13 research outputs found
The necessity of drawing up the annual production plan and the importance of establishment crop structure for next agricultural year
Planning represents establishment and substantiate the objectives, accomplish tasks and necessary resources for appropriate period plan ( of perspective, annual, quarterly, monthly). Drawing up annual production plan into a ferm is required primarily for evolution or involution recorded by economical phenomenes, which directly determines the operation of the farm. After determining the annual production plan can establish structures and cultures for the next agricultural year using modeling and simulation methods. Following the application of modeling and simulation methods in a farm resulting optimal dimensions of business operations with profit maximization in terms of economic efficiency increased
Informed consent procedures in patients with an acute inability to provide informed consent
Purpose: Enrolling traumatic brain injury (TBI) patients with an inability to provide informed consent in research is challenging. Alternatives to patient consent are not sufficiently embedded in European and national legislation, which allows procedural variation and bias. We aimed to quantify variations in informed consent policy and practice. Methods: Variation was explored in the CENTER-TBI study. Policies were reported by using a questionnaire and national legislation. Data on used informed consent procedures were available for 4498 patients from 57 centres across 17 European countries. Results: Variation in the use of informed consent procedur
Tracheal intubation in traumatic brain injury
Background: We aimed to study the associations between pre- and in-hospital tracheal intubation and outcomes in traumatic brain injury (TBI), and whether the association varied according to injury severity. Methods: Data from the international prospective pan-European cohort study, Collaborative European NeuroTrauma Effectiveness Research for TBI (CENTER-TBI), were used (n=4509). For prehospital intubation, we excluded self-presenters. For in-hospital intubation, patients whose tracheas were intubated on-scene were excluded. The association between intubation and outcome was analysed with ordinal regression with adjustment for the International Mission for Prognosis and Analysis of Clinical Trials in TBI variables and extracranial injury. We assessed whether the effect of intubation varied by injury severity by testing the added value of an interaction term with likelihood ratio tests. Results: In the prehospital analysis, 890/3736 (24%) patients had their tracheas intubated at scene. In the in-hospital analysis, 460/2930 (16%) patients had their tracheas intubated in the emergency department. There was no adjusted overall effect on functional outcome of prehospital intubation (odds ratio=1.01; 95% confidence interval, 0.79–1.28; P=0.96), and the adjusted overall effect of in-hospital intubation was not significant (odds ratio=0.86; 95% confidence interval, 0.65–1.13; P=0.28). However, prehospital intubation was associated with better functional outcome in patients with higher thorax and abdominal Abbreviated Injury Scale scores (P=0.009 and P=0.02, respectively), whereas in-hospital intubation was associated with better outcome in patients with lower Glasgow Coma Scale scores (P=0.01): in-hospital intubation was associated with better functional outcome in patients with Glasgow Coma Scale scores of 10 or lower. Conclusion: The benefits and harms of tracheal intubation should be carefully evaluated in patients with TBI to optimise benefit. This study suggests that extracranial injury should influence the decision in the prehospital setting, and level of consciousness in the in-hospital setting. Clinical trial registration: NCT02210221
Arrhythmogenic Cardiomyopathy. Impact of Genotype, Clinical Course, and Long-Term Outcome
Background: Arrhythmogenic Cardiomyopathy (AC) is characterized by ventricular arrhythmias and structural and functional ventricular abnormalities. The genetic substrate is mostly found in genes encoding desmosomal proteins. However, pathogenic desmosomal genes mutations are identified in 60% of patients. In the remaining 40%, unclassified genetic variants or no genetic variation at all can be found. Moreover, the impact of the genotype on clinical course remains to be defined. The increased ventricular arrhythmia susceptibility is presumably due to activation delay. Therefore, detection of activation delay, preferably by non-invasive techniques, may improve risk management. Although AC is considered a progressive cardiomyopathy, information on outcomes during long-term follow-up is limited.
Objectives: 1) to evaluate the desmosomal and non-desmosomal genetic contribution, facilitate interpretation of genetic screening results, and to define the impact of genotype on disease course and 2) to evaluate invasive and non-invasive measurements of arrhythmic substrate and to define the long-term outcome of AC. The ultimate goal of this thesis was to support and improve early diagnosis and patient management in AC.
