First cohomology groups for finite groups of Lie type in defining characteristic

Let G be a finite group of Lie type, defined over a field k of characteristic p > 0 . We find explicit bounds for the dimensions of the first cohomology groups for with coefficients in simple kG-modules. We proceed by bounding the number of composition factors of Weyl modules for simple algebraic groups independently of P and using this to deduce bounds for the 1-cohomology of simple algebraic groups. If γl denotes the (finite) maximum of the dimensions of the 1-cohomology groups over all Lie groups of rank l we find bounds for the growth rate of the sequence. {γl}We show that log γl is O(l3log l

Bounding the dimensions of rational cohomology groups

Let $k$ be an algebraically closed field of characteristic $p > 0$, and let $G$ be a simple simply-connected algebraic group over $k$ that is defined and split over the prime field $\mathbb{F}_p$. In this paper we investigate situations where the dimension of a rational cohomology group for $G$ can be bounded by a constant times the dimension of the coefficient module. We then demonstrate how our results can be applied to obtain effective bounds on the first cohomology of the symmetric group. We also show how, for finite Chevalley groups, our methods permit significant improvements over previous estimates for the dimensions of second cohomology groups.Comment: 13 page

Identification of potential organ donors after aneurysmal subarachnoid hemorrhage in a population-based neurointensive care in Eastern Finland

To analyze the organ donation action in population-based neurointensive care of acute aneurysmal subarachnoid hemorrhage (aSAH) and to seek factors that would improve the identification of potential organ donors (PODs) and increase the donor conversion rate (DCR) after aSAH. The Kuopio Intracranial Aneurysm Database, prospective since 1995, includes all aSAH patients admitted to the Kuopio University Hospital (KUH) from its defined Eastern Finnish catchment population. We analyzed 769 consecutive acute aSAH patients from 2005 to 2015, including their data from the Finnish Transplantation Unit and the national clinical registries. We analyzed PODs vs. actual donors among the 145 (19%) aSAH patients who died within 14 days of admission. Finland had implemented the national presumed consent (opt-out) within the study period in the end of 2010. We retrospectively identified 83 (57%) PODs while only 49 (34%) had become actual donors (total DCR 59%); the causes for non-donorship were 15/34 (44%) refusals of consent, 18/34 (53%) medical contraindications for donation, and 1/34 (3%) failure of recognition. In 2005-2010, there were 11 refusals by near relatives with DCR 52% (29/56) and only three in 2011-2015 with DCR 74% (20/27). Severe condition on admission (Hunt and Hess grade IV or V) independently associated with the eventual POD status. Nearly 20% of all aSAH patients acutely admitted to neurointensive care from a defined catchment population died within 14 days, almost half from cardiopulmonary causes at a median age of 69 years. Of all aSAH patients, 11% were considered as potential organ donors (PODs). Donor conversion rate (DCR) was increased from 52 to 74% after the national presumed consent (opt-out). Implicitly, DCR among aSAH patients could be increased by admitting them to the intensive care regardless of dismal prognosis for the survival, along a dedicated organ donation program for the catchment population.Peer reviewe

Posttraumatic epilepsy in intensive care unit-treated pediatric traumatic brain injury patients

publishedVersionPeer reviewe

Pharmacokinetics of a novel sublingual spray formulation of the antimalarial drug artemether in African children with malaria

