Accessing the vasculature in cancer: revising an old hallmark.

The classic cancer hallmark, inducing angiogenesis, was born out of the long-held notion that tumours could grow only if new vessels were formed. The attempts, based on this premise, to therapeutically restrain angiogenesis in hopes of controlling tumour growth have been less effective than expected. This is partly because primary and metastatic tumours can grow without angiogenesis. The discovery of nonangiogenic cancers and the mechanisms they use to exploit normal vessels, called 'vessel co-option,' has opened a new field in cancer biology. Consequently, the cancer hallmark, 'inducing angiogenesis,' has been modified to 'inducing or accessing vasculature.'

Dynamics of Daily Glioblastoma Evolution During Chemoradiation Therapy on the 0.35T Magnetic Resonance Imaging-Linear Accelerator.

PURPOSE: Glioblastoma changes during chemoradiation therapy are inferred from magnetic resonance imaging (MRI) before and after treatment but are rarely investigated due to logistics of frequent MRI. Using a combination MRI-linear accelerator (MRI-linac), we evaluated changes during daily chemoradiation therapy. METHODS AND MATERIALS: Patients with glioblastoma were prospectively imaged daily during chemoradiation therapy on 0.35T MRI-linac and at 3 timepoints with and without contrast on standalone high-field MRI. Tumor or edema (lesion) and resection cavity dynamics throughout treatment were analyzed and compared with standalone T1 postcontrast (T1+C) and T2 volumes. RESULTS: Of 36 patients included in this analysis, 8 had cavity only, 12 had lesion only, and 16 had both cavity and lesion. Of these, 64% had lesion growth and 46% had cavity shrinkage during treatment on MRI-linac scans. The average MRI-linac migration distance was 1.3 cm (range, 0-4.1 cm) for lesion and 0.6 cm (range, 0.1-2.1 cm) for cavity. Standalone versus MRI-linac volumes correlated strongly with R2 values: 0.991 (T2 vs MRI-linac cavity), 0.972 (T1+C vs MRI-linac cavity), and 0.973 (T2 vs MRI-linac lesion). There was a moderate correlation between T1+C and MRI-linac lesion (R2 = 0.609), despite noncontrast MRI-linac inability to separate contrast enhancement from surrounding nonenhancing tumor and edema. From pretreatment to posttreatment in patients with all available scans (n = 35), T1+C and MRI-linac lesions changed together-shrank (n = 6), grew (n = 12), or unchanged (n = 8)-in 26 (74%) patients. Another 9 patients (26%) had growth on MRI-linac, although the T1+C component shrank. In no patient did T1+C lesion grow while MRI-linac lesion shrank. CONCLUSIONS: Anatomic changes are seen in patients with glioblastoma imaged daily on MRI-linac throughout the chemoradiation therapy course. As surgical resection cavities shrink, margins may be reduced to save normal brain. Patients with unresected or growing lesions may require margin expansions to cover changes. Limited volume glioblastoma boost trials could consider triggered gadolinium contrast administration for evaluation of adaptive radiation therapy when lesion growth is seen on noncontrast MRI-linac.

Analytical Gradients for Electron-Attached and Ionized States for the Algebraic-Diagrammatic Construction Scheme for the Electron Propagator up to Third Order.

The derivation and implementation of analytical gradients for methods based on the non-Dyson algebraic diagrammatic construction for the electron propagator, IP-ADC and EA-ADC, up to the third order is presented. Using nuclear gradients, ground-state equilibrium structures for small open-shell systems are calculated. In addition, we investigated the performance of IP/EA-ADC methods for the calculation of adiabatic ionization potentials and electron affinities for medium-sized organic molecules.

Comparing third-party responsibility with intention attribution: An fMRI investigation of moral judgment.

