Floristic Records in the Platte and Loup River Bottomlands of Platte County, Nebraska

A recent inventory of vascular plants in the Loup and Platte riverbottoms in Platte County has greatly increased knowledge of the area\u27s flora. Of the 542 species of vascular plants now known to grow in the county, 289 were discovered after 1977, with more than 100 of those after 1990. 425 native and 117 naturalized species are known so far. Nearly 700 native and naturalized alien species are expected to occur in the county, based upon totals from nearby counties. Thus, almost 150 years after European settlement, more than 20% of the species remain unverified; of those, many are undoubtedly nonnative. The riverbottoms of the county have the bestpreserved native flora and are today much richer in species than the uplands, which are more heavily impacted by agricultur

Hydrothermal formation of heavy rare earth element (HREE)– xenotime deposits at 100 °C in a sedimentary basin

Most rare earth element deposits form from magmatic fluids, but there have also been discoveries of heavy rare earth element (HREE)– enriched hydrothermal xenotime deposits within sedimentary basins. As xenotime is notoriously insoluble, the question arises as to whether these lesser-known deposits form at typical basin temperatures or by influx of much hotter magmatic-hydrothermal fluids. The Browns Range District in northern Western Australia hosts deposits of xenotime that are enriched in HREEs and also uranium. The ore bodies consist of fault-controlled hydrothermal quartz-xenotime breccias that crosscut Archean basement rocks and overlying Paleoproterozoic sandstones. Analyses of fluid inclusions show that the xenotime precipitated at remarkably low temperatures, between 100 and 120 °C, in response to decompression boiling. The inclusions contain high excess concentrations of yttrium (10−3 mol/kg), REEs (1–7 × 10−5 mol/kg), and uranium (4 × 10−5 mol/kg) in equilibrium with xenotime at these low temperatures, showing that availability of phosphate limited the amount of xenotime precipitated. The analyses further identify SO4 2– and Cl– as the ligands that facilitated the elevated REE and uranium solubilities. These findings establish that significant REE transport and deposition is feasible at basin temperatures, and hence they raise the potential of unconformity settings for REE exploration. Moreover, the aqueous metal contents support a genetic link between this type of ore fluid and world-class Proterozoic unconformity-related uranium deposits elsewhere

Adjuvant low-dose interferon α2a with or without dacarbazine compared with surgery alone: a prospective-randomized phase III DeCOG trial in melanoma patients with regional lymph node metastasis

Background: More than half of patients with melanoma that has spread to regional lymph nodes develop recurrent disease within the first 3 years after surgery. The aim of the study was to improve disease-free survival (DFS) and overall survival (OS) with interferon (IFN) α2a with or without dacarbazine (DTIC) compared with observation alone. Patients and methods: A total of 444 patients from 42 centers of the German Dermatologic Cooperative Oncology Group who had received a complete lymph node dissection for pathologically proven regional node involvement were randomized to receive either 3 MU s.c. of IFNα2a three times a week for 2 years (Arm A) or combined treatment with same doses of IFNα2a plus DTIC 850 mg/m2 every 4-8 weeks for 2 years (Arm B) or to observation alone (Arm C). Treatment was discontinued at first sign of relapse. Results: A total of 441 patients were eligible for intention-to-treat analysis. Kaplan-Meier 4-year OS rate of those who had received IFNα2a was 59%. For those with surgery alone, survival was 42% (A versus C, P = 0.0045). No improvement of survival was found for the combined treatment Arm B with 45% survival rate (B versus C, P = 0.76). Similarly, DFS rates showed significant benefit for Arm A, and not for Arm B. Multivariate Cox model confirmed that Arm A has an impact on OS (P = 0.005) but not Arm B (P = 0.34). Conclusions: 3 MU interferon α2a given s.c. three times a week for 2 years significantly improved OS and DFS in patients with melanoma that had spread to the regional lymph nodes. Interestingly, the addition of DTIC reversed the beneficial effect of adjuvant interferon α2a therap

Prospective assessment of a gene signature potentially predictive of clinical benefit in metastatic melanoma patients following MAGE-A3 immunotherapeutic (PREDICT)

