645 research outputs found
Developing a nanoparticle test for prostate cancer scoring
<p>Abstract</p> <p>Background</p> <p>Over-diagnosis and treatment of prostate cancer has been a major problem in prostate cancer care and management. Currently the most relevant prognostic factor to predict a patient's risk of death due to prostate cancer is the Gleason score of the biopsied tissue samples. However, pathological analysis is subjective, and the Gleason score is only a qualitative estimate of the cancer malignancy. Molecular biomarkers and diagnostic tests that can accurately predict prostate tumor aggressiveness are rather limited.</p> <p>Method</p> <p>We report here for the first time the development of a nanoparticle test that not only can distinguish prostate cancer from normal and benign conditions, but also has the potential to predict the aggressiveness of prostate cancer quantitatively. To conduct the test, a prostate tissue lysate sample is spiked into a blood serum or human IgG solution and the spiked sample is incubated with a citrate-protected gold nanoparticle solution. IgG is known to adsorb to citrate-protected gold nanoparticles to form a "protein corona" on the nanoparticle surface. From this study, we discovered that certain tumor-specific molecules can interact with IgG and change the adsorption behavior of IgG to the gold nanoparticles. This change is reflected in the nanoparticle size of the assay solution and detected by a dynamic light scattering technique. Assay data were analyzed by one-way ANOVA for multiple variant analysis, and using the Student <it>t-</it>test or nonparametric Mann-Whitney <it>U-</it>tests for pairwise analyses.</p> <p>Results</p> <p>An inverse, quantitative correlation of the average nanoparticle size of the assay solution with tumor status and histological diagnostic grading was observed from the nanoparticle test. IgG solutions spiked with prostate tumor tissue exhibit significantly smaller nanoparticle size than the solutions spiked with normal and benign tissues. The higher grade the tumor is, the smaller the nanoparticle size is. The test particularly revealed large differences among the intermediate Grade 2 tumors, and suggested the need to treat them differently.</p> <p>Conclusion</p> <p>Development of a new nanoparticle test may provide a quantitative measure of the prostate cancer aggressiveness. If validated in a larger study of patients with prostate cancer, this test could become a new diagnostic tool in conjunction with Gleason Score pathology diagnostics to better distinguish aggressive cancer from indolent tumor.</p
Decision-Making Competence and Attempted Suicide
Objective: The propensity of people vulnerable to suicide to make poor life decisions is increasingly well documented. Do they display an extreme degree of decision biases? The present study used a behavioral decision approach to examine the susceptibility of low-lethality and high-lethality suicide attempters to common decision biases, which may ultimately obscure alternative solutions and deterrents to suicide in a crisis. Method: We assessed older and middle-aged individuals who made high-lethality (medically serious; N=31) and low-lethality suicide attempts (N=29). Comparison groups included suicide ideators (N=30), non-suicidal depressed (N=53), and psychiatrically healthy participants (N=28). Attempters, ideators, and non-suicidal depressed participants had unipolar non-psychotic major depression. Decision biases included sunk cost (inability to abort an action for which costs are irrecoverable), framing (responding to superficial features of how a problem is presented), under/overconfidence (appropriateness of confidence in knowledge), and inconsistent risk perception. Data were collected between June of 2010 and February of 2014. Results: Both high- and low-lethality attempters were more susceptible to framing effects, as compared to the other groups included in this study (p< 0.05, ηp2 =.06). In contrast, low-lethality attempters were more susceptible to sunk costs than both the comparison groups and high-lethality attempters (p< 0.01, ηp2 =.09). These group differences remained after accounting for age, global cognitive performance, and impulsive traits. Premorbid IQ partially explained group differences in framing effects. Conclusion: Suicide attempters’ failure to resist framing may reflect their inability to consider a decision from an objective standpoint in a crisis. Low-lethality attempters’ failure to resist sunk cost may reflect their tendency to confuse past and future costs of their behavior, lowering their threshold for acting on suicidal thoughts
The formation, properties and impact of secondary organic aerosol: current and emerging issues