Neuroimaging studies demonstrate that moral responsibility judgments activate the social cognition network, presumably reflecting mentalising processes. Conceptually, establishing an agent's intention is a sub-process of responsibility judgment. However, the relationship between both processes on a neural level is poorly understood. To date, neural correlates of responsibility and intention judgments have not been compared directly. The present fMRI study compares neural activation elicited by third-party judgments of responsibility and intention in response to animated pictorial stimuli showing harm events. Our results show that the social cognition network, in particular Angular Gyrus (AG) and right Temporo-Parietal Junction (RTPJ), showed stronger activation during responsibility vs. intention evaluation. No greater activations for the reverse contrast were observed. Our imaging results are consistent with conceptualisations of intention attribution as a sub-process of responsibility judgment. However, they question whether the activation of the social cognition network, particularly AG/RTPJ, during responsibility judgment is limited to intention evaluation.

Far-future hydrology will differentially change the phosphorus transfer continuum.

Climate change is likely to exacerbate land to water phosphorus (P) transfers, causing a degradation of water quality in freshwater bodies in Northwestern Europe. Planning for mitigation measures requires an understanding of P loss processes under such conditions. This study assesses how climate induced changes to hydrology will likely influence the P transfer continuum in six contrasting river catchments using Irish national observatories as exemplars. Changes or stability of total P (TP) and total reactive P (TRP) transfer processes were estimated using far-future scenarios (RCP4.5 and RCP8.5) of modelled river discharge under climate change and observed links between hydrological regimes (baseflow and flashiness indices) and transfer processes (mobilisation and delivery indices). While there were no differences in P mobilisation between RCP4.5 and RCP8.5, both mobilisation and delivery were higher for TP. Comparing data from 2080 (2070-2099) with 2020 (2010-2039), suggests that P mobilisation is expected to be relatively stable for the different catchments. While P delivery is highest in hydrologically flashy catchments, the largest increases were in groundwater-fed catchments in RCP8.5 (+ 22% for TRP and + 24% for TP). The inter-annual variability of P delivery in the groundwater-fed catchments is also expected to increase. Since the magnitude of a P source may not fully define its mobility, and hydrological connections of mobilisation areas are expected to increase, we recommend identifying critical mobilisation areas to target future mitigation strategies. These are hydrologically connected areas where controls such as soil/bedrock chemistry, biological activity and hydrological processes are favourable for P mobilisation.

Movement synchrony among dance performers predicts brain synchrony among dance spectators.

Performing dance is an intrinsically social art form where at least one person moves while another person watches. Dancing in groups promotes social bonding, but how does group dance affect the people watching? A group of dancers and dance novices watched a 30 min dance video individually in an fMRI scanner. In a follow-up behavioural study, the same people watched the video again and provided continuous enjoyment ratings. Firstly, we computed cross-recurrence of continuous enjoyment ratings and inter-subject correlations (ISCs) in fMRI separately for both groups, and with the choreographer of the dance work. At both behavioural and neural levels, dancers responded more similarly to each other than novices. ISCs among dancers extended beyond brain areas involved in audio-visual integration and sensory areas of human movement perception into motor areas, suggesting greater sensorimotor familiarity with the observed dance movements in the expert group. Secondly, we show that dancers' brain activations and continuous ratings are more similar to the choreographer's ratings in keeping with sharing an aesthetic and artistic perspective when viewing the dance. Thirdly, we show that movement synchrony among performers is the best predictor of brain synchrony among both expert and novice spectators. This is consistent with the idea that changes in emergent movement synchrony are a key aesthetic feature of performing dance. Finally, ISCs across perceptual and motor brain areas were primarily driven by movement acceleration and synchrony, whereas ISCs in orbital and pre-frontal brain areas were overall weaker and better explained by the continuous enjoyment ratings of each group. Our findings provide strong evidence that the aesthetic appreciation of dance involves a common experience between dance spectators and the choreographer. Moreover, the similarity of brain activations and of enjoyment increases with shared knowledge of - and practice in - the artform that is being experienced, in this case contemporary performing dance.

Fourth-Order Algebraic Diagrammatic Construction for Electron Detachment and Attachment: The IP- and EA-ADC(4) Methods.

