Slow nucleation rates in Chain Inflation with QCD Axions or Monodromy

The previous proposal (by two of us) of chain inflation with the QCD axion is shown to fail. The proposal involved a series of fast tunneling events, yet here it is shown that tunneling is too slow. We calculate the bubble nucleation rates for phase transitions in the thick wall limit, approximating the barrier by a triangle. A similar problem arises in realization of chain inflation in the string landscape that uses series of minima along the monodromy staircase around the conifold point. The basic problem is that the minima of the potential are too far apart to allow rapid enough tunneling in these two models. We entertain the possibility of overcoming this problem by modifying the gravity sector to a Brans-Dicke theory. However, one would need extremely small values for the Brans-Dicke parameter. Many successful alternatives exist, including other "axions" (with mass scales not set by QCD) or potentials with comparable heights and widths that do not suffer from the problem of slow tunneling and provide successful candidates for chain inflation.Comment: 6 pages, 1 figur

Inflating with the QCD Axion

We show that the QCD axion can drive inflation via a series of tunneling events. For axion models with a softly broken $Z_N$ symmetry, the axion potential has a series of $N$ local minima and may be modeled by a tilted cosine. Chain inflation results along this tilted cosine: the field tunnels from an initial minimum near the top of the potential through a series of ever lower minima to the bottom. This results in sufficient inflation and reheating. QCD axions, potentially detectable in current searches, may thus simultaneously solve problems in particle physics and provide inflation.Comment: 5 pages, 1 figure, revised for submission to PR

Dorsal root ganglion macrophages contribute to both the initiation and persistence of neuropathic pain.

Paralleling the activation of dorsal horn microglia after peripheral nerve injury is a significant expansion and proliferation of macrophages around injured sensory neurons in dorsal root ganglia (DRG). Here we demonstrate a critical contribution of DRG macrophages, but not those at the nerve injury site, to both the initiation and maintenance of the mechanical hypersensitivity that characterizes the neuropathic pain phenotype. In contrast to the reported sexual dimorphism in the microglial contribution to neuropathic pain, depletion of DRG macrophages reduces nerve injury-induced mechanical hypersensitivity and expansion of DRG macrophages in both male and female mice. However, fewer macrophages are induced in the female mice and deletion of colony-stimulating factor 1 from sensory neurons, which prevents nerve injury-induced microglial activation and proliferation, only reduces macrophage expansion in male mice. Finally, we demonstrate molecular cross-talk between axotomized sensory neurons and macrophages, revealing potential peripheral DRG targets for neuropathic pain management

Outcomes of Randomized Clinical Trials of Interventions to Enhance Social, Emotional, and Spiritual Components of Wisdom: A Systematic Review and Meta-analysis.

ImportanceWisdom is a neurobiological personality trait made up of specific components, including prosocial behaviors, emotional regulation, and spirituality. It is associated with greater well-being and happiness.ObjectiveTo evaluate the effectiveness of interventions to enhance individual components of wisdom.Data sourcesMEDLINE and PsycINFO databases were searched for articles published through December 31, 2018.Study eligibility criteriaRandomized clinical trials that sought to enhance a component of wisdom, used published measures to assess that component, were published in English, had a minimum sample size of 40 participants, and presented data that enabled computation of effect sizes were included in this meta-analysis.Data extraction and synthesisRandom-effect models were used to calculate pooled standardized mean differences (SMDs) for each wisdom component and random-effects meta-regression to assess heterogeneity of studies.Main outcomes and measuresImprovement in wisdom component using published measures.ResultsFifty-seven studies (N = 7096 participants) met review criteria: 29 for prosocial behaviors, 13 for emotional regulation, and 15 for spirituality. Study samples included people with psychiatric or physical illnesses and from the community. Of the studies, 27 (47%) reported significant improvement with medium to large effect sizes. Meta-analysis revealed significant pooled SMDs for prosocial behaviors (23 studies; pooled SMD, 0.43 [95% CI, 0.22-0.3]; P = .02), emotional regulation (12 studies; pooled SMD, 0.67 [95% CI, 0.21-1.12]; P = .004), and spirituality (12 studies; pooled SMD, 1.00 [95% CI, 0.41-1.60]; P = .001). Heterogeneity of studies was considerable for all wisdom components. Publication bias was present for prosocial behavior and emotional regulation studies; after adjusting for it, the pooled SMD for prosocial behavior remained significant (SMD, 0.4 [95% CI, 0.16-0.78]; P = .003). Meta-regression analysis found that effect sizes did not vary by wisdom component, although for trials on prosocial behaviors, large effect sizes were associated with older mean participant age (β, 0.08 [SE, 0.04]), and the reverse was true for spirituality trials (β, -0.13 [SE, 0.04]). For spirituality interventions, higher-quality trials had larger effect sizes (β, 4.17 [SE, 1.07]), although the reverse was true for prosocial behavior trials (β, -0.91 [SE 0.44]).Conclusions and relevanceInterventions to enhance spirituality, emotional regulation, and prosocial behaviors are effective in a proportion of people with mental or physical illnesses and from the community. The modern behavioral epidemics of loneliness, suicide, and opioid abuse point to a growing need for wisdom-enhancing interventions to promote individual and societal well-being

