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This work focuses on construction of a bridge from QCD (quantum chromodynamics), the theory of quarks, gluons, and their interactions, to nuclear structure, an obvious but unattained objective ever since the introduction of QCD in 1973. The bridge footing on one side of the chasm is QCD in the non-perturbative regime, only now beginning to yield to massively parallel computation in a Monte-Carlo space-time lattice formulation of QCD called LQCD (lattice quantum chromodynamics) that is our only tool for such problems. The resulting trickle of information about the nucleon interaction comes in the form of a fuzzy spectrum for two nucleons in a periodic box. It can be expected that the spectrum will sharpen and even eventually include a spectrum for three nucleons in a box with the introduction of larger and faster supercomputers as well as more clever algorithms. Fundamentally though, limits on what can be accomplished in LQCD are set by the famous fermion sign problem. Results in LQCD are produced as a small residual of the sum of large positive and negative contributions from the Monte-Carlo trials and accuracy only improves slowly with the number of expensive trials.The bridge footing on the other side of the chasm is the configuration interaction shell model, which is commonly used for nuclear structure calculations from a microscopic Hamiltonian expressed in the colorless degrees of freedom of QCD we call nucleons. As currently executed, this method is a model, the two- and possibly three-body interaction in use lacking a rigorous connection to QCD or direct accounting for contributions from scattering outside the model space. Nucleons, like quarks, are fermions and a fermion sign like problem exists in these calculations as well. The configuration interaction shell model is formulated in an antisymmetrized harmonic oscillator basis that grows with the number of permutations of identical nucleons in the model space. However, fantastically e cient parallel sparse matrix techniques for finding low lying eigenstates exist, allowing quite large problems to be solved.One footing of the bridge is solid and the other is nearing completion. Construction of the bridge itself then faces three major problems addressed in this dissertation, construction of the effective nuclear interaction from observables, finite volume effects associated with the periodic volume in which LQCD results are calculated, and the construction of the A-body effective Hamiltonian from the two body effective interaction.An effective theory is a organized and complete parameterized approximation limited to and preserving the known symmetries of an underlying theory (QCD in this case), constrained to some regime (energies below the mass of the pion in this case), and expressed in degrees of freedom suitable for solving the problem at hand (nucleons in a harmonic oscillator basis below an energy cutoff for the nuclear structure problem). An effective theory has a formal relationship to the underlying theory that a model does not. Unlike a model, a small number of observables may be used to fix the lowest order expansion parameters of the effective theory approximation with the expectation that the approximation remains valid in other situations for which observables are not available.The first portion of this work focuses on the construction of a harmonic oscillator based effective theory (HOBET) from observables in a spherical harmonic oscillator basis. It builds on the prior work of Haxton, Song, and Luu in demonstrating the construction of an convergent effective theory from a known potential, establishing the form of the required effective theory expansion. The new work required the extension of HOBET to a theory no longer limited to bound states and with continuity in energy, enabling uniform treatment of bound and continuum states. Here the expansion parameters are instead derived from phase shift observables at continuum energies. A key insight developed during this work was the way in which the effective theory constructed at an energy is connected to the boundary constraints of the wave function. Using known techniques, Lu ̈scher’s method and the HAL QCD potential method, to transform the LQCD spectrum in periodic box to infinite volume phase shifts produces a successful mechanism for fitting the effective interaction without knowledge of the details of the potential.The techniques for converting LQCD results to phase shifts have issues such as uncontrolled systematics related to the volume size and range of the interaction as well as suspect perturbative expansions. These issues motivated an investigation into the possibility of directly constructing the effective theory in a periodic volume. This new construction relies heavily on the previous insight about the connection of the effective theory to the wave function boundary constraints. A key result is that the kernel of the effective theory, which captures scattering through the excluded degrees of freedom, is in fact independent of the boundary conditions. It can be fit in the periodic volume context and then transplanted into an infinite volume spherical formulation of the effective theory by a straightforward basis transformation. Finite volume effects are automatically handled in the process. Of immediate interest to the LQCD community is that accurate phase shifts can be easily extracted from the effective theory, avoiding systematic and finite volume errors in existing methods.With a two body effective interaction in hand the last step to a usable bridge is the construction of an A-body interaction in terms of the two body one. The exact form this construction is not settled yet, but one promising structure with leading contributions that can be calculated is explored.The assembly of these three pieces completes the bridge, producing a way to perform nuclear structure calculations that is formally connected to the underlying theory of QCD.

