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ObjectivesStudies of neurocognitively elite older adults, termed SuperAgers, have identified clinical predictors and neurobiological indicators of resilience against age-related neurocognitive decline. Despite rising rates of older persons living with HIV (PLWH), SuperAging (SA) in PLWH remains undefined. We aimed to establish neuropsychological criteria for SA in PLWH and examined clinically relevant correlates of SA.Methods734 PLWH and 123 HIV-uninfected participants between 50 and 64 years of age underwent neuropsychological and neuromedical evaluations. SA was defined as demographically corrected (i.e., sex, race/ethnicity, education) global neurocognitive performance within normal range for 25-year-olds. Remaining participants were labeled cognitively normal (CN) or impaired (CI) based on actual age. Chi-square and analysis of variance tests examined HIV group differences on neurocognitive status and demographics. Within PLWH, neurocognitive status differences were tested on HIV disease characteristics, medical comorbidities, and everyday functioning. Multinomial logistic regression explored independent predictors of neurocognitive status.ResultsNeurocognitive status rates and demographic characteristics differed between PLWH (SA=17%; CN=38%; CI=45%) and HIV-uninfected participants (SA=35%; CN=55%; CI=11%). In PLWH, neurocognitive groups were comparable on demographic and HIV disease characteristics. Younger age, higher verbal IQ, absence of diabetes, fewer depressive symptoms, and lifetime cannabis use disorder increased likelihood of SA. SA reported increased independence in everyday functioning, employment, and health-related quality of life than non-SA.ConclusionsDespite combined neurological risk of aging and HIV, youthful neurocognitive performance is possible for older PLWH. SA relates to improved real-world functioning and may be better explained by cognitive reserve and maintenance of cardiometabolic and mental health than HIV disease severity. Future research investigating biomarker and lifestyle (e.g., physical activity) correlates of SA may help identify modifiable neuroprotective factors against HIV-related neurobiological aging. (JINS, 2019, 25, 507-519).

BackgroundDuring antiretroviral therapy, HIV RNA can be detected in cerebrospinal fluid (CSF) when it is undetectable in plasma, a condition termed 'CSF viral escape'. The aim of the current study was to determine the prevalence and risk factors for CSF viral escape in two large cohorts in the USA.MethodsA total of 1264 HIV-infected volunteers enrolled in two US cohorts at their most recent visit between 2003 and 2011 were included in this cross-sectional analysis if their HIV RNA level in plasma was less than 50 copies/ml while receiving stable antiretroviral therapy (ART) (>6 months) and if they had HIV RNA measured in CSF at their most recent visit between 2003 and 2011. Potential risk factors were identified using univariable and multivariable regression.ResultsCSF viral escape was detected in 55 adults (4.4%; 95% CI: 3.4-5.6), who had a median CSF HIV RNA of 155 copies/ml [interquartile range (IQR: 80-283)]. Patients with or without CSF viral escape had similar rates of neurocognitive impairment (38.2 vs. 37.7%; P = 0.91). CSF viral escape was independently associated with the use of ritonavir-boosted protease inhibitors [odds ratio (OR): 2.0; 95% CI: 1.1-3.8] or unboosted atazanavir (OR: 5.1; 95% CI: 1.3-16.1), CSF pleocytosis (OR: 7.6; 95% CI: 4.2-13.7) and abnormal CSF total protein (OR: 2.1; 95% CI: 1.1-3.7).ConclusionsIn this large study of aviremic patients receiving ART, CSF viral escape was uncommon and was linked to evidence of central nervous system inflammation and the use of protease inhibitors, but not with worse neurocognitive performance.

