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Technologies are increasingly enrolled in projects to involve civilians in the work of policy-making, often under the label of 'civic technology'. But conventional forms of participation through transactions such as voting provide limited opportunities for engagement. In response, some civic tech groups organize around issues of shared concern to explore new forms of democratic technologies. How does their work affect the relationship between publics and public servants? This paper explores how a Civic Tech Toronto creates a platform for civic engagement through the maintenance of an autonomous community for civic engagement and participation that is casual, social, nonpartisan, experimental, and flexible. Based on two years of action research, including community organizing, interviews, and observations, this paper shows how this grassroots civic tech group creates a civic platform that places a diverse range of participants in contact with the work of public servants, helping to build capacities and relationships that prepare both publics and public servants for the work of participatory democracy. The case shows that understanding civic tech requires a lens beyond the mere analysis or production of technical artifacts. As a practice for making technologies that is social and participatory, civic tech creates alternative modes of technology development and opportunities for experimentation and learning, and it can reconfigure the roles of democratic participants., Will appear in CSCW1 2023

Circular dichroism (CD) measurements help characterize optically active molecules and higher-order biomolecular structures. The harmonization of interlaboratory CD measurements requires minimizing measurement uncertainties and determinate errors. Most CD measurements utilize a single-wavelength intensity measurement at a spectral peak to calibrate the intensities of the ultraviolet wavelength range. However, such a single-wavelength calibration is inherently less precise than using the CD instrument's spectrum over the entire measured spectral range. A more thorough and informative calibration can be achieved by remapping the spectrum into what we call a spectral similarity plot. This process allows a straightforward, quantitative evaluation of the shape congruence between two spectra over the full spectral range. While preliminary analyses suggest spectral similarity plots can be utilized with a variety of different spectrometry methods, here we illustrate the process applied to circular dichroism. Spectral similarity plots are highly sensitive to deviations due to differences in concentration, pathlength, source and detector properties, circular polarization balance, as well as wavelength nonlinearities and shifts. Deviations in these properties can be quantitated by a linear least squares fit of the remapped data. The remapping enables protocols to correct spectra toward congruence between two spectra. The spectra similarity comparison provides an objective, unambiguous test of the CD instrument quality when, for example, compared to a carefully calibrated system as shown in the examples described in the text.

This study utilizes geostatistical modelling of magnetic susceptibility (MS) for geophysical prospection of archaeological stratigraphy at the Middle Stone Age rock shelter site of Pinnacle Point 5-6 North. These models are overlaid onto high-resolution photography of the stratigraphic sequence to study the lateral and vertical changes within the magnetic signature of the archaeological sequence and correlate these changes to micromorphological interpretations previously made at the site. In situ analysis is reinforced by laboratory magnetic mineralogical analysis utilizing MS; frequency-dependent susceptibility (chi(FD)); isothermal remanent magnetization; and anhysteric remanent magnetization to understand the composition of the magnetic minerals creating the in situ signature. This study shows that there is consistent variation in the magnetic signatures of the sequence that can be mapped with in situ MS; there is a correlation with laboratory analysis of magnetic mineralogy, which provides insight into changes in human behaviour; and our models correlate well with micromorphological interpretations of the site. info:eu-repo/semantics/publishedVersion

In 2005, the Evangelical Lutheran Church in America’s (ELCA) Churchwide Assembly authorized the formation of a task force to prepare a social statement on genetics and faith. Although the Churchwide Assembly voted to adopt the social statement in August of 2011 by a wide margin, there had been an earlier controversy. In June 2010, an article in the Dakota Farmer questioned whether the ELCA was accusing farmers of “sin” for planting genetically engineered crop seeds. At least two churches in rural North Dakota cited this factor as a reason for leaving the ELCA. Seven synods with strong farmer constituencies proposed resolutions challenging the social statement. This paper explores how the opposition used agrarianism and libertarianism to attack the ELCA’s use of the Christian concept of the common good in the social statement. This case reveals the challenges that the Church faces when contributing to ethical deliberations on controversial issues.

Non-conservative and permutationally-invariant Markov state models inform understanding and control of self-assembling optical matter systems.

Non-significant alteration in the immune and stromal landscape of the ovarian cortex with metformin use.

