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1.
Cell ; 186(6): 1092-1096, 2023 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-36931238

RESUMEN

Noa Hourvitz is a graduate of the Science Training Encouraging Peace (STEP) program. The STEP Program funds pairs of Israeli and Palestinian students to study together for the length of their graduate degrees. She writes about the friendship she developed with her STEP partner and how science bridged political barriers.


Asunto(s)
Estudiantes , Femenino , Humanos , Política , Israel , Árabes
2.
Cell ; 181(6): 1218-1231.e27, 2020 06 11.
Artículo en Inglés | MEDLINE | ID: mdl-32492404

RESUMEN

The discovery of the 2,000-year-old Dead Sea Scrolls had an incomparable impact on the historical understanding of Judaism and Christianity. "Piecing together" scroll fragments is like solving jigsaw puzzles with an unknown number of missing parts. We used the fact that most scrolls are made from animal skins to "fingerprint" pieces based on DNA sequences. Genetic sorting of the scrolls illuminates their textual relationship and historical significance. Disambiguating the contested relationship between Jeremiah fragments supplies evidence that some scrolls were brought to the Qumran caves from elsewhere; significantly, they demonstrate that divergent versions of Jeremiah circulated in parallel throughout Israel (ancient Judea). Similarly, patterns discovered in non-biblical scrolls, particularly the Songs of the Sabbath Sacrifice, suggest that the Qumran scrolls represent the broader cultural milieu of the period. Finally, genetic analysis divorces debated fragments from the Qumran scrolls. Our study demonstrates that interdisciplinary approaches enrich the scholar's toolkit.


Asunto(s)
Secuencia de Bases/genética , Genética/historia , Piel/metabolismo , Animales , Cristianismo/historia , Historia Antigua , Humanos , Israel , Judaísmo/historia
3.
Annu Rev Biochem ; 83: 1-44, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24437663

RESUMEN

My scientific journeys began at Oxford nearly 50 years ago. My paths have taken me from magnetic resonance through enzyme systems to antibodies, which led directly to glycobiology. Oxford University's first industrial grant helped the development of the technology for isolating and sequencing oligosaccharides from glycoproteins. This technology was disseminated through a spin-off company, Oxford GlycoSystems, and by the establishment of the Glycobiology Institute. The technology gave rise to the concept of glycoforms, which allow diversification of a protein's properties. Iminosugars, which are glucosidase inhibitors, can interfere with the initial steps of glycan processing on proteins and inhibit three-dimensional folding of glycoproteins. Glucosidase targets for therapy include viral envelope glycoproteins. Clinical trials of an iminosugar as an antiviral for dengue virus are under way. Another iminosugar activity, inhibition of glycolipid synthesis, resulted in a drug for Gaucher disease, which was approved worldwide in 2002. The success of the company and the institute allowed me to undertake several initiatives, in the United Kingdom and abroad, that might help the paths of future generations of scientists.


Asunto(s)
Glicómica/historia , Alergia e Inmunología/historia , Animales , Antígenos , Investigación Biomédica/historia , Diseño de Fármacos , Inglaterra , Glucosidasas/química , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Israel
4.
Proc Natl Acad Sci U S A ; 121(29): e2318465121, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-38968094

RESUMEN

Media exposure to graphic images of violence has proliferated in contemporary society, particularly with the advent of social media. Extensive exposure to media coverage immediately after the 9/11 attacks and the Boston Marathon bombings (BMB) was associated with more early traumatic stress symptoms; in fact, several hours of BMB-related daily media exposure was a stronger correlate of distress than being directly exposed to the bombings themselves. Researchers have replicated these findings across different traumatic events, extending this work to document that exposure to graphic images is independently and significantly associated with stress symptoms and poorer functioning. The media exposure-distress association also appears to be cyclical over time, with increased exposure predicting greater distress and greater distress predicting more media exposure following subsequent tragedies. The war in Israel and Gaza, which began on October 7, 2023, provides a current, real-time context to further explore these issues as journalists often share graphic images of death and destruction, making media-based graphic images once again ubiquitous and potentially challenging public well-being. For individuals sharing an identity with the victims or otherwise feeling emotionally connected to the Middle East, it may be difficult to avoid viewing these images. Through a review of research on the association between exposure to graphic images and public health, we discuss differing views on the societal implications of viewing such images and advocate for media literacy campaigns to educate the public to identify mis/disinformation and understand the risks of viewing and sharing graphic images with others.


