© 2020 Elsevier Inc. We give a simple recursion labeled by binary sequences which computes rational q,t-Catalan power series, both in relatively prime and non relatively prime cases. It is inspired by, but not identical to recursions due to B. Elias, M. Hogancamp, and A. Mellit, obtained in their study of link homology. We also compare our recursion with the Hogancamp-Mellit's recursion and verify a connection between the Khovanov-Rozansky homology of N,M-torus links and the rational q,t-Catalan power series for general positive N,M.
Localized radiation therapy can be an effective treatment for cancer but is associated with localized and systemic side effects. Several studies have noted changes in complete blood count (CBC) parameters including decreases in the absolute lymphocyte count (ALC) and increases in the neutrophil:lymphocyte ratio (NLR). These changes could reflect immunosuppression and may contribute to decreased efficacy of immunotherapies used to treat cancer. We hypothesized that dogs would demonstrate decreased ALCs during a course of radiotherapy. A retrospective study was conducted on 203 dogs receiving definitive-intent radiotherapy. Demographic information, CBC values and details of the radiotherapy protocol were collected. The mean lymphocyte count pre-treatment was 1630.68 cells/μL (SD ± 667.56) with a mean NLR of 3.66 (SD ± 4.53). The mean lymphocyte count mid-treatment was 1251.07 cells/μL (SD ± 585.96) and the mean NLR was 6.23 (SD ± 4.99). There was a significant decrease in the mean lymphocyte count by 351.41 lymphocytes/μL (SD ± 592.32) between pre-treatment and mid-treatment (P < .0001), and a corresponding significant increase in the mean NLR of 0.93 (P = .02). Lymphopenia grade increased in 33.5% of dogs and was significant (P = .03). The ALC decrease was not correlated with the volume irradiated (P = .27), but correlated with the irradiated volume:body weight ratio (P = .03). A subset of patients (n = 35) with additional CBCs available beyond the mid-treatment time point demonstrated significant and sustained downward trends in the ALC compared with baseline. Although severe lymphopenia was rare, these decreases, especially if sustained, could impact adjuvant therapy for their cancer.
PURPOSE:Stomal stenosis has been reported to occur in 12% to 45% of patients following Malone antegrade continence enema and Mitrofanoff appendicostomy. The standard stoma technique entails excision of the distal appendix. We evaluated a novel technique with preservation of the appendiceal tip and vessels, and opening the lumen in a more proximal and vascular area to determine whether the incidence of stenosis would be decreased. MATERIALS AND METHODS:Medical records of patients who underwent appendicostomy for Malone antegrade continence enema or urinary diversion were retrospectively evaluated. We included cases with a minimum of 1 year of followup and those in which the distal portion of a complete appendix was oriented for use as the stomal end in the umbilicus. Variables such as age, gender, body mass index, antegrade continence enema or urinary diversion, open or laparoscopic approach, cecal and appendiceal adhesions, retrocecal position, cecal imbrication, technique and stenosis were recorded. Cox proportional hazards analyses were performed to determine association of covariates. RESULTS:A total of 123 patients met inclusion criteria. The incidence of stenosis following standard stoma technique was 13% (12 of 93 patients) with a median followup of 9.4 years. Of these cases 75% occurred within 1 year of surgery. Stomal stenosis did not occur after the new stoma technique in 30 patients with a median followup of 3.3 years. Only technique cohort (standard vs new) was associated with stenosis (p=0.04). CONCLUSIONS:Stomal stenosis of appendicostomy may be lessened by preservation of the distal appendiceal vasculature and tip, and opening the lumen in a more proximal location.