Supplementary Data File S1

Supplementary Legend

Automated microdissection and immunohistochemical analysis of the human ovarian cortex.

Purpose:The ovarian cancer risk factors of age and ovulation are curious because ovarian cancer incidence increases in postmenopausal women, long after ovulations have ceased. To determine how age and ovulation underlie ovarian cancer risk, we assessed the effects of these risk factors on the ovarian microenvironment.Experimental Design:Aged C57/lcrfa mice (0–33 months old) were generated to assess the aged ovarian microenvironment. To expand our findings into human aging, we assembled a cohort of normal human ovaries (n = 18, 21–71 years old). To validate our findings, an independent cohort of normal human ovaries was assembled (n = 9, 41–82 years old).Results:We first validated the presence of age-associated murine ovarian fibrosis. Using interdisciplinary methodologies, we provide novel evidence that ovarian fibrosis also develops in human postmenopausal ovaries across two independent cohorts (n = 27). Fibrotic ovaries have an increased CD206+:CD68+ cell ratio, CD8+ T-cell infiltration, and profibrotic DPP4+αSMA+ fibroblasts. Metformin use was associated with attenuated CD8+ T-cell infiltration and reduced CD206+:CD68+ cell ratio.Conclusions:These data support a novel hypothesis that unifies the primary nonhereditary ovarian cancer risk factors through the development of ovarian fibrosis and the formation of a premetastatic niche, and suggests a potential use for metformin in ovarian cancer prophylaxis.See related commentary by Madariaga et al., p. 523

Ovarian aging heterogeneity is not replicated by VCD treatment

Gene ontology features in metformin vs. fibrotic human ovaries

Grouped Nanostring data with gliptin samples omitted.

Gene ontology features in metformin vs. non-fibrotic human ovaries

Differential gene expression in non-fibrotic, fibrotic, and metformin ovaries with samples from women taking gliptins omitted.

Gene annotations used to generate cell type scores

Gene ontology features in fibrotic vs. non-fibrotic human ovaries

IntroductionAdipocytes in the tumour microenvironment are highly dynamic cells that have an established role in tumour progression, but their impact on anti-cancer therapy resistance is becoming increasingly difficult to overlook.MethodsWe investigated the role of adipose tissue and adipocytes in response to oncolytic virus (OV) therapy in adipose-rich tumours such as breast and ovarian neoplasms.ResultsWe show that secreted products in adipocyte-conditioned medium significantly impairs productive virus infection and OV-driven cell death. This effect was not due to the direct neutralization of virions or inhibition of OV entry into host cells. Instead, further investigation of adipocyte secreted factors demonstrated that adipocyte-mediated OV resistance is primarily a lipid-driven phenomenon. When lipid moieties are depleted from the adipocyte-conditioned medium, cancer cells are re-sensitized to OV-mediated destruction. We further demonstrated that blocking fatty acid uptake by cancer cells, in a combinatorial strategy with virotherapy, has clinical translational potential to overcome adipocyte-mediated OV resistance.DiscussionOur findings indicate that while adipocyte secreted factors can impede OV infection, the impairment of OV treatment efficacy can be overcome by modulating lipid flux in the tumour milieu.

Background Parkinson’s disease (PD) is a common neurodegenerative disorder in older adults that is associated with neuroinflammation, oxidative stress, and characterized by loss of dopaminergic cells. Illicit stimulants increase oxidative stress and are associated with increased risk of PD. Prescription stimulants are similar in mechanism to illicit stimulants, yet their influence on PD is not well described. This study aims to determine if prescription stimulants influence risk of PD among older adults with attention-deficit and hyperactivity disorder (ADHD). Methods We implemented a retrospective observational cohort design utilizing the TriNetX database which sources from the electronic health records of 57 healthcare organizations. Inclusion criteria were ADHD diagnosis and age ≥50. Those exposed to stimulants and the unexposed controls were matched based on demographics and known risk factors for PD. The outcome of interest was the incidence of PD over a 30-year follow-up period. We utilized TriNetX software for hazard ratio (HR) analysis. Results Among the 59,471 individuals treated with prescription stimulants 131 of them developed PD, and there were 272 individuals who developed PD that were not prescribed stimulants. This analysis yielded a HR of 0.419 (HR = 0.419 [95% CI 0.34, 0.516], P = 0.0013). Conclusion Illicit stimulants are associated with increased risk of PD, but this study suggests prescribed stimulants may not impart that same risk. The reduced risk in this cohort may be due to protection from illicit substance use and oxidative stress, however additional study exploring the relationship between prescription stimulants and PD is warranted.