Asunto(s)
Medios de Comunicación de Masas , Terrorismo , Humanos , Terrorismo/psicología , Israel , Guerra , Medios de Comunicación Sociales , Trastornos por Estrés Postraumático/psicología , Estrés Psicológico/psicología
5.
Proc Natl Acad Sci U S A ; 121(22): e2313496121, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38771874

RESUMEN

Closing the achievement gap for minority students in higher education requires addressing the lack of belonging these students experience. This paper introduces a psychological intervention that strategically targets key elements within the learning environment to foster the success of minority students. The intervention sought to enhance Palestinian minority student's sense of belonging by increasing the presence of their native language. We tested the effectiveness of the intervention in two field experiments in Israel (n > 20,000), at the height of the COVID-19 pandemic when all classes were held via Zoom. Lecturers in the experimental condition added a transcript of their names in Arabic to their default display (English/Hebrew only). Our findings revealed a substantial and positive impact on Palestinian student's sense of belonging, class participation, and overall grades. In experiment 1, Palestinian student's average grade increased by 10 points. In experiment 2, there was an average increase of 4 points among Palestinian students' semester grade. Our intervention demonstrates that small institutional changes when carefully crafted can have a significant impact on minority populations. These results have significant implications for addressing educational disparities and fostering inclusive learning environment.


Asunto(s)
Árabes , COVID-19 , Grupos Minoritarios , Estudiantes , Humanos , Israel , Grupos Minoritarios/educación , Grupos Minoritarios/psicología , Estudiantes/psicología , COVID-19/epidemiología , Femenino , Árabes/psicología , Masculino , Aprendizaje , Educación a Distancia/métodos , SARS-CoV-2
6.
Development ; 150(18)2023 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-37746870

RESUMEN

Priti Agarwal is a Postdoctoral Researcher in Ronen Zaidel-Bar's lab (Tel Aviv University, Israel) interested in deciphering the mechanical regulation of organogenesis. Priti is one of the cohort of Development's first Pathway to Independence Programme Fellows, which aims to support postdocs in obtaining their first faculty position. We met with Priti over Teams to learn more about her career using the Caenorhabditis elegans gonad as a model system and the future of her research as she seeks an independent position.


Asunto(s)
Caenorhabditis elegans , Gónadas , Humanos , Femenino , Animales , Israel , Modelos Biológicos , Organogénesis
7.
PLoS Pathog ; 20(9): e1012591, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39348417

RESUMEN

Parasites, including pathogens, can adapt to better exploit their hosts on many scales, ranging from within an infection of a single individual to series of infections spanning multiple host species. However, little is known about how the genomes of parasites in natural communities evolve when they face diverse hosts. We investigated how Bartonella bacteria that circulate in rodent communities in the dunes of the Negev Desert in Israel adapt to different species of rodent hosts. We propagated 15 Bartonella populations through infections of either a single host species (Gerbillus andersoni or Gerbillus pyramidum) or alternating between the two. After 20 rodent passages, strains with de novo mutations replaced the ancestor in most populations. Mutations in two mononucleotide simple sequence repeats (SSRs) that caused frameshifts in the same adhesin gene dominated the evolutionary dynamics. They appeared exclusively in populations that encountered G. andersoni and altered the dynamics of infections of this host. Similar SSRs in other genes are conserved and exhibit ON/OFF variation in Bartonella isolates from the Negev Desert dunes. Our results suggest that SSR-based contingency loci could be important not only for rapidly and reversibly generating antigenic variation to escape immune responses but that they may also mediate the evolution of host specificity.


