Prophecy, alchemy and strategies of dissident communication: a 1630 letter from the Bohemian chiliast Paul Felgenhauer (1593-c.1677) to the Leipzig physician Arnold Kerner

This article concerns a short but significant letter of April 1630 from the Bohemian prophet, alchemist and theosopher Paul Felgenhauer (1593-c. 1677) to the Leipzig alchemist and physician Arnold Kerner. The letter is presented in transcription, with an annotated English translation. It is prefaced by an introduction incorporating a new biographical account of Felgenhauer, which draws on overlooked or unknown manuscript material preserved in Germany and England. The letter itself shines a rare light on a variety of different areas of interest concerning Felgenhauer's life and activities in the years prior to 1630. These areas include his immediate contacts and associates (such as with the Silesian prophet Christoph Kotter), interest and undertakings in alchemical experimentation, publishing and bibliographical activities, methods of communication, his circle of wider contacts and the nature and extent of broader interpersonal and epistolary networks in which he participated. However, it also illuminates tangential issues, such as the scale of social and informational economy in a heterodox correspondence network, the intricacies of dissident book production in the United Provinces, the history of trade in Leipzig, the role of commercial agents in facilitating contact between dissident personalities throughout the Holy Roman Empire, and the postal history of Bremen

Effective Screened Potentials of Strongly Coupled Semiclassical Plasma

The pseudopotentials of particle interaction of astrongly coupled semiclassical plasma, taking into account bothquantum-mechanical effects of diffraction at short distances andalso screening field effects at large distances are obtained. Thelimiting cases of potentials are considered.Comment: 15 pages, TeX, 7 figure

Cataract, abnormal electroretinogram and visual evoked potentials in a child with SMA-LED2 - extending the phenotype.

This case report describes a girl who presented antenatal arthrogryposis and postnatal hypotonia, generalized and respiratory weakness, joint deformities particularly affecting the lower limbs and poor swallow. By 5 months, cataracts, abnormal electroretinograms, visual evoked potentials and global developmental impairments were recognized. No causative variants were identified on targeted gene panels. After her unexpected death at 11 months, gene-agnostic trio whole exome sequencing revealed a likely pathogenic de novo BICD2 missense variant, NM_001003800.1, c.593T>C, p.(Leu198Pro), confirming the diagnosis of spinal muscular atrophy lower extremity predominant type 2 (SMA-LED2). We propose that cataracts and abnormal electroretinograms are novel features of SMA-LED2

The key role of forests in meeting climate targets requires science for credible mitigation

Forests contribute to climate change mitigation by conserving and enhancing the carbon sink and through reducing greenhouse gas emissions from deforestation. Yet the inclusion of forests in international climate agreements has been complex, often considered a secondary mitigation option or treated separately, like Cinderella excluded from the ball. In the lead up to the Paris Climate Agreement, countries submitted their Intended Nationally Determined Contributions (INDCs), including climate mitigation targets. Assuming full implementation of INDCs, we show that land use, and forests in particular, emerge as a key component of the Paris Agreement: turning globally from a net anthropogenic source during 1990-2010 (1.3 ± 1.1 GtCO2e/y) to a net sink of carbon by 2030 (up to -1.1 ± 0.5 GtCO2e/y), and providing a quarter of emission reductions planned by countries. Realizing and tracking this mitigation potential requires more confidence in numbers, including reconciling estimates between country reports and scientific studies. This represents a challenge and an opportunity for the scientific community.JRC.D.1-Bio-econom

Late Maastrichtian carbon isotope stratigraphy and cyclostratigraphy of the Newfoundland Margin (Site U1403, IODP Expedition 342)

Earth’s climate during the Maastrichtian (latest Cretaceous) was punctuated by brief warming and cooling episodes, accompanied by perturbations of the global carbon cycle. Superimposed on a long-term cooling trend, the middle Maastrichtian is characterized by deep-sea warming and relatively high values of stable carbon-isotope ratios, followed by strong climatic variability towards the end of the Cretaceous. A lack of knowledge on the timing of climatic change inhibits our understanding of underlying causal mechanisms. We present an integrated stratigraphy from Integrated Ocean Drilling Program (IODP) Site U1403, providing an expanded deep ocean record from the North Atlantic (Expedition 342, Newfoundland Margin). Distinct sedimentary cyclicity suggests that orbital forcing played a major role in depositional processes, which is confirmed by statistical analyses of high resolution elemental data obtained by X-ray fluorescence (XRF) core scanning. Astronomical calibration reveals that the investigated interval encompasses seven 405-kyr cycles (Ma4051 to Ma4057) and spans the 2.8 Myr directly preceding the Cretaceous/Paleocene (K/Pg) boundary. A high-resolution carbon-isotope record from bulk carbonates allows us to identify global trends in the late Maastrichtian carbon cycle. Low-amplitude variations (up to 0.4‰) in carbon isotopes at Site U1403 match similar scale variability in records from Tethyan and Pacific open-ocean sites. Comparison between Site U1403 and the hemipelagic restricted basin of the Zumaia section (northern Spain), with its own well-established independent cyclostratigraphic framework, is more complex. Whereas the pre-K/Pg oscillations and the negative values of the Mid-Maastrichtian Event (MME) can be readily discerned in both the Zumaia and U1403 records, patterns diverge during a ~ 1 Myr period in the late Maastrichtian (67.8–66.8 Ma), with Site U1403 more reliably reflecting global carbon cycling. Our new carbon isotope record and cyclostratigraphy offer promise for Site U1403 to serve as a future reference section for high-resolution studies of late Maastrichtian paleoclimatic change