Reirradiation practices for children with diffuse intrinsic pontine glioma

Background: Diffuse intrinsic pontine gliomas (DIPGs) are a leading cause of brain tumor deaths in children. Current standard of care includes focal radiation therapy (RT). Despite clinical improvement in most patients, the effect is temporary and median survival is less than 1 year. The use and benefit of reirradiation have been reported in progressive DIPG, yet standardized approaches are lacking. We conducted a survey to assess reirradiation practices for DIPG in North America. Methods: A 14-question REDCap survey was disseminated to 396 North American physicians who care for children with CNS tumors. Results: The response rate was 35%. Participants included radiation-oncologists (63%; 85/135) and pediatric oncologists/neuro-oncologists (37%; 50/135). Most physicians (62%) treated 1 to 5 DIPG patients per year, with 10% treating more than 10 patients per year. Reirradiation was considered a treatment option by 88% of respondents. Progressive disease and worsening clinical status were the most common reasons to consider reirradiation. The majority (84%) surveyed considered reirradiation a minimum of 6 months following initial RT. Doses varied, with median total dose of 2400 cGy (range, 1200-6000 cGy) and fraction size of 200 cGy (range, 100-900 cGy). Concurrent use of systemic agents with reirradiation was considered in 46%, including targeted agents (37%), biologics (36%), or immunotherapy (25%). One-time reirradiation was the most common practice (71%). Conclusion: Although the vast majority of physicians consider reirradiation as a treatment for DIPG, total doses and fractionation varied. Further clinical trials are needed to determine the optimal radiation dose and fractionation for reirradiation in children with progressive DIPG

The role of Neuropilin-1 in COVID-19

Neuropilin-1 (NRP-1), a member of a family of signaling proteins, was shown to serve as an entry factor and potentiate SARS Coronavirus 2 (SARS-CoV-2) infectivity in vitro. This cell surface receptor with its disseminated expression is important in angiogenesis, tumor progression, viral entry, axonal guidance, and immune function. NRP-1 is implicated in several aspects of a SARS-CoV-2 infection including possible spread through the olfactory bulb and into the central nervous system and increased NRP-1 RNA expression in lungs of severe Coronavirus Disease 2019 (COVID-19). Up-regulation of NRP-1 protein in diabetic kidney cells hint at its importance in a population at risk of severe COVID-19. Involvement of NRP-1 in immune function is compelling, given the role of an exaggerated immune response in disease severity and deaths due to COVID-19. NRP-1 has been suggested to be an immune checkpoint of T cell memory. It is unknown whether involvement and up-regulation of NRP-1 in COVID-19 may translate into disease outcome and long-term consequences, including possible immune dysfunction. It is prudent to further research NRP-1 and its possibility of serving as a therapeutic target in SARS-CoV-2 infections. We anticipate that widespread expression, abundance in the respiratory and olfactory epithelium, and the functionalities of NRP-1 factor into the multiple systemic effects of COVID-19 and challenges we face in management of disease and potential long-term sequelae