Asunto(s)
Infecciones por Bartonella , Bartonella , Especificidad del Huésped , Repeticiones de Microsatélite , Animales , Bartonella/genética , Bartonella/patogenicidad , Especificidad del Huésped/genética , Infecciones por Bartonella/microbiología , Repeticiones de Microsatélite/genética , Gerbillinae/microbiología , Adaptación Fisiológica/genética , Israel , Evolución Molecular
8.
Blood ; 144(12): 1300-1313, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-38905634

RESUMEN

ABSTRACT: Neutrophils are the first line of defense against invading pathogens. Neutrophils execute and modulate immune responses by generating reactive oxygen species (ROS). Chronic granulomatous disease (CGD) is a primary immune deficiency disorder of phagocytes, caused by inherited mutations in the genes of the nicotinamide adenine dinucleotide phosphate reduced oxidase enzyme. These mutations lead to failure of ROS generation followed by recurrent bacterial and fungal infections, frequently associated with hyperinflammatory manifestations. We report a multicenter cumulative experience in diagnosing and treating patients with CGD. From 1986 to 2021, 2918 patients experiencing frequent infections were referred for neutrophil evaluation. Among them, 110 patients were diagnosed with CGD: 56 of Jewish ancestry, 48 of Arabic ancestry, and 6 of non-Jewish/non-Arabic ancestry. As opposed to other Western countries, the autosomal recessive (AR) CGD subtypes were predominant in Israel (71/110 patients). Thirty-nine patients had X-linked CGD, in most patients associated with severe infections (clinical severity score ≥3) and poor outcomes, presenting at a significantly earlier age than AR-CGD subtypes. The full spectrum of infections and hyperinflammatory manifestations is described. Six patients had hypomorphic mutations with significantly milder phenotype, clinical severity score ≤2, and better outcomes. Hematopoietic stem cell transplantation was implemented in 39 of 110 patients (35.5%). Successful engraftment was achieved in 92%, with 82% long-term survival and 71% full clinical recovery. CGD is a complex disorder requiring a multiprofessional team. Early identification of the genetic mutation is essential for prompt diagnosis, suitable management, and prevention.


Asunto(s)
Estudios de Asociación Genética , Enfermedad Granulomatosa Crónica , Mutación , Humanos , Enfermedad Granulomatosa Crónica/genética , Enfermedad Granulomatosa Crónica/terapia , Masculino , Femenino , Niño , Preescolar , Lactante , Adolescente , Estudios de Cohortes , Adulto , Adulto Joven , Neutrófilos/patología , Neutrófilos/metabolismo , Neutrófilos/inmunología , NADPH Oxidasas/genética , Israel/epidemiología , Trasplante de Células Madre Hematopoyéticas
9.
Proc Natl Acad Sci U S A ; 120(16): e2218621120, 2023 04 18.
Artículo en Inglés | MEDLINE | ID: mdl-37040414

RESUMEN

Intergroup prejudice is pervasive in many contexts worldwide, leading to discrimination and conflict. Existing research suggests that prejudice is acquired at an early age and that durably improving intergroup relations is extremely challenging, often requiring intense interventions. Building on existing research in social psychology and inspired by the Israeli TV series "You Can't Ask That," which depicts charismatic children from minority groups broaching sensitive topics at the core of intergroup relations, we develop a month-long diversity education program. Our program exposed students to the TV series and facilitated follow-up classroom discussions in which students constructively addressed various sensitive topics at the core of intergroup relations and learned about intergroup similarities, intragroup heterogeneity, and the value of taking others' perspectives. Through two field experiments implemented in Israeli schools, we show that integrating our intervention into school curricula improved Jewish students' attitudes toward minorities and increased some pro-diversity behavior up to 13 wk posttreatment. We further provide suggestive evidence that the intervention was effective by encouraging students to take their outgroups' perspectives and address an element of scalability by delegating implementation responsibilities to classroom teachers in our second study. Our findings suggest that theoretically informed intensive education programs are a promising route to reducing prejudice at a young age.


