Multivariate data analysis (MVDA) is getting popular across the spectroscopic community. To assess accurate results, the obtained data should be preprocessed prior to utilization of any MVDA ...algorithm. The process of data normalization or "internal standardization" is widely used across a broad range of applications. In this manuscript we investigate the utilization of Laser-Induced Breakdown Spectroscopy (LIBS) coupled with MVDA. However, many articles regarding the use of MVDA on data from LIBS do not provide any information about the data pretreatment. This work describes the impact of LIBS data normalization approaches on MVDA classification accuracy. Also, the impact of classical data preprocessing (mean centering and scaling) exploiting the prior utilization of MVDA was studied. This issue was investigated exploiting simple soft independent modelling of class analogies algorithm. The findings were generalized for three sample matrices (steel, Al alloys, and sedimentary ores). Furthermore, the selection of an appropriate normalization algorithm is not trivial since the spectrum of each sample matrix is composed of a different number of elements and corresponding elemental lines.
Normalization of data is significant and should be chosen according to the sample matrix under investigation.
To evaluate the relationship between burnout and perceived major medical errors among American surgeons.
Despite efforts to improve patient safety, medical errors by physicians remain a common cause ...of morbidity and mortality.
Members of the American College of Surgeons were sent an anonymous, cross-sectional survey in June 2008. The survey included self-assessment of major medical errors, a validated depression screening tool, and standardized assessments of burnout and quality of life (QOL).
Of 7905 participating surgeons, 700 (8.9%) reported concern they had made a major medical error in the last 3 months. Over 70% of surgeons attributed the error to individual rather than system level factors. Reporting an error during the last 3 months had a large, statistically significant adverse relationship with mental QOL, all 3 domains of burnout (emotional exhaustion, depersonalization, and personal accomplishment) and symptoms of depression. Each one point increase in depersonalization (scale range, 0-33) was associated with an 11% increase in the likelihood of reporting an error while each one point increase in emotional exhaustion (scale range, 0-54) was associated with a 5% increase. Burnout and depression remained independent predictors of reporting a recent major medical error on multivariate analysis that controlled for other personal and professional factors. The frequency of overnight call, practice setting, method of compensation, and number of hours worked were not associated with errors on multivariate analysis.
Major medical errors reported by surgeons are strongly related to a surgeon's degree of burnout and their mental QOL. Studies are needed to determine how to reduce surgeon distress and how to support surgeons when medical errors occur.
Summary Background Traditional methods of reporting adverse events in clinical trials are inadequate for modern cancer treatments with chronic administration. Conventional analysis and display of ...maximum grade adverse events do not capture toxicity profiles that evolve over time or longer lasting, lower grade toxic effects; we aimed to address this shortcoming in this study. Methods We developed an analytic approach and standardised, comprehensive format, the Toxicity over Time (ToxT) approach, which combines graphs and adverse event tabular displays with multiple longitudinal statistical techniques into a readily applicable method to study toxic effects. Plots visualising summary statistics or individual patient data over discrete timepoints were combined with statistical methods including the following longitudinal techniques: repeated measures models that describe the changes in adverse events across all cycles of treatment; time-to-event analyses of first and worst grade toxicity; and area under the curve (AUC) analyses summarising adverse event profiles over the entire course of a study, including chronic low-grade events. We applied ToxT analysis to adverse event data from two completed North Central Cancer Treatment Group (NCCTG/Alliance) trials: N9741 ( NCT00003594 ), in which different combinations of oxaliplatin, 5-fluorouracil, and irinotecan were investigated for metastatic colorectal cancer, and 979254, in which survivors of breast cancer were given venlafaxine or placebo for control of hot flashes. Findings In trial NCCTG 979254 there was a higher incidence of late-occurring dry mouth in patients who were given venlafaxine than in those given placebo (week 1 baseline: 13% six incidence in 48 patients, SD 5 vs 22% 11/49, SD 6; p=0·20; week 5: 49% 24/49, 7 vs 2% 1/46, 2; p<0·0001). In trial NCCTG N9741 there was an increased incidence of early nausea for patients given irinotecan plus oxaliplatin (IROX) compared with those given 5-fluorouracil plus oxaliplatin (FOLFOX; cycle 1 mean grade nausea 1·1 SD 1·0 vs 0·6 0·7; p<0·0001). Event charts showed earlier occurrences of higher grades of diarrhoea for patients given IROX compared with those given FOLFOX, and the AUC analysis shows a higher magnitude of diarrhoea consistently over time throughout the study in patients given IROX versus those given FOLFOX (mean AUC 4·2 SD 5·2 vs 2·9 4·2; p<0·0001). Interpretation The ToxT analytical approach incorporates the dimension of time into adverse event assessment and offers a more comprehensive depiction of toxic effects than present methods. With new, continuously administered targeted agents, immunotherapy, and maintenance regimens, these improved longitudinal analyses are directly relevant to patients and are crucial in cancer clinical trials. Funding National Cancer Institute of the National Institutes of Health and the Mayo Comprehensive Cancer Center.
