Late Bronze Age Hoard studied by PIXE

The hoards of metallic objects belonging to the Late European Bronze Age can be interpreted differently depending on the type, number and composition of the artefacts. PIXE analysis has been performed in nine items from the Hoard of Freixanda in Portugal comprising 4 socket axes, a palstave axe, a ring, a chisel, a dagger, and a casting debris. Besides the composition of the main matrix elements, that is Cu and Sn, the amount of trace elements of interest like, As, Pb, Ni and Ag has been determined using this ion beam technique. The high tin content alloy and the high purity of the metals from the Freixanda hoard are characteristic of the Portuguese and Spanish Late Bronze Age metallurgy, supporting the idea of a regional production

Zileuton™ loaded in polymer micelles effectively reduce breast cancer circulating tumor cells and intratumoral cancer stem cells

Tumor recurrence, metastatic spread and progressive gain of chemo-resistance of advanced cancers are sustained by the presence of cancer stem cells (CSCs) within the tumor. Targeted therapies with the aim to eradicate these cells are thus highly regarded. However, often the use of new anti-cancer therapies is hampered by pharmacokinetic demands. Drug delivery through nanoparticles has great potential to increase efficacy and reduce toxicity and adverse effects. However, its production has to be based on intelligent design. Likewise, we developed polymeric nanoparticles loaded with Zileuton™, a potent inhibitor of cancer stem cells (CSCs), which was chosen based on high throughput screening. Its great potential for CSCs treatment was subsequently demonstrated in in vitro and in in vivo CSC fluorescent models. Encapsulated Zileuton™ reduces amount of CSCs within the tumor and effectively blocks the circulating tumor cells (CTCs) in the blood stream and metastatic spread

Kinematics of electrons near a Van Hove singularity

A two dimensional electronic system, where the Fermi surface is close to a Van Hove singularity, shows a variety of weak coupling instabilities, and it is a convenient model to study the interplay between antiferromagnetism and anisotropic superconductivity. We present a detailed analysis of the kinematics of the electron scattering in this model. The similitudes, and differences, between a standard Renormalization Group approach and previous work based on parquet summations of log$^2$ divergences are analyzed, with emphasis on the underlying physical processes. General properties of the phase diagram are discussed.Comment: 5 pages, 3 postscript figure

Behind the scenes: mechanisms regulating climatic patterns of dissolved organic carbon uptake in headwater streams

Large variability in dissolved organic carbon (DOC) uptake rates has been reported for headwater streams, but the causes of this variability are still not well understood. Here we assessed acetate uptake rates across 11 European streams comprising different ecoregions by using whole-reach pulse acetate additions. We evaluated the main climatic and biogeochemical drivers of acetate uptake during two seasonal periods. Our results show a minor influence of sampling periods but a strong effect of climate and dissolved organic matter (DOM) composition on acetate uptake. In particular, mean annual precipitation explained half of the variability of the acetate uptake velocities (VfAcetate) across streams. Temperate streams presented the lowest VfAcetate, together with humic-like DOM and the highest stream respiration rates. In contrast, higher VfAcetate were found in semiarid streams, with protein-like DOM, indicating a dominance of reactive, labile compounds. This, together with lower stream respiration rates and molar ratios of DOC to nitrate, suggests a strong C limitation in semiarid streams, likely due to reduced inputs from the catchment. Overall, this study highlights the interplay of climate and DOM composition and its relevance to understand the biogeochemical mechanisms controlling DOC uptake in streams.Theauthors were supported by the following funding: N. C. by a Generalitat de Catalunya-Beatriu de Pinós grant (BP2016–00215), E. E. by a predoctoral grant from the Basque Government, A. G. B. by a Generalitat de Catalunya-Beatriu de Pinós (BP-00385-2016), A. M. G. F. by a predoctoral research grant (BES-2013-065770) from the Spanish Ministry of Economy and Competitiveness, P. R. L. by a Ramón Areces Foundation Postdoctoral Scholarship, and A. L. by a Kempe Foundation stipend. DOMIPEX project was funded by the First Call of Collaborative Projects among Young Researchers of the Iberian Association of Limnology (AIL; 2013–2015)

Towards an improved understanding of biogeochemical processes across surface-groundwater interactions in intermittent rivers and ephemeral streams

Surface-groundwater interactions in intermittent rivers and ephemeral streams (IRES), waterways which do not flow year-round, are spatially and temporally dynamic because of alternations between flowing, non-flowing and dry hydrological states. Interactions between surface and groundwater often create mixing zones with distinct redox gradients, potentially driving high rates of carbon and nutrient cycling. Yet a complete understanding of how underlying biogeochemical processes across surface-groundwater flowpaths in IRES differ among various hydrological states remains elusive. Here, we present a conceptual framework relating spatial and temporal hydrological variability in surface water-groundwater interactions to biogeochemical processing hotspots in IRES. We combine a review of theIRES biogeochemistry literature with concepts of IRES hydrogeomorphology to: (i) outline common distinctions among hydrological states in IRES; (ii) use these distinctions, together with considerations of carbon, nitrogen, and phosphorus cycles within IRES, to predict the relative potential for biogeochemical processing across different reach-scale processing zones (flowing water, fragmented pools, hyporheic zones, groundwater, and emerged sediments); and (iii) explore the potential spatial and temporal variability of carbon and nutrient biogeochemical processing across entire IRES networks. Our approach estimates the greatest reach-scale potential for biogeochemical processing when IRES reaches are fragmented into isolated surface water pools, and highlights the potential of relatively understudied processing zones, such as emerged sediments. Furthermore, biogeochemical processing in fluvial networks dominated by IRES is likely more temporally than spatially variable. We conclude that biogeochemical research in IRES would benefit from focusing on interactions between different nutrient cycles, surface-groundwater interactions in non-flowing states, and consideration of fluvial network architecture. Our conceptual framework outlines opportunities to advance studies and expand understanding of biogeochemistry in IRES

