasets such as in molecular biology, text, and speech. We introduce a pipeline called DeepMapper, which allows analysis of very high dimensional datasets without intermediate filtering and dimension reduction, thus preserving the full texture of the data, enabling detection of small variations normally deemed 'noise'. We demonstrate that DeepMapper can identify very small perturbations in large datasets with mostly random variables, and that it is superior in speed and on par in accuracy to prior work in processing large datasets with large numbers of features.

Policy and market forces delay real estate price declines on the US coast.

Despite increasing risks from sea-level rise (SLR) and storms, US coastal communities continue to attract relatively high-income residents, and coastal property values continue to rise. To understand this seeming paradox and explore policy responses, we develop the Coastal Home Ownership Model (C-HOM) and analyze the long-term evolution of coastal real estate markets. C-HOM incorporates changing physical attributes of the coast, economic values of these attributes, and dynamic risks associated with storms and flooding. Resident owners, renters, and non-resident investors jointly determine coastal property values and the policy choices that influence the physical evolution of the coast. In the coupled system, we find that subsidies for coastal management, such as beach nourishment, tax advantages for high-income property owners, and stable or increasing property values outside the coastal zone all dampen the effects of SLR on coastal property values. The effects, however, are temporary and only delay precipitous declines as total inundation approaches. By removing subsidies, prices would more accurately reflect risks from SLR but also trigger more coastal gentrification, as relatively high-income owners enter the market and self-finance nourishment. Our results suggest a policy tradeoff between slowing demographic transitions in coastal communities and allowing property markets to adjust smoothly to risks from climate change.

The equivalence of psychodynamic therapy and cognitive behavioral therapy for depressive disorders in adults: A meta-analytic review.

BACKGROUND: Meta-analyses on the relative efficacy of psychodynamic psychotherapy (PDT) and cognitive behavioral therapy (CBT) for depressive disorders are limited by heterogeneity in diagnostic samples and comparators and a lack of equivalence testing. OBJECTIVE: We addressed this through a meta-analytic test of the equivalence of manualized PDT and CBT in treating adults with depressive disorders as determined by diagnostic interviews. Sensitivity analyses evaluated the impact of pretreatment differences, mixed diagnostic samples, author allegiance, study quality, year of publication and outliers on findings. METHOD: A comprehensive literature search across multiple databases using reliable screening methods identified nine randomized controlled trials directly comparing manualized PDT and CBT for diagnosed depressive disorders in adults. Following pre-registration, we employed random effect models for our meta-analyses and two one-sided test procedures for equivalence testing. RESULTS: Independent raters determined that all studies were of adequate quality. Immediately posttreatment, depressive symptoms were statistically equivalent across PDT and CBT (k = 9; g = -0.11, 90% confidence interval [90% CI]: -0.24 to 0.02, pequivalence = .048, pNHST = .212, I2 = 32.7). At follow-up, the longest time point within a year, depressive symptoms were neither statistically equivalent nor statistically different (k = 6; g = -0.16, 90% CI: -0.31 to -0.02, pequivalence = .184, pNHST = .126, I2 = 0.00). CONCLUSION: The efficacy of manualized PDT is equal to manualized CBT immediately at posttreatment for depressive disorders in the adult general population. Nevertheless, insufficient data exists to reach a conclusion regarding equivalence at follow-up.

Toward a coordinated understanding of hydro-biogeochemical root functions in tropical forests for application in vegetation models.

Tropical forest root characteristics and resource acquisition strategies are underrepresented in vegetation and global models, hampering the prediction of forest-climate feedbacks for these carbon-rich ecosystems. Lowland tropical forests often have globally unique combinations of high taxonomic and functional biodiversity, rainfall seasonality, and strongly weathered infertile soils, giving rise to distinct patterns in root traits and functions compared with higher latitude ecosystems. We provide a roadmap for integrating recent advances in our understanding of tropical forest belowground function into vegetation models, focusing on water and nutrient acquisition. We offer comparisons of recent advances in empirical and model understanding of root characteristics that represent important functional processes in tropical forests. We focus on: (1) fine-root strategies for soil resource exploration, (2) coupling and trade-offs in fine-root water vs nutrient acquisition, and (3) aboveground-belowground linkages in plant resource acquisition and use. We suggest avenues for representing these extremely diverse plant communities in computationally manageable and ecologically meaningful groups in models for linked aboveground-belowground hydro-nutrient functions. Tropical forests are undergoing warming, shifting rainfall regimes, and exacerbation of soil nutrient scarcity caused by elevated atmospheric CO2. The accurate model representation of tropical forest functions is crucial for understanding the interactions of this biome with the climate.

