In this paper an experimental and theoretical study of the deformation of a spherical liquid droplet colliding with a flat surface is presented. The theoretical model accounts for the presence of inertia, viscous, gravitation, surface tension, and wetting effects, including the phenomenon of contact-angle hysteresis. Experiments with impingement surfaces of different wettability were performed. The study showed that the maximum splat radius decreased as the value of the advancing contact angle increased. The effect of impact velocity on droplet spreading was more pronounced when the wetting was limited. The experimental results were compared to the numerical predictions in terms of droplet deformation, splat radius, and splat height. The theoretical model predicted well the deformation of the impacting droplet, not only in the spreading phase, but also during recoiling and oscillation. The wettability of the substrate upon which the droplet impinges was found to affect significantly all phases of the spreading process, including the formation and development of a ring structure around the splat.
Schizophrenia is a severe mental disorder that affects 0.5–1% of the population worldwide. Current diagnostic methods are based on psychiatric interviews, which are subjective in nature. The lack of disease biomarkers to support objective laboratory tests has been a long-standing bottleneck in the clinical diagnosis and evaluation of schizophrenia. Here we report a global metabolic profiling study involving 112 schizophrenic patients and 110 healthy subjects, who were divided into a training set and a test set, designed to identify metabolite markers. A panel of serum markers consisting of glycerate, eicosenoic acid, β-hydroxybutyrate, pyruvate and cystine was identified as an effective diagnostic tool, achieving an area under the receiver operating characteristic curve (AUC) of 0.945 in the training samples (62 patients and 62 controls) and 0.895 in the test samples (50 patients and 48 controls). Furthermore, a composite panel by the addition of urine β-hydroxybutyrate to the serum panel achieved a more satisfactory accuracy, which reached an AUC of 1 in both the training set and the test set. Multiple fatty acids and ketone bodies were found significantly (P<0.01) elevated in both the serum and urine of patients, suggesting an upregulated fatty acid catabolism, presumably resulting from an insufficiency of glucose supply in the brains of schizophrenia patients.
IMPORTANCE Understanding adverse effects of contemporary treatment approaches for men with favorable-risk and unfavorable-risk localized prostate cancer could inform treatment selection. OBJECTIVE To compare functional outcomes associated with prostate cancer treatments over 5 years after treatment. DESIGN, SETTING, AND PARTICIPANTS Prospective, population-based cohort study of 1386 men with favorable-risk (clinical stage cT1 to cT2bN0M0, prostate-specific antigen [PSA] Յ20 ng/mL, and Grade Group 1-2) prostate cancer and 619 men with unfavorable-risk (clinical stage cT2cN0M0, PSA of 20-50 ng/mL, or Grade Group 3-5) prostate cancer diagnosed in 2011 through 2012, accrued from 5 Surveillance, Epidemiology and End Results Program sites and a US prostate cancer registry, with surveys through September 2017. EXPOSURES Treatment with active surveillance (n = 363), nerve-sparing prostatectomy (n = 675), external beam radiation therapy (EBRT; n = 261), or low-dose-rate brachytherapy (n = 87) for men with favorable-risk disease and treatment with prostatectomy (n = 402) or EBRT with androgen deprivation therapy (n = 217) for men with unfavorable-risk disease. MAIN OUTCOMES AND MEASURES Patient-reported function, based on the 26-item Expanded Prostate Index Composite (range, 0-100), 5 years after treatment. Regression models were adjusted for baseline function and patient and tumor characteristics. Minimum clinically important difference was 10 to 12 for sexual function, 6 to 9 for urinary incontinence, 5 to 7 for urinary irritative symptoms, and 4 to 6 for bowel and hormonal function. RESULTS A total of 2005 men met inclusion criteria and completed the baseline and at least 1 postbaseline survey (median [interquartile range] age, 64 [59-70] years; 1529 of 1993 participants [77%] were non-Hispanic white). For men with favorable-risk prostate cancer, nerve-sparing prostatectomy was associated with worse urinary incontinence at 5 years
This article presents a theoretical study of the deformation of a spherical liquid droplet impinging upon a flat surface. The study accounts for the presence of surface tension during the spreading process. The theoretical model is solved numerically utilizing deforming finite elements and grid generation to simulate accurately the large deformations, as well as the domain nonuniformities characteristic of the spreading process. The results document the effects of impact velocity, droplet diameter, surface tension, and material properties on the fluid dynamics of the deforming droplet. Two liquids with markedly different thermophysical properties, water and liquid tin, are utilized in the numerical simulations because of their relevance in the industrial processes of spray cooling and spray deposition, respectively. The occurrence of droplet recoiling and mass accumulation around the splat periphery are standout features of the numerical simulations and yield a nonmonotonic dependence of the maximum splat radius on time.