To determine the incidence of burnout among American surgeons and evaluate personal and professional characteristics associated with surgeon burnout.
: Burnout is a syndrome of emotional exhaustion ...and depersonalization that leads to decreased effectiveness at work. A limited amount of information exists about the relationship between specific demographic and practice characteristics with burnout among American surgeons.
Members of the American College of Surgeons (ACS) were sent an anonymous, cross-sectional survey in June 2008. The survey evaluated demographic variables, practice characteristics, career satisfaction, burnout, and quality of life (QOL). Burnout and QOL were measured using validated instruments.
Of the approximately 24,922 surgeons sampled, 7905 (32%) returned surveys. Responders had been in practice 18 years, worked 60 hours per week, and were on call 2 nights/wk (median values). Overall, 40% of responding surgeons were burned out, 30% screened positive for symptoms of depression, and 28% had a mental QOL score >1/2 standard deviation below the population norm. Factors independently associated with burnout included younger age, having children, area of specialization, number of nights on call per week, hours worked per week, and having compensation determined entirely based on billing. Only 36% of surgeons felt their work schedule left enough time for personal/family life and only 51% would recommend their children pursue a career as a physician/surgeon.
Burnout is common among American surgeons and is the single greatest predictor of surgeons' satisfaction with career and specialty choice. Additional research is needed to identify individual, organizational, and societal interventions that preserve and promote the mental health of American surgeons.
Remote estimation of Sun‐induced chlorophyll fluorescence emitted by terrestrial vegetation can provide an unparalleled opportunity to track spatiotemporal variations of photosynthetic efficiency. ...Here we provide the first direct experimental evidence that the two peaks of the chlorophyll fluorescence spectrum can be accurately mapped from high‐resolution radiance spectra and that the signal is linked to variations in actual photosynthetic efficiency. Red and far red fluorescence measured using a novel airborne imaging spectrometer over a grass carpet treated with an herbicide known to inhibit photosynthesis was significantly higher than the corresponding signal from an equivalent untreated grass carpet. The reflectance signal of the two grass carpets was indistinguishable, confirming that the fast dynamic changes in fluorescence emission were related to variations in the functional status of actual photosynthesis induced by herbicide application. Our results from a controlled experiment at the local scale illustrate the potential for the global mapping of terrestrial photosynthesis through space‐borne measurements of chlorophyll fluorescence.
Key Points
A novel high‐resolution airborne sensor is flown
Both red and far red Sun‐induced fluorescence signals are accurately quantified
Red and far red fluorescence tracks variations in photosynthetic efficiency
Although signaling from phosphatidylinositol 3-kinase (PI3K) and AKT to mechanistic target of rapamycin (mTOR) is prominently dysregulated in high-grade glial brain tumors, blockade of PI3K or AKT ...minimally affects downstream mTOR activity in glioma. Allosteric mTOR inhibitors, such as rapamycin, incompletely block mTORC1 compared with mTOR kinase inhibitors (TORKi). Here, we compared RapaLink-1, a TORKi linked to rapamycin, with earlier-generation mTOR inhibitors. Compared with rapamycin and Rapalink-1, TORKi showed poor durability. RapaLink-1 associated with FKBP12, an abundant mTOR-interacting protein, enabling accumulation of RapaLink-1. RapaLink-1 showed better efficacy than rapamycin or TORKi, potently blocking cancer-derived, activating mutants of mTOR. Our study re-establishes mTOR as a central target in glioma and traces the failure of existing drugs to incomplete/nondurable inhibition of mTORC1.
