Regulatory T cells enhance Th17 migration in psoriatic arthritis which is reversed by anti-TNF

Regulatory T cells (Treg) prevent the migration of effector T cells toward sites of inflammation, thereby limiting disease progression. We investigated this aspect of Treg function using psoriatic arthritis (PsA) as an exemplar of chronic inflammation. Patients with PsA had an increased Th17:Treg ratio which was reversed by anti-tumor necrosis factor (TNF) therapy. Utilizing an in vitro migration assay, Treg from patients with PsA treated with conventional therapy paradoxically boosted CCR6(+) effector T-cell (a surrogate for Th17) migration toward CCL20. In contrast, Treg from patients with PsA treated with anti-TNF suppressed CCL20-driven effector T-cell migration. The boosting effect of TNF blockade upon Treg suppression of migration was accompanied by increased effector T-cell CCL20 production and enhanced interaction between Treg and effector T cells. This study provides mechanistic insight into Treg modulation of effector T-cell migration in patients with chronic inflammation and how this can be targeted by therapy

Reproductive biology and ex situ conservation of the genus Restrepia (Orchidaeae)

The genus Restrepia is well known to orchid enthusiasts but its micromorphology has not been described, and its pollination and breeding systems have not been investigated. The aim of this investigation was, therefore, to add to existing knowledge so that the resultant data could be used to facilitate ex situ conservation initiatives. A detailed electron microscopy study (SEM) of the floral organs was performed. This confirmed the structure of the dorsal sepal and lateral petal osmophores, their secretory nature together with that of the synsepal and the labellum. It was postulated how, by manipulating different labellar surface textures, the flower might use these ‘tactile guides’ to steer the insect (fly) through the flower. The cirrhi were postulated to help by destabilising the pollinator in flight, trapping it and bringing about pollination. The papillate structure of the calli was established and their optical properties investigated. Media comparison investigations established that Western medium supported the highest germination rates and, with the addition of banana supplement, the highest rates for seedling growth and development. This represented the first protocol for axenic germination of Restrepia in the literature (Millner et al., 2008) and provided a tested methodology for investigating breeding systems and producing Restrepia plant material for both scientific and horticultural purposes. Self-pollinations were found to produce fewer embryos compared to cross-pollinations. The operation of self-incompatibility (SI) was confirmed by the study of pollen tube growth which further confirmed the time interval between pollination and fertilisation. A time line from pollination/fertilisation to flowering was established. The type of SI in operation was best explained by gametophytic incompatibility. This demonstrated that it was possible to raise Restrepia hybrids and species from seed, by performing intraspecific crosses so helping to preserve them for posterity and relieve pressure on wild populations. Narrow endemic Restrepia species face combined threats from habitat loss, habitat degradation and problems of viable seed production due to the effects of SI and inbreeding depression (ID). Recently developed online resources, such as GeoCAT, were used to perform a Red List assessment in order to identify the degree of threat individual species faced, both globally and nationally. All species were classified as facing substantial levels of threat; although this was lessened for populations in protected habitats. Conservation is needed for cultivated collections as well as these wild populations by keeping alive existing knowledge and expertise in growing these species.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

An analysis of mental imagery in grades two, three, four and five

Thesis (Ed.M.)--Boston UniversityImagery may be defined as a picture seen in one's mind. It is the ability to create pictures, to hear sounds, to smell odors, to taste, and to feel in one's mind as one reads. All these factors contribute to the varying degrees of mental imagery possessed by different individuals. It may be assumed that people visualize when they read. A writer may give a description of a person or a place, and the reader can recreate the scene in his own mind. The reader's picture may be clear or it may be vague. However, since every individual is different the same sentence or paragraph may appear differently to the subjects being tested. [TRUNCATED

What is the Definition of Cure in Non-small Cell Lung Cancer?

