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Background and Objective: Chest x‐ray (CXR) remains a core component of health monitoring guidelines for workers at risk of exposure to crystalline silica. There has however been a lack of evidence regarding the sensitivity of CXR to detect silicosis in artificial stone benchtop industry workers. Methods: Paired CXR and high‐resolution computed tomography (HRCT) images were acquired from 110 artificial stone benchtop industry workers. Blinded to the clinical diagnosis, each CXR and HRCT was independently read by two thoracic radiologists from a panel of seven, in accordance with International Labour Office (ILO) methodology for CXR and International Classification of HRCT for Occupational and Environmental Respiratory Diseases. Accuracy of screening positive (ILO major category 1, 2 or 3) and negative (ILO major category 0) CXRs were compared with identification of radiological features of silicosis on HRCT. Results: CXR was positive for silicosis in 27/110 (24.5%) workers and HRCT in 40/110 (36.4%). Of the 83 with a negative CXR (ILO category 0), 15 (18.1%) had silicosis on HRCT. All 11 workers with ILO category 2 or 3 CXRs had silicosis on HRCT. In 99 workers ILO category 0 or 1 CXRs, the sensitivity of screening positive CXR compared to silicosis identified by HRCT was 48% (95%CI 29–68) and specificity 97% (90–100). Conclusion: Compared to HRCT, sensitivity of CXR was low but specificity was high. Reliance on CXR for health monitoring would provide false reassurance for many workers, delay management and underestimate the prevalence of silicosis in the artificial stone benchtop industry. The use of CXR to screen artificial stone benchtop industry workers for silicosis has low sensitivity compared to HRCT chest, especially for early‐stage disease. Reliance on chest x‐ray for screening will fail to identify many workers with artificial stone silicosis and underestimate the prevalence of respiratory disease in this industry. [ABSTRACT FROM AUTHOR]

One of the primary obstacles in current cancer treatments lies in the extensive heterogeneity of genetic and epigenetic changes that occur in each arising tumour. However, an additional challenge persists, as certain types of cancer display shared immune deficiencies in the antigen processing machinery (APM). This includes the downregulation of human leukocyte antigen (HLA) class I molecules, which serve as peptide antigen receptors for T lymphocyte recognition that plays a crucial role in killing emerging tumours. Consequently, this contributes to immune escape in metastatic disease. Notably, current cell-based immunotherapies primarily focusing on T lymphocytes and the implementation of immune checkpoint inhibitor modalities have largely ignored the crucial task of reversing immune escape. This oversight may explain the limited success of these approaches becoming more effective cancer immunotherapies. Hence, there is a critical need to prioritize the discovery of new therapeutic candidates that can effectively address immune escape and synergize with evolving immunotherapy strategies. In this context, we identified curcuphenol in a cell-based screen from a library of marine extracts as a chemical entity that reverses the immuneescape phenotype of metastatic cancers. To advance these findings toward clinical efficacy, the present study describes the synthesis of analogues of naturally occurring curcuphenol with enhanced chemical properties and biological efficacy. Here we test the hypothesis that these curcuphenol analogues can evoke the power of the immune system to reduce the growth of metastatic disease in tumour bearing animals. Our findings indicate that these compounds effectively restore the expression of APM genes in metastatic tumours and inhibit the growth of highly invasive tumours in preclinical models, thereby counteracting the common immune evasion phenomenon observed in metastatic cancers. We conclude that cancer immunotherapies capable of boosting APM expression, hold great potential in maximizing the effectiveness of immune blockade inhibitors and eradicating invasive tumours. [ABSTRACT FROM AUTHOR]

