Environmental changes and violent conflict

This letter reviews the scientific literature on whether and how environmental changes affect the risk of violent conflict. The available evidence from qualitative case studies indicates that environmental stress can contribute to violent conflict in some specific cases. Results from quantitative large-N studies, however, strongly suggest that we should be careful in drawing general conclusions. Those large-N studies that we regard as the most sophisticated ones obtain results that are not robust to alternative model specifications and, thus, have been debated. This suggests that environmental changes may, under specific circumstances, increase the risk of violent conflict, but not necessarily in a systematic way and unconditionally. Hence there is, to date, no scientific consensus on the impact of environmental changes on violent conflict. This letter also highlights the most important challenges for further research on the subject. One of the key issues is that the effects of environmental changes on violent conflict are likely to be contingent on a set of economic and political conditions that determine adaptation capacity. In the authors' view, the most important indirect effects are likely to lead from environmental changes via economic performance and migration to violent conflict. © 2012 IOP Publishing Ltd

Pressure and Flow Properties of Cannulae for Extracorporeal Membrane Oxygenation I: Return (Arterial) Cannulae

Adequate extracorporeal membrane oxygenation support in the adult requires cannulae permitting blood flows up to 6-8 L/minute. In accordance with Poiseuille's law, flow is proportional to the fourth power of cannula inner diameter and inversely proportional to its length. Poiseuille's law can be applied to obtain the pressure drop of an incompressible, Newtonian fluid (such as water) flowing in a cylindrical tube. However, as blood is a pseudoplastic non-Newtonian fluid, the validity of Poiseuille's law is questionable for prediction of cannula properties in clinical practice. Pressure-flow charts with non-Newtonian fluids, such as blood, are typically not provided by the manufacturers. A standardized laboratory test of return (arterial) cannulae for extracorporeal membrane oxygenation was performed. The aim was to determine pressure-flow data with human whole blood in addition to manufacturers' water tests to facilitate an appropriate choice of cannula for the desired flow range. In total, 14 cannulae from three manufacturers were tested. Data concerning design, characteristics, and performance were graphically presented for each tested cannula. Measured blood flows were in most cases 3-21% lower than those provided by manufacturers. This was most pronounced in the narrow cannulae (15-17 Fr) where the reduction ranged from 27% to 40% at low flows and 5-15% in the upper flow range. These differences were less apparent with increasing cannula diameter. There was a marked disparity between manufacturers. Based on the measured results, testing of cannulae including whole blood flows in a standardized bench test would be recommended.info:eu-repo/semantics/publishedVersio

The genomic landscape across 474 surgically accessible epileptogenic human brain lesions

Understanding the exact molecular mechanisms involved in the etiology of epileptogenic pathologies with or without tumor activity is essential for improving treatment of drug-resistant focal epilepsy. Here, we characterize the landscape of somatic genetic variants in resected brain specimens from 474 individuals with drug-resistant focal epilepsy using deep whole-exome sequencing (>350×) and whole-genome genotyping. Across the exome, we observe a greater number of somatic single-nucleotide variants (SNV) in low-grade epilepsy-associated tumors (LEAT; 7.92 ± 5.65 SNV) than in brain tissue from malformations of cortical development (MCD; 6.11 ± 4 SNV) or hippocampal sclerosis (HS; 5.1 ± 3.04 SNV). Tumor tissues also had the largest number of likely pathogenic variant carrying cells. LEAT had the highest proportion of samples with one or more somatic copy number variants (CNV; 24.7%), followed by MCD (5.4%) and HS (4.1%). Recurring somatic whole chromosome duplications affecting Chromosome 7 (16.8%), chromosome 5 (10.9%), and chromosome 20 (9.9%) were observed among LEAT. For germline variant-associated MCD genes such as TSC2, DEPDC5, and PTEN, germline SNV were frequently identified within large loss of heterozygosity regions, supporting the recently proposed 'second hit' disease mechanism in these genes. We detect somatic variants in twelve established lesional epilepsy genes and demonstrate exome-wide statistical support for three of these in the etiology of LEAT (e.g., BRAF) and MCD (e.g., SLC35A2 and MTOR). We also identify novel significant associations for PTPN11 with LEAT and NRAS Q61 mutated protein with a complex MCD characterized by polymicrogyria and nodular heterotopia. The variants identified in NRAS are known from cancer studies to lead to hyperactivation of NRAS, which can be targeted pharmacologically. We identify large recurrent 1q21-q44 duplication including AKT3 in association with focal cortical dysplasia type 2a with hyaline astrocytic inclusions, another rare and possibly under-recognized brain lesion. The clinical genetic analyses showed that the numbers of somatic SNV across the exome and the fraction of affected cells were positively correlated with the age at seizure onset and surgery in individuals with LEAT. In summary, our comprehensive genetic screen sheds light on the genome-scale landscape of genetic variants in epileptic brain lesions, informs the design of gene panels for clinical diagnostic screening, and guides future directions for clinical implementation of epilepsy surgery genetics

