Diagnosis of Guillain–Barré syndrome in children and validation of the Brighton criteria

To describe the key diagnostic features of pediatric Guillain–Barré syndrome (GBS) and validate the Brighton criteria. Retrospective cohort study of all children (<18 years) diagnosed with GBS between 1987 and 2013 at Sophia Children’s Hospital, Erasmus MC, Rotterdam. Clinical information was collected and the sensitivity of the Brighton criteria was calculated. 67 children (35 boys) were included, with a median age of 5.0 years [interquartile range (IQR) 3.0–10.0 years]. Bilateral limb weakness was present at hospital admission in 93% of children, and at nadir in all patients. Children presented with tetraparesis in 70% or with paraparesis in 23%. Reduced reflexes in paretic limbs were observed at hospital admission in 82% and during follow-up in all children. The progressive phase lasted median 6 days (IQR 3–8 days) and less than 4 weeks in all children. A monophasic disease course was seen in 97%, including 5 children with a treatment-related fluctuation. Two children had a later relapse at 9 weeks and 19 weeks after onset. 77% of the children showed an elevated protein level in CSF. Nerve conduction studies showed evidence for a poly(radiculo)neuropathy in 91% of the children. 46 children had a complete data set, the sensitivity of the Brighton criteria level 1 was 72% (95% CI 57–84) and 96% (95% CI 85–99) for level 2 and 98% (95% CI 88–100) for level 3. The majority of the pediatric GBS patients presented in this cohort fulfilled the current diagnostic criteria

The soft supersymmetry breaking in D=5 supergravity compactified on S_1/Z_2 orbifolds

We study the origin of the supersymmetry breaking induced by the mediation of gravity and the radion multiplet from the hidden to the visible brane in the context of the N=2, D=5 supergravity compactified on S_1/Z_2 orbifolds. The soft supersymmetry breaking terms for scalar masses, trilinear scalar couplings and gaugino masses are calculated to leading order in the five dimensional Newton's constant k_5^2 and the gravitino mass m_{3/2}. These are finite and non-vanishing, with the scalar soft masses be non-tachyonic, and are all expressed in terms of the gravitino mass and the length scale R of the fifth dimension. The soft supersymmetry breaking parameters are thus correlated and the phenomenological implications are discussed.Comment: 16 pages, 3 figures, 1 Table, final version to appear in Physics Letters B, slightly shortened, comments added, typos correcte

The influence of single-nucleotide polymorphisms on overall survival and toxicity in cabazitaxel-treated patients with metastatic castration-resistant prostate cancer

Purpose: Cabazitaxel, used in patients with metastatic castration-resistant prostate cancer (mCRPC), is associated with adverse events which may require dose reductions or discontinuation of treatment. We investigated the potential association of single-nucleotide polymorphisms (SNPs) in genes encoding drug transporters and drug-metabolizing enzymes with cabazitaxel toxicity, overall survival (OS) and pharmacokinetics (PK). Methods: A total of 128 cabazitaxel-treated mCRPC patients, of whom prospectively collected data on toxicity and OS were available and 24 mCRPC patients with available cabazitaxel PK measurements, were genotyped using genomic DNA obtained from EDTA blood. The SLCO1B1 (388A > G; *1B; rs2306283 and 521 T > C; *5; rs4149056 and haplotype SLCO1B1*15), SLCO1B3 (334 T > G; rs4149117), CYP3A4 (*22; rs35599367), CYP3A5 (*3; rs776746), ABCB1 (3435C > T; rs1045642), and TUBB1 (57 + 87A > C; rs463312) SNPs were tested for their association with clinical and PK parameters by univariate/multivariate logistic regression, log-rank test, or Kruskal–Wallis test. Results: The SLCO1B1*15 haplotype was significantly associated with a lower incidence of leukopenia and neutropenia (p = 0.020 and p = 0.028, respectively). Patients harboring a homozygous variant for SLCO1B1*1B experienced higher rate ≥ grade 3 (p = 0.042). None of the SNPs were associated with pharmacokinetics or OS. Conclusions: In this study, SLCO1B1 (SLCO1B1*15 and SLCO1B1*1B) was associated with cabazitaxel-induced adverse events in mCRPC patients. As the associations were opposite to previous studies in other drugs and contradicted an underlying pharmacokinetic rationale, these findings are likely to be false-positive and would ideally be validated with even larger (pharmacokinetic) cohorts

