Thalamic inflammation after brain trauma is associated with thalamo-cortical white matter damage

Background Traumatic brain injury can trigger chronic neuroinflammation, which may predispose to neurodegeneration. Animal models and human pathological studies demonstrate persistent inflammation in the thalamus associated with axonal injury, but this relationship has never been shown in vivo. Findings Using [11C]-PK11195 positron emission tomography, a marker of microglial activation, we previously demonstrated thalamic inflammation up to 17 years after traumatic brain injury. Here, we use diffusion MRI to estimate axonal injury and show that thalamic inflammation is correlated with thalamo-cortical tract damage. Conclusions These findings support a link between axonal damage and persistent inflammation after brain injury

Aquatic community response to volcanic eruptions on the Ecuadorian Andean flank: evidence from the palaeoecological record

Aquatic ecosystems in the tropical Andes are under increasing pressure from human modification of the landscape (deforestation and dams) and climatic change (increase of extreme events and 1.5 °C on average temperatures are projected for AD 2100). However, the resilience of these ecosystems to perturbations is poorly understood. Here we use a multi-proxy palaeoecological approach to assess the response of aquatic ecosystems to a major mechanism for natural disturbance, volcanic ash deposition. Specifically, we present data from two Neotropical lakes located on the eastern Andean flank of Ecuador. Laguna Pindo (1°27.132′S–78°04.847′W) is a tectonically formed closed basin surrounded by a dense mid-elevation forest, whereas Laguna Baños (0°19.328′S–78°09.175′W) is a glacially formed lake with an inflow and outflow in high Andean Páramo grasslands. In each lake we examined the dynamics of chironomids and other aquatic and semi-aquatic organisms to explore the effect of thick (> 5 cm) volcanic deposits on the aquatic communities in these two systems with different catchment features. In both lakes past volcanic ash deposition was evident from four large tephras dated to c.850 cal year BP (Pindo), and 4600, 3600 and 1500 cal year BP (Baños). Examination of the chironomid and aquatic assemblages before and after the ash depositions revealed no shift in composition at Pindo, but a major change at Baños occurred after the last event around 1500 cal year BP. Chironomids at Baños changed from an assemblage dominated by Pseudochironomus and Polypedilum nubifer-type to Cricotopus/Paratrichocladius type-II, and such a dominance lasted for approximately 380 years. We suggest that, despite potential changes in the water chemistry, the major effect on the chironomid community resulted from the thickness of the tephra being deposited, which acted to shallow the water body beyond a depth threshold. Changes in the aquatic flora and fauna at the base of the trophic chain can promote cascade effects that may deteriorate the ecosystem, especially when already influenced by human activities, such as deforestation and dams, which is frequent in the high Andes

Comparative effectiveness of standard vs. AI-assisted PET/CT reading workflow for pre-treatment lymphoma staging: a multi-institutional reader study evaluation

2024 Frood, Willaime, Miles, Chambers, Al-Chalabi, Ali, Hougham, Brooks, Petrides, Naylor, Ward, Sulkin, Chaytor, Strouhal, Patel and Scarsbrook.Background: Fluorine-18 fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) is widely used for staging high-grade lymphoma, with the time to evaluate such studies varying depending on the complexity of the case. Integrating artificial intelligence (AI) within the reporting workflow has the potential to improve quality and efficiency. The aims of the present study were to evaluate the influence of an integrated research prototype segmentation tool implemented within diagnostic PET/CT reading software on the speed and quality of reporting with variable levels of experience, and to assess the effect of the AI-assisted workflow on reader confidence and whether this tool influenced reporting behaviour. Methods: Nine blinded reporters (three trainees, three junior consultants and three senior consultants) from three UK centres participated in a two-part reader study. A total of 15 lymphoma staging PET/CT scans were evaluated twice: first, using a standard PET/CT reporting workflow; then, after a 6-week gap, with AI assistance incorporating pre-segmentation of disease sites within the reading software. An even split of PET/CT segmentations with gold standard (GS), false-positive (FP) over-contour or false-negative (FN) under-contour were provided. The read duration was calculated using file logs, while the report quality was independently assessed by two radiologists with >15 years of experience. Confidence in AI assistance and identification of disease was assessed via online questionnaires for each case. Results: There was a significant decrease in time between non-AI and AI-assisted reads (median 15.0 vs. 13.3 min, p < 0.001). Sub-analysis confirmed this was true for both junior (14.5 vs. 12.7 min, p = 0.03) and senior consultants (15.1 vs. 12.2 min, p = 0.03) but not for trainees (18.1 vs. 18.0 min, p = 0.2). There was no significant difference between report quality between reads. AI assistance provided a significant increase in confidence of disease identification (p < 0.001). This held true when splitting the data into FN, GS and FP. In 19/88 cases, participants did not identify either FP (31.8%) or FN (11.4%) segmentations. This was significantly greater for trainees (13/30, 43.3%) than for junior (3/28, 10.7%, p = 0.05) and senior consultants (3/30, 10.0%, p = 0.05). Conclusions: The study findings indicate that an AI-assisted workflow achieves comparable performance to humans, demonstrating a marginal enhancement in reporting speed. Less experienced readers were more influenced by segmentation errors. An AI-assisted PET/CT reading workflow has the potential to increase reporting efficiency without adversely affecting quality, which could reduce costs and report turnaround times. These preliminary findings need to be confirmed in larger studies