Muscle and nerve pathology in Dunnigan familial partial lipodystrophy

Objective: To characterize muscle and nerve pathology in Dunnigan familial partial lipodystrophy (FPLD). Methods: We used conventional histology, immunohistochemistry, messenger RNA (mRNA) expression, gene sequencing, and clinical studies of 13 patients with neuromuscular involvement. Results: The clinical findings consisted of muscle hypertrophy (12/13), severe myalgias (9/13), and multiple nerve entrapment syndromes (8/13). Skeletal muscle histology demonstrated marked Type 1 and 2 muscle fiber hypertrophy and nonspecific myopathic changes, whereas numerous paranodal myelin swellings (tomacula) were found in sural nerve biopsies. We found that myostatin mRNA expression was reduced in patients with FPLD vs controls. We sequenced the myostatin gene in our subjects, but found no mutations. We then investigated whether or not SMAD, the intracellular mediator of myostatin signaling, might be impaired in patients with FPLD. We found that in FPLD muscle, a large number of SMAD molecules adhered to the nuclear membrane and were not found within the nucleus, compared with normal muscle or muscle from a patient with a non-FPLD lamin A/C disease. Conclusion: The myopathy and neuropathy associated with Dunnigan familial partial lipodystrophy are distinct from other lamin A/C disorders. We hypothesize that the lipodystrophy-associated mutation interferes with SMAD signaling, linking this type of lipodystrophy to the phenotypically similar myostatin deficiency

Development and Validation of Prediction Models for Developmental and Intellectual Outcome Following Pediatric Epilepsy Surgery

Cloppenborg T, van Schooneveld M, Hagemann A, et al. Development and Validation of Prediction Models for Developmental and Intellectual Outcome Following Pediatric Epilepsy Surgery. Neurology. 2021: 10.1212/WNL.0000000000013065.**Background and Objectives:** To (1) identify predictors of postoperative intelligence and developmental quotients (IQ/DQ) and (2) develop and validate clinically applicable IQ/DQ prediction models. **Methods:** We retrospectively analyzed neuropsychological outcomes and their possible determinants for children treated in Bethel and Utrecht since 1990. We performed separate analyses for patients with IQ and those with only DQ available. We developed prediction models based on presurgical determinants to predict dichotomized levels of performance (IQ≥85, IQ≥70, DQ≥50). **Results:** IQ/DQ data before and two years after surgery were available for 492 patients (IQ n=365, DQ n=127). At a cutoff-level ±10 points, the chance of improvement was considerably higher than the chance of deterioration (IQ 37.3% vs. 6.6% and DQ 31.5% vs. 15.0%, respectively). Presurgical IQ/DQ was the strongest predictor of postoperative cognition (IQ r=0.85, p<.001, DQ: r=0.57, p<.001). Two IQ models were developed in the Bethel cohort (n=258) and externally validated in the Utrecht cohort (n=102). For DQ, we developed the model in the Bethel cohort and used 10-fold cross-validation. Models allowed good prediction at all three cutoff-levels (correct classification for IQ≥85=86%, IQ≥70=91%, DQ≥50=76%). External validation of the IQ models showed high accuracy (IQ≥85: 0.82, CI 0.75-0.91, IQ≥70: 0.84, CI 0.77-0.92) and excellent discrimination (ROC curves IQ≥85: AUC 0.90, CI 0.84-0.96; IQ≥70: AUC 0.92, CI 0.87-0.97). **Discussion:** After epilepsy surgery in children, the risk of cognitive deterioration is very low. Presurgical development has a strong impact on the postoperative trajectory. The presented models can improve presurgical counseling of patients and parents by reliably predicting cognitive outcomes. **Classification of Evidence:** This study provides Class II evidence that for children undergoing epilepsy surgery presurgical IQ/DQ was the strongest predictor of postoperative cognition

Trends in epilepsy surgery: stable surgical numbers despite increasing presurgical volumes

Cloppenborg T, May TW, Blümcke I, et al. Trends in epilepsy surgery: stable surgical numbers despite increasing presurgical volumes. Journal of Neurology, Neurosurgery &amp; Psychiatry. 2016;87(12):1322-1329