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Debate persists regarding the nature of age-related deficits in inhibition, and whether inhibitory functioning depends on working memory systems. The current research aimed to measure age-related differences in inhibition and working memory, characterize the relationship between inhibitory functions and working memory performance, and determine how these relationships are affected by age. Toward these ends, we measured performance on a range of established paradigms in 60 young adults (18-30 years) and 60 older adults (60-88 years). Our findings support age-related increases in reflexive inhibition (based on the fixation offset effect and inhibition of return) and age-related decrements in volitional inhibition (based on several paradigms: antisaccade, Stroop, flanker, and Simon). This evidence of stronger reflexive inhibition combined with weaker volitional inhibition suggests that age-related deterioration of cortical structures may allow subcortical structures to operate less controlled. Regarding working memory, older adults had lower backward digit scores and lower forward and backward spatial scores. However, of the 32 analyses (16 in each age group) that tested for dependence of inhibitory functioning on working memory functioning, only one (in young adults) indicated that inhibition performance significantly depended on working memory performance. These results indicate that inhibition and working memory function largely independently in both age groups, and age-related working memory difficulties cannot account for age-related declines in inhibitory control.

Purpose: Combination therapies are a promising approach for improving cancer treatment, but it is challenging to predict their resulting adverse events in a real-world setting., Experimental Design: We provide here a proof-of-concept study using 15 million patient records from the FDA Adverse Event Reporting System (FAERS). Complex adverse event frequencies of drugs or their combinations were visualized as heat maps onto a two-dimensional grid. Adverse event frequencies were shown as colors to assess the ratio between individual and combined drug effects. To capture these patterns, we trained a convolutional neural network (CNN) autoencoder using 7,300 single-drug heat maps. In addition, statistical synergy analyses were performed on the basis of BLISS independence or χ2 testing., Results: The trained CNN model was able to decode patterns, showing that adverse events occur in global rather than isolated and unique patterns. Patterns were not likely to be attributed to disease symptoms given their relatively limited contribution to drug-associated adverse events. Pattern recognition was validated using trial data from ClinicalTrials.gov and drug combination data. We examined the adverse event interactions of 140 drug combinations known to be avoided in the clinic and found that near all of them showed additive rather than synergistic interactions, also when assessed statistically., Conclusions: Our study provides a framework for analyzing adverse events and suggests that adverse drug interactions commonly result in additive effects with a high level of overlap of adverse event patterns. These real-world insights may advance the implementation of new combination therapies in clinical practice., (©2024 The Authors; Published by the American Association for Cancer Research.)

The transportation sector is among the highest contributors to the increase in greenhouse gas emissions in European nations, with private cars emerging as the primary source. Although reducing emissions presents a formidable challenge, the emergence of battery electric vehicles (BEVs) offers a promising and sustainable avenue toward achieving zero greenhouse gases within the transportation infrastructure. Since the 1990s, the Norwegian parliament has fervently supported this transition, leveraging public awareness campaigns and a range of financial incentives for its users nationwide. The widespread utilization of BEVs promises substantial health benefits, including ensuring cleaner air for all citizens regardless of their socioeconomic status and fostering improvements in public health outcomes. This transition potentially curtails hundreds of thousands of annual deaths attributed to climate change, enhances the quality of life, bolsters civilian productivity, and fuels economic and population growth. The adoption of BEVs offers a myriad of advantages, including reduced health risks and premature mortality, as well as a quieter environment with diminished noise pollution. Nonetheless, the integration of BEVs necessitates robust road infrastructure with considerable maintenance costs, alongside limitations on driving range for users. Concerns arise regarding potential particle emissions from BEV tire wear due to the increased weight of batteries compared to conventional vehicles. Rapid acceleration capabilities may accelerate tire degradation, contributing to higher particle emissions, of which only 10% to 20% remain suspended in the air, whereas the majority settles on road surfaces, posing a threat to nearby aquatic ecosystems when washed into water bodies and soils. While BEVs hold promise for valuable benefits, successful policy creation and implementation require a detailed awareness of their limitations and challenges to ensure a comprehensive approach to sustainable mobility and public health improvement. Therefore, more research on the limitations of BEVs can help inform improved tactics for maximizing their benefits while limiting potential disadvantages., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Acquired radioresistance is the primary contributor to treatment failure of radiotherapy, with ferroptosis is identified as a significant mechanism underlying cell death during radiotherapy. Although resistance to ferroptosis has been observed in both clinical samples of radioresistant cells and cell models, its mechanism remains unidentified. Herein, our investigation revealed that radioresistant cells exhibited greater tolerance to Glutathione Peroxidase 4 (GPX4) inhibitors and, conversely, increased sensitivity to ferroptosis suppressor protein 1 (FSP1) inhibitors compared to their sensitive counterparts. This observation suggested that FSP1 might play a dominant role in the development of radioresistance. Notably, the knockout of FSP1 demonstrated considerably superior efficacy in resensitizing cells to radiotherapy compared to the knockout of GPX4. To elucidate the driving force behind this functional shift, we conducted a metabolomic assay, which revealed an upregulation of Coenzyme Q (CoQ) synthesis and a downregulation of glutathione synthesis in the acquired radioresistance cells. Mechanistically, CoQ synthesis was found to be supported by aarF domain containing kinase 3-mediated phosphorylation of CoQ synthases, while the downregulation of Solute carrier family 7 member 11 led to decreased glutathione synthesis. Remarkably, our retrospective analysis of clinical response data further validated that the additional administration of statin during radiotherapy, which could impede CoQ production, effectively resensitized radioresistant cells to radiation. In summary, our findings demonstrate a dependency shift from GPX4 to FSP1 driven by altered metabolite synthesis during the acquisition of radioresistance. Moreover, we provide a promising therapeutic strategy for reversing radioresistance by inhibiting the FSP1-CoQ pathway., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: With increasing survival rates of adolescents and young adults (AYAs) with breast cancer, health-related quality of life (HRQoL) becomes more important. An important aspect of HRQoL is sexual QoL. This study examined long-term sexual QoL of AYA breast cancer survivors, compared sexual QoL scores with that of other AYA cancer survivors, and identified factors associated with long-term sexual QoL of AYA breast cancer survivors., Materials and Methods: Data of the SURVAYA study were utilized for secondary analyses. Sexual QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life cancer survivorship core questionnaire (EORTC QLQ-SURV100). Descriptive statistics were used to describe sexual QoL of AYA cancer survivors. Linear regression models were constructed to examine the effect of cancer type on sexual QoL and to identify factors associated with sexual QoL., Results: Of the 4010 AYA cancer survivors, 944 had breast cancer. Mean sexual QoL scores of AYA breast cancer survivors ranged from 34.5 to 60.0 for functional domains and from 25.2 to 41.5 for symptom-orientated domains. AYA breast cancer survivors reported significantly lower sexual QoL compared to AYA survivors of other cancer types on all domains. Age, time since diagnosis, relationship status, educational level, chemotherapy, hormonal therapy, breast surgery, body image, and coping were associated with sexual QoL of AYA breast cancer survivors., Conclusions: AYA breast cancer survivors experience decreased sexual QoL in the long term (5-20 years) after diagnosis and worse score compared to AYA survivors of other cancer types, indicating a clear need to invest in supportive care interventions for those at risk, to enhance sexual well-being., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Many patients with a malignant (i.e., grade II-IV) glioma are of working age, yet they are rarely included in "cancer and work" studies. Here, we explored (1) the work-related experiences and unmet needs of patients with a malignant glioma and (2) the experiences and needs of relevant healthcare and occupational (health) professionals ("professionals") in providing work-related support to this patient group., Methods: Individual semi-structured interviews were held with patients with a malignant glioma who were of working age and had an employment contract at diagnosis, and relevant professionals. Interviews were transcribed verbatim and analysed thematically., Results: Patients (n = 22) were on average 46 ± 13 years of age (64% male) and diagnosed with a grade II (n = 12), III (n = 4), or IV glioma (n = 6). Professionals (n = 16) had on average 15 ± 9 years of relevant work experience with the patient group. Four themes emerged from the data: (1) having a malignant glioma: experienced consequences on work ability, (2) communicating about the consequences of a malignant glioma at work, (3) distilling the right approach: generic or tailored work-related support, and (4) accessibility of work-related support., Conclusions: Glioma-specific consequences on patients' work ability necessitate better communication between, and tailored guidance for, patients, relevant professionals, and the workplace. Suggestions for improvement, e.g., the periodic use of comprehensive neuropsychological assessments, are provided in the article., Implications for Cancer Survivors: Patients with a malignant glioma would benefit from tailored and proactive outreach about work-related issues bv relevant professionals., (© 2023. The Author(s).)

