Dynamic changes in conjunctival dendritic cell numbers, anatomical position and phenotype during experimental allergic conjunctivitis

Dendritic cells (DCs) are a subset of antigen-presenting cells (APCs) that are involved in the initiation and control of the immune response to antigens present at the interface with the environment. A limited number of groups have studied DCs in human and animal conjunctiva but no data is available concerning the different DC subsets present in the conjunctival tissue. The aims of this study are to characterize the phenotypes and numbers of DCs present in the murine model of allergic conjunctivitis using the technique of immunohistochemistry so as to aid the understanding of the mechanisms involved in allergic eye disease. A double immunofluorescence method was used to analyze the phenotypic distribution and density of DC subsets in the mouse conjunctival tissues of the allergic model using a panel of antibodies: CD11c, as a general marker of DCs, coupled with another DC subset marker such as Langerin for Langerhans cells (LCs), CD11b for myeloid DCs (mDCs) and mPDCA-1 for plasmacytoid DCs (pDCs). In the na?ve conjunctiva, mDCs were consistently detected in the subepithelial layer and substantia propria. In the epithelium and the subepithelial layer, very few LCs and virtually no pDCs were observed. Following allergen challenge, there was a marked influx of mDCs and pDCs, but no LCs, into the subepithelial layer and throughout the substantia propria. These results indicate that conjunctival DC subsets may play an important role in the immune-regulatory processes involved in the inflammatory component of allergic conjunctivitis.     

Implementation of a metastatic malignancy of unknown primary origin service led by a palliative physician

Background: Cancer of unknown primary is the fourth most common cause of cancer death in the United Kingdom. National guidance in 2010 recommended the establishment of a dedicated unknown primary team to facilitate targeted investigation and symptom control. A service development project was undertaken to identify those affected by malignancy of unknown origin and institute a pathway for coordinating their care led by a palliative physician.

Method: In order to describe the patient population and illness trajectory and to assess the effect of the new pathway on the clinical outcomes we used a retrospective and prospective comparative case notes survey to identify the pre- and post-pathway population. This took place in secondary care. Inclusion criteria were patients with metastatic disease with no known primary; exclusion criteria were where the site of metastasis was so suggestive of a primary that it would be managed as per that disease process. 88 patients were included.Results: Mean age was 72.5 years. The mean survival time from presentation was 81.8 days. There was no difference pre or during pathway implementation in age, performance status or survival time. There was no reduction in the numbers referred for tumour directed therapy. There was a non-statistically significant reduction in the number who died in hospital during the pathway implementation.

Conclusions: This study suggests having a metastatic malignancy of unknown primary origin service led by a palliative physician does not reduce the number referred for tumour directed therapy. It also adds evidence of the poor prognosis and thus the need for early palliative care input.     

From “Bibbid-Bobbidi-Boo” to Scrooge: an update and comparative analysis of the portrayal of older characters in recent Disney animated films

Disney animated films continue to be a medium viewed by millions of young audiences across the world. As such, Disney content messages – which are often repeatedly viewed by children – and correlating implications should frequently be assessed. The objective for this investigation was to evaluate the portrayal of older adults in more recent Disney animated films (from 2004 to 2016) to provide both an update and comparative analysis to previous explorations. Results suggest comparable findings: we note a similarity in the overall negative portrayal of older characters in recent Disney animated films compared to previous films. Furthermore, we observed a decrease in “neutral” or general aging qualities, as well as a slight increase in the number of older adults depicted as “the villain.” Implications and observations are offered in efforts to improve ageist representations, particularly in a medium that is exceptionally prevalent in the lives of many young people.     

