Cellular Radiosensitivity: How much better do we understand it?

Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation

The LHC Injection Tests

A series of LHC injection tests was performed in August and September 2008. The first saw beam injected into sector 23; the second into sectors 78 and 23; the third into sectors 78-67 and sectors 23-34-45. The fourth, into sectors 23-34-45, was performed the evening before the extended injection test on the 10th September which saw both beams brought around the full circumference of the LHC. The tests enabled the testing and debugging of a number of critical control and hardware systems; testing and validation of instrumentation with beam for the first time; deployment, and validation of a number of measurement procedures. Beam based measurements revealed a number of machine configuration issues that were rapidly resolved. The tests were undoubtedly an essential precursor to the successful start of LHC beam commissioning. This paper provides an outline of preparation for the tests, the machine configuration and summarizes the measurements made and individual system performance

The Role of Electroencephalography in Predicting Post-Stroke Seizures and an Updated Prognostic Model (SeLECT-EEG)

Objective: Seizures negatively impact stroke outcomes, highlighting the need for reliable predictors of post-stroke epilepsy. Although acute symptomatic seizures are a known risk factor, most stroke survivors who develop epilepsy do not experience them. Early electroencephalography (EEG) findings may enhance risk prediction, particularly in patients without acute symptomatic seizures, aiding in patient management and counseling. Methods: We conducted a multicenter cohort study using data from 1,105 stroke survivors (mean age 71 years, 54% male) with neuroimaging-confirmed ischemic stroke who underwent EEG within 7 days post-stroke. Electrographic biomarkers, including epileptiform activity and regional slowing, were analyzed for their association with post-stroke epilepsy using Cox proportional hazards regression and Fine–Gray subdistribution hazard models, adjusted for differences in EEG timing and patient characteristics. Results: Post-stroke epilepsy developed in 119 patients (11%), whereas 233 (21%) had acute symptomatic seizures. The 5-year epilepsy risk was 42% (95% confidence interval [CI]: 30–49%) in patients with epileptiform activity versus 13% (95% CI: 9–16%) in those without. Regional slowing doubled the 5-year epilepsy risk (23%, 95% CI: 17–30% vs 11%, 95% CI: 7–16%). Epileptiform activity (subdistribution hazard ratio: 2.3, 95% CI: 1.5–3.4, p < 0.001) and regional slowing (subdistribution hazard ratio: 1.7, 95% CI: 1.1–2.7, p = 0.02) were independently associated with post-stroke epilepsy. A novel prognostic model, SeLECT-EEG (concordance statistic: 0.75, 95% CI: 0.71–0.80), outperformed the previous standard (SeLECT2.0; 0.71, 95% CI: 0.65–0.76, p < 0.001). Interpretation: Electrographic biomarkers improve post-stroke epilepsy prediction beyond clinical risk factors. The SeLECT-EEG model enhances early risk stratification, particularly in patients without acute symptomatic seizures, informing management strategies and patient counseling. ANN NEUROL 2025

Staged treatment response in status epilepticus: Lessons from the SENSE registry.

Although in epilepsy patients the likelihood of becoming seizure-free decreases substantially with each unsuccessful treatment, to our knowledge this has been poorly investigated in status epilepticus (SE). We aimed to evaluate the proportion of SE cessation and functional outcome after successive treatment steps. We conducted a post hoc analysis of a prospective, observational, multicenter cohort (Sustained Effort Network for treatment of Status Epilepticus [SENSE]), in which 1049 incident adult SE episodes were prospectively recorded at nine European centers. We analyzed 996 SE episodes without coma induction before the third treatment step. Rates of SE cessation, mortality (in ongoing SE or after SE control), and favorable functional outcome (assessed with modified Rankin scale) were evaluated after each step. SE was treated successfully in 838 patients (84.1%), 147 (14.8%) had a fatal outcome (36% of them died while still in SE), and 11 patients were transferred to palliative care while still in SE. Patients were treated with a median of three treatment steps (range 1-13), with 540 (54.2%) receiving more than two steps (refractory SE [RSE]) and 95 (9.5%) more than five steps. SE was controlled after the first two steps in 45%, with an additional 21% treated after the third, and 14% after the fourth step. Likelihood of SE cessation (p &lt; 0.001), survival (p = 0.003), and reaching good functional outcome (p &lt; 0.001) decreased significantly between the first two treatment lines and the third, especially in patients not experiencing generalized convulsive SE, but remained relatively stable afterwards. The significant worsening of SE prognosis after the second step clinically supports the concept of RSE. However, and differing from findings in human epilepsy, RSE remains treatable in about one third of patients, even after several failed treatment steps. Clinical judgment remains essential to determine the aggressiveness and duration of SE treatment, and to avoid premature treatment cessation in patients with SE

