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  • Jahnson, S., et al. (author)
  • Thromboembolism in Muscle-Invasive Bladder Cancer. A Population-based Nationwide Study
  • 2021
  • In: Bladder Cancer. - : IOS Press. - 2352-3727 .- 2352-3735. ; 7:2, s. 161-171
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Routine VTE prophylaxis within 30 days of radical cystectomy (RC) for urinary bladder cancer (UBC) is used to protect from venous thromboembolism (VTE). However, randomized studies and nationwide population-based studies are lacking. OBJECTIVE: To study VTE and risk factors for VTE in muscle-invasive UBC in a nationwide population-based series, with a focus on the association with RC with and without chemotherapy. MATERIALS AND METHODS: We studied all patients with clinical stage T2-T4 UBC diagnosed 1997 to 2014 in the Bladder Cancer Data Base Sweden (BladderBaSe). Previous VTE events and risk factors for VTE were registered from 1987. Cox regression analyses and Kaplan-Meier curves were performed to study risk factors for VTE and cumulative incidence of VTE. RESULTS: In 9720 patients (71% males) with a median age of 74 years 546 (5.6%) had VTE after diagnosis. In Cox analyses controlling for patient's and tumour characteristics, and risk factors for VTE, VTE after diagnosis and first treatment date were associated with chemotherapy with or without RC. Cumulative incidence of VTE increased during 24 months after diagnosis and first treatment date. VTE were less common in patients with previous cardiovascular disease. CONCLUSION: VTE was commonly observed after 30 days from diagnosis and from first treatment date in patients with T2-T4 UBC, particularly after chemotherapy. The findings suggest that long-term intervention studies of benefit and possible harms of VTE prophylaxis after UBC should be undertaken.
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  • Liedberg, F., et al. (author)
  • Preoperative upper tract invasive diagnostic modalities are associated with intravesical recurrence following surgery for upper tract urothelial carcinoma : A population-based study
  • 2023
  • In: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 83:Suppl. 1, s. S720-S721
  • Journal article (other academic/artistic)abstract
    • Introduction & Objectives: Evidence based mainly on small retrospective series points to an increased risk of intravesical recurrence (IVR) after preoperative diagnostic ureteroscopy (URS) in upper tract urothelial carcinoma (UTUC). We investigated if preoperative invasive diagnostic modalities (IDM) are associated with IVR after radical surgery for UTUC. Secondly, risk of death from urothelial cancer and all causes was investigated.Materials & Methods: We investigated a population-based cohort of 1038 consecutive patients subjected to radical surgery for UTUC 2015–2019 in Sweden, using the Bladder Cancer Data Base Sweden (BladderBaSe 2.0), comprising all patients in the Swedish National Registry of Urinary Bladder Cancer. Risk estimates of IVR, death from urothelial cancer, and all causes following IDM (antegrade/retrograde uretero-pyelography and/or selective urine cytology/barbotage, and URS with or without concomitant biopsy) was assessed using multivariable Cox regression models adjusted for age, gender, clinical tumour stage, tumour location (renal pelvis/ureter/both), ipsilateral bladder cuff excision, previous bladder cancer, comorbidity, and educational level.Results: The study included 536 cases with and 502 without preoperative IDM. IDM was associated with increased risk of IVR (HR 1.24, 95% CI 1.03-1.52) and risk of urothelial cancer death (HR 1.56, CI 1.12-2.18), compared to no IDM after a median follow-up of 1.3 yrs. Stratified analysis for tumor location showed that IDM was associated with risk of IVR in ureteric cancer (HR 1.66, 95% CI 1.21-2.28) but not in renal pelvic cancer (HR 1.07, 95% CI 0.81-1.41). Limitations include the observational setting and the lack of information on tumour grade, multifocality and preoperative hydronephrosis.Conclusions: Worse outcomes for patients subjected to preoperative IDM highlight the need for carefully considering diagnostic decisions for UTUC patients, specifically in tumours located in the ureter.
