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Abstract Background The clinical translation of positron emission tomography (PET) radiotracers for cancer management presents complex challenges. We have developed consensus-based recommendations for preclinical and clinical assessment of novel and established radiotracers, applied to image different cancer types, to improve the standardisation of translational methodologies and accelerate clinical implementation. Methods A consensus process was developed using the RAND/UCLA Appropriateness Method (RAM) to gather insights from a multidisciplinary panel of 38 key stakeholders on the appropriateness of preclinical and clinical methodologies and stakeholder engagement for PET radiotracer translation. Panellists independently completed a consensus survey of 57 questions, rating each on a 9-point Likert scale. Subsequently, panellists attended a consensus meeting to discuss survey outcomes and readjust scores independently if desired. Survey items with median scores ≥ 7 were considered ‘required/appropriate’, ≤ 3 ‘not required/inappropriate’, and 4–6 indicated ‘uncertainty remained’. Consensus was determined as ~ 70% participant agreement on whether the item was ‘required/appropriate’ or ‘not required/not appropriate’. Results Consensus was achieved for 38 of 57 (67%) survey questions related to preclinical and clinical methodologies, and stakeholder engagement. For evaluating established radiotracers in new cancer types, in vitro and preclinical studies were considered unnecessary, clinical pharmacokinetic studies were considered appropriate, and clinical dosimetry and biodistribution studies were considered unnecessary, if sufficient previous data existed. There was ‘agreement without consensus’ that clinical repeatability and reproducibility studies are required while ‘uncertainty remained’ regarding the need for comparison studies. For novel radiotracers, in vitro and preclinical studies, such as dosimetry and/or biodistribution studies and tumour histological assessment were considered appropriate, as well as comprehensive clinical validation. Conversely, preclinical reproducibility studies were considered unnecessary and ‘uncertainties remained’ regarding preclinical pharmacokinetic and repeatability evaluation. Other consensus areas included standardisation of clinical study protocols, streamlined regulatory frameworks and patient and public involvement. While a centralised UK clinical imaging research infrastructure and open access federated data repository were considered necessary, there was ‘agreement without consensus’ regarding the requirement for a centralised UK preclinical imaging infrastructure. Conclusions We provide consensus-based recommendations, emphasising streamlined methodologies and regulatory frameworks, together with active stakeholder engagement, for improving PET radiotracer standardisation, reproducibility and clinical implementation in oncology.

Sepsis, the leading cause of mortality in hospitals, currently lacks effective early diagnostics. A new cellular host response test, the IntelliSep test, may provide an indicator of the immune dysregulation characterizing sepsis. The objective of this study was to examine the correlation between the measurements performed using this test and biological markers and processes associated with sepsis. Phorbol myristate acetate (PMA), an agonist of neutrophils known to induce neutrophil extracellular trap (NET) formation, was added to whole blood of healthy volunteers at concentrations of 0, 200, and 400 nM and then evaluated using the IntelliSep test. Separately, plasma from a cohort of subjects was segregated into Control and Diseased populations and tested for levels of NET components (citrullinated histone (cit-H3) DNA and neutrophil elastase (NE) DNA) using customized ELISA assays and correlated with ISI scores from the same patient samples. Significant increases in IntelliSep Index (ISI) scores were observed with increasing concentrations of PMA in healthy blood (0 and 200: p < 10-10; 0 and 400: p < 10-10). Linear correlation was observed between the ISI and quantities of NE DNA and Cit-H3 DNA in patient samples. Together these experiments demonstrate that the IntelliSep test is associated with the biological processes of leukocyte activation and NETosis and may indicate changes consistent with sepsis.

