Animal residues found on tiny Lower Paleolithic tools reveal their use in butchery

Stone tools provide a unique window into the mode of adaptation and cognitive abilities of Lower Paleolithic early humans. The persistently produced large cutting tools (bifaces/handaxes) have long been an appealing focus of research in the reconstruction of Lower Paleolithic survival strategies, at the expenses of the small flake tools considered by-products of the stone production process rather than desired end products. Here, we use use-wear, residues and technological analyses to show direct and very early evidence of the deliberate production and use of small flakes for targeted stages of the prey butchery process at the late Lower Paleolithic Acheulian site of Revadim, Israel. We highlight the significant role of small flakes in Lower Paleolithic adaptation alongside the canonical large handaxes. Our results demonstrate the technological and cognitive flexibility of early human groups in the Levant and beyond at the threshold of the departure from Lower Paleolithic lifeways

Early evidence of stone tool use in bone working activities at Qesem Cave, Israel

For a long while, the controversy surrounding several bone tools coming from pre-Upper Palaeolithic contexts favoured the view of Homo sapiens as the only species of the genus Homo capable of modifying animal bones into specialised tools. However, evidence such as South African Early Stone Age modified bones, European Lower Palaeolithic flaked bone tools, along with Middle and Late Pleistocene bone retouchers, led to a re-evaluation of the conception of Homo sapiens as the exclusive manufacturer of specialised bone tools. The evidence presented herein include use wear and bone residues identified on two flint scrapers as well as a sawing mark on a fallow deer tibia, not associated with butchering activities. Dated to more than 300 kya, the evidence here presented is among the earliest related to tool-assisted bone working intended for non-dietary purposes, and contributes to the debate over the recognition of bone working as a much older behaviour than previously thought. The results of this study come from the application of a combined methodological approach, comprising use wear analysis, residue analysis, and taphonomy. This approach allowed for the retrieval of both direct and indirect evidence of tool-assisted bone working, at the Lower Palaeolithic site of Qesem Cave (Israel)

Measurable Residual Disease (MRD) as a Surrogate Efficacy-Response Biomarker in AML

In acute myeloid leukemia (AML) many patients experience relapse, despite the achievement of morphological complete remission; therefore, conventional morphologic criteria are currently considered inadequate for assessing the quality of the response after treatment. Quantification of measurable residual disease (MRD) has been established as a strong prognostic marker in AML and patients that test MRD negative have lower relapse rates and better survival than those who test positive. Different techniques, varying in their sensitivity and applicability to patients, are available for the measurement of MRD and their use as a guide for selecting the most optimal postremission therapy is an area of active investigation. Although still controversial, MRD prognostic value promises to support drug development serving as a surrogate biomarker, potentially useful for accelerating the regulatory approval of new agents. In this review, we will critically examine the methods used to detect MRD and its potential role as a study endpoint

ACUTE LEUKEMIA AND LATENT TUBERCULOSIS INFECTION IN ITALY: QUANTIFERON-TB TEST SCREENING IN A LOW TUBERCULOSIS INCIDENCE COUNTRY

background: identification of latent tuberculosis infection (LTBI) is a critical step of tuberculosis surveillance, especially in low-incidence countries. however, it is limited to situations with a higher probability of developing active disease, e.g., patients with hematological malignancies. according to guidelines, in TB non-endemic countries, no clear screening program is established at diagnosis for patients with acute leukemia (AL). the primary endpoint of this study was to establish the prevalence of LTBI in patients with a diagnosis of AL using quanti FERON (QFT)-TB. Secondarily, radiological and clinical features driving the increased risk of LTBI were evaluated. methods: QFT-TB screening was performed before induction or consolidation in all patients with AL (myeloid and lymphoid) treated at our Institution between october 2019 and august 2023. results: we accrued 62 patients, of whom 7 (11,3%) tested positive, without any symptoms or signs of active TB, and 2 (3,2%) resulted as indeterminate. all positive patients started prophylaxis with isoniazid 300 mg daily, while patients whose test was indeterminate did not receive any prophylaxis. active TB was excluded by imaging, as well as microscopic, cultural, and molecular examination on bronchoalveolar lavage if signs of any infection were detected. during the 46 months of observation, no patients developed TB reactivation. conclusions: despite the low sample size, 1/10 of our patients had prior TB exposure, hinting that LTBI could be more common than expected in italy. this finding suggests implementing TB screening in the pre-treatment setting, particularly at a time when more active treatments are becoming available also for patients ineligible for intensive chemotherapy

Outcome of COVID-19 patients with haematological malignancies after the introduction of vaccination and monoclonal antibodies. Results from the HM-COV 2.0 study

