We report on ν(e) and ν(e) appearance in ν(μ) and ν(μ) beams using the full MINOS data sample. The comparison of these ν(e) and ν(e) appearance data at a 735 km baseline with θ13 measurements by ...reactor experiments probes δ, the θ23 octant degeneracy, and the mass hierarchy. This analysis is the first use of this technique and includes the first accelerator long-baseline search for ν(μ) → ν(e). Our data disfavor 31% (5%) of the three-parameter space defined by δ, the octant of the θ23, and the mass hierarchy at the 68% (90%) C.L. We measure a value of 2sin(2)(2θ13)sin(2)(θ23) that is consistent with reactor experiments.
Inconsistent findings between laboratories are hampering scientific progress and are of increasing public concern. Differences in laboratory environment is a known factor contributing to poor ...reproducibility of findings between research sites, and well-controlled multisite efforts are an important next step to identify the relevant factors needed to reduce variation in study outcome between laboratories. Through harmonization of apparatus, test protocol, and aligned and non-aligned environmental variables, the present study shows that behavioral pharmacological responses in Shank2 knockout (KO) rats, a model of synaptic dysfunction relevant to autism spectrum disorders, were highly replicable across three research centers. All three sites reliably observed a hyperactive and repetitive behavioral phenotype in KO rats compared to their wild-type littermates as well as a dose-dependent phenotype attenuation following acute injections of a selective mGluR1 antagonist. These results show that reproducibility in preclinical studies can be obtained and emphasizes the need for high quality and rigorous methodologies in scientific research. Considering the observed external validity, the present study also suggests mGluR1 as potential target for the treatment of autism spectrum disorders.
The effect of branching on the chain dynamics of model branched polyethylene was studied by solid state 2H and 13C NMR. Methyl branched polyethylene models with branches at every 15th (PE15) and 21st ...(PE21) chain carbon were synthesized with deuterons placed either at the carbon alpha to the branching point or in the middle of the chain between branches. Line shape analysis of the temperature-dependent 2H spectra revealed that the distribution of motional amplitudes in the solid state is homogeneous along the crystalline chain but heterogeneous in the less constrained amorphous phase. The 13C and 2H longitudinal spin relaxation data obtained at different positions along the chain are explained in terms of the segmental dynamics as a function of branch incorporation into the crystals. A detailed analysis of the chain dynamics in the conformationally disordered phase exhibited in PE15 is also provided.
Objective
We aimed to investigate how the presence of fetal anomalies and different X chromosome variants influences Cell‐free DNA (cfDNA) screening results for monosomy X.
Methods
From a multicenter ...retrospective survey on 673 pregnancies with prenatally suspected or confirmed Turner syndrome, we analyzed the subgroup for which prenatal cfDNA screening and karyotype results were available. A cfDNA screening result was defined as true positive (TP) when confirmatory testing showed 45,X or an X‐chromosome variant.
Results
We had cfDNA results, karyotype, and phenotype data for 55 pregnancies. cfDNA results were high risk for monosomy X in 48/55, of which 23 were TP and 25 were false positive (FP). 32/48 high‐risk cfDNA cases did not show fetal anomalies. Of these, 7 were TP. All were X‐chromosome variants. All 16 fetuses with high‐risk cfDNA result and ultrasound anomalies were TP. Of fetuses with abnormalities, those with 45,X more often had fetal hydrops/cystic hygroma, whereas those with “variant” karyotypes had different anomalies.
Conclusion
Both, 45,X or X‐chromosome variants can be detected after a high‐risk cfDNA result for monosomy X. When there are fetal anomalies, the result is more likely a TP. In the absence of fetal anomalies, it is most often an FP or X‐chromosome variant.
Key points
What is already known about this topic?
Cell‐free DNA (cfDNA) screening can detect monosomy X and other X chromosome variants associated with a Turner syndrome phenotype, but performance is poorer than for trisomy 21.
Little is known about the performance of cfDNA screening for X chromosome abnormalities in the presence of fetal structural anomalies.
What does this study add?
A positive cfDNA screening result for monosomy X is more often confirmed when fetal anomalies are detected.
In the absence of fetal anomalies, a positive cfDNA screening result is more often a false positive or associated with mosaicism or other X‐chromosome variants.
