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Background and Purpose: Clinical trials in spinocerebellar ataxia type 3 (SCA3) will require biomarkers for use as outcome measures., Methods: To evaluate total tau (t-tau), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCHL1) and neurofilament light-chain (NfL) as fluid biomarkers in SCA3, ATXN3 mutation carriers (n = 143) and controls (n = 172) were clinically assessed, and the plasma concentrations of the four proteins were analysed on the Simoa HD-1 platform. Eleven ATXN3 mutation carrier cerebrospinal fluid samples were analysed for t-tau and phosphorylated tau (p-tau 181 ). A transgenic SCA3 mouse model (MJDTg) was used to measure cerebellar t-tau levels., Results: Plasma t-tau levels were higher in mutation carriers below the age of 50 compared to controls, and the Inventory of Non-Ataxia Signs was associated with t-tau in ataxic patients (p = 0.004). Pre-ataxic carriers showed higher cerebrospinal fluid t-tau and p-tau 181 concentrations compared to ataxic patients (p = 0.025 and p = 0.014, respectively). Cerebellar t-tau was elevated in MJDTg mice compared to wild-type (p = 0.033) only in the early stages of the disease. GFAP and UCHL1 did not show higher levels in mutation carriers compared to controls. Plasma NfL concentrations were higher in mutation carriers compared to controls, and differences were greater for younger carriers. The Scale for the Assessment and Rating of Ataxia was the strongest predictor of NfL in ataxic patients (p < 0.001)., Conclusion: Our results suggest that tau might be a marker of early disease stages in SCA3. NfL can discriminate mutation carriers from controls and is associated with different clinical variables. Longitudinal studies are required to confirm their potential role as biomarkers in clinical trials., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Many countries are introducing low-dose computed tomography screening programmes for people at high risk of lung cancer. Effective communication strategies that convey risks and benefits, including unfamiliar concepts and outcome probabilities based on population risk, are critical to achieving informed choice and mitigating inequalities in uptake., Methods: This study investigated the acceptability of an aspect of NHS England's communication strategy in the form of a leaflet that was used to invite and inform eligible adults about the Targeted Lung Health Check (TLHC) programme. Acceptability was assessed in terms of how individuals engaged with, comprehended and responded to the leaflet. Semi-structured, 'think aloud' interviews were conducted remotely with 40 UK screening-naïve current and former smokers (aged 55-73). The verbatim transcripts were analysed thematically using a coding framework based on the Dual Process Theory of cognition., Results: The leaflet helped participants understand the principles and procedures of screening and fostered cautiously favourable intentions. Three themes captured the main results of the data analysis: (1) Response-participants experienced anxiety about screening results and further investigations, but the involvement of specialist healthcare professionals was reassuring; (2) Engagement-participants were rapidly drawn to information about lung cancer prevalence, and benefits of screening, but deliberated slowly about early diagnosis, risks of screening and less familiar symptoms of lung cancer; (3) Comprehension-participants understood the main principles of the TLHC programme, but some were confused by its rationale and eligibility criteria. Radiation risks, abnormal screening results and numerical probabilities of screening outcomes were hard to understand., Conclusion: The TLHC information leaflet appeared to be acceptable to the target population. There is scope to improve aspects of comprehension and engagement in ways that would support informed choice as a distributed process in lung cancer screening., Patient or Public Contribution: The insight and perspectives of patient representatives directly informed and improved the design and conduct of this study., (© 2022 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Background: Lung cancer is the leading cause of cancer death in the world. A significant minority of lung cancer patients have never smoked (14% in the UK, and ranging from 10% to 25% worldwide). Current evidence suggests that never-smokers encounter delays during the diagnostic pathway, yet it is unclear how their experiences and reasons for delayed diagnoses differ from those of current and former smokers. This rapid review assessed literature about patient experiences in relation to symptom awareness and appraisal, help-seeking, and the lung cancer diagnostic pathway, comparing patients with and without a smoking history., Methods: MEDLINE, PsychINFO and Google Scholar were searched for studies (2010-2020) that investigated experiences of the pathway to diagnosis for patients with and without a smoking history. Findings are presented using a narrative synthesis., Results: Analysis of seven quantitative and three qualitative studies revealed that some delays during symptom appraisal and diagnosis are unique to never-smokers. Due to the strong link between smoking and lung cancer, and low awareness of non-smoking related lung cancer risk factors and symptoms, never-smokers do not perceive themselves to be at risk. Never-smokers are also likely to evaluate their experiences in comparison with other non-smoking related cancers, where prognosis is likely better, potentially leading to lower satisfaction with healthcare., Conclusion: Never-smokers appear to have different experiences in relation to symptom appraisal and diagnosis. However, evidence in relation to help-seeking, and what is driving diagnostic delays for never-smoker patients specifically is lacking., (© 2021 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd.)

