Pulsar timing arrays seek and study gravitational waves (GWs) through the angular two-point correlation function of timing residuals they induce in pulsars. The two-point correlation function induced by the standard transverse-traceless GWs is the famous Hellings-Downs curve, a function only of the angle between the two pulsars. Additional polarization modes (vector or scalar) that may arise in alternative-gravity theories have different angular correlation functions. Furthermore, anisotropy, linear, or circular polarization in the stochastic GW background gives rise to additional structure in the two-point correlation function that cannot be written simply in terms of the angular separation of the two pulsars. In this Letter, we provide a simple formula for the most general two-point correlation function-or overlap reduction function (ORF)-for a gravitational-wave background with an arbitrary polarization state, possibly containing anisotropies in its intensity and polarization (linear and/or circular). We provide specific expressions for the ORFs sourced by the general-relativistic transverse-traceless GW modes as well as vector (or spin-1) modes that may arise in alternative-gravity theories.

In 2021, the Youth Research Council (“YRC”) was formed to bring together high school students in the Northern Virginia region of the United States to conduct research on topics important to those youth (“YRC Fellows”). In its inaugural year, YRC Fellows designed a multi-method study to explore the effects of racial microaggressions on the mental health of their peers and to better understand how young people resist racial microaggressions and their often-deleterious effects on mental health. This article details the YRC’s full process, from formation of research questions to sharing findings in critical and participatory ways, as a model of youth participatory action research (YPAR). In addition to describing the ways in which the YRC embodies a YPAR epistemology, we are also showing our methods. To do this, we have built the article around a transcribed conversation held in July 2023 with the intention of teasing out and sorting through the implications of the YRC’s findings based on our first two years of research. The authors of this article include YRC Fellows and university-based researchers who facilitate the YRC.

Clinical studies have reported rising pre-treatment HIV drug resistance during antiretroviral treatment (ART) scale-up in Africa, but representative data are limited. We estimated population-level drug resistance trends during ART expansion in Uganda. We analyzed data from the population-based open Rakai Community Cohort Study conducted at agrarian, trading, and fishing communities in southern Uganda between 2012 and 2019. Consenting participants aged 15-49 were HIV tested and completed questionnaires. Persons living with HIV (PLHIV) provided samples for viral load quantification and virus deep-sequencing. Sequence data were used to predict resistance. Population prevalence of class-specific resistance and resistance-conferring substitutions were estimated using robust log-Poisson regression. Data from 93,622 participant-visits, including 4,702 deep-sequencing measurements, showed that the prevalence of NNRTI resistance among pre-treatment viremic PLHIV doubled between 2012 and 2017 (PR:1.98, 95%CI:1.34-2.91), rising to 9.61% (7.27-12.7%). The overall population prevalence of pre-treatment viremic NNRTI and NRTI resistance among all participants decreased during the same period, reaching 0.25% (0.18% - 0.33%) and 0.05% (0.02% - 0.10%), respectively ( p- values for trend = 0.00015, 0.002), coincident with increasing treatment coverage and viral suppression. By the final survey, population prevalence of resistance contributed by treatment-experienced PLHIV exceeded that from pre-treatment PLHIV, with NNRTI resistance at 0.54% (0.44%-0.66%) and NRTI resistance at 0.42% (0.33% - 0.53%). Overall, NNRTI and NRTI resistance was predominantly attributable to rtK103N and rtM184V. While 10.52% (7.97%-13.87%) and 9.95% (6.41%-15.43%) of viremic pre-treatment and treatment-experienced PLHIV harbored the inT97A mutation, no major dolutegravir resistance mutations were observed. Despite rising NNRTI resistance among pre-treatment PLHIV, overall population prevalence of pre-treatment resistance decreased due to treatment uptake. Most NNRTI and NRTI resistance is now contributed by treatment-experienced PLHIV. The high prevalence of mutations conferring resistance to components of current first-line ART regimens among PLHIV with viremia is potentially concerning. National Institutes of Health and the Gates Foundation. Evidence before the study: We searched PubMed for studies matching the keywords "hiv" "resistance" "longitudinal" "cohort" "population" published since 2004 (the beginning of antiretroviral therapy (ART) availability in sub-Saharan Africa) and identified 50 studies. We excluded 34 studies not based in sub-Saharan Africa, five studies primarily concerned with infection with other pathogens (e.g. HBV, M. tuberculosis ), two studies concerned with insulin resistance, one sequencing-methods paper, and one paper concerned with host susceptibility to HIV infection. The remaining seven studies were not population-based meaning that the study population was not all persons but e.g. people living with HIV enrolled in care at a given clinic. Population-based cohort are essential for monitoring HIV drug resistance in both treated and untreated individuals, including those people who may go undetected in clinical settings, capturing evolutionary dynamics of resistance in real-world conditions. Added value of this study: We estimated the prevalence of drug resistance over five consecutive survey rounds of a population-based open-cohort study in southern Uganda between 2012 and 2019 during a period of intense treatment scale-up. We show that among the entire population regardless of HIV status, 0.8% and 0.5% of individuals harbor viremic resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside-reverse transcriptase inhibitors (NRTIs), respectively, of which the majority is dual-class NNRTI/NRTI resistance. Despite a two-fold increase in the prevalence of NNRTI resistance among pre-treatment viremic PLHIV, the overall prevalence of pre-treatment viremic resistance in the entire population decreased by more than 50% due to increased treatment initiation and population viral load suppression. The majority of resistance in recent survey rounds was contributed by treatment-experienced PLHIV. Among treatment-experienced viremic PLHIV, we observe a substantial burden of mutations that confer resistance to the NNRTI and NRTI components of dolutegravir and cabotegravir based regimens e.g. rtM184V (34%) rtY181C (15%), rtG190A (12%), rtK65R (12%), and rtK101E (9.5%). The integrase strand transfer inhibitor (INSTI) resistance mutation inT97A was observed in about a tenth of viremic PLHIV.These results provide the first longitudinal population-based estimates of temporal trends in the prevalence of drug resistance during ART program expansion in a high-burden setting. Further, they provide critical insight into the landscape of prevalent drug resistance substitutions circulating in this population.Implications of all the available evidence: Scale-up of HIV treatment has increased the prevalence of drug resistance mutations among viremic people living with HIV in sub-Saharan Africa. The relatively high prevalence of NNRTI resistance has prompted a recent shift to first-line regimens including dolutegravir (an INSTI) in combination with NRTIs. The high prevalence of mutations conferring resistance to components of current first-line regimens in our population warrants continued monitoring of treatment failures and the prevalence of drug resistance in high burden settings.