Mirror syndrome is a rare and serious maternal condition associated with immune and non-immune fetal hydrops after 16 weeks of gestational age. Subjacent conditions associated with fetal hydrops may ...carry different risks for Mirror syndrome. Fetuses with Turner syndrome are frequently found to be hydropic on ultrasound. We designed a retrospective multicenter study to evaluate the risk for Mirror syndrome among pregnancies complicated with Turner syndrome and fetal hydrops. Data were extracted from a questionnaire sent to specialists in maternal fetal medicine in Germany. Out of 758 cases, 138 fulfilled our inclusion criteria and were included in the analysis. Of the included 138, 66 presented with persisting hydrops at or after 16 weeks. The frequency of placental hydrops/placentomegaly was rather low (8.1%). Of note, no Mirror syndrome was observed in our study cohort. We propose that the risk of this pregnancy complication varies according to the subjacent cause of fetal hydrops. In Turner syndrome, the risk for Mirror syndrome is lower than that reported in the literature. Our observations are relevant for clinical management and parental counseling.
Biomarkers, such as C-reactive protein CRP and procalcitonin PCT, are insufficiently sensitive or specific to stratify patients with sepsis. We investigate the prognostic value of pancreatic stone ...protein/regenerating protein (PSP/reg) concentration in patients with severe infections.
PSP/reg, CRP, PCT, tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL1-β), IL-6 and IL-8 were prospectively measured in cohort of patients ≥ 18 years of age with severe sepsis or septic shock within 24 hours of admission in a medico-surgical intensive care unit (ICU) of a community and referral university hospital, and the ability to predict in-hospital mortality was determined.
We evaluated 107 patients, 33 with severe sepsis and 74 with septic shock, with in-hospital mortality rates of 6% (2/33) and 25% (17/74), respectively. Plasma concentrations of PSP/reg (343.5 vs. 73.5 ng/ml, P < 0.001), PCT (39.3 vs. 12.0 ng/ml, P < 0.001), IL-8 (682 vs. 184 ng/ml, P < 0.001) and IL-6 (1955 vs. 544 pg/ml, P < 0.01) were significantly higher in patients with septic shock than with severe sepsis. Of note, median PSP/reg was 13.0 ng/ml (IQR: 4.8) in 20 severely burned patients without infection. The area under the ROC curve for PSP/reg (0.65 95% CI: 0.51 to 0.80) was higher than for CRP (0.44 0.29 to 0.60), PCT 0.46 0.29 to 0.61), IL-8 (0.61 0.43 to 0.77) or IL-6 (0.59 0.44 to 0.75) in predicting in-hospital mortality. In patients with septic shock, PSP/reg was the only biomarker associated with in-hospital mortality (P = 0.049). Risk of mortality increased continuously for each ascending quartile of PSP/reg.
Measurement of PSP/reg concentration within 24 hours of ICU admission may predict in-hospital mortality in patients with septic shock, identifying patients who may benefit most from tailored ICU management.
A previous study demonstrates that most of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Brazilian strains fell in three local clades that were introduced from Europe around late ...February 2020. Here we investigated in more detail the origin of the major and most widely disseminated SARS-CoV-2 Brazilian lineage B.1.1.33. We recovered 190 whole viral genomes collected from 13 Brazilian states from February 29 to April 31, 2020 and combined them with other B.1.1 genomes collected globally. Our genomic survey confirms that lineage B.1.1.33 is responsible for a variable fraction of the community viral transmissions in Brazilian states, ranging from 2% of all SARS-CoV-2 genomes from Pernambuco to 80% of those from Rio de Janeiro. We detected a moderate prevalence (5-18%) of lineage B.1.1.33 in some South American countries and a very low prevalence (<1%) in North America, Europe, and Oceania. Our study reveals that lineage B.1.1.33 evolved from an ancestral clade, here designated B.1.1.33-like, that carries one of the two B.1.1.33 synapomorphic mutations. The B.1.1.33-like lineage may have been introduced from Europe or arose in Brazil in early February 2020 and a few weeks later gave origin to the lineage B.1.1.33. These SARS-CoV-2 lineages probably circulated during February 2020 and reached all Brazilian regions and multiple countries around the world by mid-March, before the implementation of air travel restrictions in Brazil. Our phylodynamic analysis also indicates that public health interventions were partially effective to control the expansion of lineage B.1.1.33 in Rio de Janeiro because its median effective reproductive number (
) was drastically reduced by about 66% during March 2020, but failed to bring it to below one. Continuous genomic surveillance of lineage B.1.1.33 might provide valuable information about epidemic dynamics and the effectiveness of public health interventions in some Brazilian states.