HIV-associated neurocognitive disorders (HANDs) persist even with virologic suppression on combination antiretroviral therapy (cART), and the underlying pathophysiological mechanisms are not well understood. We performed structural magnetic resonance imaging and MR spectroscopy (MRS) in HIV+ individuals without major neurocognitive comorbidities. Study participants were classified as neurocognitively unimpaired (NU), asymptomatic (ANI), mild neurocognitive disorder (MND), or HIV-associated dementia (HAD). Using structural MRI, we measured volumes of cortical and subcortical gray matter and total and abnormal white matter (aWM). Using single-voxel MRS, we estimated metabolites in frontal gray matter (FGM) and frontal white matter (FWM) and basal ganglia (BG) regions. Adjusted odds ratios were used to compare HAND to NU. Among 253 participants, 40% met HAND criteria (21% ANI, 15% MND, and 4% HAD). Higher risk of HAND was associated with more aWM. Both HAD and MND also had smaller gray and white matter volumes than NU. Among individuals with undetectable plasma HIV RNA, structural volumetric findings were similar to the overall sample. MND had lower FWM creatine and higher FGM choline relative to NU, whereas HAD and ANI had lower BG N-acetyl aspartate relative to NU. In the virologically suppressed subgroup, however, ANI and MND had higher FGM choline compared to NU. Overall, HAND showed specific alterations (more aWM and inflammation; less gray matter volume and lower NAA). Some MR measures differentiated less severe subtypes of HAND from HAD. These MR alterations may represent legacy effects or accumulating changes, possibly related to medical comorbidities, antiretroviral therapy, or chronic effects of HIV brain infection.

Abstract Background The opioid crisis has necessitated new approaches to managing chronic pain. The Veterans Health Administration (VHA) Whole Health model of care, with its focus on patient empowerment and emphasis on nonpharmacological approaches to pain management, is a promising strategy for reducing patients’ use of opioids. We aim to assess whether the VHA’s Whole Health pilot program impacted longitudinal patterns of opioid utilization among patients with chronic musculoskeletal pain. Methods A cohort of 4,869 Veterans with chronic pain engaging in Whole Health services was compared with a cohort of 118,888 Veterans receiving conventional care. All patients were continuously enrolled in VHA care from 10/2017 through 3/2019 at the 18 VHA medical centers participating in the pilot program. Inverse probability of treatment weighting and multivariate analyses were used to adjust for observable differences in patient characteristics between exposures and conventional care. Patients exposed to Whole Health services were offered nine complementary and integrative health therapies alone or in combination with novel Whole Health services including goal-setting clinical encounters, Whole Health coaching, and personal health planning. Main measures The main measure was change over an 18-month period in prescribed opioid doses starting from the six-month period prior to qualifying exposure. Results Prescribed opioid doses decreased by -12.0% in one year among Veterans who began complementary and integrative health therapies compared to similar Veterans who used conventional care; -4.4% among Veterans who used only Whole Health services such as goal setting and coaching compared to conventional care, and -8.5% among Veterans who used both complementary and integrative health therapies combined with Whole Health services compared to conventional care. Conclusions VHA’s Whole Health national pilot program was associated with greater reductions in prescribed opioid doses compared to secular trends associated with conventional care, especially when Veterans were connected with complementary and integrative health therapies.

Preparation of scientific publications includes transaction costs as an integral part. The aim of the work was to analyze the changes over the past 50 years in transaction costs in the publication process and the impact of these costs on the results of publication activities. The article discusses the changes that have taken place in the procedure for choosing a publishing house, methods of the manuscript design, translation of the text, compiling a list of references, interaction with publishers and other issues of preparing scientific publications. It is shown that the reduction of transaction costs is one of the most important ways to increase the scientific and publication activity of teachers and researchers.

