Occupational Histories of Cancer Patients in a Canadian Cancer Treatment Centre and the Generated Hypothesis Regarding Breast Cancer and Farming

Occupational exposures increase cancer risks. The Windsor Regional Cancer Centre in Windsor, Ontario, was the first Canadian cancer treatment center to collect the work histories of its patients, which were recorded using a computer-based questionnaire. Breast cancer cases represented the largest respondent group. The lifetime occupational histories of 299 women with newly diagnosed breast cancers were compared with those of 237 women with other cancers. Odds ratios (ORs) were calculated using logistic regression, adjusting for age, social class, and education. The OR for women £ 55 years of age with breast cancer who had ever farmed, compared with women of the same age with other cancers, was 9.05 (95% CI 1.06, 77.43). Patients’ occupational histories can help to inform understanding of cancer etiology and prevention. This effort points to a need for investigation of the possible association between breast cancer and agricultural hazards such as pesticides

Protein synthesis is associated with high-speed dynamics and broad-band stability of functional hubs in the brain.

L-[1-(11)C]leucine PET can be used to measure in vivo protein synthesis in the brain. However, the relationship between regional protein synthesis and on-going neural dynamics is unclear. We use a graph theoretical approach to examine the relationship between cerebral protein synthesis (rCPS) and both static and dynamical measures of functional connectivity (measured using resting state functional MRI, R-fMRI). Our graph theoretical analysis demonstrates a significant positive relationship between protein turnover and static measures of functional connectivity. We compared these results to simple measures of metabolism in the cortex using [(18)F]FDG PET). Whilst some relationships between [(18)F]FDG binding and graph theoretical measures was present, there remained a significant relationship between protein turnover and graph theoretical measures, which were more robustly explained by L-[1-(11)C]Leucine than [(18)F]FDG PET. This relationship was stronger in dynamics at a faster temporal resolution relative to dynamics measured over a longer epoch. Using a Dynamic connectivity approach, we also demonstrate that broad-band dynamic measures of Functional Connectivity (FC), are inversely correlated with protein turnover, suggesting greater stability of FC in highly interconnected hub regions is supported by protein synthesis. Overall, we demonstrate that cerebral protein synthesis has a strong relationship independent of tissue metabolism to neural dynamics at the macroscopic scale

Tuberculosis in Dr Granville's mummy: a molecular re-examination of the earliest known Egyptian mummy to be scientifically examined and given a medical diagnosis

‘Dr Granville's mummy’ was described to the Royal Society of London in 1825 and was the first ancient Egyptian mummy to be subjected to a scientific autopsy. The remains are those of a woman, Irtyersenu, aged about 50, from the necropolis of Thebes and dated to about 600 BC. Augustus Bozzi Granville (1783–1872), an eminent physician and obstetrician, described many organs still in situ and attributed the cause of death to a tumour of the ovary. However, subsequent histological investigations indicate that the tumour is a benign cystadenoma. Histology of the lungs demonstrated a potentially fatal pulmonary exudate and earlier studies attempted to associate this with particular disease conditions. Palaeopathology and ancient DNA analyses show that tuberculosis was widespread in ancient Egypt, so a systematic search for tuberculosis was made, using specific DNA and lipid biomarker analyses. Clear evidence for Mycobacterium tuberculosis complex DNA was obtained in lung tissue and gall bladder samples, based on nested PCR of the IS6110 locus. Lung and femurs were positive for specific M. tuberculosis complex cell-wall mycolic acids, demonstrated by high-performance liquid chromatography of pyrenebutyric acid–pentafluorobenzyl mycolates. Therefore, tuberculosis is likely to have been the major cause of death of Irtyersenu

Starting a conversation about estimands with public partners involved in clinical trials: a co-developed tool

Background: Clinical trials aim to draw conclusions about the effects of treatments, but a trial can address many different potential questions. For example, does the treatment work well for patients who take it as prescribed? Or does it work regardless of whether patients take it exactly as prescribed? Since different questions can lead to different conclusions on treatment benefit, it is important to clearly understand what treatment effect a trial aims to investigate—this is called the ‘estimand’. Using estimands helps to ensure trials are designed and analysed to answer the questions of interest to different stakeholders, including patients and public. However, there is uncertainty about whether patients and public would like to be involved in defining estimands and how to do so. Public partners are patients and/or members of the public who are part of, or advise, the research team. We aimed to (i) co-develop a tool with public partners that helps explain what an estimand is and (ii) explore public partner’s perspectives on the importance of discussing estimands during trial design. Methods: An online consultation meeting was held with 5 public partners of mixed age, gender and ethnicities, from various regions of the UK. Public partner opinions were collected and a practical tool describing estimands, drafted before the meeting by the research team, was developed. Afterwards, the tool was refined, and additional feedback sought via email. Results: Public partners want to be involved in estimand discussions. They found an introductory tool, to be presented and described to them by a researcher, helpful for starting a discussion about estimands in a trial design context. They recommended storytelling, analogies and visual aids within the tool. Four topics related to public partners’ involvement in defining estimands were identified: (i) the importance of addressing questions that are relevant to patients and public in trials, (ii) involving public partners early on, (iii) a need for education and communication for all stakeholders and (iv) public partners and researchers working together. Conclusions: We co-developed a tool for researchers and public partners to use to facilitate the involvement of public partners in estimand discussions