Objective: Quantitative extracellular volume fraction (ECV) mapping with MRI is commonly used to investigate in vivo diffuse myocardial fibrosis. This study aimed to validate ECV measurements against ex vivo histology of myocardial tissue samples from patients with aortic valve stenosis or hypertrophic cardiomyopathy., Materials and Methods: Sixteen patients underwent MRI examination at 3 T to acquire native T 1 maps and post-contrast T 1 maps after gadobutrol administration, from which hematocrit-corrected ECV maps were estimated. Intra-operatively obtained myocardial tissue samples from the same patients were stained with picrosirius red for quantitative histology of myocardial interstitial fibrosis. Correlations between in vivo ECV and ex vivo myocardial collagen content were evaluated with regression analyses., Results: Septal ECV was 30.3% ± 4.6% and correlated strongly (n = 16, r = 0.70; p = 0.003) with myocardial collagen content. Myocardial native T 1 values (1206 ± 36 ms) did not correlate with septal ECV (r = 0.41; p = 0.111) or with myocardial collagen content (r = 0.32; p = 0.227)., Discussion: We compared myocardial ECV mapping at 3 T against ex vivo histology of myocardial collagen content, adding evidence to the notion that ECV mapping is a surrogate marker for in vivo diffuse myocardial fibrosis., (© 2023. The Author(s).)

Background: Despite improvements in acute stroke therapies and rehabilitation strategies, many stroke patients are left with long-term upper limb motor impairment. We assessed whether an inhibitory repetitive transcranial magnetic stimulation treatment paradigm started within 3 weeks after stroke onset promotes upper limb motor recovery., Methods: We performed a single-center randomized, sham-controlled clinical trial. Patients with ischemic stroke or intracerebral hemorrhage and unilateral upper limb motor impairment were randomized to 10 daily sessions of active or sham continuous theta-burst stimulation (cTBS) of the contralesional primary motor cortex combined with standard upper limb therapy, started within 3 weeks after stroke onset. The primary outcome was the change in the Action Research Arm Test score from baseline (pretreatment) at 3 months after stroke. Secondary outcomes included the score on the modified Rankin Scale at 3 months and the length of stay at the rehabilitation center. Statistical analyses were performed using mixed models for repeated measures., Results: We enrolled 60 patients between April 2017 and February 2021, of whom 29 were randomized to active cTBS and 31 to sham cTBS. One patient randomized to active cTBS withdrew consent before the intervention and was excluded from the analyses. The mean difference in the change in Action Research Arm Test score from baseline at 3 months poststroke was 9.6 points ([95% CI, 1.2-17.9]; P =0.0244) in favor of active cTBS. Active cTBS was associated with better scores on the modified Rankin Scale at 3 months (OR, 0.2 [95% CI, 0.1-0.8]; P =0.0225) and with an 18 days shorter length of stay at the rehabilitation center than sham cTBS ([95% CI, 0.0-36.4]; P =0.0494). There were no serious adverse events., Conclusions: Ten daily sessions of cTBS of the contralesional primary motor cortex combined with upper limb training, started within 3 weeks after stroke onset, promote recovery of the upper limb, reduce disability and dependence and leads to earlier discharge from the rehabilitation center., Registration: URL: https://trialsearch.who.int/; Unique identifier: NTR6133., Competing Interests: Disclosures J.J.T. Vink is a part-time employee of and Dr Neggers is the CEO and shareholder of Brain Science Tools B.V. Data analysis was performed during J.J.T. Vink’s part-time employment at Brain Science Tools B.V. Dr van der Worp is consultant for Bayer and receives funding from the Dutch Heart Foundation, Horizon 2020 Framework Programme and Stryker. The other authors report no conflicts.

Purpose: To develop a free-breathing (FB) 2D radial balanced steady-state free precession cine cardiac MRI method with 100% respiratory gating efficiency using respiratory auto-calibrated motion correction (RAMCO) based on a motion-sensing camera., Methods: The signal from a respiratory motion-sensing camera was recorded during a FB retrospectively electrocardiogram triggered 2D radial balanced steady-state free precession acquisition using pseudo-tiny-golden-angle ordering. With RAMCO, for each acquisition the respiratory signal was retrospectively auto-calibrated by applying different linear translations, using the resulting in-plane image sharpness as a criterium. The auto-calibration determines the optimal magnitude of the linear translations for each of the in-plane directions to minimize motion blurring caused by bulk respiratory motion. Additionally, motion-weighted density compensation was applied during radial gridding to minimize through-plane and non-bulk motion blurring. Left ventricular functional parameters and sharpness scores of FB radial cine were compared with and without RAMCO, and additionally with conventional breath-hold Cartesian cine on 9 volunteers., Results: FB radial cine with RAMCO had similar sharpness scores as conventional breath-hold Cartesian cine and the left ventricular functional parameters agreed. For FB radial cine, RAMCO reduced respiratory motion artifacts with a statistically significant difference in sharpness scores (P < 0.05) compared to reconstructions without motion correction., Conclusion: 2D radial cine imaging with RAMCO allows evaluation of left ventricular functional parameters in FB with 100% respiratory efficiency. It eliminates the need for breath-holds, which is especially valuable for patients with no or impaired breath-holding capacity. Validation of the proposed method on patients is warranted., (© 2022 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: Medulloblastoma is a rare tumor in adults. The objective of this nationwide, multicenter study was to evaluate the toxicity and efficacy of the Dutch treatment protocol for adult medulloblastoma patients., Methods: Adult medulloblastoma patients diagnosed between 2010 and 2018 were identified in the Dutch rare tumors registry or nationwide pathology database. Patients with intention to treat according to the national treatment protocol were included. Risk stratification was performed based on residual disease, histological subtype and extent of disease. All patients received postoperative radiotherapy [craniospinal axis 36 Gy/fossa posterior boost 19.8 Gy (14.4 Gy in case of metastases)]. High-risk patients received additional neoadjuvant (carboplatin-etoposide), concomitant (vincristine) and adjuvant chemotherapy (carboplatin-vincristine-cyclophosphamide) as far as feasible by toxicity. Methylation profiling, and additional next-generation sequencing in case of SHH-activated medulloblastomas, were performed., Results: Forty-seven medulloblastoma patients were identified, of whom 32 were treated according to the protocol. Clinical information and tumor material was available for 28 and 20 patients, respectively. The histological variants were mainly classic (43%) and desmoplastic medulloblastoma (36%). Sixteen patients (57%) were considered standard-risk and 60% were SHH-activated medulloblastomas. Considerable treatment reductions and delays in treatment occurred due to especially hematological and neurotoxicity. Only one high-risk patient could complete all chemotherapy courses. 5-years progression-free survival (PFS) and overall survival (OS) for standard-risk patients appeared worse than for high-risk patients (PFS 69% vs. 90%, OS 81% vs. 90% respectively), although this wasn't statistically significant., Conclusion: Combined chemo-radiotherapy is a toxic regimen for adult medulloblastoma patients that may result in improved survival., (© 2023. The Author(s).)

Background and Aims: A new novel virus, Langya virus (LayV), was detected in China in August 2022, 3 years after the COVID-19 pandemic. LayV is similar to the previously discovered Mojiang henipavirus. Other zoonotic henipaviruses include the Hendra and Nipah viruses. The emergence of the zoonotic Langya virus is attributed to climate change and wildlife encroachment, as LayV is detected in shrews. Those who are infected in China showed various symptoms, but no deaths have been recorded yet. This review aims to shed light on the current state of Langya virus outbreak, its infection control efforts, and the remaining challenges that need to be addressed to curb the outbreak., Methods: We utilized online publication databases such as PubMed, Google Scholar, and Scopus in writing this review article., Results: A surveillance study on thirty-five febrile patients in Eastern China identified the Langya virus outbreak. The current efforts from the Chinese government and health authorities to reduce the transmission and spread of Langya virus such as isolation and characterization of LayV, challenges associated with the increase in cases of LayV, and trackable recommendations such as strengthening the healthcare system in China, sensitization of people about risks associated with Langya virus outbreaks, creating an intensive surveillance system network, etc. were discussed., Conclusion: It is germane and pertinent that the Chinese government and health authorities continue to intensify efforts against Langya virus and address the challenges to effectively reduce transmission., Competing Interests: Competing interestsThere are competing interests., (© The Author(s) 2023.)

Introduction: Increasingly more adolescent and young adult (AYA, aged 18-39 years) patients with an uncertain and/or poor cancer prognosis (UPCP) are gaining life-years because of novel treatments or refinement of established therapies, and sometimes even face the prospect of long-term disease control. This study aims to examine the challenges of AYAs with a UPCP in daily life to inform the development of AYA care programs., Methods: Semi-structured in-depth interviews were conducted among AYAs with a UPCP. Since we expected differences in experiences between three AYA subgroups, we interviewed patients of these subgroups (1): traditional survivors (2), low-grade glioma survivors, and (3) new survivors. Interviews were analyzed using elements of grounded theory. AYA patients were actively involved as research partners., Results: In total 46 AYAs with UPCP participated and shared their challenges in daily life. They were on average 33.4 years old (age range 23-44) and most of them were women (63%). The most common tumor types were low-grade gliomas (16), sarcomas (7), breast cancers (6), and lung cancers (6). We identified five primary themes: (1) feeling inferior to previous self and others (e.g. feeling useless, who wants me in a relationship), (2) feeling of being alone (e.g. lonely thoughts, nobody really gets me), (3) ongoing confrontation (e.g. it is always there, own decline), (4) grief about life (e.g. grief about life I did not get, grief about old life), and (5) loss of control over the future (e.g. not able to make future plans, waiting for growth). Although all of the challenges were identified in the three AYA subgroups, the perceived intensity of the challenges differed slightly between the subgroups., Discussion: AYAs living with a UPCP experience challenges associated to their sense of altered identity, their position in the social network, and the future uncertainties. This study highlights the importance to recognize and acknowledge the unique challenges of this group. To provide age-specific care, it is important to embed acceptance and commitment therapy and AYA peer support within the healthcare system and other care programs to support AYAs to live well with their disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Burgers, van den Bent, Dirven, Lalisang, Tromp, Compter, Kouwenhoven, Bos, de Langen, Reuvers, Franssen, Frissen, Harthoorn, Dickhout, Noordhoek, van der Graaf and Husson.)

Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I-IV cancer patients and in half of 352 stage I-III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening., Competing Interests: Declaration of interests M.G. Best, R.J.A.N., and T.W. are inventors on relevant patent applications (PCT/NL2011/050518 and PCT/NL2018/050110). R.J.A.N. and T.W. are shareholders of Illumina, Inc. M.H. is chief formulation officer at Nurish.Me, Inc., and Camelina Sun LLC and has equity in those companies (whose business activities are unrelated to the present work). D.M.P. and D.K.L. are shareholders of ExBiome BV., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Over the years, technology has revolutionized the operations of many industries, ranging from manufacturing and agriculture to financial institutions which are usually the first users of innovations. Owing to the recent technological trends in the financial sector, such as mobile money, artificial intelligence, and medical robotics, as well as the rapidly increasing human population and the emergence of new patterns of disease, it is necessary for the healthcare sector to adopt new strategies to deliver efficient and effective healthcare services. Financial technology (FinTech), a combination of financial services and technology, entails the incorporation of modern, innovative technologies by industries into their financial services. FinTech is an endless array of applications, products, and services which includes mobile banking, cryptocurrency, insurance, and investment apps among many others. Any enterprise that employs technology to enhance or automate financial services and processes is referred to as FinTech. This fast-growing industry serves the interests of both the business sector and the consuming public. There have been many applications and uses of FinTech, however, its employment in the field of health remains to be explored further and maximized, particularly in the developing world like Africa. This paper aims to explore the prospects of FinTech for healthcare in Africa., Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

The COVID-19 outbreak has had a great impact on the social, economic, and health systems of Thailand. A variety of measures to curb the spread of the disease were implemented since the beginning of the pandemic, including a strict national lockdown protocol. The Thai government aimed to achieve herd immunity through an efficient vaccination programme. Initially, vaccine supply shortage and a lack of vaccine options plagued the health system, but this has since been improved. Continuous monitoring of the situation through research is being carried out to assess the level of immunity among the population whereby the current general recommendation is presently a fourth booster dose for adults. Hurdles towards achieving herd immunity remain. One such issue is the low level of vaccine literacy among those that are unvaccinated or inadequately vaccinated. Another obstacle is the sizeable rate of hesitancy towards getting booster doses. Achieving herd immunity in the Thai population would require multilateral cooperation, improved health promotion to target population groups, such as older adults, and a developed distribution system for those with limited access, such as those in the rural areas., Competing Interests: The author declares no competing interests., (© 2022 The Authors. Public Health Challenges published by John Wiley & Sons Ltd.)

Background: Adolescents and young adults (AYAs, aged 18-39 years) with advanced cancer have an increased life expectancy due to improvements and refinements in cancer therapies, resulting in a growing group of AYAs living with an uncertain and/or poor cancer prognosis (UPCP). To date, no studies have examined the difficulties of health care professionals (HCPs) providing care to AYAs with a UPCP. This study aimed to understand the challenges in daily clinical practice experienced by HCPs from different disciplines who provide palliative as well as general care to AYAs with a UPCP., Methods: HCPs from a variety of backgrounds (e.g. clinical nurse specialists, medical oncologists, neurologists psychologists) were invited for a semi-structured interview. The interviews were transcribed verbatim and analysed using reflexive thematic analysis. Two AYA patients were actively involved as research partners to increase the relevance of the study design and to optimise interpretation of results., Results: Forty-nine HCPs were interviewed. Overall, we found that the threat of premature death within this young patient group increased emotional impact on HCPs and evoked a feeling of unfairness, which was an extra motivation for HCPs to provide the most optimal care possible. We generated four key themes: (i) emotional confrontation (e.g. feeling helplessness and experiencing a greater sense of empathy), (ii) questioning own professional attitude and skills, (iii) navigating uncertainty (e.g. discussing prognosis and end of life) and (iv) obstacles in the health care organisation (e.g. lack of knowledge and clarity about responsibilities)., Conclusions: HCPs experienced unique emotional and practical challenges when providing care to AYAs with a UPCP. The results from this study highlight the need to develop an education module for HCPs treating AYAs with UPCP to increase their own well-being and optimise the delivery of person- and age-adjusted care., Competing Interests: Disclosure The authors have declared no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: To assess errors associated with EPI-accelerated intracardiac 4D flow MRI (4DEPI) with EPI factor 5, compared with non-EPI gradient echo (4DGRE)., Methods: Three 3T MRI experiments were performed comparing 4DEPI to 4DGRE: steady flow through straight tubes, pulsatile flow in a left-ventricle phantom, and intracardiac flow in 10 healthy volunteers. For each experiment, 4DEPI was repeated with readout and blip phase-encoding gradient in different orientations, parallel or perpendicular to the flow direction. In vitro flow rates were compared with timed volumetric collection. In the left-ventricle phantom and in vivo, voxel-based speed and spatio-temporal median speed were compared between sequences, as well as mitral and aortic transvalvular net forward volume., Results: In steady-flow phantoms, the flow rate error was largest (12%) for high velocity (>2 m/s) with 4DEPI readout gradient parallel to the flow. Voxel-based speed and median speed in the left-ventricle phantom were ≤5.5% different between sequences. In vivo, mean net forward volume inconsistency was largest (6.4 ± 8.5%) for 4DEPI with nonblip phase-encoding gradient parallel to the main flow. The difference in median speed for 4DEPI versus 4DGRE was largest (9%) when the 4DEPI readout gradient was parallel to the flow., Conclusions: Velocity and flow rate are inaccurate for 4DEPI with EPI factor 5 when flow is parallel to the readout or blip phase-encoding gradient. However, mean differences in flow rate, voxel-based speed, and spatio-temporal median speed were acceptable (≤10%) when comparing 4DEPI to 4DGRE for intracardiac flow in healthy volunteers., (© 2021 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Objectives: The current research addressed gaps in the literature regarding short-term computerized cognitive retest performance in young and older adults using two integrated speed-accuracy metrics. The aims were: (a) to advance the aging literature on short-term retest performance using a computerized cognitive battery and a retest schedule that included both within- and between-day time points, and (b) to assess the test-retest reliability of two integrated speed-accuracy metrics, inverse efficiency scores (IES) and balanced integration scores (BIS)., Method: Twenty young (18-23 years) and thirty older (65-71 years) men completed a battery measuring a range of cognitive functions, six times over three testing days, each 1 week apart., Result: Compared to young adults, older adults exhibited steeper within- and between-day performance gains in IES and BIS, which may reflect a combination of lower initial cognitive ability and familiarity, indicating that older adults may require more familiarization on computerized tests. Relative to unadjusted reaction times, IES reliability appeared comparable in older adults, but slightly lower among young adults. The reliability of BIS was lower than unadjusted reaction times and IES in both age groups., Discussion: Our findings provide guidance for researchers wanting to combine speed and accuracy into a single performance metric in repeated testing contexts.

Non-invasively measured brain activity is related to progression-free survival in glioma patients, suggesting its potential as a marker of glioma progression. We therefore assessed the relationship between brain activity and increasing tumor volumes on routine clinical magnetic resonance imaging (MRI) in glioma patients. Postoperative magnetoencephalography (MEG) was recorded in 45 diffuse glioma patients. Brain activity was estimated using three measures (absolute broadband power, offset and slope) calculated at three spatial levels: global average, averaged across the peritumoral areas, and averaged across the homologues of these peritumoral areas in the contralateral hemisphere. Tumors were segmented on MRI. Changes in tumor volume between the two scans surrounding the MEG were calculated and correlated with brain activity. Brain activity was compared between patient groups classified into having increasing or stable tumor volume. Results show that brain activity was significantly increased in the tumor hemisphere in general, and in peritumoral regions specifically. However, none of the measures and spatial levels of brain activity correlated with changes in tumor volume, nor did they differ between patients with increasing versus stable tumor volumes. Longitudinal studies in more homogeneous subgroups of glioma patients are necessary to further explore the clinical potential of non-invasively measured brain activity., (© 2021. The Author(s).)