Secondary organic aerosol (SOA) accounts for a significant fraction of ambient tropospheric aerosol and a detailed knowledge of the formation, properties and transformation of SOA is therefore required to evaluate its impact on atmospheric processes, climate and human health. The chemical and physical processes associated with SOA formation are complex and varied, and, despite considerable progress in recent years, a quantitative and predictive understanding of SOA formation does not exist and therefore represents a major research challenge in atmospheric science. This review begins with an update on the current state of knowledge on the global SOA budget and is followed by an overview of the atmospheric degradation mechanisms for SOA precursors, gas-particle partitioning theory and the analytical techniques used to determine the chemical composition of SOA. A survey of recent laboratory, field and modeling studies is also presented. The following topical and emerging issues are highlighted and discussed in detail: molecular characterization of biogenic SOA constituents, condensed phase reactions and oligomerization, the interaction of atmospheric organic components with sulfuric acid, the chemical and photochemical processing of organics in the atmospheric aqueous phase, aerosol formation from real plant emissions, interaction of atmospheric organic components with water, thermodynamics and mixtures in atmospheric models. Finally, the major challenges ahead in laboratory, field and modeling studies of SOA are discussed and recommendations for future research directions are proposed
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Multi-generation OH oxidation as a source for highly oxygenated organic molecules from aromatics
Recent studies have recognised highly oxygenated organic molecules (HOMs) in the atmosphere as important in the formation of secondary organic aerosol (SOA). A large number of studies have focused on HOM formation from oxidation of biogenically emitted monoterpenes. However, HOM formation from anthropogenic vapours has so far received much less attention. Previous studies have identified the importance of aromatic volatile organic compounds (VOCs) for SOA formation. In this study, we investigated several aromatic compounds, benzene (C6H6), toluene (C7H8), and naphthalene (C10H8), for their potential to form HOMs upon reaction with hydroxyl radicals (OH). We performed flow tube experiments with all three VOCs and focused in detail on benzene HOM formation in the Julich Plant Atmosphere Chamber (JPAC). In JPAC, we also investigated the response of HOMs to NOx and seed aerosol. Using a nitrate-based chemical ionisation mass spectrometer (CI-APi-TOF), we observed the formation of HOMs in the flow reactor oxidation of benzene from the first OH attack. However, in the oxidation of toluene and naphthalene, which were injected at lower concentrations, multi-generation OH oxidation seemed to impact the HOM composition. We tested this in more detail for the benzene system in the JPAC, which allowed for studying longer residence times. The results showed that the apparent molar benzene HOM yield under our experimental conditions varied from 4.1% to 14.0%, with a strong dependence on the OH concentration, indicating that the majority of observed HOMs formed through multiple OH-oxidation steps. The composition of the identified HOMs in the mass spectrum also supported this hypothesis. By injecting only phenol into the chamber, we found that phenol oxidation cannot be solely responsible for the observed HOMs in benzene experiments. When NOx was added to the chamber, HOM composition changed and many oxygenated nitrogen-containing products were observed in CI-APi-TOF. Upon seed aerosol injection, the HOM loss rate was higher than predicted by irreversible condensation, suggesting that some undetected oxygenated intermediates also condensed onto seed aerosol, which is in line with the hypothesis that some of the HOMs were formed in multi-generation OH oxidation. Based on our results, we conclude that HOM yield and composition in aromatic systems strongly depend on OH and VOC concentration and more studies are needed to fully understand this effect on the formation of HOMs and, consequently, SOA. We also suggest that the dependence of HOM yield on chamber conditions may explain part of the variability in SOA yields reported in the literature and strongly advise monitoring HOMs in future SOA studies.Peer reviewe
Evolution of the complex refractive index in the UV spectral region in ageing secondary organic aerosol
The chemical and physical properties of secondary organic aerosol (SOA)
formed by the photochemical degradation of biogenic and anthropogenic
volatile organic compounds (VOC) are as yet still poorly constrained. The evolution
of the complex refractive index (RI) of SOA, formed from purely biogenic VOC
and mixtures of biogenic and anthropogenic VOC, was studied over a diurnal
cycle in the SAPHIR photochemical outdoor chamber in Jülich, Germany.
The correlation of RI with SOA chemical and physical properties such as
oxidation level and volatility was examined. The RI was retrieved by a newly
developed broadband cavity-enhanced spectrometer for aerosol optical
extinction measurements in the UV spectral region (360 to 420 nm). Chemical
composition and volatility of the particles were monitored by a high-resolution time-of-flight aerosol mass spectrometer, and a volatility tandem
differential mobility analyzer. SOA was formed by ozonolysis of either (i) a
mixture of biogenic VOC (α-pinene and limonene), (ii) biogenic VOC
mixture with subsequent addition of an anthropogenic VOC
(<i>p</i>-xylene-d<sub>10</sub>), or (iii) a mixture of biogenic and anthropogenic VOC.
The SOA aged by ozone/OH reactions up to 29.5 h was found to be
non-absorbing in all cases. The SOA with <i>p</i>-xylene-d<sub>10</sub> showed an
increase of the scattering component of the RI correlated with an increase
of the O / C ratio and with an increase in the SOA density. There was a
greater increase in the scattering component of the RI when the SOA was
produced from the mixture of biogenic VOCs and anthropogenic VOC than from
the sequential addition of the VOCs after approximately the same ageing time.
