Child Health Providers\u27 Precautionary Discussion of Emotions During Communication about Results of Newborn Genetic Screening

Objective To demonstrate a quantitative abstraction method for Communication Quality Assurance projects to assess physicians\u27 communication about hidden emotions after newborn genetic screening. Design Communication quality indicator analysis. Setting Standardized parent encounters performed in practicing physicians\u27 clinics or during educational workshops for residents. Participants Fifty-nine pediatrics residents, 53 pediatricians, and 31 family physicians. Intervention Participants were asked to counsel standardized parents about a screening result; counseling was recorded, transcribed, and parsed into statements (each with 1 subject and 1 predicate). Pairs of abstractors independently compared statements with a data dictionary containing explicit-criteria definitions. Outcome Measures Four groups of precautionary empathy behaviors (assessment of emotion, anticipation/validation of emotion, instruction about emotion, and caution about future emotion), with definitions developed for both definite and partial instances. Results Only 38 of 143 transcripts (26.6%) met definite criteria for at least 1 of the precautionary empathy behaviors. When partial criteria were counted, this number increased to 80 of 143 transcripts (55.9%). The most common type of precautionary empathy was the instruction about emotion behavior (eg, don\u27t be worried ), which may sometimes be leading or premature. Conclusions Precautionary empathy behaviors were rare in this analysis. Further study is needed, but this study should raise concerns about the quality of communication services after newborn screening

Time-course of effects of external beam radiation on [18F]FDG uptake in healthy tissue and bone marrow.

The utility of PET for monitoring responses to radiation therapy have been complicated by metabolically active processes in surrounding normal tissues. We examined the time-course of [18F]FDG uptake in normal tissues using small animal-dedicated PET during the 2 month period following external beam radiation. Four mice received 12 Gy of external beam radiation, in a single fraction to the left half of the body. Small animal [18F]FDG-PET scans were acquired for each mouse at 0 (pre-radiation), 1, 2, 3, 4, 5, 8, 12, 19, 24, and 38 days following irradiation. [18F]FDG activity in various tissues was compared between irradiated and non-irradiated body halves before, and at each time point after irradiation. Radiation had a significant impact on [18F]FDG uptake in previously healthy tissues, and time-course of effects differed in different types of tissues. For example, liver tissue demonstrated increased uptake, particularly over days 3-12, with the mean left to right uptake ratio increasing 52% over mean baseline values (p < 0.0001). In contrast, femoral bone marrow uptake demonstrated decreased uptake, particularly over days 2-8, with the mean left to right uptake ratio decreasing 26% below mean baseline values (p = 0.0005). Significant effects were also seen in lung and brain tissue. Radiation had diverse effects on [18F]FDG uptake in previously healthy tissues. These kinds of data may help lay groundwork for a systematically acquired database of the time-course of effects of radiation on healthy tissues, useful for animal models of cancer therapy imminently, as well as interspecies extrapolations pertinent to clinical application eventually

Identification of Rare High-Avidity, Tumor-Reactive CD8+ T Cells by Monomeric TCR-Ligand Off-Rates Measurements on Living Cells.

The avidity of the T-cell receptor (TCR) for antigenic peptides presented by the peptide-MHC (pMHC) on cells is a key parameter for cell-mediated immunity. Yet a fundamental feature of most tumor antigen-specific CD8(+) T cells is that this avidity is low. In this study, we addressed the need to identify and select tumor-specific CD8(+) T cells of highest avidity, which are of the greatest interest for adoptive cell therapy in patients with cancer. To identify these rare cells, we developed a peptide-MHC multimer technology, which uses reversible Ni(2+)-nitrilotriacetic acid histidine tags (NTAmers). NTAmers are highly stable but upon imidazole addition, they decay rapidly to pMHC monomers, allowing flow-cytometric-based measurements of monomeric TCR-pMHC dissociation rates of living CD8(+) T cells on a wide avidity spectrum. We documented strong correlations between NTAmer kinetic results and those obtained by surface plasmon resonance. Using NTAmers that were deficient for CD8 binding to pMHC, we found that CD8 itself stabilized the TCR-pMHC complex, prolonging the dissociation half-life several fold. Notably, our NTAmer technology accurately predicted the function of large panels of tumor-specific T cells that were isolated prospectively from patients with cancer. Overall, our results demonstrated that NTAmers are effective tools to isolate rare high-avidity cytotoxic T cells from patients for use in adoptive therapies for cancer treatment