Objectives: This study sought to clinically validate a novel 3-dimensional (3D) ultrafast cardiac magnetic resonance (CMR) protocol including cine (anatomy and function) and late gadolinium enhancement (LGE), each in a single breath-hold., Background: CMR is the reference tool for cardiac imaging but is time-consuming., Methods: A protocol comprising isotropic 3D cine (Enhanced sensitivity encoding [SENSE] by Static Outer volume Subtraction [ESSOS]) and isotropic 3D LGE sequences was compared with a standard cine+LGE protocol in a prospective study of 107 patients (age 58 ± 11 years; 24% female). Left ventricular (LV) mass, volumes, and LV and right ventricular (RV) ejection fraction (LVEF, RVEF) were assessed by 3D ESSOS and 2D cine CMR. LGE (% LV) was assessed using 3D and 2D sequences., Results: Three-dimensional and LGE acquisitions lasted 24 and 22 s, respectively. Three-dimensional and LGE images were of good quality and allowed quantification in all cases. Mean LVEF by 3D and 2D CMR were 51 ± 12% and 52 ± 12%, respectively, with excellent intermethod agreement (intraclass correlation coefficient [ICC]: 0.96; 95% confidence interval [CI]: 0.94 to 0.97) and insignificant bias. Mean RVEF 3D and 2D CMR were 60.4 ± 5.4% and 59.7 ± 5.2%, respectively, with acceptable intermethod agreement (ICC: 0.73; 95% CI: 0.63 to 0.81) and insignificant bias. Both 2D and 3D LGE showed excellent agreement, and intraobserver and interobserver agreement were excellent for 3D LGE., Conclusions: ESSOS single breath-hold 3D CMR allows accurate assessment of heart anatomy and function. Combining ESSOS with 3D LGE allows complete cardiac examination in <1 min of acquisition time. This protocol expands the indication for CMR, reduces costs, and increases patient comfort., Competing Interests: Funding Support and Author Disclosures Funding included Instituto de Salud Carlos III (ISCIII) and the European Regional Development Fund (ERDF) Grants DTS17/00136 to Dr. Ibáñez and PI19/01704 to Dr. Fernandez-Jimenez; Spanish Society of Cardiology Translational Research Grant 2016 to Dr. Ibáñez; European Research Council ERC-CoG 819775-MATRIX to Dr. Ibáñez; Comunidad de Madrid S2017/BMD-3867-RENIM-CM to Drs. Desco and Ibáñez; and Ministerio de Ciencia e Innovación (MICINN) RETOS2019-107332RB-I00 to Dr. Ibáñez. Dr. Fernandez-Jimenez received funding from the European Union Horizon 2020 research and innovation programme under Marie Skłodowska-Curie Hrant Agreement No. 707642. The CNIC is supported by the ISCIII, the MICINN, and the Pro CNIC Foundation. Drs. Fernandez-Jimenez, Nothnagel, Fuster, Ibáñez, and Javier Sánchez-González are inventors of a joint patent (Philips/CNIC) for the new cine imaging method here described and validated/protected under the IP #2014P00960EP. Drs. Nothnagel, Kouwenhoven, Clemence, and Javier Sánchez-González are Philips employees. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To develop a new 3D radial trajectory based on the natural spiral phyllotaxis (SP), with variable anisotropic FOV., Theory & Methods: A 3D radial trajectory based on the SP with favorable interleaving properties for cardiac imaging has been proposed by Piccini et al (Magn Reson Med. 2011;66:1049-1056), which supports a FOV with a fixed anisotropy. However, a fixed anisotropy can be inefficient when sampling objects with different anisotropic dimensions. We extend Larson's 3D radial method to provide variable anisotropic FOV for spiral phyllotaxis (VASP). Simulations were performed to measure distance between successive projections, analyze point spread functions, and compare aliasing artifacts for both VASP and conventional SP. VASP was fully implemented on a whole-body clinical MR scanner. Phantom and in vivo cardiac images were acquired at 1.5 tesla., Results: Simulations, phantom, and in vivo experiments confirmed that VASP can achieve variable anisotropic FOV while maintaining the favorable interleaving properties of SP. For an anisotropic FOV with 100:100:35 ratio, VASP required ~65% fewer radial projections than the conventional SP to satisfy Nyquist criteria. Alternatively, when the same number of radial projections were used as in conventional SP, VASP produced fewer aliasing artifacts for anisotropic objects within the excited imaging volumes., Conclusion: We have developed a new method (VASP), which enables variable anisotropic FOV for 3D radial trajectory with SP. For anisotropic objects within the excited imaging volumes, VASP can reduce scan times and/or reduce aliasing artifacts., (© 2020 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Objectives: To identify intra- and interpersonal sociodemographic, injury-related, and psychological variables measured at admission of inpatient rehabilitation that predict psychological distress among dyads of individuals with spinal cord injury (SCI) or acquired brain injury (ABI) and their significant others (ie, individuals close to the individual with a disability, mostly family members) 6 months after discharge. Differences in predictors were investigated for persons with SCI or ABI and their significant others and were compared between diagnoses., Design: Prospective longitudinal study., Setting: Twelve Dutch rehabilitation centers., Participants: Dyads (N=157) consisting of adults with SCI or ABI who were admitted to inpatient rehabilitation and their adult significant others., Interventions: Not applicable., Main Outcome Measures: Psychological distress (Hospital Anxiety and Depression Scale)., Results: Sociodemographic and injury-related variables were not or were only weakly associated with psychological distress among individuals with SCI or ABI and their significant others 6 months after discharge. Bivariately, higher baseline psychological distress, lower scores on adaptive psychological characteristics (combination of self-efficacy, proactive coping, purpose in life, resilience), and higher scores on maladaptive psychological characteristics (combination of passive coping, neuroticism, appraisals of threat and loss) were related to higher psychological distress, as well as crosswise between individuals with SCI or ABI and their significant others, although less strongly. Combined prediction models showed that psychological distress among persons with SCI or ABI was predicted by education level of their significant other, their own baseline psychological distress, and their own maladaptive psychological characteristics (explained variance, 41.9%). Among significant others, only their own baseline psychological distress predicted psychological distress (explained variance, 40.4%). Results were comparable across diagnoses., Conclusions: Although a dyadic connection was shown, primarily one's own baseline psychological distress and psychological characteristics were important in the prediction of later psychological distress among both individuals with SCI or ABI and their significant others. Screening based on these variables could help to identify persons at risk for psychological distress., (Copyright © 2020 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: Contrast-enhanced magnetic resonance angiography (CE-MRA) is a well-established non-invasive imaging technique for the assessment of peripheral artery disease (PAD). A subtractionless method using modified Dixon (mDixon) fat suppression showed superior image quality at 1.5T over the common subtraction method, using a three-positions stepping table approach with a single dose of contrast agent. The aim of this study was to investigate the feasibility of subtractionless first-pass peripheral MRA at 3T in patients with known or suspected PAD and to compare the performance in terms of vessel-to-background contrast (VBC), signal-to-noise ratio (SNR), and subjective image quality to conventional subtraction MRA. Methods: Ten patients [mean age 69 years ± 12 standard deviation (SD)] with known or suspected PAD were examined on a clinical 3T scanner (Ingenia, Philips Healthcare, Best, Netherlands) at three table positions using subtractionless and subtraction first-pass peripheral MRA. Two readers rated image quality on a four- point scale. Interobserver agreement was expressed in quadratic weighted κ values. VBC was assessed with a semi-automated process and SNR was compared in a healthy volunteer. Results: Subjective image quality was significantly better with the subtractionless method overall (mean image quality for mDixon imaging: 2.88 ± 0.32 SD vs. for subtraction imaging: 2.57 ± 0.48 SD; P < 0.001) and per table position (abdominal position: 2.88 ± 0.32 vs. 2.57 ± 0.48 SD; P < 0.001); upper leg position: (2.97 ± 0.15 SD vs. 2.68 ± 0.37 SD; P < 0.001; lower leg position: 2.60 ± 0.50 SD vs. 2.13 ± 0.60 SD; P < 0.001). Vessel-to-background contrast increased by 22% with the subtractionless method overall (mean VBC for mDixon imaging: 23.16 ± 8.4 SD vs. for subtraction imaging: 19.00 ± 8.1 SD; factor 1.22, P < 0.001). SNR was 82% higher with the subtractionless method (overall SNR gain 1.82; P < 0.001). Conclusion: This study demonstrated the feasibility and robustness of subtractionless first-pass peripheral MRA at 3T in patients with known or suspected PAD using a three- positions stepping table approach with a single dose of contrast agent. It showed increased image quality compared to the conventional subtraction method and superior performance in terms of SNR and vessel-to-background contrast., (Copyright © 2020 Weiss, Eggers, Stehning, Kouwenhoven, Nassar, Pieske, Stawowy, Schnackenburg and Kelle.)

