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Dissecting the molecular basis of adaptation remains elusive despite our ability to sequence genomes and transcriptomes. At present, most genomic research on selection focusses on signatures of selective sweeps in patterns of heterozygosity. Other research has studied changes in patterns of gene expression in evolving populations but has not usually identified the genetic changes causing these shifts in expression. Here we attempt to go beyond these approaches by using machine learning tools to explore interactions between the genome, transcriptome, and life-history phenotypes in two groups of 10 experimentally evolved Drosophila populations subjected to selection for opposing life history patterns. Our findings indicate that genomic and transcriptomic data have comparable power for predicting phenotypic characters. Looking at the relationships between the genome and the transcriptome, we find that the expression of individual transcripts is influenced by many sites across the genome that are differentiated between the two types of populations. We find that single-nucleotide polymorphisms (SNPs), transposable elements, and indels are powerful predictors of gene expression. Collectively, our results suggest that the genomic architecture of adaptation is highly polygenic with extensive pleiotropy. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess COVID-19 vaccine confidence among healthcare personnel in the safety net sector of the United States and Puerto Rico. This study aimed to examine the extent to which increased knowledge and positive attitudes toward COVID-19 vaccine safety and efficacy were associated with healthcare workers' COVID-19 vaccination status and their recommendation of the vaccine to all patients. Methods: Online survey data were collected from health care workers working in Free and Charitable Clinics across the United States and Federally Qualified Health Centers in Puerto Rico. The survey consisted of 62 questions covering various demographic measures and constructs related to healthcare workers' vaccination status, beliefs, and recommendations for COVID-19 vaccination. Statistical analyses, including multivariate analysis, were conducted to identify the factors associated with the COVID-19 vaccine status and recommendations among healthcare personnel. Results: Among the 2273 respondents, 93% reported being vaccinated against COVID-19. The analysis revealed that respondents who believed that COVID-19 vaccines were efficacious and safe were three times more likely to be vaccinated and twice as likely to recommend them to all their patients. Respondents who believed they had received adequate information about COVID-19 vaccination were 10 times more likely to be vaccinated and four times more likely to recommend it to all their patients. Conclusions: The study results indicate that healthcare workers' confidence in COVID-19 vaccines is closely tied to their level of knowledge, positive beliefs, and attitudes about vaccine safety and efficacy. The study emphasizes the significance of healthcare workers feeling well informed and confident in their knowledge to recommend the vaccine to their patients. These findings have important implications for the development of strategies to boost COVID-19 vaccine confidence among healthcare workers and increase vaccine uptake among patients. [ABSTRACT FROM AUTHOR]

Förster Resonance Energy transfer (FRET) is a nonradiative process that may occur from an electronically excited donor to an acceptor when the emission spectrum of the donor overlaps with the absorption spectrum of the acceptor. FRET experiments have been done in the gas phase based on specially designed mass‐spectroscopy setups with the goal to obtain structural information on biomolecular ions labeled with a FRET pair (i.e., donor and acceptor dyes) and to shed light on the energy‐transfer process itself. Ions are accumulated in a radio‐frequency ion trap or a Penning trap where mass selection of those of interest takes place, followed by photoexcitation. Gas‐phase FRET is identified from detection of emitted light either from the donor, the acceptor, or both, or from a fragmentation channel that is specific to the acceptor when electronically excited. The challenge associated with the first approach is the collection and detection of photons emitted from a thin ion cloud that is not easily accessible while the second approach relies both on the photophysical and chemical behavior of the acceptor. In this review, we present the different instrumentation used for gas‐phase FRET, including a discussion of advantages and disadvantages, and examples on how the technique has provided important structural information that is not easily obtainable otherwise. Furthermore, we describe how the spectroscopic properties of the dyes are affected by nearby electric fields, which is readily discernable from experiments on simple model systems with alkyl or π‐conjugated bridges. Such spectral changes can have a significant effect on the FRET efficiency. Ideas for new directions are presented at the end with special focus on cold‐ion spectroscopy. [ABSTRACT FROM AUTHOR]

Ligand-induced conformational changes are critical to the function of many membrane proteins and arise from numerous intramolecular interactions. In the photocycle of the model membrane protein bacteriorhodopsin (bR), absorption of a photon by retinal triggers a conformational cascade that results in pumping a proton across the cell membrane. While decades of spectroscopy and structural studies have probed this photocycle in intricate detail, changes in intramolecular energetics that underlie protein motions have remained elusive to experimental quantification. Here, we measured these energetics on the millisecond time scale using atomic-force-microscopy-based single-molecule force spectroscopy. Precisely, timed light pulses triggered the bR photocycle while we measured the equilibrium unfolding and refolding of the terminal 8-amino-acid region of bR's G-helix. These dynamics changed when the EF-helix pair moved ~9 Å away from this end of the G helix during the "open" portion of bR's photocycle. In ~60% of the data, we observed abrupt light-induced destabilization of 3.4 ± 0.3 kcal/mol, lasting 38 ± 3 ms. The kinetics and pH-dependence of this destabilization were consistent with prior measurements of bR's open phase. The frequency of light-induced destabilization increased with the duration of illumination and was dramatically reduced in the triple mutant (D96G/F171C/F219L) thought to trap bR in its open phase. In the other ~40% of the data, photoexcitation unexpectedly stabilized a longer-lived putative misfolded state. Through this work, we establish a general single-molecule force spectroscopy approach for measuring ligand-induced energetics and lifetimes in membrane proteins. [ABSTRACT FROM AUTHOR]

After overexposure to loud music, we experience a decrease in our ability to hear (robustness), which usually recovers (resilience). Here, we exploited the amenable auditory system of the desert locust, Schistocerca gregaria , to measure how robustness and resilience depend on age. We found that gene expression changes are dominated by age as opposed to noise exposure. We measured sound-evoked nerve activity for young and aged locusts directly, after 24 hours and 48 hours after noise exposure. We found that both young and aged locusts recovered their auditory nerve function over 48 hours. We also measured the sound-evoked transduction current in individual auditory neurons, and although the transduction current magnitude recovered in the young locusts after noise exposure, it failed to recover in the aged locusts. A plastic mechanism compensates for the decreased transduction current in aged locusts. We suggest key genes upregulated in young noise-exposed locusts that mediate robustness to noise exposure and find potential candidates responsible for compensatory mechanisms in the auditory neurons of aged noise-exposed locusts. [ABSTRACT FROM AUTHOR]

Objective: Co‐occurring anti‐tripartite motif‐containing protein 9 and 67 autoantibodies (TRIM9/67‐IgG) have been reported in only a very few cases of paraneoplastic cerebellar syndrome. The value of these biomarkers and the most sensitive methods of TRIM9/67‐IgG detection are not known. Methods: We performed a retrospective, multicenter study to evaluate the cerebrospinal fluid and serum of candidate TRIM9/67‐IgG cases by tissue‐based immunofluorescence, peptide phage display immunoprecipitation sequencing, overexpression cell‐based assay (CBA), and immunoblot. Cases in which TRIM9/67‐IgG was detected by at least 2 assays were considered TRIM9/67‐IgG positive. Results: Among these cases (n = 13), CBA was the most sensitive (100%) and revealed that all cases had TRIM9 and TRIM67 autoantibodies. Of TRIM9/67‐IgG cases with available clinical history, a subacute cerebellar syndrome was the most common presentation (n = 7/10), followed by encephalitis (n = 3/10). Of these 10 patients, 70% had comorbid cancer (7/10), 85% of whom (n = 6/7) had confirmed metastatic disease. All evaluable cancer biopsies expressed TRIM9 protein (n = 5/5), whose expression was elevated in the cancerous regions of the tissue in 4 of 5 cases. Interpretation: TRIM9/67‐IgG is a rare but likely high‐risk paraneoplastic biomarker for which CBA appears to be the most sensitive diagnostic assay. ANN NEUROL 2023;94:1086–1101 [ABSTRACT FROM AUTHOR]

