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AbstractBackgroundMultimorbidity of intestinal cancer (IC), type 2 diabetes (T2D) and obesity is a complex set of diseases, affected by environmental and genetic risk factors. High‐fat diet (HFD) and oral bacterial infection play important roles in the etiology of these diseases through inflammation and various biological mechanisms.MethodsTo study the complexity of this multimorbidity, we used the collaborative cross (CC) mouse genetics reference population. We aimed to study the multimorbidity of IC, T2D, and obesity using CC lines, measuring their responses to HFD and oral bacterial infection. The study used 63 mice of both sexes generated from two CC lines (IL557 and IL711). For 12 weeks, experimental mice were maintained on specific dietary regimes combined with co‐infection with oral bacteria Porphyromonas gingivalis and Fusobacterium nucleatum, while control groups were not infected. Body weight (BW) and results of a intraperitoneal glucose tolerance test (IPGTT) were recorded at the end of 12 weeks, after which length and size of the intestines were assessed for polyp counts.ResultsPolyp counts ranged between 2 and 10 per CC line. The combination of HFD and infection significantly reduced (P < .01) the colon polyp size of IL557 females to 2.5 cm2, compared to the other groups. Comparing BW gain, IL557 males on HFD gained 18 g, while the females gained 10 g under the same conditions and showed the highest area under curve (AUC) values of 40 000‐45 000 (min mg/dL) in the IPGTT.ConclusionThe results show that mice from different genetic backgrounds respond differently to a high fat diet and oral infection in terms of polyp development and glucose tolerance, and this effect is gender related.

Administration of street-level bureaucrats requires prior knowledge of what affects their use of discretion. However, there is a lack of understanding as to what influences their decision-making when choosing between claims made by the state or by its citizens. Without such knowledge, public administration at the street-level can sustain the perception that street-level bureaucrats have a state-preference bias, lowering citizens’ view of public service delivery by those perceived as the face of governance. This study focuses on decisions street-level bureaucrats make when resolving disputes between citizens and other state officials. Using real-world resolutions made over three decades by lower-court judges in Israeli civil tax disputes, the findings reveal a link between factors associated with street-level bureaucrats’ common characteristics and state favoritism in their resolutions. The findings also imply that policymakers who want to mitigate such outcomes can use citizen administrative participation-based influencers to promote street-level bureaucrats’ pro-citizen tendencies.

Truss lattices are common in a wide variety of engineering applications, due to their high ratio of strength versus relative density. They are used both as the interior support for other structures, and as structures on their own. Using 3D sphere packing, we propose a set of methods for generating truss lattices that fill the interior of B-rep models, polygonal or (trimmed) NURBS based, of arbitrary shape. Once the packing of the spheres has been established, beams between the centers of adjacent spheres are constructed, as spline based B-rep geometry. We also demonstrate additional capabilities of our methods, including connecting the truss lattice to (a shell of) the B-rep model, as well as constructing a tensor-product trivariate volumetric representation of the truss lattice - an important step towards direct compatibility for analysis. RYC-2017-22649

The melting of a homopolymer double-stranded (ds) deoxyribonucleic acid (DNA) in the dilute limit is studied numerically in the presence of an attractive and impenetrable surface on a simple cubic lattice. The two strands of the DNA are modeled using two self-avoiding walks, capable of interacting at complementary sites, thereby mimicking the base pairing. The impenetrable surface is modeled by restricting the DNA configurations at the $z\geq 0$ plane, with attractive interactions for monomers at $z=0$. Further, we consider two variants for $z=0$ occupations by ds segments, where one or two surface interactions are counted. This consideration has significant consequences, to the extent of changing the stability of the bound phase in the adsorbed state. Interestingly, adsorption changes from critical to first-order with a modified exponent on coinciding with the melting transition. For simulations, we use the pruned and enriched Rosenbluth algorithm. Comment: 11 page and, 7 figures

Abstract Background Pathogenic bacteria are often asymptomatically carried in the nasopharynx. Bacterial carriage can be reduced by vaccination and has been used as an alternative endpoint to clinical disease in randomised controlled trials (RCTs). Vaccine efficacy ( VE ) is usually calculated as 1 minus a measure of effect. Estimates of vaccine efficacy from cross-sectional carriage data collected in RCTs are usually based on prevalence odds ratios (PORs) and prevalence ratios (PRs), but it is unclear when these should be measured. Methods We developed dynamic compartmental transmission models simulating RCTs of a vaccine against a carried pathogen to investigate how VE can best be estimated from cross-sectional carriage data, at which time carriage should optimally be assessed, and to which factors this timing is most sensitive. In the models, vaccine could change carriage acquisition and clearance rates (leaky vaccine); values for these effects were explicitly defined ( f a c q , 1 / f d u r ). POR and PR were calculated from model outputs. Models differed in infection source: other participants or external sources unaffected by the trial. Simulations using multiple vaccine doses were compared to empirical data. Results The combined VE against acquisition and duration calculated using POR ( V E ˆ a c q . d u r , ( 1 − P O R ) × 100 ) best estimates the true VE ( V E a c q . d u r , ( 1 − f a c q × f d u r ) × 100 ) for leaky vaccines in most scenarios. The mean duration of carriage was the most important factor determining the time until V E ˆ a c q . d u r first approximates V E a c q . d u r : if the mean duration of carriage is 1–1.5 months, up to 4 months are needed; if the mean duration is 2–3 months, up to 8 months are needed. Minor differences were seen between models with different infection sources. In RCTs with shorter intervals between vaccine doses it takes longer after the last dose until V E ˆ a c q . d u r approximates V E a c q . d u r . Conclusion The timing of sample collection should be considered when interpreting vaccine efficacy against bacterial carriage measured in RCTs.

