Uterine Prolapse in an Adult Richardson's Ground Squirrel, Spermophilus richardsonii

During a study of Richardson's Ground Squirrel (Spermophilus richardsonii) populations in southern Saskatchewan, we captured one adult female with a partially prolapsed uterus. This is the first known case of uterine prolapse in a Richardson's Ground Squirrel

Vacancy clustering and diffusion in silicon: Kinetic lattice Monte Carlo simulations

Diffusion and clustering of lattice vacancies in silicon as a function of temperature, concentration, and interaction range are investigated by Kinetic Lattice Monte Carlo simulations. It is found that higher temperatures lead to larger clusters with shorter lifetimes on average, which grow by attracting free vacancies, while clusters at lower temperatures grow by aggregation of smaller clusters. Long interaction ranges produce enhanced diffusivity and fewer clusters. Greater vacancy concentrations lead to more clusters, with fewer free vacancies, but the size of the clusters is largely independent of concentration. Vacancy diffusivity is shown to obey power law behavior over time, and the exponent of this law is shown to increase with concentration, at fixed temperature, and decrease with temperature, at fixed concentration.Comment: 14 pages, 12 figures. To appear in Physical Review

Syndemics and the PrEP Cascade: Results from a Sample of Young Latino Men Who Have Sex with Men.

Young Latino men who have sex with men (MSM) are a highly vulnerable population for HIV infection. Pre-exposure prophylaxis (PrEP) is a novel biomedical HIV prevention tool that may aid in reducing the disparity in HIV incidence among Latino MSM. However, PrEP use is disproportionally low among Latino MSM and, therefore, identifying barriers along the PrEP continuum of care (the "PrEP cascade") would provide insight into how to best deploy PrEP interventions. Syndemics theory is a prominent framework employed in HIV prevention; however, to date, no known studies have applied this theory to PrEP. Thus, the aim of the current study was to explore the association between syndemics and the PrEP cascade, including the degree to which psychosocial and structural syndemic constructs are related to the PrEP cascade. Participants were 151 young Latino MSM (M age = 24 years; SD = 3) residing in San Diego, California, who completed a battery of online self-report measures. Results indicated high levels of syndemic indicators and varying levels of engagement across the PrEP cascade. As syndemic indicators increased, the odds of engagement across the PrEP cascade were significantly lowered. Psychosocial and structural syndemic factors accounted for unique variance in the PrEP cascade. Results highlight the need for combination interventions that address both psychosocial and structural barriers to PrEP use and persistence among young Latino MSM

The surface of iron molybdate catalysts used for the selective oxidation of methanol

The oxidation of methanol to formaldehyde is a major chemical process carried out catalytically and iron molybdate is one of the major catalysts for this process. In this paper we explore the nature of the active and selective surfaces of iron molybdate catalysts and show that the effective catalysts comprise molybdenum rich surfaces. We conclude that it is therefore important to maximise the surface area of these active catalysts and to this end we have studied catalysts made using a new physical grinding method with oxalic acid. For super-stoichiometric materials (Fe:Mo = 1:2.2) the reaction data show that physical mixing produces effective catalysts, possibly offering an improvement over the conventional co-precipitation method

Obesity is not associated with progression to end stage renal disease in patients with biopsy-proven glomerular diseases

Background: Body mass index (BMI) is associated with renal disease progression in unspecified CKD. The relationship between BMI and primary glomerular disease (GN) may be more complex. We aimed to evaluate the association between BMI and renal disease progression in patients with primary glomerular disease (GN). Methods: This was a single-centre retrospective cohort study performed in adult patients with biopsy-proven primary GN (excluding minimal change disease) from January 2000 to December 2015, with follow-up data until June 2017. BMI at time of biopsy was categorised as ≤25 kg/m2, > 25 to ≤30 kg/m2 and > 30 kg/m2. We used univariate and multivariate survival analyses to evaluate factors associated with progression to a composite endpoint of stage 5 CKD or renal replacement therapy (Major Adverse Renal Event - MARE) censoring for competing risk of death using Fine and Gray subdistribution hazards model. Results: We included 560 patients with biopsy-proven primary GN and available BMI data: 66.1% were male with median age 54.8 (IQR 41.1–66.2) years and BMI 28.2 (IQR 24.9–32.1) kg/m2. Those with BMI 25-30 kg/m2 (n = 210) and with BMI > 30 kg/m2 (n = 207) were older (p = 0.007) with higher systolic and diastolic blood pressures (p = 0.02 and 0.004 respectively) than those with BMI < 25 kg/m2 (n = 132). There was a greater proportion of focal segmental glomerulosclerosis in those with higher BMI (3.9% in BMI < 25 kg/m2, 7.9% in BMI 25–30 kg/m2 and 10.7% in BMI > 30 kg/m2 of biopsies (p = 0.01)), but similar proportions of other GN diagnoses across BMI groups. Baseline eGFR (p = 0.40) and uPCR (p = 0.17) were similar across BMI groups. There was no interaction between BMI and time to MARE (log-rank p = 0.98) or death (log-rank p = 0.42). Censoring for competing risk of death, factors associated with progression to MARE were: younger age, lower baseline eGFR and higher uPCR, but not BMI (SHR 0.99, 95%CI 0.97–1.01, p = 0.31) nor blood pressure or GN diagnosis. Conclusion: BMI was not associated with progression to MARE in this patient cohort with primary GN. Efforts should be directed to managing other known risk factors for CKD progression

