Artificial neural networks (ANNs) form a class of powerful multivariate analysis techniques, yet their routine use in the surface analysis community is limited. Principal component analysis (PCA) is ...more commonly employed to reduce the dimensionality of large data sets and highlight key characteristics. Herein, we discuss the strengths and weaknesses of PCA and ANNs as methods for investigation and interpretation of a complex multivariate sample set. Using time-of-flight secondary ion mass spectrometry (ToF-SIMS) we acquired spectra from an antibody and its proteolysis fragments with three primary-ion sources to obtain a panel of 72 spectra and a characteristic peak list of 775 fragment ions. We describe the use of ANNs as a means to interpret the ToF-SIMS spectral data, highlight the optimal neural network design and computational parameters, and discuss the technique limitations. Further, employing Bi3 + as the primary-ion source, ANNs can accurately classify antibody fragments from the parent antibody based on ToF-SIMS spectra.
Vaporisation and liquid phase thermal decomposition, TD, of two halide ion ionic liquids, 1-octyl-3-methylimidazolium chloride, C8C1ImCl, and 1-octyl-3-methylimidazolium iodide, C8C1ImI, are ...investigated using temperature programmed desorption (TPD) line of sight mass spectrometry (LOSMS) at ultra-high vacuum (UHV). The ability to use MS to distinguish between vaporisation and TD allows the thermodynamics/kinetics of both vaporisation and TD to be investigated within the same experiments. Vaporisation of both halide ion ionic liquids is demonstrated. For both C8C1ImCl and C8C1ImI the vapour is shown to be composed of neutral ion pairs (NIPs). The enthalpy of vaporisation at temperature T, ΔvapHT, was experimentally determined as ΔvapH455 = 151 ± 10 kJ mol(-1) for C8C1ImCl and ΔvapH480 = 149 ± 8 kJ mol(-1) for C8C1ImI. Extrapolation of ΔvapHT to the reference temperature, 298 K, gave ΔvapH298 = 166 ± 10 kJ mol(-1) for C8C1ImCl and ΔvapH298 = 167 ± 8 kJ mol(-1) for C8C1ImI, higher than most ΔvapH298 values measured to date for other C8C1Im(+)-containing ionic liquids. In addition, predictions of ΔvapH298 for other halide ion ionic liquids are made. Liquid phase TD is shown to proceed via nucleophilic substitution to give two sets of products: 1-octylimidazole and methylhalide, and 1-methylimidazole and 1-octylhalide. The activation energy of TD at a temperature T, Ea,TD,T, is measured for the nucleophilic substitution of C8C1ImI to give methyliodide; Ea,TD,480 = 136 ± 15 kJ mol(-1). Ea,TD,T is measured for the nucleophilic substitution of C8C1ImCl to give methylchloride; Ea,TD,455 = 132 ± 10 kJ mol(-1). The fact that ΔvapHT and Ea,TD,T are the same (within error) for both ionic liquids is commented upon, and conclusions are drawn as to the thermal stability of these ionic liquids.
Studies that have shown clinical depression to be a risk factor for cardiac events after coronary artery bypass graft (CABG) surgery have had small sample sizes, short follow-up, and have not had ...adequate power to assess mortality. We sought to assess whether depression is associated with an increased risk of mortality.
We assessed 817 patients undergoing CABG at Duke University Medical Center between May, 1989, and May, 2001. Patients completed the Center for Epidemiological Studies-Depression (CES-D) scale before surgery, 6 months after CABG, and were followed-up for up to 12 years.
In 817 patients there were 122 deaths (15%) in a mean follow-up of 5·2 years. 310 patients (38%) met the criterion for depression (CES-D ⩾16): 213 (26%) for mild depression (CES-D 16–26) and 97 (12%) for moderate to severe depression (CES-D ⩾27). Survival analyses, controlling for age, sex, number of grafts, diabetes, smoking, left ventricular ejection fraction, and previous myocardial infarction, showed that patients with moderate to severe depression at baseline (adjusted hazard ratio HR 2·4, 95% CI 1·4–4·0; p=0·001) and mild or moderate to severe depression that persisted from baseline to 6 months (adjusted HR 2·2, 1·2–4·2; p=0·015) had higher rates of death than did those with no depression.
Despite advances in surgical and medical management of patients after CABG, depression is an important independent predictor of death after CABG and should be carefully monitored and treated if necessary.
Vascular access is one of the most commonly performed invasive procedures in medicine. Ultrasound-guided vascular access has been shown to improve patient safety, decrease associated complications ...and increase first attempt success rates, however, the risk for a posterior venous wall puncture (PVWP) still exists. To reduce this complication, needle guides have been used, though, current methods have limited accessibility and generalizability. Thus, the aim of this article is to describe how a self-made needle block constructed with materials present in a central line kit can reduce the incidence of PVWP and its associated complications in novice POCUS users.
The clinical management of bladder cancer has seen little change over the last three decades and there is pressing need to identify more effective treatments for advanced disease. Low clinical use of ...neoadjuvant therapies stems from historical limitations in the ability to predict patients most likely to respond to combination chemotherapies. This article focuses on recent molecular and genetic studies, highlighting promising clinical trials and retrospective studies, and discusses emerging trials that use predictive biomarkers to match patients with therapies to which they are most likely to respond. The implementation of predictive genomic and molecular biomarkers will revolutionize urologic oncology and the clinical management of bladder cancer.
