Publications by authors named "Knutsen A"

Introduction: Computational head injury models are promising tools for understanding and predicting traumatic brain injuries. However, most available head injury models are "average" models that employ a single set of head geometry (e.g.

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Severe combined immunodeficiency (SCID) is characterized by a severe deficiency in T cell numbers. We analyzed data collected (n = 307) for PHA-based T cell proliferation from the PIDTC SCID protocol 6901, using either a radioactive or flow cytometry method. In comparing the two groups, a smaller number of the patients tested by flow cytometry had <10% of the lower limit of normal proliferation as compared to the radioactive method (p = 0.

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Background: The Primary Immune Deficiency Treatment Consortium (PIDTC) enrolled children in the United States and Canada onto a retrospective multicenter natural history study of hematopoietic cell transplantation (HCT).

Objective: We investigated outcomes of HCT for severe combined immunodeficiency (SCID).

Methods: We evaluated the chronic and late effects (CLE) after HCT for SCID in 399 patients transplanted from 1982 to 2012 at 32 PIDTC centers.

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We describe the case of a 10-month-old boy with vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb abnormalities (VACTERL) association and athymia who developed Omenn syndrome.

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Article Synopsis
  • Chronic granulomatous disease (CGD) is a serious immunodeficiency often treated with hematopoietic cell transplantation (HCT), which has shown a 3-year overall survival rate of 82% in patients studied.
  • Pre-existing inflammatory conditions and infections before HCT did not significantly impact survival, but a lower performance score and HLA mismatches were detrimental to outcomes.
  • Post-transplant, patients experienced significant health improvements, with reduced disease burden and lower medication use compared to non-transplant patients, indicating HCT is a robust treatment option for CGD.
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Background: Severe combined immunodeficiency (SCID) is fatal unless durable adaptive immunity is established, most commonly through allogeneic haematopoietic cell transplantation (HCT). The Primary Immune Deficiency Treatment Consortium (PIDTC) explored factors affecting the survival of individuals with SCID over almost four decades, focusing on the effects of population-based newborn screening for SCID that was initiated in 2008 and expanded during 2010-18.

Methods: We analysed transplantation-related data from children with SCID treated at 34 PIDTC sites in the USA and Canada, using the calendar time intervals 1982-89, 1990-99, 2000-09, and 2010-18.

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Noninvasive measurements of brain deformation in human participants in vivo are needed to develop models of brain biomechanics and understand traumatic brain injury (TBI). Tagged magnetic resonance imaging (tagged MRI) and magnetic resonance elastography (MRE) are two techniques to study human brain deformation; these techniques differ in the type of motion and difficulty of implementation. In this study, oscillatory strain fields in the human brain caused by impulsive head acceleration and measured by tagged MRI were compared quantitatively to strain fields measured by MRE during harmonic head motion at 10 and 50 Hz.

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Purpose: Few studies have focused on the late adverse events after oncologic treatment in pelvic cancer patients. Here, the treatment effect/interventions were studied on late side effects as GI, sexual, and urinary symptoms in pelvic cancer patients who visited a highly specialized rehabilitation clinic in Linköping.

Methods: This retrospective longitudinal cohort study included 90 patients who had at least one visit at the rehabilitation clinic for late adverse events at Linköping University hospital between 2013 to 2019.

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Introduction: The value of adjuvant chemotherapy for rectal cancer patients is debated and varies in different subgroups. One such subgroup is mucinous adenocarcinoma (MAC), which is more treatment resistant compared to non-mucinous adenocarcinoma (NMAC). To date, mucinous histology is not taken into account when deciding on adjuvant treatment strategy.

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Article Synopsis
  • - Traumatic brain injury (TBI) is a significant health issue for both military and civilian groups, with ongoing challenges in understanding how different types of impacts lead to injuries.
  • - The study introduces the ANGUS phantom, a synthetic brain model made from polyacrylamide gel, designed to simulate human brain properties and improve research on TBI without using animal models.
  • - Mechanical comparisons between the ANGUS phantom and human subjects show that while the phantom accurately mimics responses to certain types of impacts, it falls short in modeling responses to rotational impacts, highlighting areas for further research.
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Article Synopsis
  • Patients with inherited CARMIL2 or CD28 deficiencies show defective T cell signaling, but CARMIL2's role is less understood.
  • Research indicates that the mutant CARMIL2 alleles affect T cell activation and lead to specific immunological issues including low counts of memory T cells and NK cells, as well as weak antibody responses.
  • CARMIL2 deficiency leads to serious health issues by age 10, including frequent infections and inflammation, and milder symptoms are observed in patients with somatic reversions in T cells.
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Background: Shearer et al in 2014 articulated well-defined criteria for the diagnosis and classification of severe combined immunodeficiency (SCID) as part of the Primary Immune Deficiency Treatment Consortium's (PIDTC's) prospective and retrospective studies of SCID.