Introduction Delirium and multiple long-term conditions (MLTC) share numerous risk factors and have been shown individually to be associated with adverse outcomes following hospitalisation. However, the extent to which these common ageing syndromes have been studied together is unknown. This scoping review aims to summarise our knowledge to date on the interrelationship between MLTC and delirium. Methods Searches including terms for delirium and MLTC in adult human participants were performed in PubMed, EMBASE, Medline, Psycinfo and CINAHL. Descriptive analysis was used to summarise findings, structured according to Synthesis Without Meta-analysis reporting guidelines. Results After removing duplicates, 5256 abstracts were screened for eligibility, with 313 full-texts sought along with 17 additional full-texts from references in review articles. In total, 140 met inclusion criteria and were included in the final review. Much of the literature explored MLTC as a risk factor for delirium (n  = 125). Fewer studies explored the impact of MLTC on delirium presentation (n  = 5), duration (n  = 3) or outcomes (n  = 6) and no studies explored how MLTC impacts the treatment of delirium or whether having delirium increases risk of developing MLTC. The most frequently used measures of MLTC and delirium were the Charlson Comorbidity Index (n  = 98/140) and Confusion Assessment Method (n  = 81/140), respectively. Conclusion Existing literature largely evaluates MLTC as a risk factor for delirium. Major knowledge gaps identified include the impact of MLTC on delirium treatment and the effect of delirium on MLTC trajectories. Current research in this field is limited by significant heterogeneity in defining both MLTC and delirium. [ABSTRACT FROM AUTHOR]

THREE WORLDS Memoir of an Arab-Jew AVI SHLAIM 336pp. Oneworld. 25 [pounds sterling]. At the start of his absorbing, contentious memoir, the Iraqi Jewish historian Avi Shlaim describes himself, aged [...]

Cell-based cancer immunotherapy has achieved significant advancements, providing a source of hope for cancer patients. Notwithstanding the considerable progress in cell-based immunotherapy, the persistently low response rates and the exorbitant costs associated with their implementation still present a formidable challenge in clinical settings. In the landscape of cellbased cancer immunotherapies, an uncharted territory involves Type 2 innate lymphoid cells (ILC2s) and interleukin-33 (IL-33) which promotes ILC2 functionality, recognized for their inherent ability to enhance immune responses. Recent discoveries regarding their role in actuating cytolytic T lymphocyte responses, including curbing tumor growth rates and hindering metastasis, have added a new dimension to our understanding of the IL-33/ILC2 axis. These recent insights may hold significant promise for ILC2 cell-based immunotherapy. Nevertheless, the prospect of adoptively transferring ILC2s to confer immune protection against tumors has yet to be investigated. The present study addresses this hypothesis, revealing that ILC2s isolated from the lungs of tumor-bearing mice, and tumor infiltrating ILC2s when adoptively transferred after tumor establishment at a ratio of one ILC2 per sixty tumor cells, leads to an influx of tumor infiltrating CD4+ and CD8+ T lymphocytes as well as tumor infiltrating eosinophils resulting in a remarkable reduction in tumor growth. Moreover, we find that post-adoptive transfer of ILC2s, the number of tumor infiltrating ILC2s is inversely proportional to tumor size. Finally, we find corollaries of the IL-33/ILC2 axis enhancing the infiltration of eosinophils in human prostate carcinomas patients' expressing high levels of IL-33 versus those expressing low levels of IL-33. Our results underscore the heightened efficacy of adoptively transferred ILC2s compared to alternative approaches, revealing an approximately one hundred fifty-fold superiority on a cell-per-cell basis over CAR T-cells in the specific targeting and elimination of tumors within the same experimental model. Overall, this study demonstrates the functional significance of ILC2s in cancer immunosurveillance and provides the proof of concept of the potential utility of ILC2 cell-based cancer immunotherapies. [ABSTRACT FROM AUTHOR]

Key message: Swyer‐James‐MacLeod Syndrome is a rare obliterative lung disease typically caused by childhood infection resulting in arrested pulmonary development. Imaging findings include unilateral hyperlucency on chest x‐ray, and hyperlucency, hypovascularity and expiratory gas trapping on computed tomography. Recognition of abnormal imaging can lead to earlier diagnosis and institution of appropriate management. [ABSTRACT FROM AUTHOR]

