Heraldic seizure

AbstractBackground: The term heraldic seizures indicates epileptic seizures caused by cerebrovascular disease, believed to be triggered by silent ischemia and occurring before a stroke. This fact widens the spectrum of possible interrelations between epilepsy and cerebrovascular disease outside the well known context of post-stroke epilepsy. Methods: This is a case report of a healthy 67-year-old male who had a new onset epileptic seizure prior to a lobar intracerebral hemorrhage (ICH). This man began to suffer myoclonic jerks in his left arm which progressed to a generalized tonic–clonic seizure. At the emergency area the physical and neurological examination were unremarkable and a CT scan was normal. The next day the patient developed left hemiparesis, hemianopsia and confusion and a new CT scan showed right parietal–occipital ICH. Conclusions: This case report exemplifies the concept of heraldic seizures, showing a patient who had a focal seizure preceding an intracerebral hemorrhage. Our etiologic diagnostic work led us to a diagnosis of probable amyloid angiopathy. We suggest that cerebral amyloid angiopathy (CAA) may be the underlying cause, since it may be the origin of both the late event (ICH) and the heralding seizures, resulting from concurrent ischemia

Recurrence properties of hypercyclic operators

[EN] We generalize the notions of hypercyclic operators, U-frequently hypercyclic operators and frequently hypercyclic operators by introducing a new concept in linear dynamics, namely A-hypercyclicity. We then state an A-hypercyclicity criterion, inspired by the hypercyclicity criterion and the frequent hypercyclicity criterion, and we show that this criterion characterizes the A-hypercyclicity for weighted shifts. We also investigate which density properties can the sets N(x, U) = {n is an element of N; T-n x is an element of U} have for a given hypercyclic operator, and we study the new notion of reiteratively hypercyclic operators.This work is supported in part by MEC and FEDER, Project MTM2013-47093-P, and by GVA, Projects PROMETEOII/2013/013 and ACOMP/2015/005. The second author was a postdoctoral researcher of the Belgian FNRS.Bès, JP.; Menet, Q.; Peris Manguillot, A.; Puig-De Dios, Y. (2016). Recurrence properties of hypercyclic operators. Mathematische Annalen. 366(1):545-572. https://doi.org/10.1007/s00208-015-1336-3S5455723661Badea, C., Grivaux, S.: Unimodular eigenvalues, uniformly distributed sequences and linear dynamics. Adv. Math. 211, 766–793 (2007)Bayart, F., Grivaux, S.: Frequently hypercyclic operators. Trans. Amer. Math. Soc. 358, 5083–5117 (2006)Bayart, F., Grivaux, S.: Invariant Gaussian measures for operators on Banach spaces and linear dynamics. Proc. Lond. Math. Soc. 94, 181–210 (2007)Bayart, F., Matheron, É.: Dynamics of linear operators, Cambridge Tracts in Mathematics, 179. Cambridge University Press, Cambridge (2009)Bayart, F., Matheron, É.: (Non-)weakly mixing operators and hypercyclicity sets. Ann. Inst. Fourier 59, 1–35 (2009)Bayart, F., Ruzsa, I.: Difference sets and frequently hypercyclic weighted shifts. Ergodic Theory Dynam. Syst. 35, 691–709 (2015)Bergelson, V.: Ergodic Ramsey Theory- an update, Ergodic Theory of $$\mathbb{Z}^d$$ Z d -actions. Lond. Math. Soc. Lecture Note Ser. 28, 1–61 (1996)Bernal-González, L., Grosse-Erdmann, K.-G.: The Hypercyclicity Criterion for sequences of operators. Studia Math. 157, 17–32 (2003)Bès, J., Peris, A.: Hereditarily hypercyclic operators. J. Funct. Anal. 167, 94–112 (1999)Bonilla, A., Grosse-Erdmann, K.-G.: Frequently hypercyclic operators and vectors. Ergodic Theory Dynam. Syst. 27, 383–404 (2007)Bonilla, A., Grosse-Erdmann, K.-G.: Erratum: Ergodic Theory Dynam. Systems 29, 1993–1994 (2009)Chan, K., Seceleanu, I.: Hypercyclicity of shifts as a zero-one law of orbital limit points. J. Oper. Theory 67, 257–277 (2012)Costakis, G., Sambarino, M.: Topologically mixing hypercyclic operators. Proc. Amer. Math. Soc. 132, 385–389 (2004)Furstenberg, H.: Recurrence in ergodic theory and combinatorial number theory. Princeton University Press, Princeton (1981)Giuliano, R., Grekos, G., Mišík, L.: Open problems on densities II, Diophantine Analysis and Related Fields 2010. AIP Conf. Proc. 1264, 114–128 (2010)Grosse-Erdmann, K.-G.: Hypercyclic and chaotic weighted shifts. Studia Math. 139, 47–68 (2000)Grosse-Erdmann, K.-G., Peris, A.: Frequently dense orbits. C. R. Math. Acad. Sci. Paris 341, 123–128 (2005)Grosse-Erdmann, K.G., Peris, A.: Weakly mixing operators on topological vector spaces, Rev. R. Acad. Cienc. Exactas Fís. Nat. Ser. A Math. RACSAM, 104, 413–426 (2010)Grosse-Erdmann, K.G., Peris Manguillot, A.: Linear chaos, Universitext. Springer, London (2011)Menet, Q.: Linear chaos and frequent hypercyclicity. Trans. Amer. Math. Soc. arXiv:1410.7173Puig, Y.: Linear dynamics and recurrence properties defined via essential idempotents of $$\beta {\mathbb{N}}$$ β N (2014) arXiv:1411.7729 (preprint)Salas, H.N.: Hypercyclic weighted shifts. Trans. Amer. Math. Soc. 347, 993–1004 (1995)Salat, T., Toma, V.: A classical Olivier’s theorem and statistical convergence. Ann. Math. Blaise Pascal 10, 305–313 (2003)Shkarin, S.: On the spectrum of frequently hypercyclic operators. Proc. Am. Math. Soc. 137, 123–134 (2009

