Search

Abstract Background Alzheimer’s disease (AD) and Parkinson’s disease (PD) are leading neurodegenerative disorders marked by protein aggregation, with AD featuring amyloid-beta (Aβ) and tau proteins, and PD alpha-synuclein (αSyn). Dementia with Lewy bodies (DLB) often presents with a mix of these pathologies. This study explores naturally occurring autoantibodies (nAbs), including Immunoglobulin (Ig)G, IgM, and IgA, which target αSyn, Aβ and tau to maintain homeostasis and were previously found altered in AD and PD patients, among others. Main text We extended this investigation across AD, PD and DLB patients investigating both the affinities of IgGs and levels of IgGs, IgMs and IgAs towards αSyn, Aβ and tau utilizing chemiluminescence assays. We confirmed that AD and PD patients exhibited lower levels of high-affinity anti-Aβ and anti-αSyn IgGs, respectively, than healthy controls. AD patients also showed diminished levels of high-affinity anti-αSyn IgGs, while anti-tau IgG affinities did not differ significantly across groups. However, DLB patients exhibited increased anti-αSyn IgG but decreased anti-αSyn IgM levels compared to controls and PD patients, with AD patients showing a similar pattern. Interestingly, AD patients had higher anti-Aβ IgG but lower anti-Aβ IgA levels than DLB patients. DLB patients had reduced anti-Aβ IgM levels compared to controls, and anti-tau IgG levels were lower in AD than PD patients, who had reduced anti-tau IgM levels compared to controls. AD patients uniquely showed higher anti-tau IgA levels. Significant correlations were observed between clinical measures and nAbs, with negative correlations between anti-αSyn IgG affinity and levels in DLB patients and a positive correlation with anti-αSyn IgA levels in PD patients. Disease-specific changes in nAb levels and affinity correlations were identified, highlighting altered immune responses. Conclusion This study reveals distinctive nAb profiles in AD, DLB, and PD, pinpointing specific immune deficiencies against pathological proteins. These insights into the autoreactive immune system’s role in neurodegeneration suggest nAbs as potential markers for vulnerability to protein aggregation, offering new avenues for understanding and possibly diagnosing these conditions.

Colorectal cancer (CRC) is one of the most prevalent cancer types worldwide, exhibiting significant variance in incidence rates across different ethnicities and geographical regions. Notably, there is a rising incidence of CRC among younger adults, particularly evident in advanced stages, with a more pronounced trend observed in developing nations. Epigenetic alterations potentially play a role in the early onset of CRC and could elucidate interpopulation disparities. This study aimed to examine DNA methylation levels in the tumor suppressor genes MLH1 and p16INK4a, comparing Nepalese and Swedish patients with CRC.

ABSTRACTThe oral commensal Fusobacterium nucleatum can spread to extra-oral sites, where it is associated with diverse pathologies, including pre-term birth and cancer. Due to the evolutionary distance of F. nucleatum to other model bacteria, we lack a deeper understanding of the RNA regulatory networks that allow this bacterium to adapt to its various niches. As a first step in that direction, we recently showed that F. nucleatum harbors a global stress response governed by the extracytoplasmic function sigma factor, σE, which displays a striking functional conservation with Proteobacteria and includes a noncoding arm in the form of a regulatory small RNA (sRNA), FoxI. To search for putative additional σE-dependent sRNAs, we comprehensively mapped the 5′ and 3′ ends of transcripts in the model strain ATCC 23726. This enabled the discovery of FoxJ, a ~156-nucleotide sRNA previously misannotated as the 5′ untranslated region (UTR) of ylmH. FoxJ is tightly controlled by σE and activated by the same stress conditions as is FoxI. Both sRNAs act as mRNA repressors of the abundant porin FomA, but FoxJ also regulates genes that are distinct from the target suite of FoxI. Moreover, FoxJ differs from other σE-dependent sRNAs in that it also positively regulates genes at the post-transcriptional level. We provide preliminary evidence for a new mode of sRNA-mediated mRNA activation, which involves the targeting of intra-operonic terminators. Overall, our study provides an important resource through the comprehensive annotation of 5′ and 3′ UTRs in F. nucleatum and expands our understanding of the σE response in this evolutionarily distant bacterium.IMPORTANCEThe oral microbe Fusobacterium nucleatum can colonize secondary sites, including cancer tissue, and likely deploys complex regulatory systems to adapt to these new environments. These systems are largely unknown, partly due to the phylogenetic distance of F. nucleatum to other model organisms. Previously, we identified a global stress response mediated by σE that displays functional conservation with the envelope stress response in Proteobacteria, comprising a coding and noncoding regulatory arm. Through global identification of transcriptional start and stop sites, we uncovered the small RNA (sRNA) FoxJ as a novel component of the noncoding arm of the σE response in F. nucleatum. Together with its companion sRNA FoxI, FoxJ post-transcriptionally modulates the synthesis of envelope proteins, revealing a conserved function for σE-dependent sRNAs between Fusobacteriota and Proteobacteria. Moreover, FoxJ activates the gene expression for several targets, which is a mode of regulation previously unseen in the noncoding arm of the σE response.