Background: Stage at diagnosis of breast cancer varies by socio-economic status (SES), with lower SES associated with poorer survival. We investigated associations between SES (indexed by education), and the likelihood of attributing breast symptoms to breast cancer., Method: We conducted an online survey with 961 women (47-92 years) with variable educational levels. Two vignettes depicted familiar and unfamiliar breast changes (axillary lump and nipple rash). Without making breast cancer explicit, women were asked 'What do you think this […..] could be?' After the attribution question, women were asked to indicate their level of agreement with a cancer avoidance statement ('I would not want to know if I have breast cancer')., Results: Women were more likely to mention cancer as a possible cause of an axillary lump (64%) compared with nipple rash (30%). In multivariable analysis, low and mid education were independently associated with being less likely to attribute a nipple rash to cancer (OR 0.51, 0.36-0.73 and OR 0.55, 0.40-0.77, respectively). For axillary lump, low education was associated with lower likelihood of mentioning cancer as a possible cause (OR 0.58, 0.41-0.83). Although cancer avoidance was also associated with lower education, the association between education and lower likelihood of making a cancer attribution was independent., Conclusion: Lower education was associated with lower likelihood of making cancer attributions for both symptoms, also after adjustment for cancer avoidance. Lower likelihood of considering cancer may delay symptomatic presentation and contribute to educational differences in stage at diagnosis. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Background: Studies of body mass index (BMI) change have focused on understanding growth trajectories from childhood to adolescence and adolescence to adulthood, but few have explored BMI trajectories solely in elementary (grades K-5) school children. This report complements these studies by exploring changes in obesity status using analytic methods developed to investigate categorical changes in life-course events., Methods: Sequences of a 4-state BMI variable (underweight, normal, overweight, and obese) were calculated using height and weight data collected annually (2008-2013) from 414 kindergarten and first-grade students participating in the Community and Schools Together (CAST) project. These sequences were explored using the TraMineR software package to investigate the distribution of sequences and states, calculate transition rates among states, and examine clustering of sequences., Results: Aggregated cluster solutions were identified consisting of either 4 clusters (normal, stepped, mixed, and obese) or 3 clusters (aggregation of obese cluster cases into stepped cluster) with membership in the former predicted by ethnicity and socioeconomic status (SES) and the latter by SES alone. Transition rate patterns among states varied markedly by cluster and state., Conclusion: The finding of early emergence of stable obesity states, especially in Hispanic children confirms the need for early childhood interventions to influence BMI., (© 2016, American School Health Association.)

Little research has explored the views of patients referred to specialist genetic eye clinics. Future service development must be informed by the perspectives of patients to ensure services are accessible and meet their needs. Semi-structured telephone interviews were undertaken with patients referred to the Genetic Eye Clinic in Manchester, UK. Participants were interviewed before their first appointment. The interview transcripts were analysed using Interpretative Phenomenological Analysis (IPA). Nine interviews took place. Five participants were adults with sight loss and 4 were the parent/carer of a child patient. The major themes identified were: expectations of a medical-genetic focus to the clinic, psychological adjustment to the diagnosis of an eye condition impacting on counselling and support needs, lack of preparation and restricted expectations due to unfamiliarity with the service and positive attitudes towards genetic research and testing. Key motivating factors for patients attending specialist ophthalmic genetic services are medical-genetic orientated, including accurate diagnostic and prognostic information, participation in research and clarification of recurrence risks. Some barriers to patients accessing and fully engaging with services were identified. There is a need to raise awareness of the specialist service amongst the public, patient organisations and professionals. Facilitating patient preparation for clinic could improve patient outcomes, and the need for integrated services is reinforced. The results feed into the development of a best practice model for the delivery of specialist ophthalmic genetic services.

