Abstract Cross-sectional studies have found that individuals with depressive disorders or symptoms have elevated levels of inflammatory markers predictive of coronary artery disease, including ...interleukin-6 (IL-6) and C-reactive protein (CRP). Due to the paucity of prospective studies, however, the directionality of the depression–inflammation relationship is unclear. We evaluated the longitudinal associations between depressive symptoms and both IL-6 and CRP among 263 healthy, older men and women enrolled in the Pittsburgh Healthy Heart Project, a 6-year prospective cohort study. During the baseline and follow-up visits, participants completed the Beck Depression Inventory-II (BDI-II) to assess depressive symptoms and underwent blood draws to quantify serum IL-6 and CRP. Path analyses revealed that baseline BDI-II ( β = 0.18, p = 0.01, ΔR2 = 0.02) was a predictor of 6-year change in IL-6, even after adjustment for demographic, biomedical, and behavioral factors as well as other negative emotions. Of all the factors examined, only body-mass index was a stronger predictor of IL-6 change than depressive symptoms. In contrast to these results, baseline IL-6 did not predict 6-year change in BDI-II. Evidence of a weak bidirectional relationship between BDI-II and CRP was also observed; however, neither of these longitudinal associations was significant. The present findings indicate that depressive symptoms may precede and augment some inflammatory processes relevant to coronary artery disease among healthy, older adults. Therefore, our results imply that depression may lead to inflammation and that inflammation may be one of the mechanisms through which depression contributes to cardiovascular risk.
Neonicotinoid insecticides provide crop protection via water solubility and systemicity, yet these chemical characteristics, combined with high toxicity to non-target invertebrates (e.g., honeybees), ...elicit concern of environmental transport. Neonicotinoids have been detected in soil and surface water throughout North America; however, no investigation has defined a direct connection to planted seed dressings. We quantified the physical transport of thiamethoxam (TMX), a neonicotinoid, under field conditions. We planted TMX-coated corn seeds and maintained plots with and without viable crops (n = 3 plots per treatment) to determine plant influence on pesticide transport. TMX concentrations were measured in soil and drainage throughout the growing season. Storm-generated runoff was the dominant transport mechanism (maximum TMX concentration 1.72 ± 0.605 μg L−1; no viable plants), followed by shallow (<72 cm) lateral drainage (0.570 ± 0.170 μg L−1; no viable plants), and deep (110 cm) drainage (0.170 ± 0.265 μg L−1; viable plants). Soil samples confirmed vertical and lateral movement within 23 and 36 days of planting, respectively. Plants facilitated downward migration of TMX in soil but restricted TMX drainage. Altogether, these study results revealed that neonicotinoids can be transported from seed coatings both above and through the soil profile, which may enable migration into surrounding ecosystems.
Note: The sizes of flux arrows reflect relative differences in drainage losses of TMX as detailed in the manuscript. Display omitted
•Thiamethoxam was transported from corn seed coatings throughout the growing season.•Low intensity storms produced the highest levels of TMX in early season runoff.•Plants enhanced vertical mobility of TMX but constrained losses to drainage outflow.
Jet substructure has emerged as a critical tool for LHC searches, but studies so far have relied heavily on shower Monte Carlo simulations, which formally approximate QCD at the leading-log level. We ...demonstrate that systematic higher-order QCD computations of jet substructure can be carried out by boosting global event shapes by a large momentum Q and accounting for effects due to finite jet size, initial-state radiation (ISR), and the underlying event (UE) as 1/Q corrections. In particular, we compute the 2-subjettiness substructure distribution for boosted Z→qqover ¯ events at the LHC at next-to-next-to-next-to-leading-log order. The calculation is greatly simplified by recycling known results for the thrust distribution in e(+)e(-) collisions. The 2-subjettiness distribution quickly saturates, becoming Q independent for Q > or approximately equal to 400 GeV. Crucially, the effects of jet contamination from ISR/UE can be subtracted out analytically at large Q without knowing their detailed form. Amusingly, the Q=∞ and Q=0 distributions are related by a scaling by e up to next-to-leading-log order.