In this work we aimed to investigate the feasibility of using a new pulse sequence called Relaxation-Enhanced Angiography without Contrast and Triggering (REACT) for free-breathing non-contrast-enhanced MR angiography (NCE-MRA) for multiple anatomies on 3T. Two magnetization-preparation pulses were incorporated with a three-dimensional dual-echo Dixon sequence. A T2-prep pulse, followed by a non-selective inversion pulse with a short inversion time, together suppressed tissue with short T1 and T2, while enhancing the signal of native blood with long T1 and T2. A two-point non-balanced gradient-echo Dixon method, based on dual-echo acquisition with semi-flexible echo times for water-fat separation, was used for improved fat suppression over a large field of view. General image quality, vasculature visibility, and clinical indications of the proposed method were investigated in healthy subjects and patients in both torso and extremities based on visual inspection. Preliminary results from REACT obtained in free-breathing with no cardiac triggering showed uniform suppression of background tissue over the field of view and robust blood-to-tissue contrast over multiple anatomies. Future clinical studies are warranted for further investigation of its diagnostic performance and limitations., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: When glioma patients experience long-term seizure freedom the question arises whether antiepileptic drugs (AEDs) should be continued. As no prospective studies exist on seizure recurrence in glioma patients after AED withdrawal, we evaluated the decision-making process to withdraw AEDs in glioma patients, and seizure outcome after withdrawal., Methods: Patients with a histologically confirmed low grade or anaplastic glioma were included. Eligible patients were seizure free ≥ 1 year from the date of last antitumor treatment, or ≥ 2 years since the last seizure when seizures occurred after the end of the last antitumor treatment. Patients and neuro-oncologists made a shared decision on the preferred AED treatment (i.e. AED withdrawal or continuation). Primary outcomes were: (1) outcome of the shared decision-making process and (2) rate of seizure recurrence., Results: Eighty-three patients fulfilled all eligibility criteria. However, in 12/83 (14%) patients, the neuro-oncologist had serious objections to AED withdrawal. Therefore, 71/83 (86%) patients were analyzed; In 46/71 (65%) patients it was decided to withdraw AED treatment. In the withdrawal group, 26% (12/46) had seizure recurrence during follow-up. Seven of these 12 patients (58%) had tumor progression, of which three within 3 months after seizure recurrence. In the AED continuation group, 8% (2/25) of patients had seizure recurrence of which one had tumor progression., Conclusion: In 65% of patients a shared decision was made to withdraw AEDs, of which 26% had seizure recurrence. AED withdrawal should only be considered in carefully selected patients with a presumed low risk of tumor progression.

Superconductors and semiconductors are crucial platforms in the field of quantum computing. They can be combined to hybrids, bringing together physical properties that enable the discovery of new emergent phenomena and provide novel strategies for quantum control. The involved semiconductor materials, however, suffer from disorder, hyperfine interactions or lack of planar technology. Here we realise an approach that overcomes these issues altogether and integrate gate-defined quantum dots and superconductivity into germanium heterostructures. In our system, heavy holes with mobilities exceeding 500,000 cm 2  (Vs) -1 are confined in shallow quantum wells that are directly contacted by annealed aluminium leads. We observe proximity-induced superconductivity in the quantum well and demonstrate electric gate-control of the supercurrent. Germanium therefore has great promise for fast and coherent quantum hardware and, being compatible with standard manufacturing, could become a leading material for quantum information processing.

Objective: This study aimed to investigate the advantages of recently developed cardiac imaging techniques of fat-water separation and feature tracking to characterize better individuals with chronic myocardial infarction (MI)., Materials and Methods: Twenty patients who had a previous MI underwent CMR imaging. The study protocol included routine cine and late gadolinium enhancement (LGE) technique. In addition, mDixon LGE imaging was performed in every patient. Left ventricular (LV) circumferential (Ecc LV ) and radial (Err LV ) strain were calculated using dedicated software (CMR 42 , Circle, Calgary, Canada). The extent of global scar was measured in LGE and fat-water separated images to compare conventional and recent CMR imaging techniques., Results: The infarct size derived from conventional LGE and fat-water separated images was similar. However, detection of lipomatous metaplasia was only possible with mDixon imaging. Subjects with fat deposition demonstrated a significantly smaller percentage of fibrosis than those without fat (10.68 ± 5.07% vs. 13.83 ± 6.30%; p = 0.005). There was no significant difference in Ecc LV or Err LV between myocardial segments containing fibrosis only and fibrosis with fat. However, Ecc LV and Err LV values were significantly higher in myocardial segments adjacent to fibrosis with fat deposition than in those adjacent to LGE only., Conclusions: Advanced CMR imaging ensures more detailed tissue characterization in patients with chronic MI without a relevant increase in imaging and post-processing time. Fatty metaplasia may influence regional myocardial deformation especially in the myocardial segments adjacent to scar tissue. A simplified and shortened myocardial viability CMR protocol might be useful to better characterize and stratify patients with chronic MI.

Background: Patients with neglect ignore or respond slower to contralesional stimuli. Neglect negatively influences independence in activities of daily living (ADL). Prism adaptation (PA) is one of the most frequently studied treatments, yet there is little evidence regarding positive effects on neglect behavior in ADL., Objective: To assess whether PA in the subacute phase ameliorates neglect in situations of varying complexity., Methods: A total of 70 neglect patients admitted for inpatient stroke rehabilitation received either PA or sham adaptation (SA) for 2 weeks, with full access to standard treatment. There were 7 time-dependent measurements (baseline and 1-4, 6, and 14 weeks after start of treatment). The primary outcome was change of neglect as observed during basic ADL with the Catherine Bergego Scale (CBS). Secondary outcomes were changes in performance on a dynamic multitask (ie, the Mobility Assessment Course [MAC]) and a static paper-and-pencil task (ie, a shape cancellation task [SC])., Results: In all, 34 patients received PA and 35 SA. There were significant time-dependent improvements in performance as measured with the CBS, MAC, and SC (all F > 15.57; P < .001). There was no significant difference in magnitude of improvement between groups on the CBS, MAC, and SC (all F < 2.54; P > .113]., Conclusions: No beneficial effects of PA over SA in the subacute phase poststroke were observed, which was comparable for situations of varying complexity. Heterogeneity of the syndrome, time post-stroke onset, and the content of treatment as usual are discussed. Basic knowledge on subtypes and recovery patterns would aid the development of tailored treatment.

Introduction: High-grade chondrosarcoma, high-grade glioma and intrahepatic cholangiocarcinoma are aggressive types of cancer with a dismal outcome. This is due to the lack of effective treatment options, emphasising the need for novel therapies. Mutations in the genes IDH1 and IDH2 (isocitrate dehydrogenase 1 and 2) occur in 60% of chondrosarcoma, 80% of WHO grade II-IV glioma and 20% of intrahepatic cholangiocarcinoma. IDH1/2 -mutated cancer cells produce the oncometabolite D -2-hydroxyglutarate ( D -2HG) and are metabolically vulnerable to treatment with the oral antidiabetic metformin and the oral antimalarial drug chloroquine., Methods and Analysis: We describe a dose-finding phase Ib/II clinical trial, in which patients with IDH1/2 -mutated chondrosarcoma, glioma and intrahepatic cholangiocarcinoma are treated with a combination of metformin and chloroquine. Dose escalation is performed according to a 3+3 dose-escalation scheme. The primary objective is to determine the maximum tolerated dose to establish the recommended dose for a phase II clinical trial. Secondary objectives of the study include (1) determination of pharmacokinetics and toxic effects of the study therapy, for which metformin and chloroquine serum levels will be determined over time; (2) investigation of tumour responses to metformin plus chloroquine in IDH1/2 -mutated cancers using CT/MRI scans; and (3) whether tumour responses can be measured by non-invasive D -2HG measurements (mass spectrometry and magnetic resonance spectroscopy) of tumour tissue, serum, urine, and/or bile or next-generation sequencing of circulating tumour DNA (liquid biopsies). This study may open a novel treatment avenue for IDH1/2 -mutated high-grade chondrosarcoma, glioma and intrahepatic cholangiocarcinoma by repurposing the combination of two inexpensive drugs that are already approved for other indications., Ethics and Dissemination: This study has been approved by the medical-ethical review committee of the Academic Medical Center, Amsterdam, The Netherlands. The report will be submitted to a peer-reviewed journal., Trial Registration Number: This article was registered at ClinicalTrials.gov identifier (NCT02496741): Pre-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The aim of this study was to identify predictors, available at admission, of physical independence at discharge from inpatient rehabilitation. Secondary aims were to identify predictors of functional gain and length of stay (LOS). We included 1310 adult stroke patients who were admitted for inpatient rehabilitation in five Dutch rehabilitation centres. Data on the Utrecht Scale for Evaluation of Clinical Rehabilitation at admission and discharge (physical and cognitive independence, mood, pain and fatigue), age, sex and in a subsample stroke characteristics as well were collected. A prediction model was created using random coefficient analysis. None of the stroke characteristics were independently associated with physical independence or functional gain at discharge, or LOS. Higher physical and cognitive independence scores and severe pain at admission were predictors of higher physical independence scores at discharge. Furthermore, lower physical independence scores, higher cognitive independence scores, less pain at admission and younger age predicted more functional gain. Finally, lower physical and cognitive independence scores at admission and younger age predicted longer LOS. Physical independence at admission was the most robust predictor for rehabilitation outcome in a Dutch rehabilitation setting. To a lesser extent, age, cognitive independence and pain predicted rehabilitation outcome after stroke. Treatment of cognition and pain should be taken into account during rehabilitation. Further work needs to be carried out to establish whether focusing on these factors improves outcome after rehabilitation.

