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Intracranial pressure dynamics, cerebral autoregulation, and brain perfusion after decompressive craniectomy in malignant middle cerebral artery infarction : is there a role for invasive monitoring?
No full textObjective Malignant middle cerebral artery infarction (MMI) is a severe neurological condition. Decompressive craniectomy (DC) is an established lifesaving surgical treatment. However, the role of neurocritical care with monitoring and management of the intracranial pressure (ICP), pressure reactivity index (PRx), cerebral perfusion pressure (CPP), and optimal perfusion pressure (CPPopt) remain unclear. This study aims to examine the dynamics of these variables post-DC in relation to clinical outcome. Methods This retrospective study included 70 MMI patients who underwent DC with ICP monitoring of at least 12 hours and available data of clinical outcome (modified Rankin Scale [mRS] at 6 months). The associations between mRS and cerebral physiology (ICP, PRx, CPP, and ∆CPPopt) was analysed and presented in different outcome heatmaps over the first 7 days following DC. Results ICP above 15 mmHg was associated with unfavourable outcome, particularly for longer durations. As PRx exceeded zero, outcome worsened progressively, and values above 0.5 correlated to poor outcome regardless of duration. As CPP dropped below 80 mmHg, there was a transition from favourable to unfavourable outcome. Negative ∆CPPopt, particularly below -20 mmHg, corresponded to unfavourable outcome. In two-variable heatmaps, elevated PRx combined with high ICP, low CPP or negative ∆CPPopt correlated with worse outcome. Conclusion Invasive ICP-monitoring may provide prognostic information for long-term recovery in MMI patients post-DC. The study highlighted disease-specific optimal physiological intervals for ICP, PRx, CPP, and ΔCPPopt. Of particular interest, the autoregulatory variable, PRx, influenced the safe and dangerous ICP, CPP, and ∆CPPopt intervals
Validation and diagnostic study of cloudburst events over the Himalayan region using IMDAA and ERA5
No full textA cloudburst is characterised by intense localised rainfall over a brief period, often resulting in significant damage, particularly in high-elevation areas like the Himalayan region. Consequently, it is crucial to anticipate these disastrous events to avoid the associated damage. The objective is to compare the performance of two reanalysis datasets i.e. Indian Monsoon Data Assimilation and Analysis (IMDAA) and fifth-generation European Centre for Medium-Range Weather Forecasts (ERA5), to comprehend the atmospheric dynamics associated with the cloudburst events over the Himalayan region. Four cloudburst cases are analysed during the Southwest Monsoon season, affecting areas at elevations between 1600 and 2100 meters. Daily accumulated rainfall from both reanalyses is compared with the Global Precipitation Measurement (GPM). The results indicate that IMDAA outperforms ERA5, with a mean Pearson correlation of 0.56 versus 0.35, though both datasets underestimate rainfall. IMDAA shows a minor underestimation with a mean bias of -0.74 mm, while ERA5 underestimates more significantly, with a mean bias of -2.52 mm. Additionally, various atmospheric parameters, including vertically integrated moisture transport, relative humidity, wind fields, potential vorticity, outgoing longwave radiation, and various instability indices, are analysed to investigate the mechanisms behind these cloudburst events. Overall, the high-resolution IMDAA reanalysis outperformed the low-resolution ERA5
Biodistribution and toxicity evaluation of oncolytic adenovirus Adf35(OGN) in Syrian hamster and mouse
