Rapidly frequency-tuneable, in-vacuum, and magnetic levitation chopper for fast modulation of infrared light.

We present an in-vacuum mechanical chopper running at high speed and integrated into a magnetic levitating motor for modulating optical beams up to 200 kHz. The compact chopper rotor allows fast acceleration (10 kHz s-1 as standard) for rapid tuning of the modulation frequency, while 1 mm diameter slots provide high optical throughput for larger infrared beams. The modulation performances are assessed using a reference visible laser and the high brightness, broadband, infrared (IR) beam of synchrotron radiation at the MIRIAM beamline B22 at Diamond Light Source, UK. For our application of IR nanospectroscopy, minimizing the temporal jitter on the modulated beam due to chopper manufacturing and control tolerances is essential to limit the noise level in measurements via lock-in detection, while high modulation frequencies are needed to achieve high spatial resolution in photothermal nanospectroscopy. When reaching the maximum chopping frequency of 200 kHz, the jitter was found to be 0.9% peak-to-peak. The described chopper now replaces the standard ball-bearing chopper in our synchrotron-based FTIR photothermal nanospectroscopy system, and we demonstrate improved spectroscopy results on a 200 nm thickness polymer film.

Aluminosilicate haloes preserve complex life approximately 800 million years ago.

Mudstone-hosted microfossils are a major component of the Proterozoic fossil record, particularly dominating the record of early eukaryotic life. Early organisms possessed no biomineralized parts to resist decay and controls on their fossilization in mudstones are poorly understood. Consequently, the Proterozoic fossil record is compromised-we do not know whether changing temporal/spatial patterns of microfossil occurrences reflect evolution or the distribution of favourable fossilization conditions. We investigated fossilization within the approximately 1000 Ma Lakhanda Group (Russia) and the approximately 800 Ma Svanbergfjellet and Wynniatt formations (Svalbard and Arctic Canada). Vertical sections of microfossils and surrounding matrices were extracted from thin sections by focused ion beam milling. Elemental mapping and synchrotron-based infrared microspectroscopy revealed that microfossils are surrounded by haloes rich in aluminium, probably hosted in kaolinite. Kaolinite has been implicated in Cambrian Burgess Shale-type (BST) fossilization and is known to slow the growth of degraders. The Neoproterozoic mudstone microfossil record may be biased to tropical settings conducive to kaolinite formation. These deposits lack metazoan fossils even though they share fossilization conditions with younger BST deposits that are capable of preserving non-mineralizing metazoans. Thus metazoans, at least those typically preserved in BST deposits, were probably absent from sedimentary environments before approximately 800 Ma.

Synchrotron Photothermal Infrared Nanospectroscopy of Drug-Induced Phospholipidosis in Macrophages.

Synchrotron resonance-enhanced infrared atomic force microscopy (RE-AFM-IR) is a near-field photothermal vibrational nanoprobe developed at Diamond Light Source (DLS), capable of measuring mid-infrared absorption spectra with spatial resolution around 100 nm. The present study reports a first application of synchrotron RE-AFM-IR to interrogate biological soft matter at the subcellular level, in this case, on a cellular model of drug-induced phospholipidosis (DIPL). J774A-1 macrophages were exposed to amiodarone (10 µM) or medium for 24 h and chemically fixed. AFM topography maps revealed amiodarone-treated cells with enlarged cytoplasm and very thin regions corresponding to collapsed vesicles. IR maps of the whole cell were analyzed by exploiting the RE-AFM-IR overall signal, i.e., the integrated RE-AFM-IR signal amplitude versus AFM-derived cell thickness, also on lateral resolution around 100 nm. Results show that vibrational band assignment was possible, and all characteristic peaks for lipids, proteins, and DNA/RNA were identified. Both peak ratio and unsupervised chemometric analysis of RE-AFM-IR nanospectra generated from the nuclear and perinuclear regions of untreated and amiodarone-treated cells showed that the perinuclear region (i.e., cytoplasm) of amiodarone-treated cells had significantly elevated band intensities in the regions corresponding to phosphate and carbonyl groups, indicating detection of phospholipid-rich inclusion bodies typical for cells with DIPL. The results of this study are of importance to demonstrate not only the applicability of Synchrotron RE-AFM-IR to soft biological matters with subcellular spatial resolution but also that the spectral information gathered from an individual submicron sample volume enables chemometric identification of treatment and biochemical differences between mammalian cells.