•The TORKi MLN0128 shows poor residence time, underlying poor in vivo efficacy•RapaLink-1 shows improved potency compared with rapamycin and MLN0128•RapaLink-1 binding to FKBP12 results in targeted and durable inhibition of mTORC1•RapaLink-1 crosses the blood-brain barrier, blocking three brain cancer models in vivo
Fan et al. target mTORC1 activity in glioblastoma (GBM) with RapaLink-1, which is comprised of rapamycin linked to an mTOR kinase inhibitor. RapaLink-1 decreases mTORC1 activity in the brain and suppresses the growth of GBM xenografts and a genetically engineered mouse model of brain cancer in vivo.
Flavanols may provide protection against insulin resistance, but little is known about the amounts and types of flavanols that may be efficacious.
This study was designed to determine whether cocoa ...flavanols, over a range of intakes, improve biomarkers of glucose regulation, inflammation and hemostasis in obese adults at risk for insulin resistance. As an adjunct, green tea and cocoa flavanols were compared for their ability to modulate these biomarkers. In a randomized crossover design, 20 adults consumed a controlled diet for 5 days along with four cocoa beverages containing 30-900 mg flavanol per day, or tea matched to a cocoa beverage for monomeric flavanol content.
Cocoa beverages produced no significant changes in glucose, insulin, total area under the concentration-time curve (AUC) for glucose or total insulin AUC. As the dose of cocoa flavanols increased, total 8-isoprostane concentrations were lowered (linear contrast, P=0.02), as were C-reactive protein (CRP) concentrations (linear contrast, P=0.01). The relationship between cocoa flavanol levels and interleukin-6 (IL-6) concentrations was quadratic, suggesting that a maximum effective dose was achieved (quadratic contrast, P=0.01). There were no significant effects on measured indices of glucose regulation, nor on those of total 8-isoprostane, CRP and IL-6 concentrations, when cocoa and green tea were compared. However, relative to cocoa, green tea lowered fibrinogen concentrations (P=0.0003).
Short-term intake of cocoa and green tea flavanols does not appear to improve glucose metabolism; they do affect selected markers of one or more measures of oxidative stress, inflammation or hemostasis in obese adults at risk for insulin resistance.
The world is combating an ongoing COVID-19 pandemic with health-care systems, society and economies impacted in an unprecedented way. It is unclear how many people have contracted the causative ...coronavirus (SARS-CoV-2) unknowingly and are asymptomatic. Therefore, reported COVID-19 cases do not reflect the true scale of outbreak. Here we present the prevalence and distribution of antibodies to SARS-CoV-2 in a healthy adult population of the Netherlands, which is a highly affected country, using a high-performance immunoassay. Our results indicate that one month into the outbreak (i) the seroprevalence in the Netherlands was 2.7% with substantial regional variation, (ii) the hardest-hit areas showed a seroprevalence of up to 9.5%, (iii) the seroprevalence was sex-independent throughout age groups (18-72 years), and (iv) antibodies were significantly more often present in younger people (18-30 years). Our study provides vital information on the extent of exposure to SARS-CoV-2 in a country where social distancing is in place.
Temporal lobe seizures are accompanied by complex behavioral phenomena including loss of consciousness, dystonic movements and neuroendocrine changes. These phenomena may arise from extended neural ...networks beyond the temporal lobe. To investigate this, we imaged cerebral blood flow (CBF) changes during human temporal lobe seizures with single photon emission computed tomography (SPECT) while performing continuous video/EEG monitoring. We found that temporal lobe seizures associated with loss of consciousness produced CBF increases in the temporal lobe, followed by increases in bilateral midline subcortical structures. These changes were accompanied by marked bilateral CBF decreases in the frontal and parietal association cortex. In contrast, temporal lobe seizures in which consciousness was spared were not accompanied by these widespread CBF changes. The CBF decreases in frontal and parietal association cortex were strongly correlated with increases in midline structures such as the mediodorsal thalamus. These results suggest that impaired consciousness in temporal lobe seizures may result from focal abnormal activity in temporal and subcortical networks linked to widespread impaired function of the association cortex.
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