Introduction: Diuretics are a mainstay therapy for congestive heart failure (CHF); however, over one-third of patients develop diuretic resistance. Second-generation artificial intelligence (AI) systems introduce variability into treatment regimens to overcome the compensatory mechanisms underlying the loss of effectiveness of diuretics. This open-labeled, proof-of-concept clinical trial sought to investigate the ability to improve diuretic resistance by implementing algorithm-controlled therapeutic regimens. Methods: Ten CHF patients with diuretic resistance were enrolled in an open-labeled trial where the Altus Care™ app managed diuretics' dosage and administration times. The app provides a personalized therapeutic regimen creating variability in dosages and administration times within pre-defined ranges. Response to therapy was measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) score, 6-minute walk test (SMW), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and renal function. Results: The second-generation, AI-based, personalized regimen alleviated diuretic resistance. All evaluable patients demonstrated clinical improvement within ten weeks of intervention. A dose reduction (based on a three-week average before and last three weeks of intervention) was achieved in 7/10 patients (70 %, p = 0.042). The KCCQ score improved in 9/10 (90 %, p = 0.002), the SMW improved in 9/9 (100 %, p = 0.006), NT-proBNP was decreased in 7/10 (70 %, p = 0.02), and serum creatinine was decreased in 6/10 (60 %, p = 0.05). The intervention was associated with reduced number of emergency room visits and the number of CHF-associated hospitalizations. Summary: The results support that the randomization of diuretic regimens guided by a second-generation personalized AI algorithm improves the response to diuretic therapy. Prospective controlled studies are needed to confirm these findings.

BACKGROUND Cellular stressors influence the development of clonal hematopoiesis (CH). We hypothesized that environmental, inflammatory, and genotoxic stresses drive the emergence of CH in lung transplant recipients. METHODS We performed a cross-sectional cohort study of 85 lung transplant recipients to characterize CH prevalence. We evaluated somatic variants using duplex error-corrected sequencing and germline variants using whole exome sequencing. We evaluated CH frequency and burden using χ2 and Poisson regression, and we evaluated associations with clinical and demographic variables and clinical outcomes using χ2, logistic regression, and Cox regression. RESULTS CH in DNA damage response (DDR) genes TP53, PPM1D, and ATM was increased in transplant recipients compared with a control group of older adults (28% versus 0%, adjusted OR [aOR], 12.9 [1.7–100.3], P = 0.0002). Age (OR, 1.13 [1.03–1.25], P = 0.014) and smoking history (OR 4.25 [1.02–17.82], P = 0.048) were associated with DDR CH. Germline variants predisposing to idiopathic pulmonary fibrosis were identified but not associated with CH. DDR CH was associated with increased cytomegalovirus viremia versus patients with no (OR, 7.23 [1.95–26.8], P = 0.018) or non-DDR CH (OR, 7.64 [1.77–32.89], P = 0.024) and mycophenolate discontinuation (aOR, 3.8 [1.3–12.9], P = 0.031). CONCLUSION CH in DDR genes is prevalent in lung transplant recipients and is associated with posttransplant outcomes including cytomegalovirus activation and mycophenolate intolerance. FUNDING NIH/NHLBI K01HL155231 (LKT), R25HL105400 (LKT), Foundation for Barnes-Jewish Hospital (LKT), Evans MDS Center at Washington University (KAO, MJW), ASH Scholar Award (KAO), NIH K12CA167540 (KAO), NIH P01AI116501 (AEG, DK), NIH R01HL094601 (AEG), and NIH P01CA101937 (DCL).

Background:. Targeted muscle reinnervation (TMR) outcome studies reveal the benefit amputees experience and the potential functional improvement by optimizing neurocutaneous signaling for myoelectric prosthesis control. However, there are still many settings where these techniques are not offered to patients requiring lower extremity amputations or neuroma reconstruction. With growing consistency in the literature, it is helpful to systematize the nerve transfers described for lower extremity TMR and to simplify its integration into reconstructive care. Methods:. A systematic literature review was performed and contained the following inclusion criteria: original cases of primary or secondary lower extremity amputation defects or nerve-related pain that underwent TMR with clearly described target muscles for each nerve transfer. Studies were excluded if the cases had been previously described or contained incomplete data. The primary outcomes were nerves transferred and muscles targeted. Target muscle options were presented in tables specific to anatomic region, and cross-sectional schematics were created for intraoperative assistance. Results:. Seventeen studies presenting original cases with clearly described nerve transfers and target muscles in the lower extremity were included in the review. Target muscle selection for all nerve transfers at the transfemoral and transtibial levels were presented in separate tables. Conclusions:. Reports of early experience at multiple institutions identify trends in the selection of certain target muscles for nerve transfers in transfemoral and transtibial TMR. Familiarity with these common target muscles and nerve transfers can simplify intraoperative decision-making and enhance integration of lower extremity TMR in amputation care and in the treatment of nerve-related pain.