Modeling and designing health care payment innovations for medical imaging

Payment innovations that better align incentives in health care are a promising approach to reduce health care costs and improve quality of care. Designing effective payment systems, however, is challenging due to the complexity of the health care system with its many stakeholders and their often conflicting objectives. There is a lack of mathematical models that can comprehensively capture and efficiently analyze the complex, multi-level interactions and thereby predict the effect of new payment systems on stakeholder decisions and system-wide outcomes. To address the need for multi-level health care models, we apply multiscale decision theory (MSDT) and build upon its recent advances. In this paper, we specifically study the Medicare Shared Savings Program (MSSP) for Accountable Care Organizations (ACOs) and determine how this incentive program affects computed tomography (CT) use, and how it could be redesigned to minimize unnecessary CT scans. The model captures the multi-level interactions, decisions and outcomes for the key stakeholders, i.e., the payer, ACO, hospital, primary care physicians, radiologists and patients. Their interdependent decisions are analyzed game theoretically, and equilibrium solutions - which represent stakeholders’ normative decision responses - are derived. Our results provide decision-making insights for the payer on how to improve MSSP, for ACOs on how to distribute MSSP incentives among their members, and for hospitals on whether to invest in new CT imaging systems.     

Prevalence and determinants of low protein intake in very old adults: insights from the Newcastle 85+ Study

Purpose

The very old (aged ≥ 85 years), fastest growing age group in most western societies, are at especially high risk of muscle mass and strength loss. The amount, sources and timing of protein intake may play important roles in the aetiology and management of sarcopenia. This study investigated the prevalence and determinants of low protein intake in 722 very old adults participating in the Newcastle 85+ Study.

Methods

Protein intake was estimated with 2 × 24-h multiple pass recalls (24 h-MPR) and contribution (%) of food groups to protein intake was calculated. Low protein intake was defined as intake < 0.8 g of protein per adjusted body weight per day. A backward stepwise multivariate linear regression model was used to explore socioeconomic, health and lifestyle predictors of protein intake.

Results

Twenty-eight percent (n = 199) of the community-living very old in the Newcastle 85+ Study had low protein intake. Low protein intake was less likely when participants had a higher percent contribution of meat and meat products to total protein intake (OR 0.97, 95% CI 0.95, 1.00) but more likely with a higher percent contribution of cereal and cereal products and non-alcoholic beverages. Morning eating occasions contributed more to total protein intake in the low than in the adequate protein intake group (p < 0.001). Being a woman (p < 0.001), having higher energy intake (p < 0.001) and higher tooth count (p = 0.047) was associated with higher protein intake in adjusted models.

Conclusion

This study provides novel evidence on the prevalence of low protein intake, diurnal protein intake patterns and food group contributors to protein intake in the very old.

     

Toxicological and ecotoxicological properties of gas-to-liquid (GTL) products. 2. Ecotoxicology

Gas-to-liquid (GTL) products are synthetic hydrocarbons produced from natural gas using a catalytic process known as the Fischer–Tropsch process. This process yields a synthetic crude oil that consists of saturated hydrocarbons which can subsequently be refined to a range of products analogous to those obtained from petroleum refining. However, in contrast to their petroleum-derived analogs, GTL products are essentially free of unsaturated or aromatic compounds and do not contain any sulfur-, oxygen-, or nitrogen-containing compounds. Under new chemical substance notification requirements, an extensive testing program covering the entire portfolio of GTL products has been undertaken to assess their hazardous properties to human health and environment. The results of these studies have been summarized in a two-part review. Part 1 provides an overview of the mammalian toxicity hazardous properties of the various GTL products. This second part of the review focuses on the aquatic, sediment, terrestrial, and avian toxicity studies which assess the ecotoxicological hazard profile of the GTL products. Many challenges were encountered during these tests relating to dosing, analysis and interpretation of results. These are discussed with the intent to share experiences to help inform and shape future regulatory mandates for testing of poorly soluble complex substances. As was the case with the mammalian toxicology review, there were a few cases where adverse effects were found, but overall the GTL products were found to exert minimal adverse ecotoxicological effects and these were less severe than effects observed with their conventional, petroleum-derived analogs.