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  • 1
    In: BJOG: An International Journal of Obstetrics & Gynaecology, Wiley, Vol. 130, No. 8 ( 2023-07), p. 881-890
    Abstract: Deceleration area (DA) and capacity (DC) of the fetal heart rate can help predict risk of intrapartum fetal compromise. However, their predictive value in higher risk pregnancies is unclear. We investigated whether they can predict the onset of hypotension during brief hypoxaemia repeated at a rate consistent with early labour in fetal sheep with pre‐existing hypoxaemia. Design Prospective, controlled study. Setting Laboratory. Sample Chronically instrumented, unanaesthetised near‐term fetal sheep. Methods One‐minute complete umbilical cord occlusions (UCOs) were performed every 5 minutes in fetal sheep with baseline p a O 2 〈 17 mmHg (hypoxaemic, n  = 8) and 〉 17 mmHg (normoxic, n  = 11) for 4 hours or until arterial pressure fell 〈 20 mmHg. Main outcome measures DA, DC and arterial pressure. Results Normoxic fetuses showed effective cardiovascular adaptation without hypotension and mild acidaemia (lowest arterial pressure 40.7 ± 2.8 mmHg, pH 7.35 ± 0.03). Hypoxaemic fetuses developed hypotension (lowest arterial pressure 20.8 ± 1.9 mmHg, P   〈  0.001) and acidaemia (final pH 7.07 ± 0.05). In hypoxaemic fetuses, decelerations showed faster falls in FHR over the first 40 seconds of UCOs but the final deceleration depth was not different to normoxic fetuses. DC was modestly higher in hypoxaemic fetuses during the penultimate ( P  = 0.04) and final ( P  = 0.012) 20 minutes of UCOs. DA was not different between groups. Conclusion Chronically hypoxaemic fetuses had early onset of cardiovascular compromise during labour‐like brief repeated UCOs. DA was unable to identify developing hypotension in this setting, while DC only showed modest differences between groups. These findings highlight that DA and DC thresholds need to be adjusted for antenatal risk factors, potentially limiting their clinical utility.
    Type of Medium: Online Resource
    ISSN: 1470-0328 , 1471-0528
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2036469-6
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  • 2
    In: Movement Disorders Clinical Practice, Wiley, Vol. 9, No. 4 ( 2022-05), p. 473-478
    Abstract: Quantitative measurement of eye movements can reveal subtle progression in neurodegenerative diseases. Objective To determine if quantitative measurements of eye movements may reveal subtle progression of fragile X‐associated tremor and ataxia (FXTAS). Methods Prosaccade (PS) and antisaccade (AS) behavior was analyzed in 25 controls, 57 non‐FXTAS carriers, and 46 carriers with FXTAS. Results Symptomatic individuals with FXTAS had longer AS latencies, increased rates of AS errors, and increased AS dysmetria relative to non‐FXTAS carriers and controls. These deficits, along with PS latency and velocity, were greater in advanced FXTAS stages. Conclusion AS deficits differentiated FXTAS from non‐FXTAS premutation carriers implicating top‐down control and frontostriatal deterioration. However, the absence of group differences between non‐FXTAS carriers and controls in AS and PS markers suggests saccade performance may not be a sensitive enough measure for detecting conversion to FXTAS, but instead more helpful as translational biomarkers of FXTAS progression.