We present a non-Dyson fourth-order algebraic diagrammatic construction formulation of the electron propagator, featuring the distinct IP- and EA-ADC(4) schemes for the treatment of ionization and electron attachment processes. The algebraic expressions have been derived automatically using the intermediate state representation approach and implemented in the Q-Chem quantum-chemical program package. The performance of the novel methods is assessed with respect to high-level reference data for ionization potentials and electron affinities of closed- and open-shell systems. While only minor improvements over the corresponding third-order methods are observed for one-hole ionization and one-particle electron attachment processes from closed-shell systems (MAEIP-ADC(4) = 0.27 eV and MAEEA-ADC(4) = 0.05 eV), a significantly enhanced performance is found in case of open-shell reference states (MAEIP-ADC(4) = 0.11 eV and MAEEA-ADC(4) = 0.02 eV). A particularly appealing feature of the novel methods is their accurate treatment of satellite transitions. For closed-shell reference states, we obtain accuracies of MAEIP-ADC(4) = 0.81 eV and MAEEA-ADC(4) = 0.27 eV, while in case of open-shell reference states, mean absolute errors of MAEIP-ADC(4) = 0.15 eV and MAEEA-ADC(4) = 0.27 eV are found.

Population structure and pathogen interaction of Escherichia coli in freshwater: Implications of land-use for water quality and public health in Aotearoa New Zealand.

Freshwater samples (n = 199) were obtained from 41 sites with contrasting land-uses (avian, low impact, dairy, urban, sheep and beef, and mixed sheep, beef and dairy) and the E. coli phylotype of 3980 isolates (20 per water sample enrichment) was determined. Eight phylotypes were identified with B1 (48.04%), B2 (14.87%) and A (14.79%) the most abundant. Escherichia marmotae (n = 22), and Escherichia ruysiae (n = 1), were rare (0.68%) suggesting that these environmental strains are unlikely to confound water quality assessments. Phylotypes A and B1 were overrepresented in dairy and urban sites (p < 0.0001), whilst B2 were overrepresented in low impact sites (p < 0.0001). Pathogens ((Salmonella, Campylobacter, Cryptosporidium or Giardia) and the presence of diarrhoeagenic E. coli-associated genes (stx and eae) were detected in 89.9% (179/199) samples, including 80.5% (33/41) of samples with putative non-recent faecal inputs. Quantitative PCR to detect microbial source tracking targets from human, ruminant and avian contamination were concordant with land-use type and E. coli phylotype abundance. This study demonstrated that a potential recreational health risk remains where pathogens occurred in water samples with low E. coli concentration, potential non-recent faecal sources, low impact sites and where human, ruminant and avian faecal sources were absent.

The influence of biotic and abiotic factors on the bacterial microbiome of gentoo penguins (Pygoscelis papua) in their natural environment.

The microbiome is a key factor in the health, well-being, and success of vertebrates, contributing to the adaptive capacity of the host. However, the impact of geographic and biotic factors that may affect the microbiome of wild birds in polar environments is not well defined. To address this, we determined the bacterial 16S rRNA gene sequence profiles in faecal samples from pygoscelid penguin populations in the Scotia Arc, focusing on gentoo penguins. This mesopredatory group breeds in defined colonies across a wide geographic range. Since diet could influence microbiome structure, we extracted dietary profiles from a eukaryotic 18S rRNA gene sequence profile. The bacterial microbiome profiles were considered in the context of a diverse set of environmental and ecological measures. Integrating wide geographic sampling with bacterial 16S and eukaryotic 18S rRNA gene sequencing of over 350 faecal samples identified associations between the microbiome profile and a suite of geographic and ecological factors. Microbiome profiles differed according to host species, colony identity, distance between colonies, and diet. Interestingly there was also a relationship between the proportion of host DNA (in relation to total 18S rRNA gene signal) and the microbiome, which may reflect gut passage time. Colony identity provided the strongest association with differences in microbiome profiles indicating that local factors play a key role in the microbiome structure of these polar seabirds. This may reflect the influence of local transfer of microbes either via faecal-oral routes, during chick feeding or other close contact events. Other factors including diet and host species also associate with variation in microbiome profile, and in at least some locations, the microbiome composition varies considerably between individuals. Given the variation in penguin microbiomes associated with diverse factors there is potential for disruption of microbiome associations at a local scale that could influence host health, productivity, and immunological competence. The microbiome represents a sensitive indicator of changing conditions, and the implications of any changes need to be considered in the wider context of environmental change and other stressors.

