Scale-Invariant Quadratic Gravity and the Ghost Problem

In this thesis we investigate several phenomena in quantum gravity with a specific empha- sis on scale-invariant models of quadratic gravity whose actions contain all three independent squares of the Riemann tensor. After discussing the different ways in which scale invariance can manifest and reviewing how spontaneous symmetry breaking may occur as a result of quantum effects, we marry these concepts by constructing a model of gravity and matter that dynamically generates the Planck and electroweak scales through the spontaneous breaking of scale symme- try, thus describing an origin for the very concept of mass. We also demonstrate that this same scale-invariant model describes a period of cosmic inflation that is consistent with modern ob- servations. A simpler realization of this model with the same important features is then defined by including quantum effects that result from the traditionally neglected spin-2 ghost degrees of freedom that are inherently present in this type of theory. The second part of this work is devoted to studying the role of these spin-2 ghosts, which generically appear as negative norm states that threaten unitarity at the quantum level. We derive rigorous and novel covariant operator quanti- zations of both globally scale-invariant quadratic gravity in the phase of broken symmetry and of locally invariant conformal gravity in the unbroken phase. This leads us to establish the notion of “conditional unitary” wherein the broken phase theory is shown to be unitary up to very high energies, and grants a new perspective on the ghost problem in quantum gravity as a whole

Washington County Asset Map and Needs Assessment: Building a Network to Serve Youths at Risk for Serious Mental Illness

This study is the first in a series of planned investigations into pathways to care for adolescents and young adults with serious mental illness in Washington County. Resources were identified that may support a network for identifying and accessing services. Over 120 agencies were categorized into one of seven types: education, mental health, health, substance use / recovery, community / library, and law enforcement. Web-based information was collected for 85 of these agencies and representatives of 47 of these agencies were interviewed about challenges, collaborations, and ideas for solutions. We found a great deal of collaboration among agencies within different service sectors. For example, there is regular collaboration among health agencies, among educational agencies, and among agencies serving children and families. We identified networks that support the LGBTQ+ community as well as victims of domestic violence. Three agencies stood out with number and type of collaborations regarding youth and mental illness: Healthy Acadia, the Community Caring Collaborative, and the Aroostook Mental Health Center. We collated information about types of obstacles into these categories by frequency of mention: Lack of Services / Providers, Stigma / Community Culture, Transportation / Distance, Information Shortage, Cost, and Mistrust of Providers. Five areas of ideas from interviewees to address these challenges are provided. We end this report by highlighting some national, state, county, and local efforts to address these challenges as well as next steps for our research team

Washington County Asset Map and Needs Assessment : Building a Network to Serve Youths at Risk for Serious Mental Illness

This study is the first in a series of planned investigations into pathways to care for adolescents and young adults with serious mental illness in Washington County. Resources were identified that may support a network for identifying and accessing services. Over 120 agencies were categorized into one of seven types: education, mental health, health, substance use / recovery, community / library, and law enforcement. Web-based information was collected for 85 of these agencies and representatives of 47 of these agencies were interviewed about challenges, collaborations, and ideas for solutions. We found a great deal of collaboration among agencies within different service sectors. For example, there is regular collaboration among health agencies, among educational agencies, and among agencies serving children and families. We identified networks that support the LGBTQ+ community as well as victims of domestic violence. Three agencies stood out with number and type of collaborations regarding youth and mental illness: Healthy Acadia, the Community Caring Collaborative, and the Aroostook Mental Health Center. We collated information about types of obstacles into these categories by frequency of mention: Lack of Services / Providers, Stigma / Community Culture, Transportation / Distance, Information Shortage, Cost, and Mistrust of Providers. Five areas of ideas from interviewees to address these challenges are provided. We end this report by highlighting some national, state, county, and local efforts to address these challenges as well as next steps for our research team

Unified Emergence of Energy Scales and Cosmic Inflation

In the quest for unification of the Standard Model with gravity, classical scale invariance can be utilized to dynamically generate the Planck mass $M_\mathrm{Pl}$. Then, the relation of Planck scale physics to the scale of electroweak symmetry breaking $\mu_H$ requires further explanation. In this paper, we propose a model that uses the spontaneous breaking of scale invariance in the scalar sector as a unified origin for dynamical generation of both scales. Using the Gildener-Weinberg approximation, only one scalar acquires a vacuum expectation value of $v_S \sim (10^{16-17})\,\mathrm{GeV}$, thus radiatively generating $M_\mathrm{Pl} \approx \beta_S^{1/2} v_S$ and $\mu_H$ via the neutrino option with right handed neutrino masses $m_N = y_M v_S \sim 10^7 \,\mathrm{GeV}$. Consequently, active SM neutrinos are given a mass with the inclusion of a type-I seesaw mechanism. Furthermore, we adopt an unbroken $Z_2$ symmetry and a $Z_2$-odd set of right-handed Majorana neutrinos $\chi$ that do not take part in the neutrino option and are able to produce the correct dark matter relic abundance (dominantly) via inflaton decay. The model also describes cosmic inflation and the inflationary CMB observables are predicted to interpolate between those of $R^2$ and linear chaotic inflationary model and are thus well within the strongest experimental constraints.Comment: 21+10 pages, 11 figures, 1 table, v2: matches published versio

