Seven lessons from manyfield inflation in random potentials

We study inflation in models with many interacting fields subject to randomly generated scalar potentials. We use methods from non-equilibrium random matrix theory to construct the potentials and an adaption of the ‘transport method’ to evolve the two-point correlators during inflation. This construction allows, for the first time, for an explicit study of models with up to 100 interacting fields supporting a period of ‘approximately saddle-point’ inflation. We determine the statistical predictions for observables by generating over 30,000 models with 2–100 fields supporting at least 60 efolds of inflation. These studies lead us to seven lessons: i) Manyfield inflation is not single-field inflation, ii) The larger the number of fields, the simpler and sharper the predictions, iii) Planck compatibility is not rare, but future experiments may rule out this class of models, iv) The smoother the potentials, the sharper the predictions, v) Hyperparameters can transition from stiff to sloppy, vi) Despite tachyons, isocurvature can decay, vii) Eigenvalue repulsion drives the predictions. We conclude that many of the ‘generic predictions’ of single-field inflation can be emergent features of complex inflation models

A new class of de Sitter vacua in type IIB large volume compactifications

We construct a new class of metastable de Sitter vacua of flux compactifications of type IIB string theory. These solutions provide a natural extension of the `Large Volume Scenario' anti-de Sitter vacua, and can analogously be realised at parametrically large volume and weak string coupling, using standard ${\cal N}=1$ supergravity. For these new vacua, a positive vacuum energy is achieved from the inclusion of a small amount of flux-induced supersymmetry breaking in the complex structure and axio-dilaton sector, and no additional `uplift' contribution (e.g.~from anti-branes) is required. We show that the approximate no-scale structure of the effective theory strongly influences the spectrum of the stabilised moduli: one complex structure modulus remains significantly lighter than the supersymmetry breaking scale, and metastability requires only modest amounts of tuning. After discussing these general results, we provide a recipe for constructing de Sitter vacua on a given compactification manifold, and give an explicit example of a de Sitter vacuum for the compactification on the Calabi-Yau orientifold realised in $\mathbb{CP}^4_{11169}$. Finally, we note that these solutions have intriguing implications for phenomenology, predicting no superpartners in the spectrum below $\sim$50 TeV, and no WIMP dark matter.Comment: 34 page

A new bound on axion-like particles

Axion-like particles (ALPs) and photons can quantum mechanically interconvert when propagating through magnetic fields, and ALP-photon conversion may induce oscillatory features in the spectra of astrophysical sources. We use deep (370 ks), short frame time Chandra observations of the bright nucleus at the centre of the radio galaxy M87 in the Virgo cluster to search for signatures of light ALPs. The absence of substantial irregularities in the X-ray power-law spectrum leads to a new upper limit on the photon-ALP coupling, $g_{a\gamma}$: using a conservative model of the cluster magnetic field consistent with Faraday rotation measurements from M87 and M84, we find $g_{a \gamma} < 2.6\times10^{-12}$ GeV$^{-1}$ at 95% confidence level for ALP masses $m_a \leq 10^{-13}$ eV. Other consistent magnetic field models lead to stronger limits of $g_{a \gamma} \lesssim 1.1$--$1.5 \times 10^{-12}$ GeV$^{-1}$. These bounds are all stronger than the limit inferred from the absence of a gamma-ray burst from SN1987A, and rule out a substantial fraction of the parameter space accessible to future experiments such as ALPS-II and IAXO

DQB1*0602 rather than DRB1*1501 confers susceptibility to multiple sclerosis-like disease induced by proteolipid protein (PLP)