Because of scarcity, vulnerability and heterogeneity in the population of circulating tumor cells (CTCs), the CTC isolation system relying on immunoaffinity interaction exhibits inconsistent efficiencies for all types of cancers...

Toward the end of the Pleistocene, the world experienced a mass extinction of megafauna. In North America these included its proboscideans—the mammoths and mastodons. Researchers in conservation biology, paleontology, and archaeology have debated the role played by human predation in these extinctions. They point to traces of human butchery, such as cut marks and other bone surface modifications (BSM), as evidence of human-animal interactions—including predation and scavenging, between early Americans and proboscideans. However, others have challenged the validity of the butchery evidence observed on several proboscidean assemblages, largely due to questions of qualitative determination of the agent responsible for creating BSM. This study employs a statistical technique that relies on three-dimensional (3D) imaging data and 3D geometric morphometrics to determine the origin of the BSM observed on the skeletal remains of the Bowser Road mastodon (BR mastodon), excavated in Middletown, New York. These techniques have been shown to have high accuracy in identifying and distinguishing among different types of BSM. To better characterize the BSM on the BR mastodon, we compared them quantitatively to experimental BSM resulting from a stone tool chopping experiment using “Arnold,” the force-calibrated chopper. This study suggests that BSM on the BR mastodon are not consistent with the BSM generated by the experimental chopper. Future controlled experiments will compare other types of BSM to those on BR. This research contributes to continued efforts to decrease the uncertainty surrounding human-megafauna associations at the level of the archaeological site and faunal assemblage—specifically that of the BR mastodon assemblage. Consequently, we also contribute to the dialogue surrounding the character of the human-animal interactions between early Americans and Late Pleistocene megafauna, and the role of human foraging behavior in the latter’s extinction.

Aims Stemmed tibial components are frequently used in revision total knee arthroplasty (TKA). The purpose of this study was to evaluate patient satisfaction, overall pain, and diaphyseal tibial pain in patients who underwent revision TKA with cemented or uncemented stemmed tibial components. Methods This is a retrospective cohort study involving 110 patients with revision TKA with cemented versus uncemented stemmed tibial components. Patients who underwent revision TKA with stemmed tibial components over a 15-year period at a single institution with at least two-year follow-up were assessed. Pain was evaluated through postal surveys. There were 63 patients with cemented tibial stems and 47 with uncemented stems. Radiographs and Knee Society Scores were used to evaluate for objective findings associated with pain or patient dissatisfaction. Postal surveys were analyzed using Fisher’s exact test and the independent-samples t-test. Logistic regression was used to adjust for age, sex, and preoperative bone loss. Results No statistically significant differences in stem length, operative side, or indications for revision were found between the two cohorts. Tibial pain at the end of the stem was present in 25.3% (16/63) of cemented stems and 25.5% (12/47) of uncemented stems (p = 1.000); 74.6% (47/63) of cemented patients and 78.7% (37/47) of uncemented patients were satisfied following revision TKA (p = 0.657). Conclusion There were no differences in patient satisfaction, overall pain, and diaphyseal tibial pain in cemented and uncemented stemmed tibial components in revision TKA. Patient factors, rather than implant selection and surgical technique, likely play a large role in the presence of postoperative pain. Stemmed tibial components have been shown to be a possible source of pain in revision TKA. There is no difference in patient satisfaction or postoperative pain with cemented or uncemented stemmed tibial components in revision TKA. Cite this article: Bone Joint J 2021;103-B(6 Supple A):165–170.