Readthrough of Premature Termination Codons in the Adenomatous Polyposis Coli Gene Restores Its Biological Activity in Human Cancer Cells

The APC tumor suppressor gene is frequently mutated in human colorectal cancer, with nonsense mutations accounting for 30% of all mutations in this gene. Reintroduction of the WT APC gene into cancer cells generally reduces tumorigenicity or induces apoptosis. In this study, we explored the possibility of using drugs to induce premature termination codon (PTC) readthrough (aminoglycosides, negamycin), as a means of reactivating endogenous APC. By quantifying the readthrough of 11 nonsense mutations in APC, we were able to identify those giving the highest levels of readthrough after treatment. For these mutations, we demonstrated that aminoglycoside or negamycin treatment led to a recovery of the biological activity of APC in cancer cell lines, and showed that the level of APC activity was proportional to the level of induced readthrough. These findings show that treatment with readthrough inducers should be considered as a potential strategy for treating cancers caused by nonsense mutations APC gene. They also provide a rational basis for identifying mutations responsive to readthrough inducers

Characterization of individuals at high risk of developing melanoma in Latin America: bases for genetic counseling in melanoma

PURPOSE: CDKN2A is the main high-risk melanoma-susceptibility gene, but it has been poorly assessed in Latin America. We sought to analyze CDKN2A and MC1R in patients from Latin America with familial and sporadic multiple primary melanoma (SMP) and compare the data with those for patients from Spain to establish bases for melanoma genetic counseling in Latin America. METHODS: CDKN2A and MC1R were sequenced in 186 Latin American patients from Argentina, Brazil, Chile, Mexico, and Uruguay, and in 904 Spanish patients. Clinical and phenotypic data were obtained. RESULTS: Overall, 24 and 14% of melanoma-prone families in Latin America and Spain, respectively, had mutations in CDKN2A. Latin American families had CDKN2A mutations more frequently (P = 0.014) than Spanish ones. Of patients with SMP, 10% of those from Latin America and 8.5% of those from Spain had mutations in CDKN2A (P = 0.623). The most recurrent CDKN2A mutations were c.-34G>T and p.G101W. Latin American patients had fairer hair (P = 0.016) and skin (P < 0.001) and a higher prevalence of MC1R variants (P = 0.003) compared with Spanish patients. CONCLUSION: The inclusion criteria for genetic counseling of melanoma in Latin America may be the same criteria used in Spain, as suggested in areas with low to medium incidence, SMP with at least two melanomas, or families with at least two cases among first- or second-degree relatives.Genet Med 18 7, 727-736

