Las falacias del historiador.

El autor describe con gran acidez humorística los vicios y fallos más co-munes, pero no por ello más conocidos, del oficio del historiador. Sus hallaz-gos en este sector son extrapolables a otros sectores de la actividad científica y creativa, donde muchos escritores y autores caen en las mismas falacias con presunción, falta de tacto, inseguridad y falta de rigor por. ABSTRACTS L'auteur décrit avec maitrise des falacies et erreurs typiques du métier de l'historien. Ce sont des erreurs trés communs mais pas trés reconnus, et on peut les trouver aussi bien dans d'autres secteurs de l'activité scientifique et créative, oit les m6mes falacies sont utilisés ayee vanité, manque de tacte, d'insécurité et manque de rigueur par de nombreux écrivains et auteurs. Der Autor bescreibt humorvolí die nicht gut bekannt aber sehr generále Fehíer im schriftliche Geschichte. Die sind sehr alítágliche aher weniger William HACKETT flsnER es profesor de la Brandeis University. Además de Historian's Fallacies, ha publicado Growing Oíd itt A,nerica. Oxford University Press, 1978; Albion s Seed: Faur Rritish Folkways itt America. Oxford University Press, 1989; Paul Revere's Ride. Oxford Ijniversity Press, 1994; Tite Crear Wave: Price Revolurion and tite Rhythm of J-fisrory. Oxford University Press. 1996. 293 David Hacketr Fis/ter Las lá/acias del historiador analysierte Fehíer, die man kann aucb in andere wissentschaftliche und kreative Felde finden, wo diese betrtihige Sátze gemacht sind inimer wenn der Autor unsicher, weniger exakt oder stólz Uber seine Werke ist.S L'auteur décrit avec maitrise des falacies et erreurs typiques du métier de l'historien. Ce sont des erreurs trés communs mais pas trés reconnus, et on peut les trouver aussi bien dans d'autres secteurs de l'activité scientifique et créative, oit les m6mes falacies sont utilisés ayee vanité, manque de tacte, d'insécurité et manque de rigueur par de nombreux écrivains et auteurs. Der Autor bescreibt humorvolí die nicht gut bekannt aber sehr generále Fehíer im schriftliche Geschichte. Die sind sehr alítágliche aher weniger William HACKETT flsnER es profesor de la Brandeis University. Además de Historian's Fallacies, ha publicado Growing Oíd itt A,nerica. Oxford University Press, 1978; Albion s Seed: Faur Rritish Folkways itt America. Oxford University Press, 1989; Paul Revere's Ride. Oxford Ijniversity Press, 1994; Tite Crear Wave: Price Revolurion and tite Rhythm of J-fisrory. Oxford University Press. 1996. 293 David Hacketr Fis/ter Las lá/acias del historiador analysierte Fehíer, die man kann aucb in andere wissentschaftliche und kreative Felde finden, wo diese betrtihige Sátze gemacht sind inimer wenn der Autor unsicher, weniger exakt oder stólz Uber seine Werke ist

Las falacias del historiador.

El autor describe con gran acidez humorística los vicios y fallos más co-munes, pero no por ello más conocidos, del oficio del historiador. Sus hallaz-gos en este sector son extrapolables a otros sectores de la actividad científica y creativa, donde muchos escritores y autores caen en las mismas falacias con presunción, falta de tacto, inseguridad y falta de rigor por. ABSTRACTS L'auteur décrit avec maitrise des falacies et erreurs typiques du métier de l'historien. Ce sont des erreurs trés communs mais pas trés reconnus, et on peut les trouver aussi bien dans d'autres secteurs de l'activité scientifique et créative, oit les m6mes falacies sont utilisés ayee vanité, manque de tacte, d'insécurité et manque de rigueur par de nombreux écrivains et auteurs. Der Autor bescreibt humorvolí die nicht gut bekannt aber sehr generále Fehíer im schriftliche Geschichte. Die sind sehr alítágliche aher weniger William HACKETT flsnER es profesor de la Brandeis University. Además de Historian's Fallacies, ha publicado Growing Oíd itt A,nerica. Oxford University Press, 1978; Albion s Seed: Faur Rritish Folkways itt America. Oxford University Press, 1989; Paul Revere's Ride. Oxford Ijniversity Press, 1994; Tite Crear Wave: Price Revolurion and tite Rhythm of J-fisrory. Oxford University Press. 1996. 293 David Hacketr Fis/ter Las lá/acias del historiador analysierte Fehíer, die man kann aucb in andere wissentschaftliche und kreative Felde finden, wo diese betrtihige Sátze gemacht sind inimer wenn der Autor unsicher, weniger exakt oder stólz Uber seine Werke ist

Harnessing a High Cargo-Capacity Transposon for Genetic Applications in Vertebrates

Viruses and transposons are efficient tools for permanently delivering foreign DNA into vertebrate genomes but exhibit diminished activity when cargo exceeds 8 kilobases (kb). This size restriction limits their molecular genetic and biotechnological utility, such as numerous therapeutically relevant genes that exceed 8 kb in size. Furthermore, a greater payload capacity vector would accommodate more sophisticated cis cargo designs to modulate the expression and mutagenic risk of these molecular therapeutics. We show that the Tol2 transposon can efficiently integrate DNA sequences larger than 10 kb into human cells. We characterize minimal sequences necessary for transposition (miniTol2) in vivo in zebrafish and in vitro in human cells. Both the 8.5-kb Tol2 transposon and 5.8-kb miniTol2 engineered elements readily function to revert the deficiency of fumarylacetoacetate hydrolase in an animal model of hereditary tyrosinemia type 1. Together, Tol2 provides a novel nonviral vector for the delivery of large genetic payloads for gene therapy and other transgenic applications

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Las falacias del historiador

El autor describe con gran acidez humorística los vicios y fallos más comunes, pero no por ello más conocidos, del oficio del historiador. Sus hallazgos en este sector son extrapolables a otros sectores de la actividad científica y creativa donde muchos escritores y autores caen en las mismas falacias con presunción, falta de tacto, inseguridad y falta de rigor por

Historians' Fallacies : Toward A Logic of Historical Thought

New Yorkxiii, 338 p.; 20 c