Asunto(s)
Actitud , Prejuicio , Niño , Humanos , Israel , Instituciones Académicas , Grupos Minoritarios
10.
Proc Natl Acad Sci U S A ; 120(17): e2213563120, 2023 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-37068234

RESUMEN

Recent excavations of Late Antiquity settlements in the Negev Highlands of southern Israel uncovered a society that established commercial-scale viticulture in an arid environment [D. Fuks et al., Proc. Natl. Acad. Sci. U.S.A. 117, 19780-19791 (2020)]. We applied target-enriched genome-wide sequencing and radiocarbon dating to examine grapevine pips that were excavated at three of these sites. Our analyses revealed centuries long and continuous grape cultivation in the Southern Levant. The genetically diverse pips also provided clues to ancient cultivation strategies aimed at improving agricultural productivity and ensuring food security. Applying genomic prediction analysis, a pip dated to the eighth century CE was determined to likely be from a white grape, to date the oldest to be identified. In a kinship analysis, another pip was found to be descendant from a modern Greek cultivar and was thus linked with several popular historic wines that were once traded across the Byzantine Empire. These findings shed light on historical Byzantine trading networks and on the genetic contribution of Levantine varieties to the classic Aegean landscape.


Asunto(s)
Vitis , Vino , Historia Antigua , Vitis/genética , ADN Antiguo , Arqueología , Israel
11.
Lancet ; 403(10441): 2293-2306, 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38705160

RESUMEN

BACKGROUND: Adding ibrutinib to standard immunochemotherapy might improve outcomes and challenge autologous stem-cell transplantation (ASCT) in younger (aged 65 years or younger) mantle cell lymphoma patients. This trial aimed to investigate whether the addition of ibrutinib results in a superior clinical outcome compared with the pre-trial immunochemotherapy standard with ASCT or an ibrutinib-containing treatment without ASCT. We also investigated whether standard treatment with ASCT is superior to a treatment adding ibrutinib but without ASCT. METHODS: The open-label, randomised, three-arm, parallel-group, superiority TRIANGLE trial was performed in 165 secondary or tertiary clinical centres in 13 European countries and Israel. Patients with previously untreated, stage II-IV mantle cell lymphoma, aged 18-65 years and suitable for ASCT were randomly assigned 1:1:1 to control group A or experimental groups A+I or I, stratified by study group and mantle cell lymphoma international prognostic index risk groups. Treatment in group A consisted of six alternating cycles of R-CHOP (intravenous rituximab 375 mg/m2 on day 0 or 1, intravenous cyclophosphamide 750 mg/m2 on day 1, intravenous doxorubicin 50 mg/m2 on day 1, intravenous vincristine 1·4 mg/m2 on day 1, and oral prednisone 100 mg on days 1-5) and R-DHAP (or R-DHAOx, intravenous rituximab 375 mg/m2 on day 0 or 1, intravenous or oral dexamethasone 40 mg on days 1-4, intravenous cytarabine 2 × 2 g/m2 for 3 h every 12 h on day 2, and intravenous cisplatin 100 mg/m2 over 24 h on day 1 or alternatively intravenous oxaliplatin 130 mg/m2 on day 1) followed by ASCT. In group A+I, ibrutinib (560 mg orally each day) was added on days 1-19 of R-CHOP cycles and as fixed-duration maintenance (560 mg orally each day for 2 years) after ASCT. In group I, ibrutinib was given the same way as in group A+I, but ASCT was omitted. Three pairwise one-sided log-rank tests for the primary outcome of failure-free survival were statistically monitored. The primary analysis was done by intention-to-treat. Adverse events were evaluated by treatment period among patients who started the respective treatment. This ongoing trial is registered with ClinicalTrials.gov, NCT02858258. FINDINGS: Between July 29, 2016 and Dec 28, 2020, 870 patients (662 men, 208 women) were randomly assigned to group A (n=288), group A+I (n=292), and group I (n=290). After 31 months median follow-up, group A+I was superior to group A with 3-year failure-free survival of 88% (95% CI 84-92) versus 72% (67-79; hazard ratio 0·52 [one-sided 98·3% CI 0-0·86]; one-sided p=0·0008). Superiority of group A over group I was not shown with 3-year failure-free survival 72% (67-79) versus 86% (82-91; hazard ratio 1·77 [one-sided 98·3% CI 0-3·76]; one-sided p=0·9979). The comparison of group A+I versus group I is ongoing. There were no relevant differences in grade 3-5 adverse events during induction or ASCT between patients treated with R-CHOP/R-DHAP or ibrutinib combined with R-CHOP/R-DHAP. During maintenance or follow-up, substantially more grade 3-5 haematological adverse events and infections were reported after ASCT plus ibrutinib (group A+I; haematological: 114 [50%] of 231 patients; infections: 58 [25%] of 231; fatal infections: two [1%] of 231) compared with ibrutinib only (group I; haematological: 74 [28%] of 269; infections: 52 [19%] of 269; fatal infections: two [1%] of 269) or after ASCT (group A; haematological: 51 [21%] of 238; infections: 32 [13%] of 238; fatal infections: three [1%] of 238). INTERPRETATION: Adding ibrutinib to first-line treatment resulted in superior efficacy in younger mantle cell lymphoma patients with increased toxicity when given after ASCT. Adding ibrutinib during induction and as maintenance should be part of first-line treatment of younger mantle cell lymphoma patients. Whether ASCT adds to an ibrutinib-containing regimen is not yet determined. FUNDING: Janssen and Leukemia & Lymphoma Society.