Effectiveness and tolerability of 12-Month Brivaracetam in the real world: EXPERIENCE, an international pooled analysis of individual patient records

Background and Objective Real-world evidence studies of brivaracetam (BRV) have been restricted in scope, location, and patient numbers. The objective of this pooled analysis was to assess effectiveness and tolerability of brivaracetam (BRV) in routine practice in a large international population. Methods EXPERIENCE/EPD332 was a pooled analysis of individual patient records from multiple independent non-interventional studies of patients with epilepsy initiating BRV in Australia, Europe, and the United States. Eligible study cohorts were identified via a literature review and engagement with country lead investigators, clinical experts, and local UCB Pharma scientific/medical teams. Included patients initiated BRV no earlier than January 2016 and no later than December 2019, and had ≥ 6 months of follow-up data. The databases for each cohort were reformatted and standardised to ensure information collected was consistent. Outcomes included ≥ 50% reduction from baseline in seizure frequency, seizure freedom (no seizures within 3 months before timepoint), continuous seizure freedom (no seizures from baseline), BRV discontinuation, and treatment-emergent adverse events (TEAEs) at 3, 6, and 12 months. Patients with missing data after BRV discontinuation were considered non-responders/not seizure free. Analyses were performed for all adult patients (≥ 16 years), and for subgroups by seizure type recorded at baseline; by number of prior antiseizure medications (ASMs) at index; by use of BRV as monotherapy versus polytherapy at index; for patients who switched from levetiracetam to BRV versus patients who switched from other ASMs to BRV; and for patients with focal-onset seizures and a BRV dose of ≤ 200 mg/day used as add-on at index. Analysis populations included the full analysis set (FAS; all patients who received at least one BRV dose and had seizure type and age documented at baseline) and the modified FAS (all FAS patients who had at least one seizure recorded during baseline). The FAS was used for all outcomes other than ≥ 50% seizure reduction. All outcomes were summarised using descriptive statistics. Results Analyses included 1644 adults. At baseline, 72.0% were 16–49 years of age and 92.2% had focal-onset seizures. Patients had a median (Q1, Q3) of 5.0 (2.0, 8.0) prior antiseizure medications at index. At 3, 6, and 12 months, respectively, ≥ 50% seizure reduction was achieved by 32.1% (n = 619), 36.7% (n = 867), and 36.9% (n = 822) of patients; seizure freedom rates were 22.4% (n = 923), 17.9% (n = 1165), and 14.9% (n = 1111); and continuous seizure freedom rates were 22.4% (n = 923), 15.7% (n = 1165), and 11.7% (n = 1111). During the whole study follow-up, 551/1639 (33.6%) patients discontinued BRV. TEAEs since prior visit were reported in 25.6% (n = 1542), 14.2% (n = 1376), and 9.3% (n = 1232) of patients at 3, 6, and 12 months, respectively. Conclusions This pooled analysis using data from a variety of real-world settings suggests BRV is effective and well tolerated in routine clinical practice in a highly drug-resistant patient population

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Determination of the Failure Susceptibility of a Flat Die used in Biomass Pelletizing Machines by means of FEA based Design Exploration