Las características de las raíces de los bosques tropicales y las estrategias de adquisición de recursos están subrepresentadas en modelos de vegetación, lo que dificulta la predicción del efecto de cambio de clima para estos ecosistemas ricos en carbono. Los bosques tropicales a menudo tienen combinaciones únicas a nivel mundial de alta biodiversidad taxonómica y funcional, estacionalidad de precipitación, y suelos infértiles, dando lugar a patrones distintos en los rasgos y funciones de las raíces en comparación con los ecosistemas de latitudes más altas. Integramos los avances recientes en nuestra comprensión de la función subterránea de los bosques tropicales en modelos de vegetación, centrándonos en la adquisición de agua y nutrientes. Ofrecemos comparaciones de avances recientes en la comprensión empírica y de modelos de las características de las raíces que representan procesos funcionales importantes en los bosques tropicales. Nos centramos en: (1) estrategias de raíces finas para adquisición de recursos del suelo, (2) acoplamiento y compensaciones entre adquisición del agua y de nutrientes, y (3) vínculos entre funciones sobre tierra y debajo del superficie en bosques tropicales. Sugerimos vías para representar estas comunidades de plantas extremadamente diversas en grupos computacionalmente manejables y ecológicamente significativos en modelos. Los bosques tropicales se están calentando, tienen cambios en los regímenes de lluvias, y tienen una exacerbación de la escasez de nutrientes del suelo causada por el elevado CO2 atmosférico. La representación precisa de las funciones de los bosques tropicales en modelos es crucial para comprender las interacciones de este bioma con el clima.

A comparison of the effect of two types of brief psychodynamic group therapy on perfectionism-related attitudes, self-relatedness, and self-esteem.

Objective: This randomized controlled trial investigated the efficacy of dynamic relational group therapy (DRT) relative to group psychodynamic supportive therapy (PST) in improving perfectionism-related attitudes and components of the perfectionistic self-relationship. Method: Based on a comprehensive conceptualization of perfectionism, 80 community-recruited, highly perfectionistic individuals were randomly allocated to 12 sessions of group DRT (n = 41; 5 groups) or group PST (n = 39; 5 groups). Patients completed measures of dysfunctional attitudes, self-criticism, self-esteem, and self-reassurance at pre-, mid-, and post-treatment, and six months post-treatment. Results: Multigroup latent growth curve modeling revealed significant (p < .05) decreases in dysfunctional attitudes, concern over mistakes, two types of self-criticism, and self-esteem problems, along with a significant increase in self-reassurance, from pre-treatment to six-month follow-up in both DRT and PST. Moderate-to-large between-group differences favoring DRT over PST were found for dysfunctional attitudes and self-reassurance. A majority of patients in both conditions maintained reliable improvement at six-month follow-up in dysfunctional attitudes, concern over mistakes, and self-criticism focused on inadequacy. Conclusion: Findings provide evidence for the use of psychodynamic group therapy approaches in treating perfectionism-related attitudes and self-relational elements of perfectionism, and support the relative efficacy of DRT for dysfunctional attitudes and self-reassurance.

Automatic Self Recriminations: Development and Validation of a Measure of Self-Condemnatory Internal Dialogue.

This article introduces a measure of self-condemnatory internal dialogue as an element of the relationship with the self: The Automatic Self-Recrimination Scale (ASRS). Using the construct validation approach to test construction, we describe the initial development of items and report on findings from a clinical and nonclinical sample showing the ASRS is best understood as a multidimensional measure of self-critical internal dialogue composed of one higher-order factor and four lower-order facets: Not Mattering, Self as Failure, Undeserving Self, and Loathsomeness. The overall scale and four subscales demonstrated acceptable internal consistency and test-retest reliability. Moreover, there was evidence of good convergent and incremental validity of the ASRS subscales with measures of perfectionism, self-criticism, and dysfunctional attitudes. Overall, the ASRS appears to be a reliable and valid measure of an automatic self-recriminatory internal dialogue.

The influence of carbon dioxide on cerebral metabolism and oxygen consumption: combining multimodal monitoring with dynamic systems modelling.