Asunto(s)
Adenina , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Linfoma de Células del Manto , Piperidinas , Rituximab , Trasplante Autólogo , Vincristina , Humanos , Linfoma de Células del Manto/terapia , Linfoma de Células del Manto/tratamiento farmacológico , Adenina/análogos & derivados , Adenina/administración & dosificación , Adenina/uso terapéutico , Piperidinas/administración & dosificación , Piperidinas/uso terapéutico , Persona de Mediana Edad , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Vincristina/administración & dosificación , Vincristina/uso terapéutico , Rituximab/administración & dosificación , Rituximab/uso terapéutico , Adulto , Ciclofosfamida/administración & dosificación , Ciclofosfamida/uso terapéutico , Anciano , Europa (Continente) , Trasplante de Células Madre Hematopoyéticas/métodos , Prednisona/administración & dosificación , Prednisona/uso terapéutico , Doxorrubicina/administración & dosificación , Adulto Joven , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico , Adolescente , Israel , Resultado del Tratamiento
12.
N Engl J Med ; 386(18): 1712-1720, 2022 05 05.
Artículo en Inglés | MEDLINE | ID: mdl-35381126

RESUMEN

BACKGROUND: On January 2, 2022, Israel began administering a fourth dose of BNT162b2 vaccine to persons 60 years of age or older. Data are needed regarding the effect of the fourth dose on rates of confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and of severe coronavirus disease 2019 (Covid-19). METHODS: Using the Israeli Ministry of Health database, we extracted data on 1,252,331 persons who were 60 years of age or older and eligible for the fourth dose during a period in which the B.1.1.529 (omicron) variant of SARS-CoV-2 was predominant (January 10 through March 2, 2022). We estimated the rate of confirmed infection and severe Covid-19 as a function of time starting at 8 days after receipt of a fourth dose (four-dose groups) as compared with that among persons who had received only three doses (three-dose group) and among persons who had received a fourth dose 3 to 7 days earlier (internal control group). For the estimation of rates, we used quasi-Poisson regression with adjustment for age, sex, demographic group, and calendar day. RESULTS: The number of cases of severe Covid-19 per 100,000 person-days (unadjusted rate) was 1.5 in the aggregated four-dose groups, 3.9 in the three-dose group, and 4.2 in the internal control group. In the quasi-Poisson analysis, the adjusted rate of severe Covid-19 in the fourth week after receipt of the fourth dose was lower than that in the three-dose group by a factor of 3.5 (95% confidence interval [CI], 2.7 to 4.6) and was lower than that in the internal control group by a factor of 2.3 (95% CI, 1.7 to 3.3). Protection against severe illness did not wane during the 6 weeks after receipt of the fourth dose. The number of cases of confirmed infection per 100,000 person-days (unadjusted rate) was 177 in the aggregated four-dose groups, 361 in the three-dose group, and 388 in the internal control group. In the quasi-Poisson analysis, the adjusted rate of confirmed infection in the fourth week after receipt of the fourth dose was lower than that in the three-dose group by a factor of 2.0 (95% CI, 1.9 to 2.1) and was lower than that in the internal control group by a factor of 1.8 (95% CI, 1.7 to 1.9). However, this protection waned in later weeks. CONCLUSIONS: Rates of confirmed SARS-CoV-2 infection and severe Covid-19 were lower after a fourth dose of BNT162b2 vaccine than after only three doses. Protection against confirmed infection appeared short-lived, whereas protection against severe illness did not wane during the study period.