Cancer metabolism adapts the metabolic network of its tissue of origin. However, breast cancer is not a disease of a single origin. Multiple epithelial populations serve as the culprit cell of origin for specific breast cancer subtypes, yet our knowledge of the metabolic network of normal mammary epithelial cells is limited. Using a multi-omic approach, here we identify the diverse metabolic programmes operating in normal mammary populations. The proteomes of basal, luminal progenitor and mature luminal cell populations revealed enrichment of glycolysis in basal cells and of oxidative phosphorylation in luminal progenitors. Single-cell transcriptomes corroborated lineage-specific metabolic identities and additional intra-lineage heterogeneity. Mitochondrial form and function differed across lineages, with clonogenicity correlating with mitochondrial activity. Targeting oxidative phosphorylation and glycolysis with inhibitors exposed lineage-rooted metabolic vulnerabilities of mammary progenitors. Bioinformatics indicated breast cancer subtypes retain metabolic features of their putative cell of origin. Thus, lineage-rooted metabolic identities of normal mammary cells may underlie breast cancer metabolic heterogeneity and targeting these vulnerabilities could advance breast cancer therapy.

Herbivore distribution throughout Africa is strongly linked to mean annual precipitation. We use that relationship to predict functional group composition of herbivore communities during the last glacial maximum (ca. 21 ka) on the now submerged Palaeo-Agulhas Plain (PAP), South Africa. We used metabolic large herbivore biomass (MLHB) from 39 South African protected areas, in five functional groups (characterized by behavior and physiology). We examined how modern factors influenced MLHB and considered the effects of biome, annual rainfall, percentage winter rainfall, and protected area size. Overall, biome was the most important factor influencing the relationship between MLHB and rainfall. In general, MLHB increased with rainfall, but not for the grassland biome. Outside grasslands, most functional groups’ metabolic biomass increased with increasing rainfall, irrespective of biome, except for medium-sized social mixed feeder species in savanna and thicket. Protected area size was influential for medium-sized social mixed feeders and large browsers and rainfall influenced medium-sized social mixed feeders, offering some perspectives on spatial constraints on past large herbivore biomass densities. These results improve our understanding of the likely herbivore community composition and relative biomass structure on the PAP, an essential driver of how early humans utilized large mammals as a food resource.

Background: Brain size has been associated with intelligence of various orders and families of animals, leading to the concept of encephalization. Brain size scales with body weight between species within mammals to approximately the 0.67 power. However, within species, this scaling exponent appears to be much smaller (approximately 0.27 power). Aim: We examined whether this relationship has persisted in dogs over the 120 years since this was originally observed. Methods: Comparative cross-sectional study of magnetic resonance imaging (MRI) data obtained from 127 dogs, compared to historical data from 157 dogs and 24 non-dog canid species. Results: Brain size in dogs measured by MRI had a scaling exponent virtually identical to that observed previously (0.24 vs. 0.26). However, the proportionality constant was smaller, suggesting that dogs in the study cohort had relatively smaller brains than the historical cohort. Absolute brain size appeared to have both a lower and upper limit in dogs. When compared to non-dogs canids, the most appropriate “representative” size for a “typical dog” when examining allometric scaling across Canidae appeared to be approximately 10–15 kg. Conclusions: We interpreted the slight reduction in relative brain size to be a function of increased obesity in the study cohort compared to dogs examined 120 years ago. Further, we suggest that dog brains have a finite lower size limit. Finally, concepts of encephalization should not be applied to dogs.

Household heating using wood stoves is common practice in many rural areas of the United States (US) and can lead to elevated concentrations of indoor fine particulate matter (PM2.5 ). We collected 6-day measures of indoor PM2.5 during the winter and evaluated household and stove-use characteristics in homes at three rural and diverse study sites. The median indoor PM2.5 concentration across all homes was 19 µg/m3 , with higher concentrations in Alaska (median = 30, minimum = 4, maximum = 200, n = 10) and Navajo Nation homes (median = 29, minimum = 3, maximum = 105, n = 23) compared with Montana homes (median = 16, minimum = 2, maximum = 139, n = 59). Households that had not cleaned the chimney within the past year had 65% higher geometric mean PM2.5 compared to those with chimney cleaned within 6 months (95% confidence interval [CI]: -1, 170). Based on a novel wood stove grading method, homes with low-quality and medium-quality stoves had substantially higher PM2.5 compared to homes with higher-quality stoves (186% higher [95% CI: 32, 519] and 161% higher; [95% CI:27, 434], respectively). Our findings highlight the need for, and complex nature of, regionally appropriate interventions to reduce indoor air pollution in rural wood-burning regions. Higher-quality stoves and behavioral practices such as regular chimney cleaning may help improve indoor air quality in such homes.