Policy brief on the organic approach to inputs – Plant protection products, fertilisers, veterinary drugs and feed additives explained

The plant and animal health care strategy in organic farming strengthensagro-biodiversity, protects the environment as well as animal and human health. In addition to fully exploiting preventive options, the use of external inputs such as plant protection products, fertilisers or veterinarymedicinal productsis allowed to prevent inacceptable losses in productivity or animal suffering. However, external inputs need to comply with organic standardsas well as European legislationand aretherefore carefully evaluated before any decision on acceptance is taken.Organic farming systems should aim at reducing dependency on off-farm fertilisers to the lowest feasable level to ensure closed nutrient cycles and avoid nutrient leakage and contamination. This policy brief explains the underlying principles and the procedures for evaluation of inputs, focusing on plant protection products, fertilisers, feed additives and veterinary medicinal products used in organic farming under European legislation. The case study in Annex I on plant protection products provides a full picture on the processes and criteria for authorisation, the assessment of new inputs accordingtothe suitability in organic farming, the history of utilised substances and possible trade-offs and concerns

Betriebsmittelliste 2010 für die Schweiz

Die Betriebsmittelliste beinhaltet alle für den biologischen Landbau in der Schweiz zugelassenen Dünger und Substrate, Pflanzenschutzmittel, Reinigungs-, Desinfektions- und Hygienemittel, Mittel gegen Parasiten sowie Futter- und Siliermittel. Die Liste ist für die Produzenten von Bio Suisse verbindlich. Grundsätzlich dürfen auf Bio Suisse-Betrieben ausschliesslich die in der Betriebsmittelliste aufgeführten Produkte eingesetzt werden. Ausnahmen sind in den Einleitungen der einzelnen Kapitel vermerkt

Genetic determinants of co-accessible chromatin regions in activated T cells across humans.

Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4+ T cells in up to 105 healthy donors. We found that regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, consistent with the three-dimensional chromatin organization measured by in situ Hi-C in T cells. Fifteen percent of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (local-ATAC-QTLs). Local-ATAC-QTLs have the largest effects on co-accessible peaks, are associated with gene expression and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulate cis-regulatory elements, in isolation or in concert, to influence gene expression

Self-associated molecular patterns mediate cancer immune evasion by engaging Siglecs on T cells

© 2018, American Society for Clinical Investigation. This article has been published in final form at https://doi.org/10.1172/JCI120612First-generation immune checkpoint inhibitors, including anti-CTLA-4 and anti-programmed death 1 (anti-PD-1) antibodies, have led to major clinical progress, yet resistance frequently leads to treatment failure. Thus, new targets acting on T cells are needed. CD33-related sialic acid-binding immunoglobulin-like lectins (Siglecs) are pattern-recognition immune receptors binding to a range of sialoglycan ligands, which appear to function as self-associated molecular patterns (SAMPs) that suppress autoimmune responses. Siglecs are expressed at very low levels on normal T cells, and these receptors were not until recently considered as interesting targets on T cells for cancer immunotherapy. Here, we show an upregulation of Siglecs, including Siglec-9, on tumor-infiltrating T cells from non-small cell lung cancer (NSCLC), colorectal, and ovarian cancer patients. Siglec-9-expressing T cells coexpressed several inhibitory receptors, including PD-1. Targeting of the sialoglycan-SAMP/Siglec pathway in vitro and in vivo resulted in increased anticancer immunity. T cell expression of Siglec-9 in NSCLC patients correlated with reduced survival, and Siglec-9 polymorphisms showed association with the risk of developing lung and colorectal cancer. Our data identify the sialoglycan-SAMP/Siglec pathway as a potential target for improving T cell activation for immunotherapy.Peer reviewe