Asunto(s)
COVID-19 , SARS-CoV-2 , Vacuna BNT162 , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19 , Humanos , Israel/epidemiología
13.
N Engl J Med ; 387(3): 227-236, 2022 07 21.
Artículo en Inglés | MEDLINE | ID: mdl-35767475

RESUMEN

BACKGROUND: Limited evidence is available on the real-world effectiveness of the BNT162b2 vaccine against coronavirus disease 2019 (Covid-19) and specifically against infection with the omicron variant among children 5 to 11 years of age. METHODS: Using data from the largest health care organization in Israel, we identified a cohort of children 5 to 11 years of age who were vaccinated on or after November 23, 2021, and matched them with unvaccinated controls to estimate the vaccine effectiveness of BNT162b2 among newly vaccinated children during the omicron wave. Vaccine effectiveness against documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and symptomatic Covid-19 was estimated after the first and second vaccine doses. The cumulative incidence of each outcome in the two study groups through January 7, 2022, was estimated with the use of the Kaplan-Meier estimator, and vaccine effectiveness was calculated as 1 minus the risk ratio. Vaccine effectiveness was also estimated in age subgroups. RESULTS: Among 136,127 eligible children who had been vaccinated during the study period, 94,728 were matched with unvaccinated controls. The estimated vaccine effectiveness against documented infection was 17% (95% confidence interval [CI], 7 to 25) at 14 to 27 days after the first dose and 51% (95% CI, 39 to 61) at 7 to 21 days after the second dose. The absolute risk difference between the study groups at days 7 to 21 after the second dose was 1905 events per 100,000 persons (95% CI, 1294 to 2440) for documented infection and 599 events per 100,000 persons (95% CI, 296 to 897) for symptomatic Covid-19. The estimated vaccine effectiveness against symptomatic Covid-19 was 18% (95% CI, -2 to 34) at 14 to 27 days after the first dose and 48% (95% CI, 29 to 63) at 7 to 21 days after the second dose. We observed a trend toward higher vaccine effectiveness in the youngest age group (5 or 6 years of age) than in the oldest age group (10 or 11 years of age). CONCLUSIONS: Our findings suggest that as omicron was becoming the dominant variant, two doses of the BNT162b2 messenger RNA vaccine provided moderate protection against documented SARS-CoV-2 infection and symptomatic Covid-19 in children 5 to 11 years of age. (Funded by the European Union through the VERDI project and others.).


Asunto(s)
Vacuna BNT162 , COVID-19 , SARS-CoV-2 , Eficacia de las Vacunas , Vacuna BNT162/uso terapéutico , COVID-19/epidemiología , COVID-19/prevención & control , Niño , Preescolar , Humanos , Israel/epidemiología , SARS-CoV-2/efectos de los fármacos , Eficacia de las Vacunas/estadística & datos numéricos , Vacunas Sintéticas/uso terapéutico , Vacunas de ARNm/uso terapéutico
14.
N Engl J Med ; 386(17): 1603-1614, 2022 04 28.
Artículo en Inglés | MEDLINE | ID: mdl-35417631