A profound knowledge of pollutant emissions and transport processes is essential to better assess the impact on local air quality, which ultimately affects human health. This is of special importance in the proximity of airports, as flight activities are a major source of ultrafine aerosol particles (UFP) that are associated with adverse health effects. A quantification of the aerosol population in the horizontal and in particular in the vertical distribution has not been sufficiently characterized so far, but is of crucial relevance, as the atmospheric boundary layer (ABL) is strongly interacting with aerosols. For this purpose, the fixed-wing research drone called ALADINA (Application of Light-weight Aircraft for Detecting in-situ Aerosol) was operated at a distance of approximately 4 km downwind of the German airport Berlin Brandenburg (BER) on October 11–19, 2021. During the investigation period, 140 vertical profiles of different meteorological parameters and aerosol particle sizes were obtained on six measurement days between the surface and up to a maximum altitude of 750 m above ground level (a.g.l.). The investigations indicate several features: The stability of the ABL is a key characteristic for the vertical distribution of aerosol population with highest concentrations close to ground. Inversion layers further enhance horizontal transport so that airport pollutants can be moved to a further distance away. The airborne observations of total particle number concentration (TNC) coincide with ground-based data from fix-point sites. They show a high variability depending on the distance to the plume as well as upwind position and highest concentrations of TNC related to rush hours of airport operations.

Abstract Global climate change poses significant societal and political challenges. The rapid increase in the near-surface air temperatures and the drastic retreat of the Arctic sea ice during summer are not well represented by climate models. The data sets introduced here intend to help improving the current understanding of the ongoing Arctic climate changes. In particular, this study considers observations from 24 helicopter flights (June–September 2020) and 5 flights with the helicopter-towed probe HELiPOD (May–July 2020) during MOSAiC. Distributions of various surface types (white ice/snow, bright melt ponds, dark melt ponds, open water, and bare ice) were determined using fisheye camera images. They were related to collocated broadband irradiance measurements to analyse the temporal and spatial changes of the surface albedo. Multiple linear regression was applied to assign the measured areal albedo to the corresponding surface-types. The resulting surface-type fractions, the albedo data and respective upward and downward broadband solar irradiances of several flights throughout the melting and refreezing season are provided.

Abstract Objective To determine the effect of dose calculation accuracy on inverse linear energy transfer (LET) optimization for intensity‐modulated proton therapy, and to determine whether adding more beams would improve the plan robustness to different dose calculation engines. Methods Two sets of intensity‐modulated proton therapy plans using two, four, six, and nine beams were created for 10 prostate cancer patients: one set was optimized with dose constraints (DoseOpt) using the pencil beam (PB) algorithm, and the other set was optimized with additional LET constraints (LETOpt) using the Monte Carlo (MC) algorithm. Dose distributions of DoseOpt plans were then recalculated using the MC algorithm, and the LETOpt plans were recalculated using the PB algorithm. Dosimetric indices of targets and critical organs were compared between the PB and MC algorithms for both sets of plans. Results For DoseOpt plans, dose differences between the PB and MC algorithms were minimal. However, the maximum dose differences in LETOpt plans were 11.11% and 15.85% in the dose covering 98% and 2% (D2) of the clinical target volume, respectively. Furthermore, the dose to 1 cc of the bladder differed by 11.42 Gy (relative biological effectiveness). Adding more beams reduced the discrepancy in target coverage, but the errors in D2 of the structure were increased with the number of beams. Conclusion High modulation of LET requires high dose calculation accuracy during the optimization and final dose calculation in the inverse treatment planning for intensity‐modulated proton therapy, and adding more beams did not improve the plan robustness to different dose calculation algorithms.