Purpose: The process of invasion and metastasis formation of tumor cells can be studied by following the migration of labeled cells over prolonged time periods. This report investigates the applicability of iron oxide nanoparticles as a magnetic resonance imaging (MRI) contrast agent for cell labeling., Methods: γFe2 O3 nanoparticles prepared with direct flame spray pyrolysis are biofunctionalized with poly-l-lysine (PLL). The nanoparticles within the cells were observed with transmission electron microscopy, bright-field microscopy, and magnetorelaxometry. MRI of labeled cells suspended in agarose was used to estimate the detection limit., Results: PLL-coated particles are readily taken up, stored in intracellular clusters, and gradually degraded by the cells. During cell division, the nanoparticle clusters are divided and split between daughter cells. The MRI detection limit was found to be 25 cells/mm(3) for R2*, and 70 cells/mm(3) for R2. The iron specificity, however, was higher for R2 images. Due to the degradation of intracellular γFe2 O3 to paramagnetic iron ions within 13 days, the R1, R2, and R2* contrast gradually decreased over this time period to approximately 50% of its initial value., Conclusions: These results suggest that PLL-coated γFe2 O3 nanoparticles can be used as an MRI contrast agent for long-term studies of cell migration. Magn Reson Med 71:1896-1905, 2014. © 2013 Wiley Periodicals, Inc., (Copyright © 2013 Wiley Periodicals, Inc.)

The barrier heights involved in the abstraction of a hydrogen atom from n-butanol by the hydroperoxyl radical have been computed with both compound (CBS-QB3, CBS-APNO, G3) and coupled cluster methods. In particular, the benchmark computations CCSD(T)/cc-pVTZ//MP2/6-311G(d,p) were used to determine that the barrier heights increase in the order alpha < gamma < beta < delta < OH. Two prereaction hydrogen-bonded complexes are formed, one of which connects the TGt conformer of n-butanol to the alpha and beta transition states and the other connects to the gamma and OH channels from the TGg conformer. Four postreaction complexes were also found which link the transition states to the products, hydrogen peroxide + C(4)H(9)O radical. Abstraction from the terminal delta carbon atom does not involve either a pre or postreaction complex. A number of DFT functionals-B3LYP, BMK, MPWB1K, BB1K, MPW1K, and M05-2X-were tested to see whether the correct ranking could be obtained with computationally less expensive methods. Only the later functional predicts the correct order but requires a basis set of 6-311++G(df,pd) to achieve this. However, the absolute values obtained do not agree that well with the benchmarks; the composite G3 method predicts the correct order and comes closest (< or = 2 kJ, mol (-1)) in absolute numerical terms for H-abstraction from carbon., (2009 Wiley Periodicals, Inc.)

New and improved strategies are eagerly sought for the rapid identification of microorganisms, particularly in mixtures. Mass spectrometry remains a powerful tool for this purpose. Small acid-soluble proteins (SASPs), which are relatively abundant in Bacillus spores, represent potential biomarkers for species characterization. Despite sharing extensive sequence homology, these proteins differ sufficiently in sequence for discrimination between species. This work focuses on the differences in sequence between SASPs from various Bacillus species. Compilation of SASP sequences from protein database searches, followed by in silico trypsin digestion and analysis of the resulting fragments, identified several species-specific peptides that could be targeted for analysis using mass spectrometry. This strategy was tested and found to be successful in the characterization of Bacillus spores both from individual species and in mixtures. Analysis was performed using an ion trap mass spectrometer with an atmospheric pressure MALDI source. This instrumentation offers the advantage of increased speed of analysis and accurate precursor ion selection for tandem mass spectrometric analysis compared with vacuum matrix-assisted laser desorption/ionization and time-of-flight instruments. The identification and targeting of species-specific peptides using this type of instrumentation offers a rapid, efficient strategy for the identification of Bacillus spores and can potentially be applied to different microorganisms., (Copyright 2005 John Wiley & Sons, Ltd.)

Amazonian localized cutaneous leishmaniasis (LCL) is caused by parasites of the subgenera Leishmania and Viannia. Respectively, these parasites may cause diffuse cutaneous leishmaniasis (DCL) and mucocutaneous leishmaniasis (MCL). This, together with differing skin test responses, suggests some species-specificity in cell mediated immunity. In this study, T cell responses (proliferative and interferon-gamma) to crude and defined antigens were examined in paired samples pre and post chemotherapy. Untreated L. (L.) amazonensis LCL patients showed lower responses to crude leishmanial antigens than the L. (V.) spp. group. L. (V.) braziliensis antigen was a more potent stimulator of T cell responses than L. (L.) amazonensis antigen in all patient groups. Few positive responses were seen to the L. (L.) amazonensis glycoprotein GP46. A substantial proportion of LCL patients did respond to the L. (L.) pifanoi amastigote antigens A2, and the surface membrane glycoprotein P8. DCL patients were poor responders to all leishmanial antigens, except GP46. In contrast, MCL patients were good responders to all antigens except GP46 and A2. A significant rise in the response to P8 and A2 antigen was seen post treatment across all LCL and MCL patients, indicating that these antigens might provide suitable vaccine candidates.