Efficacy and safety of rechallenge with [177Lu]Lu-PSMA-I&T radioligand therapy in metastatic castration resistant prostate cancer.

BACKGROUND: The purpose of this study was to evaluate the safety and outcome of rechallenge [177Lu]Lu-PSMA-I&T in newly progressed mCRPC patients after response to initial [177Lu]Lu-PSMA radioligand therapy (PRLT). METHODS: We retrospectively included 18 patients who underwent rechallenge with [177Lu]Lu-PSMA-I&T. All patients presented with (i) newly progressed disease after response to initial PRLT; (ii) a [68Ga]Ga-PSMA-11 PET/CT confirming the presence of PSMA-positive metastases; iii) ECOG performance status 0-1. Adverse events were graded according to CTCAE v5.0. Response was assessed by PSA and classified according to PCWG3 recommendations. For patients who underwent restaging with [68Ga]Ga-PSMA-11 PET/CT, imaging response was categorised according to adapted PERCIST v1.0. In patients with discordant [68Ga]Ga-PSMA-11 PET/CT and PSA, other available imaging modalities were evaluated to confirm disease status. Overall survival (OS) was calculated from the first cycle of initial PRLT and rechallenge PRLT, respectively, until last patient contact or death. RESULTS: Patients were initially treated with a median of 5 cycles (range 4-7) and were rechallenged after a median of 9 months (range 3-13). Each patient received a median of 4 (range 2-7) rechallenge cycles (median cumulative activity 26.1 GBq). None of the patients experienced life-threatening G4 adverse events during either treatment period. Grade 3 adverse events included one case of anaemia, one case of thrombocytopenia, and one case of renal failure. In 8/18 patients long-term toxicities were evaluated. Serious toxicities (≥ Grade 3) occurred in 3/8 patients (n = 1 G4 thrombocytopenia, n = 1 G4 renal failure and n = 1 pancytopenia and G4 renal failure). Best PSA50%-response was observed in 44% of patients and PSA-disease control was confirmed in 56% of patients at the last cycle. Of the 12/18 patients restaged by imaging, 6/12 (50%) patients had disease control (partial response/stable disease), 1/12 had a mixed response, and 5/12 had progression. After a median follow-up time of 25 months (range 14-44), 10 patients had died, 7 were still alive, and one patient was lost at follow-up. The median OS was 29 months (95%CI, 14.3-43.7 months) for the initial treatment and 11 months (95%CI, 8.1-13.8 months) for the first rechallenge course. CONCLUSION: More than half of patients benefit from rechallenge PRLT. Our analysis suggests that rechallenge may prolong survival in selected patients, with an acceptable safety profile.

Casimir Effect in MEMS: Materials, Geometries, and Metrologies-A Review.

Casimir force densities, i.e., force per area, become very large if two solid material surfaces come closer together to each other than 10 nm. In most cases, the forces are attractive. In some cases, they can be repulsive depending on the solid materials and the fluid medium in between. This review provides an overview of experimental and theoretical studies that have been performed and focuses on four main aspects: (i) the combinations of different materials, (ii) the considered geometries, (iii) the applied experimental measurement methodologies and (iv) a novel self-assembly methodology based on Casimir forces. Briefly reviewed is also the influence of additional parameters such as temperature, conductivity, and surface roughness. The Casimir effect opens many application possibilities in microelectromechanical systems (MEMS) and nanoelectromechanical systems (NEMS), where an overview is also provided. The knowledge generation in this fascinating field requires interdisciplinary approaches to generate synergetic effects between technological fabrication metrology, theoretical simulations, the establishment of adequate models, artificial intelligence, and machine learning. Finally, multiple applications are addressed as a research roadmap.

Adverse childhood experiences, gender, and suicidality among Florida high school students: Examining intervening mechanisms.