Sinking particles were studied by analyzing samples collected in a sediment trap at 180 m depth in the Gotland Basin, eastern Baltic Sea between 1999 and 2020. The aim of this study was to determine the temporal variability of the particle flux and its components and how their changes are linked to phytoplankton blooms. The variables studied included total particle flux, particulate organic carbon and nitrogen, biogenic silica, C:N ratio and the isotopic composition of organic carbon and nitrogen. The total particle flux and its components reached maximum values in 2003, 2012 and 2015. Long-term means over the 22-year period of the total particle flux and its components particulate organic carbon and nitrogen, biogenic silica were estimated at around 152, 22, 3 and 8 mg m−2 d−1, respectively. The C:N ratio and the isotopic composition of organic carbon and nitrogen showed high variability around their long-term means of 9, -25‰ and 4‰, respectively. The annual variability of the components of the flux particulate organic carbon (3–65 mg m−2 d−1), particulate organic nitrogen (0.4–9 mg m−2 d−1) and biogenic silica (1–24 mg m−2 d−1) exhibited the same general pattern as the total particle flux (11–450 mg m−2 d−1) over the study period. On the seasonal scale, sinking material in summer contributed roughly one-third (31%) to the total particle flux, followed by winter (27%), spring (24%) and autumn (19%). The highest particle flux occurred mostly in April, July and November, during and after the appearance of phytoplankton blooms in the Gotland Basin. The phytoplankton community changed from silicon-rich species to nitrogen-fixing cyanobacteria, indicating a shift in nitrogen sources from nitrate-based to N2-based over the year. The spring bloom, dominated by diatoms, was characterized by a lighter carbon and heavier nitrogen isotopic composition, while the summer bloom, mainly of diazotrophic cyanobacteria, was characterized in contrary by heavier carbon and lighter nitrogen isotopes. Although no trend was found in the data, the variability observed in the sinking material was related to the changes over time in the phytoplankton community in the Gotland Basin. The findings of this study provide new and valuable information for our understanding of the temporal variability of sinking material linked to the development of phytoplankton blooms and nutrient sources in the Gotland Basin, and underscore the importance of continued monitoring to understand the potential impacts of environmental changes on this fragile ecosystem.

Measurement(s) Wind speed, Wind direction, Temperature, Relative humidity, Soil Moisture, Soil Temperature, Air Pressure, Radiative Fluxes near the surface • range, elevation azimut, radial velocity, wind vectors • Brightness temperatures • Reflectivity, range, elevation azimut • Trace gas concentrations • Aeorosol optical depth • Sky images, visible and infrared • Temperature, Humidity and Windprofiles • Temperature, Relative Humidity and Black Carbon Concentration • Temperature, Humidity, vertical wind speed Technology Type(s) weather station, energy balance station • Lidar, Sodar, UHF-Profiler • Microwave Radiometer • Rain radar and Cloud radar • Trace gas analyser • Photometer • Cloud camera • Radiosoundings • UAV • Eddy Correlation Factor Type(s) Precipitation and Cloudformation • turbulent fluxes of heat and moisture • Vertical temperature, humidity and wind profiles Sample Characteristic - Environment Atmosphere Sample Characteristic - Location West Africa

There exist passionate debates about the best way to teach children to read. Since the Bush administration, school districts receiving federal funds have been required to have research evidence justifying their methods of teaching reading, and in recent years the need for evidence-based practices have intensified with the "Science of Reading" movement. Last year the country's largest school system changed from balanced reading to three other programs for teaching children to read. In this study we examined the empirical evidence regarding the effectiveness of the three newly adopted reading programs for the country's largest school system. Our study consisted of website review of the research evidence provided by the three publishing companies regarding the effectiveness of their reading programs. Borrowing from studies of program effectiveness, we applied three criteria for analyzing the quality of research used by the publishers to document their program effectiveness. These criteria were the following: (1) Comparative clinical trials; (2) replication of results and (3) publication of evidence in professional journals. The results of our analyses indicated that only one of the selected reading programs was supported with empirical evidence meeting our criteria regarding program effectiveness. We argue that teachers, not programs, are what best affects children's learning to read. Overly simplified and politicized methods of teaching reading lacking empirical evidence of effectiveness are unlikely to accomplish this important goal.