Abstract Interplanetary (IP) shocks are perturbations observed in the solar wind. IP shocks correlate well with solar activity, being more numerous during times of high sunspot numbers. Earth‐bound IP shocks cause many space weather effects that are promptly observed in geospace and on the ground. Such effects can pose considerable threats to human assets in space and on the ground, including satellites in the upper atmosphere and power infrastructure. Thus, it is of great interest to the space weather community to (a) keep an accurate catalog of shocks observed near Earth, and (b) be able to forecast shock occurrence as a function of the solar cycle (SC). In this work, we use a supervised machine learning regression model to predict the number of shocks expected in SC25 using three previously published sunspot predictions for the same cycle. We predict shock counts to be around 275 ± 10, which is ∼47% higher than the shock occurrence in SC24 (187 ± 8), but still smaller than the shock occurrence in SC23 (343 ± 12). With the perspective of having more IP shocks on the horizon for SC25, we briefly discuss many opportunities in space weather research for the remainder years of SC25. The next decade or so will bring unprecedented opportunities for research and forecasting effects in the solar wind, magnetosphere, ionosphere, and on the ground. As a result, we predict SC25 will offer excellent opportunities for shock occurrences and data availability for conducting space weather research and forecasting.

Exposure therapy is a first-line, empirically validated treatment for anxiety, obsessive-compulsive, and trauma-related disorders. Extinction learning is the predominant theoretical framework for exposure therapy, whereby repeated disconfirmation of a feared outcome yields fear reduction over time. Although this framework has strong empirical support and substantial translational utility, extinction learning is unlikely to be the sole process underlying the therapeutic effects of exposure therapy. In our clinic, we commonly treat obsessive-compulsive disorder (OCD) patients successfully with exposure therapy even when some or all of their feared outcomes are not amenable to disconfirmation and, by extension, to extinction learning. Herein, we present a generic clinical vignette illustrating a commonly encountered feared outcome in OCD that cannot be disconfirmed through exposure (damnation resulting from blasphemous thoughts). We describe two specific non-extinction-based strategies we commonly employ in such cases, and we associate these strategies with known change mechanisms that might account for their effectiveness: (1) non-associative habituation to aversive stimuli, and (2) fear-memory elicitation and subsequent reconsolidation. We discuss the limitations inherent in the reverse-translational approach taken and its opportunities for expanding the framework of exposure therapy.

Sexual violence has been found to have psychosocial and sexual ramifications for men who have sex with men (MSM) but has not been studied in the Middle East. We assessed the prevalence and correlates of experiences of child and post-child sexual violence among young MSM residing in Beirut, Lebanon. In total, 226 MSM, aged 18 to 29, were recruited with long-chain peer referrals and administered a survey that included questions on history of being pressured to have sex, as well as specific forms of sexual harassment and abuse, in addition to measures of psychosocial functioning and sexual behavior. Logistic regression analysis was used to examine correlates of child sex abuse and experiences of sexual violence post-childhood; 17.3% experienced sexual abuse as a child (below age 13), while 63.3% experienced any form of sexual violence post-childhood-furthermore, 48.7% had experienced being forced or pressured to have sex during their lifetime, including 32.3% prior to age 18. Participants who experienced child sex abuse were more likely to experience abusive relationships in adulthood, as well as at least one type of sexual harassment/abuse post-childhood. Experience of any sexual violence post-childhood was correlated with greater recent sexuality-related discrimination and more recent male sex partners. These findings reveal a high prevalence of sexual violence among MSM in Beirut, both in childhood and post-childhood. More research within the Middle East is needed to better understand the drivers of sexual violence in this population, and how to best provide prevention and coping services.

The Middle East and North Africa (MENA) is one of only two global regions where rates of HIV are currently on the rise. In Lebanon, new HIV infections are increasing most rapidly among young men who have sex with men (YMSM). While, the majority of YMSM in Lebanon report having recently engaged in condomless anal intercourse, many report reluctance to seek HIV prevention services for fear of stigma and discrimination. Pre-exposure prophylaxis (PrEP) is an effective alternative HIV prevention strategy but there is a dearth of research looking at willingness to take PrEP among YMSM in MENA. This study is the first to delineate factors associated with willingness to take PrEP among a cohort of 218 YMSM recruited from Beirut, Lebanon. Over half (55.5%) reported willingness to take PrEP. At the bivariate level, knowledge of HIV risk, awareness of PrEP, being in a relationship, greater judgementalism about sex in communication with peers, greater number of types of gay-related discrimination experienced, sense of community among YMSM, having had recent condomless anal sex with positive or unknown status partner, and the use of substances just prior to or during sex were each associated with greater willingness to take PrEP. When entered into a linear regression analysis, use of substances just prior to or during sex and sense of community among YMSM remained significant predictors of PrEP willingness. Intervention efforts focused on increasing PrEP uptake among YMSM in MENA should consider the influence substance use and social factors on willingness to take PrEP.

