Diffusion tensor imaging for the detection of hypoxic-ischemic injury in newborns

This article does not have an abstract

Adult performance on Piaget\u27s water level task and its relation of spatial orientation and visualization

Recent studies have indicated that performance on Piaget\u27s water level task is related to spatial ability. The present study examined the relationship of adult performance on the water level task to spatial orienta­ tion ability, visualization ability and verbal ability. A sample of college stud ents, thirty males and thirty females, were classified as either sophisticated or naive in water level task performance. The students were then given two tests of spatial ability; in addition, a measure of verbal ability was obtained. Spatial orientation ability was measured by the Guilford-Zimmerman Spatial Orientation Test, visualization by the Re­vised Minnesota Paper Form Board Test and verbal ability by the College Entrance Examination Board test of verbal ability. Three two-factor analyses of variance were used to examine the data. The results revealed that both spatial ability tests were significantly related to performance on the water level task. Sophisticated subjects, regardless of sex, evidenced significantly better spatial ability than naive subjects. No significant relationship with verbal ability was found. It was concluded that adult performance on the water level task is related to spatial ability and not to a cognitive based process for the conception of space

Diffusion tensor imaging for the detection of hypoxic-ischemic injury in newborns

This article does not have an abstract

Harnessing the tumor draining lymph node for effective anti-tumor immunity in breast cancer and melanoma

Part 1: Technical aspects of TDLN immune monitoring Viable cell scrapings of the surgically retrieved and bisected SLN offer a unique opportunity to study tumor induced and/or immune modulator effects. In chapter 2, as part of a special issue on new guidelines for DC research for the European Journal of Immunology (submitted), we describe our method of obtaining viable LN cell suspensions and their use for flowcytomety based characterization of TDLN DC subsets. Cryopreservation of SLN single-cell suspensions allows for simultaneous phenotypic multi-parameter analyses and minimizes operator dependent variability. This would be of particular importance for immune monitoring in future multi-center trials. In Chapter 3, we tested the feasibility of cryopreservation of viable SLN cell samples for flowcytometric analysis, by comparing quantitative DC and T Cell analyses of SLN cell samples after freeze-thawing with direct analysis of fresh SLN cell samples (n=9). Although these techniques should not be employed interchangeably in the same trial, cryopreservation and thawing is a valid alternative to direct analysis of fresh viable lymph node cells, without introducing cryo-dependent variance between SLN samples. Part 2: Breast cancer In order to unravel the immune landscape in BrC TDLN, in Chapter 4, we describe the results of a comprehensive flow cytometry–assisted study of viable cells from BrC SLN (n=58) in a comparative analysis with healthy (i.e. prophylactic mastectomy-derived) axillary lymph nodes (HLN, n=17) and show that BrC induced immune suppression coincides with selectively hampered activation of LNR DC subsets. The knowledge that CpG-B can preferentially activate these LNR DC subsets but also induce STAT-3 (a known poor prognostic indicator in BrC and the master switch of tumor induced immune suppression) prompted the ex-vivo functional validation of combined TLR9 targeting and JAK2/STAT3 inhibition as a potential treatment strategy in breast cancer patients. In Chapter 5 Immune modulatory effects of CpG-B with or without the JAK2/STAT3 inhibitor AG490 are assessed in ex vivo cultured BrC SLN-derived single-cell suspensions (N=26). Although CpG-B alone induced activation of all DC subsets, combined inhibition of the JAK2/STAT3 pathway resulted in superior DC maturation and most profoundly so for LNR DC subsets. Most importantly, combined CpG-B and JAK2/STAT3 inhibition (but not CpG-B alone) significantly enhanced BrC specific T cell reactivity. Part 3: melanoma In this part of the thesis we aimed to investigate the involvement of TDLN in the biological activity of CTLA-4 inhibitors in melanoma. In chapter 6, the clinical safety and tolerability and immunological effects of a single dose of anti-CTLA-4 (tremelimumab) injected intradermally at the tumor excision site (for optimal TDLN access) 1 week prior to SLNB in patients with early-stage melanoma (n=13) are reported. Critical findings in this study underscore the importance of immune modulation of TDLN in generating de novo as well as boosting “dormant“ anti-tumor T cell responses and support the concept of local instead of systemic anti-CTLA-4 blockade. In chapter 7, we review the results of recent (pre)clinical studies pointing to the key role of TDLN in the efficacy of immune checkpoint blockade (ICB) further discuss the evidence that therapeutic targeting of TDLN may ensure sufficient antitumor T cell activation and subsequent tumor infiltration to facilitate effective ICB. In Chapter 8 the studies described in this thesis are summarized and further discussed and in Chapter 9 the main findings of these studies are integrated to highlight clinical implications and future directions in breast cancer and melanoma immunotherapy