In search of late-stage planetary building blocks

Genetic contributions to the final stages of planetary growth, including materials associated with the giant Moon forming impact, late accretion, and late heavy bombardment are examined using siderophile elements. Isotopic similarities between the Earth and Moon for both lithophile and siderophile elements collectively lead to the suggestion that the genetics of the building blocks for Earth, and the impactor involved in the Moon-forming event were broadly similar, and shared some strong genetic affinities with enstatite chondrites. The bulk genetic fingerprint of materials subsequently added to Earth by late accretion, defined as the addition of ~0.5 wt.% of Earth's mass to the mantle, following cessation of core formation, was characterized by 187Os/188Os and Pd/Ir ratios that were also similar to those in some enstatite chondrites. However, the integrated fingerprint of late accreted matter differs from enstatite chondrites in terms of the relative abundances of certain other HSE, most notably Ru/Ir. The final ≤0.05 wt.% addition of material to the Earth and Moon, believed by some to be part of a late heavy bombardment, included a component with much more fractionated relative HSE abundances than evidenced in the average late accretionary component. Heterogeneous 182W/184Wisotopic compositions of some ancient terrestrial rocks suggest that some very early formed mantle domains remained chemically distinct for long periods of time following primary planetary accretion. This evidence for sluggish mixing of the early mantle suggests that if late accretionary contributions to the mantle were genetically diverse, it may be possible to isotopically identify the disparate primordial components in the terrestrial rock record using the siderophile element tracers Ru and Mo.NASA grants NNX13AF83G and NNA14AB07A NSF-CSEDI grants EAR1160728 and EAR1265169

Interactive effects of vascular risk burden and advanced age on cerebral blood flow.

Vascular risk factors and cerebral blood flow (CBF) reduction have been linked to increased risk of cognitive impairment and Alzheimer's disease (AD); however the possible moderating effects of age and vascular risk burden on CBF in late life remain understudied. We examined the relationships among elevated vascular risk burden, age, CBF, and cognition. Seventy-one non-demented older adults completed an arterial spin labeling MR scan, neuropsychological assessment, and medical history interview. Relationships among vascular risk burden, age, and CBF were examined in a priori regions of interest (ROIs) previously implicated in aging and AD. Interaction effects indicated that, among older adults with elevated vascular risk burden (i.e., multiple vascular risk factors), advancing age was significantly associated with reduced cortical CBF whereas there was no such relationship for those with low vascular risk burden (i.e., no or one vascular risk factor). This pattern was observed in cortical ROIs including medial temporal (hippocampus, parahippocampal gyrus, uncus), inferior parietal (supramarginal gyrus, inferior parietal lobule, angular gyrus), and frontal (anterior cingulate, middle frontal gyrus, medial frontal gyrus) cortices. Furthermore, among those with elevated vascular risk, reduced CBF was associated with poorer cognitive performance. Such findings suggest that older adults with elevated vascular risk burden may be particularly vulnerable to cognitive change as a function of CBF reductions. Findings support the use of CBF as a potential biomarker in preclinical AD and suggest that vascular risk burden and regionally-specific CBF changes may contribute to differential age-related cognitive declines

Regulatory T Cells Control Effector T Cell Inflammation in Human Prediabetes

A disparate array of plasma/serum markers provides evidence for chronic inflammation in human prediabetes, a condition that is most closely replicated by standard mouse models of obesity and metaflammation. These remain largely nonactionable and contrast with our rich understanding of inflammation in human type 2 diabetes. New data show that inflammatory profiles produced by CD4+ T cells define human prediabetes as a unique inflammatory state. Regulatory T cells (Treg) control mitochondrial function and cytokine production by CD4+ effector T cells (Teff) in prediabetes and type 2 diabetes by supporting T helper (Th)17 or Th1 cytokine production, respectively. These data suggest that Treg control of Teff metabolism regulates inflammation differentially in prediabetes compared with type 2 diabetes. Queries of genes that impact mitochondrial function or pathways leading to transcription of lipid metabolism genes identified the fatty acid importer CD36 as highly expressed in Treg but not Teff from subjects with prediabetes. Pharmacological blockade of CD36 in Treg from subjects with prediabetes decreased Teff production of the Th17 cytokines that differentiate overall prediabetes inflammation. We conclude that Treg control CD4+ T cell cytokine profiles through mechanisms determined, at least in part, by host metabolic status. Furthermore, Treg CD36 uniquely promotes Th17 cytokine production by Teff in prediabetes