Generalized estimating equations to estimate the ordered stereotype logit model for panel data

By modeling the effects of predictor variables as a multiplicative function of regression parameters being invariant over categories, and category-specific scalar effects, the ordered stereotype logit model is a flexible regression model for ordinal response variables. In this article, we propose a generalized estimating equations (GEE) approach to estimate the ordered stereotype logit model for panel data based on working covariance matrices, which are not required to be correctly specified. A simulation study compares the performance of GEE estimators based on various working correlation matrices and working covariance matrices using local odds ratios. Estimation of the model is illustrated using a real-world dataset. The results from the simulation study suggest that GEE estimation of this model is feasible in medium-sized and large samples and that estimators based on local odds ratios as realized in this study tend to be less efficient compared with estimators based on a working correlation matrix. For low true correlations, the efficiency gains seem to be rather small and if the working covariance structure is too flexible, the corresponding estimator may even be less efficient compared with the GEE estimator assuming independence. Like for GEE estimators more generally, if the true correlations over time are high, then a working covariance structure which is close to the true structure can lead to considerable efficiency gains compared with assuming independence.Peer ReviewedPostprint (published version

Comparative analysis of enzymatically produced novel linear DNA constructs with plasmids for use as DNA vaccines

The use of DNA to deliver vaccine antigens offers many advantages, including ease of manufacture and cost. However, most DNA vaccines are plasmids and must be grown in bacterial culture, necessitating elements which are either unnecessary for effective gene delivery (e.g. bacterial origins of replication) or undesirable (e.g. antibiotic resistance genes). Removing these elements may improve the safety profile of DNA for the delivery of vaccines. Here we describe a novel, double-stranded, linear DNA construct produced by an enzymatic process that solely encodes an antigen expression cassette, comprising antigen, promoter, polyA tail and telomeric ends. We compared these constructs (called ‘Doggybones’ because of their shape) with conventional plasmid DNA. Using luciferase-expressing constructs, we demonstrated that expression levels were equivalent between Doggybones and plasmids both in vitro and in vivo. When mice were immunized with DNA constructs expressing the HIV envelope protein gp140, equivalent humoral and cellular responses were induced. Immunizations with either construct type expressing haemagluttinin were protective against H1N1 influenza challenge. This is the first example of an effective DNA vaccine which can be produced on a large scale by enzymatic processes

Sommerfeld Enhancement from Multiple Mediators

We study the Sommerfeld enhancement experienced by a scattering object that couples to a tower of mediators. This can occur in, e.g., models of secluded dark matter when the mediator scale is generated naturally by hidden-sector confinement. Specializing to the case of a confining CFT, we show that off-resonant values of the enhancement can be increased by ~ 20% for cases of interest when (i) the (strongly-coupled) CFT admits a weakly-coupled dual description and (ii) the conformal symmetry holds up to the Planck scale. Larger enhancements are possible for lower UV scales due to an increase in the coupling strength of the tower.Comment: 17p, 2 figures; v2 JHEP version (inconsequential typo fixed, references added

Freeze-In Production of FIMP Dark Matter

We propose an alternate, calculable mechanism of dark matter genesis, "thermal freeze-in," involving a Feebly Interacting Massive Particle (FIMP) interacting so feebly with the thermal bath that it never attains thermal equilibrium. As with the conventional "thermal freeze-out" production mechanism, the relic abundance reflects a combination of initial thermal distributions together with particle masses and couplings that can be measured in the laboratory or astrophysically. The freeze-in yield is IR dominated by low temperatures near the FIMP mass and is independent of unknown UV physics, such as the reheat temperature after inflation. Moduli and modulinos of string theory compactifications that receive mass from weak-scale supersymmetry breaking provide implementations of the freeze-in mechanism, as do models that employ Dirac neutrino masses or GUT-scale-suppressed interactions. Experimental signals of freeze-in and FIMPs can be spectacular, including the production of new metastable coloured or charged particles at the LHC as well as the alteration of big bang nucleosynthesis.Comment: 30 pages, 7 figures, PDFLaTex. References adde