Sediment-hosted marine sulfur cycling has played a significant role in regulating Earth's surface chemistry over our planet's history. Microbially-mediated reactions involving sulfur are often accompanied by sulfur isotope fractionation that, in turn, is captured by sulfate and sulfide minerals, providing the opportunity to track changes in the microbial utilization of sulfur and thus the marine sulfur cycle. Studying sulfur diagenesis within the Bornholm Basin, Baltic Sea, we explore the interplay between carbon, sulfur and iron, focusing on the fate of sulfur and the dynamics of the sulfur and oxygen isotopic response as a function of the varying thickness of the organic carbon-rich Holocene Mud Layer (HML) across the basin. Using a one-dimensional reaction-transport model, porewater sulfate and sulfide profiles were used to calculate net sulfate reduction rates (SRR) and net sulfide production rates, respectively. These calculations suggest a positive relationship between the thickness of the HML and net rates of sulfate reduction and sulfide production. Given that ascending sulfide is enriched in 34S relative to that produced in-situ, a heightened sulfide flux promotes spatially variable precipitation of 34S-enriched pyrite (δ34S ≈ −10‰) close to the sediment–water interface. Modeling results indicate that this isotopically “heavy” sulfide is formed as a consequence of mixing between ascending sulfide (up to +6.3‰) and that produced in-situ (ca. −40‰). Further, we show that the sulfur and oxygen isotopic composition of porewater sulfate is controlled by the net SRR: when the net SRR is high (i.e., in sulfide-replete settings) the downcore increase in δ18OSO4 is dampened relative to increase in δ34SSO4, whereas when net SRR is low (i.e., in iron-rich parts of the basin) downcore δ18OSO4 values increase while δ34SSO4 values remain invariant. We conclude that sedimentation rates and open system diffusion strongly influence the distribution of sulfur species and their sulfur isotopic composition, as well as the oxygen isotopic composition of sulfate, through the interaction between iron, sulfur and methane. This work highlights the importance of considering diffusion to better understand open system diagenesis and the δ34S signatures of sulfate and sulfide in both modern settings and ancient rocks.

This article engages in the explanation and interpretation of three unclear words, dyofe, meiarak and kitana, that appear in the Babylonian Talmud, Tractate Eruvin 104a–b. The words are part of the Talmudic text and the article addresses the various meanings ascribed to them and explains them. This is required because of the contradiction and confusion that exist in the explanation and interpretation of these three words. The research method employed involves examining the various explanations given by the commentators, comparing the words with other sources and checking their suggested meanings in Talmudic dictionaries. The research results show different versions of these three words and the conclusions indicate that the different versions change their possible explanation and interpretation. Contribution: The innovation of this article is in presenting the various sources of these words, noting their various versions and the different interpretations that derive from them. The article also describes the interpretive development of these words, as well as noting the commentators who offer explanations for the two first words, which generate contradictory meanings.

ABSTRACTBackgroundUnderstanding and monitoring the demographics of SARS-CoV-2 infection can inform strategies for prevention. Surveillance monitoring has suggested that the age distribution of people infected with SARS-CoV-2 has changed since the pandemic began, but no formal analysis has been performed.MethodsRetrospective review of SARS-CoV-2 molecular testing results from a national reference laboratory was performed. Result distributions by age and positivity were compared between early period (March-April 2020) and late periods (June-July 2020) of the COVID-19 pandemic. Additionally, a sub-analysis compared changing age distributions between inpatients and outpatients.ResultsThere were 277,601 test results of which 19320 (7.0%) were positive. The median age of infected people declined over time (p < 0.0005). In March-April, the median age of positive people was 40.8 years (Interquartile range (IQR): 29.0 – 54.1). In June-July, the median age of positive people was 35.8 years (IQR: 24.0 – 50.2). The positivity rate of patients under 50 increased from 6.0 to 10.6 percent and the positivity rate for those over 50 decreased from 6.3 to 5.0 percent between the early and late periods. The trend was only observed for outpatient populations.ConclusionsWe confirm that there is a trend toward decreasing age among persons with laboratory- confirmed SARS-CoV-2 infection, but that these trends seem to be specific to the outpatient population. Overall, this suggests that observed age-related trends are driven by changes in testing patterns rather than true changes in the epidemiology of SARS-CoV-2 infection. This calls for caution in interpretation of routine surveillance data until testing patterns stabilize.SummaryWe used national reference laboratory data to compare ages of patients tested for SARS-CoV-2 in March/April 2020 vs. June/July. Median age declined overall, but increased for inpatients, suggesting that declining age is due to changes in surveillance, not COVID-19 epidemiology.