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Background Detection of homozygous deletion of the p16 gene (CDKN2A) by fluorescence in situ hybridization (FISH) has been investigated as an ancillary technique in the diagnosis of malignant mesothelioma. Method This retrospective study reviewed the results of all p16 FISH tests performed at a regional mesothelioma centre from February 2012 to November 2019 in cases of possible mesothelioma to examine the diagnostic utility of this test as well as patients characteristics and survival in p16 FISH positive mesothelioma versus p16 FISH negative mesothelioma. Results P16 FISH testing was requested in 216 pathological samples in the study period. The test failure rate was 4% (10/216). Median time from request to result was 10 days (IQR 7–13, range 1–30). The sensitivity, specificity, NPV and PPV were 60 %, 100 %, 39 % and 100 % respectively. There were no false positive results and this genetic aberration was only detected in cases of mesothelioma. The prevalence of p16 FISH positive mesothelioma was higher in cytological specimens compared to histological specimens (75 % vs 58 %, p = 0.03) and lower in women compared to men (33 % vs 66 %, p = 0.003). P16 FISH positive mesothelioma was associated with significantly worse survival (median overall survival 285 vs 339 days, p = 0.0018). This remained significant after adjusting for confounding variables (OR 4.4, 95 %CI 1.84–11.14, p = 0.001). Conclusions In this study, 60 % of mesotheliomas harbour a homozygous deletion of CDKN2A and can be accurately, reliably and efficiently identified by p16 FISH testing. This test can be embedded within routine practice in mesothelioma pathways to enhance diagnostic accuracy.

INTRODUCTION: A proportion of patients with lung cancer will not be suitable for anti-cancer treatment and are managed with best supportive care (BSC). The aim of this retrospective case series analysis was to critically review the use of diagnostic and staging investigations in patients who were ultimately managed with BSC. METHODS: A retrospective review of all lung cancer patients with a multidisciplinary team outcome of BSC from 01 June 2018 to 01 June 2019 was performed. Patients were categorised into those with an early BSC decision and those that underwent further investigations prior to a BSC decision (investigations beyond initial computed tomography (CT)). Patient demographics, clinical characteristics and outcomes were collated and analysed. RESULTS: Seventy-seven lung cancer patients managed with BSC were identified. Patients were elderly (average age 79 years), functionally limited (80% World Health Organization performance status ≥3), frail (70% clinical frailty score ≥6) and had advanced stage disease (90% stage III/IV). Thirty-one (40%) underwent further investigations beyond the initial CT prior to the BSC decision. The most common types of further investigations were endobronchial ultrasound-guided transbronchial needle aspiration (27/31; 74%), positron emission tomography – CT (18/31; 45%) and CT-guided lung biopsy (7/31; 23%). This is despite high levels of consultant chest physician review at first assessment (71%), cancer nurse specialist involvement (97%), specialist palliative care involvement (65%), a high pathological confirmation rate of sampling procedures (89%) and adequacy of molecular testing. The most common reason for a BSC recommendation was a lack of fitness for systemic therapy (17/31; 55%). Six out of thirty-one (19%) patients deteriorated rapidly and died on the cancer pathway and 5/31 (16%) patients had inadequate renal function for systemic anti-cancer treatment. There was low utilisation of serum epidermal growth factor receptor mutation testing across the study cohort (2/77; 3%). DISCUSSION: In an older, functionally limited and frail patient with lung cancer, there is a risk of over-investigation. Impaired renal function is an important clinical factor to identify early to support discussions in this cohort. There will always be an unavoidable proportion of patients that undergo further investigations (often in search of rare targetable mutations) and are then ultimately recommended for best supportive care; such cases could form the basis of specific review and learning for lung cancer services.

Although eosinophils are important contributors to mucosal immune responses, mechanisms that regulate their accumulation in mucosal-associated lymphoid tissues remain ill-defined. Combining bone marrow chimeras and pharmacological inhibition approaches, here we find that lymphotoxin-beta receptor (LTβR) signaling during the neonatal period is required for the accumulation of eosinophils in the mesenteric lymph nodes (MLN) during an enteric viral infection in adult male and female mice. We demonstrate that MLN stromal cells express genes that are important for eosinophil migration and survival, such as Ccl-11 (eotaxin-1), Ccl7, Ccl9, and Cxcl2, and that expression of most of these genes is downregulated as a consequence of neonatal LTβR blockade. We also find that neonatal LTβR signaling is required for the generation of a rotavirus-specific IgA antibody response in the adult MLN, but eosinophils are dispensable for this response. Collectively, our studies reveal a role for neonatal LTβR signaling in regulating eosinophil numbers in the adult MLN.

In the coming decades, greater numbers of people will either have Alzheimer’s Disease or a related dementia or will take care of a family member with dementia. The dementia syndromes are associated with increased risk of medical, social, and behavioral complications in both the person with dementia (PWD) and the caregiver (CG), many of which are preventable. These complications, and the dementia itself, can impede access to care and ultimately hasten residential care placement, which can be both undesirable and costly. A nearly universal unmet need in PWD/CG dyads is dementia-specific education. Therefore, it is vital we find ways to support and provide education to CG/PWD dyads to manage dementia in the community and home setting. MIND at Home is a dementia-care model developed and tested at Johns Hopkins University School of Medicine to minimize dementia complications and delay institutionalization by training non-clinical Memory Care Coordinators (MCCs) working under clinical supervision to support and guide PWD/CG dyads in the community. MCCs collaborate with CGs and PWDs in the community using an individualized care plan structured around the dyads’ specific dementia-related needs. This presentation will describe how the MIND at Home team used handheld tablets to connect MCCs to clinicians from participants’ homes, and will report on challenges encountered, strategies to address them, and participant and caregiver satisfaction with the telehealth experience.