Family composition and age at menarche: findings from the international Health Behaviour in School-Aged Children Study

This research was funded by The University of St Andrews and NHS Health Scotland.Background Early menarche has been associated with father absence, stepfather presence and adverse health consequences in later life. This article assesses the association of different family compositions with the age at menarche. Pathways are explored which may explain any association between family characteristics and pubertal timing. Methods Cross-sectional, international data on the age at menarche, family structure and covariates (age, psychosomatic complaints, media consumption, physical activity) were collected from the 2009–2010 Health Behaviour in School-aged Children (HBSC) survey. The sample focuses on 15-year old girls comprising 36,175 individuals across 40 countries in Europe and North America (N = 21,075 for age at menarche). The study examined the association of different family characteristics with age at menarche. Regression and path analyses were applied incorporating multilevel techniques to adjust for the nested nature of data within countries. Results Living with mother (Cohen’s d = .12), father (d = .08), brothers (d = .04) and sisters (d = .06) are independently associated with later age at menarche. Living in a foster home (d = −.16), with ‘someone else’ (d = −.11), stepmother (d = −.10) or stepfather (d = −.06) was associated with earlier menarche. Path models show that up to 89% of these effects can be explained through lifestyle and psychological variables. Conclusions Earlier menarche is reported amongst those with living conditions other than a family consisting of two biological parents. This can partly be explained by girls’ higher Body Mass Index in these families which is a biological determinant of early menarche. Lower physical activity and elevated psychosomatic complaints were also more often found in girls in these family environments.Publisher PDFPeer reviewe

Mechanisms of Psychological Distress following War in the Former Yugoslavia: The Role of Interpersonal Sensitivity

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This study was funded by a grant from the European Commission, contract number INCO-CT-2004-509176. AN was supported by a Clinical Early Career Research Fellowship (113295) and a Project Grant (104288

Intraregional variability in chironomid-inferred temperature estimates and the influence of river inundations on lacustrine chironomid assemblages.

Floodplain lakes are rarely analysed for fossil chironomids and usually not incorporated in modern chironomid-climate calibration datasets because of the potential complex hydrological processes that could result from flooding of the lakes. In order to investigate this potential influence of river inundations on fossil chironomid assemblages, 13 regularly inundated lakes and 20 lakes isolated from riverine influence were sampled and their surface sediments analysed for subfossil chironomid assemblages. The physical and chemical settings of all lakes were similar, although the variation in the environmental variables was higher in the lakes isolated from riverine influence. Chironomid concentration and taxon richness show significant differences between the two classes of lakes, and the variation in these variables is best explained by loss-on-ignition of the sediments (LOI). Relative chironomid abundances show some differences between the two groups of lakes, with several chironomid taxa occurring preferentially in one of the two lake-types. The variability in chironomid assemblages is also best explained by LOI. Application of a chironomid-temperature inference model shows that both types of lakes reconstruct July air temperatures that are equal to, or slightly underestimating, the measured temperature of the region. We conclude that, although there are some differences between the chironomid assemblages of floodplain lakes and of isolated lakes, these differences do not have a major effect on chironomid-based temperature reconstruction. © 2007 Springer Science+Business Media B.V

A falls prevention programme to improve quality of life, physical function and falls efficacy in older people receiving home help services: study protocol for a randomised controlled trial