No full textOncolytic adenovirus has been widely evaluated as a cancer treatment agent with tolerable toxicity profile. We have recently developed a new oncolytic adenovirus Adf35(OGN) with two immunostimulatory transgenes alpha-1,3-galactosyltransferase (GGTA1) from Sus scrofa and neutrophil-activating protein (NAP) from Helicobacter pylori. Adf35(OGN) can kill tumor cells and trigger a strong immune response against tumor antigens. Here, we report the toxicity and biodistribution of Adf35(OGN) in Syrian hamster and GGTA1-knockout mouse. The virus was delivered subcutaneously in naïve hamsters and intratumorally in GGTA1-knockout mouse in multiple doses at dosages of 1–5 × 1011 viral particles (VP)/kg. The virus did not replicate in any tissues, evidenced as low or no viral copies detected by qPCR. The virus was also found at low levels in biofluids (saliva, urine, and feces), indicating that spread to the environment is low with a low risk of secondary infections via shedding. The virus did not cause any biochemical, hematological, or histopathological alterations. In summary, Adf35(OGN) has a good safety profile in these animal models and these results support future clinical evaluation for Adf35(OGN)
Online Learning for Intelligent Thermal Management of Interference-Coupled and Passively Cooled Base Stations
No full textPassively cooled base stations (PCBSs) have emerged to deliver better cost and energy efficiency. However, passive cooling necessitates intelligent thermal control via traffic management, i.e., the instantaneous data traffic or throughput of a PCBS directly impacts its thermal performance. This is particularly challenging for outdoor deployment of PCBSs because the heat dissipation efficiency is uncertain and fluctuates over time. What is more, the PCBSs are interference-coupled in multi-cell scenarios. Thus, a higher-throughput PCBS leads to higher interference to the other PCBSs, which, in turn, would require more resource consumption to meet their respective throughput targets. In this paper, we address online decision-making for maximizing the total downlink throughput for a multi-PCBS system subject to constraints related on operating temperature. We demonstrate that a reinforcement learning (RL) approach, specifically soft actor-critic (SAC), can successfully perform throughput maximization while keeping the PCBSs cool, by adapting the throughput to time-varying heat dissipation conditions. Furthermore, we design a denial and reward mechanism that effectively mitigates the risk of overheating during the exploration phase of RL. Simulation results show that our approach achieves up to 88.6% of the global optimum. This is very promising, as our approach operates without prior knowledge of future heat dissipation efficiency, which is required by the global optimum
Effects of Melatonin on Caco-2 cells with a Synchronized Circadian Rhythm
No full textThe circadian rhythm is a 24-hour cycle that regulates physiological and mental processes across organisms. In peripheral tissues, the rhythm is regulated by so-called clock genes, such as BMAL1 and PER2, which maintain the synchronization through feedback loops. Almost half of human genes are regulated by clock gene expression. Melatonin, a metabolite produced by gut microbiota, has previously been shown to affect gene expression, as well as supporting the sleep-wake cycle and regulating immune responses. In vitro cell cultures often involve unsynchronized cells, which do not follow the same rhythm, they can however, be synchronized to produce a more physiologically relevant model. In this study, Caco-2 cells were synchronized using dexamethasone, and were thereafter used to investigate melatonin's effect on clock gene expression of BMAL1 and PER2. Gene expression analysis of the target genes and housekeeping genes GAPDH and RPLP0 was performed using qPCR. The results were inconclusive regarding melatonin's effect on clock gene expression. Further analyses revealed instead that exposure to melatonin caused a significant increase in variance of housekeeping genes. These findings highlight the importance of housekeeping gene validation and I provide suggestions for a solution applicable in future similar research; Performing validation of housekeeping genes in the presence of intended exposures, as well as on the intended cell line for greater reliability.