RESUMEN

BACKGROUND: With large waves of infection driven by the B.1.1.529 (omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), alongside evidence of waning immunity after the booster dose of coronavirus disease 2019 (Covid-19) vaccine, several countries have begun giving at-risk persons a fourth vaccine dose. METHODS: To evaluate the early effectiveness of a fourth dose of the BNT162b2 vaccine for the prevention of Covid-19-related outcomes, we analyzed data recorded by the largest health care organization in Israel from January 3 to February 18, 2022. We evaluated the relative effectiveness of a fourth vaccine dose as compared with that of a third dose given at least 4 months earlier among persons 60 years of age or older. We compared outcomes in persons who had received a fourth dose with those in persons who had not, individually matching persons from these two groups with respect to multiple sociodemographic and clinical variables. A sensitivity analysis was performed with the use of parametric Poisson regression. RESULTS: The primary analysis included 182,122 matched pairs. Relative vaccine effectiveness in days 7 to 30 after the fourth dose was estimated to be 45% (95% confidence interval [CI], 44 to 47) against polymerase-chain-reaction-confirmed SARS-CoV-2 infection, 55% (95% CI, 53 to 58) against symptomatic Covid-19, 68% (95% CI, 59 to 74) against Covid-19-related hospitalization, 62% (95% CI, 50 to 74) against severe Covid-19, and 74% (95% CI, 50 to 90) against Covid-19-related death. The corresponding estimates in days 14 to 30 after the fourth dose were 52% (95% CI, 49 to 54), 61% (95% CI, 58 to 64), 72% (95% CI, 63 to 79), 64% (95% CI, 48 to 77), and 76% (95% CI, 48 to 91). In days 7 to 30 after a fourth vaccine dose, the difference in the absolute risk (three doses vs. four doses) was 180.1 cases per 100,000 persons (95% CI, 142.8 to 211.9) for Covid-19-related hospitalization and 68.8 cases per 100,000 persons (95% CI, 48.5 to 91.9) for severe Covid-19. In sensitivity analyses, estimates of relative effectiveness against documented infection were similar to those in the primary analysis. CONCLUSIONS: A fourth dose of the BNT162b2 vaccine was effective in reducing the short-term risk of Covid-19-related outcomes among persons who had received a third dose at least 4 months earlier. (Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.).


Asunto(s)
Vacuna BNT162 , Vacunas contra la COVID-19 , COVID-19 , Inmunización Secundaria , SARS-CoV-2 , Vacuna BNT162/uso terapéutico , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19/uso terapéutico , Humanos , Inmunización Secundaria/estadística & datos numéricos , Israel/epidemiología , Persona de Mediana Edad , ARN Mensajero , Resultado del Tratamiento
15.
Gastroenterology ; 166(5): 815-825.e22, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38331205

RESUMEN

BACKGROUND & AIMS: In this nationwide study, we explored whether early initiation of biologics is associated with improved outcomes in children and adults with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: All patients diagnosed with CD or UC in Israel (2005-2020) were included in the Epidemiology Group of the Israeli Inflammatory Bowel Disease Research Nucleus cohort, encompassing 98% of the population. We compared disease duration at biologics initiation (ie, 0-3 months, >3-12 months, >1-2 years, and >2-3 years) using the cloning, censoring, and weighting by inverse probabilities method to emulate a target trial, adjusting for time-varying confounders and selection bias. RESULTS: Of the 34,375 included patients (of whom 5240 [15%] were children), 7452 of 19,264 (39%) with CD and 2235 of 15,111 (15%) with UC received biologics. In CD, by 10 years postdiagnosis, the probability of CD-related surgery decreased gradually but modestly with earlier initiation of biologics; a significant difference was noted between >2-3 years (31%) and 0-3 months (18%; P = .02; number needed to treat, 7.7), whereas there was no difference between the 0-3-month and >3-12-month periods. The 10-year probability of steroid dependency for the 0-3-month period (19%) differed both from the >2-3-year (31%; P < .001) and 1-2-year periods (37%; P < .001). In UC, no significant differences in colectomy or steroid dependency rates were observed between the treatment initiation periods. Similar trends were noted in the pediatric population. CONCLUSIONS: Very early initiation of biologics was not associated with some outcomes except for a modest risk reduction of surgery and steroid dependency for CD, which requires confirmation in future studies. In UC, early introduction of biologics was not associated with reduced risk of colectomy or steroid dependency.