Sex-specific effects of microbiome perturbations on cerebral Aβ amyloidosis and microglia phenotypes.

We demonstrated that an antibiotic cocktail (ABX)-perturbed gut microbiome is associated with reduced amyloid-β (Aβ) plaque pathology and astrogliosis in the male amyloid precursor protein (APP)SWE /presenilin 1 (PS1)ΔE9 transgenic model of Aβ amyloidosis. We now show that in an independent, aggressive APPSWE/PS1L166P (APPPS1-21) mouse model of Aβ amyloidosis, an ABX-perturbed gut microbiome is associated with a reduction in Aβ pathology and alterations in microglial morphology, thus establishing the generality of the phenomenon. Most importantly, these latter alterations occur only in brains of male mice, not in the brains of female mice. Furthermore, ABX treatment lead to alterations in levels of selected microglial expressed transcripts indicative of the "M0" homeostatic state in male but not in female mice. Finally, we found that transplants of fecal microbiota from age-matched APPPS1-21 male mice into ABX-treated APPPS1-21 male restores the gut microbiome and partially restores Aβ pathology and microglial morphology, thus demonstrating a causal role of the microbiome in the modulation of Aβ amyloidosis and microglial physiology in mouse models of Aβ amyloidosis

Discovery of an eclipsing X-ray binary with a 32.69 hour period in M101: an analog of Her X-1 or LMC X-4?

We report the discovery of an eclipsing X-ray binary in M101, the first such system to be discovered outside the Local Group. Based on a sequence of 25 Chandra observations that sample a wide range of orbital phases, we find a period of 32.688 $\pm$ 0.002 hours, which we interpret as an orbital period. The folded light curve exhibits an eclipse lasting about 8 hours, suggesting a compact orbit in an nearly edge-on configuration. The X-ray binary has an average luminosity of $L_X(0.3-8 {\rm keV}) \approx 1.3\times10^{38}$ erg/sec, with only one out of the 25 observations significantly lower in flux than the average light curve.The presence of the eclipse and the $\sim$ 1.4-day orbital period suggests that this source is an analog of the well studied eclipsing X-ray binary pulsars Her X-1 or LMC X-4. Combining the Chandra data and the HST ACS/WFC images, we have identified several possible optical counterparts, including an O5-O3 star with V = 25.0. Follow-up optical monitoring observations should be able to identify the donor and further constrain the orbital properties.Comment: 24 pages, 9 figures, 2 tables, ApJ in pres

Preintervention arterial remodeling affects clinical outcome following stenting: an intravascular ultrasound study

AbstractOBJECTIVESThe study was done to elucidate the relationship between baseline arterial remodeling and clinical outcome following stenting.BACKGROUNDThe impact of preintervention arterial remodeling on subsequent vessel response and clinical outcome has been reported following nonstent coronary interventions. However, in stented segments, the impact of preintervention remodeling on clinical outcome has not been clarified.METHODSPreintervention remodeling was assessed in 108 native coronary lesions by using intravascular ultrasound (IVUS). Positive remodeling (PR) was defined as vessel area (VA) at the target lesion greater than that of average reference segments. Intermediate or negative remodeling (IR/NR) was defined as VA at the target lesion less than or equal to that of average reference segment. Remodeling index expressed as a continuous variable was defined as VA at the target lesion site divided by that of average reference segments.RESULTSPositive remodeling was present in 59 (55%) and IR/NR in 49 (45%) lesions. Although final minimal stent areas were similar (7.76 ± 1.80 vs. 8.09 ± 1.90 mm2, p = 0.36), target vessel revascularization (TVR) rate at nine-month follow-up was significantly higher in the PR group (22.0% vs. 4.1%, p = 0.01). By multivariate logistic regression analysis, higher remodeling index was the only independent predictor of TVR (p = 0.02).CONCLUSIONSLesions with PR before intervention appear to have a worse clinical outcome following IVUS-guided stenting. Intravascular ultrasound imaging before stenting may be helpful to stratify lesions at high risk for accelerated intimal proliferation

