One-step transformation of 2-oxa-3-azabicyclo[2.2.1]hept-5-ene and methyl 2,3-diazabicyclo[2.2.1]heptane-2-carboxylate to ion uptake systems

Linker generated duplexes of the title compounds- prepared from cyclopentadiene- with possibility for positioning of four oxygen in the cavity, are shown to be excellent ion uptake systems. Mass spectrometric doping studies with lithium, sodium, potassium and silver ions, show a clear preference for lithium complexation. The lithium salts of the best examples have been prepared and characterized

Serum Lipid Profile and Electrocardiographic Changes in Young Smokers

Smoking represents an important and rapidly growing global cause of cardiovascular mortality and morbidity.Cigarrette smoking is one of the major modifiable risk factors of cardiovascular disease, unless smokers are able to quit, approximately 40% of them will die prematurely.The need of the hour is timely intervention through smoking cessation.Our study was carried out in young smokers to demonstrate the effects of smoking on lipid profile and electrocardiographic changes. We aimed to study the effect of smoking on lipid profile and electrocardiographic changes in young smokers.The study design was a cross sectional study comprising 75 male smokers and 75 healthy controls.Smoking history and physical examination was done .Fasting sample was analysed for lipid profile and electrocardiograph of all subjects were recorded.The statistical anaylsis between mean values were evaluated by student‘t' test. Statistical significance was assessed by chi-square test, p<0.001 was considered to be significant.The mean pulse rate, the mean systolic blood pressure, abnormal lipid profile and prolonged Qt interval were significantly higher in smokers (p<0.001).We demonstrated significant lipid abnormalities and electrocardiographic changes in young smokers who form an important risk group and target population in whom smoking cessation counseling should be carried out to decrease long term cardiovascular risk

Early management of acute severe UC in the biologics era: development and international validation of a prognostic clinical index to predict steroid response

Objectives We aimed to determine whether changes in acute severe colitis (ASC) management have translated to improved outcomes and to develop a simple model predicting steroid non-response on admission. Design Outcomes of 131 adult ASC admissions (117 patients) in Oxford, UK between 2015 and 2019 were compared with data from 1992 to 1993. All patients received standard treatment with intravenous corticosteroids and endoscopic disease activity scoring (Ulcerative Colitis Endoscopic Index of Severity (UCEIS)). Steroid non-response was defined as receiving medical rescue therapy or surgery. A predictive model developed in the Oxford cohort was validated in Australia and India (Gold Coast University Hospital 2015–2020, n=110; All India Institute of Medical Sciences, New Delhi 2018–2020, n=62). Results In the 2015–2019 Oxford cohort, 15% required colectomy during admission vs 29% in 1992–1993 (p=0.033), while 71 (54%) patients received medical rescue therapy (27% ciclosporin, 27% anti-tumour necrosis factor, compared with 27% ciclosporin in 1992–1993 (p=0.0015). Admission C reactive protein (CRP) (false discovery rate, p=0.00066), albumin (0.0066) and UCEIS scores (0.015) predicted steroid non-response. A four-point model was developed involving CRP of ≥100 mg/L (one point), albumin of ≤25 g/L (one point), and UCEIS score of ≥4 (1 point) or ≥7 (2 points). Patients scoring 0, 1, 2, 3 and 4 in the validation cohorts had steroid response rates of 100, 75.0%, 54.9%, 18.2% and 0%, respectively. Scoring of ≥3 was 84% (95% CI 0.70 to 0.98) predictive of steroid failure (OR 11.9, 95% CI 10.8 to 13.0). Colectomy rates in the validation cohorts were were 8%–11%. Conclusions Emergency colectomy rates for ASC have halved in 25 years to 8%–15% worldwide. Patients who will not respond to corticosteroids are readily identified on admission and may be prioritised for early intensification of therapy