We used delay-interval interference to investigate the nature of the differential outcomes effect (DOE) in pigeons. Birds were trained on a delayed matching-to-sample (DMS) task under either common outcome or differential outcome conditions, and then presented with visual interference during the delay period. Consistent with previous literature, the common outcomes birds were slower to learn the DMS task than the differential outcomes birds. The common outcome birds were also more impaired by the visual interference than the differential outcomes birds. Our findings are consistent with the view that the birds trained with common outcomes were likely remembering the sample stimulus during the delay period, and hence were disrupted by the visual interference, whereas the birds trained with differential outcomes were likely relying on the different emotional reactions elicited by the different outcomes to guide their choice behaviour, and hence were less affected by the visual interference. Our findings suggest that the DOE is not truly evidence of anticipatory mediation of short-term retention in pigeons, but rather emotionally driven decision making, which is not truly anticipatory in nature.

Purpose: To prospectively assess the feasibility, image quality, and diagnostic accuracy of high-dose dobutamine stress magnetic resonance imaging (DSMR) using steady-state free precession (SSFP) cine imaging at 3T applying a dual-source radiofrequency (RF) excitation magnetic resonance imaging (MRI) system with parallel transmission and patient adaptive local RF shimming., Materials and Methods: DSMR using SSFP cine imaging was performed in 44 patients at 3T scheduled for a clinically indicated coronary angiography. The effect of conventional versus dual-source RF transmission was assessed regarding homogeneity of the B1 field, contrast-to-noise ratios (CNRs) at rest, image quality, and diagnostic accuracy of DSMR using long and short axis., Results: The mean percentage of the intended flip angle within the heart increased from 88 ± 9.1% with single-source to 103 ± 5.6% (P < 0.001) dual-source RF transmission. CNR increased for dual-source particularly at the apex (63.4 ± 24.2 vs. 36.5 ± 16.5, P < 0.001) but also at the base of the left ventricle (LV) (50.1 ± 14.8 vs. 39.3 ± 15.8, P < 0.001). Image quality of dual-source was higher both at rest (2.8 ± 0.5 vs. 2.6 ± 0.7, P < 0.001) and stress (2.5 ± 0.7 vs. 2.0 ± 1.0, P < 0.001). The number of segments with severe artifacts or nondiagnostic image quality at stress was lower with dual-source RF transmission (8% vs. 27%, P < 0.001). The diagnostic accuracy of DSMR in coronary territories using dual-source RF transmission was significantly higher (77% vs. 65%, P = 0.04)., Conclusion: Patient adaptive local RF shimming using dual-source RF transmission provided significantly improved image quality and higher diagnostic accuracy of SSFP during DSMR at 3T compared to conventional RF transmission., (© 2015 Wiley Periodicals, Inc.)

Background: The purpose of this work was to evaluate different magnetization preparation and readout sequences for modified Look-Locker inversion recovery (MOLLI) toward improved T1 mapping in the heart. Elements investigated include: catalyzation sequences to prepare the magnetization before readout, alternate k-space trajectories, a spoiled gradient recalled echo readout, and a 5b(3b)3b MOLLI sampling scheme ('b' denoting beats)., Methods: Conventional 3b(3b)3b(3b)5b MOLLI with a linear k-space trajectory was compared to four variants in simulations, in vitro and in vivo (at 3T). Variants were centric conventional MOLLI, centric-paired conventional MOLLI, linear 5b(3b)3b MOLLI and spoiled gradient recalled echo MOLLI. Each of these was applied with three magnetization catalyzation methods, and T1 measurement accuracy and precision were evaluated in simulations via a Monte Carlo algorithm, in a set of calibrated phantoms, and in ten healthy volunteers. Contrast-to-noise, heart rate dependence and B1+ dependence were also evaluated., Results: A linear k-space trajectory was superior in vitro to centric and centric-paired trajectories. Of the catalyzation methods, preparation of transverse magnetization only-using a linearly increasing flip angle catalyzation-improved MOLLI T1 measurement accuracy, precision, and map quality versus methods that include catalyzation of the longitudinal magnetization. The 5b(3b)3b MOLLI scheme offered comparable native T1 measurement accuracy and precision to conventional MOLLI, despite its shortened acquisition., Conclusions: MOLLI T1 measurement accuracy, precision, and map quality depend on the method of catalyzation of magnetization prior to image acquisition, as well as on the readout method and MOLLI sampling scheme used., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: Intramyocardial hemorrhage and area at risk are both prognostic markers in acute myocardial infarction (AMI). Myocardial T2 and T2 * mapping have been used to detect such tissue changes at 1.5T but these techniques are challenging at 3.0T due to additional susceptibility variation. We studied T2 and T2 * myocardial mapping techniques at 3.0T on a system employing B1 shimming and compared two different methods of B0 shimming., Materials and Methods: Fifteen volunteers and six AMI patients were scanned on a 3T system. Volume and image-based (IB) B0 shimming techniques were implemented. Single breath-hold, multiecho gradient, and spin echo sequences were employed from which T2 * and T2 maps were calculated., Results: In volunteers, there was no significant difference in mean values obtained with volume or IB shimming for T2 mapping (39.1 ± 6.0 msec vs. 39.4 ± 6.1 msec; P > 0.05) or for T2 * mapping (24.2 ± 6.7 msec vs. 24.1 ± 5.2 msec; P > 0.05). There were no significant regional differences in mean T2 values between septal, anterior, and posterior segments with either shimming technique (all P > 0.05); but there were significant regional differences in mean T2 * values using volume shimming (27.8 ± 5.2 msec vs. 28.4 ± 5.8 msec vs. 15.9 ± 8.3 msec; P < 0.05)-but not with IB shimming (25.7 ± 5.4 msec vs. 25.3 ± 5.9 msec vs. 18.7 ± 4.6 msec; P > 0.05)., Conclusion: At 3.0T, cardiac T2 mapping is robust. Although T2 * mapping is prone to more regional heterogeneity this can be reduced by using IB instead of conventional volume B0 shimming., (© 2014 Wiley Periodicals, Inc.)

Background: The purpose of this study was to establish the feasibility of three-dimensional (3D) balanced steady-state-free-precession (bSSFP) myocardial perfusion cardiovascular magnetic resonance (CMR) at 3T using local RF shimming with dual-source RF transmission, and to compare it with spoiled gradient echo (TGRE) acquisition., Methods: Dynamic contrast-enhanced 3D bSSFP perfusion imaging was performed on a 3T MRI scanner equipped with dual-source RF transmission technology. Images were reconstructed using k-space and time broad-use linear acquisition speed-up technique (k-t BLAST) and compartment based principle component analysis (k-t PCA)., Results: In phantoms and volunteers, local RF shimming with dual source RF transmission significantly improved B1 field homogeneity compared with single source transmission (P=0.01). 3D bSSFP showed improved signal-to-noise, contrast-to-noise and signal homogeneity compared with 3D TGRE (29.8 vs 26.9, P=0.045; 23.2 vs 21.6, P=0.049; 14.9% vs 12.4%, p=0.002, respectively). Image quality was similar between bSSFP and TGRE but there were more dark rim artefacts with bSSFP. k-t PCA reconstruction reduced artefacts for both sequences compared with k-t BLAST. In a subset of five patients, both methods correctly identified those with coronary artery disease., Conclusion: Three-dimensional bSSFP myocardial perfusion CMR using local RF shimming with dual source parallel RF transmission at 3T is feasible and improves signal characteristics compared with TGRE. Image artefact remains an important limitation of bSSFP imaging at 3T but can be reduced with k-t PCA.

Background: Region-specific types of neglect (peripersonal and extrapersonal) have been dissociated, yet, differential behavioural consequences are unknown., Objective: The aim of the current study was to investigate behavioural consequences at the level of basic activities of daily living of region-specific neglect, using the Catherine Bergego Scale (CBS)., Methods: 118 stroke patients were screened within the first two weeks after admission to the rehabilitation center for inpatient rehabilitation., Results: Patients with peripersonal neglect and patients with neglect for both regions had significantly higher total score on the CBS compared to nonneglect patients. Total scores for patients with extrapersonal neglect were comparable to non-neglect patients. ADL impairments were found across activities (e.g., looking towards one side, forgetting body parts, colliding) for both patients with peripersonal neglect and patients with neglect for both regions. Patients with extrapersonal neglect were only impaired on the item on way finding., Conclusions: When diagnosing neglect, it is relevant to distinguish the type of region-specific neglect and, where needed, to adjust the rehabilitation program accordingly. As the CBS is not developed to typically measure ADL in extrapersonal neglect, it would be of importance to add other (instrumental) activities that heavily rely on processing information in farther space.