Hypercapnia increases cerebral blood flow. The effects on cerebral metabolism remain incompletely understood although studies show an oxidation of cytochrome c oxidase, Complex IV of the mitochondrial respiratory chain. Systems modelling was combined with previously published non-invasive measurements of cerebral tissue oxygenation, cerebral blood flow, and cytochrome c oxidase redox state to evaluate any metabolic effects of hypercapnia. Cerebral tissue oxygen saturation and cytochrome oxidase redox state were measured with broadband near infrared spectroscopy and cerebral blood flow velocity with transcranial Doppler ultrasound. Data collected during 5-min hypercapnia in awake human volunteers were analysed using a Fick model to determine changes in brain oxygen consumption and a mathematical model of cerebral hemodynamics and metabolism (BrainSignals) to inform on mechanisms. Either a decrease in metabolic substrate supply or an increase in metabolic demand modelled the cytochrome oxidation in hypercapnia. However, only the decrease in substrate supply explained both the enzyme redox state changes and the Fick-calculated drop in brain oxygen consumption. These modelled outputs are consistent with previous reports of CO2 inhibition of mitochondrial succinate dehydrogenase and isocitrate dehydrogenase. Hypercapnia may have physiologically significant effects suppressing oxidative metabolism in humans and perturbing mitochondrial signalling pathways in health and disease.

Lumbar Bone Stress Injuries and Nonunited Defects in Elite Australian Cricket Players.

OBJECTIVE: To describe the presentation and management of lumbar bone stress injuries (LBSI), recurrent LBSI, and lumbar nonunited defects in elite Australian male and female cricket players. DESIGN: Retrospective case series. SETTING: Professional domestic and international cricket teams over 13 seasons. PARTICIPANTS: Elite Australian cricket players. INDEPENDENT VARIABLES: Symptomatic LBSI requiring time off cricket and lumbar nonunited defects, both confirmed by imaging. MAIN OUTCOME MEASURES: Incidence, presentation, history, healing, and management. RESULTS: 211 LBSI were identified at an average incidence of 5.4 per 100 players per season. LBSI were most common in male pace bowlers younger than 20 years of age (58.1 per 100 players per season), however, were also observed in older players, females, and non-pace bowlers. Recurrent LBSI accounted for 33% (27%-40%) of all LBSI. Median days to return to match availability was 182 (128-251) days for all LBSI, with a shorter time frame observed for new and less severe injuries, and male spin bowlers. Healing was demonstrated in 87% (81%-91%) of all LBSI cases. 29 nonunited defects were identified and predisposed subsequent pain, LBSI, and spondylolisthesis. CONCLUSIONS: LBSI are experienced by approximately 5.4 in every 100 elite Australian cricket players per season, with a high time cost of approximately 4 to 8 months. Nonunited defects also have a high time cost with associated subsequent lumbar spine issues. The findings of this study reinforce the importance of early detection and conservative management of LBSI, particularly for younger male pace bowlers and players with recurrent LBSI, which may be supported by MRI.

Topical ivermectin 1.0% cream in the treatment of ocular demodicosis.

PURPOSE: Ocular demodicosis can cause debilitating ocular surface disease. As ivermectin is effective at reducing Demodex proliferation in rosacea, this study investigated the efficacy of topical ivermectin 1.0% cream in treating ocular demodicosis. METHODS: This retrospective single-centre clinical practice chart analysis involved the off-label treatment of patients who had ocular demodicosis with topical ivermectin 1.0 % cream (Soolantra, Galderma Ltd, UK) applied nightly to the lid margins of both eyes for 3 months. Ocular surface health was assessed at baseline when the treatment was prescribed and followed up at 3 and 12 months after baseline. Slit lamp biomicroscopy was used to take digital images of the upper eyelid lashes. Manual image analysis with ImageJ was conducted by a masked assessor to quantify signs of ocular demodicosis including the number of lashes with collarettes, with visible Demodex tails and with follicle pouting. RESULTS: Data from a total of 75 patients with ocular demodicosis were analysed for this study (mean age 66.6 ± 13.9 years, 44 female). The numbers of lashes with collarettes (Median [Interquartile range]: 8 [4-13] at baseline to 0 [0-2] at the final visit, p < 0.001) and lashes with follicle pouting (3 [1-5] at baseline to 0 [0-1.8] at the final visit, p < 0.001) decreased with treatment. Any sign of lashes with visible tails was eliminated by the final visit (p < 0.007). Fluorescein staining severity score also improved, particularly from baseline (1 [0-2]) to the second visit (0 [0-1], p < 0.001). CONCLUSIONS: The findings of this study show evidence for the efficacy of a 3-month course of topical ivermectin 1.0% cream in treating ocular demodicosis as indicated by reduction in collarettes, follicle pouting and visible Demodex tails. More research is warranted to improve the diagnosis, management and monitoring of this condition which is often overlooked or misdiagnosed.

