Efficacy and pharmacokinetics of intravenous paracetamol in the critically ill patient

Introduction: Paracetamol (PCM) is a drug with analgesic and antipyretic properties. Despite its frequent use, little is known about its efficacy and pharmacokinetics (PK) when intravenously administered in the critically ill patient. A previous study suggests that therapeutic concentrations are not always reached [1]. The primary aim of this open-label, multiple-dose study was to evaluate intravenous PCM therapy in critically ill, secondary aim was to study the PK of intravenous PCM. Methods: Ventilated patients needing PCM treatment according to our ICU protocol (1 g PCM intravenously four times daily) were eligible for inclusion. Excluded were those with severe liver failure and those treated with PCM on the time of admission to the ICU. Blood samples were collected at 0, 30, 60, 180 and 300 minutes after the first and, if possible, the fifth and 21st doses. A computerized model was used to estimate population PK. Results: Nineteen patients were included of which 13 were male, with a mean APACHE IV score of 94.8. No antipyretic effect could be measured in any of the patients. PK parameters have been calculated for all patients after the first PCM dose. The half-life was 2.2 hours, the volume of distribution was 1.03 l/kg, and the clearance was 0.33 l/kg/hour. Data from 15 patients could be analysed after the fifth dose and from five patients after the 21st dose. The PK of intravenous PCM in our population show a biphasic profile (Figure 1). One hour after the dose, the mean serum concentration level was below the therapeutic level. In 18 out of 19 patients serum concentration dropped below 5 mg/ml before the next dose, resulting in a lack of build-up of a suitable therapeutic level of PCM after multiple dosages. Conclusions: The recommended dose of 1 g intravenous PCM four times daily is not sufficient to achieve a therapeutic effect in critically ill patients. This can be explained by the low serum levels reached. These results warrant the development of an adequate dosing scheme for intravenous PCM followed by a large clinical trial studying the effects and safety of this regimen in critically ill patients

Helicobacter pylori infection is not correlated with subclinical thrombocytopenia: A cross-sectional study

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Measurement of (anti)deuteron and (anti)proton production in DIS at HERA

The first observation of (anti)deuterons in deep inelastic scattering at HERA has been made with the ZEUS detector at a centre-of-mass energy of 300--318 GeV using an integrated luminosity of 120 pb-1. The measurement was performed in the central rapidity region for transverse momentum per unit of mass in the range 0.3<p_T/M<0.7. The particle rates have been extracted and interpreted in terms of the coalescence model. The (anti)deuteron production yield is smaller than the (anti)proton yield by approximately three orders of magnitude, consistent with the world measurements.Comment: 26 pages, 9 figures, 5 tables, submitted to Nucl. Phys.

Deep inelastic inclusive and diffractive scattering at Q2Q^2 values from 25 to 320 GeV2^2 with the ZEUS forward plug calorimeter

Deep inelastic scattering and its diffractive component, $ep \to e^{\prime}\gamma^* p \to e^{\prime}XN$, have been studied at HERA with the ZEUS detector using an integrated luminosity of 52.4 pb$^{-1}$. The $M_X$ method has been used to extract the diffractive contribution. A wide range in the centre-of-mass energy $W$ (37 -- 245 GeV), photon virtuality $Q^2$ (20 -- 450 GeV$^2$) and mass $M_X$ (0.28 -- 35 GeV) is covered. The diffractive cross section for $2 < M_X < 15$ GeV rises strongly with $W$, the rise becoming steeper as $Q^2$ increases. The data are also presented in terms of the diffractive structure function, $F^{\rm D(3)}_2$, of the proton. For fixed $Q^2$ and fixed $M_X$, \xpom F^{\rm D(3)}_2 shows a strong rise as \xpom \to 0, where \xpom is the fraction of the proton momentum carried by the Pomeron. For Bjorken-$x < 1 \cdot 10^{-3}$, \xpom F^{\rm D(3)}_2 shows positive $\log Q^2$ scaling violations, while for $x \ge 5 \cdot 10^{-3}$ negative scaling violations are observed. The diffractive structure function is compatible with being leading twist. The data show that Regge factorisation is broken.Comment: 89 pages, 27 figure

Measurement of dijet photoproduction for events with a leading neutron at HERA

Differential cross sections for dijet photoproduction and this process in association with a leading neutron, e+ + p -> e+ + jet + jet + X (+ n), have been measured with the ZEUS detector at HERA using an integrated luminosity of 40 pb-1. The fraction of dijet events with a leading neutron was studied as a function of different jet and event variables. Single- and double-differential cross sections are presented as a function of the longitudinal fraction of the proton momentum carried by the leading neutron, xL, and of its transverse momentum squared, pT^2. The dijet data are compared to inclusive DIS and photoproduction results; they are all consistent with a simple pion-exchange model. The neutron yield as a function of xL was found to depend only on the fraction of the proton beam energy going into the forward region, independent of the hard process. No firm conclusion can be drawn on the presence of rescattering effects.Comment: 40 pages, 18 figure

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Advances in food mycology

XIV+37hlm.;c

40 GHz optical-millimetre wave generation with a dual polarisation distributed feedback fibre laser

Optical-millimetre wave generation in a dual polarisation mode distributed feedback fibre laser is demonstrated. by fabricating the laser in an elliptical core erbium doped fibre, the birefringence increases the frequency separation of the two polarisation modes, enabling a 40GHz heterodyne signal to be generated with a 3dB beat linewidth of 900Hz