Nucleon-Gold Collisions at 200 AGeV Using Tagged d+Au Interactions in PHOBOS

Forward calorimetry in the PHOBOS detector has been used to study charged hadron production in d+Au, p+Au and n+Au collisions at sqrt(s_nn) = 200 GeV. The forward proton calorimeter detectors are described and a procedure for determining collision centrality with these detectors is detailed. The deposition of energy by deuteron spectator nucleons in the forward calorimeters is used to identify p+Au and n+Au collisions in the data. A weighted combination of the yield of p+Au and n+Au is constructed to build a reference for Au+Au collisions that better matches the isospin composition of the gold nucleus. The p_T and centrality dependence of the yield of this improved reference system is found to match that of d+Au. The shape of the charged particle transverse momentum distribution is observed to extrapolate smoothly from pbar+p to central d+Au as a function of the charged particle pseudorapidity density. The asymmetry of positively- and negatively-charged hadron production in p+Au is compared to that of n+Au. No significant asymmetry is observed at mid-rapidity. These studies augment recent results from experiments at the LHC and RHIC facilities to give a more complete description of particle production in p+A and d+A collisions, essential for the understanding the medium produced in high energy nucleus-nucleus collisions.Comment: 17 pages, 18 figure

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Participant and spectator scaling of spectator fragments in Au + Au and Cu + Cu collisions at √sNN = 19.6 and 22.4 GeV

Spectator fragments resulting from relativistic heavy ion collisions, consisting of single protons and neutrons along with groups of stable nuclear fragments up to nitrogen (Z=7), are measured in PHOBOS. These fragments are observed in Au+Au (√sNN =19.6GeV) and Cu+Cu (22.4 GeV) collisions at high pseudorapidity (η). The dominant multiply-charged fragment is the tightly bound helium (α), with lithium, beryllium, and boron all clearly seen as a function of collision centrality and pseudorapidity. We observe that in Cu+Cu collisions, it becomes much more favorable for the α fragments to be released than lithium. The yields of fragments approximately scale with the number of spectator nucleons, independent of the colliding ion. The shapes of the pseudorapidity distributions of fragments indicate that the average deflection of the fragments away from the beam direction increases for more central collisions. A detailed comparison of the shapes for α and lithium fragments indicates that the centrality dependence of the deflections favors a scaling with the number of participants in the collision.United States. Department of Energy (Grant DE-AC02-98CH10886)United States. Department of Energy (Grant DE-FG02-93ER40802)United States. Department of Energy (Grant DE-FG02-94ER40818)United States. Department of Energy (Grant DE-FG02-94ER40865)United States. Department of Energy (Grant DE-FG02- 99ER41099)United States. Department of Energy (Grant DE-AC02-06CH11357)National Science Foundation (U.S.) (Grant 9603486)National Science Foundation (U.S.) (Grant 0072204)National Science Foundation (U.S.) (Grant 0245011

CDX2 as a Prognostic Biomarker in Stage II and Stage III Colon Cancer

BACKGROUND: The identification of high-risk stage II colon cancers is key to the selection of patients who require adjuvant treatment after surgery. Microarray-based multigene-expression signatures derived from stem cells and progenitor cells hold promise, but they are difficult to use in clinical practice. METHODS: We used a new bioinformatics approach to search for biomarkers of colon epithelial differentiation across gene-expression arrays and then ranked candidate genes according to the availability of clinical-grade diagnostic assays. With the use of subgroup analysis involving independent and retrospective cohorts of patients with stage II or stage III colon cancer, the top candidate gene was tested for its association with disease-free survival and a benefit from adjuvant chemotherapy. RESULTS: The transcription factor CDX2 ranked first in our screening test. A group of 87 of 2115 tumor samples (4.1%) lacked CDX2 expression. In the discovery data set, which included 466 patients, the rate of 5-year disease-free survival was lower among the 32 patients (6.9%) with CDX2-negative colon cancers than among the 434 (93.1%) with CDX2-positive colon cancers (hazard ratio for disease recurrence, 3.44; 95% confidence interval [CI], 1.60 to 7.38; P = 0.002). In the validation data set, which included 314 patients, the rate of 5-year disease-free survival was lower among the 38 patients (12.1%) with CDX2 protein–negative colon cancers than among the 276 (87.9%) with CDX2 protein–positive colon cancers (hazard ratio, 2.42; 95% CI, 1.36 to 4.29; P = 0.003). In both these groups, these findings were independent of the patient's age, sex, and tumor stage and grade. Among patients with stage II cancer, the difference in 5-year disease-free survival was significant both in the discovery data set (49% among 15 patients with CDX2-negative tumors vs. 87% among 191 patients with CDX2-positive tumors, P = 0.003) and in the validation data set (51% among 15 patients with CDX2-negative tumors vs. 80% among 106 patients with CDX2-positive tumors, P = 0.004). In a pooled database of all patient cohorts, the rate of 5-year disease-free survival was higher among 23 patients with stage II CDX2-negative tumors who were treated with adjuvant chemotherapy than among 25 who were not treated with adjuvant chemotherapy (91% vs. 56%, P = 0.006). CONCLUSIONS: Lack of CDX2 expression identified a subgroup of patients with high-risk stage II colon cancer who appeared to benefit from adjuvant chemotherapy. (Funded by the National Comprehensive Cancer Network, the National Institutes of Health, and others.