BACKGROUND: Adverse childhood experiences (ACEs) represent a key risk factor for suicidal thoughts and behaviors among adolescents. However, the intervening mechanisms linking ACEs and suicidality, and whether such processes vary by gender, remain underexplored. OBJECTIVE: The present study examines whether the relationships between ACEs and the likelihood of experiencing suicidal thoughts and attempting suicide are indirect through depressive symptoms and low self-control. This study also investigates whether these direct and indirect paths might be moderated by gender. PARTICIPANTS AND SETTING: The analyses make use of data on a statewide representative sample of students enrolled in public high schools in Florida (N = 23,078) from the 2022 Florida Youth Substance Abuse Survey (FYSAS). METHODS: Generalized structural equation modeling (GSEM) was used to estimate the direct and indirect effects of ACEs on the likelihood of suicidal thoughts and attempting suicide. The indirect effects were assessed using bootstrapping, and between-gender differences in the coefficients were tested. RESULTS: ACEs has direct associations with depressive symptoms, low self-control, and both suicidality outcomes. The effects of ACEs on suicidal thoughts are indirect through both depressive symptoms and low self-control, and the effects of ACEs on suicide attempts are indirect through depressive symptoms. Limited gender differences in these pathways emerge. CONCLUSIONS: For male and female youth, ACEs are associated with heightened depression symptoms and reduced self-control, and both of these factors partially explain the previously established relationship between ACEs and suicidality.

The greenbeard gene tgrB1 regulates altruism and cheating in Dictyostelium discoideum.

Greenbeard genetic elements encode rare perceptible signals, signal recognition ability, and altruism towards others that display the same signal. Putative greenbeards have been described in various organisms but direct evidence for all the properties in one system is scarce. The tgrB1-tgrC1 allorecognition system of Dictyostelium discoideum encodes two polymorphic membrane proteins which protect cells from chimerism-associated perils. During development, TgrC1 functions as a ligand-signal and TgrB1 as its receptor, but evidence for altruism has been indirect. Here, we show that mixing wild-type and activated tgrB1 cells increases wild-type spore production and relegates the mutants to the altruistic stalk, whereas mixing wild-type and tgrB1-null cells increases mutant spore production and wild-type stalk production. The tgrB1-null cells cheat only on partners that carry the same tgrC1-allotype. Therefore, TgrB1 activation confers altruism whereas TgrB1 inactivation causes allotype-specific cheating, supporting the greenbeard concept and providing insight into the relationship between allorecognition, altruism, and exploitation.

The intersection of race, ethnicity, and gender and the prevalence of suicidal thoughts and behaviors.

The prevalence of suicidal thoughts and behaviors across distinct intersections of race/ethnicity and gender among adolescents remains understudied. The current study seeks to address this important gap in suicide scholarship using a statewide representative sample of U.S. Florida middle school and high school adolescents. Data drawn from the 2022 Florida Youth Substance Abuse Survey (FYSAS) (N = 41,764) were analyzed to examine disparities in suicidal thoughts and suicide attempts among 26 racial/ethnic and gender subgroups of middle school and high school aged adolescents. Survey-weighted prevalence estimates for both suicidality outcomes were generated, and binary contrasts were used to assess the statistical significance of the differences in the probabilities between members of each subgroup and youth belonging to all other subgroups. Our results indicate that the prevalence of suicidal thoughts and attempts was highly gendered and varied according to racial/ethnic subgroups. Native American girls reported more suicidal thoughts (49.9%) and attempts (16.5%) in the past 12 months than any race/gender group. Other racial/ethnic and gender groups that reported particularly high rates of suicidal thoughts and attempts were West Indian/Caribbean female adolescents (48.8% and 13.4%, respectively), Puerto Rican female adolescents (48.5% and 14.7%, respectively), and Black/non-Hispanic female adolescents (19.9% and 15.6%, respectively). Because certain gender and race/ethnic subgroups are at an increased risk for suicidality, more research is needed to better understand the risk and protective factors to determine which suicide prevention strategies might best serve each group.

A novel cubic-exp evaluation algorithm considering non-symmetrical axial response signals of confocal microscopes.