Results: The studies in this thesis showed that in 58% of Dutch AC index patients, a pathogenic desmosomal mutation was found. A non-desmosomal phospholamban (PLN) mutation was identified in 13% of patients, explaining 32% of the up-till-then genetically unexplained cases. PLN mutation carriers more often had low voltages and negative T waves in left precordial leads on their ECG and additional left ventricular abnormalities compared to desmosomal mutation carriers. An algorithm composed of in silico prediction program scores combined with the variant minor allele frequency and the in vitro mRNA analysis improved the prediction of pathogenicity of unclassified variants and facilitated interpretation of genetic screening results in AC. Genotype-phenotype correlation analysis showed that the genotype impacted the phenotype and clinical course. With invasive evaluation of arrhythmogenic substrate in AC patients, electrical abnormalities were mostly shown in the subtricuspid and RV outflow tract area. ECG criteria for non-invasive detection of activation delay mostly in the RV outflow tract already exist in the 2010 diagnostic Task Force Criteria. ECG criteria reflecting electrical abnormalities and activation delay mostly in the subtricuspid area might be: 1) late isolated potentials in inferior leads, 2) negative T waves in inferior leads, and 3) left axis deviation. Assessment of the clinical, genetic, and long-term follow-up data of 1001 individuals showed that long-term outcomes were favorable in diagnosed and appropriately treated index patients and family members. In index-patients, long-term outcome was determined by ICD implantation but remarkably not by mutation status and familial background of disease. In family members, long-term outcome was determined by symptoms at presentation and the presence of mutations.
Conclusions: The non-desmosomal PLN mutation is an important contributor to AC in The Netherlands and results in a specific phenotype. Genetic screening results interpretation can be improved by in silico and in vitro techniques. The genotype has important implications for the disease course. Non-invasive parameters of activation delay may improve early diagnosis and risk management. Long-term outcome of AC is favorable when diagnosed and appropriately treated
The Netherlands Arrhythmogenic Cardiomyopathy Registry: design and status update
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Mitochondrial dynamics in visual cortex are limited in vivo and not affected by axonal structural plasticity.
Mitochondria buffer intracellular Ca2+ and provide energy [1]. Because synaptic structures with high Ca2+ buffering [2–4] or energy demand [5] are often localized far away from the soma, mitochondria are actively transported to these sites [6–11]. Also, the removal and degradation of mitochondria are tightly regulated [9, 12, 13], because dysfunctional mitochondria are a source of reactive oxygen species, which can damage the cell [14]. Deficits in mitochondrial trafficking have been proposed to contribute to the pathogenesis of Parkinson’s disease, schizophrenia, amyotrophic lateral sclerosis, optic atrophy, and Alzheimer’s disease [13, 15–19]. In neuronal cultures, about a third of mitochondria are motile, whereas the majority remains stationary for several days [8, 20]. Activity-dependent mechanisms cause mitochondria to stop at synaptic sites [7, 8, 20, 21], which affects synapse function and maintenance. Reducing mitochondrial content in dendrites decreases spine density [22, 23], whereas increasing mitochondrial content or activity increases it [7]. These bidirectional interactions between synaptic activity and mitochondrial trafficking suggest that mitochondria may regulate synaptic plasticity. Here we investigated the dynamics of mitochondria in relation to axonal boutons of neocortical pyramidal neurons for the first time in vivo. We find that under these circumstances practically all mitochondria are stationary, both during development and in adulthood. In adult visual cortex, mitochondria are preferentially localized at putative boutons, where they remain for several days. Retinal-lesion-induced cortical plasticity increases turnover of putative boutons but leaves mitochondrial turnover unaffected. We conclude that in visual cortex in vivo, mitochondria are less dynamic than in vitro, and that structural plasticity does not affect mitochondrial dynamics
Functional assessment of potential splice site variants in arrhythmogenic right ventricular dysplasia/cardiomyopathy
Genetics of disease, diagnosis and treatmen
Impact of genotype on clinical course in arrhythmogenic right ventricular dysplasia/cardiomyopathy-associated mutation carriers
Cardiolog