    Type of Medium: Online Resource
    ISSN: 2330-1619 , 2330-1619
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2772809-2
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  • 3
    Online Resource
    Online Resource
    Wiley ; 2018
    In:  The Journal of Physiology Vol. 596, No. 23 ( 2018-12), p. 5485-5489
    In: The Journal of Physiology, Wiley, Vol. 596, No. 23 ( 2018-12), p. 5485-5489
    Type of Medium: Online Resource
    ISSN: 0022-3751 , 1469-7793
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 1475290-6
    SSG: 12
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  • 4
    In: Annals of Neurology, Wiley, Vol. 92, No. 6 ( 2022-12), p. 1066-1079
    Abstract: Seizures are more common in the neonatal period than at any other stage of life. Phenobarbital is the first‐line treatment for neonatal seizures and is at best effective in approximately 50% of babies, but may contribute to neuronal injury. Here, we assessed the efficacy of phenobarbital versus the synthetic neurosteroid, ganaxolone, to moderate seizure activity and neuropathology in neonatal lambs exposed to perinatal asphyxia. Methods Asphyxia was induced via umbilical cord occlusion in term lambs at birth. Lambs were treated with ganaxolone (5mg/kg/bolus then 5mg/kg/day for 2 days) or phenobarbital (20mg/kg/bolus then 5mg/kg/day for 2 days) at 6 hours. Abnormal brain activity was classified as stereotypic evolving (SE) seizures, epileptiform discharges (EDs), and epileptiform transients (ETs) using continuous amplitude‐integrated electroencephalographic recordings. At 48 hours, lambs were euthanized for brain pathology. Results Asphyxia caused abnormal brain activity, including SE seizures that peaked at 18 to 20 hours, EDs, and ETs, and induced neuronal degeneration and neuroinflammation. Ganaxolone treatment was associated with an 86.4% reduction in the number of seizures compared to the asphyxia group. The total seizure duration in the asphyxia+ganaxolone group was less than the untreated asphyxia group. There was no difference in the number of SE seizures between the asphyxia and asphyxia+phenobarbital groups or duration of SE seizures. Ganaxolone treatment, but not phenobarbital, reduced neuronal degeneration within hippocampal CA1 and CA3 regions, and cortical neurons, and ganaxolone reduced neuroinflammation within the thalamus. Interpretation Ganaxolone provided better seizure control than phenobarbital in this perinatal asphyxia model and was neuroprotective for the newborn brain, affording a new therapeutic opportunity for treatment of neonatal seizures. ANN NEUROL 2022;92:1066–1079
    Type of Medium: Online Resource
    ISSN: 0364-5134 , 1531-8249
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2037912-2
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  • 5
    In: The Journal of Physiology, Wiley
    Abstract: Hypoxia‐ischaemia (HI) before birth is a key risk factor for stillbirth and severe neurodevelopmental disability in survivors, including cerebral palsy, although there are no reliable biomarkers to detect at risk fetuses that may have suffered a transient period of severe HI. We investigated time and frequency domain measures of fetal heart rate variability (FHRV) for 3 weeks after HI in preterm fetal sheep at 0.7 gestation (equivalent to preterm humans) until 0.8 gestation (equivalent to term humans). We have previously shown that this is associated with delayed development of severe white and grey matter injury, including cystic white matter injury (WMI) resembling that observed in human preterm infants. HI was associated with suppression of time and frequency domain measures of FHRV and reduced their circadian rhythmicity during the first 3 days of recovery. By contrast, circadian rhythms of multiple measures of FHRV were exaggerated over the final 2 weeks of recovery, mediated by a greater reduction in FHRV during the morning nadir, but no change in the evening peak. These data suggest that the time of day at which FHRV measurements are taken affects their diagnostic utility. We further propose that circadian changes in FHRV may be a low‐cost, easily applied biomarker of antenatal HI and evolving brain injury. image Key points Hypoxia‐ischaemia (HI) before birth is a key risk factor for stillbirth and probably for disability in survivors, although there are no reliable biomarkers for antenatal brain injury. In preterm fetal sheep, acute HI that is known to lead to delayed development of severe white and grey matter injury over 3 weeks, was associated with early suppression of multiple time and frequency domain measures of fetal heart rate variability (FHRV) and loss of their circadian rhythms during the first 3 days after HI. Over the final 2 weeks of recovery after HI, exaggerated circadian rhythms of frequency domain FHRV measures were observed. The morning nadirs were lower with no change in the evening peak of FHRV. Circadian changes in FHRV may be a low‐cost, easily applied biomarker of antenatal HI and evolving brain injury.