The overrepresentation of people with serious mental illnesses in the criminal legal system has spurred the development of crisis response models to improve or reduce police response to a mental health crisis. However, limited research has explored preferences for crisis response, and no research in the United States has examined the responses desired by mental health care clients or their family members. This study aimed to understand the experiences of people with serious mental illnesses interacting with police and to learn about their preferences for crisis response models. The authors interviewed 50 clients with serious mental illnesses and a history of arrest who were enrolled in a randomized controlled trial of a police–mental health linkage system, as well as 18 of their family members and friends. Data were coded with deductive and inductive approaches and were grouped into larger themes. Clients and family or friends described needing a calm environment and empathy during a crisis. They selected a nonpolice response as their first choice and response from a crisis intervention team as their last choice among four options, highlighting the importance of trained responders and past negative interactions with police. However, they also noted concerns about safety and the shortcomings of a nonpolice response. These findings build understanding about clients' and family members' preferences for crisis response and highlight concerns that are relevant for policy makers. [ABSTRACT FROM AUTHOR]

Curcuphenol, a common component of the culinary spices, naturally found in marine invertebrates and plants, has been identified as a novel candidate for reversing immune escape by restoring expression of the antigen presentationmachinery (APM) in invasive cancers, thereby resurrecting the immune recognition of metastatic tumours. Two synthetic curcuphenol analogues, were prepared by informed design that demonstrated consistent induction of APM expression in metastatic prostate and lung carcinoma cells. Both analogues were subsequently found to possess a previously undescribed histone deacetylase (HDAC)-enhancing activity. Remarkably, the H3K27ac ChIPseq analysis of curcuphenol-treated cells reveals that the induced epigenomic marks closely resemble the changes in genome-wide pattern observed with interferon-γ, a cytokine instrumental for orchestrating innate and adaptive immunity. These observations link dietary components to modifying epigenetic programs that modulate gene expression guiding poised immunity. [ABSTRACT FROM AUTHOR]

Genetic and epigenetic events have been implicated in the downregulation of the cellular antigen processing and presentation machinery (APM), which in turn, has been associated with cancer evasion of the immune system. When these essential components are lacking, cancers develop the ability to subvert host immune surveillance allowing cancer cells to become invisible to the immune system and, in turn, promote cancer metastasis. Here we describe and validate the first highthroughput cell-based screening assay to identify chemical extracts and unique chemical entities that reverse the downregulation of APM components in cell lines derived from metastatic tumours. Through the screening of a library of 480 marine invertebrate extracts followed by bioassay-guided fractionation, curcuphenol, a common sesquiterpene phenol derived from turmeric, was identified as the active compound of one of the extracts. We demonstrate that curcuphenol induces the expression of the APM components, TAP-1 and MHC-I molecules, in cell lines derived from both metastatic prostate and lung carcinomas. Turmeric and curcumins that contain curcuphenol have long been utilized not only as a spice in the preparation of food, but also in traditional medicines for treating cancers. The remarkable discovery that a common component of spices can increase the expression of APM components in metastatic tumour cells and, therefore reverse immune-escape mechanisms, provides a rationale for the development of foods and advanced nutraceuticals as therapeutic candidates for harnessing the power of the immune system to recognize and destroy metastatic cancers. [ABSTRACT FROM AUTHOR]

Objective: The recovery paradigm in the context of serious mental illnesses pertains to several characteristics of community functioning, adjustment, and integration, among other constructs. Additional rating scales would be beneficial for measuring various facets of community functioning for research that is recovery oriented as opposed to symptom focused. The Community Navigation Scale was developed as part of the Opening Doors to Recovery project to address several aspects of navigating community resources.Methods: After item development, the 21-item Community Navigation Scale was used across two studies with 340 participants who had serious mental illnesses. Factor analysis revealed three potential factors, and subscales were computed.Results: The social and physical well-being subscale (seven items, Cronbach's α=0.82) addressed community involvement, volunteering, finding enjoyable activities, and engaging in positive health behaviors. The accessing external resources subscale (nine items, Cronbach's α=0.80) tapped one's ability to obtain needed resources, ranging from medications to housing and from small appliances to classes in the community. The home and self-maintenance subscale (five items, Cronbach's α=0.73) measured abilities around shopping, cooking, cell phone use, house cleaning, and personal grooming and hygiene. Initial validity of the subscales was suggested through correlations with the Multnomah Community Ability Scale (r=0.65, 0.55, and 0.41 for social and physical well-being, accessing external resources, and home and self-maintenance, respectively).Conclusions: The Community Navigation Scale assesses dimensions of community functioning among persons with serious mental illnesses and may add to the array of research and clinical measures pertinent to recovery outcomes. Additional research on its psychometric properties is warranted. [ABSTRACT FROM AUTHOR]