Dopamine signaling in the adult ventral forebrain regulates behavior, stress response, and memory formation and in neurodevelopment regulates neural differentiation and cell migration. Excessive dopamine levels, including those due to cocaine use in utero and in adults, could lead to long-term adverse consequences. The mechanisms underlying both homeostatic and pathological changes remain unclear, in part due to the diverse cellular responses elicited by dopamine and the reliance on animal models that exhibit species-specific differences in dopamine signaling. In this study, we use the human-derived ventral forebrain organoid model of Xiang–Tanaka and characterize their response to cocaine or dopamine. We explore dosing regimens of dopamine or cocaine to simulate acute or chronic exposure. We then use calcium imaging, cAMP imaging, and bulk RNA-sequencing to measure responses to cocaine or dopamine exposure. We observe an upregulation of inflammatory pathways in addition to indicators of oxidative stress following exposure. Using inhibitors of reactive oxygen species (ROS), we then show ROS to be necessary for multiple transcriptional responses of cocaine exposure. These results highlight novel response pathways and validate the potential of cerebral organoids as in vitro human models for studying complex biological processes in the brain. [ABSTRACT FROM AUTHOR]

This article is a tribute to Rasanayagam (Rudy) Rudran, a renowned primatologist and conservationist. Born in Sri Lanka, Rudy conducted groundbreaking research on langurs and blue monkeys, studying their behavior and ecology. He faced challenges and adapted to socio-political conditions during his fieldwork in Uganda and Venezuela. Rudy also made significant contributions to conservation efforts in Sri Lanka, including the establishment of national parks and raising environmental awareness among the local population. He continued to work on primate conservation even after retiring from the Smithsonian Institution. Rudy's legacy as a teacher and mentor in the field of conservation is widely recognized and respected. [Extracted from the article]

Context. This commentary is based on an innovative approach to the development of predictive analytics. It is centered on the development of predictive models for varying stages of chronic disease through integrating all types of datasets, adds various new features to a theoretically driven data warehousing, creates purpose-specific prediction models, and integrates multi-criteria predictions of chronic disease progression based on a biomedical evolutionary learning platform. After merging across-center databases based on the risk factors identified from modeling the predictors of chronic disease progression, the collaborative investigators could conduct multi-center verification of the predictive model and further develop a clinical decision support system coupled with visualization of a shared decision-making feature for patient care. The Study Problem. The success of health services management research is dependent upon the stability of pattern detection and the usefulness of nosological classification formulated from big-data-to-knowledge research on chronic conditions. However, longitudinal observations with multiple waves of predictors and outcomes are needed to capture the evolution of polychronic conditions. Motivation. The transitional probabilities could be estimated from big-data analysis with further verification. Simulation or predictive models could then generate a useful explanatory pathogenesis of the end-stage-disorder or outcomes. Hence, the clinical decision support system for patient-centered interventions could be systematically designed and executed. Methodology. A customized algorithm for polychronic conditions coupled with constraints-oriented reasoning approaches is suggested. Based on theoretical specifications of causal inquiries, we could mitigate the effects of multiple confounding factors in conducting evaluation research on the determinants of patient care outcomes. This is what we consider as the mechanism for avoiding the black-box expression in the formulation of predictive analytics. The remaining task is to gather new data to verify the practical utility of the proposed and validated predictive equation(s). More specifically, this includes two approaches guiding future research on chronic disease and care management: (1) To develop a biomedical evolutionary learning platform to predict the risk of polychronic conditions at various stages, especially for predicting the micro- and macro-cardiovascular complications experienced by patients with Type 2 diabetes for multidisciplinary care; and (2) to formulate appropriate prescriptive intervention services, such as patient-centered care management interventions for a high-risk group of patients with polychronic conditions. Conclusions. The commentary has identified trends, challenges, and solutions in conducting innovative AI-based healthcare research that can improve understandings of disease-state transitions from diabetes to other chronic polychronic conditions. Hence, better predictive models could be further formulated to expand from inductive (problem solving) to deductive (theory based and hypothesis testing) inquiries in care management research. [ABSTRACT FROM AUTHOR]

The present study describes an efficient protocol for the micropropagation of Centratherum punctatum Cass. through transverse thin cell layers (tTCLs). The effect of plant growth regulators (PGRs), thickness of tTCLs, and source of tTCLs were evaluated. The tTCLs of varying thickness (0.5 to 5.0 mm) were excised from 10-d-old leaf and 45-d-old node and cultured on Murashige and Skoog (MS) medium supplemented with various concentrations of PGRs (BAP, TDZ, KN; 0.1 to 2.0 mg L−1), alone or in combination with NAA (0.1 to 1.0 mg L−1) for shoot induction. The leaf and node tTCLs responded with direct shoot regeneration. A significant effect of thickness or width on shoot induction was observed. For leaf, 1.0-mm-wide and for node 2.0-mm-thick tTCLs showed a maximum response. MS medium supplemented with 1.5 mg L−1 TDZ and 1.0 mg L−1 BAP in combination with 0.2 mg L−1 NAA was found to be optimum for shoot induction from tTCLs of leaf (96% response with 41.5 shoots per explant) and node (87% response with 11.9 shoots per explant), respectively. Rhizogenesis was obtained when micropropagated shoots were transferred to half strength MS medium supplemented with various concentrations (0.25 to 2.0 mg L−1) of IBA. The rooted plantlets were eventually acclimatized and transferred to soil. The clonal fidelity assessment by SCoT markers of the mother plant and micropropagated plants revealed their genetic similarity. Chlorophyll content estimation indicated lower levels in in vitro plants, which increased to a comparable level to that of field-grown plants after 3 mo of acclimatization, showing absence of stress during acclimatization. The procedure described here is a promising tool for micropropagation of C. punctatum as it produces high-frequency healthy shoots from a minimum explant source. [ABSTRACT FROM AUTHOR]

The aim of the present study was to characterize the pigment from the fungus Fusarium chlamydosporum following the evaluation of its anti-inflammatory activity on RAW 264.7 macrophage cell line. The red pigment extracted from F. chlamydosporum was subjected to series of purification techniques wherein the pigment was identified to be lycopene. The cytotoxicity of the pigment as well as evaluation of anti-inflammatory activity was carried out on normal human lung fibroblast MRC-5 cell line and LPS-stimulated RAW 264.7 macrophage cell line, respectively. The inhibition of cytokines IL-1β and IL-6 was assessed by indirect ELISA. The gene expression of COX-2 and IL-1β in lycopene-treated cells was carried out by real-time PCR wherein the expressions of both the pro-inflammatory markers were found to be down-regulated. The study concludes the production of lycopene from F. chlamydosporum when grown in a complex medium. The pigment showed profound anti-inflammatory activity in vitro. The present findings of lycopene production by the fungus F. chlamydosporum can be a major break-through in the research field for the production of natural pigments with high yield against various ailments. [ABSTRACT FROM AUTHOR]