Background: Hippocampal atrophy is a key pathologic and magnetic resonance imaging (MRI) feature of human Alzheimer’s disease (AD). Hippocampal atrophy has not been documented via MRI in canine cognitive dysfunction (CCD), which is considered as the dog model of human AD.Aim: The purpose of this retrospective comparative volumetric MRI study was to compare total hippocampal volumes between successfully aging (control) dogs and dogs diagnosed with CCD.Methods: Mimics® software was used to derive total hippocampal volumes and total brain volumes from the MRI studies of 42 aging dogs (≥ 9 years): 16 dogs diagnosed with CCD and 26 successfully aging controls. Hippocampal volumes were normalized to total brain volume and these values were compared between groups using Mann–Whitney U tests.Results: Total hippocampal volume normalized to total brain volume was significantly less for CCD patients compared with control dogs (p = 0.04).Conclusion: The results of this study suggest that – similar to human AD – hippocampal atrophy is a pathological feature of CCD. This finding has potential importance for both investigating disease mechanisms related to dementia as well as future hippocampal-targeted therapies.

Linear-bottlebrush, amphiphilic copolymers were grafted from the surface of silica (SiO2) nanoparticles to form “nanoparticle micelles” that, regardless of the concentration, possess the capability to encapsulate and stabilize non-polar structures in aqueous media. These nanoparticles afford high water dispersibility and enhanced oil encapsulation from their inherent architectural design. Utilizing well-established techniques, such as surface-initiated ring-opening polymerization (SI-ROP) and surface-initiated atom transfer radical polymerization (SI-ATRP), to effectively fine-tune the ratio of hydrophobic (poly(caprolactone), PCL) to hydrophilic (poly[oligo(ethylene glycol)methyl methacrylate mono-methyl ether], POEGMA) copolymer composition, enhances oil encapsulation while maintaining aqueous solubility. Preliminary oil encapsulation was quantified with differential scanning calorimetry (DSC) using two different types of crude oil. These nanoparticles offer an alternative dispersant system to replace commercially used Corexit™ 9500 by effectively breaking up disastrous oil slicks and minimizing the long-term effects of dispersant additives in the environment.

Matching the treatment to an individual patient's tumor state can increase therapeutic efficacy and reduce tumor recurrence. Circulating tumor cells (CTCs) derived from solid tumors are promising subjects for theragnostic analysis. To analyze how CTCs represent tumor states, we established cell lines from CTCs, primary and metastatic tumors from a mouse model and provided phenotypic and multiomic analyses of these cells. CTCs and metastatic cells, but not primary tumor cells, shared stochastic mutations and similar hypomethylation levels at transcription start sites. CTCs and metastatic tumor cells shared a hybrid epithelial/mesenchymal transcriptome state with reduced adhesive and enhanced mobilization characteristics. We tested anti-cancer drugs on tumor cells from a metastatic breast cancer patient. CTC responses mirrored the impact of drugs on metastatic rather than primary tumors. Our multiomic and clinical anti-cancer drug response results reveal that CTCs resemble metastatic tumors and establish CTCs as an

Millions of rural U.S. households are heated with wood stoves. Wood stove use can lead to high indoor concentrations of fine particulate matter [airborne particlesWe assessed the impact of low-cost educational and air filtration interventions on childhood LRTI and indoorThe Kids Air Quality Interventions for Reducing Respiratory Infections (KidsAIR) study was a parallel three-arm (education, portable air filtration unit, control), post-only randomized trial in households from Alaska, Montana, and Navajo Nation (Arizona and New Mexico) with a wood stove and one or more childrenThere were 61 LRTI cases from 14,636 child-weeks of follow-up among 461 children. In the intent-to-treat analysis, children in the education arm [We did not observe meaningful differences in LRTI or indoor