There are several hundreds of genes overexpressed in a typical breast cancer cell, and their overexpression is often assumed to have a pro-cancer function, but what percentage of these overexpressed genes have a role in promoting and maintaining tumorigenicity isn’t known. To address this question, we screened an unbiased set of seventy-five genes overexpressed in breast cancer for their ability to induce malignant transformation and for breast cancer cell expression dependency. Barcoded open-reading frames under the control of a constitutive promoter were tested by pooled screening for their ability to promote tumor formation of premalignant mammary epithelial cells and growth in 2D and 3D culture. We found that growth in 3D cell culture was more strongly correlated with tumorigenic growth than was 2D growth, validating a long-standing hypothesis. Genes with high activity in promoting both 3D growth and in vivo tumor formation included CEACAM5, CXCL8, NKX2-5, PYGO2 and WWTR1/TAZ. To screen for corresponding tumor dependencies on these six genes, we performed shRNA screening of breast cancer cell lines and found uniform dependency on expression of the Hippo pathway transcriptional activator WWTR1, selective dependencies on CEACAM5 expression, but no consistent effects for the other three genes. Since breast cancer dependency upon WWTR1 is well established, we focused our follow-up studies on CEACAM5. We confirmed that CEACAM5 overexpression conferred tumorigenicity to pre-malignant mammary epithelial cells and that reduced expression selectively decreased the clonogenicity of luminal breast cancer cell lines. Protein analysis indicated that CEACAM5 activated Cdk4/6 and mTOR signaling. We also determined that CEACAM5 overexpression strongly promoted cell number increase in 3D spheroid culture by a novel mechanism that increased the number of epithelial cell layers from a single layer to multiple layers. These results outline a strategy for functional genomic identification of cancer targets, starting with a set of genes overexpressed in cancer, then using pooled approaches to identify those that promote tumorigenicity and cancer cell dependency, followed by validation experiments and exploration of oncogenic mechanisms. We propose that larger screens would substantially increase the number of potential targets for treating breast cancer.

Persons identifying as Hispanic or Latino (Hispanic) represent the second largest racial/ethnic group in the United States (1), yet understanding of the impact of coronavirus disease 2019 (COVID-19) in this population is limited. To evaluate COVID-19 health disparities in the community and inform public health, health system, and community-based interventions, local public health authorities analyzed the sociodemographic characteristics of persons who were diagnosed, hospitalized, and who died with COVID-19 in Denver, Colorado. During the first 7 months of the COVID-19 epidemic in Denver (March 6-October 6, 2020) the majority of adult COVID-19 cases (54.8%), hospitalizations (62.1%), and deaths (51.2%) were among persons identifying as Hispanic, more than double the proportion of Hispanic adults in the Denver community (24.9%) (1). Systemic drivers that influence how Hispanic persons live and work increase their exposure risks: compared with non-Hispanic persons, Hispanic persons with COVID-19 in Denver reported larger household sizes and were more likely to report known exposures to household and close contacts with COVID-19, working in an essential industry, and working while ill. Reducing the disproportionate incidence of COVID-19 morbidity and mortality among Hispanic persons will require implementation of strategies that address upstream social and environmental factors that contribute to an increased risk for both infection and transmission and that facilitate improved access to culturally congruent care.

Recent designs have allowed hollow cathode gas plasma sources to be adopted for use in plasma-enhanced atomic layer deposition with the benefit of lower oxygen contamination for non-oxide films (a brief review of this is provided). From a design perspective, the cathode metal is of particular interest since—for a given set of conditions—the metal work function should determine the density of electron emission that drives the hollow cathode effect. However, we found that relatively rapid surface modification of the metal cathodes in the first hour or more of operation has a stronger influence. Langmuir probe measurements and hollow cathode electrical characteristics were used to study nitrogen and oxygen plasma surface modification of aluminum and stainless-steel hollow cathodes. It was found that the nitridation and oxidation of these metal cathodes resulted in higher plasma densities, in some cases by more than an order of magnitude, and a wider range of pressure operation. Moreover, it was initially thought that the use of aluminum cathodes would not be practical for gas plasma applications, as aluminum is extremely soft and susceptible to sputtering; however, it was found that oxide and nitride modification of the surface could protect the cathodes from such problems, possibly making them viable.

