We report the observation of a new structure in the Λb0π+π− spectrum using the full LHCb data set of pp collisions, corresponding to an integrated luminosity of 9 fb−1, collected at s=7, 8, and 13 ...TeV. A study of the structure suggests its interpretation as a superposition of two almost degenerate narrow states. The masses and widths of these states are measured to be mΛb(6146)0=6146.17±0.33±0.22±0.16 MeV,mΛb(6152)0=6152.51±0.26±0.22±0.16 MeV,ΓΛb(6146)0=2.9±1.3±0.3 MeV,ΓΛb(6152)0=2.1±0.8±0.3 MeV,with a mass splitting of Δm=6.34±0.32±0.02 MeV, where the first uncertainty is statistical, the second systematic. The third uncertainty for the mass measurements derives from the knowledge of the mass of the Λb0 baryon. The measured masses and widths of these new excited states suggest their possible interpretation as a doublet of Λb(1D)0 states.
We undertake a five solar-cycle (SC 19 - 23) ≈55-year (December 1954 to August 2009) study of the high latitude polarity inversion lines (PILs) using the recently digitized McIntosh Archive (McA) of ...solar synoptic (Carrington) maps. We looked at the evolution of the median solar latitudes of primary and secondary PILs, and of the polar coronal hole (CH) boundary for all 732 Carrington Rotations (CRs). We found hemispheric differences in the “Rush to the Poles” (RttP) where the polar CH gaps are often longer in the southern hemisphere (SH), and the secondary PIL reaches its polemost latitude at the end of its RttP later and more poleward than in the northern hemisphere (NH). The latitude oscillations found after this poleward peak are also stronger and often longer in the SH than in the NH, and exhibit a 22-year variation. The location variations in the CH boundaries and PILs appear to be at least partly associated with similar variations in the magnetic field. We also found equatorward expansions of the polar CHs by ≈50% and equatorward shifts in the PILs that were part of a disturbance that propagated ≈15°/CR from the SH to the NH in the descending phase of SC 23.
The provision of sufficient basal insulin to normalize fasting plasma glucose levels may reduce cardiovascular events, but such a possibility has not been formally tested.
We randomly assigned 12,537 ...people (mean age, 63.5 years) with cardiovascular risk factors plus impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes to receive insulin glargine (with a target fasting blood glucose level of ≤95 mg per deciliter 5.3 mmol per liter) or standard care and to receive n-3 fatty acids or placebo with the use of a 2-by-2 factorial design. The results of the comparison between insulin glargine and standard care are reported here. The coprimary outcomes were nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes and these events plus revascularization or hospitalization for heart failure. Microvascular outcomes, incident diabetes, hypoglycemia, weight, and cancers were also compared between groups.
The median follow-up was 6.2 years (interquartile range, 5.8 to 6.7). Rates of incident cardiovascular outcomes were similar in the insulin-glargine and standard-care groups: 2.94 and 2.85 per 100 person-years, respectively, for the first coprimary outcome (hazard ratio, 1.02; 95% confidence interval CI, 0.94 to 1.11; P=0.63) and 5.52 and 5.28 per 100 person-years, respectively, for the second coprimary outcome (hazard ratio, 1.04; 95% CI, 0.97 to 1.11; P=0.27). New diabetes was diagnosed approximately 3 months after therapy was stopped among 30% versus 35% of 1456 participants without baseline diabetes (odds ratio, 0.80; 95% CI, 0.64 to 1.00; P=0.05). Rates of severe hypoglycemia were 1.00 versus 0.31 per 100 person-years. Median weight increased by 1.6 kg in the insulin-glargine group and fell by 0.5 kg in the standard-care group. There was no significant difference in cancers (hazard ratio, 1.00; 95% CI, 0.88 to 1.13; P=0.97).
When used to target normal fasting plasma glucose levels for more than 6 years, insulin glargine had a neutral effect on cardiovascular outcomes and cancers. Although it reduced new-onset diabetes, insulin glargine also increased hypoglycemia and modestly increased weight. (Funded by Sanofi; ORIGIN ClinicalTrials.gov number, NCT00069784.).