The depth discrimination in confocal microscopy is based on the digital analysis of depth response signals obtained by each camera pixel during measurement. Various signal-processing algorithms are used for this purpose. The accuracy of these algorithms is inter alia restricted by the axial symmetry of the signals. However, in practice response signals are rather asymmetrical especially in case of measurement objects with critical surface structures such as edges or steep flanks. We present a novel signal-processing algorithm based on an exponential function with a cubic argument to handle asymmetrical and also symmetrical depth response signals. Results obtained by this algorithm are compared to those of commonly used signal processing algorithms. It turns out that the novel algorithm is more robust, more accurate and exhibits a repeatability of a similar order compared to other algorithms. RESEARCH HIGHLIGHTS: A novel, more robust algorithm with improved accuracy in peak extraction especially for asymmetrical response signals in confocal microscopy is introduced and validated. Improved accuracy is demonstrated for height and layer thickness measurements.

The trial tax and the intersection of race/ethnicity, gender, and age in criminal court sentencing.

OBJECTIVE: Prior research consistently demonstrates that defendants convicted at trial are sentenced more harshly than those who plead guilty. Additionally, a vast literature has shown that Black and Hispanic defendants, and especially young minority males, are particularly disadvantaged in sentencing, though these effects may be conditional on various legal and case-processing factors. However, it remains unclear how the mode of conviction might moderate these inequalities according to offenders' combined race/ethnicity, gender, and age. HYPOTHESES: I expected that mode of conviction would moderate the joint effects of race/ethnicity, gender, and age on the imposition of a sentence to prison and on sentence length such that young minority males convicted at trial would receive more severe punishments than members of other subgroups. METHOD: The analyses made use of data on defendants sentenced for noncapital felony crimes in Florida circuit courts over a 12-year period (N = 1,076,500). Hurdle regression models and marginal effects analysis were used. RESULTS: Greater sentencing disparities in absolute as well as relative terms between young minority males and other race/ethnicity, gender, and age subgroups were found among trial cases than among plea cases. Further, Black and Hispanic males were subjected to trial taxes that were substantially larger than those of other subgroups. CONCLUSIONS: These findings suggest that defendants who plead guilty are generally sentenced according to predictable and standardized "going rates" of punishment, whereas the enhanced discretion afforded judges in trial cases as well as racialized "bad facts" about defendants that emerge at trial may drive inequalities in punishment. Thus, extralegal sentencing disparities tied to mode of conviction are an area in which criminal justice reform efforts might be directed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Differential Exposure to Adverse Childhood Experiences Among Florida High School Students: The Intersection of Race, Ethnicity, and Gender.

PURPOSE: The prevalence of exposure to adverse childhood experiences (ACEs) across distinct intersections of race/ethnicity and gender among adolescents remains relatively unknown. The current study seeks to address this important gap in the literature using a statewide representative sample of Florida high school students. METHODS: Data drawn from the 2020 Florida Youth Substance Abuse Survey (FYSAS) (N = 20,438) were analyzed to examine differences in ACE exposure among 26 racial/ethnic and gender subgroups of high-school aged youth. Lifetime exposure to ACEs was constructed using 10 different ACE categories to measure ACEs prevalence as reported exposure to 1+ ACEs and 4+ ACEs. RESULTS: Exposure to ACEs was highly gendered and varied according to racial/ethnic subgroup. While notable differences across gender and racial/ethnic groups emerged when measuring prevalence as exposure to 1+ ACEs, several of these disparities were further amplified when prevalence was measured as exposure to 4+ ACEs. Native American female adolescents represented the group at greatest risk of high exposure to ACEs, with more than 50% of such youth reporting exposure to 4+ ACEs. DISCUSSION: The prevalence of ACE exposure varies significantly across race/ethnic and gender subgroups of youth. These intersections should be considered for prevention efforts and clinical treatments of trauma exposure as ACEs may be linked to certain outcomes or behaviors based on high exposure in certain subpopulations of youth.

Global Soil Hydraulic Properties dataset based on legacy site observations and robust parameterization.