Feedback mediated by cosmic rays (CRs) is an important process in galaxy formation. Because CRs are long-lived and because they are transported along the magnetic field lines independently of any gas flow, they can efficiently distribute their feedback energy within the galaxy. We present an in-depth investigation of (i) how CRs launch galactic winds from a disc that is forming in a |$10^{11} \, \rm {M}_\odot$| halo and (ii) the state of CR transport inside the galactic wind. To this end, we use the arepo moving-mesh code and model CR transport with the two-moment description of CR hydrodynamics. This model includes the CR interaction with the gyroresonant Alfvén waves that enable us to self-consistently calculate the CR diffusion coefficient and CR transport speeds based on coarse-grained models for plasma physical effects. This delivers insight into key questions such as whether the effective CR transport is streaming-like or diffusive-like, how the CR diffusion coefficient and transport speed change inside the circumgalactic medium, and to what degree the two-moment approximation is needed to faithfully capture these effects. We find that the CR-diffusion coefficient reaches a steady state in most environments with the notable exception of our newly discovered Alfvén-wave dark regions where the toroidal wind magnetic field is nearly perpendicular to the CR pressure gradient so that CRs are unable to excite the gyroresonant Alfvén waves. However, CR transport itself cannot reach a steady state and is not well described by either the CR streaming paradigm, the CR diffusion paradigm, or a combination of both. [ABSTRACT FROM AUTHOR]

Drosophila experimental evolution, with its well-defined selection protocols, has long supplied useful genetic material for the analysis of functional physiology. While there is a long tradition of interpreting the effects of large-effect mutants physiologically, identifying and interpreting gene-to-phenotype relationships has been challenging in the genomic era, with many labs not resolving how physiological traits are affected by multiple genes throughout the genome. Drosophila experimental evolution has demonstrated that multiple phenotypes change because of the evolution of many loci across the genome, creating the scientific challenge of sifting out differentiated but noncausal loci for individual characters. The fused lasso additive model method allows us to infer some of the differentiated loci that have relatively greater causal effects on the differentiation of specific phenotypes. The experimental material that we use in the present study comes from 50 populations that have been selected for different life histories and levels of stress resistance. Differentiation of cardiac robustness, starvation resistance, desiccation resistance, lipid content, glycogen content, water content, and body masses was assayed among 40–50 of these experimentally evolved populations. Through the fused lasso additive model, we combined physiological analyses from eight parameters with whole-body pooled-seq genomic data to identify potentially causally linked genomic regions. We have identified approximately 2,176 significantly differentiated 50-kb genomic windows among our 50 populations, with 142 of those identified genomic regions that are highly likely to have a causal effect connecting specific genome sites to specific physiological characters. [ABSTRACT FROM AUTHOR]

The Turkana Jet in northern Kenya is shown to modulate the climate of southwest Ethiopia’s Omo River Valley using in situ hydrometeorological data, satellite measurements, and atmospheric reanalyses from decadal to diurnal time scales. Temporal statistics from lowland (2.58–58N, 358–388E) and highland (68–98N, 358–388E) areas show that 850-hPa westward airflow over Lake Turkana is stronger in March and October but is weakened when western Indian Ocean sea temperatures become warmer than usual at intervals of 2–7 years. A case study on 24 March 2019 reveals how a stronger Turkana Jet induces warming and drying of the Omo Valley. A second case study on 27 September 2018 reveals Hadley cell subsidence over the southern flank of the Turkana Jet. We demonstrate how nocturnal airflow draining off the mountains joins the channelized jet. Satellite and atmospheric reanalyses exhibit realistic diurnal cycles in the east Omo mountains, but some products have incorrect phase and warm bias. Omo Valley soil moisture and runoff exhibit little trend in historical records and model projections; however, unpredictable multiyear wet and dry spells and a growing demand for water are ongoing concerns. [ABSTRACT FROM AUTHOR]

Introduction: Immediate implant placement in conjunction with partial extraction therapy has been shown to result in functional osseo‐ and dento‐integration with partial preservation of the periodontal ligament (PDL) in humans. Strategic buccal root retention for PDL preservation is a biologically driven procedure that maintains alveolar ridge dimensions and esthetics, while allowing for implant placement. The aim of this study was to conduct a systematic review of longitudinal clinical outcomes of PDL‐mediated ridge preservation in conjunction with implant placement in adults, compared with conventional immediate implant placement with total extractions. The primary outcome for this study was marginal bone level (MBL) changes after strategic buccal root retention implant placement techniques. Materials and Methods: To address a predefined PICOS question, a systematic search of randomized clinical trials and cohort studies with at least 10 participants per group and a minimum 12‐month follow‐up was conducted. A two‐phase systematic selection strategy, data extraction, and risk of bias assessment, was performed independently and in duplicate. Randomized trials were quantitatively analyzed in a meta‐analysis. Results: Ten human studies fulfilled the predefined criteria and were included; three clinical trials and seven cohort studies, for a total of 506 patients and 587 implants. PDL‐mediated implant placement of single‐rooted periodontally healthy teeth was found to reduce marginal peri‐implant bone loss and buccal plate changes as compared to conventional immediate implants across studies, while implant survival and success rates were comparable between the two procedures. A meta‐analysis found that bone changes were significantly less when retention of the buccal root section was performed as compared to total extractions (standardized mean difference: [−4.53, −0.11]); the three clinical trials were, however, largely heterogeneous (I2: 93.1%; Q = 28.98, p < 0.001). Conclusion: Strategic retention of the buccal root section has a benefit in terms of dimensional ridge stability over conventional immediate implantation when implemented in carefully selected cases of single‐rooted teeth. [ABSTRACT FROM AUTHOR]

Objective: Patients with bipolar disorder spend most of their clinical lifetime in the depressive phase of their illness. However, antidepressants are discouraged in the treatment of bipolar depression due to concerns over manic induction and drug ineffectiveness. Some reports suggest that monoamine oxidase inhibitors (MAOIs) may be safe and effective compared to other antidepressants in treating bipolar depression. The present study compared the safety and effectiveness of MAOI therapy in patients with bipolar versus unipolar depression. Methods: Data were collected from approximately 2500 clinical research charts of patients treated with MAOI therapy at a university mood disorder clinic between 1983 and 2015. A mixed‐effects model was created with patient entered as the random effect. The model included the primary diagnosis (i.e., either unipolar or bipolar depression) and other clinical covariates as fixed‐effect predictors. Results: Patients with bipolar depression demonstrated lower post‐treatment clinical global impressions/severity scores versus patients with unipolar depression (p = 0.04). Neither group demonstrated a full syndromal manic or hypomanic episode. A higher proportion of patients with bipolar depression reported myoclonic tics and tremors, which may have resulted from concomitant lithium use. Amongst the covariates, only the number of prior antidepressant trials predicted poorer outcomes from MAOI therapy. Conclusion: MAOIs may be more effective—and as safe—for patients with bipolar depression versus unipolar depression. Future studies should explore this possible advantage using a larger sample size. [ABSTRACT FROM AUTHOR]