Chinese students are more likely than US students to hold a malleable view of success in school, yet are more likely to hold fixed mindsets about intelligence. We demonstrate that this apparently contradictory pattern of cross-cultural differences holds true across multiple samples and is related to how students conceptualize intelligence and its relationship with academic achievement. Study 1 (N > 15,000) confirmed that US students endorsed more growth mindsets than Chinese students. Importantly, US students' mathematics grades were positively related to growth mindsets with a medium-to-large effect, but for Chinese students, this association was slightly negative. Study 2 conceptually replicated Study 1 findings with US and Chinese college samples, and further discovered that cross-cultural differences in intelligence mindset beliefs corresponded to how students defined intelligence. Together, these studies demonstrated systematic cross-cultural differences in intelligence mindset and suggest that intelligence mindsets are not necessarily associated with academic motivation or success in the same way across cultures.

A striking characteristic of human thought is that we form representations about abstract kinds (Giraffes have purple tongues), despite experiencing only particular individuals (This giraffe has a purple tongue). These generic generalizations have been hypothesized to be a cognitive default, that is, more basic and automatic than other forms of generalization, including those involving quantifiers such as "all" or "most." In support of this hypothesis, children often recall quantified statements (e.g., "All/many/most bears climb trees") as generic ("Bears climb trees"), and do so more frequently than the reverse error of recalling generics as quantified. The present study provides a strong test of the generics-as-default position by testing whether even numerically quantified statements (e.g., "Five giraffes have purple tongues") are recalled as generic. Two groups of three-year-old children (N = 74) were tested: those who held a correct numerical interpretation of five ("5-knowers"), and those who did not ("non-5-knowers"). Results indicate that non-5-knowers often defaulted to the generic in recall after hearing a number (e.g., recalling "Five giraffes." as "Giraffes."), whereas 5-knowers did not. Thus, consistent with the generic-as-default hypothesis, before children have a specific numerosity assigned to "five," they display a tendency to recall numerically quantified phrases as generic.

Although children's use of speech registers such as Baby Talk is well documented, little is known about their understanding of Foreigner Talk, a register addressed to non-native speakers. In Study 1, 4- to 8-year-old children and adults (N = 125) heard 4 registers (Foreigner Talk, Baby Talk, Peer Talk, and Teacher Talk) and predicted who would receive each. By 5 years, children selected the target addressee of Foreigner Talk above chance. In Study 2, 5- to 8-year-old children and adults (N = 94) completed a register match task manipulating 3 addressee cues: language, appearance, and origin. Prior to 7-8 years of age, children did not use the language cue alone when identifying the addressee of Foreigner Talk, and at no age did children use one cue more than another. In contrast, adults made use of language and appearance more than the origin cue. These findings suggest that an understanding of Foreigner Talk emerges by school age yet also undergoes developmental change.

Decades of research suggest that learning styles, or the belief that people learn better when they receive instruction in their dominant way of learning, may be one of the most pervasive myths about cognition. Nonetheless, little is known about what it means to believe in learning styles. The present investigation uses one theoretical framework--psychological essentialism--to explore the content and consistency of people's learning style beliefs. Psychological essentialism is a belief that certain categories (such as dogs, girls, or visual learners) have an underlying reality or true nature that is biologically based and highly predictive of many other features (Gelman, 2003). We tested the prevalence of erroneous essentialist beliefs regarding learning styles in both educators and noneducators, including that learning styles are innate, unchanging, discrete, and wired into the brain. In each of two experiments, we identified two groups of learning style believers, with one group holding an essentialist interpretation of learning styles, and the other group holding a nonessentialist interpretation of learning styles. No differences were found between educators' and noneducators' beliefs. In fact, only one factor was found to be a significant predictor of learning style beliefs for educators: the age of the population with whom they work. Specifically, those who worked with younger children were more likely to interpret learning styles in an essentialist way. Together the findings demonstrate that learning style beliefs are far more complex and variable than previously recognized.

