86 research outputs found
Calculating the energy spectra of magnetic molecules: application of real- and spin-space symmetries
The determination of the energy spectra of small spin systems as for instance
given by magnetic molecules is a demanding numerical problem. In this work we
review numerical approaches to diagonalize the Heisenberg Hamiltonian that
employ symmetries; in particular we focus on the spin-rotational symmetry SU(2)
in combination with point-group symmetries. With these methods one is able to
block-diagonalize the Hamiltonian and thus to treat spin systems of
unprecedented size. In addition it provides a spectroscopic labeling by
irreducible representations that is helpful when interpreting transitions
induced by Electron Paramagnetic Resonance (EPR), Nuclear Magnetic Resonance
(NMR) or Inelastic Neutron Scattering (INS). It is our aim to provide the
reader with detailed knowledge on how to set up such a diagonalization scheme.Comment: 29 pages, many figure
Neutralization of the Plasmodium-encoded MIF ortholog confers protective immunity against malaria infection
Plasmodium species produce an ortholog of the cytokine macrophage migration inhibitory factor, PMIF, which modulates the host inflammatory response to malaria. Using a novel RNA replicon-based vaccine, we show the impact of PMIF immunoneutralization on the host response and observed improved control of liver and blood-stage Plasmodium infection, and complete protection from re-infection. Vaccination against PMIF delayed blood-stage patency after sporozoite infection, reduced the expression of the Th1-associated inflammatory markers TNF-alpha, IL-12, and IFN-gamma during blood-stage infection, augmented Tfh cell and germinal center responses, increased anti-Plasmodium antibody titers, and enhanced the differentiation of antigen-experienced memory CD4 T cells and liver-resident CD8 T cells. Protection from re-infection was recapitulated by the adoptive transfer of CD8 or CD4 T cells from PMIF RNA immunized hosts. Parasite MIF inhibition may be a useful approach to promote immunity to Plasmodium and potentially other parasite genera that produce MIF orthologous proteins
Biomarkers in Natural Fish Populations Indicate Adverse Biological Effects of Offshore Oil Production
Despite the growing awareness of the necessity of a sustainable development, the global economy continues to depend largely on the consumption of non-renewable energy resources. One such energy resource is fossil oil extracted from the seabed at offshore oil platforms. This type of oil production causes continuous environmental pollution from drilling waste, discharge of large amounts of produced water, and accidental spills.Samples from natural populations of haddock (Melanogrammus aeglefinus) and Atlantic cod (Gadus morhua) in two North Sea areas with extensive oil production were investigated. Exposure to and uptake of polycyclic aromatic hydrocarbons (PAHs) were demonstrated, and biomarker analyses revealed adverse biological effects, including induction of biotransformation enzymes, oxidative stress, altered fatty acid composition, and genotoxicity. Genotoxicity was reflected by a hepatic DNA adduct pattern typical for exposure to a mixture of PAHs. Control material was collected from a North Sea area without oil production and from remote Icelandic waters. The difference between the two control areas indicates significant background pollution in the North Sea.It is most remarkable to obtain biomarker responses in natural fish populations in the open sea that are similar to the biomarker responses in fish from highly polluted areas close to a point source. Risk assessment of various threats to the marine fish populations in the North Sea, such as overfishing, global warming, and eutrophication, should also take into account the ecologically relevant impact of offshore oil production
Dative for Accusative Case Interchange in Epistolary Formulas in Greek Papyrus Letters
Efficacy of halopeRIdol to decrease the burden of Delirium In adult Critically ill patiEnts (EuRIDICE): study protocol for a prospective randomised multi-centre double-blind placebo-controlled clinical trial in the Netherlands
Introduction Delirium in critically ill adults is associated
with prolonged hospital stay, increased mortality and
greater cognitive and functional decline. Current practice
guideline recommendations advocate the use of nonpharmacological strategies to reduce delirium. The
routine use of scheduled haloperidol to treat delirium is
not recommended given a lack of evidence regarding its
ability to resolve delirium nor improve relevant short-term
and longer-term outcomes. This study aims to evaluate
the efficacy and safety of haloperidol for the treatment of
delirium in adult critically ill patients to reduce days spent
with coma or delirium.
Methods and analysis EuRIDICE is a prospective, multicentre, randomised, double-blind, placebo-controlled
trial. Study population consists of adult intensive care
unit (ICU) patients without acute neurological injury who
have delirium based on a positive Intensive Care Delirium
Screening Checklist (ICDSC) or Confusion Assessment
Method for the ICU (CAM-ICU) assessment. Intervention
is intravenous haloperidol 2.5mg (or matching placebo)
every 8 hours, titrated daily based on ICDSC or CAMICU positivity to a maximum of 5mg every 8 hours,
until delirium resolution or ICU discharge. Main study
endpoint is delirium and coma-free days (DCFD) up
to 14 days after randomisation. Secondary endpoints
include (1) 28-day and 1-year mortality, (2) cognitive and
functional performance at 3 and 12 months, (3) patient
and family delirium and ICU experience, (4) psychological
sequelae during and after ICU stay, (4) safety concerns
associated with haloperidol use and (5) cost-effectiveness.
Differences in DCFDs between haloperidol and placebo
group will be analysed using Poisson regression analysis.
Study recruitment started in February 2018 and continues.
Ethics and dissemination The study has been approved
by the Medical Ethics Committee of the Erasmus University
Medical Centre Rotterdam (MEC2017-511) and by the
Institutional Review Boards of the participating sites. Its
results will be disseminated via peer-reviewed publication
and conference presentations
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
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