The increase of the scattering component was inversely correlated with the
SOA volatility. Two RI retrievals determined for the pure biogenic SOA
showed a constant RI for up to 5 h of ageing. Mass spectral characterization
shows the three types of the SOA formed in this study have a significant
amount of semivolatile components. The influence of anthropogenic VOCs on
the oxygenated organic aerosol as well as the atmospheric implications are
discussed
Correlation of pretreatment drug induced apoptosis in ovarian cancer cells with patient survival and clinical response
Background
This study was performed to determine if a chemotherapy-induced apoptosis assay (MiCK) could predict the best therapy for patients with ovarian cancer.
Methods
A prospective, multi-institutional and blinded trial of the assay was conducted in 104 evaluable ovarian cancer patients treated with chemotherapy. The MiCK assay was performed prior to therapy, but treating physicians were not told of the results and selected treatment only on clinical criteria. Outcomes (response, time to relapse, and survival) were compared to the drug-induced apoptosis observed in the assay.
Results
Overall survival in primary therapy, chemotherapy naïve patients with Stage III or IV disease was longer if patients received a chemotherapy which was best in the MiCK assay, compared to shorter survival in patients who received a chemotherapy that was not the best. (p < 0.01, hazard ratio HR 0.23). Multivariate model risk ratio showed use of the best chemotherapy in the MiCK assay was the strongest predictor of overall survival (p < 0.01) in stage III or IV patients. Standard therapy with carboplatin plus paclitaxel (C + P) was not the best chemotherapy in the MiCK assay in 44% of patients. If patients received C + P and it was the best chemotherapy in the MiCK assay, they had longer survival than those patients receiving C + P when it was not the best chemotherapy in the assay (p = 0.03). Relapse-free interval in primary therapy patients was longer if patients received the best chemotherapy from the MiCK assay (p = 0.03, HR 0.52). Response rates (CR + PR) were higher if physicians used an active chemotherapy based on the MiCK assay (p = 0.03).
Conclusion
The MiCK assay can predict the chemotherapy associated with better outcomes in ovarian cancer patients. This study quantifies outcome benefits on which a prospective randomized trial can be developed
Joint modelling compared with two stage methods for analysing longitudinal data and prospective outcomes: A simulation study of childhood growth and BP
© The Author(s) 2014. There is a growing debate with regards to the appropriate methods of analysis of growth trajectories and their association with prospective dependent outcomes. Using the example of childhood growth and adult BP, we conducted an extensive simulation study to explore four two-stage and two joint modelling methods, and compared their bias and coverage in estimation of the (unconditional) association between birth length and later BP, and the association between growth rate and later BP (conditional on birth length). We show that the two-stage method of using multilevel models to estimate growth parameters and relating these to outcome gives unbiased estimates of the conditional associations between growth and outcome. Using simulations, we demonstrate that the simple methods resulted in bias in the presence of measurement error, as did the two-stage multilevel method when looking at the total (unconditional) association of birth length with outcome. The two joint modelling methods gave unbiased results, but using the re-inflated residuals led to undercoverage of the confidence intervals. We conclude that either joint modelling or the simpler two-stage multilevel approach can be used to estimate conditional associations between growth and later outcomes, but that only joint modelling is unbiased with nominal coverage for unconditional associations
Molecular identification of organic vapors driving atmospheric nanoparticle growth
Particles formed in the atmosphere via nucleation provide about half the number of atmospheric cloud condensation nuclei, but in many locations, this process is limited by the growth of the newly formed particles. That growth is often via condensation of organic vapors. Identification of these vapors and their sources is thus fundamental for simulating changes to aerosol-cloud interactions, which are one of the most uncertain aspects of anthropogenic climate forcing. Here we present direct molecular-level observations of a distribution of organic vapors in a forested environment that can explain simultaneously observed atmospheric nanoparticle growth from 3 to 50 nm. Furthermore, the volatility distribution of these vapors is sufficient to explain nanoparticle growth without invoking particle-phase processes. The agreement between observed mass growth, and the growth predicted from the observed mass of condensing vapors in a forested environment thus represents an important step forward in the characterization of atmospheric particle growth.Peer reviewe
Design of a split Hopkinson pressure bar with partial lateral confinement
This paper presents the design of a modified split Hopkinson pressure bar (SHPB) where partial lateral con-
finement of the specimen is provided by the inertia of a fluid annulus contained in a long steel reservoir. In
contrast to unconfined testing, or a constant cell pressure applied before axial loading, lateral restraint is permitted
to develop throughout the axial loading: this enables the high-strain-rate shear behaviour of soils to be
characterised under conditions which are more representative of buried explosive events. A pressure transducer
located in the wall of the reservoir allows lateral stresses to be quantified, and a dispersion-correction
technique is used to provide accurate measurements of axial stress and strain. Preliminary numerical modelling
is utilised to inform the experimental design, and the capability of the apparatus is demonstrated with
specimen results for a dry quartz sand
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