Comparison of resident performance in interpreting mammography results using a probabilistic or a natural frequency presentation: a multi-institutional randomized experimental study.

BACKGROUND: Residents are being increasingly challenged on how best to integrate diagnostic information in making decisions about patient care. The aim of this study is to assess the ability of residents to accurately integrate statistical data from a screening mammography test in order to estimate breast cancer probability and to investigate whether a simple alteration of the representation mode of probabilities into natural frequencies facilitates these computations. METHODS: A multi-institutional randomized controlled study of residents was performed in eight major hospitals in the city of Athens. Residents were asked to estimate the positive predictive value of the screening mammography test given its sensitivity and 1-specificity as well as the prevalence of breast cancer in the relevant population. One version of the scenario was presented in the single-event probability format that is commonly used in the medical literature, while the other used the natural frequency representation. The two questionnaire versions were randomly assigned to the participants. RESULTS: Out of 200 residents, 153 completed and returned the questionnaire (response rate 76.5%). Although more than one-third of the residents reported excellent or close to excellent familiarity with sensitivity and positive predictive value, the majority of responses (79.1%) were incorrect. However, a significantly higher proportion of residents in the natural frequency group (n = 88) selected the correct response compared with residents (n = 65) in the single-event probability group (28.4% vs 10.8%; 95% confidence intervals of the difference between the two proportions = 5.6-29.7%; P < 0.01). DISCUSSION: Residents more often correctly understand test performance accuracy when test characteristics are presented to them as natural frequency representations than the more common approach of presenting single event probabilities. Educators and journal editors should be aware of this facilitative effect.

Nano-contact microscopy of supracrystals.

BACKGROUND: Highly ordered three-dimensional colloidal crystals (supracrystals) comprised of 7.4 nm diameter Au nanocrystals (with a 5% size dispersion) have been imaged and analysed using a combination of scanning tunnelling microscopy and dynamic force microscopy. RESULTS: By exploring the evolution of both the force and tunnel current with respect to tip-sample separation, we arrive at the surprising finding that single nanocrystal resolution is readily obtained in tunnelling microscopy images acquired more than 1 nm into the repulsive (i.e., positive force) regime of the probe-nanocrystal interaction potential. Constant height force microscopy has been used to map tip-sample interactions in this regime, revealing inhomogeneities which arise from the convolution of the tip structure with the ligand distribution at the nanocrystal surface. CONCLUSION: Our combined STM-AFM measurements show that the contrast mechanism underpinning high resolution imaging of nanoparticle supracrystals involves a form of nanoscale contact imaging, rather than the through-vacuum tunnelling which underpins traditional tunnelling microscopy and spectroscopy.

Critical assessment of the evidence for striped nanoparticles.

There is now a significant body of literature which reports that stripes form in the ligand shell of suitably functionalised Au nanoparticles. This stripe morphology has been proposed to strongly affect the physicochemical and biochemical properties of the particles. We critique the published evidence for striped nanoparticles in detail, with a particular focus on the interpretation of scanning tunnelling microscopy (STM) data (as this is the only technique which ostensibly provides direct evidence for the presence of stripes). Through a combination of an exhaustive re-analysis of the original data, in addition to new experimental measurements of a simple control sample comprising entirely unfunctionalised particles, we show that all of the STM evidence for striped nanoparticles published to date can instead be explained by a combination of well-known instrumental artefacts, or by issues with data acquisition/analysis protocols. We also critically re-examine the evidence for the presence of ligand stripes which has been claimed to have been found from transmission electron microscopy, nuclear magnetic resonance spectroscopy, small angle neutron scattering experiments, and computer simulations. Although these data can indeed be interpreted in terms of stripe formation, we show that the reported results can alternatively be explained as arising from a combination of instrumental artefacts and inadequate data analysis techniques.