The present study investigates the relation between language environment and language delay in 63 British-English speaking children (19 typical talkers (TT), 22 late talkers (LT), and 22 late bloomers (LB) aged 13 to 18 months. Families audio recorded daily routines and marked the new words their child produced over a period of 6 months. To investigate how language environments differed between talker types and how environments corresponded with children's developing lexicons, we evaluated contextual diversity—a word property that measures semantic richness—and network properties of language environments in tandem with developing vocabularies. The language environment experienced by the three talker types differed in their structural properties, with LT environments being least contextually diverse and least well-connected in relation to network properties. Notably, LBs' language environments were more like those of TTs. Network properties of language environments also correlate with the rate of vocabulary growth over the study period. By comparing differences between language environments and lexical network development, we also observe results consistent with contributions to lexical development from different learning strategies for expressive vocabularies and different environments for receptive vocabularies. We discuss the potential consequences that structural differences in parental speech might have on language development and the contribution of this work to the debate on quantity versus quality. [ABSTRACT FROM AUTHOR]

Cognitive science invokes semantic networks to explain diverse phenomena, from memory retrieval to creativity. Research in these areas often assumes a single underlying semantic network that is shared across individuals. Yet, recent evidence suggests that content, size, and connectivity of semantic networks are experience-dependent, implying sizable individual and age-related differences. Here, we investigate individual and age differences in the semantic networks of younger and older adults by deriving semantic networks from both fluency and similarity rating tasks. Crucially, we use a megastudy approach to obtain thousands of similarity ratings per individual to allow us to capture the characteristics of individual semantic networks. We find that older adults possess lexical networks with smaller average degree and longer path lengths relative to those of younger adults, with older adults showing less interindividual agreement and thus more unique lexical representations relative to younger adults. Furthermore, this approach shows that individual and age differences are not evenly distributed but, rather, are related to weakly connected, peripheral parts of the networks. All in all, these results reveal the interindividual differences in both the content and the structure of semantic networks that may accumulate across the life span as a function of idiosyncratic experiences. [ABSTRACT FROM AUTHOR]

Policies are assumed to rarely change after enactment. Punctuated equilibrium theory argues this is because law makers shift attention away from policies after enactment, letting them run on autopilot. I argue that the periods between punctuations deserves study, and that what law makers do is design institutions to make policies path dependent so they can only change within limited parameters—if at all. It may also be that interest groups opposing new policies are still able to shape the way they evolve, pushing against intended paths. In this article I test the influence of path dependence versus group opposition in state charter school policies. I find some evidence of path dependence, but I also find that, to some extent, opposing interests can still change these laws after enactment. Furthermore, I find these policies became increasingly similar over time, partially because of path dependence, but also because of the influence of opposing interests. Related Articles: Ertas, Nevbahar. 2015. "Policy Narratives and Public Opinion concerning Charter Schools." Politics & Policy 43(3): 426–51. https://doi.org/10.1111/polp.12120. Kwon, Sung‐Wook, and Sylvia Gonzalez‐Gorman. 2019. "Influence of Local Political Institutions on Policy Punctuation in Three Policy Areas." Politics & Policy 47(2): 300–25. https://doi.org/10.1111/polp.12295. Patrick, Barbara. 2016. "Performance Policies and Workforce Development: Can the Market Model Be Successfully Implemented in the Public Arena?" Politics & Policy 44(6): 1116–57. https://doi.org/10.1111/polp.12185. [ABSTRACT FROM AUTHOR]

Do lobbyists always advocate for the interests of the members or clients employing them, or, under competing pressures, do they sometimes take positions on bills reflecting the interests of lawmakers or other lobbyists? Do they, in fact, lobby strategically by making choices that balance competing pressures in pursuit of goals like furthering their careers? Most lobbying research assumes that interest groups and lobbyists are the same, but I argue that the interests of lobbyists may be different from those they represent, which I test with a model of strategic lobbying using data on positions lobbyists took on bills in Congress from 2006 to 2017 made available by MapLight. I find that lobbyists sometimes do take positions at odds with member interests under pressure from legislators, other lobbyists, and the president, though some groups can constrain their lobbyists. I conclude by speculating on what this means for lobbying as a form of representation. [ABSTRACT FROM AUTHOR]

Area‐restricted search is the capacity to change search effort adaptively in response to resource encounters or expectations, from directional exploration (global, extensive search) to focused exploitation (local, intensive search). This search pattern is used by numerous organisms, from worms and insects to humans, to find various targets, such as food, mates, nests, and other resources. Area‐restricted search has been studied for at least 80 years by ecologists, and more recently in the neurological and psychological literature. In general, the conditions promoting this search pattern are: (1) clustered resources; (2) active search (e.g. not a sit‐and‐wait predator); (3) searcher memory for recent target encounters or expectations; and (4) searcher ignorance about the exact location of targets. Because area‐restricted search adapts to resource encounters, the search can be performed at multiple spatial scales. Models and experiments have demonstrated that area‐restricted search is superior to alternative search patterns that do not involve a memory of the exact location of the target, such as correlated random walks or Lévy walks/flights. Area‐restricted search is triggered by sensory cues whereas concentrated search in the absence of sensory cues is associated with other forms of foraging. Some neural underpinnings of area‐restricted search are probably shared across metazoans, suggesting a shared ancestry and a shared solution to a common ecological problem of finding clustered resources. Area‐restricted search is also apparent in other domains, such as memory and visual search in humans, which may indicate an exaptation from spatial search to other forms of search. Here, we review these various aspects of area‐restricted search, as well as how to identify it, and point to open questions. [ABSTRACT FROM AUTHOR]

We consider the Seiberg-Witten solution of pure N = 2 gauge theory in four dimensions, with gauge group SU(N). A simple exact series expansion for the dependence of the 2(N − 1) Seiberg-Witten periods aI(u), aDI(u) on the N − 1 Coulomb-branch moduli un is obtained around the ℤ2N-symmetric point of the Coulomb branch, where all un vanish. This generalizes earlier results for N = 2 in terms of hypergeometric functions, and for N = 3 in terms of Appell functions. Using these and other analytical results, combined with numerical computations, we explore the global structure of the Kähler potential K = 1 2 ∑ I Im( a ¯ IaDI), which is single valued on the Coulomb branch. Evidence is presented that K is a convex function, with a unique minimum at the ℤ2N-symmetric point. Finally, we explore candidate walls of marginal stability in the vicinity of this point, and their relation to the surface of vanishing Kähler potential. [ABSTRACT FROM AUTHOR]

This study investigates the influence of semantic maturation on early lexical development by examining the impact of contextual diversity—known to influence semantic development—on word promotion from receptive to productive vocabularies (i.e., comprehension‐expression gap). Study 1 compares the vocabularies of 3685 American‐English‐speaking typical talkers (TTs) and late talkers (LTs; 16–30 months old; 1257 females, 1021 gender unknown; ethnicity unknown; data downloaded in 2018) and finds that LTs, with a longer preverbal phase, produced nouns with lower contextual diversity (R2 =.80), but verbs with higher contextual diversity (R2 =.13). Study 2 compares computational network growth models of semantic maturation and finds that verbs require more semantic maturation than nouns, and TTs produce words that are more semantically mature than LTs. [ABSTRACT FROM AUTHOR]