    Type of Medium: Online Resource
    ISSN: 0022-3751 , 1469-7793
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 1475290-6
    SSG: 12
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  • 6
    In: Alzheimer's & Dementia, Wiley, Vol. 11, No. 2 ( 2015-02), p. 111-125
    Abstract: An international Delphi panel has defined a harmonized protocol (HarP) for the manual segmentation of the hippocampus on MR. The aim of this study is to study the concurrent validity of the HarP toward local protocols, and its major sources of variance. Methods Fourteen tracers segmented 10 Alzheimer's Disease Neuroimaging Initiative (ADNI) cases scanned at 1.5 T and 3T following local protocols, qualified for segmentation based on the HarP through a standard web‐platform and resegmented following the HarP. The five most accurate tracers followed the HarP to segment 15 ADNI cases acquired at three time points on both 1.5 T and 3T. Results The agreement among tracers was relatively low with the local protocols (absolute left/right ICC 0.44/0.43) and much higher with the HarP (absolute left/right ICC 0.88/0.89). On the larger set of 15 cases, the HarP agreement within (left/right ICC range: 0.94/0.95 to 0.99/0.99) and among tracers (left/right ICC range: 0.89/0.90) was very high. The volume variance due to different tracers was 0.9% of the total, comparing favorably to variance due to scanner manufacturer (1.2), atrophy rates (3.5), hemispheric asymmetry (3.7), field strength (4.4), and significantly smaller than the variance due to atrophy (33.5%, P   〈  .001), and physiological variability (49.2%, P   〈  .001). Conclusions The HarP has high measurement stability compared with local segmentation protocols, and good reproducibility within and among human tracers. Hippocampi segmented with the HarP can be used as a reference for the qualification of human tracers and automated segmentation algorithms.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    Language: English
    Publisher: Wiley
    Publication Date: 2015
    detail.hit.zdb_id: 2201940-6
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  • 7
    In: The Journal of Physiology, Wiley, Vol. 601, No. 10 ( 2023-05), p. 2017-2041
    Abstract: Brief repeated fetal hypoxaemia during labour can trigger intrapartum decelerations of the fetal heart rate (FHR) via the peripheral chemoreflex or the direct effects of myocardial hypoxia, but the relative contribution of these two mechanisms and how this balance changes with evolving fetal compromise remain unknown. In the present study, chronically instrumented near‐term fetal sheep received surgical vagotomy ( n  = 8) or sham vagotomy (control, n  = 11) to disable the peripheral chemoreflex and unmask myocardial hypoxia. One‐minute complete umbilical cord occlusions (UCOs) were performed every 2.5 min for 4 h or until arterial pressure fell below 20 mmHg. Hypotension and severe acidaemia developed progressively after 65.7 ± 7.2 UCOs in control fetuses and 49.5 ± 7.8 UCOs after vagotomy. Vagotomy was associated with faster development of metabolic acidaemia and faster impairment of arterial pressure during UCOs without impairing centralization of blood flow or neurophysiological adaptation to UCOs. During the first half of the UCO series, before severe hypotension developed, vagotomy was associated with a marked increase in FHR during UCOs. After the onset of evolving severe hypotension, FHR fell faster in control fetuses during the first 20 s of UCOs, but FHR during the final 40 s of UCOs became progressively more similar between groups, with no difference in the nadir of decelerations. In conclusion, FHR decelerations were initiated and sustained by the peripheral chemoreflex at a time when fetuses were able to maintain arterial pressure. After the onset of evolving hypotension and acidaemia, the peripheral chemoreflex continued to initiate decelerations, but myocardial hypoxia became progressively more important in sustaining and deepening decelerations. image Key points Brief repeated hypoxaemia during labour can trigger fetal heart rate decelerations by either the peripheral chemoreflex or myocardial hypoxia, but how this balance changes with fetal compromise is unknown. Reflex control of fetal heart rate was disabled by vagotomy to unmask the effects of myocardial hypoxia in chronically instrumented fetal sheep. Fetuses were then subjected to repeated brief hypoxaemia consistent with the rates of uterine contractions during labour. We show that the peripheral chemoreflex controls brief decelerations in their entirety at a time when fetuses were able to maintain normal or increased arterial pressure. The peripheral chemoreflex still initiated decelerations even after the onset of evolving hypotension and acidaemia, but myocardial hypoxia made an increasing contribution to sustain and deepen decelerations.