Objective: To assess the diagnostic performance of lateral flow immunochromatographic assays (LFAs) of 4 different manufacturers to identify SARS-CoV-2 antibodies (IgM, IgG, or total), comparing them ...with the nucleic acid amplification test (NAAT) or the clinical defined test (definite or probable SARS-CoV-2 infection, respectively). Methods: One hundred nineteen serum samples were randomly selected by convenience and distributed in the following groups: (1) group with SARS-CoV-2 infection (n = 82; RT-qPCR positive definite, n = 70 and probable n = 12); (2) other diseases (n = 27; other viruses identified n = 8 and SARS of other etiologies n = 19); and (3) healthy control group (n = 10). LFAs of 4 manufacturers were compared: MedTest Coronavirus (COVID-19) IgG/IgM (MedLevensohn, Brazil); COVID-19 IgG/IgM ECO Test (Ecodiagnóstica, Brazil); Camtech COVID-19 IgM/IgG Rapid Test Kit (Camtech Diagnostics Pte Ltd, Singapore); and 1-Step COVID-19 Test for total antibodies (Guangzhou Wondfo Biotech Co., China). Results: The 4 tests studied showed high diagnostic performance characteristics for the diagnoses of definite or probable SARS-CoV-2 infection. The best measures were for the Wondfo test: sensitivity (86.59%; 95% CI: 77.26–93.11%), specificity (100%; 90.51–100%), DOR (257; 60–1,008), LR+ (33.43; 4.82–231.85), LR− (0.13; 0.08–0.23), accuracy (90.76%; 84.06–95.29%), and Matthews correlation coefficient (MCC) 0.82. Although considering only the probable SARS-CoV-2 infection (PCR−) cases, all the kits studied showed limited values. Conclusion: Our data demonstrate the excellent performance of LFA for the diagnoses of definite or probable SARS-CoV-2 infection. There was substantial heterogeneity in sensitivities of IgM and IgG antibodies among the different kits. LFA tests cannot replace molecular diagnostics but should be used as an additional screening tool.
Ventilator-associated pneumonia (VAP) is the most common hospital-acquired, life-threatening infection. Poor outcome and health-care costs of nosocomial pneumonia remain a global burden. Currently, ...physicians rely on their experience to discriminate patients with good and poor outcome. However, standardized prognostic measures might guide medical decisions in the future. Pancreatic stone protein (PSP)/regenerating protein (reg) is associated with inflammation, infection, and other disease-related stimuli. The prognostic value of PSP/reg among critically ill patients is unknown. The aim of this pilot study was to evaluate PSP/reg in VAP.
One hundred one patients with clinically diagnosed VAP were assessed. PSP/reg was retrospectively analyzed using deep-frozen serum samples from VAP onset up to day 7. The main end point was death within 28 days after VAP onset.
Serum PSP/reg was associated with the sequential organ failure assessment score from VAP onset (Spearman rank correlation coefficient 0.49 P < .001) up to day 7. PSP/reg levels at VAP onset were elevated in nonsurvivors (n = 20) as compared with survivors (117.0 ng/mL 36.1-295.3 vs 36.3 ng/mL 21.0-124.0 P = .011). The areas under the receiver operating characteristic curves of PSP/reg to predict mortality/survival were 0.69 at VAP onset and 0.76 at day 7. Two PSP/reg cutoffs potentially allow for identification of individuals with a particularly good and poor outcome. Whereas PSP/reg levels below 24 ng/mL at VAP onset were associated with a good chance of survival, levels above 177 ng/mL at day 7 were present in patients with a very poor outcome.
Serum PSP/reg is a biomarker related to organ failure and outcome in patients with VAP.
ISRCTN.org; No.: ISRCTN61015974; URL: www.isrctn.org.
The junction dynamics in a selectively deuterated model polymer network containing junctions on every 21st chain carbon is studied by solid state 2H echo NMR. Polymer networks are prepared via ...acyclic triene metathesis of deuteron‐labeled symmetric trienes with deuteron probes precisely placed at the alpha carbon relative to the junction point. The effect of decreasing the cross‐link density on the junction dynamics is studied by introduction of polybutadiene chains in‐between junctions. The networks are characterized by swelling, gel content, and solid state 1H MAS NMR. Line shape analysis of the 2H quadrupolar echo spectra reveals that the degree of motion anisotropy and the distribution of motion correlation times depend on the cross‐link density and structural heterogeneity of the polymer networks. A detailed model of the junction dynamics at different temperatures is proposed and explained in terms of the intermolecular cooperativity in densely‐packed systems.
The molecular dynamics of the junction points in polymer networks are studied by solid state 2H NMR. Model networks with deuterium probes placed at the network junctions are prepared via metathesis polycondensation. Simulation of the 2H NMR spectra reveals details of the local dynamics as a function of temperature and cross‐link density.
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