Enduring intensity for healing : the patient perspective of intensive outpatient treatment for PTSD
No full textBackground:Prolonged exposure is widely regarded as a first-line treatment for alleviating symptoms of post-traumatic stress disorder (PTSD); however, it is often associated with high dropout rates and may not always be sufficiently efficacious. Intensified treatment has been suggested as a solution to increase treatment efficacy and reduce dropout rates, but little is known about patients' preferences for this type of treatment.Objective:To investigate patients' experiences of prolonged exposure delivered in an intensive format (iPE). Method:Semi-structured interviews were conducted with 12 participants after completion of iPE. Results:Thematic analysis of the data yielded one overarching theme 'Brutal Yet Worth It,' accompanied by five subthemes: Building Blocks of Commitment, Strength through collective support, Overcoming challenges of the intensive treatment week, Therapeutic gains of the intensive treatment, and Facilitating and Enabling Treatment Progress. The participants described short-term discomfort and demands, contrasted with the recognition of substantial benefits that extended beyond PTSD symptom reduction. The interplay of individual attributes and experience of social support emerged as crucial factors shaping the experience. Conclusions:Participants described the iPE experience as intense and demanding, yet transformative and worthwhile in the interviews. These findings highlight the complex and multifaceted experiences of patients undergoing PE delivered in an intensive format. The findings could offer valuable insights for designing more well-received PTSD treatments, leading to enhancements in the overall quality of intensified treatment approaches.Antecedentes: La exposición prolongada es ampliamente considerada como un tratamiento de primera línea para aliviar los síntomas del trastorno de estrés postraumático (TEPT); sin embargo, suele asociarse con altas tasas de abandono y puede no ser siempre lo suficientemente eficaz. Se ha sugerido el tratamiento intensivo como solución para aumentar la eficacia del tratamiento y reducir las tasas de abandono, pero se sabe poco sobre las preferencias de los pacientes por este tipo de tratamiento. Objetivo: Investigar las experiencias de los pacientes con exposición prolongada administrada en un formato intensivo (EPi). Método: Se realizaron entrevistas semiestructuradas con 12 participantes después de finalizar la EPi. Resultados: El análisis temático reflexivo de los datos arrojó un tema general: ‘Brutal, pero vale la pena’, acompañado de cinco subtemas: Elementos fundamentales del compromiso, Fortalecimiento a través del apoyo colectivo, Superación de los desafíos de la semana de tratamiento intensivo, Beneficios terapéuticos del tratamiento intensivo y Permitir y facilitar el progreso del tratamiento. Los participantes describieron malestar y exigencia en el corto plazo, en contraste con el reconocimiento de beneficios sustanciales que se extendieron más allá de la reducción de los síntomas del TEPT. La interacción entre los atributos individuales y la experiencia de apoyo social surgieron como factores cruciales que moldearon la experiencia. Conclusiones: En las entrevistas, los participantes describieron la experiencia de EPi como intensa y exigente, pero a la vez transformadora y valiosa. Estos hallazgos resaltan la complejidad y la multifacética experiencia de los pacientes sometidos a EP en un formato intensivo. Estos hallazgos podrían ofrecer información valiosa para diseñar tratamientos para el TEPT con mayor aceptación, lo que se traduciría en mejoras en la calidad general de los enfoques de tratamiento intensivo
Oligodendroglia vulnerability in the human dorsal striatum in Parkinson's disease
No full textOligodendroglia are the responsible cells for myelination in the central nervous system and their involvement in Parkinson's disease (PD) is poorly understood. We performed sn-RNA-seq and image-based spatial transcriptomics of human caudate nucleus and putamen (dorsal striatum) from PD and control brain donors to elucidate the diversity of oligodendroglia and how they are affected by the disease. We profiled a total of similar to 200.000 oligodendroglial nuclei, defining 15 subclasses, from precursor to mature cells, 4 of which are disease-associated. These PD-specific populations are characterized by the overexpression of heat shock proteins, as well as distinct expression signatures related to immune responses, myelination alterations, and disrupted cell signaling pathways. We have also identified impairments in cell communication and oligodendrocyte development, evidenced by changes in neurotransmitter receptors expression and cell adhesion molecules. In addition, we observed significant disruptions in oligodendrocyte development, with aberrant differentiation trajectories and shifts in cell proportions, particularly in the transition from mature oligodendrocytes to disease-associated states. Quantitative immunohistochemical analysis revealed decreased myelin levels in the PD striatum, which correlated with transcriptomic alterations. Furthermore, spatial transcriptomics mapping revealed the distinct localization of disease-associated populations within the striatum, with evidence of impaired myelin integrity. Thus, we uncover oligodendroglia as a critical cell type in PD and a potential new therapeutic target for myelin-based interventions
Epidemiological outcomes and policy implementation in the Nordic countries during the COVID-19 pandemic