When reasoning about a representation (e.g., a toy lion), children often engage in "iconic realism," whereby representations are reported to have properties of their real-life referents. The present studies examined an inverse difficulty that we dub "representational disregard": overlooking (i.e., disregarding) a representation's objective, non-symbolic features. In three experiments (N=302), children (3-6 years) and adults saw a series of representations (pictures and toys) and were tested on how often they endorsed a property that was true of the real-world referent (e.g., reporting that a toy lion is dangerous; iconic realism) or rejected a property that was true of the representation (e.g., denying that a toy elephant can be lifted with one hand; representational disregard). We found that representational disregard and realism were separable tendencies. Children (and to a lesser extent, adults) displayed both, but at different rates for pictures than for toys. We conclude that children's reasoning about representations includes a bias to overlook the features of the representation itself. Further, although pictures and toys are both representations, they provoke ontologically distinct interpretations. We discuss the implications of these results for a variety of important conceptual tasks, including learning to read, draw, or objectively evaluate scientific evidence.

Liver transplantation can be a life-saving treatment for end-stage hepatic disease. Unfortunately, some recipients develop ischemia-reperfusion injury (IRI) that leads to poor short- and long-term outcomes. Recent work has shown neutrophils contribute to IRI by undergoing NETosis, a form of death characterized by DNA ejection resulting in inflammatory extracellular traps. In this issue of the JCI, Hirao and Kojima et al. report that sphingosine-1-phosphate (S1P) expression induced by liver transplant–mediated IRI triggers NETosis. They also provide evidence that neutrophil expression of the carcinoembryonic antigen–related cell adhesion molecule-1 (CC1) long isoform inhibited NETosis by controlling S1P receptor–mediated autophagic flux. These findings suggest stimulating regulatory mechanisms that suppress NETosis could be used to prevent IRI.

Abstract Background: Varicella zoster virus (VZV) exposure seriously threatens immunocompromised hosts. Postexposure prophylaxis (PEP) using immune globulins is considered the standard of care; however, the available literature is mainly based on its use in pediatric patients. Here, we describe a widespread VZV exposure among immunocompromised adults treated with VZV-specific immunoglobulins (VZVSIG), and we discuss management and outcomes. Methods: We conducted a retrospective study to describe the exposure of immunocompromised patients to a single healthcare worker with primary VZV in 2019. Patients were grouped by their overall risk for infection, and those at risk received a single intramuscular dose of 625 IU of VZVSIG and were followed for 1 year. Results: In total, 83 patients received PEP at 3 months after exposure, thus were probably unrelated to the event. Adverse events related to VZVSIG (pyrexia) were reported in 2 patients (2.4%). Conclusions: Our findings demonstrate the utility of VZVSIG as PEP in one of the largest cohorts of immunocompromised adults to date. No early varicella infection was found following exposure, supporting the current recommendations of the VZVSIG administration.

