Shift in lateralization during illusory self‐motion: EEG responses to visual flicker at 10 Hz and frequency‐specific modulation by tACS

Self‐motion perception is a key aspect of higher vestibular processing, suggested to rely upon hemispheric lateralization and alpha‐band oscillations. The first aim of this study was to test for any lateralization in the EEG alpha band during the illusory sense of self‐movement (vection) induced by large optic flow stimuli. Visual stimuli flickered at alpha frequency (approx. 10 Hz) in order to produce steady state visually evoked potentials (SSVEP s), a robust EEG measure which allows probing the frequency‐specific response of the cortex. The first main result was that differential lateralization of the alpha SSVEP response was found during vection compared with a matched random motion control condition, supporting the idea of lateralization of visual–vestibular function. Additionally, this effect was frequency‐specific, not evident with lower frequency SSVEP s. The second aim of this study was to test for a causal role of the right hemisphere in producing this lateralization effect and to explore the possibility of selectively modulating the SSVEP response. Transcranial alternating current stimulation (tACS ) was applied over the right hemisphere simultaneously with SSVEP recording, using a novel artefact removal strategy for combined tACS ‐EEG . The second main result was that tACS enhanced SSVEP amplitudes, and the effect of tACS was not confined to the right hemisphere. Subsequent control experiments showed the effect of tACS requires the flicker frequency and tACS frequency to be closely matched and tACS to be of sufficient intensity. Combined tACS ‐SSVEP s are a promising method for future investigation into the role of neural oscillations and for optimizing tACS

XEOM 1 : a novel microscopy system for the chemical imaging of heritage metal surfaces

Background: We describe a novel microscopy system which can obtain chemical maps from the surfaces of heritage metals in air or a controlled environment. The microscope, x-ray excited optical microscope Mk 1 (XEOM 1), forms images from x-ray excited optical luminescence (XEOL) induced by illuminating a few square millimetres of the sample with monochromated x-rays (broad beam or macroprobe illumination). XEOL is a spectroscopy tool in its own right and can, under the right circumstances, also be a vehicle for x-ray absorption spectroscopy. This (usually) synchrotron based technique provides information on the chemical state and short-range atomic order of the top few microns of a surface. It is thus well suited to heritage metal corrosion studies and is complementary to synchrotron x-ray diffraction. Results: Imaging can be performed by scanning the sample under an x-ray microprobe. We show elsewhere that the power density needed for image acquisition on a reasonable time-scale is high enough to damage a patina and modify its chemistry. Although the damaged region may be invisible to the human eye, the data are characteristic of the damage and not the native chemistry of the surface. A macrobeam power density can be 4 orders of magnitude smaller than that for a microbeam and no surface modification was observed on test samples. Features of the instrument are demonstrated using copper test surfaces with a spatially varying patination to establish the ground work for the imaging of copper, cuprite, nantokite and atacamite/paratacamite and a first application from a bronze chain mail link. In parallel we have developed a suite of imaging software which can process XEOM image stacks to produce reduced data sets characteristic of various aspects of the surface chemical map. These include edge-shift (oxidation state) images and edge height (high contrast) images and spectra from user defined regions of interest. Conclusions: The technique can map the oxidation state of a surface from shifts in the absorption edge energy across columns of pixels in an image set, and map particular compounds from their characteristic XANES spectra. Optically filtered images give improved chemical selectivity and the data sets contain as yet untapped information sources

On the causes of mid-Pliocene warmth and polar amplification

The mid-Pliocene (~ 3 to 3.3 Ma ago), is a period of sustained global warmth in comparison to the late Quaternary (0 to ~ 1 Ma ago), and has potential to inform predictions of long-term future climate change. However, given that several processes potentially contributed, relatively little is understood about the reasons for the observed warmth, or the associated polar amplification. Here, using a modelling approach and a novel factorisation method, we assess the relative contributions to mid-Pliocene warmth from: elevated CO2, lowered orography, and vegetation and ice sheet changes. The results show that on a global scale, the largest contributor to mid-Pliocene warmth is elevated CO2. However, in terms of polar amplification, changes to ice sheets contribute significantly in the Southern Hemisphere, and orographic changes contribute significantly in the Northern Hemisphere. We also carry out an energy balance analysis which indicates that that on a global scale, surface albedo and atmospheric emmissivity changes dominate over cloud changes. We investigate the sensitivity of our results to uncertainties in the prescribed CO2 and orographic changes, to derive uncertainty ranges for the various contributing processes