(Re) defining salesperson motivation: current status, main challenges, and research directions

The construct of motivation is one of the central themes in selling and sales management research. Yet, to-date no review article exists that surveys the construct (both from an extrinsic and intrinsic motivation context), critically evaluates its current status, examines various key challenges apparent from the extant research, and suggests new research opportunities based on a thorough review of past work. The authors explore how motivation is defined, major theories underpinning motivation, how motivation has historically been measured, and key methodologies used over time. In addition, attention is given to principal drivers and outcomes of salesperson motivation. A summarizing appendix of key articles in salesperson motivation is provided

Genome Sequencing Reveals Widespread Virulence Gene Exchange among Human Neisseria Species

Commensal bacteria comprise a large part of the microbial world, playing important roles in human development, health and disease. However, little is known about the genomic content of commensals or how related they are to their pathogenic counterparts. The genus Neisseria, containing both commensal and pathogenic species, provides an excellent opportunity to study these issues. We undertook a comprehensive sequencing and analysis of human commensal and pathogenic Neisseria genomes. Commensals have an extensive repertoire of virulence alleles, a large fraction of which has been exchanged among Neisseria species. Commensals also have the genetic capacity to donate DNA to, and take up DNA from, other Neisseria. Our findings strongly suggest that commensal Neisseria serve as reservoirs of virulence alleles, and that they engage extensively in genetic exchange

Machine learning algorithms performed no better than regression models for prognostication in traumatic brain injury

Objective: We aimed to explore the added value of common machine learning (ML) algorithms for prediction of outcome for moderate and severe traumatic brain injury. Study Design and Setting: We performed logistic regression (LR), lasso regression, and ridge regression with key baseline predictors in the IMPACT-II database (15 studies, n = 11,022). ML algorithms included support vector machines, random forests, gradient boosting machines, and artificial neural networks and were trained using the same predictors. To assess generalizability of predictions, we performed internal, internal-external, and external validation on the recent CENTER-TBI study (patients with Glasgow Coma Scale <13, n = 1,554). Both calibration (calibration slope/intercept) and discrimination (area under the curve) was quantified. Results: In the IMPACT-II database, 3,332/11,022 (30%) died and 5,233(48%) had unfavorable outcome (Glasgow Outcome Scale less than 4). In the CENTER-TBI study, 348/1,554(29%) died and 651(54%) had unfavorable outcome. Discrimination and calibration varied widely between the studies and less so between the studied algorithms. The mean area under the curve was 0.82 for mortality and 0.77 for unfavorable outcomes in the CENTER-TBI study. Conclusion: ML algorithms may not outperform traditional regression approaches in a low-dimensional setting for outcome prediction after moderate or severe traumatic brain injury. Similar to regression-based prediction models, ML algorithms should be rigorously validated to ensure applicability to new populations