Background: The primary strategy for urinary diversion in radical cystectomy patients involves incorporation of autologous gastrointestinal conduits into the urinary tract which leads to deleterious consequences including chronic infections and metabolic abnormalities. This report investigates the efficacy of an acellular, tubular bi-layer silk fibroin (BLSF) graft to function as an alternative urinary conduit in a porcine model of urinary diversion.Materials and methods: Unilateral urinary diversion with stented BLSF conduits was executed in five adult female, Yucatan mini-swine over a 3 month period. Longitudinal imaging analyses including ultrasonography, retrograde ureteropyelography and video-endoscopy were carried out monthly. Histological, immunohistochemical (IHC), and histomorphometric assessments were performed on neoconduits at harvest.Results: All animals survived until scheduled euthanasia and displayed moderate hydronephrosis (Grades 1–3) in reconstructed collecting systems over the course of the study period. Stented BLSF constructs supported formation of vascularized, retroperitoneal tubes capable of facilitating external urinary drainage. By 3 months post-operative, neoconduits contained α-smooth muscle actin+ and SM22α+ smooth muscle as well as uroplakin 3A+ and pan-cytokeratin + urothelium. However, the degree of tissue regeneration in neotissues was significantly lower in comparison to ureteral controls as determined by histomorphometry. In addition, neoconduit stenting was necessary to prevent stomal occlusion.Conclusion: BLSF biomaterials represent emerging platforms for urinary conduit construction and may offer a functional replacement for conventional urinary diversion techniques following further optimization of mechanical properties and regenerative responses.

ObjectivesHuman immunodeficiency virus (HIV) disproportionately affects Hispanics/Latinos in the United States, yet little is known about neurocognitive impairment (NCI) in this group. We compared the rates of NCI in large well-characterized samples of HIV-infected (HIV+) Latinos and (non-Latino) Whites, and examined HIV-associated NCI among subgroups of Latinos.MethodsParticipants included English-speaking HIV+ adults assessed at six U.S. medical centers (194 Latinos, 600 Whites). For overall group, age: M=42.65 years, SD=8.93; 86% male; education: M=13.17, SD=2.73; 54% had acquired immunodeficiency syndrome. NCI was assessed with a comprehensive test battery with normative corrections for age, education and gender. Covariates examined included HIV-disease characteristics, comorbidities, and genetic ancestry.ResultsCompared with Whites, Latinos had higher rates of global NCI (42% vs. 54%), and domain NCI in executive function, learning, recall, working memory, and processing speed. Latinos also fared worse than Whites on current and historical HIV-disease characteristics, and nadir CD4 partially mediated ethnic differences in NCI. Yet, Latinos continued to have more global NCI [odds ratio (OR)=1.59; 95% confidence interval (CI)=1.13-2.23; p

BackgroundMitochondria are abundant organelles critical for energy metabolism and brain function. Mitochondrial DNA (mtDNA), released during cellular injury and as part of the innate immune response to viral pathogens, contains CpG motifs that act as TLR-9 ligands. We investigated relationships between cerebrospinal fluid (CSF) cell-free mtDNA levels and HIV viral load (VL), biomarkers of inflammation and iron transport, and neurocognitive (NC) function in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) cohort.MethodsWe quantified cell-free mtDNA in CSF by droplet digital PCR in 332 CHARTER participants who underwent comprehensive neuropsychiatric evaluation. NC performance was assessed using the global deficit score (GDS) as either a continuous or a binary measure (GDS ≥ 0.5, impaired vs. GDS

The publication activity of research teams and scientists is determined by the number and quality of scientific publications for a certain period of time. Recently, the country has been taking active measures to increase publication activity. The purpose of this work was to study and analyze changes in factors affecting the publication activity of researchers and teachers and to identify the main trends in this process. The following issues were considered: assessment of the publication activity of researchers; trends in the development of the journal and publishing industry; changes in the requirements for papers and their writing. As a result, the main trends in changes in factors influencing the publication activity of researchers and lecturers were identified.

When fitting hierarchical regression models, maximum likelihood (ML) estimation has computational (and, for some users, philosophical) advantages compared to full Bayesian inference, but when the number of groups is small, estimates of the covariance matrix [sigma] of group-level varying coefficients are often degenerate. One can do better, even from a purely point estimation perspective, by using a prior distribution or penalty function. In this article, we use Bayes modal estimation to obtain positive definite covariance matrix estimates. We recommend a class of Wishart (not inverse-Wishart) priors for [sigma] with a default choice of hyperparameters, that is, the degrees of freedom are set equal to the number of varying coefficients plus 2, and the scale matrix is the identity matrix multiplied by a value that is large relative to the scale of the problem. This prior is equivalent to independent gamma priors for the eigenvalues of [sigma] with shape parameter 1.5 and rate parameter close to 0. It is also equivalent to independent gamma priors for the variances with the same hyperparameters multiplied by a function of the correlation coefficients. With this default prior, the posterior mode for [sigma] is always strictly positive definite. Furthermore, the resulting uncertainty for the fixed coefficients is less underestimated than under classical ML or restricted maximum likelihood estimation. We also suggest an extension of our method that can be used when stronger prior information is available for some of the variances or correlations. [This paper was published in "Journal of Educational and Behavioral Statistics" (EJ1057844).]