Incidence and characterization of polyglucosan bodies in the cerebella of montserrat orioles (Icterus oberi).

Polyglucosan bodies are accumulations of insoluble glucose polymers and proteins that form intracytoplasmic inclusions in the brain, large numbers of which can be indicative of neurodegenerative diseases such as Lafora disease. Montserrat orioles (Icterus oberi) are an icterid passerine endemic to Montserrat with conservation populations maintained in captivity abroad. We demonstrate that polyglucosan bodies are unusually abundant in the cerebellar molecular and Purkinje cell layers and cerebellar peduncles of captive-bred and wild-caught Montserrat orioles. The bodies are periodic acid-Schiff positive and diastase resistant and label with concanavalin A and for ubiquitin, consistent with those seen in humans. We found no association of the polyglucosan bodies with concurrent neurological lesions or clinical signs, nor with EPM2A and EPM2B gene mutations associated with Lafora disease. We conclude that an abundance of cerebellar polyglucosan bodies may be a normal finding in aged Montserrat orioles and not a threat to the captive breeding population.

Treatment of prolonged seizure with diazepam nasal spray: An exploratory post hoc cohort analysis.

BACKGROUND: Benzodiazepines are used in first-line rescue therapy as immediate-use seizure medication for the treatment of seizure clusters and prolonged seizures. Their use varies across clinical practices and conditions, and they can be used promptly when indicated. Clinical studies have demonstrated seizure termination within 2 min when diazepam nasal spray is used to treat seizure clusters within 5 min, but the response when treating longer duration seizures in a cluster remains to be characterized. OBJECTIVE: To describe and assess timing and dosing of diazepam nasal spray in the subset of prolonged seizures within seizure clusters in a larger dataset of all treated seizure clusters collected during a long-term safety study of diazepam nasal spray. METHODS: Using timing data recorded in seizure diaries, this post hoc analysis and associated sensitivity analyses focused on prolonged seizures treated 5 to 15 min after the seizure start. Measures included time to treatment administration and time to seizure termination. Second-dose data were used as a proxy for effectiveness. RESULTS: In this group of seizure clusters treated 5 to 15 min after seizure start, median time drug administration was 6 min after seizure start, median time from drug administration to seizure termination was 7 min, and median overall seizure duration was 15 min. Sensitivity analyses by age, epilepsy type, and high seizure frequency confirmed this pattern. Use of a second dose occurred in 9.3 % of episodes, with the majority of second doses administered ≤ 4 h after the first dose. Safety results from the overall study showed 82.2 % of patients had ≥ 1 treatment-emergent adverse event (TEAE) irrespective of relationship to treatment, during a mean participation of âˆ¼ 1.5 years. In addition, 30.7 % patients had a serious TEAE, and 18.4 % had TEAEs deemed at least possibly related to the study drug, none of which were serious. No events of cardiorespiratory depression were reported. CONCLUSIONS: Although immediate use of diazepam nasal spray (within 5 min) resulted in quicker seizure termination, a treatment delay of 5 to 15 min still produced rapid termination of the seizure cluster with high first-dose effectiveness and an overall acceptable safety profile. These findings suggest that diazepam nasal spray maintains effectiveness in prolonged seizures within a cluster with delayed treatment.

Low cytoplasmic NUB1 protein exerts hypoxic cell death with poorer prognosis in oestrogen receptor negative breast cancer patients.