Background: Radiofrequency (RF) shading artifacts degrade image quality while performing cardiovascular magnetic resonance (CMR) at higher field strengths. In this article, we sought to evaluate the effect of local RF (B1 field) shimming by using a dual-source-transmit RF system for cardiac cine imaging and to systematically evaluate the effect of subject body type on the B1 field with and without local RF shimming., Methods: We obtained cardiac images from 37 subjects (including 11 patients) by using dual-transmit 3T CMR. B1 maps with and without subject-specific local RF shimming (exploiting the independent control of transmit amplitude and phase of the 2 RF transmitters) were obtained. Metrics quantifying B1 field homogeneity were calculated and compared with subject body habitus., Results: Local RF shimming across the region encompassed by the heart increased the mean flip angle (μ) in that area (88.5 ± 15.2% vs. 81.2 ± 13.3%; P = 0.0014), reduced the B1 field variation by 42.2 ± 13%, and significantly improved the percentage of voxels closer to μ (39% and 82% more voxels were closer to ± 10% and ± 5% of μ, respectively) when compared with no RF shimming. B1 homogeneity was independent of subject body type (body surface area [BSA], body mass index [BMI] or anterior-posterior/right-left patient width ratio [AP/RL]). Subject specific RF (B1) shimming with a dual-transmit system improved local RF homogeneity across all body types., Conclusion: With or without RF shimming, cardiac B1 field homogeneity does not depend on body type, as characterized by BMI, BSA, and AP/RL. For all body types studied, cardiac B1 field homogeneity was significantly improved by performing local RF shimming with 2 independent RF-transmit channels. This finding indicates the need for subject-specific RF shimming.

Introduction: There is wide interest in transferring paper-and-pencil tests to a computer-based setting, resulting in more precise recording of performance. Here, we investigated the feasibility of computer-based testing and computer-based prism adaptation (PA) to ameliorate neglect in sub-acute stroke patients admitted to a rehabilitation center., Methods: Thirty-three neglect patients were included. PA was performed with a pair of goggles with wide-field point-to-point prismatic lenses inducing an ipsilesional optical shift of 10°. A variety of digitalized neuropsychological tests were performed using an interactive tablet immediately before and after PA., Results: All 33 patients [mean age 60.36 (SD 13.30)], [mean days post-stroke 63.73 (SD 37.74)] were able to work with the tablet and to understand, perform, and complete the digitalized tests within the proposed time-frame, indicating that there is feasibility of computer-based assessment in this stage post-stroke. Analyses of the efficacy of PA indicated no significant change on any of the outcome measures, except time., Discussion: In conclusion, there is feasibility of computer-based testing in such an early stage, which makes the computer-based setting a promising technique for evaluating more ecologically valid tasks. Secondly, the computer-based PA can be considered as a reliable procedure. We can conclude from our analysis, addressing the efficacy of PA, that the effectiveness of single session PA may not be sufficient to produce short-term effects on our static tasks. Further studies, however, need to be done to evaluate the computer-based efficacy with more ecologically valid assessments in an intensive double-blind, sham-controlled multiple PA treatment design.

Purpose: To investigate the feasibility of high-dose dobutamine stress (HDDS) imaging using SSFP sequences at 3 T employing patient-adaptive local RF-shimming using a dual-source RF transmission system., Materials and Methods: 13 Patients underwent a HDDS protocol on a 3 T MRI scanner (Achieva 3.0T-TX, Philips Healthcare), equipped with a dual-source RF transmission system. SSFP cine sequences using patient-adaptive local RF-shimming (RF-S) were compared to cine images acquired without additional shimming. Image quality was evaluated on a 4-point grading scale and number of non-diagnostic segments assessed. Contrast (CN) between myocardium (SIM) and blood pool (SIB) was calculated [(SIB-SIM)/(SIB+SIM)]., Results: Image quality both at rest and maximum stress was significantly improved with RF-S (ED:3.56±0.5 vs. 3.23±0.63; ES:3.4±0.5 vs. 3.1±0.7) compared to no RF-S (ED:2.9±0.72 vs. 2.15±0.78; ES:2.64±0.74 vs. 1.95±0.76; p<0.01). The amount of non-diagnostic segments was significantly reduced when using RF-S at rest and stress (3 vs. 39; 19 vs. 78, p<0.05). All HDDS studies were diagnostic if performed with RF-S (n=13/13) in comparison to conventional shimming (n=5/13). Image contrast was improved for SSFP sequences with RF-S (0.53±0.08) compared to conventional images (0.46±0.09, p=0.06)., Conclusion: Patient-adaptive local RF-shimming using a dual-source RF transmission system allows for reliable SSFP imaging in a clinical high-dose dobutamine stress protocol at 3 T. RF-S significantly improves image quality and reduces the number of non-diagnostic myocardial segments., (© Georg Thieme Verlag KG Stuttgart · New York.)

Visuospatial neglect has been observed in the horizontal (left/right) and vertical (up/down) dimension and depends on the distance at which a task is presented (near/far). Previously, studies have mainly focused on investigating the overall severity of neglect in near and far space in a group of neglect patients instead of examining subgroups of neglect patients with different types of distance-specific neglect. We investigated the spatial specificity (near vs. far space), frequency, and severity of neglect in the horizontal and vertical dimensions in a large group of stroke patients. We used three tasks to assess neglect in near (30 cm) and far (120 cm) space: a shape cancellation, letter cancellation, and a line bisection task. Patients were divided into four groups based on their performance: a group without neglect (N-F-), a near only neglect (N+F-), a far only neglect (N-F+), and a near and far neglect group (N+F+). About 40% of our sample showed neglect. Depending on the task, N+F- was observed in 8 to 22% of the sample, whereas N-F+ varied between 8% and 11%, and N+F+ varied between 11% to 14% of the sample. The current findings indicate that horizontal and vertical biases in performance can be confined to one region of space and are task dependent. We recommend testing for far space neglect during neuropsychological assessments in clinical practice, because this cannot be diagnosed using standard paper-and-pencil tasks.

Aims: To evaluate the prognostic value and clinical utility of Ki67 tumour cell proliferation index in anaplastic oligodendroglial tumours (AOT)., Methods and Results: We performed anti-Ki67 immunostaining (MIB-1 antibody) of formalin-fixed and paraffin-embedded tumour tissue specimens of 128 patients with newly diagnosed AOT that were treated in a randomized Phase III trial. Ki67 index was assessed by three independent observers and was correlated to clinical, histopathological and molecular features (including 1p/19q co-deletion, epithelial growth factor receptor gene (EGFR) amplification, isocitrate dehydrogenase (IDH1) mutations, O6-methylguanine-DNA methyltransferase gene (MGMT) promoter methylation, and patient survival times. Intra- and inter-observer agreement of Ki67 index assessment was excellent. Univariable analysis (n = 79) showed that patients with a low Ki67 index had significantly more favourable progression-free survival (PFS) (P-value = 0.004, log-rank test) and overall survival (OS) (P-value = 0.003, log-rank test) than patients with a high Ki67 index, respectively. On multivariable analysis (n = 43), Ki67 index showed no independent association with PFS or OS., Conclusions: In AOT the Ki67 index has a strong prognostic impact on univariable analysis, but no independent influence on multivariable analysis. However, further prospective studies including larger numbers of cases and standardized evaluation of Ki67 index in conjunction with other relevant prognostic parameters are needed to draw definitive conclusions., (© 2012 Blackwell Publishing Ltd.)

Purpose: To evaluate the effect of dual-source parallel radiofrequency (RF) transmission with patient-adaptive local RF shimming on image quality, image contrast, and diagnostic confidence at routine clinical cardiac magnetic resonance (MR) imaging with use of a 3.0-T dual-channel transmit whole-body MR system., Materials and Methods: Written informed consent was obtained from all patients, and the study protocol was approved by the local institutional review board. Cardiac MR imaging was performed in 28 patients by using a 3.0-T MR unit equipped with a dual-source RF transmission system. The effect of conventional versus dual-source RF transmission on steady-state free precession (SSFP) cine sequences and turbo spin-echo (TSE) black-blood (BB) sequences was evaluated. The homogeneity of the B1 field and contrast-to-noise ratios (CNRs) were measured and tested for statistical significance with the paired t test. Images were analyzed qualitatively for homogeneity, the presence of off-resonance artifacts, and diagnostic confidence independently by two readers. Statistical significance was assessed with the Wilcoxon signed rank test. Inter- and intraobserver agreement was assessed with κ statistics., Results: Quantitative image analysis revealed that B1 homogeneity and CNR were significantly improved for images acquired with dual-source RF transmission compared with conventional RF transmission (P = .005). The quality of SSFP and TSE BB images of the left and the right ventricles showed a significant improvement with respect to image homogeneity and diagnostic confidence as evaluated by the readers (P = .0001, κ > 0.74). As a side effect, off-resonance artifacts were significantly reduced on SSFP images (P = .0001, κ > 0.76)., Conclusion: Dual-source parallel RF transmission significantly improves image homogeneity, image contrast, and diagnostic confidence compared with conventional RF transmission of cardiac SSFP and TSE BB sequences., (© RSNA, 2012.)