© 2020 Domestication and agricultural intensification dramatically altered maize and its cultivation environment. Changes in maize genetics (G) and environmental (E) conditions increased productivity under high-synthetic-input conditions. However, novel selective pressures on the rhizobiome may have incurred undesirable tradeoffs in organic agroecosystems, where plants obtain nutrients via microbially mediated processes including mineralization of organic matter. Using twelve maize genotypes representing an evolutionary transect (teosintes, landraces, inbred parents of modern elite germplasm, and modern hybrids) and two agricultural soils with contrasting long-term management, we integrated analyses of rhizobiome community structure, potential microbe-microbe interactions, and N-cycling functional genes to better understand the impacts of maize evolution and soil management legacy on rhizobiome recruitment. We show complex shifts in rhizobiome communities during directed evolution of maize (defined as the transition from teosinte to modern hybrids), with a larger effect of domestication (teosinte to landraces) than modern breeding (inbreds to hybrids) on rhizobiome structure and greater impacts of modern breeding on potential microbe-microbe interactions. Rhizobiome structure was significantly correlated with plant nutrient composition. Furthermore, plant biomass and nutrient content were affected by G x E interactions in which teosinte and landrace genotypes had better relative performance in the organic legacy soil than inbred and modern genotypes. The abundance of six N-cycling genes of relevance for plant nutrition and N loss pathways did not significantly differ between teosinte and modern rhizospheres in either soil management legacy. These results provide insight into the potential for improving maize adaptation to organic systems and contribute to interdisciplinary efforts toward developing resource-efficient, biologically based agroecosystems.
© 2020 Elsevier B.V. Accurate assessments of soil organic carbon (SOC) stocks are needed at multiple scales given their importance to both local soil health and global C cycles. Rangelands cover 54% of California, representing a large stock of SOC, but existing SOC estimates are uncertain. To improve understanding of fine-resolution SOC stocks in complex terrain and provide guidance to rangeland SOC inventories, we grid-sampled 105 locations (21-m grid cells) at two depths (0–10 and 10–30 cm) in a 10-ha annual grassland catchment in California's Central Coast Range. Soils were analyzed for bulk density, coarse fragments, SOC and texture. Monthly aerial imagery was acquired by an unmanned aerial vehicle to compare surface reflectance during two contrasting years (wet vs. dry) to SOC stocks. We found that the 0–30 cm soil thickness held 3.64 ± 0.71 kg SOC m−2 (mean ± SD) with a range of 1.97–5.49 kg SOC m−2. The 0–10 cm soil thickness stored 47% of the 0–30 cm SOC stock with SOC concentrations twice as high in the 0–10 cm layer (1.40 ± 0.38%) as in the 10–30 cm layer (0.71 ± 0.15% SOC). Multiple linear regression (MLR) models explained 50–57% of SOC variability at 0–30 and 10–30 cm, but only 25% of variability at 0–10 cm. Based on cross-validation tests, MLR outperformed spatial interpolation methods and Random Forest models, best explaining SOC stocks with five environmental covariates: wet-year greenness, mean curvature, elevation, insolation, and slope. Lower hillslope positions, concave landforms, and enhanced wet-year greenness were associated with more SOC, and explained 11%, 24%, and 31% of variability in 0–30 cm SOC stocks, respectively. This study demonstrates that the accuracy of regional-scale SOC mapping of California rangelands benefits from considering microclimatic and topographic controls at the catchment-scale, in addition to broader scale mineralogical and macroclimatic controls identified in previous SOC studies.
Hemophilia A (HA) is a bleeding disorder characterized by spontaneous and prolonged hemorrhage. The disease is caused by mutations in the coagulation factor 8 gene (F8) leading to factor VIII (FVIII) deficiency. Since FVIII is primarily produced in endothelial cells (ECs) in a non-diseased human being, ECs hold great potential for development as a cell therapy for HA. We showed that HA patient-specific induced pluripotent stem cells (HA-iPSCs) could provide a renewable supply of ECs. The HA-iPSC-derived ECs were transduced with lentiviral vectors to stably express the functional B domain deleted F8 gene, the luciferase gene, and the enhanced green fluorescent protein gene (GFP). When transplanted intramuscularly into neonatal and adult immune deficient mice, the HA-iPSC-derived ECs were retained in the animals for at least 10-16 weeks and maintained their expression of FVIII, GFP, and the endothelial marker CD31, as demonstrated by bioluminescence imaging and immunostaining, respectively. When transplanted into HA mice, these transduced HA-iPSC-derived ECs significantly reduced blood loss in a tail-clip bleeding test and produced therapeutic plasma levels (11.2%-369.2%) of FVIII. Thus, our studies provide proof-of-concept that HA-iPSC-derived ECs can serve as a factory to deliver FVIII for the treatment of HA not only in adults but also in newborns.
