37 research outputs found

    Comparisons of Three Different Investigative Interview Techniques With Young Children

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    After viewing a film of a mother hitting her son, a film not seen by the college student interviewers, children were misinformed about a detail (via exposure to a misleadingquestion) as well as explicitly coached to disclose 3 false details. The children were then interviewed by interviewers who had previously learned 1 of 3 different interviewing procedures: the Yuille Step-Wise Interview developed by J. C. Yuille, R. Hunter,R. Joffe, & J. Zaparniuk (1993); a doll play interview developed by Action for Child Protection Inc. (1994); or the Modified Structured Interview developed for this study. The Modified Structured Interview yielded more “where” information and was better at detecting if coaching had occurred. However, the interviewers were not very good at discriminating suggested versus coached versus correct witnessed information. The authors found that the deeper one digs for memories, the more one uncovers incorrect versus correct items. They concluded that although the Modified Structured Interview was superior tothe techniques currently in use, cautions are necessary

    Spatial maps of prostate cancer transcriptomes reveal an unexplored landscape of heterogeneity

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    Intra-tumor heterogeneity is one of the biggest challenges in cancer treatment today. Here we investigate tissue-wide gene expression heterogeneity throughout a multifocal prostate cancer using the spatial transcriptomics (ST) technology. Utilizing a novel approach for deconvolution, we analyze the transcriptomes of nearly 6750 tissue regions and extract distinct expression profiles for the different tissue components, such as stroma, normal and PIN glands, immune cells and cancer. We distinguish healthy and diseased areas and thereby provide insight into gene expression changes during the progression of prostate cancer. Compared to pathologist annotations, we delineate the extent of cancer foci more accurately, interestingly without link to histological changes. We identify gene expression gradients in stroma adjacent to tumor regions that allow for re-stratification of the tumor microenvironment. The establishment of these profiles is the first step towards an unbiased view of prostate cancer and can serve as a dictionary for future studies

    Massive-Scale RNA-Seq Analysis of Non Ribosomal Transcriptome in Human Trisomy 21

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    Hybridization- and tag-based technologies have been successfully used in Down syndrome to identify genes involved in various aspects of the pathogenesis. However, these technologies suffer from several limits and drawbacks and, to date, information about rare, even though relevant, RNA species such as long and small non-coding RNAs, is completely missing. Indeed, none of published works has still described the whole transcriptional landscape of Down syndrome. Although the recent advances in high-throughput RNA sequencing have revealed the complexity of transcriptomes, most of them rely on polyA enrichment protocols, able to detect only a small fraction of total RNA content. On the opposite end, massive-scale RNA sequencing on rRNA-depleted samples allows the survey of the complete set of coding and non-coding RNA species, now emerging as novel contributors to pathogenic mechanisms. Hence, in this work we analysed for the first time the complete transcriptome of human trisomic endothelial progenitor cells to an unprecedented level of resolution and sensitivity by RNA-sequencing. Our analysis allowed us to detect differential expression of even low expressed genes crucial for the pathogenesis, to disclose novel regions of active transcription outside yet annotated loci, and to investigate a plethora of non-polyadenilated long as well as short non coding RNAs. Novel splice isoforms for a large subset of crucial genes, and novel extended untranslated regions for known genes—possibly novel miRNA targets or regulatory sites for gene transcription—were also identified in this study. Coupling the rRNA depletion of samples, followed by high-throughput RNA-sequencing, to the easy availability of these cells renders this approach very feasible for transcriptome studies, offering the possibility of investigating in-depth blood-related pathological features of Down syndrome, as well as other genetic disorders

    Joint practice guidelines for radionuclide lymphoscintigraphy for sentinel node localization in oral/oropharyngeal squamous cell carcinoma

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    Involvement of the cervical lymph nodes is the most important prognostic factor for patients with oral/oropharyngeal squamous cell carcinoma (OSCC), and the decision whether to electively treat patients with clinically negative necks remains a controversial topic. Sentinel node biopsy (SNB) provides a minimally invasive method of determining the disease status of the cervical node basin, without the need for a formal neck dissection. This technique potentially improves the accuracy of histological nodal staging and avoids over-treating three-quarters of this patient population, minimizing associated morbidity. The technique has been validated for patients with OSCC, and larger-scale studies are in progress to determine its exact role in the management of this patient population. This article was designed to outline the current best practice guidelines for the provision of SNB in patients with early-stage OSCC, and to provide a framework for the currently evolving recommendations for its use. These guidelines were prepared by a multidisciplinary surgical/nuclear medicine/pathology expert panel under the joint auspices of the European Association of Nuclear Medicine (EANM) Oncology Committee and the Sentinel European Node Trial Committee

    Cell-free DNA profiling of metastatic prostate cancer reveals microsatellite instability, structural rearrangements and clonal hematopoiesis.