BACKGROUND: Falls and fall-related injuries in older adults are associated with great burdens, both for the individuals, the health care system and the society. Previous research has shown evidence for the efficiency of exercise as falls prevention. An understudied group are older adults receiving home help services, and the effect of a falls prevention programme on health-related quality of life is unclear. The primary aim of this randomised controlled trial is to examine the effect of a falls prevention programme on quality of life, physical function and falls efficacy in older adults receiving home help services. A secondary aim is to explore the mediating factors between falls prevention and health-related quality of life. METHODS: The study is a single-blinded randomised controlled trial. Participants are older adults, aged 67 or older, receiving home help services, who are able to walk with or without walking aids, who have experienced at least one fall during the last 12 months and who have a Mini Mental State Examination of 23 or above. The intervention group receives a programme, based on the Otago Exercise Programme, lasting 12 weeks including home visits and motivational telephone calls. The control group receives usual care. The primary outcome is health-related quality of life (SF-36). Secondary outcomes are leg strength, balance, walking speed, walking habits, activities of daily living, nutritional status and falls efficacy. All measurements are performed at baseline, following intervention at 3 months and at 6 months' follow-up. Sample size, based on the primary outcome, is set to 150 participants randomised into the two arms, including an estimated 15-20% drop out. Participants are recruited from six municipalities in Norway. DISCUSSION: This trial will generate new knowledge on the effects of an exercise falls prevention programme among older fallers receiving home help services. This knowledge will be useful for clinicians, for health managers in the primary health care service and for policy makers

Correlations of behavioral deficits with brain pathology assessed through longitudinal MRI and histopathology in the R6/1 mouse model of huntington's disease

Huntington's disease (HD) is caused by the expansion of a CAG repeat in the huntingtin (HTT) gene. The R6 mouse models of HD express a mutant version of exon 1 HTT and typically develop motor and cognitive impairments, a widespread huntingtin (HTT) aggregate pathology and brain atrophy. Unlike the more commonly used R6/2 mouse line, R6/1 mice have fewer CAG repeats and, subsequently, a less rapid pathological decline. Compared to the R6/2 line, fewer descriptions of the progressive pathologies exhibited by R6/1 mice exist. The association between the molecular and cellular neuropathology with brain atrophy, and with the development of behavioral phenotypes remains poorly understood in many models of HD. In attempt to link these factors in the R6/1 mouse line, we have performed detailed assessments of behavior and of regional brain abnormalities determined through longitudinal, in vivo magnetic resonance imaging (MRI), as well as an end-stage, ex vivo MRI study and histological assessment. We found progressive decline in both motor and non-motor related behavioral tasks in R6/1 mice, first evident at 11 weeks of age. Regional brain volumes were generally unaffected at 9 weeks, but by 17 weeks there was significant grey matter atrophy. This age-related brain volume loss was validated using a more precise, semi-automated Tensor Based morphometry assessment. As well as these clear progressive phenotypes, mutant HTT (mHTT) protein, the hallmark of HD molecular pathology, was widely distributed throughout the R6/1 brain and was accompanied by neuronal loss. Despite these seemingly concomitant, robust pathological phenotypes, there appeared to be little correlation between the three main outcome measures: behavioral performance, MRI-detected brain atrophy and histopathology. In conclusion, R6/1 mice exhibit many features of HD, but the underlying mechanisms driving these clear behavioral disturbances and the brain volume loss, still remain unclear. © 2013 Rattray et al

HIV Drug Resistance Surveillance Using Pooled Pyrosequencing

BACKGROUND: Surveillance for HIV transmitted drug resistance (TDR) is performed using HIV genotype results from individual specimens. Pyrosequencing, through its massive parallel sequencing ability, can analyze large numbers of specimens simultaneously. Instead of using pyrosequencing conventionally, to sequence a population of viruses within an individual, we interrogated a single combined pool of surveillance specimens to demonstrate that it is possible to determine TDR rates in HIV protease from a population of individuals. METHODOLOGY/PRINCIPAL FINDINGS: The protease region from 96 treatment naïve, HIV+ serum specimens was genotyped using standard Sanger sequencing method. The 462 bp protease amplicons from these specimens were pooled in equimolar concentrations and re-sequenced using the GS FLX Titanium system. The nucleotide (NT) and amino acid (AA) differences from the reference sequence, along with TDR mutations, detected by each method were compared. In the protease sequence, there were 212 nucleotide and 81 AA differences found using conventional sequencing and 345 nucleotide and 168 AA differences using pyrosequencing. All nucleotide and amino acid polymorphisms found at frequencies >/=5% in pyrosequencing were detected using both methods with the rates of variation highly correlated. Using Sanger sequencing, two TDR mutations, M46L and I84V, were each detected as mixtures at a frequency of 1.04% (1/96). These same TDR mutations were detected by pyrosequencing with a prevalence of 0.29% and 0.34% respectively. Phylogenetic analysis established that the detected low frequency mutations arose from the same single specimens that were found to contain TDR mutations by Sanger sequencing. Multiple clinical protease DR mutations present at higher frequencies were concordantly identified using both methods. CONCLUSIONS/SIGNIFICANCE: We show that pyrosequencing pooled surveillance specimens can cost-competitively detect protease TDR mutations when compared with conventional methods. With few modifications, the method described here can be used to determine population rates of TDR in both protease and reverse transcriptase. Furthermore, this pooled pyrosequencing technique may be generalizable to other infectious agents where a survey of DR rates is required