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Since 1991, some 2,000 Aramaic ostraca deriving from the south of Israel have appeared on the antiquities market and are now scattered in 9 museums and libraries and 21 private collections. Of these, the majority are still not formally published, and in this second volume in the series, Bezalel Porten continues the publication of this important corpus of 4th century B.C.E. economic texts. With the expert epigraphic assistance of Ada Yardeni and hand-copies by her as well, Porten here provides the second volume of texts, organized by “dossier” based on the primary personage cited in the text. Color photographs (where available), ceramic descriptions, hand-copies, transcription, translation, and commentary are provided for each text, along with tables of seven grain dossiers. This publication will become the primary resource for information on these texts, which provide insight into the economic, social, and religious lives of Idumeans in the late Persian and early Hellenistic periods.

No detailed description available for \"Textbook of Aramaic Ostraca from Idumea, volume 3\".

Some 340 Aramaic ostraca of the Persian and Hellenistic periods have been excavated at 32 sites in Israel, from Yokneam in the north to Eilat in the south, with Arad and Beersheba being the main contributory sites. By far, however, the largest cache of texts is what has come to be known as \"the Idumean ostraca\". These did not come from formal excavations but began to appear on the antiquities market in 1991. Since then, some 2,000 ostraca have reached 9 museums and libraries and 21 private collections. Of these, the majority are still not formally published, and in this volume (and those to follow), Bezalel Porten undertakes to provide a comprehensive edition of all these texts, in many cases as an editio princeps . Porten, with the expert epigraphic assistance of Ada Yardeni and hand-copies by her as well, here provides the first volume of texts, organized by \"dossier\" based on the primary personage cited in the text. Color photographs (where available), ceramic descriptions, hand-copies, transcription, translation, and commentary are provided for each text, along with figures and tables, and introductions and summaries of each dossier. An included CD contains a catalogue of all the texts and three color key-word-in-context concordances, for words, personal names, and months for the entire corpus. This publication will become the primary resource for information on these texts.

No adjuvant treatment has been established for patients who remain at high risk for hepatocellular carcinoma recurrence after curative-intent resection or ablation. We aimed to assess the efficacy of adjuvant atezolizumab plus bevacizumab versus active surveillance in patients with high-risk hepatocellular carcinoma. In the global, open-label, phase 3 IMbrave050 study, adult patients with high-risk surgically resected or ablated hepatocellular carcinoma were recruited from 134 hospitals and medical centres in 26 countries in four WHO regions (European region, region of the Americas, South-East Asia region, and Western Pacific region). Patients were randomly assigned in a 1:1 ratio via an interactive voice–web response system using permuted blocks, using a block size of 4, to receive intravenous 1200 mg atezolizumab plus 15 mg/kg bevacizumab every 3 weeks for 17 cycles (12 months) or to active surveillance. The primary endpoint was recurrence-free survival by independent review facility assessment in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT04102098. The intention-to-treat population included 668 patients randomly assigned between Dec 31, 2019, and Nov 25, 2021, to either atezolizumab plus bevacizumab (n=334) or to active surveillance (n=334). At the prespecified interim analysis (Oct 21, 2022), median duration of follow-up was 17·4 months (IQR 13·9–22·1). Adjuvant atezolizumab plus bevacizumab was associated with significantly improved recurrence-free survival (median, not evaluable [NE]; [95% CI 22·1–NE]) compared with active surveillance (median, NE [21·4–NE]; hazard ratio, 0·72 [adjusted 95% CI 0·53–0·98]; p=0·012). Grade 3 or 4 adverse events occurred in 136 (41%) of 332 patients who received atezolizumab plus bevacizumab and 44 (13%) of 330 patients in the active surveillance group. Grade 5 adverse events occurred in six patients (2%, two of which were treatment related) in the atezolizumab plus bevacizumab group, and one patient (<1%) in the active surveillance group. Both atezolizumab and bevacizumab were discontinued because of adverse events in 29 patients (9%) who received atezolizumab plus bevacizumab. Among patients at high risk of hepatocellular carcinoma recurrence following curative-intent resection or ablation, recurrence-free survival was improved in those who received atezolizumab plus bevacizumab versus active surveillance. To our knowledge, IMbrave050 is the first phase 3 study of adjuvant treatment for hepatocellular carcinoma to report positive results. However, longer follow-up for both recurrence-free and overall survival is needed to assess the benefit–risk profile more fully. F Hoffmann-La Roche/Genentech.