A high peak brilliance, laser-based Compton-scattering γ -ray source, capable of producing quasimonoenergetic photons with energies ranging from 0.1 to 0.9 MeV has been recently developed and used to ...perform nuclear resonance fluorescence (NRF) experiments. Techniques for characterization of γ -ray beam parameters are presented. The key source parameters are the size (0.01mm2 ), horizontal and vertical divergence (6×10mrad2 ), duration (16 ps), and spectrum and intensity (105photons/shot ). These parameters are summarized by the peak brilliance, 1.5×1015photons/mm2/mrad2/s/0.1% bandwidth, measured at 478 keV. Additional measurements of the flux as a function of the timing difference between the drive laser pulse and the relativistic photoelectron bunch, γ -ray beam profile, and background evaluations are presented. These results are systematically compared to theoretical models and computer simulations. NRF measurements performed on Li7 in LiH demonstrate the potential of Compton-scattering photon sources to accurately detect isotopes in situ.
Background and Objective
Periodontal disease is a highly complex chronic inflammatory disease of the oral cavity. Multiple factors influence periodontal disease, including socio‐economic status, ...genetics and age; however, inflammation elicited by the presence of specific bacteria in the subgingival space is thought to drive the majority of soft‐ and hard‐tissue destruction. Porphyromonas gingivalis is closely associated with periodontal disease. Toll‐like receptors (TLRs) and their intracellular signaling pathways play roles in the host response to P. gingivalis. The focus of the current study was to use microarray analysis to define the contributions of the TLR adaptor molecules myeloid differentiation factor 88 (MyD88) and Toll/interleukin‐1 receptor domain‐containing adaptor inducing interferon‐beta (TRIF), and aging, on the expression of TLR pathway‐associated mRNAs in response to P. gingivalis.
Material and Methods
Bone marrow‐derived macrophages (BMØ) from wild‐type (Wt), MyD88 knockout (MyD88‐KO) and TrifLps2 i.e. containing a point mutation in the lipopolysaccharide 2 (Lps2) gene rendering the Toll/interleukin (IL)‐1 receptor domain‐containing adaptor inducing interferon‐beta (TRIF) protein nonfunctional mice, at 2‐and 12‐mo of age, were cultured with P. gingivalis. Expression of genes in BMØ cultured with P. gingivalis was determined in comparison with expression of genes in BMØ cultured in medium only.
Results
Using, as criteria, a twofold increase or decrease in mRNA expression, differential expression of 32 genes was observed when Wt BMØ from 2‐mo‐old mice were cultured with P. gingivalis compared with the medium‐only control. When compared with 2‐mo‐old Wt mice, 21 and 12 genes were differentially expressed (p < 0.05) as a result of the mutations in MyD88 or TRIF, respectively. The expression of five genes was significantly (p < 0.05) reduced in Wt BMØ from 12‐mo‐old mice compared with those from 2‐mo‐old mice following culture with P. gingivalis. Age also influenced the expression of genes in MyD88‐KO and TrifLps2 mice challenged with P. gingivalis.
Conclusions
Our results indicate that P. gingivalis induces differential expression of TLR pathway‐associated genes, and both MyD88 and TRIF play roles in the expression of these genes. Age also played a role in the expression of TLR‐associated genes following stimulation of BMØ with P. gingivalis.
We performed systematic reviews using the population, intervention, comparison, outcome (PICO) format to answer the following key clinical question: Are the CHEST 2006 classifications of acute, ...subacute and chronic cough and associated management algorithms in adults that were based on durations of cough useful?
We used the CHEST Expert Cough Panel's protocol for the systematic reviews and the American College of Chest Physicians (CHEST) methodological guidelines and Grading of Recommendations Assessment, Development, and Evaluation framework. Data from the systematic reviews in conjunction with patient values and preferences and the clinical context were used to form recommendations or suggestions. Delphi methodology was used to obtain the final grading.