CBFA2T3::GLIS2 pediatric acute megakaryoblastic leukemia is sensitive to BCL-XL inhibition by navitoclax and DT2216.

ABSTRACT: Acute megakaryoblastic leukemia (AMKL) is a rare, developmentally restricted, and highly lethal cancer of early childhood. The paucity and hypocellularity (due to myelofibrosis) of primary patient samples hamper the discovery of cell- and genotype-specific treatments. AMKL is driven by mutually exclusive chimeric fusion oncogenes in two-thirds of the cases, with CBFA2T3::GLIS2 (CG2) and NUP98 fusions (NUP98r) representing the highest-fatality subgroups. We established CD34+ cord blood-derived CG2 models (n = 6) that sustain serial transplantation and recapitulate human leukemia regarding immunophenotype, leukemia-initiating cell frequencies, comutational landscape, and gene expression signature, with distinct upregulation of the prosurvival factor B-cell lymphoma 2 (BCL2). Cell membrane proteomic analyses highlighted CG2 surface markers preferentially expressed on leukemic cells compared with CD34+ cells (eg, NCAM1 and CD151). AMKL differentiation block in the mega-erythroid progenitor space was confirmed by single-cell profiling. Although CG2 cells were rather resistant to BCL2 genetic knockdown or selective pharmacological inhibition with venetoclax, they were vulnerable to strategies that target the megakaryocytic prosurvival factor BCL-XL (BCL2L1), including in vitro and in vivo treatment with BCL2/BCL-XL/BCL-W inhibitor navitoclax and DT2216, a selective BCL-XL proteolysis-targeting chimera degrader developed to limit thrombocytopenia in patients. NUP98r AMKL were also sensitive to BCL-XL inhibition but not the NUP98r monocytic leukemia, pointing to a lineage-specific dependency. Navitoclax or DT2216 treatment in combination with low-dose cytarabine further reduced leukemic burden in mice. This work extends the cellular and molecular diversity set of human AMKL models and uncovers BCL-XL as a therapeutic vulnerability in CG2 and NUP98r AMKL.

Unraveling complex causal processes that affect sustainability requires more integration between empirical and modeling approaches.

Scientists seek to understand the causal processes that generate sustainability problems and determine effective solutions. Yet, causal inquiry in nature-society systems is hampered by conceptual and methodological challenges that arise from nature-society interdependencies and the complex dynamics they create. Here, we demonstrate how sustainability scientists can address these challenges and make more robust causal claims through better integration between empirical analyses and process- or agent-based modeling. To illustrate how these different epistemological traditions can be integrated, we present four studies of air pollution regulation, natural resource management, and the spread of COVID-19. The studies show how integration can improve empirical estimates of causal effects, inform future research designs and data collection, enhance understanding of the complex dynamics that underlie observed temporal patterns, and elucidate causal mechanisms and the contexts in which they operate. These advances in causal understanding can help sustainability scientists develop better theories of phenomena where social and ecological processes are dynamically intertwined and prior causal knowledge and data are limited. The improved causal understanding also enhances governance by helping scientists and practitioners choose among potential interventions, decide when and how the timing of an intervention matters, and anticipate unexpected outcomes. Methodological integration, however, requires skills and efforts of all involved to learn how members of the respective other tradition think and analyze nature-society systems.

Hydraulic variability of tropical forests is largely independent of water availability.

Tropical rainforest woody plants have been thought to have uniformly low resistance to hydraulic failure and to function near the edge of their hydraulic safety margin (HSM), making these ecosystems vulnerable to drought; however, this may not be the case. Using data collected at 30 tropical forest sites for three key traits associated with drought tolerance, we show that site-level hydraulic diversity of leaf turgor loss point, resistance to embolism (P50 ), and HSMs is high across tropical forests and largely independent of water availability. Species with high HSMs (>1 MPa) and low P50 values (< -2 MPa) are common across the wet and dry tropics. This high site-level hydraulic diversity, largely decoupled from water stress, could influence which species are favoured and become dominant under a drying climate. High hydraulic diversity could also make these ecosystems more resilient to variable rainfall regimes.