IntroductionDespite recent modifications, the clinical definition of the acute respiratory distress syndrome (ARDS) remains non-specific, leading to under-diagnosis and under-treatment. This study was designed to test the hypothesis that a biomarker panel would be useful for biologic confirmation of the clinical diagnosis of ARDS in patients at risk of developing ARDS due to severe sepsis.MethodsThis was a retrospective case control study of 100 patients with severe sepsis and no evidence of ARDS compared to 100 patients with severe sepsis and evidence of ARDS on at least two of their first four ICU days. A panel that included 11 biomarkers of inflammation, fibroblast activation, proteolytic injury, endothelial injury, and lung epithelial injury was measured in plasma from the morning of ICU day two. A backward elimination model building strategy on 1,000 bootstrapped data was used to select the best performing biomarkers for further consideration in a logistic regression model for diagnosis of ARDS.ResultsUsing the five best-performing biomarkers (surfactant protein-D (SP-D), receptor for advanced glycation end-products (RAGE), interleukin-8 (IL-8), club cell secretory protein (CC-16), and interleukin-6 (IL-6)) the area under the receiver operator characteristic curve (AUC) was 0.75 (95% CI: 0.7 to 0.84) for the diagnosis of ARDS. The AUC improved to 0.82 (95% CI: 0.77 to 0.90) for diagnosis of severe ARDS, defined as ARDS present on all four of the first four ICU days.ConclusionsAbnormal levels of five plasma biomarkers including three biomarkers generated by lung epithelium (SP-D, RAGE, CC-16) provided excellent discrimination for diagnosis of ARDS in patients with severe sepsis. Altered levels of plasma biomarkers may be useful biologic confirmation of the diagnosis of ARDS in patients with sepsis, and also potentially for selecting patients for clinical trials that are designed to reduce lung epithelial injury.
Activating NRAS mutations are found in 15-20% of melanomas. Immune therapies have become a mainstay in advanced melanoma treatment. We sought to evaluate whether tumor genotype (e.g. NRAS mutations) correlate with benefit from immune therapy in melanoma. We identified 229 melanoma patients treated with immune therapies (interleukin-2, ipilimumab, or anti-programmed cell-death-1/ligand-1 (PD-1/PD-L1)) at three centers, and compared clinical outcomes following immune therapy for patients with or without NRAS mutations. Of the 229 melanoma patients, 60 had NRAS mutation, 53 had BRAF mutation, and 116 had NRAS/BRAF WT. The NRAS-mutant cohort had superior or a trend to superior outcomes compared to the other cohorts in terms of response to first-line immune therapy (28% vs. 16%, p=0.04), response to any line of immune therapy (32% vs. 20%, p=0.07), clinical benefit (response + stable disease lasting ≥24 weeks; 50% vs. 31%, p<0.01), and progression-free survival (median 4.1 vs. 2.9 months, p=0.09). Benefit from anti-PD-1/PD-L1 was particularly marked in the NRAS cohort (clinical benefit rate 73% vs. 35%). In an independent group of patient samples, NRAS-mutant melanoma had higher PD-L1 expression (although not statistically significant) compared to other genotypes (8/12 vs. 9/20 samples with ≥1% expression; 6/12 vs 6/20 samples with ≥5% expression), suggesting a potential mechanism for the clinical results. This retrospective study suggests that NRAS mutations in advanced melanoma correlate with increased benefit from immune-based therapies compared to other genetic subtypes. If confirmed by prospective studies, this may be explained in part by high rates of PD-L1 expression.
Despite the observation of noncovalent interactions between chalcogen atoms in X-ray crystal structures, catalysis that harnesses the power of such chalcogen−chalcogen bonding interactions to produce advanced molecules remains an unresolved problem. Here, we show that a class of extraordinary chalcogenbonding catalysts enables assembly of discrete small molecules including three β-ketoaldehydes and one indole, leading to the construction of N-heterocycles in a highly efficient manner. The strong activation ability of these rationally designed catalysts provides a general solution to the intrinsic limitations of chalcogen bonding catalysis.
Background Pediatric oncology patients are at increased risk for blood stream infections (BSI). Risk in the absence of severe neutropenia (absolute neutrophil count (ANC) ≥500/µl) is not well defined. Procedure In a retrospective cohort of febrile (temperature ≥38.0° for > 1 hour or ≥38.3°) pediatric oncology patients with ANC≥500/µl , a diagnostic prediction model for BSI was constructed using logistic regression modeling and the following candidate predictors: age, ANC, absolute monocyte count, body temperature, inpatient/outpatient presentation, sex, central venous catheter type, hypotension, chills, cancer diagnosis, stem cell transplant, upper respiratory symptoms, and exposure to cytarabine, anti-thymocyte globulin, or anti-GD2 antibody. The model was internally validated with bootstrapping methods. Results Among 932 febrile episodes in 463 patients, we identified 91 cases of BSI. Independently significant predictors for BSI were higher body temperature (Odds ratio (OR) 2.36 p<0.001), tunneled external catheter (OR 13.79 p<0.001), peripherally inserted central catheter (PICC) (OR 3.95 p=0.005), elevated ANC (OR 1.19 p=0.024), chills (OR 2.09 p=0.031) and hypotension (OR 3.08 p=0.004). Acute lymphoblastic leukemia diagnosis (OR 0.34 p=0.026), increased age (OR 0.70 p=0.049) and drug exposure (OR 0.08 p<0.001) were associated with decreased risk for BSI. The risk prediction model had a C-index of 0.898; after bootstrapping adjustment for optimism, corrected C-index 0.885. Conclusions We developed a diagnostic prediction model for BSI in febrile pediatric oncology patients without severe neutropenia. External validation is warranted before use in clinical practice.
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