Abstract Despite the growing importance of planetary Space Weather forecasting and radiation protection for science and robotic exploration and the need for accurate Space Weather monitoring and predictions, only a limited number of spacecraft have dedicated instrumentation for this purpose. However, every spacecraft (planetary or astronomical) has hundreds of housekeeping sensors distributed across the spacecraft, some of which can be useful to detect radiation hazards produced by solar particle events. In particular, energetic particles that impact detectors and subsystems on a spacecraft can be identified by certain housekeeping sensors, such as the Error Detection and Correction (EDAC) memory counters, and their effects can be assessed. These counters typically have a sudden large increase in a short time in their error counts that generally match the arrival of energetic particles to the spacecraft. We investigate these engineering datasets for scientific purposes and perform a feasibility study of solar energetic particle event detections using EDAC counters from seven European Space Agency Solar System missions: Venus Express, Mars Express, ExoMars‐Trace Gas Orbiter, Rosetta, BepiColombo, Solar Orbiter, and Gaia. Six cases studies, in which the same event was observed by different missions at different locations in the inner Solar System are analyzed. The results of this study show how engineering sensors, for example, EDAC counters, can be used to infer information about the solar particle environment at each spacecraft location. Therefore, we demonstrate the potential of the various EDAC to provide a network of solar particle detections at locations where no scientific observations of this kind are available.

Background: The clinical translation of positron emission tomography (PET) radiotracers for cancer management presents complex challenges. We have developed consensus-based recommendations for preclinical and clinical assessment of novel and established radiotracers, applied to image different cancer types, to improve the standardisation of translational methodologies and accelerate clinical implementation. Methods: A consensus process was developed using the RAND/UCLA Appropriateness Method (RAM) to gather insights from a multidisciplinary panel of 38 key stakeholders on the appropriateness of preclinical and clinical methodologies and stakeholder engagement for PET radiotracer translation. Panellists independently completed a consensus survey of 57 questions, rating each on a 9-point Likert scale. Subsequently, panellists attended a consensus meeting to discuss survey outcomes and readjust scores independently if desired. Survey items with median scores ≥ 7 were considered 'required/appropriate', ≤ 3 'not required/inappropriate', and 4–6 indicated 'uncertainty remained'. Consensus was determined as ~ 70% participant agreement on whether the item was 'required/appropriate' or 'not required/not appropriate'. Results: Consensus was achieved for 38 of 57 (67%) survey questions related to preclinical and clinical methodologies, and stakeholder engagement. For evaluating established radiotracers in new cancer types, in vitro and preclinical studies were considered unnecessary, clinical pharmacokinetic studies were considered appropriate, and clinical dosimetry and biodistribution studies were considered unnecessary, if sufficient previous data existed. There was 'agreement without consensus' that clinical repeatability and reproducibility studies are required while 'uncertainty remained' regarding the need for comparison studies. For novel radiotracers, in vitro and preclinical studies, such as dosimetry and/or biodistribution studies and tumour histological assessment were considered appropriate, as well as comprehensive clinical validation. Conversely, preclinical reproducibility studies were considered unnecessary and 'uncertainties remained' regarding preclinical pharmacokinetic and repeatability evaluation. Other consensus areas included standardisation of clinical study protocols, streamlined regulatory frameworks and patient and public involvement. While a centralised UK clinical imaging research infrastructure and open access federated data repository were considered necessary, there was 'agreement without consensus' regarding the requirement for a centralised UK preclinical imaging infrastructure. Conclusions: We provide consensus-based recommendations, emphasising streamlined methodologies and regulatory frameworks, together with active stakeholder engagement, for improving PET radiotracer standardisation, reproducibility and clinical implementation in oncology. [ABSTRACT FROM AUTHOR]

