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The benefit of the PET/CT imaging modality resides in its fusion of anatomic detail of the HN region with the sensitivity of detecting tumors with increased metabolic activity at distant sites. Treatment was altered in 30.9% of our previously untreated HN cancer patients because of this imaging technique, with altered treatment including upstaging, diagnosing distant and unresectable disease, and working-up second primary malignancies. The false-positive findings did not result in additional morbidity to these patients. Although PET/CT is sensitive in detecting occult cervical nodal metastases, it does not yet have the ability to replace neck dissection as the diagnostic standard of care. This study supports the use of PET/CT in patients with newly diagnosed HN cancer because of its high PPV and superiority of detecting distant metastases and synchronous lesions.

Genomic selection offers several routes for increasing the genetic gain or efficiency of plant breeding programmes. In various species of livestock, there is empirical evidence of increased rates of genetic gain from the use of genomic selection to target different aspects of the breeder’s equation. Accurate predictions of genomic breeding value are central to this, and the design of training sets is in turn central to achieving sufficient levels of accuracy. In summary, small numbers of close relatives and very large numbers of distant relatives are expected to enable predictions with higher accuracy. To quantify the effect of some of the properties of training sets on the accuracy of genomic selection in crops, we performed an extensive field-based winter wheat trial. In summary, this trial involved the construction of 44 F 2:4 bi- and tri-parental populations, from which 2992 lines were grown on four field locations and yield was measured. For each line, genotype data were generated for 25 K segregating SNP markers. The overall heritability of yield was estimated to 0.65, and estimates within individual families ranged between 0.10 and 0.85. Genomic prediction accuracies of yield BLUEs were 0.125–0.127 using two different cross-validation approaches and generally increased with training set size. Using related crosses in training and validation sets generally resulted in higher prediction accuracies than using unrelated crosses. The results of this study emphasise the importance of the training panel design in relation to the genetic material to which the resulting prediction model is to be applied. Electronic supplementary material The online version of this article (10.1007/s00122-019-03327-y) contains supplementary material, which is available to authorized users.

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Senescent cells interact with the surrounding microenvironment achieving diverse functional outcomes. We have recently identified that NOTCH1 can drive ‘lateral induction’ of a unique senescence phenotype in adjacent cells by specifically upregulating the NOTCH ligand JAG1. Here we show that NOTCH signalling can modulate chromatin structure autonomously and non-autonomously. In addition to senescence-associated heterochromatic foci (SAHF), oncogenic RAS-induced senescent (RIS) cells exhibit a massive increase in chromatin accessibility. NOTCH signalling suppresses SAHF and increased chromatin accessibility in this context. Strikingly, NOTCH-induced senescent cells, or cancer cells with high JAG1 expression, drive similar chromatin architectural changes in adjacent cells through cell–cell contact. Mechanistically, we show that NOTCH signalling represses the chromatin architectural protein HMGA1, an association found in multiple human cancers. Thus, HMGA1 is involved not only in SAHFs but also in RIS-driven chromatin accessibility. In conclusion, this study identifies that the JAG1–NOTCH–HMGA1 axis mediates the juxtacrine regulation of chromatin architecture.

ABSTRACTshow that NOTCH signalling represses the chromatin architectural protein HMGA1, an association found in a range of human cancers. Thus, HMGA1 is involved not only in SAHFs, but also RIS-specific NFR formation. In conclusion, this study identifies that the JAG1-NOTCH-HMGA1 axis mediates the juxtacrine regulation of chromatin architecture.

People are increasingly looking for health-related information and support to empower their sel f-management and decision making. Online health communities have not only become an important alternative source of patientcentered information but also appear to serve an emotional support role in connecting patients who have similar medical conditions. Trust is critical to sustain their continuous use and enhance their involvement. This is because each community member is typically identified onl y by a pseudonym, important personal information is often revealed, the quality of information provided by others varies, and the consequences of acting on incorrec t advice can be severe. Using semi-structured interviews and data from postings, thi s study qualitatively explores the trust development betw een users of forum-based online health communities. Based on data from a w ide range of medical conditions, we formulated a three-process framew ork for establishing trust that conceptualizes how users build trust through the text-based medium and how they progress from one process to another. We contribute to theory by extending exi sting variance theories in trust to a hybrid process theory whi ch explains the dynamic progression from one state to another. It suggests several design foci that can enhance user experience of these forums.