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  • Bairnsfather, JE, et al. (author)
  • Investigating the Relationship Between Childhood Music Practice and Pitch-Naming Ability in Professional Musicians and a Population-Based Twin Sample
  • 2022
  • In: Twin research and human genetics : the official journal of the International Society for Twin Studies. - : Cambridge University Press (CUP). - 1832-4274. ; 25:3, s. 140-148
  • Journal article (peer-reviewed)abstract
    • The relationship between pitch-naming ability and childhood onset of music training is well established and thought to reflect both genetic predisposition and music training during a critical period. However, the importance of the amount of practice during this period has not been investigated. In a population sample of twins (N = 1447, 39% male, 367 complete twin pairs) and a sample of 290 professional musicians (51% male), we investigated the role of genes, age of onset of playing music and accumulated childhood practice on pitch-naming ability. A significant correlation between pitch-naming scores for monozygotic (r = .27, p < .001) but not dizygotic twin pairs (r = −.04, p = .63) supported the role of genetic factors. In professional musicians, the amount of practice accumulated between ages 6 and 11 predicted pitch-naming accuracy (p = .025). In twins, age of onset was no longer a significant predictor once practice was considered. Combined, these findings are in line with the notion that pitch-naming ability is associated with both genetic factors and amount of early practice, rather than just age of onset per se. This may reflect a dose–response relation between practice and pitch-naming ability in genetically predisposed individuals. Alternatively, children who excel at pitch-naming may have an increased tendency to practice.
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  • Bergengren, Oskar, et al. (author)
  • Short term outcomes after robot assisted and open cystectomy- A nation-wide population-based study
  • 2023
  • In: Ejso. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 49:4, s. 868-874
  • Journal article (peer-reviewed)abstract
    • Introduction: We aimed to compare short term outcomes after robot assisted radical cystectomy (RARC) and open radical cystectomy (ORC) for urinary bladder cancer in a large population.Materials and methods: We included all patients without distant metastases who underwent either RARC or ORC with ileal conduit between 2011 and 2019 registered in the Bladder cancer data Base Sweden (BladderBaSe) 2.0. Primary outcome was unplanned readmissions within 90 days, and secondary out-comes within 90 days of surgery were reoperations, Clavien 3-5 complications, total days alive and out of hospital, and mortality. The analysis was carried out using multivariate regression models.Results: Out of 2905 patients, 832 were operated with RARC and 2073 with ORC. Robotic procedures were to a larger extent performed during later years, at high volume centers (47% vs 17%), more often for organ-confined disease (82% vs. 72%) and more frequently in patients with high socioeconomic status (26% vs. 21%). Patients operated with RARC were more commonly readmitted (29% vs. 25%). In multi -variable analysis RARC was associated with decreased risk of Clavien 3-5 complications (OR 0.58, 95% CI 0.47-0.72), reoperations (OR 0.53, 95% CI 0.39-0.71) and had more days alive and out of hospital (mean difference 3.7 days, 95% CI 2.4-5.0).Conclusion: This study illustrates the "real-world" effects of a gradual and nation-wide introduction of RARC. Patients operated with RARC had fewer major complications and reoperations but were more frequently readmitted compared to ORC. The observed differences were largely due to more wound related complications among patients treated with ORC.(c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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  • Dankiewicz, Josef, et al. (author)
  • Targeted hypothermia versus targeted Normothermia after out-of-hospital cardiac arrest (TTM2): A randomized clinical trial - Rationale and design
  • 2019
  • In: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 217, s. 23-31
  • Journal article (peer-reviewed)abstract
    • Background: Less than 500 participants have been included in randomized trials comparing hypothermia with regular care for out-of-hospital cardiac arrest patients, and many of these trials were small and at a high risk of bias. Consequently, the accrued data on this potentially beneficial intervention resembles that of a drug following small phase II trials. A large confirmatory trial is therefore warranted. Methods: The TTM2-trial is an international, multicenter, parallel group, investigator-initiated, randomized, superiority trial in which a target temperature of 33°C after cardiac arrest will be compared with a strategy to maintain normothermia and early treatment of fever (≥37.8°C). Participants will be randomized within 3 hours of return of spontaneous circulation with the intervention period lasting 40 hours in both groups. Sedation will be mandatory for all patients throughout the intervention period. The clinical team involved with direct patient care will not be blinded to allocation group due to the inherent difficulty in blinding the intervention. Prognosticators, outcome-assessors, the steering group, the trial coordinating team, and trial statistician will be blinded. The primary outcome will be all-cause mortality at 180 days after randomization. We estimate a 55% mortality in the control group. To detect an absolute risk reduction of 7.5% with an alpha of 0.05 and 90% power, 1900 participants will be enrolled. The main secondary neurological outcome will be poor functional outcome (modified Rankin Scale 4–6) at 180 days after arrest. Discussion: The TTM2-trial will compare hypothermia to 33°C with normothermia and early treatment of fever (≥37.8°C) after out-of-hospital cardiac arrest. © 2019
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  • Fagerstedt, P, et al. (author)
  • Lateral turns in the Lamprey. I. Patterns of motoneuron activity
  • 2001
  • In: Journal of neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 86:5, s. 2246-2256
  • Journal article (peer-reviewed)abstract
    • The activity of motoneurons during lateral turns was studied in a lower vertebrate, the lamprey, to investigate how a supraspinal command for the change of direction during locomotion is transmitted from the brain stem and integrated with the activity of the spinal locomotor pattern generator. Three types of experiments were performed. 1) The muscular activity during lateral turns in freely swimming adult lampreys was recorded by electromyography (EMG). It was characterized by increased cycle duration and increased duration, intensity, and cycle proportion of the bursts on the side toward which the animal turns. 2) Electrical stimulation of the skin on one side of the head in a head-spinal cord preparation of the lamprey during fictive locomotion elicited asymmetric ventral root burst activity with similar characteristics as observed in the EMG of intact lampreys during lateral turns. The cycle duration and ventral root burst intensity, duration, and cycle proportion on the side of the spinal cord contralateral to the stimulus were increased; hence a fictive lateral turn away from the stimulus could be produced. The fictive turn propagated caudally with decreasing amplitude. The increase in burst duration during the turn correlated well with the increase in cycle duration, while changes in contralateral burst intensity and burst duration did not co-vary. Turning responses varied depending on the timing (phase) of the skin stimulation: stimuli in the first two-thirds of a cycle evoked a turn in the same cycle, whereas stimuli in the last third gave a turn in the following cycle. The largest turns were evoked by stimuli in the first third of a cycle. 3) Fictive turns were abolished after transection of the trigeminal nerve or a rhombencephalic midline split, but not in a rhombencephalic preparation with transected cerebellar commissure. High spinal hemisection was sufficient to block turning toward the lesioned side, while turns toward the intact side remained. Taken together these findings suggest that the reticulospinal turn command is essentially unilateral and generated in the rhombencephalon.
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  • Fagerstedt, P, et al. (author)
  • Lateral turns in the Lamprey. II. Activity of reticulospinal neurons during the generation of fictive turns
  • 2001
  • In: Journal of neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 86:5, s. 2257-2265
  • Journal article (peer-reviewed)abstract
    • We studied the neural correlates of turning movements during fictive locomotion in a lamprey in vitro brain–spinal cord preparation. Electrical stimulation of the skin on one side of the head was used to evoke fictive turns. Intracellular recordings were performed from reticulospinal cells in the middle (MRRN) and posterior (PRRN) rhombencephalic reticular nuclei, and from Mauthner cells, to characterize the pattern of activity in these cell groups, and their possible functional role for the generation of turns. All recorded reticulospinal neurons modified their activity during turns. Many cells in both the rostral and the caudal MRRN, and Mauthner cells, were strongly excited during turning. The level of activity of cells in rostral PRRN was lower, while the lowest degree of activation was found in cells in caudal PRRN, suggesting that MRRN may play a more important role for the generation of turning behavior. The sign of the response (i.e., excitation or inhibition) to skin stimulation of a neuron during turns toward (ipsilateral), or away from (contralateral) the side of the cell body was always the same. The cells could thus be divided into four types: 1) cells that were excited during ipsilateral turns and inhibited during contralateral turns; these cells provide an asymmetric excitatory bias to spinal networks and presumably play an important role for the generation of turns; these cells were common ( n = 35; 52%) in both MRRN and PRRN; 2) cells that were excited during turns in either direction; these cells were common ( n = 19; 28%), in particular in MRRN; they could be involved in a general activation of the locomotor system after skin stimulation; some of the cells were also more activated during turns in one direction and could contribute to an asymmetric turn command; 3) one cell that was inhibited during ipsilateral turns and excited during contralateral turns; and 4) cells ( n = 12; 18%) that were inhibited during turns in either direction. In summary, our results show that, in the lamprey, the large majority of reticulospinal cells have responses during lateral turns that are indicative of a causal role for these cells in turn generation. This also suggests a considerable overlap between the command system for lateral turns evoked by skin stimulation, which was studied here, and other reticulospinal command systems, e.g., for lateral turns evoked by other types of stimuli, initiation of locomotion, and turns in the vertical planes.
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  • Karabanov, A, et al. (author)
  • Implicit and explicit learning of temporal sequences studied with the process dissociation procedure
  • 2008
  • In: Journal of neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 100:2, s. 733-739
  • Journal article (peer-reviewed)abstract
    • We studied whether temporal sequences can be learned implicitly using a process dissociation procedure (PDP). Participants performed repeated serial recalls of sequential stimuli with a random ordinal structure and fixed temporal structure. Explicit knowledge was evaluated through verbal questions and PDP analysis of two generation tasks (inclusion and exclusion). Participants were divided into two groups: in the Ordinal group, stimulus presentation was visual and the participants were instructed to repeat the ordinal structure; in the Temporal+Ordinal group, stimulus presentation was audio-visual and the participants were instructed to repeat temporal and ordinal structure. We expected predominantly implicit learning in the Ordinal group and explicit learning in the Temporal+Ordinal group. This was supported by two findings. First, a significant difference between inclusion and exclusion performance was seen only in the Temporal+Ordinal group. Second, in both groups, a negative relation was found between the degree of improvement during serial recall and a measure of explicit knowledge in the generation tasks. This relation was independent of the final level of performance during serial recall. These findings suggest that distinct implicit and explicit systems may exist for learning of temporal sequences: implicit learning is gradual and gives rise to knowledge that is inaccessible to conscious control while the explicit system is fast and results in representations that can be used to control performance in inclusion and exclusion tasks.
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  • Kozlov, Alexander K., et al. (author)
  • Mechanisms for lateral turns in lamprey in response to descending unilateral commands : a modeling study
  • 2002
  • In: Biological Cybernetics. - : Springer Science and Business Media LLC. - 0340-1200 .- 1432-0770. ; 86:1, s. 1-14
  • Journal article (peer-reviewed)abstract
    • Straight locomotion in the lamprey is, at the segmental level, characterized by alternating bursts of motor activity with equal duration and spike frequency on the left and the right sides of the body. Lateral turns are characterized by three main changes in this pattern: (1) in the turn cycle, the spike frequency, burst duration, and burst proportion (burst duration/cycle duration) increase on the turning side; (2) the cycle duration increases in both the turn cycle and the succeeding cycle; and (3) in the cycle succeeding the turn cycle, the burst duration increases on the non-turning side (rebound). We investigated mechanisms for the generation of turns in single-segment models of the lamprey locomotor spinal network. Activation of crossing inhibitory neurons proved a sufficient mechanism to explain all three changes in the locomotor rhythm during a fictive turn. Increased activation of these cells inhibits the activity of the opposite side during the prolonged burst of the turn cycle, and slows down the locomotor rhythm. Secondly, this activation of the crossing inhibitory neurons is accompanied by an increased calcium influx into the cells. This gives a suppressed activity on the turning side and a contralateral rebound after the turn, through activation of calcium-dependent potassium channels.
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  • Kozlov, A. K., et al. (author)
  • Turning behavior in lamprey in response to descending unilateral commands : Experiments and modeling
  • 2001
  • In: Neurocomputing. - 0925-2312 .- 1872-8286. ; 38, s. 1373-1378
  • Journal article (peer-reviewed)abstract
    • Steering maneuvers in vertebrates are characterized by asymmetric modulation of the cycle duration and the intensity of the symmetric rhythmic locomotor activity. In the lamprey in vitro model system, turns can be evoked by electrical skin stimuli applied to one side of the head, which give rise to descending unilateral excitatory commands. Turns are observed as increased activity on one side of the spinal cord, followed by a rebound on the other. We investigated the generation of turns in single-segment models of the lamprey locomotor spinal network, and were able to reproduce all main experimental results. Sufficient mechanisms to explain changes in the locomotor rhythm, including rebound, are asymmetric activation of crossing inhibitory neurons, accompanied by a calcium influx in these neurons.
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  • Kozlov, Alexander, et al. (author)
  • Turning behavior in lamprey in response to descending unilateral commands: experiments and modeling
  • 2000
  • Conference paper (peer-reviewed)abstract
    • Steering maneuvers in vertebrates are characterized by asymmetric modulation of the cycle duration and the intensity of the symmetric rhythmic locomotor activity. In the lamprey in vitro model system, turns can be evoked by electrical skin stimuli applied to one side of the head, which give rise to descending unilateral excitatory commands. Turns are observed as increased activity on one side of the spinal cord, followed by a rebound on the other. We investigated the generation of turns in single-segment models of the lamprey locomotor spinal network, and were able to reproduce all main experimental results. Sufficient mechanisms to explain changes in the locomotor rhythm, including rebound, are asymmetric activation of crossing inhibitory neurons, accompanied by a calcium influx in these neurons.
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