Succinate dehydrogenase (SDH)-deficient renal carcinoma has been accepted as a provisional entity in the 2013 International Society of Urological Pathology Vancouver Classification. To further define ...its morphologic and clinical features, we studied a multi-institutional cohort of 36 SDH-deficient renal carcinomas from 27 patients, including 21 previously unreported cases. We estimate that 0.05% to 0.2% of all renal carcinomas are SDH deficient. Mean patient age at presentation was 37 years (range, 14 to 76 y), with a slight male predominance (M:F=1.7:1). Bilateral tumors were observed in 26% of patients. Thirty-four (94%) tumors demonstrated the previously reported morphology at least focally, which includedsolid or focally cystic growth, uniform cytology with eosinophilic flocculent cytoplasm, intracytoplasmic vacuolations and inclusions, and round to oval low-grade nuclei. All 17 patients who underwent genetic testing for mutation in the SDH subunits demonstrated germline mutations (16 in SDHB and 1 in SDHC). Nine of 27 (33%) patients developed metastatic disease, 2 of them after prolonged follow-up (5.5 and 30 y). Seven of 10 patients (70%) with high-grade nuclei metastasized as did all 4 patients with coagulative necrosis. Two of 17 (12%) patients with low-grade nuclei metastasized, and both had unbiopsied contralateral tumors, which may have been the origin of the metastatic disease. In conclusion, SDH-deficient renal carcinoma is a rare and unique type of renal carcinoma, exhibiting stereotypical morphologic features in the great majority of cases and showing a strong relationship with SDH germline mutation. Although this tumor may undergo dedifferentiation and metastasize, sometimes after a prolonged delay, metastatic disease is rare in the absence of high-grade nuclear atypia or coagulative necrosis.
Pasture seed samples that were harvested around 1917 in New Zealand were analysed for purity, Epichloë endophyte and insects. Samples consisted of 13 packets of seed varying from 2.2 to 15.0 g and ...comprising, Chewings fescue (Festuca rubra L.), cocksfoot (Dactylis glomerata L.), oat (Avena sativa L.), perennial ryegrass (Lolium perenne L.) and red clover (Trifolium pratense L.). These findings show that in the period prior to modern seed testing laboratories only four of the 13 samples (31%) could possibly have met today's seed certification standards as it relates to seed purity. When compared with published purities and weed content of seed of the era these samples appear typical. Endophyte testing on the four ryegrass seed samples and the ryegrass contaminants found in the Chewings fescue and cocksfoot samples showed sample-to-sample variation in endophyte infection from nil to 91%. One cocksfoot sample, most likely harvested from the Banks Peninsula, contained an Argentine stem weevil. Subsequent checking of entomological collection records also revealed specimens being present in the Wellington region from 1916. Together these occurrences precede the earliest published record for the species in New Zealand by ten years and suggest that it may have been widespread at that time.
To examine longitudinal bidirectional associations between two depressive symptom clusters-the cognitive-affective and somatic-vegetative clusters--and insulin resistance, a marker of prediabetes.
...Participants were 269 adults aged 50 to 70 years without diabetes enrolled in the Pittsburgh Healthy Heart Project, a prospective cohort study. At baseline and 6-year visits, participants completed the Beck Depression Inventory-II (BDI-II) and underwent a blood draw to quantify fasting insulin and glucose. We examined baseline BDI-II total, cognitive-affective, and somatic-vegetative scores as predictors of 6-year change in the homeostatic model of assessment (HOMA) score, an estimate of insulin resistance computed from fasting insulin and glucose. We also examined baseline HOMA score as a predictor of 6-year change in BDI-II total and subscale scores.
Regression analyses, adjusted for demographic factors and baseline HOMA score, revealed that the baseline BDI-II somatic-vegetative score (β = 0.14, p = .025), but not the cognitive-affective (β = 0.001, p = .98) or total (β = 0.10, p = .11) scores, predicted 6-year HOMA change. This result persisted in models controlling for anxiety symptoms and hostility. Several factors were examined as candidate mediators; however, only change in body mass index was a significant mediator (p = .042), accounting for 23% of the observed association. Baseline HOMA score did not predict 6-year change in BDI-II total or subscale scores (all p values >.56).
Among adults aged 50 to 70 years, the somatic-vegetative symptoms of depression (e.g., fatigue, sleep disturbance, and appetite changes) may worsen insulin resistance and increase diabetes risk, partly, by increasing body mass index.
A
bstract
We introduce a new jet algorithm called XCone, for eXclusive Cone, which is based on minimizing the event shape
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-jettiness. Because
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-jettiness partitions every event into
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jet regions ...and a beam region, XCone is an exclusive jet algorithm that always returns a fixed number of jets. We use a new “conical geometric” measure for which well-separated jets are bounded by circles of radius
R
in the rapidity-azimuth plane, while overlapping jet regions automatically form nearest-neighbor “clover jets”. This avoids the split/merge criteria needed in inclusive cone algorithms. A key feature of XCone is that it smoothly transitions between the resolved regime where the
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signal jets of interest are well separated and the boosted regime where they overlap. The returned value of
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-jettiness also provides a quality criterion of how
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-jet-like the event looks. We also discuss the
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-jettiness factorization theorems that occur for various jet measures, which can be used to compute the associated exclusive
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-jet cross sections. In a companion paper 1, the physics potential of XCone is demonstrated using the examples of dijet resonances, Higgs decays to bottom quarks, and all-hadronic top pairs.