    Type of Medium: Online Resource
    ISSN: 0022-3751 , 1469-7793
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 1475290-6
    SSG: 12
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  • 8
    In: Journal of Cachexia, Sarcopenia and Muscle, Wiley, Vol. 13, No. 5 ( 2022-10), p. 2373-2382
    Abstract: Access to the liver transplant waitlist for patients with hepatocellular carcinoma (HCC) depends on tumour presentation, biology, and response to treatments. The Milan Criteria (MC) represent the benchmark for expanded criteria that incorporate additional prognostic factors. The purpose of this study was to determine the added value of skeletal muscle index (SMI) in HCC patients beyond the MC. Method Patients with HCC that were transplanted beyond the MC were included in this retrospective multicentre study. SMI was quantified using the Computed Tomography (CT) within 3 months prior to transplantation. Cox regression models were used to identify predictors of overall survival (OS). The discriminative performance of SMI extended Metroticket 2.0 and AFP models was also assessed. Results Out of 889 patients transplanted outside the MC, 528 had a CT scan within 3 months prior to liver transplantation (LT), of whom 176 (33%) were classified as sarcopenic. The median time between assessment of the SMI and LT was 1.8 months (IQR: 0.77–2.67). The median follow‐up period was 5.1 95% CI [4.7–5.5] years, with a total of 177 recorded deaths from any cause. In a linear regression model with SMI as the dependent variable, only male gender (8.55 95% CI [6.51–10.59] , P   〈  0.001) and body mass index (0.74 95% CI [0.59–0.89], P   〈  0.001) were significant. Univariable survival analysis of patients with sarcopenia versus patients without sarcopenia showed a significant difference in OS (HR 1.44 95% CI [1.07 − 1.94], P  = 0.018). Also the SMI was significant (HR 0.98 95% CI [0.96–0.99], P  = 0.014). The survival difference between the lowest SMI quartile versus the highest SMI quartile was significant (log‐rank: P  = 0.005) with 5 year OS of 57% and 71%, respectively. Data from 423 patients, describing 139 deaths, was used for multivariate analysis. Both sarcopenia (HR 1.45 95% CI [1.02 − 2.05], P  = 0.036) and SMI were (HR 0.98 95% CI [0.95–0.99], P  = 0.035) significant. On the survival scale this translates to a 5 year OS difference of 11% between sarcopenia and no sarcopenia. Whereas for SMI, this translates to a survival difference of 8% between first and third quartiles for both genders. Conclusions Overall, we can conclude that higher muscle mass contributes to a better long‐term survival. However, for individual patients, low muscle mass should not be considered an absolute contra‐indication for LT as its discriminatory performance was limited.
    Type of Medium: Online Resource
    ISSN: 2190-5991 , 2190-6009
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2586864-0
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  • 9
    In: The Journal of Physiology, Wiley, Vol. 578, No. 2 ( 2007-01-15), p. 491-506
    Type of Medium: Online Resource
    ISSN: 0022-3751
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2007
    detail.hit.zdb_id: 1475290-6
    SSG: 12
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  • 10
    Online Resource
    Online Resource
    Wiley ; 1993
    In:  The Journal of Physiology Vol. 461, No. 1 ( 1993-02-01), p. 431-449
    In: The Journal of Physiology, Wiley, Vol. 461, No. 1 ( 1993-02-01), p. 431-449
    Type of Medium: Online Resource
    ISSN: 0022-3751
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 1993
    detail.hit.zdb_id: 1475290-6
    SSG: 12
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