The representation of land surface processes in hydrological and climatic models critically depends on the soil water characteristics curve (SWCC) that defines the plant availability and water storage in the vadose zone. Despite the availability of SWCC datasets in the literature, significant efforts are required to harmonize reported data before SWCC parameters can be determined and implemented in modeling applications. In this work, a total of 15,259 SWCCs from 2,702 sites were assembled from published literature, harmonized, and quality-checked. The assembled SWCC data provide a global soil hydraulic properties (GSHP) database. Parameters of the van Genuchten (vG) SWCC model were estimated from the data using the R package 'soilhypfit'. In many cases, information on the wet- or dry-end of the SWCC measurements were missing, and we used pedotransfer functions (PTFs) to estimate saturated and residual water contents. The new database quantifies the differences of SWCCs across climatic regions and can be used to create global maps of soil hydraulic properties.

Unstructured Socializing with Peers, Low Self-Control, and Substance Use.

Research consistently finds that unstructured socializing with peers and low self-control are both positively associated with substance use among adolescents. However, largely absent from the literature is a consideration of whether unstructured socializing with peers and low self-control have differential and interactive effects when predicting usage of different classifications of drugs. The current study addresses these issues using data collected on a statewide sample of middle school and high school students who participated in the 2017 Florida Youth Substance Abuse Survey. Results indicate that (1) unstructured socializing with peers is a stronger predictor of soft drug use than low self-control, (2) low self-control is a stronger predictor of hard drug use than unstructured socializing with peers, and (3) the effect of unstructured socializing on both soft and hard drug use is diminished among adolescents who are lower in self-control.

Annual precipitation explains variability in dryland vegetation greenness globally but not locally.

Dryland vegetation productivity is strongly modulated by water availability. As precipitation patterns and variability are altered by climate change, there is a pressing need to better understand vegetation responses to precipitation variability in these ecologically fragile regions. Here we present a global analysis of dryland sensitivity to annual precipitation variations using long-term records of normalized difference vegetation index (NDVI). We show that while precipitation explains 66% of spatial gradients in NDVI across dryland regions, precipitation only accounts for <26% of temporal NDVI variability over most (>75%) dryland regions. We observed this weaker temporal relative to spatial relationship between NDVI and precipitation across all global drylands. We confirmed this result using three alternative water availability metrics that account for water loss to evaporation, and growing season and precipitation timing. This suggests that predicting vegetation responses to future rainfall using space-for-time substitution will strongly overestimate precipitation control on interannual variability in aboveground growth. We explore multiple mechanisms to explain the discrepancy between spatial and temporal responses and find contributions from multiple factors including local-scale vegetation characteristics, climate and soil properties. Earth system models (ESMs) from the latest Coupled Model Intercomparison Project overestimate the observed vegetation sensitivity to precipitation variability up to threefold, particularly during dry years. Given projections of increasing meteorological drought, ESMs are likely to overestimate the impacts of future drought on dryland vegetation with observations suggesting that dryland vegetation is more resistant to annual precipitation variations than ESMs project.

Three-dimensional transfer function of optical microscopes in reflection mode.

Three-dimensional (3D) transfer functions build the basis for a comprehensive characterization of optical imaging systems in the spatial frequency domain. Utilizing the projection-slice theorem, the 2D modulation transfer function of an incoherent imaging system can be derived from a 3D transfer function by integration with respect to the axial spatial frequency. For a diffraction limited microscope with homogeneous incoherent pupil illumination, the modulation transfer function equals the 2D autocorrelation function of a circular disc. However, until now to the best of our knowledge no 3D transfer function has been published, which exactly leads to the 2D modulation transfer function of a diffraction limited microscope in reflection mode. In this article, we derive a formula, which after integration with respect to the axial spatial frequency coordinate perfectly fits to the diffraction limited 2D modulation transfer function. The inverse three-dimensional Fourier transform of the 3D transfer function results in a complex-valued 3D point spread function, from which the depth of field, the lateral resolution and, in addition, the corresponding 3D point spread function of both, a conventional and an interference microscope, can be obtained.

