Germline heterozygous DDX41 variants in a subset of familial myelodysplasia and acute myeloid leukemia

The Brazilian National Council for Scientific and Technological Development), Bloodwise, Children with Cancer and MRC (Medical Research Council, UK)

Cosmic rays and molecular clouds

This paper deals with the cosmic-ray penetration into molecular clouds and with the related gamma--ray emission. High energy cosmic rays interact with the dense gas and produce neutral pions which in turn decay into two gamma rays. This makes molecular clouds potential sources of gamma rays, especially if they are located in the vicinity of a powerful accelerator that injects cosmic rays in the interstellar medium. The amplitude and duration in time of the cosmic--ray overdensity around a given source depend on how quickly cosmic rays diffuse in the turbulent galactic magnetic field. For these reasons, gamma-ray observations of molecular clouds can be used both to locate the sources of cosmic rays and to constrain the properties of cosmic-ray diffusion in the Galaxy.Comment: To appear in the proceedings of the San Cugat Forum on Astrophysics 2012, 27 pages, 10 figure

Molecular subgroups of medulloblastoma: the current consensus

Medulloblastoma, a small blue cell malignancy of the cerebellum, is a major cause of morbidity and mortality in pediatric oncology. Current mechanisms for clinical prognostication and stratification include clinical factors (age, presence of metastases, and extent of resection) as well as histological subgrouping (classic, desmoplastic, and large cell/anaplastic histology). Transcriptional profiling studies of medulloblastoma cohorts from several research groups around the globe have suggested the existence of multiple distinct molecular subgroups that differ in their demographics, transcriptomes, somatic genetic events, and clinical outcomes. Variations in the number, composition, and nature of the subgroups between studies brought about a consensus conference in Boston in the fall of 2010. Discussants at the conference came to a consensus that the evidence supported the existence of four main subgroups of medulloblastoma (Wnt, Shh, Group 3, and Group 4). Participants outlined the demographic, transcriptional, genetic, and clinical differences between the four subgroups. While it is anticipated that the molecular classification of medulloblastoma will continue to evolve and diversify in the future as larger cohorts are studied at greater depth, herein we outline the current consensus nomenclature, and the differences between the medulloblastoma subgroups

Fusion of RVG or gh625 to iduronate-2-sulfatase for the treatment of mucopolysaccharidosis type II

Mucopolysaccharidosis type II (MPSII) is a lysosomal storage disease caused by a mutation in the IDS gene, resulting in deficiency of the enzyme iduronate-2-sulfatase (IDS) causing heparan sulfate (HS) and dermatan sulfate (DS) accumulation in all cells. This leads to skeletal and cardiorespiratory disease with severe neurodegeneration in two thirds of sufferers. Enzyme replacement therapy is ineffective at treating neurological disease, as intravenously-delivered IDS is unable to cross the blood-brain barrier (BBB). Haematopoietic stem cell transplant is also unsuccessful, presumably due to insufficient IDS enzyme production from transplanted cells engrafting in the brain. We used two different peptide sequences (RVG and gh625), both previously published as BBB-crossing peptides, fused to IDS and delivered via haematopoietic stem cell gene therapy (HSCGT). HSCGT with LV.IDS.RVG and LV.IDS.gh625 was compared to LV.IDS.ApoEII and LV.IDS in MPSII mice at 6-months post-transplant. Levels of IDS enzyme activity in the brain and peripheral tissues were lower in LV.IDS.RVG and LV.IDS.gh625 treated mice than in LV.IDS.ApoEII and LV.IDS treated mice, despite comparable vector copy numbers. Microgliosis, astrocytosis and lysosomal swelling were partially normalised in MPSII mice treated with LV.IDS.RVG and LV.IDS.gh625. Skeletal thickening was normalised by both treatments to wild-type levels. Although reductions in skeletal abnormalities and neuropathology are encouraging, given the low levels of enzyme activity compared to control tissue from LV.IDS and LV.IDS.ApoEII transplanted mice, the RVG and gh625 peptides are unlikely to be ideal candidates for HSCGT in MPSII, and are inferior to the ApoEII peptide that we have previously demonstrated to be more effective at correcting MPSII disease than IDS alone