Abstract
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder associated with exposure to head trauma. In 2015, a panel of neuropathologists funded by the NINDS/NIBIB defined ...preliminary consensus neuropathological criteria for CTE, including the pathognomonic lesion of CTE as “an accumulation of abnormal hyperphosphorylated tau (p-tau) in neurons and astroglia distributed around small blood vessels at the depths of cortical sulci and in an irregular pattern,” based on review of 25 tauopathy cases. In 2016, the consensus panel met again to review and refine the preliminary criteria, with consideration around the minimum threshold for diagnosis and the reproducibility of a proposed pathological staging scheme. Eight neuropathologists evaluated 27 cases of tauopathies (17 CTE cases), blinded to clinical and demographic information. Generalized estimating equation analyses showed a statistically significant association between the raters and CTE diagnosis for both the blinded (OR = 72.11, 95% CI = 19.5–267.0) and unblinded rounds (OR = 256.91, 95% CI = 63.6–1558.6). Based on the challenges in assigning CTE stage, the panel proposed a working protocol including a minimum threshold for CTE diagnosis and an algorithm for the assessment of CTE severity as “Low CTE” or “High CTE” for use in future clinical, pathological, and molecular studies.
IntroductionInitial reports suggest people experiencing homelessness (PEH) are at high risk for SARS-CoV-2 infection and associated morbidity and mortality. However, there have been few longitudinal ...evaluations of the spread and impact of COVID-19 among PEH. This study will estimate the prevalence and incidence of COVID-19 infections in a cohort of PEH followed prospectively in Toronto, Canada. It will also examine associations between individual-level and shelter-level characteristics with COVID-19 infection, adverse health outcomes related to infection and vaccination. Finally, the data will be used to develop and parameterise a mathematical model to characterise SARS-CoV-2 transmission dynamics, and the transmission impact of interventions serving PEH.Design, methods and analysisKu-gaa-gii pimitizi-win will follow a random sample of PEH from across Toronto (Canada) for 12 months. 736 participants were enrolled between June and September 2021, and will be followed up at 3-month intervals. At each interval, specimens (saliva, capillary blood) will be collected to determine active SARS-CoV-2 infection and serologic evidence of past infection and/or vaccination, and a detailed survey will gather self-reported information, including a detailed housing history. To examine the association between individual-level and shelter-level characteristics on COVID-19-related infection, adverse outcomes, and vaccination, shelter and healthcare administrative data will be linked to participant study data. Healthcare administrative data will also be used to examine long-term (up to 5 years) COVID-19-related outcomes among participants.Ethics and disseminationEthical approval was obtained from the Unity Health Toronto and University of Toronto Health Sciences Research Ethics Boards (# 20-272). Ku-gaa-gii pimitizi-win was designed in collaboration with community and service provider partners and people having lived experience of homelessness. Findings will be reported to groups supporting Ku-gaa-gii pimitizi-win, Indigenous and other community partners and service providers, funding bodies, public health agencies and all levels of government to inform policy and public health programs.
Contextual fear learning is heavily dependent on the hippocampus. Despite evidence that catecholamines contribute to contextual encoding and memory retrieval, the precise temporal dynamics of their ...release in the hippocampus during behavior is unknown. In addition, new animal models are required to probe the effects of altered catecholamine synthesis on release dynamics and contextual learning.
We generated two new mouse models of altered locus coeruleus norepinephrine (LC-NE) synthesis and utilized them together with GRABNE and GRABDA sensors and in vivo fiber photometry to investigate norepinephrine (NE) and dopamine (DA) release dynamics in dorsal hippocampal CA1 during contextual fear conditioning.
We report that aversive foot-shock increases both NE and DA release in dorsal CA1, while freezing behavior associated with recall of fear memory is accompanied by decreased release. Moreover, we find that freezing at the recent timepoint is sensitive to both partial and complete loss of LC-NE synthesis throughout prenatal and postnatal development, similar to prior observations of mice with global loss of NE synthesis beginning postnatally. In contrast, freezing at the remote timepoint is compromised only by complete loss of LC-NE synthesis beginning prenatally.
Overall, these findings provide novel insights into the role of NE in contextual fear and the precise temporal dynamics of both NE and DA during freezing behavior, and highlight a complex relationship between genotype, sex, and NE signaling.
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