Construction of commercial buildings has an environmental impact because of emissions from nonroad equipment. Construction produces 7% of the U.S. greenhouse gas emissions, of which 76% originates from engines. However, there has not been an established methodology for estimating construction activity emissions at the project level for buildings and other constructed facilities. Therefore, determining where and when construction produces emissions is important, necessitating that emissions inventories (i.e., databases of project emissions by type, cost, etc.) be developed to quantify these emissions. The pollutants addressed in this paper include carbon dioxide (CO2), nitrogen oxides (NOx), total hydrocarbons (THC), carbon monoxide (CO), particulate matter (PM), and sulfur dioxide (SO2). This paper presents a methodology that provides a direct link between building construction activities and emissions. The use of this methodology is demonstrated for a commercial building case study, thereby provi...

Commercial construction operations are heavy users of nonroad equipment and diesel engines. These engines are large contributors of carbon dioxide (CO2) and other engine-based pollutants and consume large quantities of diesel fuel. This paper presents a case study to identify construction activities that cause the most emissions and fuel use on a construction project and to determine when and where these occur. The paper links emissions and fuel use of construction activities with a project schedule to establish a temporal relationship. RSMeans was used to obtain equipment productivity. Equipment emission rates and fuel use rates were obtained from the EPA’s NONROAD Model. A sensitivity analysis was conducted to investigate the effect of changes in scheduling, equipment size, and EPA engine tier on emissions and fuel use. Site construction activities proved to be the heaviest polluters and caused a significant spike in emissions early in the project. Further study is recommended to validate the tr...

The effects of four commercially available film-forming polymers (Bond, Designer, Spray Gard, Nu-Film-P) on disease severity of powdery mildew (Microsphaera alphitoides Griffon and Maubl.) on English oak (Quercus robur L.) and Guignardia leaf blotch (Guignardia aesculi (Peck) Stewart) on horsechestnut (Aesculus hippocastanum L.) were examined in a field experiment. In addition, a comparative evaluation of the fungicide penconazole, commercially used for powdery mildew control, was conducted. Effects on tree vitality were also assessed by measuring leaf chlorophyll fluorescence and chlorophyll concentrations. Irrespective of tree species, Nu-Film-P and Spray Gard did not significantly influence disease severity of powdery mildew and Guignardia leaf blotch. Likewise, no significant effects of these two film-forming polymers on chlorophyll fluorescence and chlorophyll content were recorded. Reduction in disease severity following spray applications of the film-forming polymers Bond and Designer was statistically comparable with penconazole. None of the film-forming polymers and fungicide evaluated was phytotoxic to the test trees. Results suggest that application of an appropriate film-forming polymer may provide a useful addition to existing methods of plant disease control.

The maize, cut-and-paste transposon Ac/Ds is mobile in Saccharomyces cerevisiae, and DNA sequences of repair products provide strong genetic evidence that hairpin intermediates form in host DNA during this transposition, similar to those formed for V(D)J coding joints in vertebrates. Both DNA strands must be broken for Ac/Ds to excise, suggesting that double-strand break (DSB) repair pathways should be involved in repair of excision sites. In the absence of homologous template, as expected, Ac excisions are repaired by nonhomologous end joining (NHEJ) that can involve microhomologies close to the broken ends. However, unlike repair of endonuclease-induced DSBs, repair of Ac excisions in the presence of homologous template occurs by gene conversion only about half the time, the remainder being NHEJ events. Analysis of transposition in mutant yeast suggests roles for the Mre11/Rad50 complex, SAE2, NEJ1, and the Ku complex in repair of excision sites. Separation-of-function alleles of MRE11 suggest that its endonuclease function is more important in this repair than either its exonuclease or Rad50-binding properties. In addition, the interstrand cross-link repair gene PSO2 plays a role in end joining hairpin ends that is not seen in repair of linearized plasmids and may be involved in positioning transposase cleavage at the transposon ends.

Src homology 2-containing inositol 5'-phosphatase (SHIP) inhibits immune receptor signaling through hydrolysis of the phosphatidylinositol-3 kinase (PI3K) product PI-3,4,5-P3, forming PI-3,4-P2. SHIP represses FcεRI- and cytokine-mediated mast cell activation in vitro, but little is known regarding the function of SHIP in mast cells in vivo, or the susceptibility of Ship-/- mice to mast cell-associated diseases. In this study, we found that Ship-/- mice have systemic mast cell hyperplasia, increased serum levels of IL-6, TNF, and IL-5, and heightened anaphylactic response. Further, by reconstituting mast cell-deficient mice with Ship+/+ or Ship-/- mast cells, we found that the above defects were due to loss of SHIP in mast cells. Additionally, we found that loss of SHIP in mast cells alone resulted in increased allergic asthma pathology. In summary, our data show that SHIP represses allergic inflammation and mast cell hyperplasia in vivo, and that SHIP exerts these effects specifically in mast cells.