Current prognostic biomarkers fall short in stratifying Oestrogen receptor (ER)-negative breast cancer patients regarding tumour progression risk at diagnosis. The role of AIPL1 in activating its tumour suppressor client protein, NEDD8 Ultimate Buster-1 (NUB1) remains unknown in cancer. Our study demonstrated how downregulated AIPL1 results in the deactivated NUB1 protein under hypoxic conditions. We examined the AIPL1-NUB1 pathwayin vitro using cell lines i.e. MCF-7, MDA-MB-231, RCC4 etc. NUB1 expression was assessed using Oncomine, and cBioPortal was performed to assess NUB1's prognostic significance in human cancers. In the John Radcliffe Hospital cohort (n = 122), immunohistochemistry analysis revealed downregulated AIPL1 (Log2 fold change=-0.28; p < 0.001) and upregulated NUB1 transcripts (Log2 fold change=0.59; p < 0.001) compared to adjacent normal tissues. In severe chronic hypoxia, multimerised AIPL1 localisedin the cytoplasm while NUB1 protein migrated to the nucleus, where the absence of NUB1 nuclear localisation led to cell cycle arrest. Biopsies showed that patients with lower cytoplasmic NUB1 expression (n = 57) had poorer overall survival compared to those with higher cytoplasmic expression (n = 57), HR=1.78; 95 % CI=1.01-3.35, p = 0.048. Low NUB1 protein levels in both normoxic and hypoxic conditions were associated with cell cycle arrest and upregulation ofp21 and p27 in breast cancer cell lines, correlating significantly withpoorer survival outcomes in all breast cancer and ER-negative breast cancer patients.

Elevating leadership learning: Critical considerations for training, design, and implementation.

This article focuses on the research and scholarship of leadership training. We begin by defining and giving context to the concept of leadership training. Then, we provide a high-level literature review of the history and components of leadership training (e.g., content, pedagogy, and assessment). Next, we connect leadership training with the leadership learning framework (LLF) to address common critiques of leadership training. The article concludes with projections of leadership training in the future and ethical questions for leadership educators to consider when designing leadership training programs.

Simulation dataset of annual crop growth, GHG emission and SOC stock dynamics under current and projected climate conditions for major crops with current and reduced fertiliser inputs in Southwest, England.

For mitigating the unintended environmental impacts associated with intensive farming across the world, it is crucial to understand the complex impacts of potential reductions in fertiliser use on multiple ecosystem services, including crop production, GHG emissions and changes in soil organic carbon (SOC) stocks. Using site specific spatial data and information, a novel integrated modelling approach using established agroecosystem models (SPACSYS and RothC) was implemented to evaluate the impacts of various fertiliser reductions (10 %, 30 % and 50 %) under current / baseline and projected (RCP2.6, RCP4.5 and RCP8.5) climate scenarios in a study catchment in southwest England. 48 unique combinations of soil types, climate conditions and fertiliser inputs were evaluated for five major arable crops (winter wheat, maize, winter barley, spring barley, winter oilseed rape) plus ryegrass. Modelled annual estimates of crop yields and biomass, emissions of gases with warming potentials (nitrous oxide, methane, carbon) and SOC stocks in the topsoil (0-30 cm) were tabulated for all combinations considered. These simulated data series could be further analysed to evaluate inter-annual variations and their implications for climate resilience and combined with additional data to quantify nutrient use efficiency and undertake cost- benefit analysis, and to contribute to inter-regional comparisons of fertiliser management at broad scale.

Willingness to adopt green house gas mitigation measures: Agricultural land managers in the United Kingdom.