Author(s): Lu Dong [sup.1] , Laura M. Bogart [sup.1] , Matt G. Mutchler [sup.2] , Sean J. Lawrence [sup.2] , David J. Klein, Mahlet Gizaw [sup.1] , Glenn J. Wagner [...], Perceived discrimination and medical mistrust are contributors to HIV inequities. The current study examined whether medical mistrust mediated the associations between perceived discrimination and adherence to antiretroviral therapy (ART) as well as care engagement in a sample of 304 Black adults living with HIV. Perceived discrimination and medical mistrust were measured using validated scales; ART adherence was electronically monitored for a month; care engagement was determined by medical record data. Results support significant total indirect effects from perceived discrimination (due to HIV-serostatus, race, sexual orientation) to ART adherence through three types of medical mistrust (towards healthcare organizations, one&apos;s physician, and HIV-specific mistrust). The total indirect effects were also significant for care engagement and were largely driven by mistrust towards one&apos;s own physician. Findings suggest interventions at the provider or healthcare organization levels should address medical mistrust to improve the health and well-being of Black Americans living with HIV.

The Lunar Orbital Platform - Gateway (LOP - Gateway, or simply Gateway) is a crewed platform that will be assembled and operated in the vicinity of the Moon by NASA and international partner organizations, including ESA, starting from the mid-2020s. It will offer new opportunities for fundamental and applied scientific research. The Moon is a unique location to study the deep space plasma environment. Moreover, the lunar surface and the surface-bounded exosphere are interacting with this environment, constituting a complex multi-scale interacting system. This paper examines the opportunities provided by externally mounted payloads on the Gateway in the field of space plasma physics, heliophysics and space weather, and also examines the impact of the space environment on an inhabited platform in the vicinity of the Moon. It then presents the conceptual design of a model payload, required to perform these space plasma measurements and observations. It results that the Gateway is very well-suited for space plasma physics research. It allows a series of scientific objectives with a multi-disciplinary dimension to be addressed.

Young gay men in Beirut are at significantly elevated risk of HIV infection compared with the general Lebanese population. Despite nascent HIV prevention efforts in the region, there is a need for effective community-level HIV prevention interventions tailored for young gay men. This qualitative study examined internal dynamics within Beirut's gay community as a basis for developing community-level interventions. Peer ethnographers were trained to collect field notes on conversations between young gay men in public spaces in Beirut, and conducted follow-up focus groups with young gay men. Analyses revealed three major themes: (1) the need for safe spaces in which to socialise, (2) the importance of being able to locate and connect with other young gay men, and (3) ambivalence regarding a gay community that was supportive in some ways but also fragmented and often judgemental. Study findings also confirm the existence of external threats to community such as stigma, cultural and familial norms regarding heterosexuality and criminalisation of refugee status. Understanding such community dynamics and the environmental context is central to designing effective community-based HIV prevention programmes.

In the United States, black men who have sex with men (MSM) are the group most affected by the HIV/AIDS epidemic. Pre-exposure prophylaxis (PrEP) is an important new HIV prevention strategy that may help reduce new HIV infections among black MSM. This analysis examined the association between HIV/AIDS conspiracy beliefs and intentions to adopt PrEP among 224 black MSM. The likelihood of adopting PrEP was assessed and more than half (60%) of the study population indicated a high intention to adopt PrEP. HIV/AIDS genocidal and treatment-related conspiracies were assessed using scales previously validated with black MSM. Almost two-thirds (63%) endorsed at least one of eight HIV/AIDS conspiracy beliefs presented. In multivariable analyses, black MSM who agreed with the genocidal or treatment-related conspiracy beliefs scales had a lower intention to adopt PrEP (Adjusted Odds Ratio [AOR] = 0.73, 95% CI = 0.54, 0.99 and AOR = 0.36, 95% CI = 0.23, 0.55, respectively). Our findings indicate that preexisting HIV/AIDS conspiracy beliefs may deter some black MSM from adopting PrEP. We suggest strategies PrEP implementers may want to employ to address the influence that HIV/AIDS conspiracy beliefs may have on the adoption of PrEP among black MSM, a population disproportionately affected by HIV/AIDS.