Multi-Scalar-Singlet Extension of the Standard Model - the Case for Dark Matter and an Invisible Higgs Boson

We consider a simple extension of the Standard Model by the addition of N real scalar gauge singlets \vp that are candidates for Dark Matter. By collecting theoretical and experimental constraints we determine the space of allowed parameters of the model. The possibility of ameliorating the little hierarchy problem within the multi-singlet model is discussed. The Spergel-Steinhardt solution of the Dark Matter density cusp problem is revisited. It is shown that fitting the recent CRESST-II data for Dark Matter nucleus scattering implies that the standard Higgs boson decays predominantly into pairs of Dark Matter scalars. It that case discovery of the Higgs boson at LHC and Tevatron is impossible. The most likely mass of the dark scalars is in the range 15 GeV \lsim \mvp \lsim 50 GeV with BR(h \to \vp\vp) up to 96%.Comment: 18 pages, 15 figure

Phylogeny of Basal Iguanodonts (Dinosauria: Ornithischia): An Update

The precise phylogenetic relationships of many non-hadrosaurid members of Iguanodontia, i.e., basal iguanodonts, have been unclear. Therefore, to investigate the global phylogeny of basal iguanodonts a comprehensive data matrix was assembled, including nearly every valid taxon of basal iguanodont. The matrix was analyzed in the program TNT, and the maximum agreement subtree of the resulting most parsimonious trees was then calculated in PAUP. Ordering certain multistate characters and omitting taxa through safe taxonomic reduction did not markedly improve resolution. The results provide some new information on the phylogeny of basal iguanodonts, pertaining especially to obscure or recently described taxa, and support some recent taxonomic revisions, such as the splitting of traditional “Camptosaurus” and “Iguanodon”. The maximum agreement subtree also shows a close relationship between the Asian Probactrosaurus gobiensis and the North American Eolambia, supporting the previous hypothesis of faunal interchange between Asia and North America in the early Late Cretaceous. Nevertheless, the phylogenetic relationships of many basal iguanodonts remain ambiguous due to the high number of taxa removed from the maximum agreement subtree and poor resolution of consensus trees

Sickle cell trait and priapism: a case report and review of the literature

Background A 32 year-old African-American man presented to our institution after attempting suicide via ingestion with quetiapine. He had reported a history of several days of substance abuse with alcohol, cocaine and marijuana related to a partying binge. Following this, his partner removed him from his residence resulting in a suicide attempt. During hospitalization the patient developed priapism, a condition he had not experienced before. Case presentation Given this was his first time with priapism, an extensive work-up revealed the patient had previously undiagnosed sickle cell trait, which we postulate to have been a significant factor in his development of acute priapism. Sickle cell trait is considered to be a generally benign condition except for a few rare complications under more demanding physical conditions. However, upon reviewing the literature on the association of sickle cell trait with priapism, we believe this may not be the case. Case reports and small series that appeared in the 1960s and 1970s indicated an association between priapism and sickle trait. Little has been reported recently, and the general teaching regarding sickle cell trait does not include this information. However, one case was reported with the use of phosphodiesterase-5 (PDE-5) inhibitors and the development of priapism in a patient with sickle cell trait. These medications are now first line treatment in erectile dysfunction. They act by enhancing nitric oxide (NO) production leading to relaxation of smooth muscle in the corpora cavernosa and penile arteries. Conclusion Priapism was not reported in the initial studies of these medications. Further review of the literature indicates this may be a complex relationship. Interestingly, PDE5 inhibitors also have been postulated to be protective in sickle cell disease and perhaps also sickle cell trait because priapism might be caused by reduced NO availability. In this article, we examine the evidence linking sickle cell trait to priapism, explore the implications of PDE5 use, particularly in the setting of sickle cell trait, and propose that teaching about sickle cell trait include a discussion of priapism risk

An Infrared Census of DUST in Nearby Galaxies with Spitzer (DUSTiNGS). IV. Discovery of High-redshift AGB Analogs