Background and objective: Prediction of disease course in patients with progressive pulmonary fibrosis remains challenging. The purpose of this study was to assess the prognostic value of lung fibrosis extent quantified at computed tomography (CT) using data‐driven texture analysis (DTA) in a large cohort of well‐characterized patients with idiopathic pulmonary fibrosis (IPF) enrolled in a national registry. Methods: This retrospective analysis included participants in the Australian IPF Registry with available CT between 2007 and 2016. CT scans were analysed using the DTA method to quantify the extent of lung fibrosis. Demographics, longitudinal pulmonary function and quantitative CT metrics were compared using descriptive statistics. Linear mixed models, and Cox analyses adjusted for age, gender, BMI, smoking history and treatment with anti‐fibrotics were performed to assess the relationships between baseline DTA, pulmonary function metrics and outcomes. Results: CT scans of 393 participants were analysed, 221 of which had available pulmonary function testing obtained within 90 days of CT. Linear mixed‐effect modelling showed that baseline DTA score was significantly associated with annual rate of decline in forced vital capacity and diffusing capacity of carbon monoxide. In multivariable Cox proportional hazard models, greater extent of lung fibrosis was associated with poorer transplant‐free survival (hazard ratio [HR] 1.20, p < 0.0001) and progression‐free survival (HR 1.14, p < 0.0001). Conclusion: In a multi‐centre observational registry of patients with IPF, the extent of fibrotic abnormality on baseline CT quantified using DTA is associated with outcomes independent of pulmonary function. [ABSTRACT FROM AUTHOR]

Background: Cytomegalovirus (CMV) infection leads to effector memory CD8+ T cell expansion and is associated with immune dysfunction in older adults. However, the molecular alterations of CMV-specific CD8+ T cells in CMV infected healthy young and middle-aged adults has not been fully characterized. Results: We compared CD8+ T cells specific for a CMV epitope (pp65495-503, NLV) and an influenza A virus (IAV) epitope (M158-66, GIL) from the same young and middle-aged healthy adults with serum positive for anti-CMV IgG. Compared to the IAV-specific CD8+ T cells, CMV-specific CD8+ T cells contained more differentiated effector memory (TEM and TEMRA) cells. Isolated CMV-specific central memory (TCM) but not naïve (TN) cells had a significant reduced activation-induced expansion in vitro compared to their IAV-specific counterparts. Furthermore, we found that CD70 expression was reduced in CMV-specific CD28+CD8+ TCM and that CD70+ TCM had better expansion in vitro than did CD70- TCM. Mechanistically, we showed that CD70 directly enhanced MAPK phosphorylation and CMV-specific CD8+ TCM cells had a reduced MAPK signaling upon activation. Lastly, we showed that age did not exacerbate reduced CD70 expression in CMV- specific CD8+ TCM cells. Conclusion: Our findings showed that CMV infection causes mild expansion of CMV-NLV-specific CD8+ T cells, reduced CD70 expression and signaling, and proliferation of CMV-NLV-specific CD8+ TCM cells in young and middle-aged healthy adults and revealed an age-independent and CMV infection-specific impact on CD8+ memory T cells. [ABSTRACT FROM AUTHOR]

When Anne Bronte died in 1849, aged only twenty-nine, she exhorted her sister Charlotte in her last words to 'take courage'. Instead, Charlotte blocked all reprints of her sister's second, [...]