We report on the second observing program of the active galactic nucleus NGC 4151 with simultaneous Imaging X-ray Polarimetry Explorer (IXPE; 750 ks), NuSTAR (∼60 ks), XMM-Newton (∼75 ks), and NICER (∼65 ks) pointings. NGC 4151 is the first Type-1 radio-quiet Seyfert galaxy with constrained polarization properties for the X-ray corona. Despite the lower flux state in which the source was re-observed and the resulting higher contribution of the constant reflection component in the IXPE energy band, our results are in agreement with the first detection. From polarimetric analysis, a polarization degree Π = 4.7 ± 1.3% and polarization angle Ψ = 77° ± 8° east of north (68% c.l.) were derived in the 2.0–8.0 keV energy range. Combining the two observations leads to polarization properties that are more constrained than those of the individual detections, showing Π = 4.5 ± 0.9% and Ψ = 81° ± 6° (with a detection significance of ∼4.6σ). The observed polarization angle aligns very well with the radio emission in this source, supporting, together with the significant polarization degree, a slab or wedge geometry for the X-ray corona. However, a switch in the polarization angle at low energies (37° ±7° in the 2–3.5 keV bin) suggests the presence of another component. When it is included in the spectro-polarimetric fit, a high polarization degree disfavors an interpretation in terms of a leakage through the absorbers, instead pointing to scattering from some kind of mirror. [ABSTRACT FROM AUTHOR]

We present simultaneous X-ray polarimetric and spectral observations of the bright atoll source Ser X-1 carried out with the Imaging X-ray Polarimetry Explorer (IXPE), NICER, and NuSTAR. We obtain an upper limit of 2% (99% confidence level) on the polarization degree in the 2–8 keV energy band. We detect four type-I X-ray bursts, two of which during the IXPE observation. This is the first time that has IXPE observed type-I X-ray bursts, and it allows us to place an upper limit on their polarization degree; however, due to the limited total number of counts in each burst, we obtain a relatively high upper limit (80%). We confirm the presence of reflection features in the X-ray spectrum, notably a broad iron line. Fitting the data with a relativistic reflection model, we derive a disk inclination of 25°. The spectral and polarization properties are comparable with other atolls observed by IXPE, suggesting a similar accretion geometry, and the relatively low polarization is consistent with the low inclination. [ABSTRACT FROM AUTHOR]

Computer science offers a large set of tools for prototyping, writing, running, testing, validating, sharing and reproducing results; however, computational science lags behind. In the best case, authors may provide their source code as a compressed archive and they may feel confident their research is reproducible. But this is not exactly true. James Buckheit and David Donoho proposed more than two decades ago that an article about computational results is advertising, not scholarship. The actual scholarship is the full software environment, code, and data that produced the result. This implies new workflows, in particular in peer-reviews. Existing journals have been slow to adapt: source codes are rarely requested and are hardly ever actually executed to check that they produce the results advertised in the article. ReScience is a peer-reviewed journal that targets computational research and encourages the explicit replication of already published research, promoting new and open-source implementations in order to ensure that the original research can be replicated from its description. To achieve this goal, the whole publishing chain is radically different from other traditional scientific journals. ReScience resides on GitHub where each new implementation of a computational study is made available together with comments, explanations, and software tests.

Intrinsically disordered proteins (IDPs) are an important and emerging class of materials for tailoring biointerfaces. While the importance of chain charge and resultant electrostatic interactions in controlling conformational properties of IDPs is beginning to be explored through in silico approaches, there is a dearth of experimental studies motivated toward a systematic study of these effects. In an effort to explore this relationship, we measured the conformations of two peptides derived from the intrinsically disordered neurofilament (NF) side arm domain: one depicting the wild-type sequence with four lysine-serine-proline repeats (KSP peptide) and another in which the serine residues were replaced with aspartates (KDP peptide), a strategy sometimes used to mimic phosphorylation. Using a variety of biophysical measurements including a novel application of scanning angle interference microscopy, we demonstrate that the KDP peptide assumes comparatively more expanded conformations in solution and forms significantly thicker brushes when immobilized on planar surfaces at high densities. In both settings, the peptides respond to changes in ambient ionic strength, with each peptide showing distinct stimulus-responsive characteristics. While the KDP peptide undergoes compaction with increasing ionic strength as would be expected for a polyampholyte, the KSP peptide shows biphasic behavior, with an initial compaction followed by an expanded state at a higher ionic strength. Together these results support the notion that modulation of charge on IDPs can regulate conformational and interfacial properties.