The flow field induced by multirotor drones is of high interest for atmospheric research, as it locally influences the atmosphere and therefore may have an impact on the sensors installed for atmospheric measurements. Further, on-board vibrations can cause significant interference with the measurement equipment. To investigate the near flow field, an approach combining measurements of pressure and temperature distribution in-flight and in a laboratory setup together with numerical simulations was applied. Existing high-frequency measurement equipment was piggybacked during the initial flight tests with a newly developed 25 kg quadcopter system in a low-cost early-stage-error approach to obtain initial data and experience. During the flights, high resolution sensors for measuring pressure, temperature, acceleration, and deformation were applied with different setups at different locations below one of the rotor planes, respectively, at one rotor arm, to determine the multicopter’s influence on pressure and temperature measurements, to investigate rotor arm deformations, and to obtain data to compare with numerical simulations of this rotor setup. An external Schlieren-type measurement technique was tested to visualise the rotor vortices. The applied measurement techniques proved to be suitable for acquiring the state of the rotor-induced flow, but with some limitations. The comparison of measurements and simulations showed basic agreement and allowed for the identification of necessary adaptations for subsequent studies. The interaction of the rotor wakes with the rotor arms could be identified as the main source of the measured structural vibrations. The need for necessary improvements in the measurement setup, flight operation, and simulation setup is presented in detail.

In 2015, we studied the macrozoobenthic community composition along a dissolved oxygen gradient in the deep trough of the Gulf of St. Lawrence (Canada). We sampled the seabed at nine stations using box corers (three replicates per station), starting in the outer Gulf and ending in the Lower St. Lawrence River Estuary. We found four different communities dominated by polychaetes, crustaceans, and molluscs, with the emphasis shifting from mollusc to polychaete communities as oxygen saturation decreased. Contrary to our expectations, the stations furthest upstream in the estuary with the lowest oxygen saturation levels had the highest species diversity, and also the highest density and biomass values. Key genera of the hypoxic zone included bivalves (Thyasira), cumaceans (Diastylis), amphipods (Harpinia), and polychaetes such as Ampharete, Ceratocephale, Galathowenia, and Trochochaeta. We attribute this to the stability of the environmental conditions and the absence of stress, where the constant supply of oxygen, even at low concentrations, seems to be more important than the absolute oxygen concentration.

Germany is a non-English speaking country with a large and growing number of incoming international degree-seeking students. However, their estimated dropout rates are high. This study aims to investigate whether specific challenges faced by international students (e.g., social and academic integration, language learning, financial situation, residence-permit related regulations) are associated with major change and university dropout. The discrete-time competing risk analyses of the first three semesters of an online panel survey of international students in Germany (International Student Survey; N = 3,660) show that satisfaction with the degree program's content decreases the risk of major change and university dropout. Moreover, the nationality and the associated temporary or permanent residence permit are considered in the students' educational decisions. Based on the results, we recommend improving the match between students' interest and their fields of study. Measures to prevent international students from dropping out must thus begin before they start their studies.

High levels of Fusobacterium nucleatum have been associated with poor overall survival in patients with colorectal and esophageal cancer. Here, the authors show that F. nucleatum is abundant in breast cancer samples and that the colonization by F. nucleatum accelerates tumor growth and metastasis in preclinical breast cancer models.

Este artículo se centra en los «pagamentos» (zubiji) y las «confesiones» (aluna ishguashi) de los kogi, como prácticas de conocimiento que ilustran la naturaleza ecológica del intercambio en la Sierra Nevada de Santa Marta, Colombia. Muestra cómo la reciprocidad es cuestión de alimento o nutrición y se enmarca en órdenes y asociaciones complejas semejantes a las composiciones andinas del cosmos, el territorio y la sociedad. En términos kogi, estos patrones no son simplemente formas de clasificación «analogistas», sino que constituyen una red o tejido de relaciones y flujos basados en la regulación del equilibrio ecológico como el mantenimiento de estructuras cosmológicas de soporte. Esta unidad equivale a un organismo vivo y pensante que genera y sostiene a todos los seres y cosas, a la vez que integra su forma y sustancia, su espíritu y su materia. De esta forma, el artículo arroja mayor luz sobre las dimensiones ontológicas de la región istmo-colombiana, y termina haciendo énfasis en su relevancia para entender los actuales problemas ambientales en torno a la Sierra Nevada.

Currently, the main in situ upper air database for numerical weather prediction relies on radiosonde and aircraft-based information. Typically, radiosondes are launched at specific sites daily, up to four times per day, and data are distributed worldwide via the GTS net. Aircraft observations are limited to frequent flight routes, and vertical profiles are provided in the vicinity of large cities. However, there are large areas with few radiosonde launches, in particular above the oceans and in the polar areas. In this article, the development and technical details of the unmanned aerial system LUCA (Lightweight Unmanned high Ceiling Aerial system) are described. LUCA has the potential to complement radiosonde and aircraft-based observations up to 10 km in altitude. The system ascends and descends (by electrical power) in spiral trajectories and returns to the launching site. This article discusses the requirements for obtaining high data availability under mid-European and Antarctic conditions, with highly automated take-offs and landings under high surface winds, the capacity to deal with icing, and the ability to operate under high wind speeds. The article presents technical solutions for the design and construction of the system and demonstrates its potential.