The survey for DUST in Nearby Galaxies with Spitzer (DUSTiNGS) identified several candidate Asymptotic Giant Branch (AGB) stars in nearby dwarf galaxies and showed that dust can form even in very metal-poor systems (${\boldsymbol{Z}}\sim 0.008\,{Z}_{\odot }$). Here, we present a follow-up survey with WFC3/IR on the Hubble Space Telescope (HST), using filters that are capable of distinguishing carbon-rich (C-type) stars from oxygen-rich (M-type) stars: F127M, F139M, and F153M. We include six star-forming DUSTiNGS galaxies (NGC 147, IC 10, Pegasus dIrr, Sextans B, Sextans A, and Sag DIG), all more metal-poor than the Magellanic Clouds and spanning 1 dex in metallicity. We double the number of dusty AGB stars known in these galaxies and find that most are carbon rich. We also find 26 dusty M-type stars, mostly in IC 10. Given the large dust excess and tight spatial distribution of these M-type stars, they are most likely on the upper end of the AGB mass range (stars undergoing Hot Bottom Burning). Theoretical models do not predict significant dust production in metal-poor M-type stars, but we see evidence for dust excess around M-type stars even in the most metal-poor galaxies in our sample (12+\mathrm{log}({\rm{O}}/{\rm{H}})=7.26\mbox{--}7.50). The low metallicities and inferred high stellar masses (up to ~10 ${M}_{\odot }$) suggest that AGB stars can produce dust very early in the evolution of galaxies (~30 Myr after they form), and may contribute significantly to the dust reservoirs seen in high-redshift galaxies

Secluded Dark Matter Coupled to a Hidden CFT

Models of secluded dark matter offer a variant on the standard WIMP picture and can modify our expectations for hidden sector phenomenology and detection. In this work we extend a minimal model of secluded dark matter, comprised of a U(1)'-charged dark matter candidate, to include a confining hidden-sector CFT. This provides a technically natural explanation for the hierarchically small mediator-scale, with hidden-sector confinement generating m_{gamma'}>0. Furthermore, the thermal history of the universe can differ markedly from the WIMP picture due to (i) new annihilation channels, (ii) a (potentially) large number of hidden-sector degrees of freedom, and (iii) a hidden-sector phase transition at temperatures T << M_{dm} after freeze out. The mediator allows both the dark matter and the Standard Model to communicate with the CFT, thus modifying the low-energy phenomenology and cosmic-ray signals from the secluded sector.Comment: ~50p, 8 figs; v2 JHEP versio

Assessment of a novel, capsid-modified adenovirus with an improved vascular gene transfer profile

&lt;p&gt;Background: Cardiovascular disorders, including coronary artery bypass graft failure and in-stent restenosis remain significant opportunities for the advancement of novel therapeutics that target neointimal hyperplasia, a characteristic of both pathologies. Gene therapy may provide a successful approach to improve the clinical outcome of these conditions, but would benefit from the development of more efficient vectors for vascular gene delivery. The aim of this study was to assess whether a novel genetically engineered Adenovirus could be utilised to produce enhanced levels of vascular gene expression.&lt;/p&gt; &lt;p&gt;Methods: Vascular transduction capacity was assessed in primary human saphenous vein smooth muscle and endothelial cells using vectors expressing the LacZ reporter gene. The therapeutic capacity of the vectors was compared by measuring smooth muscle cell metabolic activity and migration following infection with vectors that over-express the candidate therapeutic gene tissue inhibitor of matrix metalloproteinase-3 (TIMP-3).&lt;/p&gt; &lt;p&gt;Results: Compared to Adenovirus serotype 5 (Ad5), the novel vector Ad5T*F35++ demonstrated improved binding and transduction of human vascular cells. Ad5T*F35++ mediated expression of TIMP-3 reduced smooth muscle cell metabolic activity and migration in vitro. We also demonstrated that in human serum samples pre-existing neutralising antibodies to Ad5T*F35++ were less prevalent than Ad5 neutralising antibodies.&lt;/p&gt; &lt;p&gt;Conclusions: We have developed a novel vector with improved vascular transduction and improved resistance to human serum neutralisation. This may provide a novel vector platform for human vascular gene transfer.&lt;/p&gt