Attitudes, beliefs, behaviours and perspectives on barriers and enablers of Australian general practitioners towards non-drug interventions: A national survey

BACKGROUND: Many guidelines recommend non-drug interventions (NDIs) for managing common conditions in primary care. However, compared with drug interventions, NDIs are less widely known, promoted and used. We aim to (1) examine general practitioners' (GPs') knowledge, attitudes and practices for NDIs, including their use of the Royal Australian College of General Practitioners (RACGP) Handbook of Non-Drug Interventions (HANDI), and (2) identify factors influencing their use of NDIs and HANDI.METHODS: We conducted a web-based cross-sectional survey of practicing GP members in Australia during October-November 2022. The survey contained five sections: characteristics of GP; knowledge and use of NDIs; attitudes towards NDIs; barriers and enablers to using HANDI; and suggestions of NDIs and ideas to improve the uptake of NDIs in primary care.RESULTS: Of the 366 GPs who completed the survey, 242 (66%) were female, and 248 (74%) were ≥45 years old. One in three GPs reported that they regularly ('always') recommend NDIs to their patients when appropriate (34%), whereas one-third of GPs were unaware of HANDI (39%). GPs identified several factors that improve the uptake of HANDI, including 'access and integration of HANDI in clinical practice', 'content and support to use in practice' and 'awareness and training'.CONCLUSIONS: While many GPs are aware of the effectiveness of NDIs and often endorse their use, obstacles still prevent widespread adoption in primary care. The results of this survey can serve as a foundation for developing implementation strategies to improve the uptake of effective evidence-based NDIs in primary care.</p

An outbreak and case-control study of Salmonella Havana linked to alfalfa sprouts in South Australia, 2018

An epidemiological investigation and a retrospective case-control study were conducted into an outbreak of Salmonella Havana in alfalfa sprouts, in Adelaide, Australia. In total, 31 cases of S. Havana were notified during June and July 2018 and linked to the outbreak. Eighteen cases and 54 unmatched controls were included in a case-control study. Results from the case-control study indicated an increased risk of illness linked to the consumption of alfalfa sprouts; this was supported by trace-back, sampling and environmental investigations. This outbreak of S. Havana was caused by consumption of alfalfa sprouts from one local sprouts producer. It is unclear as to when in the production of alfalfa sprouts the contamination occurred. However, contaminated seeds and poor pest control are the most likely causes. This investigation highlights the importance of ensuring that producers take appropriate action to minimise the likelihood of contamination and to comply with legislation and standards for primary production and food safety

Evoked responses to rhythmic visual stimulation vary across sources of intrinsic alpha activity in humans

Rhythmic flickering visual stimulation produces steady-state visually evoked potentials (SSVEPs) in electroencephalogram (EEG) recordings. Based on electrode-level analyses, two dichotomous models of the underpinning mechanisms leading to SSVEP generation have been proposed: entrainment or superposition, i.e., phase-alignment or independence of endogenous brain oscillations from flicker-induced oscillations, respectively. Electrode-level analyses, however, represent an averaged view of underlying ‘source-level’ activity, at which variability in SSVEPs may lie, possibly suggesting the co-existence of multiple mechanisms. To probe this idea, we investigated the variability of SSVEPs derived from the sources underpinning scalp EEG responses during presentation of a flickering radial checkerboard. Flicker was presented between 6 and 12 Hz in 1 Hz steps, and at individual alpha frequency (IAF i.e., the dominant frequency of endogenous alpha oscillatory activity). We tested whether sources of endogenous alpha activity could be dissociated according to evoked responses to different flicker frequencies relative to IAF. Occipitoparietal sources were identified by temporal independent component analysis, maximal resting-state alpha power at IAF and source localisation. The pattern of SSVEPs to rhythmic flicker relative to IAF was estimated by correlation coefficients, describing the correlation between the peak-to-peak amplitude of the SSVEP and the absolute distance of the flicker frequency from IAF across flicker conditions. We observed extreme variability in correlation coefficients across sources, ranging from −0.84 to 0.93, with sources showing largely different coefficients co-existing within subjects. This result demonstrates variation in evoked responses to flicker across sources of endogenous alpha oscillatory activity. Data support the idea of multiple SSVEP mechanisms