<p>Abstract</p> <p>Background</p> <p>Multiple sclerosis (MS) is associated with pathogenic autoimmunity primarily focused on major CNS-myelin target antigens including myelin basic protein (MBP), proteolipidprotein (PLP), myelin oligodendrocyte protein (MOG). MS is a complex trait whereby the HLA genes, particularly class-II genes of HLA-DR15 haplotype, dominate the genetic contribution to disease-risk. Due to strong linkage disequilibrium in HLA-II region, it has been hard to establish precisely whether the functionally relevant effect derives from the DRB1*1501, DQA1*0102-DQB1*0602, or DRB5*0101 loci of HLA-DR15 haplotype, their combinations, or their epistatic interactions. Nevertheless, most genetic studies have indicated DRB1*1501 as a primary risk factor in MS. Here, we used 'HLA-humanized' mice to discern the potential relative contribution of DRB1*1501 and DQB1*0602 alleles to susceptibility to "humanized" MS-like disease induced by PLP, one of the most prominent and encephalitogenic target-antigens implicated in human MS.</p> <p>Methods</p> <p>The HLA-DRB1*1501- and HLA-DQB1*0602-Tg mice (MHC-II^-/-), and control non-HLA-DR15-relevant-Tg mice were immunized with a set of overlapping PLP peptides or with recombinant soluble PLP for induction of "humanized" MS-like disease, as well as for ex-vivo analysis of immunogenic/immunodominant HLA-restricted T-cell epitopes and associated cytokine secretion profile.</p> <p>Results</p> <p>PLP autoimmunity in both HLA-DR15-Tg mice was focused on 139-151 and 175-194 epitopes. Strikingly, however, the HLA-DRB1*1501-transgenics were refractory to disease induction by any of the overlapping PLP peptides, while HLA-DQB1*0602 transgenics were susceptible to disease induction by PLP139-151 and PLP175-194 peptides. Although both transgenics responded to both peptides, the PLP139-151- and PLP175-194-reactive T-cells were directed to Th1/Th17 phenotype in DQB1*0602-Tg mice and towards Th2 in DRB1*1501-Tg mice.</p> <p>Conclusions</p> <p>While genome studies map a strong MS susceptibility effect to the region of DRB1*1501, our findings offer a rationale for potential involvement of pathogenic DQ6-associated autoimmunity in MS. Moreover, that DQB1*0602, but not DRB1*1501, determines disease-susceptibility to PLP in HLA-transgenics, suggests a potential differential, functional role for DQB1*0602 as a predisposing allele in MS. This, together with previously demonstrated disease-susceptibility to MBP and MOG in DRB1*1501-transgenics, also suggests a differential role for DRB1*1501 and DQB1*0602 depending on target antigen and imply a potential complex 'genotype/target antigen/phenotype' relationship in MS heterogeneity.</p

A Multitrait–Multimethod Analysis of the Construct Validity of Child Anxiety Disorders in a Clinical Sample

The present study examines the construct validity of separation anxiety disorder (SAD), social phobia (SoP), panic disorder (PD), and generalized anxiety disorder (GAD) in a clinical sample of children. Participants were 174 children, 6 to 17 years old (94 boys) who had undergone a diagnostic evaluation at a university hospital based clinic. Parent and child ratings of symptom severity were assessed using the Multidimensional Anxiety Scale for Children (MASC). Diagnostician ratings were obtained from the Anxiety Disorders Interview Schedule for Children and Parents (ADIS: C/P). Discriminant and convergent validity were assessed using confirmatory factor analytic techniques to test a multitrait–multimethod model. Confirmatory factor analyses supported the current classification of these child anxiety disorders. The disorders demonstrated statistical independence from each other (discriminant validity of traits), the model fit better when the anxiety syndromes were specified than when no specific syndromes were specified (convergent validity), and the methods of assessment yielded distinguishable, unique types of information about child anxiety (discriminant validity of methods). Using a multi-informant approach, these findings support the distinctions between childhood anxiety disorders as delineated in the current classification system, suggesting that disagreement between informants in psychometric studies of child anxiety measures is not due to poor construct validity of these anxiety syndromes

Development of Sensory, Motor and Behavioral Deficits in the Murine Model of Sanfilippo Syndrome Type B

BACKGROUND: Mucopolysaccharidosis (MPS) IIIB (Sanfilippo Syndrome type B) is caused by a deficiency in the lysosomal enzyme N-acetyl-glucosaminidase (Naglu). Children with MPS IIIB develop disturbances of sleep, activity levels, coordination, vision, hearing, and mental functioning culminating in early death. The murine model of MPS IIIB demonstrates lysosomal distention in multiple tissues, a shortened life span, and behavioral changes. PRINCIPAL FINDINGS: To more thoroughly assess MPS IIIB in mice, alterations in circadian rhythm, activity level, motor function, vision, and hearing were tested. The suprachiasmatic nucleus (SCN) developed pathologic changes and locomotor analysis showed that MPS IIIB mice start their daily activity later and have a lower proportion of activity during the night than wild-type controls. Rotarod assessment of motor function revealed a progressive inability to coordinate movement in a rocking paradigm. Purkinje cell counts were significantly reduced in the MPS IIIB animals compared to age matched controls. By electroretinography (ERG), MPS IIIB mice had a progressive decrease in the amplitude of the dark-adapted b-wave response. Corresponding pathology revealed shortening of the outer segments, thinning of the outer nuclear layer, and inclusions in the retinal pigmented epithelium. Auditory-evoked brainstem responses (ABR) demonstrated progressive hearing deficits consistent with the observed loss of hair cells in the inner ear and histologic abnormalities in the middle ear. CONCLUSIONS/SIGNIFICANCE: The mouse model of MPS IIIB has several quantifiable phenotypic alterations and is similar to the human disease. These physiologic and histologic changes provide insights into the progression of this disease and will serve as important parameters when evaluating various therapies