No full textBackground During the initial phase of the COVID-19 pandemic, there was an intensive debate on which strategies would be most effective to minimize the negative societal impact of the pandemic. This study aimed to provide an overview of key epidemiological outcome measures of the disease in the Nordic countries and the subsequent policy implementation that were undertaken to curb the outbreak. Methods Time trends in test-positive infections, hospitalizations, and intensive care unit (ICU) admissions due to COVID-19 as well as COVID-19 mortality and excess mortality were compared between Denmark, Finland, Iceland, Norway, and Sweden. The epidemiological patterns were presented in relation to 13 different policies implemented to a different degree in the countries, eight of which were related to containment and five to health systems policy. A stringency index summarized the intensity of the policies. Data were collected from Our World in Data, the Oxford COVID-19 Government Response Tracker and Eurostat. The investigated time period was 1 January 2020 to 30 April 2022. Results Overall, Sweden had more infections, deaths, hospitalizations, and ICU admissions than the other Nordic countries during the first three waves of the pandemic. However, in the fourth wave, Denmark exceeded Sweden in all outcomes. The overall stringency among the Nordic countries varied broadly. The lowest average stringency index was observed in Iceland and the highest in Sweden. Excess mortality over the whole study period was lowest in Iceland while Norway had very few ICU admissions. Conclusions The Nordic countries took vastly different approaches to contain the spread of the pandemic, but the long-term impact on excess mortality was similar. The variety in policy responses and epidemiological measures bring many opportunities for learning across the countries
Are mainstream and populist right party positions on immigration converging? : A study of normalization dynamics in debates on immigration in the European Affairs Committee of the Swedish Parliament, 2012-2024
No full textPrevious research shows that mainstream and populist right parties’ positions can influence each other and converge, normalizing populist right positions. The 2015 refugee crisis made this dynamic increasingly relevant, especially regarding migration policy, as support for populist right parties increased and migration policies across Europe became stricter. While studies examine the convergence of mainstream and populist right positions on immigration for several European countries, no such research exists for Sweden, despite its shift from generous to strict refugee policies over the past decade. Therefore, this study examined whether a normalization of populist right positions on immigration, driven by the convergence of mainstream and populist right parties, occurred in Sweden over the past decade, as has been shown elsewhere in Europe. By analyzing and coding over 250 statements from the European Affairs Committee between 2012-2024, it tracked the development of Swedish parliamentary parties' immigration positions using time series graphs and textual analysis. The results showed that the normalization of populist right positions on immigration is more likely to occur concerning populist right positions on state security than criticism of the EU’s competence in the migration field. In addition, it showed that the mainstream right Moderate Party (Moderaterna) moved to a greater extent towards the populist right Sweden Democrats (Sverigedemokraterna) than the mainstream left Social Democrats (Socialdemokraterna) did. Finally, the Sweden Democrats did not move towards the position of the mainstream parties
Functional studies of structural elements in toti-like virus through the development of new fluorescence-based methods
No full textOmono River virus (OmRV), which infects Culex mosquitoes, belongs to the group of dsRNA toti-like viruses. Some members of toti-like viruses have a large negative impact on the fishing industry, which has increased the interest in understanding their propagation cycle. The structural elements of the OmRV such as the obstructed 5-fold pores and the surface crown proteins (CrPs) have been hypothesized to be of importance for viral particle replication as well as the ability of the virus to recognize and enter the host as part of the transmission cycle. In this study, a newly developed method based on fluorescence in situ hybridization (FISH) was used to observe the effect of OmRV pore mutants on viral particle genome transcription. Immobilized-metal affinity chromatography-based pull-down assays and Förster resonance energy transfer (FRET) assays were used to study the interactions between the CrPs and the viral capsid in vitro. The results show that perturbation of the obstructed pore function has a negative impact on viral propagation. One of the mutants, R925A, resulted in a reduction of viral nascent (+)ssRNA synthesis. The findings are to our knowledge the first indication that positively charged arginine residues in the pore structure might be crucial for intraparticle genome synthesis. Specific CrPs-capsid interaction could however not be detected using these in vitro methods, indicating the need for additional optimization to allow for detection of the weak and transient interactions between CrPs and capsid structure. In summary, these studies and a further development of quantitative methods will serve as starting point for and lead to a deeper understanding of the transmission cycle of the dsRNA toti-like virus family, including also the economically and societal important variants