Constraining the chronology and ecology of Late Acheulean and Middle Palaeolithic occupations at the margins of the monsoon

South Asia hosts the world’s youngest Acheulean sites, with dated records typically restricted to sub-humid landscapes. The Thar Desert marks a major adaptive boundary between monsoonal Asia to the east and the Saharo-Arabian desert belt to the west, making it a key threshold to examine patterns of hominin ecological adaptation and its impacts on patterns of behaviour, demography and dispersal. Here, we investigate Palaeolithic occupations at the western margin of the South Asian monsoon at Singi Talav, undertaking new chronometric, sedimentological and palaeoecological studies of Acheulean and Middle Palaeolithic occupation horizons. We constrain occupations of the site between 248 and 65 thousand years ago. This presents the first direct palaeoecological evidence for landscapes occupied by South Asian Acheulean-producing populations, most notably in the main occupation horizon dating to 177 thousand years ago. Our results illustrate the potential role of the Thar Desert as an ecological, and demographic, frontier to Palaeolithic populations.Results - Sediment sequence. - Luminescence dating. - Palaeoenvironmental studies. - Lithic artefacts. Discussion Method

Comparing the Importance of Iodine and Isoprene on Tropospheric Photochemistry

Isoprene, arguably the most studied biogenically emitted gas, is thought to have a large impact on tropospheric composition. Other naturally emitted species have been considered to play a less important role. Here the GEOS-Chem model is used to compare the impacts of isoprene and iodine emissions on present-day tropospheric composition. Removing isoprene emissions leads to a 3.4 burden, a smaller absolute change than the 5.9+0.60.05 whereas isoprene has a substantial impact on both (−4.34.2. Isoprene emissions and chemistry are seen as essential for tropospheric chemistry models, but iodine is often not. We suggest that iodine should receive greater attention in model development and experimental research to allow improved predictions of past, present, and future tropospheric O3

Rydberg-atom-based single-photon detection for haloscope axion searches

We propose a Rydberg-atom-based single-photon detector for signal readout in dark matter haloscope experiments between 40 ${\mu}$eV and 200 ${\mu}$eV (10 GHz and 50 GHz). At these frequencies, standard haloscope readout using linear amplifiers is limited by quantum measurement noise, which can be avoided by using a single-photon detector. Our single-photon detection scheme can offer scan rate enhancements up to a factor of $10^4$ over traditional linear amplifier readout, and is compatible with many different haloscope cavities. We identify multiple haloscope designs that could use our Rydberg-atom-based single-photon detector to search for QCD axions with masses above 40 ${\mu}$eV (10 GHz), currently a minimally explored parameter space.Comment: 15 pages, 8 figure

Challenges and opportunities for ex-offender support through community nursing

This study was a qualitative case study underpinned by “The Silences Framework” aimed at mapping the ex-offender health pathway towards identifying “touch points” in the community for the delivery of a nurse-led intervention. Participants meeting the study inclusion criteria were quantitatively ranked based on poor health. Participants scoring the lowest and endorsing their ranking through a confirmation of a health condition were selected as cases and interviewed over 6 months. Individuals in the professional networks of offenders contextualized emergent themes. The study indicated that pre-release, offenders were not prepared in prison for the continuity in access to healthcare in the community. On release, reintegration preparation did not routinely enquire whether offenders were still registered with a general practitioner or had the agency to register self in the community. Participants identified the site of post-release supervision as the “touch point” where a nurse-led intervention could be delivere

In vivo nucleus basalis of Meynert degeneration in mild cognitive impairment with Lewy bodies.

OBJECTIVES: To investigate in vivo degeneration of the cholinergic system in mild cognitive impairment with Lewy bodies (MCI-LB), we studied nucleus basalis of Meynert (NBM) volumes from structural MR images and its relation to EEG slowing and cognitive impairment. METHODS: We studied the NBM using structural MR images in 37 patients with MCI-LB, 34 patients with MCI with Alzheimer's disease (MCI-AD), and 31 healthy control participants. We also tested correlations between NBM volumes and measures of overall cognition and measures of EEG slowing in the MCI groups. RESULTS: Overall NBM volume was reduced in MCI-LB compared to controls with no significant difference between MCI-AD and controls or between the two MCI groups. The voxel-wise analysis revealed bilateral clusters of reduced NBM volume in MCI-LB compared to controls and smaller clusters in MCI-AD compared to controls. There was a significant association between overall NBM volume and measures of overall cognition in MCI-LB, but not in MCI-AD. In both MCI groups, reduced NBM volume was correlated with more severe EEG slowing. CONCLUSIONS: This study provides in vivo evidence that early cholinergic degeneration in DLB occurs at the MCI stage and is related to the severity of cognitive impairment. Furthermore, the results suggest that early EEG slowing in MCI-LB might be in part cholinergically driven. Importantly, these findings suggest an early cholinergic deficit in MCI-LB that may motivate further testing of the effectiveness of cholinesterase inhibitors in this group

Germline variation in ADAMTSL1 is associated with prognosis following breast cancer treatment in young women

To identify genetic variants associated with breast cancer prognosis we conduct a meta-analysis of overall survival (OS) and disease-free survival (DFS) in 6042 patients from four cohorts. In young women, breast cancer is characterized by a higher incidence of adverse pathological features, unique gene expression profiles and worse survival, which may relate to germline variation. To explore this hypothesis, we also perform survival analysis in 2315 patients agedPeer reviewe

Identifying parkinsonism in mild cognitive impairment.