Optical microscopes are probably the most wide-spread optical instruments in science and technology. While in biological applications microscopes are mostly operated in transmission mode, reflection-type microscopes dominate in materials science. A further important field of application of reflection microscopy is the reconstruction of the three-dimensional (3D) surface topography of an object. This kind of 3D microscopy obtains 3D image stacks by axially scanning through the focus. While in a conventional bright-field microscope point scatterers are necessary to enable height discrimination, interference microscopy even works on specularly reflecting surfaces. In both cases, according to optical systems theory the physical behaviour of the microscope is fully represented by a 3D point spread function in the object space or, equivalently, by the corresponding 3D transfer function in the spatial frequency domain. In order to be consistent with microscopic imaging theory, integrating the 3D transfer function along the axial spatial frequency is required to result in the well-known modulation transfer function of a diffraction limited optical imaging system. Since to the best of our knowledge no formula for the calculation of the 3D transfer function of a microscope operated in reflection mode has been published, we derive a mostly analytical formula, which is perfectly consistent with the modulation transfer function of a diffraction limited system. The inverse three-dimensional Fourier transform of the 3D transfer function results in a complex-valued 3D point spread function, from which the depth of field, the lateral resolution and, in addition, the corresponding 3D point spread function of both, a conventional and an interference microscope, can be obtained. Utilizing the rotational symmetry of the 3D transfer function we present a computationally efficient formula for the numerical calculation of the 3D point spread function.

3D modeling of coherence scanning interferometry on 2D surfaces using FEM.

Despite the fact that optical profilers, such as coherence scanning interferometers, are frequently used for fast and contactless topography measurements in various fields of application, measured profiles still suffer from the wave characteristics of light, which leads to systematic deviations that are still not sufficiently investigated. In order to analyze these systematic deviations and their physical relations, we apply a rigorous simulation model considering both the transfer characteristics of the measurement instrument as well as the geometry and material of different measurement objects. Simulation results are compared to measurement results for different polarizations, wavelengths and interferometer types, considering surface structures including edges, slopes and different materials as the main reasons for those deviations. Compared to former publications, a full three-dimensional (3D) modeling of the image formation with regard to two-dimensional (2D) surface structures is provided. The advantages of 3D modeling in contrast to a time efficient 2D approach are discussed. Further, an extract of an atomic force microscope (AFM) measurement result is used as the basis for the FEM simulation in one example in order to achieve most realistic simulation results.

Microsphere-assisted interferometry with high numerical apertures for 3D topography measurements.

Improving the lateral resolution is a key focus of the research on optical measuring systems to expand the fields of application for optical metrology. By means of microspheres put on an object in a microscope, and therefore used as a near-field support, it has already been shown that a superresolution of structures below Abbe's diffraction limit is possible. The following investigations give more detailed theoretical and experimental insight into the physical mechanisms responsible for the transition of near-field information to the far field. In particular, the effects of microspheres as near-field support on the behavior of phase-evaluating interference microscopes close to the optical resolution limit are studied experimentally as well as with numerical simulations. Special attention is drawn to measured data taken with a Linnik microscope of high numerical aperture. Finally, the measurement results of grating structures with a period below Abbe's diffraction limit are presented.

A GoldenBraid cloning system for synthetic biology in social amoebae.

GoldenBraid is a rapid, modular, and robust cloning system used to assemble and combine genetic elements. Dictyostelium amoebae represent an intriguing synthetic biological chassis with tractable applications in development, chemotaxis, bacteria-host interactions, and allorecognition. We present GoldenBraid as a synthetic biological framework for Dictyostelium, including a library of 250 DNA parts and assemblies and a proof-of-concept strain that illustrates cAMP-chemotaxis with four fluorescent reporters coded by one plasmid.

Adaptive high-resolution Linnik interferometry for 3D measurement of microparticles.

Tailored 3D microparticles and nanostructures lead to increasing possibilities in semiconductor industry or biomedical applications. In an interdisciplinary study we investigate the parallel production of such particles by using nanoimprint lithography in combination with their characterization based on interference microscopy. In this Letter we report on a metrological inspection, which tends to a universal measurement solution comparing the sample optically to a master object produced in the same way as the sample.

