The Osculating cone to special Brill-Noether Loci

In this paper, we describe the osculating cone to Brill-Noether loci $W^{0}_{d}(C)$ at smooth isolated points of $W^{1}_{d}(C)$ for a smooth canonically embedded curve $C$ of even genus $g=2(d-1)$. In particular, we show that the canonical curve $C$ is a component of the osculating cone. The proof is based on techniques introduced by George Kempf in 1986.Comment: 18 pages, v3: to appear in Collectanea Mathematic

Late Holocene climate and environmental changes in Kamchatka inferred from subfossil chironomid record.

This study presents a reconstruction of the Late Holocene climate in Kamchatka based on chironomid remains from a 332 cm long composite sediment core recovered from Dvuyurtochnoe Lake (Two-Yurts Lake, TYL) in central Kamchatka. The oldest recovered sediments date to about 4500 cal years BP. Chironomid head capsules from TYL reflect a rich and diverse fauna. An unknown morphotype of Tanytarsini, Tanytarsus type klein, was found in the lake sediments. Our analysis reveals four chironomid assemblage zones reflecting four different climatic periods in the Late Holocene. Between 4500 and 4000 cal years BP, the chironomid composition indicates a high lake level, well-oxygenated lake water conditions and close to modern temperatures (w13 �C). From 4000 to 1000 cal years BP, two consecutive warm intervals were recorded, with the highest reconstructed temperature reaching 16.8 �C between 3700 and 2800 cal years BP. Cooling trend, started around 1100 cal years BP led to low temperatures during the last stage of the Holocene. Comparison with other regional studies has shown that termination of cooling at the beginning of late Holocene is relatively synchronous in central Kamchatka, South Kurile, Bering and Japanese Islands and take place around 3700 cal years BP. From ca 3700 cal years BP to the last millennium, a newly strengthened climate continentality accompanied by general warming trend with minor cool excursions led to apparent spatial heterogeneity of climatic patterns in the region. Some timing differences in climatic changes reconstructed from chironomid record of TYL sediments and late Holocene events reconstructed from other sites and other proxies might be linked to differences in local forcing mechanisms or caused by the different degree of dating precision, the different temporal resolution, and the different sensitive responses of climate proxies to the climate variations. Further high-resolution stratigraphic studies in this region are needed to understand the spatially complex pattern of climate change in Holocene in Kamchatka and the surrounding region.

Sea ice and millennial-scale climate variability in the Nordic seas 90 kyr ago to present

Publisher's version, source http://doi.org/10.1038/ncomms12247In the light of rapidly diminishing sea ice cover in the Arctic during the present atmospheric warming, it is imperative to study the distribution of sea ice in the past in relation to rapid climate change. Here we focus on glacial millennial-scale climatic events (Dansgaard/Oeschger events) using the sea ice proxy IP25 in combination with phytoplankton proxy data and quantification of diatom species in a record from the southeast Norwegian Sea. We demonstrate that expansion and retreat of sea ice varies consistently in pace with the rapid climate changes 90 kyr ago to present. Sea ice retreats abruptly at the start of warm interstadials, but spreads rapidly during cooling phases of the interstadials and becomes near perennial and perennial during cold stadials and Heinrich events, respectively. Low-salinity surface water and the sea ice edge spreads to the Greenland–Scotland Ridge, and during the largest Heinrich events, probably far into the Atlantic Ocean

Zwischenbericht und Auswertungsmanual zum Projekt "KOMPETENT": (neue Formen arbeitszentrierter Lebensgestaltung ; Kompetenzenentwicklung bei Beschäftigen im IT-Bereich)

Im Rahmen des Forschungsprojekts "KOMPETENT" werden Fragen zur Lebensgestaltung und Kompetenzentwicklung von ca. 100 Beschäftigten aus dem informationstechnologischen Bereich untersucht. Dabei handelt es sich um die GründerInnen und die MitarbeiterInnen sogenannter "Startups", d.h. relativ junger und in der Regel kleiner Unternehmen aus diesem Bereich. Im Mittelpunkt der Studie steht die Frage, inwieweit sich die These einer zunehmenden Entgrenzung von Berufs- und Privatleben empirisch für jenen Bereich belegen lässt, der häufig als Prototyp neuer Arbeitsformen gilt. Die Autoren führten bisher 73 Interviews durch. Nach einem kurzen Zwischenbericht über das erste Projektjahr stellen sie im vorliegenden Arbeitspapier ein Auswertungsmanual näher vor, das sie auf der Grundlage der ersten zehn ausgewerteten Interviews entwickelt haben. (ICI2