With respect to acute cough (< 3 weeks), only three studies met our criteria for quality assessment, and all had a high risk of bias. As predicted by the 2006 CHEST Cough Guidelines, the most common causes were respiratory infections, most likely of viral cause, followed by exacerbations of underlying diseases such as asthma and COPD and pneumonia. The subjects resided on three continents: North America, Europe, and Asia. With respect to subacute cough (duration, 3-8 weeks), only two studies met our criteria for quality assessment, and both had a high risk of bias. As predicted by the 2006 guidelines, the most common causes were postinfectious cough and exacerbation of underlying diseases such as asthma, COPD, and upper airway cough syndrome (UACS). The subjects resided in countries in Asia. With respect to chronic cough (> 8 weeks), 11 studies met our criteria for quality assessment, and all had a high risk of bias. As predicted by the 2006 guidelines, the most common causes were UACS from rhinosinus conditions, asthma, gastroesophageal reflux disease, nonasthmatic eosinophilic bronchitis, combinations of these four conditions, and, less commonly, a variety of miscellaneous conditions and atopic cough in Asian countries. The subjects resided on four continents: North America, South America, Europe, and Asia.
Although the quality of evidence was low, the published literature since 2006 suggests that CHEST's 2006 Cough Guidelines and management algorithms for acute, subacute, and chronic cough in adults appeared useful in diagnosing and treating patients with cough around the globe. These same algorithms have been updated to reflect the advances in cough management as of 2017.
We study the eccentricity distribution of a thick-disc sample of stars (defined as those with Vy
> 50 km s−1 and 1 < |z|/kpc < 3) observed in the Radial Velocity Experiment (RAVE). We compare this ...distribution with those obtained in four simulations of galaxy formation taken from the literature as compiled by Sales et al. Each simulation emphasizes different scenarios for the origin of such stars (satellite accretion, heating of a pre-existing thin disc during a merger, radial migration, and gas-rich mergers). We find that the observed distribution peaks at low eccentricities and falls off smoothly and rather steeply to high eccentricities. This finding is fairly robust to changes in distances and to plausible assumptions about thin-disc contamination. Our results favour models where the majority of stars formed in the Galaxy itself on orbits of modest eccentricity and disfavour the pure satellite accretion case. A gas-rich merger origin where most of the stars form 'in situ' appears to be the most consistent with our data.
The quantum numbers of the X(3872) meson are determined to be J(PC)=1(++) based on angular correlations in B(+)→X(3872)K(+) decays, where X(3872)→π(+)π(-)J/ψ and J/ψ→μ(+)μ(-). The data correspond to ...1.0 fb(-1) of pp collisions collected by the LHCb detector. The only alternative assignment allowed by previous measurements J(PC)=2(-+) is rejected with a confidence level equivalent to more than 8 Gaussian standard deviations using a likelihood-ratio test in the full angular phase space. This result favors exotic explanations of the X(3872) state.
Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding ...variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
In phase I development, CDX-3379, an anti-ErbB3 monoclonal antibody, showed promising molecular and antitumor activity in head and neck squamous cell carcinoma (HNSCC), alone or in combination with ...cetuximab. Preliminary biomarker data raised the hypothesis of enhanced response in tumors harboring
mutations. This phase II, multicenter trial used a Simon 2-stage design to investigate the efficacy of CDX-3379 and cetuximab in 30 patients with recurrent/metastatic, HPV-negative, cetuximab-resistant HNSCC. The primary endpoint was objective response rate (ORR). Secondary endpoints included ORR in patients with somatic
mutations, progression-free survival (PFS), overall survival (OS), and safety. Thirty patients were enrolled from March 2018 to September 2020. The ORR in genomically unselected patients was 2/30 (6.7%; 95% confidence interval CI, 0.8-22.1). Median PFS and OS were 2.2 (95% CI: 1.3-3.6) and 6.6 months (95% CI: 2.7-7.5), respectively. Tissue was available in 27 patients including one of two responders. ORR was 1/10 (complete response; 10%; 95% CI 0.30-44.5) in the
-mutated versus 0/17 (0%; 95% CI: 0-19.5) in the
-wildtype cohorts. Sixteen patients (53%) experienced treatment-related adverse events (AEs) ≥ grade 3. The most common AEs were diarrhea (83%) and acneiform dermatitis (53%). Dose modification was required in 21 patients (70%). The modest ORR coupled with excessive, dose-limiting toxicity of this combination precludes further clinical development. Dual ErbB3-EGFR inhibition remains of scientific interest in HPV-negative HNSCC. Should more tolerable combinations be identified, development in an earlier line of therapy and prospective evaluation of the
hypothesis warrant consideration.
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