Purpose: Virtual reality exposure therapy (VRET) is an intervention used to treat alcohol and nicotine dependence that delivers cue exposure therapy using a virtual reality environment; however, little is known about the effects of these interventions. Method: We used systematic review methods to examine the effects of VRET on alcohol or nicotine dependence, craving, and substance use with persons with current nicotine or alcohol dependence. We conducted a comprehensive search to retrieve published and unpublished intervention studies in 18 databases and other gray literature sources. Studies were screened, and data were extracted by two independent reviewers. Results: Five studies including 212 participants were included. Effects were found for alcohol and nicotine dependence and craving; however, significant methodological issues and high risk of bias were present across studies. Conclusion: Evidence of effects of VRET is sparse, and methodological flaws and gaps in reporting were identified. Implications for practice and research are discussed.

“Virtual Reality” interventions in human services may include 360° video, augmented reality, mixed reality, and fully immersive 3-dimensional virtual reality simulations. A variety of appli...

The American Academy of Social Work and Social Welfare (AASWSW) identified 12 Grand Challenges of Social Work to unify the profession with focused research, practice and policy applications for the...

Virtual reality (VR) has emerged as a promising technological intervention for anxiety disorders. However, there are no existing standards and best practices to evaluate the effectiveness of enviro...

Nuts from F1 hybrid hazelnuts grown in Wisconsin were harvested and dried to eight different moisture contents. Nut dimensions and mass were recorded. Nuts were then subjected to uniaxial compression to determine total deformation required for rupture, rupture force, and rupture energy for each of the three major nut axes. Kernel dimensions, shell thickness, shell mass, and kernel mass of each nut were recorded after rupture. Hybrid hazelnuts and kernels were found to be smaller than European varieties. Nut geometry was found to change with nut size. When a nut is loaded, an initial crack forms along a longitudinal line parallel to the direction of applied load and then rapidly propagates until it has extended along two longitudinal lines (both parallel to the applied load), causing the shell to split into two pieces. Under lateral (Y-axis and Z-axis) loadings, the shell is split into nearly identical halves. Loading along the X-axis required the lowest rupture force, rupture energy, and rupture strain of all loading axes. Rupture force, rupture energy, and stiffness were shown to be highly correlated with moisture content. At lower moisture contents, shells fractured into more pieces. Keywords: Hazelnut, Nut cracking, Nut geometry, Nut rupture force, Shelling, Shell thickness.

Pseudomonas aeruginosa is the most common Gram-negative pathogen causing nosocomial multidrug resistant infections. It is a good biofilm producer and has the potential for contaminating medical devices. Despite the widespread use of antibacterial-impregnated catheters, little is known about the impacts of antibacterial coating on the pathogenesis of P. aeruginosa. In this study, we investigated the adaptive resistance potential of P. aeruginosa strain PAO1 in response to continuous antibiotic exposure from clindamycin/rifampicin-impregnated catheters (CR-IC). During exposure for 144 h to clindamycin and rifampicin released from CR-IC, strain PAO1 formed biofilms featuring elongated and swollen cells. There were 545 and 372 differentially expressed proteins (DEPs) identified in the planktonic and biofilm cells, respectively, by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Both Cluster of Orthologous Groups (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the planktonic cells responded to the released antibiotics more actively than the biofilm cells, with metabolism and ribosomal biosynthesis-associated proteins being significantly over-expressed. Exposure to CR-IC increased the invasion capability of P. aeruginosa for Hela cells and upregulated the expression of certain groups of virulence proteins in both planktonic and biofilm cells, including the outer membrane associated (flagella, type IV pili and type III secretion system) and extracellular (pyoverdine) virulence proteins. Continuous exposure of P. aeruginosa to CR-IC also induced the overexpression of antibiotic resistance proteins, including porins, efflux pumps, translation and transcription proteins. However, these upregulations did not change phenotypic minimum inhibitory concentration (MIC) during the experimental timeframe. The concerning association between CR-IC and overexpression of virulence factors in P. aeruginosa suggests the need for additional investigation to determine if it results in adverse clinical outcomes.