The ability of double-stranded DNA or RNA to locally melt and form kinks leads to strong nonlinear elasticity effects that qualitatively affect their packing in confined spaces. Using analytical theory and numerical simulation we show that kink formation entails a mixed spool-nematic ordering of double-stranded DNA or RNA in spherical capsids, consisting of an outer spool domain and an inner, twisted nematic domain. These findings explain the experimentally observed nematic domains in viral capsids and imply that nonlinear elasticity must be considered to predict the configurations and dynamics of double-stranded genomes in viruses, bacterial nucleoids or gene-delivery vehicles. The nonlinear elastic theory suggests that spool-nematic ordering is a general feature of strongly confined kinkable polymers.

Depression rates are disproportionately high among Black American Men. This disparity--compounded by low mental healthcare seeking rates and high incorrect diagnosis rates in men--could be related to masculine norms, including self-reliance, restrictive emotionality, and stoicism. Furthermore, men are more likely to engage in externalized behavior, such as aggression, to cope with mental health challenges; this pattern is influenced by cultural and environmental factors. Contrary to these detrimental factors, social relationships, belief in social networks, and collectivism have been associated with positive mental health in these populations. Similarly, an Afrocentric worldview (including concepts like Ubuntu and African self-consciousness) has been hypothesized to promote positive mental health outcomes among Black American men. However, little research exists on harnessing these factors as a means of increasing health-seeking behaviors in young Black males. To elucidate the effect of region, depression, African humanism, collectivism, and help-seeking values and needs concerning aggression in young Black males. This study included Black or African American participants (n = 428) identifying as male, aged 18-25 years, who responded to a Qualtrics survey with questions on region, aggression, depression, African humanism, collectivism, and help-seeking value and need. Hierarchical linear regression revealed that collectivism, humanness, value, and the need for seeking treatment were inversely associated with aggression (p < 0.001). Highlighting the effect of cultural norms and help-seeking behaviors and the aggravating effect of depression on aggression in young Black males can help to develop aggression-mitigating interventions rooted in Afrocentric Norms.

Epigenetic regulation of neuronal transcriptomic landscape is emerging to be a key coordinator of mammalian neural regeneration. Here we investigated roles of two histone 3 lysine 27 (H3K27) demethylases Kdm6a/b in controlling neuroprotection and axon regeneration. Deleting either Kdm6a or Kdm6b led to enhanced sensory axon regeneration in PNS, whereas in the CNS only deleting Kdm6a in retinal ganglion cells (RGCs) significantly enhanced optic nerve regeneration. Moreover, both Kdm6a and Kdm6b functioned to regulate RGC survival but with different mechanisms. Mechanistically, Kdm6a regulates RGC regeneration via distinct pathway from that of Pten and co-deleting Kdm6a and Pten resulted in long distance optic nerve regeneration passing the optic chiasm. In addition, RNA-seq profiling revealed that Kdm6a deletion switched the RGC transcriptomics into a developmental-like state and suppressed several known repressors of neural regeneration. Klf4 was identified as a direct downstream target of Kdm6a-H3K27me3 signaling in both sensory neurons and RGCs to regulate axon regeneration. These findings not only revealed different roles of Kdm6a and Kdm6b in regulation of neural regeneration and their underlying mechanisms, but also identified Kdm6a-mediated histone demethylation signaling as a novel epigenetic target for supporting CNS neural regeneration.