Background: FGFR2 genomic alterations are observed in 10–20% of cholangiocarcinoma (CCA). Although FGFR2 fusions are an important actionable target, FGFR2 protein expression has not been thoroughly characterized. Aims: To evaluate FGFR2 protein expression in cholangiocarcinoma harboring FGFR2 genomic alterations. Methods: FGFR2 protein expression was evaluated in 99 CCA cases with two different antibodies. FGFR2 genomic alterations were confirmed via next-generating sequencing (NGS) or FISH. Primary objective was to determine the specificity and sensitivity of FGFR2 immunohistochemistry staining for detecting FGFR2 genomic alterations. Secondary objectives included overall FGFR2 immunohistochemistry staining in CCA patients, and evaluation of whether FGFR2 expression correlates with clinical outcomes including overall survival (OS), progression-free survival (PFS), and time-to-tumor recurrence (TTR). Results: Immunohistochemistry staining with two antibodies against FGFR2, FPR2-D, and clone 98706 showed high accuracy (78.7% and 91.9%) and specificity (82.9% and 97.7%), and moderate sensitivity (53.9% and 57.1%), respectively, when compared with the standard methods for detecting FGFR2 genomic alterations. In a median follow-up of 72 months, there were no statistically significant differences in OS, PFS, and TTR, for patients with positive or negative FGFR2 staining. Conclusion: FGFR2 protein expression by immunohistochemistry has high specificity and therefore could be used to imply the presence of FGFR2 genomic alterations in the context of a positive test. In the case of a negative test, NGS or FISH would be necessary to ascertain cases with FGFR2 genomic alterations. [ABSTRACT FROM AUTHOR]

Introduction: Pregnancy, childbirth, and child well-being are identified by Healthy People 2030 as priority topics for improving the health of all Americans. New Mexico is the fifth largest state geographically with most of the state's 33 counties considered rural or frontier. Accessing health care services is challenging in this resource-poor environment. The need to provide maternal and child health (MCH) education in the state was the impetus for developing a graduate certificate in maternal and child public health. Methods: The hybrid MCH graduate certificate engaged professionals in formal training that included a public health approach to addressing MCH issues in the state's diverse communities. Grant funds paid for the tuition, books and travel for students providing an opportunity to individuals who otherwise could not have pursued graduate education and professional development. Results: Over a 4-year period, two cohorts were recruited, educated, and evaluated. The evaluations reflected an increase in competency knowledge scores for all students. Discussion: This model of MCH education was successful at delivering public health graduate education to MCH practitioners and increasing their knowledge and skills. Listening to students and communities as to what their MCH public health needs are and responding with a flexible educational model provided individuals with information and tools that could be used to improve maternal and child health and reduce health disparities in rural, tribal, and underserved communities. [ABSTRACT FROM AUTHOR]

Background: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), commonly used antihypertensive drugs, may have a protective effect against depression in older individuals, but evidence in humans is limited. Aims: We evaluated the risk of depression, among older individuals with hypertension, comparing ACE or ARB initiators to thiazide(-like) diuretic initiators. Thiazide(-like) diuretics were used as control because these drugs are not associated with mood disorders. Methods: We used a propensity score-matched new user cohort design with routinely collected data from general practices in England from the Clinical Practice Research Datalink database. We matched 12,938 pairs of new users of ACEIs/ARBs and thiazide(-like) diuretics with hypertension (mean age 67.6 years; 54.7% women). Follow-up time started on the date of drug initiation and ended on the date of treatment discontinuation plus 30 days, or switch to a comparator, occurrence of a study event, death, date of patient's transfer out of practice, or end of the study period. The primary outcome was a composite endpoint of treated depression and nonfatal and fatal self-harm. Results/outcomes: Compared to the thiazide(-like) diuretic group, ACEIs/ARBs use was not associated with a lower risk of the primary outcome (hazard ratio 0.96 (95% confidence interval: 0.79; 1.15)). Results did not differ according to lipophilicity, duration of use, and average daily dose, or class (ACEIs or ARBs). Conclusions/Interpretation: New use of ACEIs or ARBs is not associated with a lower risk of depression among individuals with hypertension. [ABSTRACT FROM AUTHOR]

Pogostemon quadrifolius is an important lateritic plant with high ethnomedicinal and ecological value. Here, we describe an efficient and rapid in vitro propagation protocol via direct regeneration from leaf explants of P. quadrifolius. In vitro leaves obtained from nodal segment culture were inoculated on Murashige and Skoog (MS) medium supplemented with different concentrations of 6-benzylaminopurine (BAP; 0.44 to 6.66 μM), thidiazuron (TDZ; 0.454 to 6.81 μM), and kinetin (KN; 0.465 to 6.97 μM) alone and in combination with α-naphthaleneacetic acid (NAA; 0.537 to 10.74 μM). The highest frequency of response (96.5%) and shoot induction (79.1 shoots per explant) was obtained on MS medium with 2.22 μM BAP and 8.055 μM NAA. The optimum root induction (98.1%) and root number (16.24) were observed in a half-strength MS medium containing 2.46 μM indole-3-butyric acid (IBA). The plantlets with well-developed roots were acclimatized in small plastic cups containing sterilized vermiculite and coconut husk mixture (1:1) and later successfully shifted to the field. To our knowledge, this is the first report of in vitro organogenesis in P. quadrifolius. This optimized protocol is cost-effective and highly efficient for the rapid mass propagation of P. quadrifolius and is a prerequisite to meet pharmaceutical and ecological needs. [ABSTRACT FROM AUTHOR]

Objective: An implicit assumption in the use of depressive severity measures to assess change during treatment, such as the Hamilton Rating Scale for Depression (HRSD), is that reductions from pre- to post-treatment that are equal to each other are of equal value. However, stakeholders' valuations of changes might depart substantially from this assumption. Method: Vignettes were constructed that reflected the six possible 1, 2, and 3-point reductions on five cognitive and four somatic symptoms derived from the HRSD. Former or currently depressed patients provided judgments of the importance of the symptom reductions. Mean importance ratings were modeled using symptom category and the pre/post-treatment combination. Differences were explored using the Tukey method. Results: Results indicated that mean ratings, from most to least important, were: Anxiety, Suicide, Depressed Mood, Work, and Guilt (the cognitive symptoms) followed by Somatic, Sleep, Appetite & Weight, and Retardation (the somatic symptoms). Participants valued reductions that resulted in posttreatment scores of zero more than expected, given the magnitude of the reductions. Conclusions: The value of reductions in symptoms captured by the HRSD, as judged by patients, appears to differ as a function of symptom category and the post-treatment score. Similar patterns might characterize other measures of depression severity. [ABSTRACT FROM AUTHOR]

Within mental health, approaches to determine whether a patient experienced "meaningful" change from treatment have predominantly involved imposing thresholds on three types of metrics derived from assessments of symptom severity: end score (posttreatment score), absolute change (pre- minus posttreatment score), and proportion of change. However, none of these approaches have considered input from the consumer. This study examined correspondences between various reductions from pre- to posttreatment symptom severity levels and patients' judgments of satisfaction with change. Former or currently depressed patients were asked to provide judgments of their satisfaction reflected in vignettes that used descriptions from the Hamilton Rating Scale for Depression. Judgments from 108 female participants were fit using four metrics: end score, absolute change, proportion of change, and the combination of end score and absolute change. Akaike information criteria (AICs) and Akaike weights were used to determine the best-fitting model. Cutoffs were calculated for the five levels of satisfaction with change. Proportion of change best accounted for variation in the patients' ratings. For "slightly … ," "somewhat … ," "moderately … ," and "very … ," the proportions of reduction that corresponded with each of these ratings of satisfaction were, respectively: 17%, 39%, 62%, and 84%. Our a priori level of satisfaction (between "somewhat" and "moderately") corresponded to a 50% reduction in pretreatment severity. This study may provide services some insight into their female patients' satisfaction with change from treatment for depression using only the proportion of reduction from pretreatment severity. A similar procedure could be applied to other diagnostic groups, as well as other constructs that attend to the patient's perspective. [ABSTRACT FROM AUTHOR]