Native Americans living in rural areas often rely upon wood stoves for home heating that can lead to elevated indoor concentrations of fine particulate matter (PMWe assessed the impact of portable air filtration units and educational approaches that incorporated elements of traditional knowledge on indoor and personal PMEldersAIR was a three-arm, pre-post randomized trial among rural households from the Navajo Nation and Nez Perce Tribe in the United States. We measured personal and indoor PMGeometric mean indoor PMThe strong partnership between academic and community partners helped facilitate a culturally acceptable approach to a clinical trial intervention within the study communities. Portable air filtration units can reduce indoor PM

Chemical characterization of cryptotephra is critical for temporally linking archaeological sites. Here, we describe cryptotephra investigations of two Middle–Upper Paleolithic sites from north‐west Italy, Arma Veirana and Riparo Bombrini. Cryptotephra are present as small (75 wt.%) with low FeO ( 1 and P2 is also a high silica rhyolite (>75 wt.%) but with higher FeO (2.33–2.65 wt.%). Shards at Riparo Bombrini (P3) are of the same composition as P1 shards at Arma Veirana, providing a distinct link between deposits at both sites. Geochemical characteristics suggest three possible sources for P1 and P3: eruptions from Lipari Island (56–37.7 ka) in Italy, the Acigöl volcanic field (200–20 ka) in Turkey and the Miocene Kirka‐Phrigian caldera (18 Ma) in Turkey. Eruptions from Lipari Island are the most likely source for P1,3 cryptotephra. This study highlights how cryptotephra can benefit archaeology, by providing a direct link between Arma Veirana and Riparo Bombrini as well as other deposits throughout the Mediterranean.

Supported metal nanoparticles are essential components of high-performing catalysts, and their structures are intensely researched. In comparison, nanoparticle spatial distribution in powder catalysts is conventionally not quantified, and the influence of this collective property on catalyst performance remains poorly investigated. Here, we demonstrate a general colloidal self-assembly method to control uniformity of nanoparticle spatial distribution on common industrial powder supports. We quantify distributions on the nanoscale using image statistics and show that the type of nanospatial distribution determines not only the stability, but also the activity of heterogeneous catalysts. Widely investigated systems (Au-TiO2 for CO oxidation thermocatalysis and Pd-TiO2 for H2 evolution photocatalysis) were used to showcase the universal importance of nanoparticle spatial organization. Spatially and temporally resolved microkinetic modeling revealed that nonuniformly distributed Au nanoparticles suffer from local depletion of surface oxygen, and therefore lower CO oxidation activity, as compared to uniformly distributed nanoparticles. Nanoparticle spatial distribution also determines the stability of Pd-TiO2 photocatalysts, because nonuniformly distributed nanoparticles sinter while uniformly distributed nanoparticles do not. This work introduces new tools to evaluate and understand catalyst collective (ensemble) properties in powder catalysts, which thereby pave the way to more active and stable heterogeneous catalysts.

Purpose: The ovarian cancer risk factors of age and ovulation are curious because ovarian cancer incidence increases in postmenopausal women, long after ovulations have ceased. To determine how age and ovulation underlie ovarian cancer risk, we assessed the effects of these risk factors on the ovarian microenvironment. Experimental Design: Aged C57/lcrfa mice (0–33 months old) were generated to assess the aged ovarian microenvironment. To expand our findings into human aging, we assembled a cohort of normal human ovaries (n = 18, 21–71 years old). To validate our findings, an independent cohort of normal human ovaries was assembled (n = 9, 41–82 years old). Results: We first validated the presence of age-associated murine ovarian fibrosis. Using interdisciplinary methodologies, we provide novel evidence that ovarian fibrosis also develops in human postmenopausal ovaries across two independent cohorts (n = 27). Fibrotic ovaries have an increased CD206+:CD68+ cell ratio, CD8+ T-cell infiltration, and profibrotic DPP4+αSMA+ fibroblasts. Metformin use was associated with attenuated CD8+ T-cell infiltration and reduced CD206+:CD68+ cell ratio. Conclusions: These data support a novel hypothesis that unifies the primary nonhereditary ovarian cancer risk factors through the development of ovarian fibrosis and the formation of a premetastatic niche, and suggests a potential use for metformin in ovarian cancer prophylaxis. See related commentary by Madariaga et al., p. 523