BackgroundJoubert syndrome (JS) is a recessively inherited ciliopathy characterised by congenital ocular motor apraxia (COMA), developmental delay (DD), intellectual disability, ataxia, multiorgan involvement, and a unique cerebellar and brainstem malformation. Over 40 JS-associated genes are known with a diagnostic yield of 60%–75%.In 2018, we reported homozygous hypomorphic missense variants of the SUFU gene in two families with mild JS. Recently, heterozygous truncating SUFU variants were identified in families with dominantly inherited COMA, occasionally associated with mild DD and subtle cerebellar anomalies.MethodsWe reanalysed next generation sequencing (NGS) data in two cohorts comprising 1097 probands referred for genetic testing of JS genes.ResultsHeterozygous truncating and splice-site SUFU variants were detected in 22 patients from 17 families (1.5%) with strong male prevalence (86%), and in 8 asymptomatic parents. Patients presented with COMA, hypotonia, ataxia and mild DD, and only a third manifested intellectual disability of variable severity. Brain MRI showed consistent findings characterised by vermis hypoplasia, superior cerebellar dysplasia and subtle-to-mild abnormalities of the superior cerebellar peduncles. The same pattern was observed in two out of three tested asymptomatic parents.ConclusionHeterozygous truncating or splice-site SUFU variants cause a novel neurodevelopmental syndrome encompassing COMA and mild JS, which likely represent overlapping entities. Variants can arise de novo or be inherited from a healthy parent, representing the first cause of JS with dominant inheritance and reduced penetrance. Awareness of this condition will increase the diagnostic yield of JS genetic testing, and allow appropriate counselling about prognosis, medical monitoring and recurrence risk.

Life expectancy has steadily increased in the last two centuries, while healthspan has been lagging behind. Survival into extreme ages strongly clusters within families which often exhibit a delayed onset of (multi)morbidity, yet the underlying protective genetic mechanisms are still largely undefined. We performed affected sib-pair linkage analysis in 212 sibships enriched for ancestral longevity and identified four genomic regions (LOD ≥3.0) at . , and . Within these regions, we prioritized 12 rare protein-altering variants in seven candidate genes ( and ) located in longevity-associated loci. Notably, a missense variant in (rs200818241), was present in two sibships. Using human- and mouse-based cell models, we showed that rs200818241 reduced protein stability and attenuated activation of the canonical cGAS-STING pathway in a cell-type specific manner. This dampened signalling mitigated inflammation and delayed cellular senescence, mechanisms that may contribute to the survival advantage of variant carriers. Our findings indicate novel rare variants and candidate genes linked to familial longevity and highlight the cGAS-STING pathway as a potential contributor to the protective mechanisms underlying human longevity.

Despite decades of efforts, the actinide-carbon triple bond has remained an elusive target, defying isolation in any compound. Herein, we report the successful stabilization of uranium-carbon triple bonds in carbide-bridged bimetallic [U≡C−Ce] units encapsulated inside fullerene cages of C72 and C78. The molecular structures of UCCe@C2n and the nature of the U≡C triple bond were characterized through X-ray crystallography and various spectroscopic analyses, revealing very short uranium-carbon bonds of 1.921(6) and 1.930(6) Å, with the metals existing in their highest oxidation states of +6 and +4 for uranium and cerium, respectively. Quantum-chemical studies further demonstrate that the C2n cages are crucial for stabilizing the [UVI≡C−CeIV] units through covalent and coordinative interactions. This work offers a new fundamental understanding of the elusive uranium-carbon triple bond and informs the design of complexes with similar bonding motifs, opening up new possibilities for creating distinctive molecular compounds and materials.