The pharmacokinetics of sublingual artemether (ArTiMist) was investigated in 91 young African children with severe malaria or who could not tolerate oral antimalarial therapy. Each received 3.0 mg/kg of body weight of artemether at 0, 8, 24, 36, 48, and 60 h or until the initiation of oral treatment. Few blood samples were drawn postdose. Plasma artemether and dihydroartemisinin (DHA) levels were measured using liquid chromatography-mass spectrometry, and the data were analyzed using established population compartmental pharmacokinetic models. Parasite clearance was prompt (median parasite clearance time, 24 h), and there were no serious adverse events. Consistent with studies in healthy adults (S. Salman, D. Bendel, T. C. Lee, D. Templeton, and T. M. E. Davis, Antimicrob Agents Chemother 59:3197-3207, 2015, http://dx.doi.org/10.1128/AAC.05013-14), the absorption of sublingual artemether was biphasic, and multiple dosing was associated with the autoinduction of the metabolism of artemether to DHA (which itself has potent antimalarial activity). In contrast to studies using healthy volunteers, pharmacokinetic modeling indicated that the first absorption phase did not avoid first-pass metabolism, suggesting that the drug is transferred to the upper intestine through postdose fluid/food intake. Simulations using the present data and those from an earlier study in older Melanesian children with uncomplicated malaria treated with artemether-lumefantrine tablets suggested that the bioavailability of sublingual artemether was at least equivalent to that after conventional oral artemether-lumefantrine (median [interquartile range] areas under the concentration-time curve for artemether, 3,403 [2,471 to 4,771] versus 3,063 [2,358 to 4,514] μg·h/liter, respectively; and for DHA, 2,958 [2,146 to 4,278] versus 2,839 [1,812 to 3,488] μg·h/liter, respectively; P≥0.42). These findings suggest that sublingual artemether could be used as prereferral treatment for sick children before transfer for definitive management of severe or moderately severe malaria

Pharmacokinetics of a Novel Sublingual Spray Formulation of the Antimalarial Drug Artemether in Healthy Adults

The pharmacokinetics of sublingual artemether (ArTiMist) was investigated in two open-label studies. In study 1, 16 healthy males were randomized to each of four single-dose treatments administered in random order: (i) 15.0 mg of sublingual artemether (5 × 3.0 actuations), (ii) 30.0 mg of sublingual artemether (10 × 3.0 mg), (iii) 30.0 mg of sublingual artemether (5 × 6.0 mg), and (iv) 30.0 mg of artemether in tablet form. In study 2, 16 healthy males were randomized to eight 30.0-mg doses of sublingual artemether given over 5 days as either 10 3.0-mg or 5 6.0-mg actuations. Frequent blood samples were drawn postdose. Plasma artemether and dihydroartemisinin levels were measured using liquid chromatography-mass spectrometry. Population compartmental pharmacokinetic models were developed. In study 1, sublingual artemether absorption was biphasic, with both rate constants being greater than that of the artemether tablets (1.46 and 1.66 versus 0.43/h, respectively). Relative to the tablets, sublingual artemether had greater bioavailability (≥1.24), with the greatest relative bioavailability occurring in the 30.0-mg dose groups (≥1.58). In study 2, there was evidence that the first absorption phase accounted for between 32% and 69% of the total dose and avoided first-pass (FP) metabolism, with an increase in FP metabolism occurring in later versus earlier doses but with no difference in bioavailability between the dose actuations. Sublingual artemether is more rapidly and completely absorbed than are equivalent doses of artemether tablets in healthy adults. Its disposition appears to be complex, with two absorption phases, the first representing pregastrointestinal absorption, as well as dose-dependent bioavailability and autoinduction of metabolism with multiple dosing

In situ geological and geochemical study of an active hydrothermal site on the North Fiji basin ridge

International audienc

Ptch2/Gas1 and Ptch1/Boc differentially regulate Hedgehog signalling in murine primordial germ cell migration.

Gas1 and Boc/Cdon act as co-receptors in the vertebrate Hedgehog signalling pathway, but the nature of their interaction with the primary Ptch1/2 receptors remains unclear. Here we demonstrate, using primordial germ cell migration in mouse as a developmental model, that specific hetero-complexes of Ptch2/Gas1 and Ptch1/Boc mediate the process of Smo de-repression with different kinetics, through distinct modes of Hedgehog ligand reception. Moreover, Ptch2-mediated Hedgehog signalling induces the phosphorylation of Creb and Src proteins in parallel to Gli induction, identifying a previously unknown Ptch2-specific signal pathway. We propose that although Ptch1 and Ptch2 functionally overlap in the sequestration of Smo, the spatiotemporal expression of Boc and Gas1 may determine the outcome of Hedgehog signalling through compartmentalisation and modulation of Smo-downstream signalling. Our study identifies the existence of a divergent Hedgehog signal pathway mediated by Ptch2 and provides a mechanism for differential interpretation of Hedgehog signalling in the germ cell niche