We examined individual-level, partnership-level, and sexual event-level factors associated with condom use during receptive anal intercourse (RAI) among 163 low-income, racially/ethnically diverse, HIV-negative men who have sex with men (MSM) in Los Angeles (2007-2010). At baseline, 3-month, and 12-month visits, computer-assisted self-interviews collected information on ≤3 recent male partners and the last sexual event with those partners. Factors associated with condom use during RAI at the last sexual event were identified using logistic generalized linear mixed models. Condom use during RAI was negatively associated with reporting ≥ high school education (adjusted odds ratio [AOR] = 0.32, 95 % confidence interval [CI] 0.11-0.96) and methamphetamine use, specifically during RAI events with non-main partners (AOR = 0.20, 95 % CI 0.07-0.53) and those that included lubricant use (AOR = 0.20, 95 % CI 0.08-0.53). Condom use during RAI varies according to individual-level, partnership-level, and sexual event-level factors that should be considered in the development of risk reduction strategies for this population.

A research-based understanding of how to develop and assess classroom presentation skills is vital for the effective development of pre-service teacher communication capabilities. This paper identifies and compares two different models of assessing pre-service teachers' presentation performance--one based on the Modes of Communication (voice, body language, words, and alignment between those elements) and another based on features of the Constructed Impression of the communication acts (confidence, clarity, engagement and appropriateness). The Modes of Communication and the Constructed Impression of 164 pre-service teacher presentations were rated. The Constructed Impression model provided a better fit to data, while averaging of Modes of Communication elements offered more accurate prediction of overall score. All elements in both models made a significant contribution to the overall perception of communication performance. The study also reports on the relative contribution of voice, body language, words and alignment to the perceived confidence, clarity, engagement and appropriateness of the pre-service teacher presentations. Implications for developing pre-service teachers' presentation capabilities are also discussed. (Contains 6 tables.)

Sepsis, the leading cause of mortality in hospitals, currently lacks effective early diagnostics. A new cellular host response test, the IntelliSep test, may provide an indicator of the immune dysregulation characterizing sepsis. The objective of this study was to examine the correlation between the measurements performed using this test and biological markers and processes associated with sepsis. Phorbol myristate acetate (PMA), an agonist of neutrophils known to induce neutrophil extracellular trap (NET) formation, was added to whole blood of healthy volunteers at concentrations of 0, 200, and 400 nM and then evaluated using the IntelliSep test. Separately, plasma from a cohort of subjects was segregated into Control and Diseased populations and tested for levels of NET components (citrullinated histone (cit-H3) DNA and neutrophil elastase (NE) DNA) using customized ELISA assays and correlated with ISI scores from the same patient samples. Significant increases in IntelliSep Index (ISI) scores were observed with increasing concentrations of PMA in healthy blood (0 and 200: p < 10−10; 0 and 400: p < 10−10). Linear correlation was observed between the ISI and quantities of NE DNA and Cit-H3 DNA in patient samples. Together these experiments demonstrate that the IntelliSep test is associated with the biological processes of leukocyte activation and NETosis and may indicate changes consistent with sepsis.

XIPE, the X-ray Imaging Polarimetry Explorer, is a mission dedicated to X-ray Astronomy. At the time of writing XIPE is in a competitive phase A as fourth medium size mission of ESA (M4). It promises to reopen the polarimetry window in high energy Astrophysics after more than 4 decades thanks to a detector that efficiently exploits the photoelectric effect and to X-ray optics with large effective area. XIPE uniqueness is time-spectrally-spatially-resolved X-ray polarimetry as a breakthrough in high energy astrophysics and fundamental physics. Indeed the payload consists of three Gas Pixel Detectors at the focus of three X-ray optics with a total effective area larger than one XMM mirror but with a low weight. The payload is compatible with the fairing of the Vega launcher. XIPE is designed as an observatory for X-ray astronomers with 75 % of the time dedicated to a Guest Observer competitive program and it is organized as a consortium across Europe with main contributions from Italy, Germany, Spain, United Kingdom, Poland, Sweden.