With tracking systems becoming more widespread in sports research and regular training and competitions, more data are available for sports analytics and performance prediction. We analyzed 2523 ski jumps from 205 athletes on five venues. For every jump, the dataset includes the 3D trajectory, 3D velocity, skis’ orientation, and metadata such as wind, starting gate, and ski jumping hill data. Using this dataset, we aimed to predict the expected jump length (xLength) inspired by the expected goals metric in soccer (xG). We evaluate the performance of a fully connected neural network, a convolutional neural network (CNN), a long short-term memory (LSTM), and a ResNet architecture to estimate the xLength. For the prediction of the jump length one second after take-off, we achieve a mean absolute error (MAE) of 5.3 m for the generalization to new athletes and an MAE of 5.9 m for the generalization to new ski jumping hills using ResNet architectures. Additionally, we investigated the influence of the input time after the take-off on the predictions’ accuracy. As expected, the MAE becomes smaller with longer inputs. Due to the real-time transmission of the sensor’s data, xLength can be updated during the flight phase and used in live TV broadcasting. xLength could also be used as an analysis tool for experts to quantify the quality of the take-off and flight phases.

Internationalization in higher education is essential, and although active learning methodologies are increasing and allow students to develop transversal skills, most still have a very local scope. In this context, the Collaborative Online International Learning (COIL) methodology is an interesting approach to benefit the students' development. It consists of an online program that involves creating multicultural teams to develop a specific learning project. Although this methodology is expanding, its use in physiology is still scarce. This paper aims to show an example of applying COIL methodology in physiology topics to enhance higher-education students' innovation and business skills. Our example project developed a sports-assessment service concept focused on physiology and biomechanics assessments. The program involved teams from Brazil, Germany, and Spain, comprising undergraduate and master students. Over 7 weeks, these teams, mentored by professors and researchers, engaged in workshops covering COIL methodology, business model design, executive summary planning, economic analyses, and communication techniques. Key outcomes included learning new concepts, developing soft skills, building confidence in innovative solution proposals, and experiencing diverse cultures. Challenges faced were language barriers, scheduling, task complexity, and logistical issues. This experience confirms the effectiveness of incorporating programs using COIL methodology into educational curriculums. Doing so exposes physiology students to innovation, entrepreneurship, and business creation while strengthening their professional connections and opening up postgraduation opportunities.

High-impact practices (HIPs), such as undergraduate research, first-year seminars, and learning communities, have been shown to generally advance college student success. However, there are often disparities in access, participation, and outcomes between white and racially/ethnically minoritized students. While scholars have critiqued HIPs and provided alternative approaches to better serve minoritized students, we know little about how federally funded programs aiming to broaden participation can serve as a mechanism advance equity. Drawing on the literature, we developed an equity-minded HIP framework to critically examine the prominence and characteristics of 38 programs aiming to broaden participation in undergraduate US STEM education funded by the National Science Foundation. We conducted a systematic examination of multimodal data from the STEM for All Multiplex repository. Findings reveal most programs included only one to two HIPs, with undergraduate research being most prominent followed by internships. Most programs included only a few elements of equity-minded design, such as providing students additional resources and faculty training, and implemented HIPs to include peer and faculty interactions. Last, most programs utilized cognitive, psychosocial, or sociocultural measures to assess the benefits to students. Only a few measured equity-mined outcomes pertaining to institutional change such as policies, resources, and practices. We highlight two exemplar programs and offer recommendations for researchers and funders to more effectively implement equity-minded HIPs to broaden participation in undergraduate STEM education.