Durante la pandemia de covid-19 en Argentina, el trabajo del sector salud se vio transformado, adecuándose de manera espontánea a las necesidades y exigencias de una emergencia epidemiológica. Se produce un aumento de la demanda de personal, se intensifica el trabajo y se despliegan nuevas estrategias, protocolos y normativas de cuidado. En este artículo presentamos algunos resultados del análisis de entrevistas realizadas a enfermeras y enfermeros sobre sus experiencias de trabajo en hospitales generales del sur del conurbano bonaerense. El objetivo es dar cuenta de los dilemas éticos que enfrenta el personal de enfermería durante la pandemia con el fin de visibilizar dificultades y posibles líneas de trabajo futuro en torno a la formación y las condiciones de trabajo del sector.

We present a case of extensive Condyloma acuminata lesions involving significant area of the penile and genital skin. He underwent a complete excision of the lesions. Reconstruction of the penile skin was performed using full-thickness skin graft. The patient recovered well with no graft contracture or disfigurement.

Bronchiolitis obliterans syndrome (BOS) is a major impediment to lung transplant survival and is generally resistant to medical therapy. Extracorporeal photophoresis (ECP) is an immunomodulatory therapy that shows promise in stabilizing BOS patients, but its mechanisms of action are unclear. In a mouse lung transplant model, we show that ECP blunts alloimmune responses and inhibits BOS through lowering airway TGF-β bioavailability without altering its expression. Surprisingly, ECP-treated leukocytes were primarily engulfed by alveolar macrophages (AMs), which were reprogrammed to become less responsive to TGF-β and reduce TGF-β bioavailability through secretion of the TGF-β antagonist decorin. In untreated recipients, high airway TGF-β activity stimulated AMs to express CCL2, leading to CCR2+ monocyte-driven BOS development. Moreover, we found TGF-β receptor 2–dependent differentiation of CCR2+ monocytes was required for the generation of monocyte-derived AMs, which in turn promoted BOS by expanding tissue-resident memory CD8+ T cells that inflicted airway injury through Blimp-1–mediated granzyme B expression. Thus, through studying the effects of ECP, we have identified an AM functional plasticity that controls a TGF-β–dependent network that couples CCR2+ monocyte recruitment and differentiation to alloimmunity and BOS.

We employed the combined WRF-Chem-RTFDDA model to forecast dust storms in the Middle East and North Africa (MENA). WRF-Chem simulates the emission, transport, mixing, and chemical transformation of trace gases and aerosols simultaneously with the meteorology. RTFDDA continuously assimilates both conventional and nonconventional meteorological observations and provides improved initial conditions for dust analyses and forecasts. WRF-Chem-RTFDDA was run at a horizontal resolution of 9 km using the dust only option without inclusion of anthropogenic aerosols and chemical reactions. The synoptic conditions of the dust events were characterized by a cold front at the low level and an upper-level low-pressure system over the Western Mediterranean. WRF-Chem-RTFDDA was run in continuous assimilation mode, assimilating meteorological observations only, and launching 48-h free forecasts (FF) every 6 h. Two cold starts (CSs) for data assimilation and dust emissions initiation were performed during the study period. NCEP/GFS global analyses and forecasts provided initial and lateral boundary conditions. No global dust model was used for initialization and no dust observations were assimilated. We analyzed the skill of the WRF-Chem-RTFDDA system in reproducing the horizontal and vertical distributions of dust by comparing the FF to Meteosat SEVIRI dust images, MODIS AOD retrievals, CALIPSO extinction coefficients and CAMS aerosols-reanalysis AOD calculations. The skill was analyzed as a function of FF lead time and of the period of time from the CSs. RMSE, bias and correlation between the modeled and CALIPSO measured extinction coefficients were also examined. WRF-Chem-RTFDDA reproduced the main features of the studied dust storms reasonably well. The time distance from the CSs played a more significant role in determining the dust-forecast skill than free-forecast lead time. Since no external dust information was provided to the model, dust emissions and dust spin-up by WRF-Chem played a critical role in dust forecasts. The vertical extent of the CALIPSO extinction coefficients were reasonably well reproduced once model emissions were spun-up. False alarms rates range from 0.03 to 0.26, with many below 0.15, indicating satisfactory performance as a warning system. This study shows the feasibility of dust forecasts using minimal input data over the MENA region.