Drug development in Alzheimer’s disease: The path to 2025

The global impact of Alzheimer’s disease (AD) continues to increase, and focused efforts are needed to address this immense public health challenge. National leaders have set a goal to prevent or effectively treat AD by 2025. In this paper, we discuss the path to 2025, and what is feasible in this time frame given the realities and challenges of AD drug development, with a focus on disease-modifying therapies (DMTs). Under the current conditions, only drugs currently in late Phase 1 or later will have a chance of being approved by 2025. If pipeline attrition rates remain high, only a few compounds at best will meet this time frame. There is an opportunity to reduce the time and risk of AD drug development through an improvement in trial design; better trial infrastructure; disease registries of well-characterized participant cohorts to help with more rapid enrollment of appropriate study populations; validated biomarkers to better detect disease, determine risk and monitor disease progression as well as predict disease response; more sensitive clinical assessment tools; and faster regulatory review. To implement change requires efforts to build awareness, educate and foster engagement; increase funding for both basic and clinical research; reduce fragmented environments and systems; increase learning from successes and failures; promote data standardization and increase wider data sharing; understand AD at the basic biology level; and rapidly translate new knowledge into clinical development. Improved mechanistic understanding of disease onset and progression is central to more efficient AD drug development and will lead to improved therapeutic approaches and targets. The opportunity for more than a few new therapies by 2025 is small. Accelerating research and clinical development efforts and bringing DMTs to market sooner would have a significant impact on the future societal burden of AD. As these steps are put in place and plans come to fruition, e.g., approval of a DMT, it can be predicted that momentum will build, the process will be self-sustaining, and the path to 2025, and beyond, becomes clearer

Combined quantitative measures of ER, PR, HER2, and KI67 provide more prognostic information than categorical combinations in luminal breast cancer.

Although most women with luminal breast cancer do well on endocrine therapy alone, some will develop fatal recurrence thereby necessitating the need to prospectively determine those for whom additional cytotoxic therapy will be beneficial. Categorical combinations of immunohistochemical measures of ER, PR, HER2, and KI67 are traditionally used to classify patients into luminal A-like and B-like subtypes for chemotherapeutic reasons, but this may lead to the loss of prognostically relevant information. Here, we compared the prognostic value of quantitative measures of these markers, combined in the IHC4-score, to categorical combinations in subtypes. Using image analysis-based scores for all four markers, we computed the IHC4-score for 2498 patients with luminal breast cancer from two European study populations. We defined subtypes (A-like (ER + and PR + : and HER2- and low KI67) and B-like (ER + and/or PR + : and HER2 + or high KI67)) by combining binary categories of these markers. Hazard ratios and 95% confidence intervals for associations with 10-year breast cancer-specific survival were estimated in Cox proportional-hazard models. We accounted for clinical prognostic factors, including grade, tumor size, lymph-nodal involvement, and age, by using the PREDICT-score. Overall, Subtypes [hazard ratio (95% confidence interval) B-like vs. A-like = 1.64 (1.25-2.14); P-value < 0.001] and IHC4-score [hazard ratio (95% confidence interval)/1 standard deviation = 1.32 (1.20-1.44); P-value < 0.001] were prognostic in univariable models. However, IHC4-score [hazard ratio (95% confidence interval)/1 standard deviation = 1.24 (1.11-1.37); P-value < 0.001; likelihood ratio chi-square (LRχ2) = 12.5] provided more prognostic information than Subtype [hazard ratio (95% confidence interval) B-like vs. A-like = 1.38 (1.02-1.88); P-value = 0.04; LRχ2 = 4.3] in multivariable models. Further, higher values of the IHC4-score were associated with worse prognosis, regardless of subtype (P-heterogeneity = 0.97). These findings enhance the value of the IHC4-score as an adjunct to clinical prognostication tools for aiding chemotherapy decision-making in luminal breast cancer patients, irrespective of subtype