Efficacy of Immune Checkpoint Inhibitors for the Treatment of Advanced Melanoma in Patients With Concomitant Chronic Lymphocytic Leukemia

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the management of advanced melanoma (AM). However, data on ICI effectiveness have largely been restricted to clinical trials, thereby excluding patients with co-existing malignancies. Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia and is associated with increased risk of melanoma. CLL alters systemic immunity and can induce T-cell exhaustion, which may limit the efficacy of ICIs in patients with CLL. We, therefore, sought to examine the efficacy of ICI in patients with these co-occurring diagnoses. PATIENTS AND METHODS: In this international multicenter study, a retrospective review of clinical databases identified patients with concomitant diagnoses of CLL and AM treated with ICI (US-MD Anderson Cancer Center, N = 24; US-Mayo Clinic, N = 15; AUS, N = 19). Objective response rates (ORRs), assessed by RECIST v1.1, and survival outcomes [overall survival (OS) and progression-free survival (PFS)] among patients with CLL and AM were assessed. Clinical factors associated with improved ORR and survival were explored. Additionally, ORR and survival outcomes were compared between the Australian CLL/AM cohort and a control cohort of 148 Australian patients with AM alone. RESULTS: Between 1997 and 2020, 58 patients with concomitant CLL and AM were treated with ICI. ORRs were comparable between AUS-CLL/AM and AM control cohorts (53% versus 48%, P = 0.81). PFS and OS from ICI initiation were also comparable between cohorts. Among CLL/AM patients, a majority were untreated for their CLL (64%) at the time of ICI. Patients with prior history of chemoimmunotherapy treatment for CLL (19%) had significantly reduced ORRs, PFS, and OS. CONCLUSIONS: Our case series of patients with concomitant CLL and melanoma demonstrate frequent, durable clinical responses to ICI. However, those with prior chemoimmunotherapy treatment for CLL had significantly worse outcomes. We found that CLL disease course is largely unchanged by treatment with ICI

Oral Ondansetron Administration in Emergency Departments to Children with Gastroenteritis: An Economic Analysis

Stephen Freedman and colleagues performed a cost analysis of the routine administration of ondansetron in both the United States and Canada and show that its routine administration to eligible children in such settings could provide substantial benefit

Primrose syndrome: Characterization of the phenotype in 42 patients

Primrose syndrome (PS; MIM# 259050) is characterized by intellectual disability (ID), macrocephaly, unusual facial features (frontal bossing, deeply set eyes, down-slanting palpebral fissures), calcified external ears, sparse body hair and distal muscle wasting. The syndrome is caused by de novo heterozygous missense variants in ZBTB20. Most of the 29 published patients are adults as characteristics appear more recognizable with age. We present 13 hitherto unpublished individuals and summarize the clinical and molecular findings in all 42 patients. Several signs and symptoms of PS develop during childhood, but the cardinal features, such as calcification of the external ears, cystic bone lesions, muscle wasting, and contractures typically develop between 10 and 16 years of age. Biochemically, anemia and increased alpha-fetoprotein levels are often present. Two adult males with PS developed a testicular tumor. Although PS should be regarded as a progressive entity, there are no indications that cognition becomes more impaired with age. No obvious genotype-phenotype correlation is present. A subgroup of patients with ZBTB20 variants may be associated with mild, nonspecific ID. Metabolic investigations suggest a disturbed mitochondrial fatty acid oxidation. We suggest a regular surveillance in all adult males with PS until it is clear whether or not there is a truly elevated risk of testicular cancer.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.published version, accepted version (12 month embargo) submitted versio

Increased Prevalence of Metabolic Syndrome in Patients with Acne Inversa

BACKGROUND: Acne inversa (AI; also designated as Hidradenitis suppurativa) is a common chronic inflammatory skin disease, localized in the axillary, inguinal and perianal skin areas that causes painful, fistulating sinuses with malodorous purulence and scars. Several chronic inflammatory diseases are associated with the metabolic syndrome and its consequences including arteriosclerosis, coronary heart disease, myocardial infraction, and stroke. So far, the association of AI with systemic metabolic alterations is largely unexplored. METHODS AND FINDINGS: A hospital-based case-control study in 80 AI patients and 100 age- and sex-matched control participants was carried out. The prevalence of central obesity (odds ratio 5.88), hypertriglyceridemia (odds ratio 2.24), hypo-HDL-cholesterolemia (odds ratio 4.56), and hyperglycemia (odds ratio 4.09) in AI patients was significantly higher than in controls. Furthermore, the metabolic syndrome, previously defined as the presence of at least three of the five alterations listed above, was more common in those patients compared to controls (40.0% versus 13.0%; odds ratio 4.46, 95% confidence interval 2.02 to 9.96; P<0.001). AI patients with metabolic syndrome also had more pronounced metabolic alterations than controls with metabolic syndrome. Interestingly, there was no correlation between the severity or duration of the disease and the levels of respective parameters or the number of criteria defining the metabolic syndrome. Rather, the metabolic syndrome was observed in a disproportionately high percentage of young AI patients. CONCLUSIONS: This study shows for the first time that AI patients have a high prevalence of the metabolic syndrome and all of its criteria. It further suggests that the inflammation present in AI patients does not have a major impact on the development of metabolic alterations. Instead, evidence is given for a role of metabolic alterations in the development of AI. We recommend monitoring of AI patients in order to correct their modifiable cardiovascular risk factors