The concept of cure from cancer is important to patients, but can be difficult to communicate in terms that are meaningful. This is because there are a number of definitions of cure that are applied by clinicians, patients and the public, and by policymakers that have a different meaning and significance. In this article, we provide a narrative review of the evidence concerning cure in lung cancer and show how the different definitions may apply in different settings. A better understanding of the various concepts of cure will improve communication with patients on this important topic. This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors

Population vs Individual Prediction of Poor Health from Results of Adverse Childhood Experiences Screening

Importance: Adverse childhood experiences (ACEs) are well-established risk factors for health problems in a population. However, it is not known whether screening for ACEs can accurately identify individuals who develop later health problems. Objective: To test the predictive accuracy of ACE screening for later health problems. Design, Setting, and Participants: This study comprised 2 birth cohorts: the Environmental Risk (E-Risk) Longitudinal Twin Study observed 2232 participants born during the period from 1994 to 1995 until they were aged 18 years (2012-2014); the Dunedin Multidisciplinary Health and Development Study observed 1037 participants born during the period from 1972 to 1973 until they were aged 45 years (2017-2019). Statistical analysis was performed from May 28, 2018, to July 29, 2020. Exposures: ACEs were measured prospectively in childhood through repeated interviews and observations in both cohorts. ACEs were also measured retrospectively in the Dunedin cohort through interviews at 38 years. Main Outcomes and Measures: Health outcomes were assessed at 18 years in E-Risk and at 45 years in the Dunedin cohort. Mental health problems were assessed through clinical interviews using the Diagnostic Interview Schedule. Physical health problems were assessed through interviews, anthropometric measurements, and blood collection. Results: Of 2232 E-Risk participants, 2009 (1051 girls [52%]) were included in the analysis. Of 1037 Dunedin cohort participants, 918 (460 boys [50%]) were included in the analysis. In E-Risk, children with higher ACE scores had greater risk of later health problems (any mental health problem: relative risk, 1.14 [95% CI, 1.10-1.18] per each additional ACE; any physical health problem: relative risk, 1.09 [95% CI, 1.07-1.12] per each additional ACE). ACE scores were associated with health problems independent of other information typically available to clinicians (ie, sex, socioeconomic disadvantage, and history of health problems). However, ACE scores had poor accuracy in predicting an individual's risk of later health problems (any mental health problem: area under the receiver operating characteristic curve, 0.58 [95% CI, 0.56-0.61]; any physical health problem: area under the receiver operating characteristic curve, 0.60 [95% CI, 0.58-0.63]; chance prediction: area under the receiver operating characteristic curve, 0.50). Findings were consistent in the Dunedin cohort using both prospective and retrospective ACE measures. Conclusions and Relevance: This study suggests that, although ACE scores can forecast mean group differences in health, they have poor accuracy in predicting an individual's risk of later health problems. Therefore, targeting interventions based on ACE screening is likely to be ineffective in preventing poor health outcomes

What characteristics of primary care and patients are associated with early death in patients with lung cancer in the UK?

Background: The UK has poor lung cancer survival rates and high early mortality, compared to other countries. We aimed to identify factors associated with early death, and features of primary care that might contribute to late diagnosis. Methods: All cases of lung cancer diagnosed between 2000 and 2013 were extracted from The Health Improvement Network database. Patients who died within 90 days of diagnosis were compared with those who survived longer. Standardised chest X-ray (CXR) and lung cancer rates were calculated for each practice. Results: Of 20 142 people with lung cancer, those who died early consulted with primary care more frequently prediagnosis. Individual factors associated with early death were male sex (OR 1.17; 95% CI 1.10 to 1.24), current smoking (OR 1.43; 95% CI 1.28 to 1.61), increasing age (OR 1.80; 95% CI 1.62 to 1.99 for age ≥80 years compared to 65–69 years), social deprivation (OR 1.16; 95% CI 1.04 to 1.30 for Townsend quintile 5 vs 1) and rural versus urban residence (OR 1.22; 95% CI 1.06 to 1.41). CXR rates varied widely, and the odds of early death were highest in the practices which requested more CXRs. Lung cancer incidence at practice level did not affect early deaths. Conclusions: Patients who die early from lung cancer are interacting with primary care prediagnosis, suggesting potentially missed opportunities to identify them earlier. A general increase in CXR requests may not improve survival; rather, a more timely and appropriate targeting of this investigation using risk assessment tools needs further assessment

Predicting death from surgery for lung cancer: a comparison of two scoring systems in two European countries