8000 cases of renal cancer are diagnosed each year in the UK, with a five-year survival rate of 50%. Treatment options are limited; a potential therapeutic target is the Src family kinases (SFKs). ...SFKs have roles in multiple oncogenic processes and promote metastases in solid tumours. The aim of this study was to investigate SFKs as potential therapeutic targets for clear cell renal cell carcinoma (ccRCC).
SFKs expression was assessed in a tissue microarray consisting of 192 ccRCC patients with full clinical follow-up. SFK inhibitors, dasatinib and saracatinib, were assessed in early ccRCC cell lines, 786-O and 769-P and a metastatic ccRCC cell line, ACHN (± Src) for effects on protein expression, apoptosis, proliferation and wound healing.
High nuclear expression of Lyn and the downstream marker of activation, paxillin, were associated with decreased patient survival. Conversely, high cytoplasmic expression of other SFK members and downstream marker of activation, focal adhesion kinase (FAK) were associated with increased patient survival. Treatment of non-metastatic 786-O and 769-P cells with dasatinib, dose dependently reduced SFK activation, shown via SFK (Y(419)) and FAK (Y(861)) phosphorylation, with no effect in metastatic ACHN cells. Dasatinib also increased apoptosis, while decreasing proliferation and migration in 786-O and 769-P cell lines, both in the presence and absence of Src protein.
Our data suggests that nuclear Lyn is a potential therapeutic target for ccRCC and dasatinib affects cellular functions associated with cancer progression via a Src kinase independent mechanism.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Chrysomelidae (Coleoptera) is a highly speciose family that has been poorly studied at the regional level in Mexico. In the present study, we estimated species richness and diversity in oak-pine ...forest, Tamaulipan thorny scrub and in tropical deciduous forests in Peregrina Canyon within the Altas Cumbres Protected Area of the northeastern state of Tamaulipas, Mexico. Sampling of Chrysomelidae consisted of five sweep net samples (200 net sweeps) within each of three sites during four sample periods: early dry season, late dry season, early wet season, and late wet season. Species were identified and total numbers per species were recorded for each sample. A total of 2,226 specimens were collected belonging to six subfamilies, 81 genera and 157 species of Chrysomelidae from the study area. Galerucinae was the most abundant subfamily with 1,828 specimens, representing 82.1% of total abundance in the study area. Lower abundance was recorded in Cassidinae (8.5%), Eumolpinae (3.6%), Cryptocephalinae (2.2%), Chrysomelinae (2.2%), and finally Criocerinae (1.3%). The highest species richness was also presented in the subfamily Galerucinae with 49% of the total obtained species followed by Cassidinae (20%), Cryptocephalinae (9.7%), Eumolpinae (9.7%), Chrysomelinae (6.5%) and Criocerinae (5.2%). The most common species were Centralaphthona fulvipennis Jacoby (412 individuals), Centralaphthona diversa (Baly) (248), Margaridisa sp.1 (219), Acallepitrix sp.1 (134), Longitarsus sp.1 (104), Heterispa vinula (Erichson) (91), Epitrix sp.1 (84) and Chaetocnema sp.1 (72). Twenty-two species were doubletons (1.97% of total abundance) and 52 were singletons (2.33%). The estimated overall density value obtained was 0.0037 individuals/m2. The greatest abundance and density of individuals were recorded at the lowest elevation site. However, alpha diversity increased with increasing altitude. Similarity values were less than 50% among the three sites indicating that each site had distinct species assemblages of Chrysomelidae. The highest abundance was obtained during the late dry season, whereas diversity indices were highest during the early wet season. The present work represents the first report of the altitudinal variation in richness, abundance, and diversity of Chrysomelidae in Mexico. These results highlight the importance of conservation of this heterogeneous habitat and establish baseline data for Chrysomelidae richness and diversity for the region.
Balancing immunosuppression after liver transplant is difficult, with clinical events common. We investigate whether a novel immune biomarker based on a laboratory platform with widespread ...availability that measures interferon γ (IFNγ) after stimulation with a lyophilized ball containing an adaptive and innate immune stimulant can predict events following transplantation. A total of 75 adult transplant recipients were prospectively monitored in a blinded, observational study; 55/75 (73.3%) patients experienced a total of 89 clinical events. Most events occurred within the first month. Low week 1 results were significantly associated with risk of early infection (area under the receiver operating characteristic curve AUROC, 0.74; P = 0.008). IFNγ ≤ 1.30 IU/mL (likelihood ratio positive, 1.93; sensitivity, 71.4%; specificity, 63.0%) was associated with the highest risk for infection with minimal rejection risk. Nearly half the cohort (27/60, 45.0%) expressed IFNγ ≤ 1.30 IU/mL. Moreover, an elevated week 1 result was significantly associated with the risk of rejection within the first month after transplant (AUROC, 0.77; P = 0.002), but no episodes of infection. On multivariate logistic regression, IFNγ ≥ 4.49 IU/mL (odds ratio, 4.75) may be an independent predictor of rejection (P = 0.05). In conclusion, low IFNγ suggesting oversuppression is associated with infections, whereas high IFNγ indicating undersuppression is associated with rejection. This assay offers the potential to allow individualization and optimization of immunosuppression that could fundamentally alter the way patients are managed following transplantation. Liver Transplantation 23 487–497 2017 AASLD.
Sneddon et al. (2018) authoritatively summarize the compelling and overwhelming evidence for fish sentience, while methodically dismantling one rather emblematic research paper (Diggles et al. 2017) ...intended to discount solid evidence of fish sentience (Lopez-Luna et al. 2017a, 2017b, 2017c, & 2017d). I explore the larger practical moral contexts within which these debates take place and argue that denials of animal sentience are really moral canards.
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