Purpose: To establish operator-independent, fully automated planning of standard cardiac geometries and to determine the impact on interstudy reproducibility of cardiac functional parameters., Materials and Methods: Cardiac MR imaging was done in 50 patients referred for left-ventricular function assessment. In all patients, first standard manual planning was performed followed by automatic planning (AUTO1) and repeat automatic planning (AUTO2) after repositioning the patient to investigate interstudy reproducibility. Cardiac functional parameters were assessed and cine scans were visually graded on a 4-point scale from nondiagnostic to excellent., Results: Overall success rate of AUTO was 94% with good to excellent geometry planning in >94% of cine standard views. Comparing manual versus fully automated planning, a high agreement of cardiac functional parameters (Lin's concordance correlation coefficient, 0.91 to 0.99) with minimal percent bias (0.24 to 3.84%) was found. In addition, a high interstudy reproducibility of automatic planning was demonstrated (Lin's concordance correlation coefficient, 0.89 to 0.99; percent bias, 0.38 to 5.04%; precision, 3.46 to 9.09%)., Conclusion: Fully automated planning of cardiac geometries could reliably be performed in patients showing a variety of cardiovascular pathologies. Standard cardiac geometries were precisely replicated and functional parameters were highly accurate., (Copyright © 2011 Wiley-Liss, Inc.)

Despite similar morphological aspects, anaplastic oligodendroglial tumors (AOTs) form a heterogeneous clinical subgroup of gliomas. The chromosome arms 1p/19q codeletion has been shown to be a relevant biomarker in AOTs and to be perfectly exclusive from EGFR amplification in gliomas. To identify new genomic regions associated with prognosis, 60 AOTs from the EORTC trial 26951 were analyzed retrospectively using BAC-array-based comparative genomic hybridization. The data were processed using a binary tree method. Thirty-three BACs with prognostic value were identified distinguishing four genomic subgroups of AOTs with different prognosis (p < 0.0001). Type I tumors (25%) were characterized by: (1) an EGFR amplification, (2) a poor prognosis, (3) a higher rate of necrosis, and (4) an older age of patients. Type II tumors (21.7%) had: (1) loss of prognostic BACs located on 1p tightly associated with 19q deletion, (2) a longer survival, (3) an oligodendroglioma phenotype, and (4) a frontal location in brain. Type III AOTs (11.7%) exhibited: (1) a deletion of prognostic BACs located on 21q, and (2) a short survival. Finally, type IV tumors (41.7%) had different genomic patterns and prognosis than type I, II and III AOTs. Multivariate analysis showed that genomic type provides additional prognostic data to clinical, imaging and pathological features. Similar results were obtained in the cohort of 45 centrally reviewed-validated cases of AOTs. Whole genome analysis appears useful to screen the numerous genomic abnormalities observed in AOTs and to propose new biomarkers particularly in the non-1p/19q codeleted AOTs.

Many interventions in upper-limb rehabilitation after cervical spinal cord injury (CSCI) use arm support (gravity compensation); however, its specific effects on kinematics and muscle activation characteristics in subjects with a CSCI are largely unknown. We conducted a cross-sectional explorative study to study these effects. Nine subjects with a CSCI performed two goal-directed arm movements (maximal reach, reach and retrieval) with and without gravity compensation. Angles at elbow and shoulder joints and muscle activation were measured and compared. Seven subjects reduced elbow extension (range 1.8°-4.5°) during the maximal reaching task with gravity compensation. In the reach and retrieval task with gravity compensation, all subjects decreased elbow extension (range 0.1°-11.0°). Eight subjects executed movement closer to the body. Regarding muscle activation, gravity compensation did not influence timing; however, the amplitude of activation decreased, especially in antigravity muscles, namely mean change +/- standard deviation of descending part of trapezius (18.2% +/- 37.5%), anterior part of deltoid (37.7% +/- 16.7%), posterior part of deltoid (32.0% +/- 13.9%), and long head biceps (49.6% +/- 20.0%). Clinical implications for the use of gravity compensation in rehabilitation (during activities of daily living or exercise therapy) should be further investigated with a larger population.

The chromosome (chr) 1p deletion is a favorable biomarker in oligodendroglial tumors and is even more powerful a marker when combined with chr 19q loss. As a result, the 1p deletion is taken into account more and more in clinical trials and the management of patients. However, the laboratory technique implemented for detection of this biomarker has been a topic of debate. To illustrate the usefulness of evaluating multiple loci, we here report two anaplastic oligodendrogliomas that were investigated using fluorescent in situ hybridization (FISH) and bacterial artificial chromosome (BAC)-array-based comparative genomic hybridization (aCGH). Indeed, segmental analysis using FISH, limited to chr 1p36 was unable to discriminate between complete and partial deletions of chrs 1p. However, complete and partial deletions of 1p are reported to have distinct clinical outcomes. Our results illustrate that aCGH (or other multiple loci technologies) provide complementary information to single locus technologies such as FISH because multiple loci technologies can evaluate the extent of the chr 1p deletion.

Objective: To test if three-dimensional (3D) cine spatial frequency-temporal frequency Broad-use Linear Acquisition Speed-up Technique (k-t BLAST) is suitable for rapid evaluation of global and regional left ventricular (LV) functional parameters and to evaluate the influence of gadolinium administration., Materials and Methods: Parameters describing global and regional LV function were evaluated in 50 subjects using a two-dimensional (2D) steady-state free precession (SSFP) and pre- and postcontrast 3D k-t BLAST techniques. Data analyses included contrast-to-noise ratio analyses, and statistical evaluations included Bland-Altman, Cohen's kappa and analysis of variance techniques., Results: Bland-Altman analyses revealed that the ejection fraction computed using the 3D k-t BLAST sequences before (bias+/-2S.D., 2.2+/-8.8) and after contrast administration (bias+/-2S.D., 2.7+/-7.6 mol) was comparable to the 2D SSFP technique. Similar agreement was noted for other global LV parameters. The myocardium-to-blood contrast in the apical slices was better in the 3D k-t BLAST sequence after contrast administration than before. Cohen's kappa values demonstrated good agreement between the sequences for evaluating regional wall motion., Conclusions: 3D k-t BLAST can yield global and regional LV functional parameters comparable to those of the 2D SSFP technique in substantially shorter scan times. In 3D k-t BLAST images, myocardium-to-blood contrast in the apical slices is better after contrast administration.

Objective: Our objective was to compare two state-of-the-art coronary MRI (CMRI) sequences with regard to image quality and diagnostic accuracy for the detection of coronary artery disease (CAD)., Subjects and Methods: Twenty patients with known CAD were examined with a navigator-gated and corrected free-breathing 3D segmented gradient-echo (turbo field-echo) CMRI sequence and a steady-state free precession sequence (balanced turbo field-echo). CMRI was performed in a transverse plane for the left coronary artery and a double-oblique plane for the right coronary artery system. Subjective image quality (1- to 4-point scale, with 1 indicating excellent quality) and objective image quality parameters were independently determined for both sequences. Sensitivity, specificity, and accuracy for the detection of significant (> or = 50% diameter) coronary artery stenoses were determined as defined in invasive catheter X-ray coronary angiography., Results: Subjective image quality was superior for the balanced turbo field-echo approach (1.8 +/- 0.9 vs 2.3 +/- 1.0 for turbo field-echo; p < 0.001). Vessel sharpness, signal-to-noise ratio, and contrast-to-noise ratio were all superior for the balanced turbo field-echo approach (p < 0.01 for signal-to-noise ratio and contrast-to-noise ratio). Of the 103 segments, 18% of turbo field-echo segments and 9% of balanced turbo field-echo segments had to be excluded from disease evaluation because of insufficient image quality. Sensitivity, specificity, and accuracy for the detection of significant coronary artery stenoses in the evaluated segments were 92%, 67%, 85%, respectively, for turbo field-echo and 82%, 82%, 81%, respectively, for balanced turbo field-echo., Conclusion: Balanced turbo field-echo offers improved image quality with significantly fewer nondiagnostic segments when compared with turbo field-echo. For the detection of CAD, both sequences showed comparable accuracy for the visualized segments.

The role of antigen-presenting cells (APC) involved in induction of T and B cell mediated autoaggressive immunity in Guillain-Barre syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is poorly understood. We studied the numbers and phenotype of dendritic cells (DC) in blood and cerebrospinal fluid (CSF) over the course of GBS and CIDP before and after immunomodulatory treatment. Four out of seven GBS patients examined prior to treatment with high-dose intravenous immunoglobulins (IvIg) had elevated numbers of CD123(+) plasmacytoid DC in the CSF, while both GBS and CIDP patients examined prior to treatment had elevated numbers of CD11c(+) myeloid DC in the CSF, as compared to patients with noninflammatory neurological diseases (OND). The percentages of blood DC expressing the cell surface marker CD1a, co-stimulatory molecules CD80 and CD86, adhesion molecule CD54, and chemokine receptors CCR1, CCR2, CCR5, and CXCR4 were not affected in GBS or CIDP. The immunohistochemistry of sural nerve biopsies revealed CD11c(+)CD83(-)CD14(-)CD16(-) immature myeloid DC at low numbers, mostly in the perineurium, without difference between CIDP patients and controls. In contrast, the numbers of CD11c(+)CD14(+)/CD16(+) macrophages were higher within the endoneurium in CIDP patients compared with the controls. The recruitment of DC to CSF in GBS and CIDP may be important in capturing antigens released from inflamed spinal nerve roots into CSF and in transferring these antigens from CSF to local lymph nodes, where naive T and B cells may be activated.