Rationale: Reliable outcome prediction in patients with fibrotic lung disease using baseline high-resolution computed tomography (HRCT) data remains challenging. Objectives: To evaluate the prognostic accuracy of a deep learning algorithm (SOFIA [Systematic Objective Fibrotic Imaging Analysis Algorithm]), trained and validated in the identification of usual interstitial pneumonia (UIP)-like features on HRCT (UIP probability), in a large cohort of well-characterized patients with progressive fibrotic lung disease drawn from a national registry. Methods: SOFIA and radiologist UIP probabilities were converted to Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED)-based UIP probability categories (UIP not included in the differential, 0-4%; low probability of UIP, 5-29%; intermediate probability of UIP, 30-69%; high probability of UIP, 70-94%; and pathognomonic for UIP, 95-100%), and their prognostic utility was assessed using Cox proportional hazards modeling. Measurements and Main Results: In multivariable analysis adjusting for age, sex, guideline-based radiologic diagnosis, anddisease severity (using total interstitial lung disease [ILD] extent on HRCT, percent predicted FVC, DlCO, or the composite physiologic index), only SOFIA UIP probability PIOPED categories predicted survival. SOFIA-PIOPED UIP probability categories remained prognostically significant in patients considered indeterminate (n = 83) by expert radiologist consensus (hazard ratio, 1.73; P < 0.0001; 95% confidence interval, 1.40-2.14). In patients undergoing surgical lung biopsy (n = 86), after adjusting for guideline-based histologic pattern and total ILD extent on HRCT, only SOFIA-PIOPED probabilities were predictive of mortality (hazard ratio, 1.75; P < 0.0001; 95% confidence interval, 1.37-2.25). Conclusions: Deep learning-based UIP probability on HRCT provides enhanced outcome prediction in patients with progressive fibrotic lung disease when compared with expert radiologist evaluation or guideline-based histologic pattern. In principle, this tool may be useful in multidisciplinary characterization of fibrotic lung disease. The utility of this technology as a decision support system when ILD expertise is unavailable requires further investigation. [ABSTRACT FROM AUTHOR]

Objective: Individuals with serious mental illnesses are overrepresented in all facets of the legal system. State-level criminal histories of patients with serious mental illnesses were analyzed to determine the proportion who had been arrested and number of lifetime arrests and charges, associations of six variables with number of arrests, and the most common charges from individuals’ first two arrests and most recent two arrests.Methods: A total of 240 patients were recruited at three inpatient psychiatric facilities and gave consent to access their criminal history. Information was extracted from Record of Arrest and Prosecution (RAP) sheets for lifetime arrests in Georgia.Results: A total of 171 (71%) had been arrested. Their mean±SD lifetime arrests were 8.6±10.1, and mean lifetime charges were 12.6±14.6. In a Poisson regression, number of arrests was associated with lower educational attainment, Black or African American race, the presence of a substance use disorder, the presence of a mood disorder, and female sex. Common early charges included marijuana possession, driving under the influence of alcohol, and burglary and shoplifting. Common recent charges included probation violations, failure to appear in court, officer obstruction–related charges, and disorderly conduct.Conclusions: Findings point to a need for policy and program development in the legal system (e.g., pertaining to charges such as willful obstruction of an officer), the mental health community (e.g., to ensure that professionals know about clients’ legal involvement and can partner in strategies to reduce arrests), and social services sectors (to address charges, such as shoplifting, often related to material disadvantage). [ABSTRACT FROM AUTHOR]

THE SECRET GARDEN, A LITTLE PRINCESS, LITTLE LORD FAUNTLEROY FRANCES HODGSON BURNETT Edited by Gretchen Holbrook Gerzina 752pp. Library of America. 29.99 [pounds sterling] (US $35). FOR CERTAIN BOOKISH GIRLS, [...]