This paper focuses on a design analysis of a flat die used in an agricultural biomass pelletizing machine by considering its high pressure loading failure susceptibility. The pellet die is one of the key elements in a pelletizing machine, and the strength of the die plate has an important role on the pellet’s quality and producibility. In fact, higher compression ratio (CR - the ratio of effective length and the internal (press channel) diameter of a die orifice/hole) will provide denser pellets which is a desired phenomenon, however, if the compression pressure is too high or CR is not determined to compensate high pressures, the raw material may block the die and the die may experience deformation failure due to overloading. If the desire is to make high quality pellets with no die failure, optimum flat die hole/orifice design parameters should be used which can provide the best CR for a specific compression pressure. This is the core motivation of this research. In this study, Finite Element Analysis (FEA) based design exploration has been utilised for a sample single hole flat die with various die geometry parameters against various compression pressure values. Following the FEA design exploration undertaken, a response surface analysis (RSA) was carried out and then estimation models (empirical equations), which could be used to calculate parameters of the die hole/orifice against applied compression pressure and failure susceptibility based on structural stress and deformation, was described. The results gained from the RSA has indicated that the estimation models have high R2 values (higher than 98 %) which could be used for adequately predicting failure susceptibility indicators. In addition to this, FEM-based simulation print-outs have provided useful stress distribution visuals on the die against different compression pressure values. Most especially, the study has highlighted that a detailed structural optimisation study may be scheduled in order to obtain die geometry design parameters with a focus on the failure susceptibility

Population-based multicase-control study in common tumors in Spain (MCC-Spain): rationale and study design

Introduction: We present the protocol of a large population-based case-control study of 5 common tumors in Spain (MCC-Spain) that evaluates environmental exposures and genetic factors. Methods: Between 2008-2013, 10,183 persons aged 20-85 years were enrolled in 23 hospitals and primary care centres in 12 Spanish provinces including 1,115 cases of a new diagnosis of prostate cancer, 1,750 of breast cancer, 2,171 of colorectal cancer, 492 of gastro-oesophageal cancer, 554 cases of chronic lymphocytic leukaemia (CLL) and 4,101 population-based controls matched by frequency to cases by age, sex and region of residence. Participation rates ranged from 57% (stomach cancer) to 87% (CLL cases) and from 30% to 77% in controls. Participants completed a face-to-face computerized interview on sociodemographic factors, environmental exposures, occupation, medication, lifestyle, and personal and family medical history. In addition, participants completed a self-administered food-frequency questionnaire and telephone interviews. Blood samples were collected from 76% of participants while saliva samples were collected in CLL cases and participants refusing blood extractions. Clinical information was recorded for cases and paraffin blocks and/or fresh tumor samples are available in most collaborating hospitals. Genotyping was done through an exome array enriched with genetic markers in specific pathways. Multiple analyses are planned to assess the association of environmental, personal and genetic risk factors for each tumor and to identify pleiotropic effects. Discussion: This study, conducted within the Spanish Consortium for Biomedical Research in Epidemiology & Public Health (CIBERESP), is a unique initiative to evaluate etiological factors for common cancers and will promote cancer research and prevention in Spain.The study was partially funded by the “Accion Transversal del Cancer”, approved on the Spanish Ministry Council on the 11th October 2007, by the Instituto de Salud Carlos III-FEDER (PI08/1770, PI08/0533, PI08/1359, PS09/00773, PS09/01286, PS09/01903, PS09/02078, PS09/01662, PI11/01403, PI11/01889, PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265, PI12/01270, PI12/00715, PI12/00150), by the Fundación Marqués de Valdecilla (API 10/09), by the ICGC International Cancer Genome Consortium CLL, by the Junta de Castilla y León (LE22A10-2), by the Consejería de Salud of the Junta de Andalucía (PI-0571), by the Conselleria de Sanitat of the Generalitat Valenciana (AP 061/10), by the Recercaixa (2010ACUP 00310), by the Regional Government of the Basque Country by European Commission grants FOOD-CT- 2006-036224-HIWATE, by the Spanish Association Against Cancer (AECC) Scientific Foundation, by the The Catalan Government DURSI grant 2009SGR1489

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially