| 1. |
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| 2. |
- Nordanstig, Annika, 1974, et al.
(författare)
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EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients (EVA-TRISP) registry: basis and methodology of a pan-European prospective ischaemic stroke revascularisation treatment registry.
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- The Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration was a concerted effort initiated in 2010 with the purpose to address relevant research questions about the effectiveness and safety of intravenous thrombolysis (IVT). The collaboration also aims to prospectively collect data on patients undergoing endovascular treatment (EVT) and hence the name of the collaboration was changed from TRISP to EVA-TRISP. The methodology of the former TRISP registry for patients treated with IVT has already been published. This paper focuses on describing the EVT part of the registry.All centres committed to collecting predefined variables on consecutive patients prospectively. We aim for accuracy and completeness of the data and to adapt local databases to investigate novel research questions. Herein, we introduce the methodology of a recently constructed academic investigator-initiated open collaboration EVT registry built as an extension of an existing IVT registry in patients with acute ischaemic stroke (AIS).Currently, the EVA-TRISP network includes 20 stroke centres with considerable expertise in EVT and maintenance of high-quality hospital-based registries. Following several successful randomised controlled trials (RCTs), many important clinical questions remain unanswered in the (EVT) field and some of them will unlikely be investigated in future RCTs. Prospective registries with high-quality data on EVT-treated patients may help answering some of these unanswered issues, especially on safety and efficacy of EVT in specific patient subgroups.This collaborative effort aims at addressing clinically important questions on safety and efficacy of EVT in conditions not covered by RCTs. The TRISP registry generated substantial novel data supporting stroke physicians in their daily decision making considering IVT candidate patients. While providing observational data on EVT in daily clinical practice, our future findings may likewise be hypothesis generating for future research as well as for quality improvement (on EVT). The collaboration welcomes participation of further centres willing to fulfill the commitment and the outlined requirements.
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| 3. |
- Scheitz, Jan F, et al.
(författare)
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Cohort profile: Thrombolysis in Ischemic Stroke Patients (TRISP): a multicentre research collaboration.
- 2018
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 8:9
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Tidskriftsartikel (refereegranskat)abstract
- The ThRombolysis in Ischemic Stroke Patients (TRISP) collaboration aims to address clinically relevant questions about safety and outcomes of intravenous thrombolysis (IVT) and endovascular thrombectomy. The findings can provide observational information on treatment of patients derived from everyday clinical practice.TRISP is an open, investigator-driven collaborative research initiative of European stroke centres with expertise in treatment with revascularisation therapies and maintenance of hospital-based registries. All participating centres made a commitment to prospectively collect data on consecutive patients with stroke treated with IVT using standardised definitions of variables and outcomes, to assure accuracy and completeness of the data and to adapt their local databases to answer novel research questions.Currently, TRISP comprises 18 centres and registers >10000IVT-treated patients. Prior TRISP projects provided evidence on the safety and functional outcome in relevant subgroups of patients who were excluded, under-represented or not specifically addressed in randomised controlled trials (ie, pre-existing disability, cervical artery dissections, stroke mimics, prior statin use), demonstrated deficits in organisation of acute stroke care (ie, IVT during non-working hours, effects of onset-to-door time on onset-to-needle time), evaluated the association between laboratory findings on outcome after IVT and served to develop risk estimation tools for prediction of haemorrhagic complications and functional outcome after IVT.Further TRISP projects to increase knowledge of the effect and safety of revascularisation therapies in acute stroke are ongoing. TRISP welcomes participation and project proposals of further centres fulfilling the outlined requirements. In the future, TRISP will be extended to include patients undergoing endovascular thrombectomy.
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| 4. |
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| 5. |
- Marto, João Pedro, et al.
(författare)
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Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry.
- 2023
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Ingår i: Neurology. - 1526-632X. ; 100:7
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Tidskriftsartikel (refereegranskat)abstract
- COVID-19-related inflammation, endothelial dysfunction, and coagulopathy may increase the bleeding risk and lower the efficacy of revascularization treatments in patients with acute ischemic stroke (AIS). We aimed to evaluate the safety and outcomes of revascularization treatments in patients with AIS and COVID-19.This was a retrospective multicenter cohort study of consecutive patients with AIS receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021 tested for severe acute respiratory syndrome coronavirus 2 infection. With a doubly robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT).Of a total of 15,128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19; of those, 5,848 (38.7%) patients received IVT-only and 9,280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted OR 1.53; 95% CI 1.16-2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20-2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23-1.99), 24-hour mortality (OR 2.47; 95% CI 1.58-3.86), and 3-month mortality (OR 1.88; 95% CI 1.52-2.33). Patients with COVID-19 also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26-1.60).Patients with AIS and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 patients receiving treatment. Current available data do not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in patients with COVID-19 or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring, and establishing prognosis.The study was registered under ClinicalTrials.gov identifier NCT04895462.
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| 6. |
- Nässel, Dick, et al.
(författare)
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A large population of diverse neurons in the Drosophila central nervous system expresses short neuropeptide F, suggesting multiple distributed peptide functions
- 2008
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Ingår i: BMC Neuroscience. - : Biomed Central. - 1471-2202. ; 9:1, s. 90-125
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Tidskriftsartikel (refereegranskat)abstract
- Background Insect neuropeptides are distributed in stereotypic sets of neurons that commonly constitute a small fraction of the total number of neurons. However, some neuropeptide genes are expressed in larger numbers of neurons of diverse types suggesting that they are involved in a greater diversity of functions. One of these widely expressed genes, snpf, encodes the precursor of short neuropeptide F (sNPF). To unravel possible functional diversity we have mapped the distribution of transcript of the snpf gene and its peptide products in the central nervous system (CNS) of Drosophila in relation to other neuronal markers. Results There are several hundreds of neurons in the larval CNS and several thousands in the adult Drosophila brain expressing snpf transcript and sNPF peptide. Most of these neurons are intrinsic interneurons of the mushroom bodies. Additionally, sNPF is expressed in numerous small interneurons of the CNS, olfactory receptor neurons (ORNs) of the antennae, and in a small set of possibly neurosecretory cells innervating the corpora cardiaca and aorta. A sNPF-Gal4 line confirms most of the expression pattern. None of the sNPF immunoreactive neurons co-express a marker for the transcription factor DIMMED, suggesting that the majority are not neurosecretory cells or large interneurons involved in episodic bulk transmission. Instead a portion of the sNPF producing neurons co-express markers for classical neurotransmitters such as acetylcholine, GABA and glutamate, suggesting that sNPF is a co-transmitter or local neuromodulator in ORNs and many interneurons. Interestingly, sNPF is coexpressed both with presumed excitatory and inhibitory neurotransmitters. A few sNPF expressing neurons in the brain colocalize the peptide corazonin and a pair of dorsal neurons in the first abdominal neuromere coexpresses sNPF and insulin-like peptide 7 (ILP7). Conclusion It is likely that sNPF has multiple functions as neurohormone as well as local neuromodulator/co-transmitter in various CNS circuits, including olfactory circuits both at the level of the first synapse and at the mushroom body output level. Some of the sNPF immunoreactive axons terminate in close proximity to neurosecretory cells producing ILPs and adipokinetic hormone, indicating that sNPF also might regulate hormone production or release.
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| 7. |
- Nässel, Dick R., et al.
(författare)
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A comparative review of short and long neuropeptide F signaling in invertebrates : Any similarities to vertebrate neuropeptide Y signaling?
- 2011
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 32:6, s. 1335-1355
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Forskningsöversikt (refereegranskat)abstract
- Neuropeptides referred to as neuropeptide F (NPF) and short neuropeptide F (sNPF) have been identified in numerous invertebrate species. Sequence information has expanded tremendously due to recent genome sequencing and EST projects. Analysis of sequences of the peptides and prepropeptides strongly suggest that NPFs and sNPFs are not closely related. However, the NPFs are likely to be ancestrally related to the vertebrate family of neuropeptide Y (NPY) peptides. Peptide diversification may have been accomplished by different mechanisms in NPFs and sNPFs; in the former by gene duplications followed by diversification and in the sNPFs by internal duplications resulting in paracopies of peptides. We discuss the distribution and functions of NPFs and their receptors in several model invertebrates. Signaling with sNPF, however, has been investigated mainly in insects, especially in Drosophila. Both in invertebrates and in mammals NPF/NPY play roles in feeding, metabolism, reproduction and stress responses. Several other NPF functions have been studied in Drosophila that may be shared with mammals. In Drosophila sNPFs are widely distributed in numerous neurons of the CNS and some gut endocrines and their functions may be truly pleiotropic. Peptide distribution and experiments suggest roles of sNPF in feeding and growth, stress responses, modulation of locomotion and olfactory inputs, hormone release, as well as learning and memory. Available data indicate that NPF and sNPF signaling systems are distinct and not likely to play redundant roles.
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| 8. |
- Pauls, Dennis, et al.
(författare)
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Endocrine signals fine-tune daily activity patterns in Drosophila
- 2021
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Ingår i: Current Biology. - : Elsevier. - 0960-9822 .- 1879-0445. ; 31:18, s. 4076-
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Tidskriftsartikel (refereegranskat)abstract
- Animals need to balance competitive behaviors to maintain internal homeostasis. The underlying mechanisms are complex but typically involve neuroendocrine signaling. Using Drosophila, we systematically manipulated signaling between energy-mobilizing endocrine cells producing adipokinetic hormone (AKH), octopaminergic neurons, and the energy-storing fat body to assess whether this neuroendocrine axis involved in starvation-induced hyperactivity also balances activity levels under ad libitum access to food. Our results suggest that AKH signals via two divergent pathways that are mutually competitive in terms of activity and rest. AKH increases activity via the octopaminergic system during the day, while it prevents high activity levels during the night by signaling to the fat body. This regulation involves feedback signaling from octopaminergic neurons to AKH-producing cells (APCs). APCs are known to integrate a multitude of metabolic and endocrine signals. Our results add a new facet to the versatile regulatory functions of APCs by showing that their output contributes to shape the daily activity pattern under ad libitum access to food.
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| 9. |
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| 10. |
- Süess, Philip, 1988-
(författare)
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Unraveling the regulatory mechanisms of pupal diapause termination
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Diapause is an essential part of many insect’s life cycle and is a developmental halt induced by environmental cues in advance of deteriorating conditions. Insects typically enter diapause to avoid unfavorable environmental conditions like low temperatures, poor food quality and the absence of conspecifics. The aim of my PhD thesis was to describe how diapause is regulated and what determines its termination timing in the green-veined white butterfly Pieris napi. Answers to these questions deepens the knowledge about species distribution and population dynamics in times of a rapidly changing climate. In ectothermic insects, developmental rate generally follows a thermal performance curve (TPC) with higher temperatures leading to a faster development. However, in the diapause of P. napi low temperatures result in a higher proportion of terminations. In Chapter I, I assessed the thermal performance of diapause termination rate in P. napi by exposing them to several different temperature treatments. The diapause termination rate follows a left-shifted TPC with an optimum termination rate at 0°C and slower termination rates toward higher temperatures. This left-shifted TPC prevents the precocious termination of diapause in autumn while at the same time enabling populations to remain synchronized over a long period. Development in insects is regulated by the major developmental hormones, insulins, juvenile hormones, ecdysone, and the prothoracicotropic hormone (PTTH). The pupal diapause is regulated by the neuropeptide PTTH produced in the brain and ecdysone produced in the prothoracic glands. In Chapter II I studied this hormonal axis by assessing PTTH levels and injections with 20-hydroxyecdysone (20E), the active form of the ecdysone pathway. The PTTH neuropeptide shows diapause stage dependent changes to haemolymph levels and intracellular structure and the sensitivity to 20E returns in a time- and temperature dependent manner correlating with diapause termination progression. This indicates that diapause termination timing is regulated by the PTTH ecdysone axis and that the ecdysteroid receptor has a central part in the regulation. Diapause is a prolonged period without the ability to replenish energy resources, insects therefore accumulate resources before diapause and reduce the metabolic rate to a minimum. In Chapter III, I investigated how the diapause physiology as well as the reduced metabolic rate affect the mode of respiration. Respiratory patterns change with diapause stages and in diapause, discontinuous gas exchange is defended even at high temperatures, supporting the finding that the diapause physiology affects the metabolic rate and with it the respiratory patterns. In Chapter IV I followed up the lead from Chapter II and tested a hypothesis on the hormonal regulation of diapause termination in which the transcription factor Foxo, the ecdysteroid receptor as well as insulin interact to regulate ecdysone sensitivity. While many findings in the transcriptome and the protein levels support the hypothesis we need further investigations into this mechanism. Furthermore, the protein levels of most proteins studied do not correlate with the mRNA levels, and while this has been described under direct developing conditions too it would be interesting to study where those different levels stem from. These findings show that the three levels, temperature, metabolic rate and the hormonal pathways are tightly linked to the diapause physiology and are most likely involved in the regulation of diapause termination timing.
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| 11. |
- von Hanxleden, Reinhard, et al.