International consensus based review and recommendations for minimum reporting standards in research on transcutaneous vagus nerve stimulation (Version 2020)

Stress and Psychopatholog

Perampanel outcomes at different stages of treatment in people with focal and generalized epilepsy treated in clinical practice: Evidence from the PERMIT study

IntroductionThe PERMIT study is the largest pooled analysis of perampanel (PER) clinical practice data conducted to date.MethodsThis post-hoc analysis of PERMIT investigated the effectiveness, safety and tolerability of PER when used as early add-on therapy (after failure of one or two previous antiseizure medications) in comparison with late add-on therapy (after failure of three or more previous antiseizure medications). Retention and effectiveness were assessed after 3, 6, and 12 months, and at the last visit (last observation carried forward). Effectiveness was assessed by seizure type (total seizures, focal seizures, generalized tonic-clonic seizures [GTCS]) and assessments included seizure freedom rate and responder rate. Safety and tolerability were assessed by evaluating adverse events (AEs) and discontinuation due to AEs.ResultsThe Full Analysis Set included 1184 and 2861 PWE treated with PER as early and late add-on therapy, respectively. Compared to the late add-on subgroup, the early add-on subgroup was characterized by later mean age at epilepsy onset, shorter mean duration of epilepsy, lower rates of intellectual disability and psychiatric comorbidity, and lower frequency of seizures per month, suggesting a less severe form of epilepsy in this subgroup. After 12 months, retention was significantly higher in the early versus late add-on subgroup (67.7% vs. 62.4%; p = 0.004). At the last visit, responder rates in the early versus late add-on subgroup were significantly higher for total seizures (68.2% vs. 39.3%; p &amp;lt; 0.001), focal seizures (65.0% vs. 36.8%; p &amp;lt; 0.001) and GTCS (83.7% vs. 67.2%; p &amp;lt; 0.001), as were seizure freedom rates (total seizures, 35.9% vs. 11.9% [p &amp;lt; 0.001]; focal seizures, 29.4% vs. 8.7% [p &amp;lt; 0.001]; GTCS, 69.0% vs. 48.1% [p &amp;lt; 0.001]). Incidence of AEs was significantly lower in the early versus late add-on subgroup (42.1% vs. 54.7%; p &amp;lt; 0.001), as was the rate of discontinuation due to AEs over 12 months (15.0% vs. 18.1%; p = 0.031).DiscussionThis study demonstrated that PER was effective and generally well tolerated when initiated as early or late add-on therapy, but it was significantly more effective and better tolerated when initiated early. These findings support PER's use as a broad-spectrum, early add-on therapy for use in PWE with focal and generalized seizures.</jats:sec

Recovery of the herbaceous layer in the young silver birch and black alder stands that developed spontaneously after a forest fire

The studies, which were conducted in southern Poland, focused on the recovery of the herb layer in 17-year-old post-fire silver birch and black alder forests. Although both types of stands, which are of the same age, developed spontaneously, the alder stands occupied damper sites (with thicker A horizons that survived the fire) than those in the birch forests. We surveyed the migration rates of 44 woodland species, primarily ancient woodland indicators, into both forests and the potential differences in these rates depending on their moisture regime and the community type represented by unburned forests, which were treated as the source of the woodland species pool. Additionally, the role of local depressions with high humidity that were covered by post-fire alder woods in the colonization process, as well as species survivorship and recolonisation, were estimated. Woodland species showed diverse migration paces among the sites; most of them migrated faster on more fertile sites with a higher humidity. Small patches of post-fire alder woods contributed to the recolonisation process since many woodland species in the herb layer survived the fire due to its high humidity, which inhibited the intensity of the forest fire. The recovery of woodland species in post-fire woods is the combined effect of regeneration, which relies on autochthonic propagules, and secondary succession, which is based on allochthonic propagules. Local depressions, which provide refuges for fire-sensitive, dispersal-limited species, contribute to their survivorship and thus to the successive recovery of herbaceous layers after a fire