OBJECTIVE:To evaluate serum estradiol (E2) concentrations during use of 90-day contraceptive vaginal rings releasing E2 75, 100, or 200 mcg/day and segesterone acetate (SA) 200 mcg/day to identify a dose that avoids hypoestrogenism. Study Design We conducted a multicenter dose-finding study in healthy, reproductive-aged women with regular cycles with sequential enrollment to increasing E2 dose groups. We evaluated serum E2 concentrations twice weekly for the primary outcome of median E2 concentrations throughout initial 30-day use (target ≥40 pg/mL). In an optional 2-cycle extension substudy, we randomized participants to 2- or 4-day ring-free intervals per 30-day cycle to evaluate bleeding and spotting based on daily diary information. RESULTS:Sixty-five participants enrolled in E2 75 (n=22), 100 (n=21), and 200 (n=22) mcg/day groups; 35 participated in the substudy. Median serum E2 concentrations in 75 and 100 mcg/day groups were <40 pg/mL. In the 200 mcg/day group, median E2 concentrations peaked on days 4-5 of CVR use at 194 pg/mL (range 114-312 pg/mL) and remained >40 pg/mL throughout 30 days; E2 concentrations were 37 pg/mL (range 28-62 pg/mL) on days 88-90 (n=11). Among the E2 200 mcg/day substudy participants, all had withdrawal bleeding following ring removal. The 2-day ring-free interval group reported zero median unscheduled bleeding and two (range 0-16) and three (range 0-19) unscheduled spotting days in extension cycles 1 and 2, respectively. The 4-day ring-free interval group reported zero median unscheduled bleeding or spotting days. CONCLUSIONS:Estradiol concentrations with rings releasing E2 200 mcg/day and SA 200 mcg/day avoid hypoestrogenism over 30-day use. Implications A 90-day contraceptive vaginal ring releasing estradiol 200 mcg/day and segesterone acetate 200 mcg/day achieves estradiol concentrations that should avoid hypoestrogenism and effectively suppresses ovulation.
Severe coronavirus disease (COVID-19) is characterized by pulmonary hyper-inflammation and potentially life-threatening "cytokine storms". Controlling the local and systemic inflammatory response in COVID-19 may be as important as anti-viral therapies. Endogenous lipid autacoid mediators, referred to as eicosanoids, play a critical role in the induction of inflammation and pro-inflammatory cytokine production. SARS-CoV-2 may trigger a cell death ("debris")-induced "eicosanoid storm", including prostaglandins and leukotrienes, which in turn initiates a robust inflammatory response. A paradigm shift is emerging in our understanding of the resolution of inflammation as an active biochemical process with the discovery of novel endogenous specialized pro-resolving lipid autacoid mediators (SPMs), such as resolvins. Resolvins and other SPMs stimulate macrophage-mediated clearance of debris and counter pro-inflammatory cytokine production, a process called inflammation resolution. SPMs and their lipid precursors exhibit anti-viral activity at nanogram doses in the setting of influenza without being immunosuppressive. SPMs also promote anti-viral B cell antibodies and lymphocyte activity, highlighting their potential use in the treatment of COVID-19. Soluble epoxide hydrolase (sEH) inhibitors stabilize arachidonic acid-derived epoxyeicosatrienoic acids (EETs), which also stimulate inflammation resolution by promoting the production of pro-resolution mediators, activating anti-inflammatory processes, and preventing the cytokine storm. Both resolvins and EETs also attenuate pathological thrombosis and promote clot removal, which is emerging as a key pathology of COVID-19 infection. Thus, both SPMs and sEH inhibitors may promote the resolution of inflammation in COVID-19, thereby reducing acute respiratory distress syndrome (ARDS) and other life-threatening complications associated with robust viral-induced inflammation. While most COVID-19 clinical trials focus on "anti-viral" and "anti-inflammatory" strategies, stimulating inflammation resolution is a novel host-centric therapeutic avenue. Importantly, SPMs and sEH inhibitors are currently in clinical trials for other inflammatory diseases and could be rapidly translated for the management of COVID-19 via debris clearance and inflammatory cytokine suppression. Here, we discuss using pro-resolution mediators as a potential complement to current anti-viral strategies for COVID-19.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.