Highly sensitive and rapid determination of tacrolimus in peripheral blood mononuclear cells by liquid chromatography–tandem mass spectrometry

After solid organ transplantation, tacrolimus is given to prevent rejection. Therapeutic drug monitoring is used to reach target concentrations of tacrolimus in whole blood. Because the site of action of tacrolimus is the lymphocyte, and tacrolimus binds ~80% to erythrocytes, the intracellular tacrolimus concentration in lymphocytes is possibly more relevant. For this purpose, we aimed to develop, improve and validate a UPLC–MS/MS method to measure tacrolimus concentrations in isolated peripheral blood mononuclear cells (PBMCs). PBMCs were isolated using a Ficoll separation technique, followed by a washing step using red blood cell lysis. A cell suspension of 50 μL containing 1 million PBMCs was used in combination with MagSiMUS-TDMPREP. To each sample we added 30 μL lysis buffer, 20 μL reconstitution buffer containing 13C2H4-tacrolimus as internal standard, 40 μL MagSiMUS-TDMPREP Type I Particle Mix and 175 μL Organic Precipitation Reagent VI for methanol-based protein precipitation. A 10 μL aliquot of the supernatant was injected into the UPLC–MS/MS system. The method was validated, resulting in high sensitivity and specificity. The method was linear (r2 = 0.997) over the range 5.0–1250 pg/1 × 106 PBMCs. The inaccuracy was <5% and the imprecision was <15%. The washing steps following Ficoll isolation could be performed at either room temperature or on ice, with no effect of the temperature on the results. A method for the analysis of tacrolimus concentrations in PBMCs was developed and successfully validated. Further research will be performed to investigate the correlation between concentrations in PBMCs and clinical outcome

Reducing unnecessary vitamin testing in general practice: barriers and facilitators according to general practitioners and patients

OBJECTIVE: There has been an increase in testing of vitamins in patients in general practice, often based on irrational indications or for non-specific symptoms, causing increasing healthcare expenditures and medicalisation of patients. So far, there is little evidence of effective strategies to reduce this overtesting in general practice. Therefore, the aim of this qualitative study was to explore the barriers and facilitators for reducing the number of (unnecessary) vitamin D and B12 laboratory tests ordered. DESIGN AND SETTING: This qualitative study, based on a grounded theory design, used semistructured interviews among general practitioners (GPs) and patients from two primary care networks (147 GPs, 195 000 patients). These networks participated in the Reducing Vitamin Testing in Primary Care Practice (REVERT) study, a clustered randomized trial comparing two de-implementation strategies to reduce test ordering in primary care in the Netherlands. PARTICIPANTS: Twenty-one GPs, with a maximum of 1 GP per practice who took part in the REVERT study, and 22 patients (who were invited by their GP during vitamin-related consultations) were recruited, from which 20 GPs and 19 patients agreed to participate in this study. RESULTS: The most important factor hampering vitamin-test reduction programmes is the mismatch between patients and medical professionals regarding the presumed appropriate indications for testing for vitamin D and B12. In contrast, the most important facilitator for vitamin-test reduction may be updating GPs' knowledge about test indications and their awareness of their own testing behaviour. CONCLUSION: To achieve a sustainable reduction in vitamin testing, guidelines with clear and uniform recommendations on evidence-based indications for vitamin testing, combined with regular (individual) feedback on test-ordering behaviour, are needed. Moreover, the general public needs access to clear and reliable information on vitamin testing. Further research is required to measure the effect of these strategies on the number of vitamin test requests. TRIAL REGISTRATION NUMBER: WAG/mb/16/039555

Search for leptophobic Z ' bosons decaying into four-lepton final states in proton-proton collisions at root s=8 TeV

Peer reviewe

Search for black holes and other new phenomena in high-multiplicity final states in proton-proton collisions at root s=13 TeV

Peer reviewe

Searches for invisible decays of the Higgs boson in pp collisions at root S=7, 8, and 13 TeV

Peer reviewe

Search for high-mass diphoton resonances in proton-proton collisions at 13 TeV and combination with 8 TeV search

Peer reviewe

Search for heavy resonances decaying into a vector boson and a Higgs boson in final states with charged leptons, neutrinos, and b quarks

Peer reviewe