Introduction Clinical parkinsonism is a core diagnostic feature for mild cognitive impairment with Lewy bodies (MCI-LB) but can be challenging to identify. A five-item scale derived from the Unified Parkinson’s Disease Rating Scale (UPDRS) has been recommended for the assessment of parkinsonism in dementia. This study aimed to determine whether the five-item scale is effective to identify parkinsonism in MCI. Methods Participants with MCI from two cohorts (n=146) had a physical examination including the UPDRS and [123I]-FP-CIT SPECT striatal dopaminergic imaging. Participants were classified as having clinical parkinsonism (P+) or no parkinsonism (P-), and with abnormal striatal dopaminergic imaging (D+) or normal imaging (D-). The five-item scale was the sum of UPDRS tremor at rest, bradykinesia, action tremor, facial expression, and rigidity scores. The ability of the scale to differentiate P+D+ and P-D- participants was examined. Results The five-item scale had an AUROC of 0.92 in Cohort 1, but the 7/8 cut-off defined for dementia had low sensitivity to identify P+D+ participants (sensitivity 25%, specificity 100%). Optimal sensitivity and specificity was obtained at a 3/4 cut-off (sensitivity 83%, specificity 88%). In Cohort 2, the five-item scale had an AUROC of 0.97, and the 3/4 cut-off derived from Cohort 1 showed sensitivity of 100% and a specificity of 82% to differentiate P+D+ from P-D- participants. The five-item scale was not effective in differentiating D+ from D- participants. Conclusions The five-item scale is effective to identify parkinsonism in MCI, but a lower threshold must be used in MCI compared with dementia

Mild cognitive impairment with Lewy bodies: neuropsychiatric supportive symptoms and cognitive profile

This is the author accepted manuscript. The final version is available from Cambridge University Press via the DOI in this recordBackground Recently published diagnostic criteria for mild cognitive impairment with Lewy bodies (MCI-LB) include five neuropsychiatric supportive features (non-visual hallucinations, systematised delusions, apathy, anxiety and depression). We have previously demonstrated that the presence of two or more of these symptoms differentiates MCI-LB from MCI due to Alzheimer’s disease (MCI-AD) with a likelihood ratio >4. The aim of this study was to replicate the findings in an independent cohort. Methods Participants ≥60 years old with MCI were recruited. Each participant had a detailed clinical, cognitive and imaging assessment including FP-CIT SPECT and cardiac MIBG. The presence of neuropsychiatric supportive symptoms was determined using the neuropsychiatric inventory (NPI). Participants were classified as MCI-AD, possible MCI-LB and probable MCI-LB based on current diagnostic criteria. Participants with possible MCI-LB were excluded from further analysis. Results Probable MCI-LB (n=28) had higher NPI total and distress scores than MCI-AD (n=30). 59% of MCI-LB had two or more neuropsychiatric supportive symptoms compared with 9% of MCI-AD (likelihood ratio 6.5, p<0.001). MCI-LB participants also had significantly greater delayed recall and a lower Trails A:Trails B ratio than MCI-AD. Conclusions 5 MCI-LB is associated with significantly greater neuropsychiatric symptoms than MCI-AD. The presence of two or more neuropsychiatric supportive symptoms as defined by MCI-LB diagnostic criteria is highly specific and moderately sensitive for a diagnosis of MCI-LB. The cognitive profile of MCI-LB differs from MCI-AD, with greater executive and lesser memory impairment, but these differences are not sufficient to differentiate MCI-LB from MCI-AD.Alzheimer’s Research UKNational Institute for Health Research (NIHR

Accuracy of dopaminergic imaging as a biomarker for mild cognitive impairment with Lewy bodies.

BACKGROUND: Dopaminergic imaging is an established biomarker for dementia with Lewy bodies, but its diagnostic accuracy at the mild cognitive impairment (MCI) stage remains uncertain. AIMS: To provide robust prospective evidence of the diagnostic accuracy of dopaminergic imaging at the MCI stage to either support or refute its inclusion as a biomarker for the diagnosis of MCI with Lewy bodies. METHOD: We conducted a prospective diagnostic accuracy study of baseline dopaminergic imaging with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computerised tomography (123I-FP-CIT SPECT) in 144 patients with MCI. Images were rated as normal or abnormal by a panel of experts with access to striatal binding ratio results. Follow-up consensus diagnosis based on the presence of core features of Lewy body disease was used as the reference standard. RESULTS: At latest assessment (mean 2 years) 61 patients had probable MCI with Lewy bodies, 26 possible MCI with Lewy bodies and 57 MCI due to Alzheimer's disease. The sensitivity of baseline FP-CIT visual rating for probable MCI with Lewy bodies was 66% (95% CI 52-77%), specificity 88% (76-95%) and accuracy 76% (68-84%), with positive likelihood ratio 5.3. CONCLUSIONS: It is over five times as likely for an abnormal scan to be found in probable MCI with Lewy bodies than MCI due to Alzheimer's disease. Dopaminergic imaging appears to be useful at the MCI stage in cases where Lewy body disease is suspected clinically