Modal analysis techniques are widely used to characterize vibrations in structures, vehicles, machinery, etc. Modal parameters obtained through modal analysis are useful for structural health monitoring and condition monitoring. The common goal is to ensure the integrity of a mechanical system through monitoring of different operational conditions. Operational conditions described by spatial measurements can for instance be used to observe the vibration characteristics of the system and its parts. Therefore, the main originality of this work is to experimentally investigate if the presence of a turbulent gas flow in seal geometries can facilitate operational modal analysis for a coupled rotor–foundation system. A consistent and automatic way of obtaining the vibration characteristics is necessary to be included in the monitoring schemes. Therefore, this work also proposes a method to automatically obtain modal parameters for a bed plate of a rotor–foundation system when the rotor is affected by active magnetic bearings and gas seals. The automatic modal parameter algorithm is built on the stabilization diagram of modal parameters obtained from the stochastic subspace identification. Intermediate results from the automatic modal parameter algorithm show that some of the distance measures i.e., d ω n , d , d ζ , dMACX, d λ , d MACX ω n , d , d MACX ζ , and d MACX λ , for modal parameters in a stabilization diagram are better suited than others when distinguishing between possible physical modes and certainly spurious poles. The frequency band of interest for the system is found to influence the number of possible physical modes identified by the automatic algorithm. Measurements from 13 roving accelerometers are combined with the automatic modal parameter algorithm to obtain the vibration characteristics of the rotor and bed plate. For different operational conditions in the seal geometry, seven modes are consistently identified as physical modes by the automatic modal parameter algorithm. The algorithm uses (i) a combination of a white noise disturbance pattern intentionally introduced into the system through the active magnetic bearings and (ii) the operational disturbance coming from the seals, non-intentionally introduced by the turbulent gas flow. The seven physical modes are also identified when (iii) the rotor–foundation system is only disturbed from the turbulent gas flow in the seals. The seven physical modes identified by the algorithm under conditions (i), (ii), and (iii) compare well to the vibration characteristics found in experiments via experimental modal analysis and impact hammer testing as well as via a mathematical model of the rotor–foundation system. [ABSTRACT FROM AUTHOR]

Thinking is complex. Over the years, several types of methods and paradigms have developed across the psychological, cognitive, and neural sciences to study such complexity. A rapidly growing multidisciplinary quantitative field of network science offers quantitative methods to represent complex systems as networks, or graphs, and study the network properties of these systems. While the application of network science to study the brain has greatly advanced our understanding of the brains structure and function, the application of these tools to study cognition has been done to a much lesser account. This topic is a collection of papers that discuss the fruitfulness of applying network science to study cognition across a wide scope of research areas from generalist accounts of memory and encoding, to individual differences, to communities, and finally to cultural and individual change. [ABSTRACT FROM AUTHOR]

Cognitive researchers often carve cognition up into structures and processes. Cognitive processes operate on structures, like vehicles driving over a map. Language alongside semantic and episodic memory are proposed to have structure, as are perceptual systems. Over these structures, processes operate to construct memory and solve problems by retrieving and manipulating information. Network science offers an approach to representing cognitive structures and has made tremendous inroads into understanding the nature of cognitive structure and process. But is the mind a network? If so, what kind? In this article, we briefly review the main metaphors, assumptions, and pitfalls prevalent in cognitive network science (maps and vehicles; one network/process to rule them all), highlight the need for new metaphors that elaborate on the map‐and‐vehicle framework (wormholes, skyhooks, and generators), and present open questions in studying the mind as a network (the challenge of capturing network change, what should the edges of cognitive networks be made of, and aggregated vs. individual‐based networks). One critical lesson of this exercise is that the richness of the mind as network approach makes it a powerful tool in its own right; it has helped to make our assumptions more visible, generating new and fascinating questions, and enriching the prospects for future research. A second lesson is that the mind as a network–though useful–is incomplete. The mind is not a network, but it may contain them. [ABSTRACT FROM AUTHOR]

The article discusses life and work of ichthyologist Paul James Struhsaker. It mentions work for exploration of Hawaii's shrimp resources which included gear development of new types of shrimp traps and surveys using them; and also mentions his interest in flatfishes and their larvae, with a manuscript on those in Hawaii in preparation that he was unable to complete prior to his death.

Radiolabelled lipophilic cations can be used to non-invasively report on mitochondrial dysfunction in diseases such as cardiovascular disease, cardiotoxicity and cancer. Several such lipophilic cations are currently used clinically to map myocardial perfusion using SPECT imaging. Since PET offers significant advantages over SPECT in terms of sensitivity, resolution and the capacity for dynamic imaging to allow pharmacokinetic modelling, we have synthesised and radiolabelled a series of NODAGA-based radiotracers, with triarylphosphonium-functionalisation, with gallium-68 to develop PET-compatible cationic complexes. To evaluate their capacity to report upon mitochondrial membrane potential, we assessed their pharmacokinetic profiles in isolated perfused rat hearts before and after mitochondrial depolarisation with the ionophore CCCP. All three tracers radiolabel with over 96% RCY, with log D7.4 values above −0.4 observed for the most lipophilic example of this family of radiotracers. The candidate tracer [68Ga]Ga4c exhibited non-preferential uptake in healthy cardiac tissue over CCCP-infused cardiac tissue. While this approach does show promise, the lipophilicity of this family of probes needs improving in order for them to be effective cardiac imaging agents. [ABSTRACT FROM AUTHOR]

Motivated by applications to soft supersymmetry breaking, we revisit the expansion of the Seiberg-Witten solution around the multi-monopole point on the Coulomb branch of pure SU(N) N = 2 gauge theory in four dimensions. At this point N − 1 mutually local magnetic monopoles become massless simultaneously, and in a suitable duality frame the gauge couplings logarithmically run to zero. We explicitly calculate the leading threshold corrections to this logarithmic running from the Seiberg-Witten solution by adapting a method previously introduced by D'Hoker and Phong. We compare our computation to existing results in the literature; this includes results specific to SU(2) and SU(3) gauge theories, the large-N results of Douglas and Shenker, as well as results obtained by appealing to integrable systems or topological strings. We find broad agreement, while also clarifying some lingering inconsistencies. Finally, we explicitly extend the results of Douglas and Shenker to finite N , finding exact agreement with our first calculation. [ABSTRACT FROM AUTHOR]