Characteristics of Children With Elevated Symptoms of Mania: The Longitudinal Assessment of Manic Symptoms (LAMS) Study

To examine differences in psychiatric symptomatology, diagnoses, demographics, functioning, and psychotropic medication exposure in children with elevated symptoms of mania (ESM+) compared to youth without ESM (ESM−)

The Hall Technique; a randomized controlled clinical trial of a novel method of managing carious primary molars in general dental practice: acceptability of the technique and outcomes at 23 months

<p>Abstract</p> <p>Background</p> <p>Scotland has high levels of untreated dental caries in primary teeth. The Hall Technique is a simplified method of managing carious primary molars using preformed metal crowns (PMCs) cemented with no local anaesthesia, caries removal or tooth preparation. This study compared the acceptability of the Hall Technique for children, their carers, and dentists, and clinical outcomes for the technique, with conventional restorations.</p> <p>Methods</p> <p>General dental practice based, split mouth, randomized controlled trial (132 children, aged 3–10). General dental practitioners (GDPs, n = 17) in Tayside, Scotland (dmft 2.7) placed conventional (Control) restorations in carious primary molars, and Hall Technique PMCs on the contralateral molar (matched clinically and radiographically). Dentists ranked the degree of discomfort they felt the child experienced for each procedure; then children, their carers and dentists stated which technique they preferred. The teeth were followed up clinically and radiographically.</p> <p>Results</p> <p>128 conventional restorations were placed on 132 control teeth, and 128 PMCs on 132 intervention teeth. Using a 5 point scale, 118 Hall PMCs (89%) were rated as no apparent discomfort up to mild, not significant; for Control restorations the figure was 103 (78%). Significant, unacceptable discomfort was recorded for two Hall PMCs (1.5%) and six Control restorations (4.5%). 77% of children, 83% of carers and 81% of dentists who expressed a preference, preferred the Hall technique, and this was significant (Chi square, p < 0.0001). There were 124 children (94% of the initial sample) with a minimum follow-up of 23 months. The Hall PMCs outperformed the Control restorations:</p> <p>a) 'Major' failures (signs and symptoms of irreversible pulpal disease): 19 Control restorations (15%); three Hall PMCs (2%) (P < 0.000);</p> <p>b) 'Minor' failures (loss of restoration, caries progression): 57 Control restorations (46%); six Hall PMCs (5%) (P < 0.000)</p> <p>c) Pain: 13 Control restorations (11%); two Hall PMCs (2%) (P = 0.003).</p> <p>Conclusion</p> <p>The Hall Technique was preferred to conventional restorations by the majority of children, carers and GDPs. After two years, Hall PMCs showed more favourable outcomes for pulpal health and restoration longevity than conventional restorations. The Hall Technique appears to offer an effective treatment option for carious primary molar teeth.</p> <p>Trial registration number</p> <p>Current Controlled Trials ISRCTN47267892 – A randomized controlled trial in primary care of a novel method of using preformed metal crowns to manage decay in primary molar teeth: the Hall technique.</p

An examination of the factorial and convergent validity of four measures of conspiracist ideation, with recommendations for researchers

A number scales have been developed to measure conspiracist ideation, but little attention has been paid to the factorial validity of these scales. We reassessed the psychometric properties of four widely-used scales, namely the Belief in Conspiracy Theories Inventory (BCTI), the Conspiracy Mentality Questionnaire (CMQ), the Generic Conspiracist Beliefs Scale (GCBS), and the One-Item Conspiracy Measure (OICM). Eight-hundred-and-three U. S. adults completed all measures, along with measures of endorsement of 9/11 and anti- vaccination conspiracy theories. Through both exploratory and confirmatory factor analysis, we found that only the BCTI had acceptable factorial validity. We failed to confirm the factor structures of the CMQ and the GBCS, suggesting these measures had poor factorial valid- ity. Indices of convergent validity were acceptable for the BCTI, but weaker for the other measures. Based on these findings, we provide suggestions for the future refinement in the measurement of conspiracist ideation