Background: HIV infection causes neuroinflammation and immune activation (NIIA) and systemic inflammation and immune activation (SIIA), which in turn drive neurodegeneration (ND). Cross-sectionally, higher levels of NIIA biomarkers correlate with increased biomarkers of ND. A more convincing confirmation would be a longitudinal demonstration. Methods: PWH in the US multisite CHARTER Aging project were assessed at a baseline visit and after 12 years using standardized evaluations. We measured a panel of 14 biomarkers of NIIA, SIIA, and ND in plasma and CSF at two time points and calculated changes from baseline to the 12-year visit. Factor analysis yielded simplified indices of NIIA, SIIA, and ND. Results: The CSF NIIA factor analysis yielded Factor1 loading on soluble tumor necrosis factor type-2 (sTNFR-II) and neopterin, and Factor2, loading on MCP1, soluble CD14, and IL-6. The SIIA factor analysis yielded Factor1 loading on CRP, D-dimer, and Neopterin; Factor2 loading on sTNFR-II. The ND analysis yielded Factor1 loading on Phosphorylated tau (p-tau) and Aβ42; Factor2 loading on NFL. NIIA Factor1, but not Factor2, correlated with increases in CSF NFL (r = 0.370, p = 0.0002). Conclusions: Increases in NIIA and SIIA in PWH were associated with corresponding increases in ND, suggesting that reducing neuro/systemic inflammation might slow or reverse neurodegeneration.

The debate surrounding school vouchers in educational policy remains contentious, with conflicting survey data presenting contradictory levels of public endorsement. To gain a more nuanced comprehension of viewpoints towards vouchers, we propose deconstructing the American populace into distinct demographic and geographical sectors. However, this approach encounters challenges due to data insufficiency arising from small sample sizes in individual segments. To address this quandary, we advocate employing a model-based simulation methodology called multilevel regression and poststratification to derive more accurate estimates of voucher attitudes. Our exploration reveals that vouchers enjoy the most favor among affluent White Catholics and Evangelicals, with popularity escalating alongside income within the White demographic. In contrast, among non-White individuals, voucher support exhibits a different pattern, with less favor observed within the middle-income bracket and greater acceptance among those in lower-income categories. Our findings shed light on the complex interplay of demographic and geographic factors influencing public opinion on school vouchers, offering valuable insights for policymakers and education reform efforts.

The paper offers an analysis of the project and the poetry book Las pandémicas. Diario colectivo de un aislamiento masivo as an instrument in the collectivization of the subject of cure in answer to the social malaise of the pandemic and the quarantine measures during 2020. In order to further determine each of these dimensions several genealogical lines are proposed, which read the poem and the project “in relationship” with a) other writing caused by the issuing of tasks, stated not as a coercion upon those who respond to them, but rather as a critical negotiation with pre-existing conditions of production; b) other writing and speech which understand words on the realm of the cure, intertwining the epistemic and the therapeutic; and c) other writing that took part in the forming of a collective subject of the present time, against the orders of authority.