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    This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.BACKGROUND: There are multiple existing and emerging therapeutic avenues for metastatic prostate cancer, with a common denominator, which is the need for predictive biomarkers. Circulating tumor DNA (ctDNA) has the potential to cost-efficiently accelerate precision medicine trials to improve clinical efficacy and diminish costs and toxicity. However, comprehensive ctDNA profiling in metastatic prostate cancer to date has been limited. METHODS: A combination of targeted and low-pass whole genome sequencing was performed on plasma cell-free DNA and matched white blood cell germline DNA in 364 blood samples from 217 metastatic prostate cancer patients. RESULTS: ctDNA was detected in 85.9% of baseline samples, correlated to line of therapy and was mirrored by circulating tumor cell enumeration of synchronous blood samples. Comprehensive profiling of the androgen receptor (AR) revealed a continuous increase in the fraction of patients with intra-AR structural variation, from 15.4% during first-line metastatic castration-resistant prostate cancer therapy to 45.2% in fourth line, indicating a continuous evolution of AR during the course of the disease. Patients displayed frequent alterations in DNA repair deficiency genes (18.0%). Additionally, the microsatellite instability phenotype was identified in 3.81% of eligible samples (≄ 0.1 ctDNA fraction). Sequencing of non-repetitive intronic and exonic regions of PTEN, RB1, and TP53 detected biallelic inactivation in 47.5%, 20.3%, and 44.1% of samples with ≄ 0.2 ctDNA fraction, respectively. Only one patient carried a clonal high-impact variant without a detectable second hit. Intronic high-impact structural variation was twice as common as exonic mutations in PTEN and RB1. Finally, 14.6% of patients presented false positive variants due to clonal hematopoiesis, commonly ignored in commercially available assays. CONCLUSIONS: ctDNA profiles appear to mirror the genomic landscape of metastatic prostate cancer tissue and may cost-efficiently provide somatic information in clinical trials designed to identify predictive biomarkers. However, intronic sequencing of the interrogated tumor suppressors challenges the ubiquitous focus on coding regions and is vital, together with profiling of synchronous white blood cells, to minimize erroneous assignments which in turn may confound results and impede true associations in clinical trials.The Belgian Foundation Against Cancer (grant number C/2014/227); Kom op tegen Kanker (Stand up to Cancer), the Flemish Cancer Society (grant number 00000000116000000206); Royal College of Surgeons/Cancer Research UK (C19198/A1533); The Cancer Research Funds of Radiumhemmet, through the PCM program at KI (grant number 163012); The Erling-Persson family foundation (grant number 4-2689-2016); the Swedish Research Council (grant number K2010-70X-20430-04-3), and the Swedish Cancer Foundation (grant number 09-0677)

    Making a case for gender-inclusive innovation through the concept of creative imitation

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    Through creative imitation, this article aims to make the case for a more inclusive view on innovation related to gender. In entrepreneurship theory, innovation is usually associated with creativity as something extraordinary, followed by generalisations of how innovation is brought about, which are based upon dichotomies that lead to exclusion of those who are expected to innovate. Innovation policy tends to associate innovation with industrial, large-scale product development, to the neglect of other types of innovations. Therefore, policy and research both tend to disregard certain innovations that are pursued by certain actors in certain areas. In particular, women entrepreneurs are neglected, as are innovations within women-dominated industries. This marginalisation is, arguably, related to how innovation is conceptualised, which this article will scrutinise by means of gender theory and narrative theory. The article highlights the example of a businesswoman who has pursued innovation in the area of wedding arrangements, which represents one of the categories that have been marginalised in research and policy on innovation. The woman's story of one of her innovations is analysed based upon data collected at dialogue seminars. This illustrates how innovation – when regarded as a mediation between creativity and imitation – appears to be both extraordinary and everyday, as well as tied to the context in which it appears. This serves to bridge dichotomies and end up with an inclusive approach in terms of who is expected to innovate, where, and what. In so doing, this article challenges common assumptions regarding innovation and offers an original interpretation of how innovation is associated to imitation and gendered relations.Validerad; 2012; 20120220 (andbra