Mapping systematic errors in helium abundance determinations using Markov Chain Monte Carlo

Monte Carlo techniques have been used to evaluate the statistical and systematic uncertainties in the helium abundances derived from extragalactic H~II regions. The helium abundance is sensitive to several physical parameters associated with the H~II region. In this work, we introduce Markov Chain Monte Carlo (MCMC) methods to efficiently explore the parameter space and determine the helium abundance, the physical parameters, and the uncertainties derived from observations of metal poor nebulae. Experiments with synthetic data show that the MCMC method is superior to previous implementations (based on flux perturbation) in that it is not affected by biases due to non-physical parameter space. The MCMC analysis allows a detailed exploration of degeneracies, and, in particular, a false minimum that occurs at large values of optical depth in the He~I emission lines. We demonstrate that introducing the electron temperature derived from the [O~III] emission lines as a prior, in a very conservative manner, produces negligible bias and effectively eliminates the false minima occurring at large optical depth. We perform a frequentist analysis on data from several "high quality" systems. Likelihood plots illustrate degeneracies, asymmetries, and limits of the determination. In agreement with previous work, we find relatively large systematic errors, limiting the precision of the primordial helium abundance for currently available spectra.Comment: 25 pages, 11 figure

Altering, Improving, And Defining The Specificities Of Crispr-Cas Nucleases

CRISPR-Cas9 nucleases have been widely adopted for genome editing applications to knockout genes or to introduce desired changes. While these nucleases have shown immense promise, two notable limitations of the wild-type form of the broadly used Streptococcus pyogenes Cas9 (SpCas9) are the restriction of targeting range to sites that contain an NGG protospacer adjacent motif (PAM), and the undesirable ability of the enzyme to cleave off-target sites that resemble the on-target site. Scarcity of PAM motifs can limit implementations that require precise targeting, whereas off-target effects can confound research applications and are important considerations for therapeutics. To improve the targeting range of SpCas9 and an orthogonal Cas9 from Staphylococcus aureus (called SaCas9), we optimized a heterologous genetic selection system that enabled us to perform directed evolution of PAM specificity. With SpCas9, we evolved two separate variants that can target NGA and NGCG PAMs1, and with SaCas9 relaxed the PAM from NNGRRT to NNNRRT2, increasing the targetability of these enzyme 2- to 4-fold. The genome-wide specificity profiles of SpCas9 and SaCas9 variants, determine by GUIDE-seq3, indicate that they are at least as, if not more, specific than the wild-type enzyme1,2. Together, these results demonstrate that the inherent PAM specificity of multiple different Cas9 orthologues can be purposefully modified to improve the accuracy of targeting. Existing strategies for improving the genome-wide specificity of SpCas9 have thus far proven to be incompletely effective and/or have other limitations that constrain their use. To address the off-target potential of SpCas9, we engineered a high-fidelity variant of SpCas9 (called SpCas9-HF1), that contains alterations designed to reduce non-specific contacts to the target strand DNA backbone. In comparison to wild-type SpCas9, SpCas9-HF1 rendered all or nearly all off-target events imperceptible by GUIDE-seq and targeted deep-sequencing methods with standard non-repetitive target sites in human cells4. Even for atypical, repetitive target sites, the vast majority of off-targets induced by SpCas9-HF1 and optimized derivatives were not detected4. With its exceptional precision, SpCas9-HF1 provides an important and easily employed alternative to wild-type SpCas9 that can eliminate off-target effects when using CRISPR-Cas9 for research and therapeutic applications. Finally, on-target activity and genome-wide specificity are two important properties of engineered nucleases that should be characterized prior to adoption of such technologies for research or therapeutic applications. CRISPR-Cas Cpf1 nucleases have recently been described as an alternative genome-editing platform5, yet their activities and genome-wide specificities remain largely undefined. Based on assessment of on-target activity across more than 40 target sites, we demonstrate that two Cpf1 orthologues function robustly in human cells with efficiencies comparable to those of the widely used Streptococcus pyogenes Cas9. We also demonstrate that four to six bases at the 3’ end of the short CRISPR RNA (crRNA) used to program Cpf1 are insensitive to single base mismatches, but that many of the other bases within the crRNA targeting region are highly sensitive to single or double substitutions6. Consistent with these results, GUIDE-seq performed in multiple cell types and targeted deep sequencing analyses of two Cpf1 nucleases revealed no detectable off-target cleavage for over half of 20 different crRNAs we examined. Our results suggest that the two Cpf1 nucleases we characterized generally possess robust on-target activity and high specificities in human cells, findings that should encourage broader use of these genome editing enzymes. 1. Kleinstiver, BP, et al. (2015) Nature, 523(7561):481-5 2. Kleinstiver, BP, et al. (2015) Nature Biotechnology, 33(12):1293-98 3. Tsai, SQ et al. (2015) Nature Biotechnology, 33(2):187-97 4. Kleinstiver, BP and Pattanayak, V, et al. (2016), Nature, 529(7587):490-5 5. Zetsche, B, et al. (2015) Cell, 163(3):759-71 6. Kleinstiver, BP and Tsai, SQ, et al. (2016), Nature Biotechnology, 34(8):869-7

Morally Respectful Listening and its Epistemic Consequences

What does it mean to listen to someone respectfully, that is, insofar as they are due recognition respect? This paper addresses that question and gives the following answer: it is to listen in such a way that you are open to being surprised. A specific interpretation of this openness to surprise is then defended