Host-control of HIV:Balance between immunity and immunopathology

Infection with HIV-1 is characterized by a gradual decline in CD4 T cells as well as chronic activation of the immune system. The balance between an adequate immune response on one side and overstimulation and immune dysfunction on the other, influences the highly variable disease course of untreated HIV-1 infection. Current antiretroviral therapy suppresses viral replication efficiently however, it does not completely restore the immune system and some level of immune activation and inflammation persists. Understanding the mechanisms of HIV-1 pathogenesis could provide novel avenues for treatment of HIV-1 infection and restoration of the observed immune imbalance. In this thesis, the immune response to HIV-1 infection in relation to disease progression and disease control is explored at the level of both the innate and the adaptive immune response. The findings of this thesis contribute to expanding our knowledge on the immune response to HIV-1 infection

Artificial intelligence for detecting periapical radiolucencies: A systematic review and meta-analysis

Objectives: Dentists’ diagnostic accuracy in detecting periapical radiolucency varies considerably. This systematic review and meta-analysis aimed to investigate the accuracy of artificial intelligence (AI) for detecting periapical radiolucency. Data: Studies reporting diagnostic accuracy and utilizing AI for periapical radiolucency detection, published until November 2023, were eligible for inclusion. Meta-analysis was conducted using the online MetaDTA Tool to calculate pooled sensitivity and specificity. Risk of bias was evaluated using QUADAS-2. Sources: A comprehensive search was conducted in PubMed/MEDLINE, ScienceDirect, and Institute of Electrical and Electronics Engineers (IEEE) Xplore databases. Studies reporting diagnostic accuracy and utilizing AI tools for periapical radiolucency detection, published until November 2023, were eligible for inclusion. Study selection: We identified 210 articles, of which 24 met the criteria for inclusion in the review. All but one study used one type of convolutional neural network. The body of evidence comes with an overall unclear to high risk of bias and several applicability concerns. Four of the twenty-four studies were included in a meta-analysis. AI showed a pooled sensitivity and specificity of 0.94 (95 % CI = 0.90–0.96) and 0.96 (95 % CI = 0.91–0.98), respectively. Conclusions: AI demonstrated high specificity and sensitivity for detecting periapical radiolucencies. However, the current landscape suggests a need for diverse study designs beyond traditional diagnostic accuracy studies. Prospective real-life randomized controlled trials using heterogeneous data are needed to demonstrate the true value of AI. Clinical significance: Artificial intelligence tools seem to have the potential to support detecting periapical radiolucencies on imagery. Notably, nearly all studies did not test fully fledged software systems but measured the mere accuracy of AI models in diagnostic accuracy studies. The true value of currently available AI-based software for lesion detection on both 2D and 3D radiographs remains uncertai

Living Information Systems and Change

The Centre for Living Information Systems Thinking (LIST) is looking at IS development in organisations undergoing change. After discussing the problems that change introduces into IS development, the paper explains the basic philosophy of the centre, and some of the areas of research that might make a contribution to the basic questions that have been derived. Some views on the subject of change in organisations will be outlined, and the change paradox will be introduced