Patients with haematological malignancies (HM) and SARS-CoV-2 infection present a higher risk of severe COVID-19 and mortality. The aim of the study was to investigate whether vaccination and monoclonal antibodies (mAbs) have modified the outcomes of HM patients with COVID-19. This is a single-centre retrospective study in HM patients hospitalized due to SARS-CoV-2 infection from March 2020 to April 2022. Patients were divided into PRE-V-mAb group (patients hospitalized before the introduction of vaccination and mAbs) and POST-V-mAb group (patients hospitalized after the use of vaccine and mAbs). A total of 126 patients were included (65 PRE-V-mAb and 61 POST-V-mAb). POST-V-mAb patients showed a significantly lower risk of intensive care unit (ICU) admission (8.2% vs. 27.7%, p = 0.005), shorter viral shedding [17 (IQR 10–28) vs. 24 days (IQR 15–50), p = 0.011] and shorter hospitalization length [13 (IQR 7–23) vs. 20 (IQR 14–41) days, p = 0.0003] compared to the PRE-V-mAb group. Nevertheless, both in-hospital and 30-day mortality rates did not significantly differ between the two groups (29.5% POST-V-mAb vs. 36.9% PRE-V-mAb and 21.3% POST-V-mAb vs. 29.2% PRE-V-mAb, respectively). At the multivariable analysis, an active malignancy (p = 0.042), a critical COVID-19 at admission (p = 0.025) and the need for high-level of oxygen support at respiratory worsening [either HFNC/CPAP (p = 0.022) or mechanical ven- tilation (p = 0.011)] were independently associated with in-hospital mortality. In the subgroup of POST-V-mAb patients, receiving therapy with mAbs was a protective factor (p = 0.033). Despite the new therapeutic and preventive strategies avail- able, HM patients with COVID-19 disease represent an extremely vulnerable group with still high mortality rates

Predictors of Early Thrombotic Events in Adult Patients with Acute Myeloid Leukemia: A Real-World Experience

Information regarding the incidence and the prognostic impact of thrombotic events (TE) in non-promyelocytic acute myeloid leukemia (AML) is sparse. Although several risk factors associated with an increased risk of TE development have been recognized, we still lack universally approved guidelines for identification and management of these complications. We retrospectively analyzed 300 consecutive patients with newly diagnosed AML. Reporting the incidence of venous TE (VTE) and arterial TE (ATE) was the primary endpoint. Secondarily, we evaluated baseline patient- and disease-related characteristics with a possible influence of VTE-occurrence probability. Finally, we evaluated the impact of TE on survival. Overall, the VTE incidence was 12.3% and ATE incidence was 2.3%. We identified three independent predictors associated with early-VTE: comorbidities (p = 0.006), platelets count >50x10e9/L (p = 0.006), and a previous history of VTE (p = 0.003). Assigning 1 point to each variable, we observed an overall cumulative incidence of VTE of 18.4% in the high-risk group (>2 points) versus 6.4% in the low-risk group (0–1 point), log-rank = 0.002. Overall, ATE, but not VTE, was associated with poor prognosis (p < 0.001). In conclusion, TE incidence in AML patients is not negligible. We proposed an early-VTE risk score that could be useful for a proper management of VTE prophylaxis

The ISTH DIC-score predicts early mortality in patients with non-promyelocitic acute myeloid leukemia

coagulation disorders frequently complicate the clinical course of acute myeloid leukemia (AML) patients. this study examined the frequency and prognostic significance, with regards of early mortality, of the presence of overt disseminated intravascular coagulation (DIC) at AML diagnosis and its correlation with clinical and biological characteristics. a retrospective analysis of 351 newly diagnosed non-promyelocytic AML patients was conducted, utilizing the 2018 ISTH DIC-Score criteria to evaluate the presence of overt DIC at AML onset. the study cohort had a median age of 65 years with a predominance of male gender (59%). overt DIC was present in 21% of cases and was associated with advanced age, comorbidities, poor performance status, hyperleukocytosis, LDH levels, NPM1 mutations, expression of CD33 and CD4, and lack of expression of CD34. With a median follow-up of 72 months (3–147 months), the 6-year overall survival (OS) was 17.4%, with patients having overt DIC showing significantly poorer outcomes (7.2% compared to 20.3 % of those without DIC, p < 0.001). patients with overt DIC showed markedly high early mortality rates at 30 (42.5% vs 8 %), 60 (49.3% vs 16.9%), and 120 days (64.4% vs 25.6%) from disease onset. In multivariate analysis overt DIC retained its independent prognostic value for early mortality. In conclusion, the prevalence and clinical relevance of DIC in non-promyelocytic AML is not negligible, underlining its potential as an unfavorable prognostic marker. In newly diagnosed patients with AML, early recognition and measure to counteract coagulation disturbances might help mitigate the elevated mortality risk associated with DIC

In BCR-ABL1 Positive B-Cell Acute Lymphoblastic Leukemia, Steroid Therapy Induces Hypofibrinogenemia

Hypofibrinogenemia (HF) in adult acute lymphoblastic leukemia (ALL) of B lineage is uncommon and mostly associated with asparaginase (ASP) delivery. Since we noticed a significant reduction in fibrinogen (FBG) plasma levels even before the first ASP dose, we aim to assess the levels of FBG during induction treatment and explore if the FBG fall correlated with therapies other than asparaginase and/or specific leukemia biological features. We retrospectively analyzed FBG levels in 115 patients with B-ALL. In 74 (64%) out of 115 patients FBG decline occurred during the steroid prephase. In univariate analysis, such a steroid-related HF was significantly associated with BCR-ABL1 rearrangement (p = 0.00158). None of those experiencing HF had significant modifications of liver function tests during induction treatment. Our retrospective study suggests that in B-ALL, steroid therapy can also induce HF and that such an event is preferentially observed in patients carrying BCR-ABL1 rearrangements. The pathogenesis of this phenomenon is still unclear. We attempt to explain it by applying the International Society of Thrombosis and Hemostasis-Disseminated Intravascular Coagulation score (ISTH-DIC score); nonetheless additional studies are needed to clarify further the mechanisms of HF in this subset of patients

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good