Abstract Purpose To assess the worst-case robust optimization IMPT plans with setup and range uncertainties and to test the hypothesis that the worst-case robust optimization strategies could cover most possible setup and range uncertainties in the real scenarios. Methods We analyzed the nominal and worst-case robust optimization IMPT plans of seven patients with head and neck cancer patients. To take uncertainties into account for the dose calculation, we performed a comprehensive simulation in which the dose was recalculated 625 times per given plan using Gaussian systematic setup and proton range uncertainties. Subsequently, based on the simulation results, we calculated the target coverage in all perturbation scenarios, as well as the ratios of target coverage located within the threshold of eight worst-case scenarios. We set the criteria for the optimized plan to be the ratios of 1) the dose delivered to 95% (D95%) of clinical target volumes 1 and 2 (CTV1 and CTV2) above 95% of the prescribed dose, and 2) the D95% of clinical target volume 3 (CTV3) above 90% of the prescribed dose in worst-case situations. Results The probability that the perturbed-dose indices of the CTVs in each scenario were within the worst-case scenario limits ranged from 89.51 to 91.22% for both the nominal and worst-case robust optimization IMPT plans. A quartile analysis showed that the selective robust optimization IMPT plans all had higher D95% values for CTV1, CTV2, and CTV3 than did the nominal IMPT plans. Conclusions The worst-case strategy for robust optimization is adequately models and covers most of the setup and range uncertainties for the IMPT treatment of head and neck patients in our center.

Air quality measurements usually consist of ground-based instrumentation at fixed locations. However, vertical profiles of pollutants are of interest for understanding processes, distribution, dilution and concentration. Therefore, a multicopter system has been developed to investigate the vertical distribution of the concentration of aerosol particles, black carbon, ozone, nitrogen oxides (NOx) and carbon monoxide and the meteorological parameters of temperature and humidity. This article presents the requirements by different users, the setup of the quadrocopter system, the instrumentation and the results of first applications. The vertical distribution of particulate matter next to a highway was strongly related to atmospheric stratification, with different concentrations below and above the temperature inversion present in the morning. After the qualification phase described in this article, two identically equipped multicopters will be used upwind and downwind of line or diffuse sources such as highways or urban areas to quantify the influence of their emissions on the local air quality.

IMPORTANCE: In the last 25 years, functional magnetic resonance imaging drug cue reactivity (FDCR) studies have characterized some core aspects in the neurobiology of drug addiction. However, no FDCR-derived biomarkers have been approved for treatment development or clinical adoption. Traversing this translational gap requires a systematic assessment of the FDCR literature evidence, its heterogeneity, and an evaluation of possible clinical uses of FDCR-derived biomarkers. OBJECTIVE: To summarize the state of the field of FDCR, assess their potential for biomarker development, and outline a clear process for biomarker qualification to guide future research and validation efforts. EVIDENCE REVIEW: The PubMed and Medline databases were searched for every original FDCR investigation published from database inception until December 2022. Collected data covered study design, participant characteristics, FDCR task design, and whether each study provided evidence that might potentially help develop susceptibility, diagnostic, response, prognostic, predictive, or severity biomarkers for 1 or more addictive disorders. FINDINGS: There were 415 FDCR studies published between 1998 and 2022. Most focused on nicotine (122 [29.6%]), alcohol (120 [29.2%]), or cocaine (46 [11.1%]), and most used visual cues (354 [85.3%]). Together, these studies recruited 19 311 participants, including 13 812 individuals with past or current substance use disorders. Most studies could potentially support biomarker development, including diagnostic (143 [32.7%]), treatment response (141 [32.3%]), severity (84 [19.2%]), prognostic (30 [6.9%]), predictive (25 [5.7%]), monitoring (12 [2.7%]), and susceptibility (2 [0.5%]) biomarkers. A total of 155 interventional studies used FDCR, mostly to investigate pharmacological (67 [43.2%]) or cognitive/behavioral (51 [32.9%]) interventions; 141 studies used FDCR as a response measure, of which 125 (88.7%) reported significant interventional FDCR alterations; and 25 studies used FDCR as an intervention outcome predictor, with 24 (96%) finding significant associations between FDCR markers and treatment outcomes. CONCLUSIONS AND RELEVANCE: Based on this systematic review and the proposed biomarker development framework, there is a pathway for the development and regulatory qualification of FDCR-based biomarkers of addiction and recovery. Further validation could support the use of FDCR-derived measures, potentially accelerating treatment development and improving diagnostic, prognostic, and predictive clinical judgments.

The direction of individual B8 solar neutrinos has been reconstructed using the SNO+ liquid scintillator detector. Prompt, directional Cherenkov light was separated from the slower, isotropic scintillation light using time information, and a maximum likelihood method was used to reconstruct the direction of individual scattered electrons. A clear directional signal was observed, correlated with the solar angle. The observation was aided by a period of low primary fluor concentration that resulted in a slower scintillator decay time. This is the first time that event-by-event direction reconstruction in high light-yield liquid scintillator has been demonstrated in a large-scale detector.