Asunto(s)
Productos Biológicos , Colitis Ulcerosa , Enfermedad de Crohn , Humanos , Israel/epidemiología , Femenino , Masculino , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/epidemiología , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/terapia , Niño , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/epidemiología , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/terapia , Adulto , Productos Biológicos/uso terapéutico , Adolescente , Resultado del Tratamiento , Factores de Tiempo , Adulto Joven , Persona de Mediana Edad , Tiempo de Tratamiento/estadística & datos numéricos , Fármacos Gastrointestinales/uso terapéutico , Colectomía
19.
J Med Genet ; 61(8): 783-787, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-38719349

RESUMEN

BACKGROUND: We aimed to analyse the efficacy and added value of a targeted Israeli expanded carrier screening panel (IL-ECSP), beyond the first-tier test covered by the Israeli Ministry of Health (IMOH) and the second-tier covered by the Health Maintenance Organisations (HMOs). METHODS: A curated variant-based IL-ECSP, tailored to the uniquely diverse Israeli population, was offered at two tertiary hospitals and a major genetics laboratory. The panel includes 1487 variants in 357 autosomal recessive and X-linked genes. RESULTS: We analysed 10 115 Israeli samples during an 18-month period. Of these, 6036 (59.7%) were tested as couples and 4079 (40.3%) were singles. Carriers were most frequently identified with mutations in the following genes: GJB2/GJB6 (1:22 allele frequency), CFTR (1:28), GBA (1:34), TYR (1:39), PAH (1:50), SMN1 (1:52) and HEXA (1:56). Of 3018 couples tested, 753 (25%) had no findings, in 1464 (48.5%) only one partner was a carrier, and in 733 (24.3%) both were carriers of different diseases. We identified 79 (2.6%) at-risk couples, where both partners are carriers of the same autosomal recessive condition, or the female carries an X-linked disease. Importantly, 48.1% of these would not have been detected by ethnically-based screening tests currently provided by the IMOH and HMOs, for example, variants in GBA, TYR, PAH and GJB2/GJB6. CONCLUSION: This is the largest cohort of targeted ECSP testing, tailored to the diverse Israeli population. The IL-ECSP expands the identification of couples at risk and empowers their reproductive choices. We recommend endorsing an expanded targeted panel to the National Genetic Carrier Screening programme.


Asunto(s)
Conexina 26 , Pruebas Genéticas , Humanos , Israel/epidemiología , Femenino , Pruebas Genéticas/métodos , Masculino , Conexina 26/genética , Conexinas/genética , Tamización de Portadores Genéticos/métodos , Mutación , Atención Preconceptiva/métodos , Frecuencia de los Genes , Asesoramiento Genético , Heterocigoto , Genes Recesivos , Adulto
20.
Proc Natl Acad Sci U S A ; 119(44): e2209117119, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36279453

RESUMEN

The Hebrew Bible and other ancient Near Eastern texts describe Egyptian, Aramean, Assyrian, and Babylonian military campaigns to the Southern Levant during the 10th to sixth centuries BCE. Indeed, many destruction layers dated to this period have been unearthed in archaeological excavations. Several of these layers are securely linked to specific campaigns and are widely accepted as chronological anchors. However, the dating of many other destruction layers is often debated, challenging the ability to accurately reconstruct the different military campaigns and raising questions regarding the historicity of the biblical narrative. Here, we present a synchronization of the historically dated chronological anchors and other destruction layers and artifacts using the direction and/or intensity of the ancient geomagnetic field recorded in mud bricks from 20 burnt destruction layers and in two ceramic assemblages. During the period in question, the geomagnetic field in this region was extremely anomalous with rapid changes and high-intensity values, including spikes of more than twice the intensity of today's field. The data are useful in the effort to pinpoint these short-term variations on the timescale, and they resolve chronological debates regarding the campaigns against the kingdoms of Israel and Judah, the relationship between the two kingdoms, and their administrations.


Asunto(s)
Biblia , Personal Militar , Humanos , Historia Antigua , Arqueología , Israel , Artefactos
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