Purpose: Exposure to narrow‐band red light, which stimulates only the long‐wavelength sensitive (LWS) cones, slows axial eye growth and produces hyperopia in tree shrews and macaque monkeys. We asked whether exposure to amber light, which also stimulates only the LWS cones but with a greater effective illuminance than red light, has a similar hyperopia‐inducing effect in tree shrews. Methods: Starting at 24 ± 1 days of visual experience, 15 tree shrews (dichromatic mammals closely related to primates) received light treatment through amber filters (BPI 500/550 dyed acrylic) either atop the cage (Filter group, n = 8, 300–400 human lux) or fitted into goggles in front of both eyes (Goggle group, n = 7). Non‐cycloplegic refractive error and axial ocular dimensions were measured daily. Treatment groups were compared with age‐matched animals (Colony group, n = 7) raised in standard colony fluorescent lighting (100–300 lux). Results: At the start of treatment, mean refractive errors were well‐matched across the three groups (p = 0.35). During treatment, the Filter group became progressively more hyperopic with age (p < 0.001). By contrast, the Goggle and Colony groups showed continued normal emmetropization. When the treatment ended, the Filter group exhibited significantly greater hyperopia (mean [SE] = 3.5 [0.6] D) compared with the Goggle (0.2 [0.8] D, p = 0.01) and Colony groups (1.0 [0.2] D, p = 0.01). However, the refractive error in the Goggle group was not different from that in the Colony group (p = 0.35). Changes in the vitreous chamber were consistent with the refractive error changes. Conclusions: Exposure to ambient amber light produced substantial hyperopia in the Filter group but had no effect on refractive error in the Goggle group. The lack of effect in the Goggle group could be due to the simultaneous activation of the short‐wavelength sensitive (SWS) and LWS cones caused by the scattering of the broad‐band light from the periphery of the goggles. [ABSTRACT FROM AUTHOR]

The prevailing maximum likelihood estimators for inferring power law models from rank-frequency data are biased. The source of this bias is an inappropriate likelihood function. The correct likelihood function is derived and shown to be computationally intractable. A more computationally efficient method of approximate Bayesian computation (ABC) is explored. This method is shown to have less bias for data generated from idealised rank-frequency Zipfian distributions. However, the existing estimators and the ABC estimator described here assume that words are drawn from a simple probability distribution, while language is a much more complex process. We show that this false assumption leads to continued biases when applying any of these methods to natural language to estimate Zipf exponents. We recommend that researchers be aware of the bias when investigating power laws in rank-frequency data. [ABSTRACT FROM AUTHOR]

We establish the existence of an infinite-dimensional fermionic symmetry in four-dimensional supersymmetric gauge theories by analyzing semiclassical photino dynamics in abelian N = 1 theories with charged matter. The symmetry is parametrized by a spinor-valued function on an asymptotic S2 at null infinity. It is not manifest at the level of the Lagrangian, but acts non-trivially on physical states, and its Ward identity is the soft photino theorem. The infinite-dimensional fermionic symmetry resides in the same N = 1 supermultiplet as the physically non-trivial large gauge symmetries associated with the soft photon theorem. [ABSTRACT FROM AUTHOR]

Background: No evidence-based therapy for borderline personality disorder (BPD) exhibits a clear superiority. However, BPD is highly heterogeneous, and different patients may specifically benefit from the interventions of a particular treatment. Methods: From a randomized trial comparing a year of dialectical behavior therapy (DBT) to general psychiatric management (GPM) for BPD, long-term (2-year-post) outcome data and patient baseline variables (n = 156) were used to examine individual and combined patient-level moderators of differential treatment response. A two-step bootstrapped and partially cross-validated moderator identification process was employed for 20 baseline variables. For identified moderators, 10-fold bootstrapped cross-validated models estimated response to each therapy, and long-term outcomes were compared for patients randomized to their model-predicted optimal v. non-optimal treatment. Results: Significant moderators surviving the two-step process included psychiatric symptom severity, BPD impulsivity symptoms (both GPM > DBT), dependent personality traits, childhood emotional abuse, and social adjustment (all DBT > GPM). Patients randomized to their model-predicted optimal treatment had significantly better long-term outcomes (d = 0.36, p = 0.028), especially if the model had a relatively stronger (top 60%) prediction for that patient (d = 0.61, p = 0.004). Among patients with a stronger prediction, this advantage held even when applying a conservative statistical check (d = 0.46, p = 0.043). Conclusions: Patient characteristics influence the degree to which they respond to two treatments for BPD. Combining information from multiple moderators may help inform providers and patients as to which treatment is the most likely to lead to long-term symptom relief. Further research on personalized medicine in BPD is needed. [ABSTRACT FROM AUTHOR]

This study investigates flow variability at different scales and its effects on the dispersion of a passive scalar in a regular street network by means of direct numerical simulations (DNS), and compared to wind tunnel (WT) measurements. Specific scientific questions addressed include: (i) sources of variability in the flow at street-network scale, (ii) the effects of such variability on both puff and continuous localised releases, (iii) additional sources of uncertainty related to experimental setups and their consequences. The street network modelled here consists of an array of rectangular buildings arranged uniformly and with periodic horizontal boundary conditions. The flow is driven by a body force at an angle of 45 degrees relative to the streets in the network. Sources of passive scalars were located near ground level at three different types of locations: a short street, an intersection between streets and a long street. Flow variability is documented at different scales: small-scale intra-street variations linked with local flow topology; inter-street flow structure differences; street-network scale variability; and larger-scale spatial variations associated with above-canopy structures. Flow statistics and the dispersion behaviour of both continuous and short-duration (puff) releases of a passive scalar in the street network are analysed and compared with the results of wind-tunnel measurements. Results agree well with the experimental data for a source location in an intersection, especially for flow statistics and mean concentration profiles for continuous releases. Larger differences arise in the comparisons of puff releases. These differences are quantified by computing several puff parameters including time of arrival, travel time, rise and decay times. Reasons for the differences are discussed in relation to the underlying flow variability identified, differences between the DNS and WT setup and uncertainties in the experimental setup. Implications for the propagation of short-duration releases in real urban areas are discussed in the light of our findings. In particular, it is highlighted that in modelling singular events such as accidental releases, characterising uncertainties is more meaningful and useful than computing ensemble averages. [ABSTRACT FROM AUTHOR]

In individuals with Marfan Syndrome (MFS), fibrillin-1 gene (FBN1) mutations can lead to vascular wall weakening and dysfunction. The experimental mouse model of MFS (Fbn1C1041G/+) has been advantageous in investigating MFS-associated life-threatening aortic aneurysms. It is well established that the MFS mouse model exhibits an accelerated-aging phenotype in elastic organs like the aorta, lung, and skin. However, the impact of Fbn1 mutations on the in vivo function and structure of various artery types with the consideration of sex and age, has not been adequately explored in real-time and a clinically relevant context. In this study, we investigate if Fbn1 mutation contributes to sex-dependent alterations in central and cerebral vascular function similar to phenotypic changes associated with normal aging in healthy control mice. In vivo ultrasound imaging of central and cerebral vasculature was performed in 6-month-old male and female MFS and C57BL/6 mice and sex-matched 12-month-old (middle-aged) healthy control mice. Our findings confirm aortic enlargement (aneurysm) and wall stiffness in MFS mice, but with exacerbation in male diameters. Coronary artery blood flow velocity (BFV) in diastole was not different but left pulmonary artery BFV was decreased in MFS and 12-month-old control mice regardless of sex. At 6 months of age, MFS male mice show decreased posterior cerebral artery BFV as compared to age-matched control males, with no difference observed between female cohorts. Reduced mitral valve early-filling velocities were indicated in MFS mice regardless of sex. Male MFS mice also demonstrated left ventricular hypertrophy. Overall, these results underscore the significance of biological sex in vascular function and structure in MFS mice, while highlighting a trend of pre-mature vascular aging phenotype in MFS mice that is comparable to phenotypes observed in older healthy controls. Furthermore, this research is a vital step in understanding MFS's broader implications and sets the stage for more in-depth future analyses, while providing data-driven preclinical justification for re-evaluating diagnostic approaches and therapeutic efficacy. [ABSTRACT FROM AUTHOR]