Rapid uptake of greenhouse gas (GHG) mitigation measures is central to reducing agricultural and land use emissions and meeting the UK Net Zero policy. The socioeconomic challenges and barriers to uptake are poorly understood, with yet unclear structural pathways to the uptake of GHG mitigation measures. Using an online survey of 201 agricultural land managers across the UK, and applying multiple linear regression and stepwise regression analysis, this research established farm and farmers' factors influencing perceptions and willingness to adopt GHG mitigation measures. The results consistently show that farm sector, farmers' business perception, and labour availability influence willingness to adopt GHG mitigation measures. Based on the farmers' qualitative feedback, other barriers to adoption include costs and concerns for profitability, lack of flexibility in land tenancy contracts, poor awareness and knowledge of the application of some GHG mitigation measures, perception about market demand e.g bioenergy crops, and scepticism about the future impacts of adopting varying GHG mitigation measures. In the midst of the ongoing net zero transition, this study identifies existing barriers to the uptake of GHG mitigation measures, and specifically, a substantial gap between farmers and the science of GHG mitigation measures and the need to incentivise a farm and farming community-led policy interventions to promote adoption of GHG mitigation measures.

A dataset of CMIP6-based climate scenarios for climate change impact assessment in Great Britain.

Climate change is a critical issue in the 21st century. Assessment of the impacts of climate change is beneficial for assisting advanced recommendations for adaptations. Climate change impact assessments require high quality local-scale climate scenarios. The future climate projections from Global Climate Models (GCMs) are problematic to use at local scale due to their coarse spatial and temporal resolution, and existing biases. It is important to have climate change scenarios based on the GCMs ensemble downscaled to local scale to account for inherent uncertainty in climate projections, and to have a sufficient large number of years to account for inter-annual climate variability and low frequency, but high impact, extreme climatic events. A dataset of future climate change scenarios was therefore generated at 26 representative sites across Great Britain based on the latest CMIP6 multi-model ensemble downscaled to local-scale by using a stochastic weather generator, LARS-WG 8.0. The data set consists of climate scenarios of daily weather of 1,000 realizations of typical years for a baseline, and very near (2030) and near-future (2050) climates, based on five GCMs and two emission scenarios (Shared Socioeconomic Pathways - SSPs viz. SSP2-4.5 and SSP5-8.5). A total of 15 GCMs from the CMIP6 ensemble were integrated in LARS-WG 8.0. LARS-WG downscales future climate projections from the GCMs and incorporates changes at local scale in the mean climate, climatic variability, and extreme events by modifying the statistical distributions of the weather variables at each site. Based on the performance of the GCMs over northern Europe and their climate sensitivity, a subset of five GCMs was selected, viz.; ACCESS-ESM1-5, CNRM-CM6-1, HadGEM3-GC31-LL, MPI-ESM1-2-LR and MRI-ESM2-0. The selected GCMs are evenly distributed among the full set of 15 GCMs. The use of a subset of GCMs substantially reduces computational time, while allowing assessment of uncertainties in impact studies related to uncertain future climate projections arising from GCMs. The 1000 years of daily weather for the baseline, as well as for very near and near-future climate change scenarios, are essential for estimating inter-annual variation, and for detecting low frequency, but high impact, extreme climatic events, such as heat waves, floods and droughts. The present dataset can be used as an input to climate change impact models in various fields, including, land and water resources, agriculture and food production, ecology and epidemiology, and human health and welfare. Researchers, breeders, farm managers, social and public sector leaders, and policymakers may benefit from this new dataset when undertaking impact assessments of climate change and decision support for mitigation and adaptation to climate change.

Dynamic properties in functional connectivity changes and striatal dopamine deficiency in Parkinson's disease.