Objective: Because of the advent of newborn screening for SCID and expanded availability of genetic sequencing, revision of the PIDTC 2014 Criteria was needed.

Methods: We developed and tested updated PIDTC 2022 SCID Definitions by analyzing 379 patients proposed for prospective enrollment into Protocol 6901, focusing on the ability to distinguish patients with various SCID subtypes.

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Computational models of the human head are promising tools for estimating the impact-induced response of the brain, and thus play an important role in the prediction of traumatic brain injury. The basic constituents of these models (i.e.

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Pre-clinical models of traumatic brain injury (TBI) have been the primary experimental tool for understanding the potential mechanisms and cellular alterations that follow brain injury, but the human relevance and translational value of these models are often called into question. Efforts to better recapitulate injury biomechanics and the use of non-rodent species with neuroanatomical similarities to humans may address these concerns and promise to advance experimental studies toward clinical impact. In addition to improving translational aspects of animal models, it is also advantageous to establish pre-clinical outcomes that can be directly compared with the same outcomes in humans.

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Questionnaires for restless legs syndrome have rarely been validated against face-to-face interviews in the general population. We aimed to validate the modified Norwegian, seven-item Cambridge-Hopkins restless legs syndrome questionnaire and a single diagnostic question for restless legs syndrome. We also aimed to stratify validity at 65 years of age.

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The consequences of forceful rotational acceleration on the central nervous system are not fully understood. While traumatic brain injury (TBI) research primarily has focused on effects related to the brain parenchyma, reports of traumatic meningeal enhancement in TBI patients may possess clinical significance. The objective of this study was to evaluate the meninges and brain for changes in dynamic contrast enhancement (DCE) magnetic resonance imaging (MRI) following closed-head impact model of engineered rotational acceleration (CHIMERA)-induced cerebral insult.

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Computational models of the brain and its biomechanical response to skull accelerations are important tools for understanding and predicting traumatic brain injuries (TBIs). However, most models have been developed using experimental data collected on animal models and cadaveric specimens, both of which differ from the living human brain. Here we describe efforts to noninvasively measure the biomechanical response of the human brain with MRI-at non-injurious strain levels-and generate data that can be used to develop, calibrate, and evaluate computational brain biomechanics models.

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Brain movement during an impact can elicit a traumatic brain injury, but tissue kinematics vary from person to person and knowledge regarding this variability is limited. This study examines spatio-temporal brain-skull displacement and brain tissue deformation across groups of subjects during a mild impact . The heads of two groups of participants were imaged while subjected to a mild (less than 350 rad s) impact during neck extension (NE, = 10) and neck rotation (NR, = 9).

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Central to the investigation of the biomechanics of traumatic brain injury (TBI) and the assessment of injury risk from head impact are finite element (FE) models of the human brain. However, many existing FE human brain models have been developed with simplified representations of the parenchyma, which may limit their applicability as an injury prediction tool. Recent advances in neuroimaging techniques and brain biomechanics provide new and necessary experimental data that can improve the biofidelity of FE brain models.

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Traumatic brain injury (TBI) causes chronic symptoms and increased risk of neurodegeneration. Axons in white matter tracts, such as the corpus callosum (CC), are critical components of neural circuits and particularly vulnerable to TBI. Treatments are needed to protect axons from traumatic injury and mitigate post-traumatic neurodegeneration.

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The rapid deformation of brain tissue in response to head impact can lead to traumatic brain injury. In vivo measurements of brain deformation during non-injurious head impacts are necessary to understand the underlying mechanisms of traumatic brain injury and compare to computational models of brain biomechanics. Using tagged magnetic resonance imaging (MRI), we obtained measurements of three-dimensional strain tensors that resulted from a mild head impact after neck rotation or neck extension.

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Natural modes and frequencies of three-dimensional (3D) deformation of the human brain were identified from in vivo tagged magnetic resonance images (MRI) acquired dynamically during transient mild acceleration of the head. Twenty 3D strain fields, estimated from tagged MRI image volumes in 19 adult subjects, were analyzed using dynamic mode decomposition (DMD). These strain fields represented dynamic, 3D brain deformations during constrained head accelerations, either involving rotation about the vertical axis of the neck or neck extension.

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Magnetic resonance imaging (MRI) is a widely used non-invasive methodology for both preclinical and clinical studies. However, MRI lacks molecular specificity. Molecular contrast agents for MRI would be highly beneficial for detecting specific pathological lesions and quantitatively evaluating therapeutic efficacy in vivo.

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