Supplemental Digital Content is available in the text Objectives: To develop and validate a classification of sleeve gastrectomy leaks able to reliably predict outcomes, from protocolized computed tomography (CT) findings and readily available variables. Summary of Background Data: Leaks post sleeve gastrectomy remain morbid and resource-consuming. Incidence, treatments, and outcomes are variable, representing heterogeneity of the problem. A predictive tool available at presentation would aid management and predict outcomes. Methods: From a prospective database (2009–2018) we reviewed patients with staple line leaks. A Delphi process was undertaken on candidate variables (80–20). Correlations were performed to stratify 4 groupings based on outcomes (salvage resection, length of stay, and complications) and predictor variables. Training and validation cohorts were established by block randomization. Results: A 4-tiered classification was developed based on CT appearance and duration postsurgery. Interobserver agreement was high (κ = 0.85, P < 0.001). There were 59 patients, (training: 30, validation: 29). Age 42.5 ± 10.8 versus 38.9 ± 10.0 years (P = 0.187); female 65.5% versus 80.0% (P = 0.211), weight 127.4 ± 31.3 versus 141.0 ± 47.9 kg, (P = 0.203). In the training group, there was a trend toward longer hospital stays as grading increased (I = 10.5 d; II = 24 d; III = 66.5 d; IV = 72 d; P = 0.005). Risk of salvage resection increased (risk ratio grade 4 = 9; P = 0.043) as did complication severity (P = 0.027). Findings were reproduced in the validation group: risk of salvage resection (P = 0.007), hospital stay (P = 0.001), complications (P = 0.016). Conclusion: We have developed and validated a classification system, based on protocolized CT imaging that predicts a step-wise increased risk of salvage resection, complication severity, and increased hospital stay. The system should aid patient management and facilitate comparisons of outcomes and efficacy of interventions. [ABSTRACT FROM AUTHOR]

Increased knee flexion and decreased knee valgus angles and decreased impact ground reaction forces (GRF) are associated with decreased anterior cruciate ligament (ACL) loading during landing. The purpose of this study was to determine the effect of tactile feedback provided by a simple device on knee flexion and valgus angles and impact GRF during landing. Kinematic and kinetic data were collected when 28 participants performed baseline, training, and evaluation jump-landing trials. During the training trials, the device was placed on participants' shanks so that participants received tactile feedback when they reached a peak knee flexion angle of a minimum of 100°. During the evaluation trials, participants were instructed to maintain the movement patterns as they learned from the training trials. Participants demonstrated significantly (P < .008) increased peak knee flexion angles, knee flexion range of motion during early landing (first 100 ms of landing) and stance time, decreased impact posterior and vertical GRF during early landing and jump height, and similar knee valgus angles during the evaluation trials compared with the baseline trials. Immediately following training with tactile feedback, participants demonstrated landing patterns associated with decreased ACL loading. This device may have advantages in application because it provides low-cost, independent, and real-time feedback. [ABSTRACT FROM AUTHOR]

Background: Chronic rhinosinusitis affects 62% of adults with bronchiectasis and is linked to greater bronchiectasis severity. However, the impact of symptoms of chronic rhinosinusitis on disease‐specific and cough‐related quality of life is unknown. Methods: In this cross‐sectional study, adults with stable bronchiectasis and chronic rhinosinusitis symptoms completed the sinonasal outcome test‐22 (SNOT‐22), quality of life–bronchiectasis questionnaire, and Leicester cough questionnaire. Bronchiectasis severity was assessed using the bronchiectasis severity index (BSI) and chest high‐resolution computed tomography (HRCT). Results: Sixty participants with bronchiectasis (mean [SD] forced expiratory volume in 1 s of 73.2 [25.5] %predicted) were included. Greater severity of chronic rhinosinusitis symptoms (based on SNOT‐22) was moderately associated with impaired cough‐related quality of life (according to the Leicester cough questionnaire; all r > −.60) and impaired bronchiectasis‐specific quality of life (based on the quality of life–bronchiectasis questionnaire), with impaired physical function (r = −.518), less vitality (r = −.631), reduced social function (r = −.546), greater treatment burden (r = −.411), and increased severity of respiratory symptoms (r = −.534). Chronic rhinosinusitis symptoms were unrelated to disease severity according to the BSI (r =.135) and HRCT scoring (all r <.200). The severity of chronic rhinosinusitis symptoms was not affected by sputum color (p =.417) or the presence of Pseudomonas aeruginosa colonization (p =.73). Conclusions: In adults with bronchiectasis, chronic rhinosinusitis has a consistent and negative impact on both cough‐related and bronchiectasis‐specific quality of life. [ABSTRACT FROM AUTHOR]