Assessment of cognitive biases and biostatistics knowledge of medical residents: a multicenter, cross-sectional questionnaire study.

PURPOSE: The aim of this study is to determine the perceived familiarity of medical residents with statistical concepts, assess their ability to integrate these concepts in clinical scenarios, and investigate their susceptibility to the gambler's fallacy and the conjunction fallacy. METHODS: A multi-institutional, cross-sectional survey of Greek medical residents was performed. Participants were asked to indicate their familiarity with basic statistical concepts and answer clinically oriented questions designed to assess their biostatistics knowledge and cognitive biases. Univariate, bivariate, and multivariate statistical models were used for the evaluation of data. RESULTS: Out of 153 respondents (76.5% response rate), only two participants (1.3%) were able to answer all seven biostatistics knowledge questions correctly while 29 residents (19%) gave incorrect answers to all questions. The proportion of correct answers to each biostatistics knowledge question ranged from 15 to 51.6%. Residents with greater self-reported familiarity were more likely to perform better on the respective knowledge question (all p<0.01). Multivariate analysis of the effect of individual resident characteristics on questionnaire performance showed that previous education outside Greece, primarily during medical school, was associated with lower biostatistics knowledge scores (p<0.001). A little more than half of the respondents (54.2%) answered the gambler's fallacy quiz correctly. Residents with higher performance on the biostatistics knowledge questions were less prone to the gambler's fallacy (odds ratio 1.38, 95% confidence intervals 1.12-1.70, p=0.003). Only 48 residents (31.4%) did not violate the conjunction rule. CONCLUSIONS: A large number of medical residents are unable to correctly interpret crucial statistical concepts that are commonly found in the medical literature. They are also especially prone to the gambler's fallacy bias, which may undermine clinical judgment and medical decision making. Formalized systematic teaching of biostatistics during residency will be required to de-bias residents and ensure that they are proficient in understanding and communicating statistical information.

The effort-reward imbalance questionnaire in Greek: translation, validation and psychometric properties in health professionals.

OBJECTIVES: The aim of the present study was to translate, adapt and validate the Effort-reward imbalance (ERI) questionnaire in a sample of Greek healthcare professionals. METHODS: An internationally recommended methodology was followed to perform translation of the ERI instrument into the Greek language. The questionnaire was then randomly administered to 600 Greek physicians, nurses, physiotherapists and laboratory staff, and 456 questionnaires with no missing data on the ERI items were returned (76% response rate). Tool validation included assessment of internal consistency, factorial structure, discriminant validity and presence of floor or ceiling effects. Criterion validity was demonstrated by investigating the association of theoretically relevant ERI summary measurements with respondents' self-rated health. RESULTS: The Greek version of the ERI questionnaire showed good psychometric properties. Cronbach's alpha values were 0.79, 0.72 and 0.75 for the three ERI scales of effort, reward and overcommitment respectively. Exploratory factor analysis yielded a 5-factor solution that closely reflected the original theoretical ERI model. Significant associations were found between respondents' age, gender and specific occupation with ERI scores. ERI ratio and "overcommitment" scores in the highest tertiles were associated with elevated odds ratios (OR) of below-average self-rated health (OR=5.38, 95% confidence intervals 1.77 to 16.38, p=0.003, and OR=3.41, 95% confidence intervals 1.39 to 8.38, p=0.007, respectively). CONCLUSIONS: The translated and adapted Greek version is comparable with the original ERI instrument in terms of validity and factorial structure and is suitable for assessment of the psychosocial work environment of Greek healthcare professionals.