CD45 Phosphatase Inhibits STAT3 Transcription Factor Activity in Myeloid Cells and Promotes Tumor-Associated Macrophage Differentiation

Recruitment of monocytic myeloid-derived suppressor cells (MDSCs) and differentiation of tumor-associated macrophages (TAMs) are the major factors contributing to tumor progression and metastasis. We demonstrated that differentiation of TAMs in tumor site from monocytic precursors was controlled by downregulation of the activity of the transcription factor STAT3. Decreased STAT3 activity was caused by hypoxia and affected all myeloid cells but was not observed in tumor cells. Upregulation of CD45 tyrosine phosphatase activity in MDSCs exposed to hypoxia in tumor site was responsible for downregulation of STAT3. This effect was mediated by the disruption of CD45 protein dimerization regulated by sialic acid. Thus, STAT3 has a unique function in the tumor environment in controlling the differentiation of MDSC into TAM, and its regulatory pathway could be a potential target for therapy

Genetically Determined Plasma Lipid Levels and Risk of Diabetic Retinopathy: A Mendelian Randomization Study.

Results from observational studies examining dyslipidemia as a risk factor for diabetic retinopathy (DR) have been inconsistent. We evaluated the causal relationship between plasma lipids and DR using a Mendelian randomization approach. We pooled genome-wide association studies summary statistics from 18 studies for two DR phenotypes: any DR (N = 2,969 case and 4,096 control subjects) and severe DR (N = 1,277 case and 3,980 control subjects). Previously identified lipid-associated single nucleotide polymorphisms served as instrumental variables. Meta-analysis to combine the Mendelian randomization estimates from different cohorts was conducted. There was no statistically significant change in odds ratios of having any DR or severe DR for any of the lipid fractions in the primary analysis that used single nucleotide polymorphisms that did not have a pleiotropic effect on another lipid fraction. Similarly, there was no significant association in the Caucasian and Chinese subgroup analyses. This study did not show evidence of a causal role of the four lipid fractions on DR. However, the study had limited power to detect odds ratios less than 1.23 per SD in genetically induced increase in plasma lipid levels, thus we cannot exclude that causal relationships with more modest effect sizes exist

Multicenter experience from the UK and Ireland of use of lumen-apposing metal stent for transluminal drainage of pancreatic fluid collections

Background and study aims: Pancreatic fluid collection (PFC) is a common complication of pancreatitis for which endoscopic ultrasound-guided drainage is first-line treatment. A new single-device, lumen-apposing, covered self-expanding metal stent (LAMS) has been licensed for PFC drainage. We therefore present our multicenter experience with the LAMS for PFC drainage in a multicenter prospective case series to assess success and complication rates. Patients and methods: All adult patients from 11 tertiary centers who had LAMS placement for PFC from July 2015 to July 2016 were included. Data including indications, technical success, clinical success, collection resolution, stent removal, early and late adverse events (AEs), mortality and recurrence at 6 months were collected. Results: 116 patients, median age 52.5 years (range 16 – 80) and 67 % male, were treated with a single LAMS in each case. The indication was walled off necrosis (WON) in 70 and pseudocyst in 46. Median size of the PFC was 11 cm (5 – 21 cm) and the estimated median necrotic volume in WON was 30 % (5 % – 90 %). Stent insertion was technically successful in 115 (99.1 %) and clinically successful in 109 (94 %). Early serious AEs (SAEs): n = 7 sepsis, n = 1 stent blockage with food, n = 1 stent migration requiring laparotomy, n = 1 stent dislodgement and n = 1 bleeding requiring emboliZation. Late AEs: n = 1 buried stent and n = 1 esophageal fistula. Non-procedure-related deaths: n = 3 (2.5 %). Conclusion: This multicenter case series demonstrates that use of the new LAMS is feasible, effective and relatively safe in draining PFC with a technical success rate of 99 % and cumulative SAE rate of 11.2 %