Background: Genomic profiling of tumor tissue may aid in identifying predictive or prognostic gene signatures (GS) in some cancers. Retrospective gene expression profiling of melanoma and non-small-cell lung cancer led to the characterization of a GS associated with clinical benefit, including improved overall survival (OS), following immunization with the MAGE-A3 immunotherapeutic. The goal of the present study was to prospectively evaluate the predictive value of the previously characterized GS. Patients and methods: An open-label prospective phase II trial ('PREDICT') in patients with MAGE-A3-positive unresectable stage IIIB-C/IV-M1a melanoma. Results: Of 123 subjects who received the MAGE-A3 immunotherapeutic, 71 (58.7%) displayed the predictive GS (GS +). The 1-year OS rate was 83.1%/83.3% in the GS+/GS- populations. The rate of progression-free survival at 12 months was 5.8%/4.1% in GS+/GS- patients. The median time-to-treatment failure was 2.7/2.4 months (GS+/GS-). There was one complete response (GS-) and two partial responses (GS+). The MAGE-A3 immunotherapeutic was similarly immunogenic in both populations and had a clinically acceptable safety profile. Conclusion: Treatment of patients with MAGE-A3-positive unresectable stage IIIB-C/IV-M1a melanoma with the MAGE-A3 immunotherapeutic demonstrated an overall 1-year OS rate of 83.5%. GS- and GS+ patients had similar 1-year OS rates, indicating that in this study, GS was not predictive of outcome. Unexpectedly, the objective response rate was lower in this study than in other studies carried out in the same setting with the MAGE-A3 immunotherapeutic. Investigation of a GS to predict clinical benefit to adjuvant MAGE-A3 immunotherapeutic treatment is ongoing in another melanoma study. This study is registered at www.clinicatrials.gov NCT00942162

Radiosensitization by BRAF inhibitor therapy—mechanism and frequency of toxicity in melanoma patients

This study shows radiosensitization by BRAF inhibitors in clinical practice and ex vivo by fluorescence in situ hybridization of chromosomal breaks. Nevertheless, radiotherapy with concomitant BRAF inhibitor therapy is feasible with an acceptable increase in toxicity. Vemurafenib is a more potent radiosensitizer than dabrafenib in both the patient study and the ex vivo experiment

Histamine receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Histamine receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Histamine Receptors [75, 163]) are activated by the endogenous ligand histamine. Marked species differences exist between histamine receptor orthologues [75]. The human and rat H3 receptor genes are subject to significant splice variance [12]. The potency order of histamine at histamine receptor subtypes is H3 = H4 > H2 > H1 [163]. Some agonists at the human H3 receptor display significant ligand bias [171]. Antagonists of all 4 histamine receptors have clinical uses: H1 antagonists for allergies (e.g. cetirizine), H2 antagonists for acid-reflux diseases (e.g. ranitidine), H3 antagonists for narcolepsy (e.g. pitolisant/WAKIX; Registered) and H4 antagonists for atopic dermatitis (e.g. ZPL-3893787; Phase IIa) [163] and vestibular neuritis (AUV) (SENS-111 (Seliforant, previously UR-63325), entered and completed vestibular neuritis (AUV) Phase IIa efficacy and safety trials, respectively) [205, 8]

Differential influence of vemurafenib and dabrafenib on patients' lymphocytes despite similar clinical efficacy in melanoma

In this study, we demonstrate that vemurafenib but not dabrafenib reduces peripheral lymphocyte counts in melanoma patients while both agents show similar clinical efficacy. Within the lymphocyte compartment, vemurafenib selectively decreases circulating CD4+ T cells and changes their phenotype and function. This indicates that selective BRAFi need to be assessed individually for immunomodulatory effects, especially, when planning combinations with immunotherapie

A Spectroscopic and Photometric Study of Short-Timescale Variability in NGC5548

Results of a ground-based optical monitoring campaign on NGC5548 in June 1998 are presented. The broad-band fluxes (U,B,V), and the spectrophotometric optical continuum flux F_lambda(5100 A) monotonically decreased in flux while the broad-band R and I fluxes and the integrated emission-line fluxes of Halpha and Hbeta remained constant to within 5%. On June 22, a short continuum flare was detected in the broad band fluxes. It had an amplitude of about ~18% and it lasted only ~90 min. The broad band fluxes and the optical continuum F_lambda(5100 A) appear to vary simultaneously with the EUV variations. No reliable delay was detected for the broad optical emission lines in response to the EUVE variations. Narrow Hbeta emission features predicted as a signature of an accretion disk were not detected during this campaign. However, there is marginal evidence for a faint feature at lambda = 4962 A with FWHM=~6 A redshifted by Delta v = 1100 km/s with respect to Hbeta_narrow.Comment: 12 pages, 7 figures, accepted for publishing in A&