Cascades and Cognitive State: Focused Attention Incurs Subcritical Dynamics

The analysis of neuronal avalanches supports the hypothesis that the human cortex operates with critical neural dynamics. Here, we investigate the relationship between cascades of activity in electroencephalogram data, cognitive state, and reaction time in humans using a multimodal approach. We recruited 18 healthy volunteers for the acquisition of simultaneous electroencephalogram and functional magnetic resonance imaging during both rest and during a visuomotor cognitive task. We compared distributions of electroencephalogram-derived cascades to reference power laws for task and rest conditions. We then explored the large-scale spatial correspondence of these cascades in the simultaneously acquired functional magnetic resonance imaging data. Furthermore, we investigated whether individual variability in reaction times is associated with the amount of deviation from power law form. We found that while resting state cascades are associated with approximate power law form, the task state is associated with subcritical dynamics. Furthermore, we found that electroencephalogram cascades are related to blood oxygen level-dependent activation, predominantly in sensorimotor brain regions. Finally, we found that decreased reaction times during the task condition are associated with increased proximity to power law form of cascade distributions. These findings suggest that the resting state is associated with near-critical dynamics, in which a high dynamic range and a large repertoire of brain states may be advantageous. In contrast, a focused cognitive task induces subcritical dynamics, which is associated with a lower dynamic range, which in turn may reduce elements of interference affecting task performance

Cancer and Construction: What Occupational Histories in a Canadian Community Reveal

From 2000 to 2002, male patients at a Canadian cancer treatment center with new-incident head-and-neck or esophageal cancers were invited to participate in a population-based study. The study population included 87 cases and 172 controls. A lifetime-history questionnaire was administered. Odds ratios (ORs) were calculated for occupational groups with a minimum of five cases, adjusted for duration of employment, age, smoking, alcohol, education, and income. A significantly increased risk was shown for construction workers (OR = 2.20; 95% CI 1.25–3.91). This investigation of a set of rare cancers over a limited time period demonstrates the feasibility of this research approach. The increased risk among construction workers supports the need for more comprehensive study of exposures in this occupational group

Cognitive deficits in people who have recovered from COVID-19.

BACKGROUND: There is growing concern about possible cognitive consequences of COVID-19, with reports of 'Long COVID' symptoms persisting into the chronic phase and case studies revealing neurological problems in severely affected patients. However, there is little information regarding the nature and broader prevalence of cognitive problems post-infection or across the full spread of disease severity. METHODS: We sought to confirm whether there was an association between cross-sectional cognitive performance data from 81,337 participants who between January and December 2020 undertook a clinically validated web-optimized assessment as part of the Great British Intelligence Test, and questionnaire items capturing self-report of suspected and confirmed COVID-19 infection and respiratory symptoms. FINDINGS: People who had recovered from COVID-19, including those no longer reporting symptoms, exhibited significant cognitive deficits versus controls when controlling for age, gender, education level, income, racial-ethnic group, pre-existing medical disorders, tiredness, depression and anxiety. The deficits were of substantial effect size for people who had been hospitalised (N = 192), but also for non-hospitalised cases who had biological confirmation of COVID-19 infection (N = 326). Analysing markers of premorbid intelligence did not support these differences being present prior to infection. Finer grained analysis of performance across sub-tests supported the hypothesis that COVID-19 has a multi-domain impact on human cognition. INTERPRETATION: Interpretation. These results accord with reports of 'Long Covid' cognitive symptoms that persist into the early-chronic phase. They should act as a clarion call for further research with longitudinal and neuroimaging cohorts to plot recovery trajectories and identify the biological basis of cognitive deficits in SARS-COV-2 survivors. FUNDING: Funding. AH is supported by the UK Dementia Research Institute Care Research and Technology Centre and Biomedical Research Centre at Imperial College London. WT is supported by the EPSRC Centre for Doctoral Training in Neurotechnology. SRC is funded by a Wellcome Trust Clinical Fellowship 110,049/Z/15/Z. JMB is supported by Medical Research Council (MR/N013700/1). MAM, SCRW and PJH are, in part, supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London

Infrared spectroscopy of Nova Cassiopeiae 1993 (V705 Cas). IV. A closer look at the dust

Nova Cassiopeiae 1993 (V705 Cas) was an archetypical dust-forming nova. It displayed a deep minimum in the visual light curve, and spectroscopic evidence for carbon, hydrocarbon and silicate dust. We report the results of fitting the infrared spectral energy distribution with the DUSTY code, which we use to determine the properties and geometry of the emitting dust. The emission is well described as originating in a thin shell whose dust has a carbon:silicate ratio of ~2:1 by number (1.26:1 by mass) and a relatively flat size distribution. The 9.7micron and 18micron silicate features are consistent with freshly-condensed dust and, while the lower limit to the grain size distribution is not well constrained, the largest grains have dimensions \~0.06micron; unless the grains in V705 Cas were anomalously small, the sizes of grains produced in nova eruptions may previously have been overestimated in novae with optically thick dust shells. Laboratory work by Grishko & Duley may provide clues to the apparently unique nature of nova UIR features.Comment: 11 pages, 9 fugure