Quadrature-based interferometry using pulsed RGB illumination.

This contribution introduces a novel image recording approach for phase retrieval in a RGB-interferometer setup with pulsed LED illumination and an oscillating reference mirror. The effective acquisition time of the interference images is below 100 µs with a repetition rate of 10 frames per second. The pulsed illumination is synchronized with the exposure gap of a Bayer-Pattern CMOS RGB camera to enable the recording of two π/2 phase shifted images with a short delay compared to the camera exposure time. The proposed quadrature method enables surface phase retrieval with a standard deviation of ≈ [3 nm, · · ·, 5 nm], depending on phase noise and actuator precision. The applicability of the reconstructed phase data to unambiguity range extension algorithms based on the exact fraction method is considered. Experimental results demonstrate the feasibility of the setup to measure the topography of samples in motion or oscillating by mechanical vibrations.

Temporal high-resolution evaluation algorithm for sinusoidally phase modulated interference signals.

In this paper, we present a practical approach for phase analysis of sinusoidally phase shifted interference signals, which are generally used to detect optical path length changes in one arm of the interferometer based on an algorithm introduced by de Groot. We describe the original algorithm from our point of view and try to emphasize the limitations and some details that need to be known for practical implementation. We introduce methods for how to overcome these limitations, and in addition, we provide an extension of the algorithm to a temporal high-resolution mode, which provides a possibility to calculate a phase value for each sampled point of an interference signal and opens new applications for the existing measurement devices without any hardware changes. Simulated and experimental results verify our extensions.

Discourse After a Batterer Intervention Program: A Qualitative Analysis of "Letters From the Future".

This exploratory study employs discourse and narrative analysis to assess men's ( n = 45) responses to a writing assignment completed at the end of a solution-focused voluntary batterer intervention program. The study finds that the men primarily use the assignment to reassure themselves of their future success, defined through traditionally male paradigms. The narrative analysis then divides the letters according to type: Participants (22.7%) use a "transformative" discourse of behavior change and intimate partner violence (IPV)-sustaining discourse (18.2%), but the plurality (38.6%) use both simultaneously. The ideological conflict demonstrated in these responses highlights how IPV-sustaining discourse is embedded within broader sociocultural discursive structures.

Fiber-bundle model with time-dependent healing mechanisms to simulate progressive failure of snow.

Snow is a heterogeneous material with strain- and/or load-rate-dependent strength. In particular, a transition from ductile-to-brittle failure behavior with increasing load rate is observed. The rate-dependent behavior can partly be explained with the existence of a unique healing mechanism in snow that stems from its high homologous temperature (temperature close to melting point). As soon as broken elements in the ice matrix get in contact, they start sintering and the structure may regain strength. Moreover, the ice matrix is subjected to viscous deformation, inducing a relaxation of local load concentrations and, therefore, further counteracting the damage process. Ideal tools for studying the failure process of heterogeneous materials are the fiber-bundle models (FBMs), which allow investigating the effects of basic microstructural characteristics on the general macroscopic failure behavior. We present an FBM with two concurrent time-dependent healing mechanisms: sintering of broken fibers and relaxation of load inhomogeneities. Sintering compensates damage by creating additional intact, load-supporting fibers which lead to an increase of the bundle strength. However, the character of the failure is not changed by sintering alone. With combined sintering and load relaxation, load is distributed from old stronger fibers to new fibers that carry fewer load. So as we additionally incorporated load redistribution to the FBM, the failure occurred suddenly without decrease of the order parameter-describing the amount of damage in the bundle-and without divergence of the fiber failure rate. Moreover, the b value, i.e., the power-law exponent of frequency-magnitude statistics of fibers breaking in load redistribution steps, at failure converged to b≈2, a value higher than that of a classical FBM without healing (b=3/2). These results indicate that healing, as the combined effect of sintering and load relaxation, changes the type of the phase transition at failure. This change of the phase transition is important for quantifying or predicting the failure (e.g., by monitoring acoustic emissions) of snow or other materials for which healing plays an important role.