Bruxism and psychotropic medications

This is an accepted manuscript of an article published by Wiley in Progress in Neurology and Psychiatry on 13/02/2020, available online: https://wchh.onlinelibrary.wiley.com/doi/10.1002/pnp.560 The accepted version of the publication may differ from the final published version.Mental Health Disorders including schizophrenia, bipolar and schizoaffective disorders are often treated using psychotropic medications with evidence that some of these medications such as antipsychotics could be associated with significant oral side-effects. In this comprehensive review, we examine the psychotropic medications mechanisms of action and their oral side-effects, with specific focus on psychotropic medications and bruxism as a major oral health complication with a negative impact on the quality of life of mental health sufferers, relevant to psychiatrists, dentists and general practitioners. Bruxism could be caused by the antipsychotics extrapyramidal side-effects through dopaminergic receptors. Bruxism as a side-effect of psychotropic medications could result in significant consequences to oral health such as tooth structure destruction and irreversible harm to the temporomandibular joint. The review findings could assist in understanding the aetiology of bruxism, establish appropriate management plan, while supporting psychiatrists and dentists to detect temporomandibular dysfunctions (TMD) such as bruxism

Limits on WWZ and WW\gamma couplings from p\bar{p}\to e\nu jj X events at \sqrt{s} = 1.8 TeV

We present limits on anomalous WWZ and WW-gamma couplings from a search for WW and WZ production in p-bar p collisions at sqrt(s)=1.8 TeV. We use p-bar p -> e-nu jjX events recorded with the D0 detector at the Fermilab Tevatron Collider during the 1992-1995 run. The data sample corresponds to an integrated luminosity of 96.0+-5.1 pb^(-1). Assuming identical WWZ and WW-gamma coupling parameters, the 95% CL limits on the CP-conserving couplings are -0.33<lambda<0.36 (Delta-kappa=0) and -0.43<Delta-kappa<0.59 (lambda=0), for a form factor scale Lambda = 2.0 TeV. Limits based on other assumptions are also presented.Comment: 11 pages, 2 figures, 2 table

Search for New Physics in e mu X Data at D0 Using Sleuth: A Quasi-Model-Independent Search Strategy for New Physics

We present a quasi-model-independent search for the physics responsible for electroweak symmetry breaking. We define final states to be studied, and construct a rule that identifies a set of relevant variables for any particular final state. A new algorithm ("Sleuth") searches for regions of excess in those variables and quantifies the significance of any detected excess. After demonstrating the sensitivity of the method, we apply it to the semi-inclusive channel e mu X collected in 108 pb^-1 of ppbar collisions at sqrt(s) = 1.8 TeV at the D0 experiment during 1992-1996 at the Fermilab Tevatron. We find no evidence of new high p_T physics in this sample.Comment: 23 pages, 12 figures. Submitted to Physical Review

Search For Heavy Pointlike Dirac Monopoles

We have searched for central production of a pair of photons with high transverse energies in $p\bar p$ collisions at $\sqrt{s} = 1.8$ TeV using $70 pb^{-1}$ of data collected with the D\O detector at the Fermilab Tevatron in 1994--1996. If they exist, virtual heavy pointlike Dirac monopoles could rescatter pairs of nearly real photons into this final state via a box diagram. We observe no excess of events above background, and set lower 95% C.L. limits of $610, 870, or 1580 GeV/c^2$ on the mass of a spin 0, 1/2, or 1 Dirac monopole.Comment: 12 pages, 4 figure

The Dijet Mass Spectrum and a Search for Quark Compositeness in bar{p}p Collisions at sqrt{s} = 1.8 TeV

Using the DZero detector at the 1.8 TeV pbarp Fermilab Tevatron collider, we have measured the inclusive dijet mass spectrum in the central pseudorapidity region |eta_jet| < 1.0 for dijet masses greater than 200 Gev/c^2. We have also measured the ratio of spectra sigma(|eta_jet| < 0.5)/sigma(0.5 < |eta_jet| < 1.0). The order alpha_s^3 QCD predictions are in good agreement with the data and we rule out models of quark compositeness with a contact interaction scale < 2.4 TeV at the 95% confidence level.Comment: 11 pages, 4 figures, 2 tables, submitted to Phys. Rev. Let

Search for High Mass Photon Pairs in p-pbar --> gamma-gamma-jet-jet Events at sqrt(s)=1.8 TeV

A search has been carried out for events in the channel p-barp --> gamma gamma jet jet. Such a signature can characterize the production of a non-standard Higgs boson together with a W or Z boson. We refer to this non-standard Higgs, having standard model couplings to vector bosons but no coupling to fermions, as a "bosonic Higgs." With the requirement of two high transverse energy photons and two jets, the diphoton mass (m(gamma gamma)) distribution is consistent with expected background. A 90(95)% C.L. upper limit on the cross section as a function of mass is calculated, ranging from 0.60(0.80) pb for m(gamma gamma) = 65 GeV/c^2 to 0.26(0.34) pb for m(gamma gamma) = 150 GeV/c^2, corresponding to a 95% C.L. lower limit on the mass of a bosonic Higgs of 78.5 GeV/c^2.Comment: 9 pages, 3 figures. Replacement has new H->gamma gamma branching ratios and corresponding new mass limit