HIVepsilon-seq-scalable characterization of intact persistent proviral HIV reservoirs in women.

IMPORTANCE: The lack of a reliable method to accurately detect when replication-competent HIV has been cleared is a major challenge in developing a cure. This study introduces a new approach called the HIVepsilon-seq (HIVε-seq) assay, which uses long-read sequencing technology and bioinformatics to scrutinize the HIV genome at the nucleotide level, distinguishing between defective and intact HIV. This study included 30 participants on antiretroviral therapy, including 17 women, and was able to discriminate between defective and genetically intact viruses at the single DNA strand level. The HIVε-seq assay is an improvement over previous methods, as it requires minimal sample, less specialized lab equipment, and offers a shorter turnaround time. The HIVε-seq assay offers a promising new tool for researchers to measure the intact HIV reservoir, advancing efforts towards finding a cure for this devastating disease.

Magnetic resonance imaging accuracy in staging early and locally advanced rectal cancer.

INTRODUCTION: Magnetic Resonance Imaging (MRI) is the standard pretreatment staging in patients with rectal cancer. Accurate tumor staging is paramount to determining the appropriate treatment course for patients diagnosed with rectal cancer. The current study aims to re-evaluate the accuracy of pre-operative MRI in staging of both early and locally advanced rectal cancer following completion of neoadjuvant therapy (NAT) compared to the pathologic stage. METHODS: A retrospective review of patients treated for rectal cancer between 2015 and 2020 at a single academic institution. All patients underwent rectal cancer protocol MRIs before surgical resection. Analysis was carried out in two groups: early rectal cancer: T1/2 N0 tumors with upfront surgical resection (N = 40); and locally advanced disease: T3 or greater or N+ disease receiving NAT, with restaging MRI following NAT (n = 63). RESULTS: 103 patients were included in analysis. MRI accuracy in early tumors was 35% ICC = 0.52 (95% CI 0.25-0.71) T stage and 66% ICC = 0 (95% CI -0.24, 0.29) for 29 patients with nodal data for N stage. There was 28% understaging of T2 tumors and 34% understaging of N0 stage by MRI. Post NAT MRI had 44% accuracy ICC = 0.57 (95% CI -0.15-0.20) T stage and 60% accuracy ICC = 0.32 (95% CI 0.08-0.52) N stage. Tumor invasion was overstaged on MRI: 40% T2, 29% T3, 90% T4. Nodal inaccuracy was due to overstaging, 61% N1, 90% N2. CONCLUSIONS: In locally advanced rectal cancer MRI overstaged tumors, this could be due to the continued effect of NAT from MRI to resection. This overstaging is of little clinical significance as it doesn't alter the treatment plan, except in cases of complete clinical response. In early rectal cancer, MRI had limited accuracy compared to pathology, understaging a quarter of patients who would benefit from NAT before surgery. Other adjunct imaging modalities should be considered to improve accuracy in staging early rectal cancer and consideration of complete response and enrollment in watch and wait protocols.

Interrogating the configurational stability of atropisomers.

Atropisomers are molecules whose stereogenicity arises from restricted rotation about a single bond. They are of current importance because of their applications in catalysis, medicine and materials science. The defining feature of atropisomeric molecules is that their stereoisomers are related to one another by bond rotation: as a result, evaluating their configurational stability (i.e., the rate at which their stereoisomers interconvert) is central to any work in this area. Important atropisomeric scaffolds include C-C linked biaryls, such as the ligand BINAP and the drug vancomycin, and C-N linked amine derivatives such as the drug telenzepine. This article focuses on the three most widely used experimental methods that are available to measure the rate of racemization in atropisomers, namely: (i) kinetic analysis of the racemization of an enantioenriched sample, (ii) dynamic HPLC and (iii) variable-temperature NMR. For each technique, an explanation of the theory is set out, followed by a detailed experimental procedure. A discussion is also included of which technique to try when confronted with a new molecular structure whose properties are not yet known. None of the three procedures require complex experimental techniques, and all can be performed by using standard analytical equipment (NMR and HPLC). The time taken to determine a racemization rate depends on which experimental method is required, but for a new compound it is generally possible to measure a racemization rate in <1 d.

Evolution: Assembling the deuterostome body plan.

Starfish, graptolites and humans look as different as can be, yet are more closely related to each other than to any other phylum. Disc-shaped Cambrian fossils join the dots between these disparate body plans to plot out their evolutionary origins.