(författare)
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WCET Tool Challenge 2011: Report
- 2011
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Ingår i: Proc. 11th International Workshop on Worst-Case Execution Time (WCET) Analysis (WCET 2011). - 9781632663153 ; , s. 104-138
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Konferensbidrag (refereegranskat)abstract
- Following the successful WCET Tool Challenges in 2006 and 2008, the third event in this series was organized in 2011, again with support from the ARTIST DESIGN Network of Excellence. Following the practice established in the previous Challenges, the WCET Tool Challenge 2011 (WCC'11) defined two kinds of problems to be solved by the Challenge participants with their tools, WCET problems, which ask for bounds on the execution time, and flow-analysis problems, which ask for bounds on the number of times certain parts of the code can be executed. The benchmarks to be used in WCC'11 were debie1, PapaBench, and an industrial-strength application from the automotive domain provided by Daimler. Two default execution platforms were suggested to the participants, the ARM7 as "simple target" and the MPC5553/5554 as a "complex target", but participants were free to use other platforms as well. Ten tools participated in WCC'11: aiT, AstrEe, Bound-T, FORTAS, METAMOC, OTAWA, SWEET, TimeWeaver, TuBound and WCA.
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| 12. |
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| 13. |
- Wegener, Konrad, et al.
(författare)
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Recent developments in grinding machines
- 2017
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Ingår i: CIRP Annals - Manufacturing Technology. - : Elsevier BV. - 1726-0604 .- 0007-8506. ; 66:2, s. 779-802
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Tidskriftsartikel (refereegranskat)abstract
- Grinding is often the final step in the process/manufacturing chain, meaning that no subsequent post-grinding correction of the surface and geometry is performed. This imposes strong requirements on grinding-machine technology and on the understanding of this finalising process. While grinding has unique capabilities it is nevertheless in competition with other machining processes. The evolution of grinding machines is driven by process requirements like accuracy, MRR, and subsurface integrity. The regeneration of the tool on the machine with dressing devices is to be regarded as unique for grinding machines, hence a grinding machine always runs two separate processes. The high accuracy of grinding has, in fact, been an obstacle to simply adopting developments from other machining processes. Also, a lack of experienced machinists and a general trend towards individualized products and one-piece flow has required a transition from an experience-based approach to a science-based approach. Development is further driven by market demands, such as cost-reduction in terms of CAPEX, footprint, TCO versus quality, and throughput, which affect business models and the machine's design and construction. Moreover, the current mega-trends – such as resource efficiency, individualization, ergonomics and Industry 4.0 – are changing the appearance of grinding machines, which is also affected by the availability of new technologies, especially sensors, actuators and the control or machine intelligence. This paper reviews the most-relevant technologies, assesses their impact and the readiness of industry to adopt them, identifies the still-open issues, and concludes with future research requirements.
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| 14. |
- Zandawala, Meet, et al.
(författare)
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A neuroendocrine pathway modulating osmotic stress in Drosophila
- 2021
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 17:3
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Tidskriftsartikel (refereegranskat)abstract
- Environmental factors challenge the physiological homeostasis in animals, thereby evoking stress responses. Various mechanisms have evolved to counter stress at the organism level, including regulation by neuropeptides. In recent years, much progress has been made on the mechanisms and neuropeptides that regulate responses to metabolic/nutritional stress, as well as those involved in countering osmotic and ionic stresses. Here, we identified a peptidergic pathway that links these types of regulatory functions. We uncover the neuropeptide Corazonin (Crz), previously implicated in responses to metabolic stress, as a neuroendocrine factor that inhibits the release of a diuretic hormone, CAPA, and thereby modulates the tolerance to osmotic and ionic stress. Both knockdown of Crz and acute injections of Crz peptide impact desiccation tolerance and recovery from chill-coma. Mapping of the Crz receptor (CrzR) expression identified three pairs of Capa-expressing neurons (Va neurons) in the ventral nerve cord that mediate these effects of Crz. We show that Crz acts to restore water/ion homeostasis by inhibiting release of CAPA neuropeptides via inhibition of cAMP production in Va neurons. Knockdown of CrzR in Va neurons affects CAPA signaling, and consequently increases tolerance for desiccation, ionic stress and starvation, but delays chill-coma recovery. Optogenetic activation of Va neurons stimulates excretion and simultaneous activation of Crz and CAPA-expressing neurons reduces this response, supporting the inhibitory action of Crz. Thus, Crz inhibits Va neurons to maintain osmotic and ionic homeostasis, which in turn affects stress tolerance. Earlier work demonstrated that systemic Crz signaling restores nutrient levels by promoting food search and feeding. Here we additionally propose that Crz signaling also ensures osmotic homeostasis by inhibiting release of CAPA neuropeptides and suppressing diuresis. Thus, Crz ameliorates stress-associated physiology through systemic modulation of both peptidergic neurosecretory cells and the fat body in Drosophila.
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