Comparison of Zotarolimus-Eluting and Sirolimus-Eluting Stents in Patients With Native Coronary Artery Disease A Randomized Controlled Trial

ObjectivesThis trial examined the relative clinical efficacy, angiographic outcomes, and safety of zotarolimus-eluting coronary stents (ZES) with a phosphorylcholine polymer versus sirolimus-eluting stents (SES).BackgroundWhether a cobalt-based alloy stent coated with the novel antiproliferative agent, zotarolimus, and a phosphorylcholine polymer may provide similar angiographic and clinical benefit compared with SES is undetermined.MethodsA prospective, multicenter, 3:1 randomized trial was conducted to evaluate the safety and efficacy of ZES (n = 323) relative to SES (n = 113) in 436 patients undergoing elective percutaneous revascularization of de novo native coronary lesions with reference vessel diameters between 2.5 mm and 3.5 mm and lesion length ≥14 mm and ≤27 mm. The primary end point was 8-month angiographic in-segment late lumen loss.ResultsAngiographic in-segment late lumen loss was significantly higher among patients treated with ZES compared with SES (0.34 ± 0.44 mm vs. 0.13 ± 0.32 mm, respectively; p < 0.001). In-hospital major adverse cardiac events were significantly lower among patients treated with ZES (0.6% vs. 3.5%, p = 0.04). In-segment binary angiographic restenosis was also higher in the ZES cohort (11.7% vs. 4.3%, p = 0.04). Total (clinically and non-clinically driven) target lesion revascularization rates at 9 months were 9.8% and 3.5% for the ZES and SES groups, respectively (p = 0.04). However, neither clinically driven target lesion revascularization (6.3% zotarolimus vs. 3.5% sirolimus, p = 0.34) nor target vessel failure (12.0% zotarolimus vs. 11.5% sirolimus, p = 1.0) differed significantly.ConclusionsCompared with SES, treatment with a phosphorylcholine polymer-based ZES is associated with significantly higher late lumen loss and binary restenosis at 8-month angiographic follow-up.(The Endeavor III CR; http://clinicaltrials.gov/ct/show/NCT00265668?order=1?

Pretreatment HLADQA1-HLADRB1 Testing for the Prevention of Azathioprine-Induced Pancreatitis in Inflammatory Bowel Disease: A Prospective Cohort Study

INTRODUCTION:Azathioprine-induced pancreatitis is an idiosyncratic and unpredictable response, occurring in up to 7% of azathioprine-exposed patients with inflammatory bowel disease (IBD). The haplotype HLADQA1-HLADRB1*07:01A\u3eC is strongly associated with azathioprine-induced pancreatitis in IBD. We aimed to evaluate whether pretreatment HLADQA1-HLADRB1*07:01A\u3eC screening will reduce the risk of azathioprine-induced pancreatitis.METHODS:Participants with IBD were screened for HLADQA1-HLADRB1*07:01A\u3eC, and participants with a variant genotype were excluded from azathioprine treatment. Wild-type participants were started on azathioprine and followed for 3 months. The incidence of pancreatitis was compared with unscreened historical controls.RESULTS:HLADQA1-HLADRB1*07:01A\u3eC screening resulted in an 11-fold reduction in the incidence of azathioprine-induced pancreatitis (n = 1/328 or 0.30% vs n = 13/373 or 3.4%). In propensity score-matched cohorts (age and sex), HLA DQA1-HLADRB1*07:01A\u3eC screening was significantly associated with a reduction in the incidence of AZA-induced pancreatitis independent of weight, glucocorticoid exposure, and smoking status (adjusted odds ratio = 0.075, 95% confidence interval = 0.01-0.58, P = 0.01). Up to 45% (n = 271/599) of participants were excluded from azathioprine therapy based on the haplotype in the HLADQA1-HLADRB1*07:01A\u3eC-screened cohort.DISCUSSION:HLADQA1-HLADRB1*07:01A\u3eC screening reduced the risk of azathioprine-induced pancreatitis; however, using this strategy to guide the use of azathioprine therapy in IBD may eliminate a large proportion of patients from being eligible for treatment with azathioprine. In regions where there is access to other IBD therapies, and given the short-term and long-term toxicities associated with azathioprine, HLADQA1-HLADRB1*07:01A\u3eC-screening may be a clinically relevant strategy for enhancing the safe use of azathioprine in IBD. In addition, cost-effectiveness analyses are needed to further solidify the utility of HLADQA1-HLADRB1*07:01A\u3eC screening in IBD populations