Objectives: Current British guidelines advocate the use of risk prediction scores such as Thoracoscore to estimate mortality prior to radical surgery for non-small cell lung cancer (NSCLC). A recent publication used the National Lung Cancer Audit (NLCA) to produce a score to predict 90 day mortality (NLCA score). The aim of this study is to validate the NLCA score, and compare its performance with Thoracoscore. Materials and methods: We performed an internal validation using 2858 surgical patients from NLCA and an external validation using 3191 surgical patients from the Danish Lung Cancer Registry (DLCR). We calculated the proportion that died within 90 days of surgery. The discriminatory power of both scores was assessed by a receiver operating characteristic (ROC) and an area under the curve (AUC) calculation. Results: Ninety day mortality was 5% in both groups. AUC values for internal and external validation of NLCA score and validation of Thoracoscore were 0.68 (95% CI 0.63–0.72), 0.60 (95% CI 0.56–0.65) and 0.60 (95% CI 0.54–0.66) respectively. Post-hoc analysis was performed using NLCA records on 15554 surgical patients to derive summary tables for 30 and 90 day mortality, stratified by procedure type, age and performance status. Conclusions: Neither score performs well enough to be advocated for individual risk stratification prior to lung cancer surgery. It may be that additional physiological parameters are required; however this is a further project. In the interim we propose the use of our summary tables that provide the real-life range of mortality for lobectomy and pneumonectomy

The impact of the ‘hub and spoke’ model of care for lung cancer and equitable access to surgery

Objectives: To determine the influence of where a patient is first seen (either surgical or non-surgical centre) and patient features on having surgery for non-small cell lung cancer (NSCLC). Design: Cross-sectional study from individual patients, between 1January 2008 and 31March 2012. Setting: Linked National Lung Cancer Audit and Hospital Episode Statistics datasets. Participants: 95 818 English patients with a diagnosis of NSCLC, of whom 12 759 (13%) underwent surgical resection. Main outcome measure: Odds of having surgery based on the empirical catchment population of the 30 thoracic surgical centres in England and whether the patient is first seen in a surgical centre or a non-surgical centre. Results: Patients were more likely to be operated on if they were first seen at a surgical centre (OR 1.37; 95% CI 1.29 to 1.45). This was most marked for surgical centres with the largest catchment populations. In these surgical centres with large catchment populations, the resection rate for local patients was 18% and for patients first seen in a non-surgical centre within catchment was 12%. Conclusions: Surgical centres that serve the largest catchment populations have high resection rates for patients first seen in their own centre but, in contrast, low resection rates for patients first seen at the surrounding centres they serve. Our findings demonstrate the importance of going further than relating resection rates to hospital volume or surgeon number, and show that there is a pressing need to design lung cancer services which enable all patients, including those first seen at non-surgical centres, to have equal access to lung cancer surgery

The role of computer-assisted radiographer reporting in lung cancer screening programmes

OBJECTIVES: Successful lung cancer screening delivery requires sensitive, timely reporting of low-dose computed tomography (LDCT) scans, placing a demand on radiology resources. Trained non-radiologist readers and computer-assisted detection (CADe) software may offer strategies to optimise the use of radiology resources without loss of sensitivity. This report examines the accuracy of trained reporting radiographers using CADe support to report LDCT scans performed as part of the Lung Screen Uptake Trial (LSUT). METHODS: In this observational cohort study, two radiographers independently read all LDCT performed within LSUT and reported on the presence of clinically significant nodules and common incidental findings (IFs), including recommendations for management. Reports were compared against a 'reference standard' (RS) derived from nodules identified by study radiologists without CADe, plus consensus radiologist review of any additional nodules identified by the radiographers. RESULTS: A total of 716 scans were included, 158 of which had one or more clinically significant pulmonary nodules as per our RS. Radiographer sensitivity against the RS was 68-73.7%, with specificity of 92.1-92.7%. Sensitivity for detection of proven cancers diagnosed from the baseline scan was 83.3-100%. The spectrum of IFs exceeded what could reasonably be covered in radiographer training. CONCLUSION: Our findings highlight the complexity of LDCT reporting requirements, including the limitations of CADe and the breadth of IFs. We are unable to recommend CADe-supported radiographers as a sole reader of LDCT scans, but propose potential avenues for further research including initial triage of abnormal LDCT or reporting of follow-up surveillance scans. KEY POINTS: • Successful roll-out of mass screening programmes for lung cancer depends on timely, accurate CT scan reporting, placing a demand on existing radiology resources. • This observational cohort study examines the accuracy of trained radiographers using computer-assisted detection (CADe) software to report lung cancer screening CT scans, as a potential means of supporting reporting workflows in LCS programmes. • CADe-supported radiographers were less sensitive than radiologists at identifying clinically significant pulmonary nodules, but had a low false-positive rate and good sensitivity for detection of confirmed cancers