    Lyftet : forskning om kvinnors företagande och initiativ i innovationssystem

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    Slutrapport för projektet Lyftet. Lyftet har haft sin bas i tvÄ forskningsmiljöer, en vid LuleÄ tekniska universitet och en vid MÀlardalens högskola. Vid bÄda dessa miljöer har man sedan ett flertal Är bedrivit forskning kring, och Àven konkret utvecklingssamarbete med, lokala projekt och initiativ dÀr kvinnor haft drivande roller i innovationsinriktat arbete, med bas i norra Norrland, Södermanland och VÀstmanland. Slutrapporten - som Àr kort och hÄller fram huvuddragen i Lyftets resultat - Àr uppdelad sÄ att var och en av projektets fyra forskare haft nÄgra sidor till förfogande att sjÀlv bestÀmma innehÄllet. Projektets forskare har olika bakgrund, och har delvis intresserat sig för olika vÀgar att teoretisera Lyftets forskningsmaterial. MÄngfalden i stil och perspektiv stimulerar till vidare utveckling. För mer fylliga vetenskapliga och debatterande resultatredovisningar finns lÀshÀnvisningar till publicerade och i nÄgra fall kommande publikationer inklusive tvÄ doktorsavhandlingar som planeras till 2010. Rapportens teman Àr; Information och brist pÄ information; Kvinnor, teknik och innovationssystem; UppvÀga eller spÀ pÄ marknadens brister?: SamhÀllets roll i teori och praktik; Entreprenörskapsdiskursens historiska rötter; Behovet av en kritisk emancipatorisk forskning; Prioriteringsmönster i Sveriges innovationspolitik; Resurscentrum som innovationssystem; Quattro helix; InnovationsinnehÄll; Att synliggöra andra perspektiv; I skÀrningspunkten mellan tre perspektiv; MÀtande i fokus; IntersektionalitetGodkÀnd; 2008; 20081027 (ysko

    Evidence of a Christmas spirit network in the brain:functional MRI study

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    Objective To detect and localise the Christmas spirit in the human brain. Design Single blinded, cross cultural group study with functional magnetic resonance imaging (fMRI). Setting Functional imaging unit and department of clinical physiology, nuclear medicine and PET in Denmark. Participants 10 healthy people from the Copenhagen area who routinely celebrate Christmas and 10 healthy people living in the same area who have no Christmas traditions. Main outcome measures Brain activation unique to the group with Christmas traditions during visual stimulation with images with a Christmas theme. Methods Functional brain scans optimised for detection of the blood oxygen level dependent (BOLD) response were performed while participants viewed a series of images with Christmas themes interleaved with neutral images having similar characteristics but containing nothing that symbolises Christmas. After scanning, participants answered a questionnaire about their Christmas traditions and the associations they have with Christmas. Brain activation maps from scanning were analysed for Christmas related activation in the “Christmas” and “non-Christmas” groups individually. Subsequently, differences between the two groups were calculated to determine Christmas specific brain activation. Results Significant clusters of increased BOLD activation in the sensory motor cortex, the premotor and primary motor cortex, and the parietal lobule (inferior and superior) were found in scans of people who celebrate Christmas with positive associations compared with scans in a group having no Christmas traditions and neutral associations. These cerebral areas have been associated with spirituality, somatic senses, and recognition of facial emotion among many other functions. Conclusions There is a “Christmas spirit network” in the human brain comprising several cortical areas. This network had a significantly higher activation in a people who celebrate Christmas with positive associations as opposed to a people who have no Christmas traditions and neutral associations. Further research is necessary to understand this and other potential holiday circuits in the brain. Although merry and intriguing, these findings should be interpreted with caution
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