By eliminating unnecessary degrees of freedom, coarse-grained (CG) models tremendously facilitate numerical calculations and theoretical analyses of complex phenomena. However, their success critically depends upon the representation of the system and the effective potential that governs the CG degrees of freedom. This work investigates the relationship between the CG representation and the many-body potential of mean force (PMF), W, which is the appropriate effective potential for a CG model that exactly preserves the structural and thermodynamic properties of a given high resolution model. In particular, we investigate the entropic component of the PMF and its dependence upon the CG resolution. This entropic component, SW, is a configuration-dependent relative entropy that determines the temperature dependence of W. As a direct consequence of eliminating high resolution details from the CG model, the coarsening process transfers configurational entropy and information from the configuration space into SW. In order to further investigate these general results, we consider the popular Gaussian Network Model (GNM) for protein conformational fluctuations. We analytically derive the exact PMF for the GNM as a function of the CG representation. In the case of the GNM, -TSW is a positive, configuration-independent term that depends upon the temperature, the complexity of the protein interaction network, and the details of the CG representation. This entropic term demonstrates similar behavior for seven model proteins and also suggests, in each case, that certain resolutions provide a more efficient description of protein fluctuations. These results may provide general insight into the role of resolution for determining the information content, thermodynamic properties, and transferability of CG models. Ultimately, they may lead to a rigorous and systematic framework for optimizing the representation of CG models. [ABSTRACT FROM AUTHOR]

We present a new numerical algorithm to solve the recently derived equations of two-moment cosmic ray hydrodynamics (CRHD). The algorithm is implemented as a module in the moving mesh Arepo code. Therein, the anisotropic transport of cosmic rays (CRs) along magnetic field lines is discretized using a path-conservative finite volume method on the unstructured time-dependent Voronoi mesh of Arepo. The interaction of CRs and gyroresonant Alfvén waves is described by short time-scale source terms in the CRHD equations. We employ a custom-made semi-implicit adaptive time stepping source term integrator to accurately integrate this interaction on the small light-crossing time of the anisotropic transport step. Both the transport and the source term integration step are separated from the evolution of the magnetohydrodynamical equations using an operator split approach. The new algorithm is tested with a variety of test problems, including shock tubes, a perpendicular magnetized discontinuity, the hydrodynamic response to a CR overpressure, CR acceleration of a warm cloud, and a CR blast wave, which demonstrate that the coupling between CR and magnetohydrodynamics is robust and accurate. We demonstrate the numerical convergence of the presented scheme using new linear and non-linear analytic solutions. [ABSTRACT FROM AUTHOR]

Catchment-scale recharge and water balance estimates are commonly made for the purposes of water resource management. Few catchments have had these estimates ground-truthed. One confounding aspect is that runoff and soil-water inputs commonly occur throughout the year; however, in climates with strong dry seasons, base flow can be directly sampled. In an experimental catchment in the Mt. Lofty Ranges of South Australia, run-of-stream hydrochemical parameters were monitored. In this Mediterranean climate during the Millennium Drought (2001–2009), the stream was reduced to disconnected groundwater-fed pools. Two groundwater types were identified: (1) high-salinity type from meta-shale bedrock with thick, clayey regolith and (2) low-salinity type from meta-sandstone bedrock with sandy regolith. End-member mixing using silica and chloride concentrations and robust 87Sr/86Sr ratios reveal an apparent groundwater-flow paradox as follows. According to chloride mass balance and spatial distribution of hydrogeological units, the low-salinity groundwater type has seven times more recharge than the high-salinity type. Over the 28-year record, low-salinity groundwater contributed 25% of stream water, whereas high-salinity groundwater contributed 2–5%. During the drought year, however, annual stream flow from the high-salinity groundwater contributed 50%, whereas low-salinity groundwater contributed 18%. High-salinity groundwater dominated dry-season base flow during all years. The paradox can be resolved as follows: The meta-sandstone terrane drains quickly following wet-season recharge and therefore contributes little to dry-season base flow. Conversely, the meta-shale terrane drains slowly and therefore provides stream flow during dry seasons and drought years. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is a leading cause of death among Peruvian women. Barriers at multiple levels impact effective screening and treatment, including a lack of knowledge about cervical cancer and how regular screening can reduce morbidity and mortality through earlier detection. The aim of this study is to assess knowledge, attitudes, and practices regarding cervical cancer and its prevention in the peri-urban communities of Oasis and Pampas in southern Lima, Peru that can be used to inform future campaigns about cervical cancer prevention.Methods: A cross-sectional survey that included several open-ended questions was administered to women in Pampas and Oasis between 2015 and 2016 to evaluate the knowledge, attitudes, and practices regarding cervical cancer and Pap smears.Results: In total, 224 women were interviewed. Knowledge about cervical cancer and Pap smears was high, and attitudes were predominantly positive among most participants. Most participants knew how often they should get Pap smears (89.7%), when to begin seeking screening (74.6%), knew the price of a Pap smear (61.9%), and felt Pap smears were important for their health (70.1%). About one third (29.5%) of premenopausal women reported receiving a Pap smear in the last year. However, open ended questions revealed some knowledge gaps around Pap smears, as well as some stigma associated to Human Papilloma Virus (HPV) infection.Conclusion: Although knowledge of cervical cancer prevention was generally high and perceptions were positive among women in peri-urban Peruvian communities, our findings revealed there is a need for education on HPV infection prevalence among sexually active individuals to reduce stigma. Future research should focus on exploring experiences with follow-up and treatment associated with abnormal Pap smears, as well as perspectives from health authorities and professionals about barriers in the early detection and treatment process for cervical cancer. [ABSTRACT FROM AUTHOR]

We examine six-dimensional quantum field theories through the lens of higher-form global symmetries. Every Yang-Mills gauge theory in six dimensions, with field strength f(2), naturally gives rise to a continuous 1-form global symmetry associated with the 2-form instanton current J(2)∼ ∗Tr (f(2) ∧ f(2)). We show that suitable mixed anomalies involving the gauge field f(2) and ordinary 0-form global symmetries, such as flavor or Poincaré symmetries, lead to continuous 2-group global symmetries, which allow two flavor currents or two stress tensors to fuse into the 2-form current J(2). We discuss several features of 2-group symmetry in six dimensions, many of which parallel the four-dimensional case. The majority of six-dimensional supersymmetric conformal field theories (SCFTs) and little string theories have infrared phases with non-abelian gauge fields. We show that the mixed anomalies leading to 2-group symmetries can be present in little string theories, but that they are necessarily absent in SCFTs. This allows us to establish a previously conjectured algorithm for computing the 't Hooft anomalies of most SCFTs from the spectrum of weakly-coupled massless particles on the tensor branch of these theories. We then apply this understanding to prove that the a-type Weyl anomaly of all SCFTs with a tensor branch must be positive, a > 0. [ABSTRACT FROM AUTHOR]