Recent studies in Parkinson's disease (PD) patients reported disruptions in dynamic functional connectivity (dFC, i.e., a characterization of spontaneous fluctuations in functional connectivity over time). Here, we assessed whether the integrity of striatal dopamine terminals directly modulates dFC metrics in two separate PD cohorts, indexing dopamine-related changes in large-scale brain network dynamics and its implications in clinical features. We pooled data from two disease-control cohorts reflecting early PD. From the Parkinson's Progression Marker Initiative (PPMI) cohort, resting-state functional magnetic resonance imaging (rsfMRI) and dopamine transporter (DaT) single-photon emission computed tomography (SPECT) were available for 63 PD patients and 16 age- and sex-matched healthy controls. From the clinical research group 219 (KFO) cohort, rsfMRI imaging was available for 52 PD patients and 17 age- and sex-matched healthy controls. A subset of 41 PD patients and 13 healthy control subjects additionally underwent 18F-DOPA-positron emission tomography (PET) imaging. The striatal synthesis capacity of 18F-DOPA PET and dopamine terminal quantity of DaT SPECT images were extracted for the putamen and the caudate. After rsfMRI pre-processing, an independent component analysis was performed on both cohorts simultaneously. Based on the derived components, an individual sliding window approach (44 s window) and a subsequent k-means clustering were conducted separately for each cohort to derive dFC states (reemerging intra- and interindividual connectivity patterns). From these states, we derived temporal metrics, such as average dwell time per state, state attendance, and number of transitions and compared them between groups and cohorts. Further, we correlated these with the respective measures for local dopaminergic impairment and clinical severity. The cohorts did not differ regarding age and sex. Between cohorts, PD groups differed regarding disease duration, education, cognitive scores and L-dopa equivalent daily dose. In both cohorts, the dFC analysis resulted in three distinct states, varying in connectivity patterns and strength. In the PPMI cohort, PD patients showed a lower state attendance for the globally integrated (GI) state and a lower number of transitions than controls. Significantly, worse motor scores (Unified Parkinson's Disease Rating Scale Part III) and dopaminergic impairment in the putamen and the caudate were associated with low average dwell time in the GI state and a low total number of transitions. These results were not observed in the KFO cohort: No group differences in dFC measures or associations between dFC variables and dopamine synthesis capacity were observed. Notably, worse motor performance was associated with a low number of bidirectional transitions between the GI and the lesser connected (LC) state across the PD groups of both cohorts. Hence, in early PD, relative preservation of motor performance may be linked to a more dynamic engagement of an interconnected brain state. Specifically, those large-scale network dynamics seem to relate to striatal dopamine availability. Notably, most of these results were obtained only for one cohort, suggesting that dFC is impacted by certain cohort features like educational level, or disease severity. As we could not pinpoint these features with the data at hand, we suspect that other, in our case untracked, demographical features drive connectivity dynamics in PD. PRACTITIONER POINTS: Exploring dopamine's role in brain network dynamics in two Parkinson's disease (PD) cohorts, we unraveled PD-specific changes in dynamic functional connectivity. Results in the Parkinson's Progression Marker Initiative (PPMI) and the KFO cohort suggest motor performance may be linked to a more dynamic engagement and disengagement of an interconnected brain state. Results only in the PPMI cohort suggest striatal dopamine availability influences large-scale network dynamics that are relevant in motor control.

Short-Term Impact of Seizures and Mitigation Opportunities.

PURPOSE OF REVIEW: The burden of epilepsy is complex and consists of elements directly related to acute seizures as well as those associated with living with a chronic neurologic disorder. The purpose of this systematic review was to characterize short-term burdens of seizures and to explore the potential value of acute treatments to mitigate these burdens apart from reducing the risk of status epilepticus. RECENT FINDINGS: A systematic literature search was conducted using PubMed to identify articles published from January 1, 2017, to June 22, 2023, that described short-term burdens and acute treatments of seizures. Primary outcomes included those related to short-term burdens of seizures and the benefits of acute treatments to reduce short-term burdens. Of the 1332 articles identified through PubMed and 17 through other sources, 27 had relevant outcomes and were included in the qualitative synthesis. Seizure emergencies negatively affected short-term quality of life and the ability to conduct normal daily living activities and were associated with physical (injury) and financial (emergency transport, hospitalization) burdens. The use of acute treatment was associated with a rapid return (≤ 1 h) to normal function/self for both patients and caregivers and potentially lower healthcare utilization and costs. Seizure action plans may improve knowledge and comfort with seizure care, empowering patients and caregivers. The short-term burden of seizures can create a substantial negative impact on patients and caregivers. Acute treatments may reduce the short-term burdens of seizures in addition to their well-described role to reduce seizure activity and the risk for status epilepticus.