IntroductionChronic kidney disease (CKD) is a global-health problem. A significant proportion of referrals to nephrologists for CKD management are early and guideline-discordant, which may lead to an excess number of referrals and increased wait-times. Various initiatives have been tested to increase the proportion of guideline-concordant referrals and decrease wait times. This paper describes the protocol for a systematic review to study the impacts of quality improvement initiatives aimed at decreasing the number of non-guideline concordant referrals, increasing the number of guideline-concordant referrals and decreasing wait times for patients to access a nephrologist.Methods and analysisWe developed this protocol by using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols (2015). We will search the following empirical electronic databases: MEDLINE, Embase, Cochrane Library, CINAHL, Web of Science, PsycINFO and grey literature for studies designed to improve guideline-concordant referrals or to reduce unnecessary referrals of patients with CKD from primary care to nephrology. Our search will include all studies published from database inception to April 2021 with no language restrictions. The studies will be limited to referrals for adult patients to nephrologists. Referrals of patients with CKD from non-nephrology specialists (eg, general internal medicine) will be excluded.Ethics and disseminationEthics approval will not be required, as we will analyse data from studies that have already been published and are publicly accessible. We will share our findings using traditional approaches, including scientific presentations, open access peer-reviewed platforms, and appropriate government and public health agencies.PROSPERO registration numberCRD42021247756.

BackgroundThe effect of hemodialysis on cardiac biomarkers is unclear. We sought to evaluate the degree and causes of intradialytic variability of high sensitivity troponin I (hs-TnI), galectin-3 (gal-3), and heart-type fatty acid binding protein (hFABP).Methodshs-TnI, gal-3, and hFABP were prospectively measured pre-dialysis and post-dialysis for 1 week every month for 6 months in 178 prevalent adult hemodialysis patients at a single center in Hamilton, Canada. The degree of change from pre-dialysis to post-dialysis for each cardiac biomarker was estimated with multilevel linear regression models.ResultsThe median change in the concentration of hs-TnI during hemodialysis was −1 ng/L (interquartile range [IQR] −1 to 2 ng/L) while gal-3 and hFABP changed by −36.3 ng/mL (IQR −27.7 to −46.8 ng/mL) and −19.41 ng/mL (IQR −13.61 to −26.87 ng/mL), respectively. The median (IQR) percentage intradialytic changes for hs-TnI, gal-3, and hFABP were 2.6% (−4.4% to 12.5%), −59.8% (−54.7% to −64.8%) and −35.3% (−28.4% to −42.1%), respectively. Ultrafiltration was associated with an increase in concentration of hs-TnI, gal-3, and hFABP (mean 0.99 ng/L, 1.05 ng/mL, and 1.9 ng/mL per L ultrafiltration, respectively, P ConclusionsUltrafiltration volume and hemodialysis treatment time influenced hs-TnI, gal-3, and hFABP concentrations during hemodialysis and should be considered when interpreting their measurement.

ObjectivesChronic kidney disease (CKD) is common; therefore, coordination of care between primary care and nephrology is important. Ontario Renal Network’s KidneyWise toolkit was developed to provide guidance on the detection and management of people with CKD in primary care (www.kidneywise.ca). The aim of this study was to evaluate the impact of the April 2015 KidneyWise toolkit release on the characteristics of primary care referrals to nephrology.Design and settingThe study was a prospective pre-post design conducted at two nephrology sites (community site: Trillium Health Partners in Mississauga, Ontario, Canada, and academic site: St Joseph’s Healthcare in Hamilton, Ontario, Canada). Referrals were compared during the 3-month time period immediately prior to, and during a 3-month period 1 year after, the toolkit release.Primary and secondary outcome measuresThe primary outcome was the change in proportion of referrals for CKD that met the KidneyWise criteria. Additional secondary referral and quality of care outcomes were also evaluated. Multivariable logistic regression was used to evaluate preselected variables for their independent association with referrals that met the KidneyWise criteria.ResultsThe proportion of referrals for CKD among people who met the KidneyWise referral criteria did not significantly change from pre-KidneyWise to post-KidneyWise implementation (44.7% vs 45.8%, respectively, adjusted OR 1.16, 95% CI 0.85 to 1.59, p=0.36). The proportion of referrals for CKD that provided a urine albumin-creatinine ratio significantly increased post-KidneyWise (25.8% vs 43.8%, adjusted OR 1.45, 95% CI 1.06 to 1.97, p=0.02). The significant independent predictors of meeting the KidneyWise referral criteria were academic site, increased age and use of the KidneyWise referral form.ConclusionsWe did not observe any change in the proportion of appropriate referrals for CKD at two large nephrology centres 1 year after implementation of the KidneyWise toolkit.