Chemokine ligand-receptor interactions critically regulate cutaneous wound healing

Background: Wound healing represents a dynamic process involving directional migration of different cell types. Chemokines, a family of chemoattractive proteins, have been suggested to be key players in cell-to-cell communication and essential for directed migration of structural cells. Today, the role of the chemokine network in cutaneous wound healing is not fully understood. Unraveling the chemokine-driven communication pathways in this complex process could possibly lead to new therapeutic strategies in wound healing disorders. Methods: We performed a systematic, comprehensive time-course analysis of the expression and function of a broad variety of cytokines, growth factors, adhesion molecules, matrixmetalloproteinases and chemokines in a murine cutaneous wound healing model. Results: Strikingly, chemokines were found to be among the most highly regulated genes and their expression was found to coincide with the expression of their matching receptors. Accordingly, we could show that resting and activated human primary keratinocytes (CCR3, CCR4, CCR6, CXCR1, CXCR3), dermal fibroblasts (CCR3, CCR4, CCR10) and dermal microvascular endothelial cells (CCR3, CCR4, CCR6, CCR8, CCR9, CCR10, CXCR1, CXCR2, CXCR3) express a distinct and functionally active repertoire of chemokine receptors. Furthermore, chemokine ligand-receptor interactions markedly improved the wound repair of structural skin cells in vitro. Conclusion: Taken together, we here present the most comprehensive analysis of mediators critically involved in acute cutaneous wound healing. Our findings suggest therapeutic approaches for the management of wound closure by targeting the chemokine network

Recommendations for a step-wise comparative approach to the evaluation of new screening tests for colorectal cancer

BACKGROUND: New screening tests for colorectal cancer continue to emerge, but the evidence needed to justify their adoption in screening programs remains uncertain.METHODS: A review of the literature and a consensus approach by experts was undertaken to provide practical guidance on how to compare new screening tests with proven screening tests.RESULTS: Findings and recommendations from the review included the following: Adoption of a new screening test requires evidence of effectiveness relative to a proven comparator test. Clinical accuracy supported by programmatic population evaluation in the screening context on an intention-to-screen basis, including acceptability, is essential. Cancer-specific mortality is not essential as an endpoint provided that the mortality benefit of the comparator has been demonstrated and that the biologic basis of detection is similar. Effectiveness of the guaiac-based fecal occult blood test provides the minimum standard to be achieved by a new test. A 4-phase evaluation is recommended. An initial retrospective evaluation in cancer cases and controls (Phase 1) is followed by a prospective evaluation of performance across the continuum of neoplastic lesions (Phase 2). Phase 3 follows the demonstration of adequate accuracy in these 2 prescreening phases and addresses programmatic outcomes at 1 screening round on an intention-to-screen basis. Phase 4 involves more comprehensive evaluation of ongoing screening over multiple rounds. Key information is provided from the following parameters: the test positivity rate in a screening population, the true-positive and false-positive rates, and the number needed to colonoscope to detect a target lesion.CONCLUSIONS: New screening tests can be evaluated efficiently by this stepwise comparative approach. Cancer 2016;122:826-39. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.</p

Skeletal carbonate mineralogy of Scottish bryozoans

This paper describes the skeletal carbonate mineralogy of 156 bryozoan species collected from Scotland (sourced both from museum collections and from waters around Scotland) and collated from literature. This collection represents 79% of the species which inhabit Scottish waters and is a greater number and proportion of extant species than any previous regional study. The study is also of significance globally where the data augment the growing database of mineralogical analyses and offers first analyses for 26 genera and four families. Specimens were collated through a combination of field sampling and existing collections and were analysed by X-ray diffraction (XRD) and micro-XRD to determine wt% MgCO3 in calcite and wt% aragonite. Species distribution data and phylogenetic organisation were applied to understand distributional, taxonomic and phylo-mineralogical patterns. Analysis of the skeletal composition of Scottish bryozoans shows that the group is statistically different from neighbouring Arctic fauna but features a range of mineralogy comparable to other temperate regions. As has been previously reported, cyclostomes feature low Mg in calcite and very little aragonite, whereas cheilostomes show much more variability, including bimineralic species. Scotland is a highly variable region, open to biological and environmental influx from all directions, and bryozoans exhibit this in the wide range of within-species mineralogical variability they present. This plasticity in skeletal composition may be driven by a combination of environmentally-induced phenotypic variation, or physiological factors. A flexible response to environment, as manifested in a wide range of skeletal mineralogy within a species, may be one characteristic of successful invasive bryozoans

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707