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Identifying communal rituals in the Paleolithic is of scientific importance, as it reflects the expression of collective identity and the maintenance of group cohesion. This study provides evidence indicating the practice of deep cave collective rituals in the Levant during the Early Upper Paleolithic (EUP) period. It is demonstrated that these gatherings occurred within a distinct ritual compound and were centered around an engraved object in the deepest part of Manot Cave, a pivotal EUP site in southwest Asia. The ritual compound, segregated from the living areas, encompasses a large gallery partitioned by a cluster of remarkable speleothems. Within this gallery, an engraved boulder stands out, displaying geometric signs suggesting a unique representation of a tortoise. Isotopic analysis of calcite crusts on the boulder's grooves revealed alignment with values found in speleothems from the cave dated to ~37 to 35 ka BP. Additionally, meticulous shape analysis of the grooves' cross-section and the discernible presence of microlinear scratches on the grooves' walls confirmed their anthropogenic origin. Examination of stalagmite laminae (36 ka BP) near the engraved boulder revealed a significant presence of wood ash particles within. This finding provides evidence for using fire to illuminate the dark, deep part of the cave during rituals. Acoustic tests conducted in various cave areas indicate that the ritual compound was well suited for communal gatherings, facilitating conversations, speeches, and hearing. Our results underscore the critical role of collective practices centered around a symbolic object in fostering a functional social network within the regional EUP communities., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: Recently, breakpoints of Enterobacterales to amikacin were changed from MIC ≤ 16 mg/L to MIC ≤ 4 mg/L based mainly on laboratory data with little supporting clinical evidence. Our aim was to investigate the relation between MIC of Enterobacterales to amikacin and mortality among patients with Enterobacterales bacteraemia from a urinary tract source treated with amikacin., Patients and Methods: This retrospective, single-centre study included patients with Enterobacterales urinary source bacteraemia treated with amikacin, with Low (MIC ≤ 4 mg/L) and High (MIC 8 or 16 mg/L) MICs. A cohort of patients treated with ertapenem was used to assess if amikacin MIC is a marker of severity independent of antimicrobial treatment. The primary outcome was 30-day mortality. Multivariate logistic regression analysis was done to assess risk factors for mortality., Results: We included 85 patients, 46 (54.1%) were male, and mean age was 79.0 years (SD 11.7). Sixty-one patients (71.8%) had Low MIC and 24 (28.2%) had High MIC. Thirty-day mortality was 8.2% and 29.2% in the Low and High MIC groups, respectively (P = 0.031). Risk factors for 30-day mortality were age, infection by Enterobacterales other than Escherichia coli and high amikacin MIC. In a cohort of 88 patients treated with ertapenem, amikacin MIC was not associated with 30-day mortality., Conclusions: We demonstrated a relation between higher amikacin MIC levels (8 and 16 mg/L) and increased 30-day mortality in patients treated with amikacin for bacteraemia secondary to a urinary source. These findings support the new CLSI breakpoint change of Enterobacterales to amikacin., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Sepsis is a life-threatening organ dysfunction syndrome caused by a dysregulated host response to infection that has a high mortality rate. Proprotein convertase subtilisin kexin 9 (PCSK9) is a serine protease secreted by the liver. Its binding to the low-density lipoprotein (LDL) receptor enhances its degradation, causing an increase in LDL levels in the blood. Objectives : Administering a PCSK9 inhibitor leading to an increase in lipid uptake by the liver may positively affect septic patients due to the increased removal of endotoxins. Methods : This preliminary study aimed to examine the safety of PCSK9 inhibitor use in septic and septic shock patients. We treated five septic patients in the intensive care unit with 300 mg of alirocumab following serious adverse events for 28 days. Results : Four of our patients did not experience any adverse events, and all of them survived. One patient died after discharge from the intensive care unit, and this death was presumably not related to the study drug. The patients rapidly recovered from the inflammatory stage of sepsis. Conclusions : Alirocumab appears safe in severe sepsis and septic shock patients. The outcome data are promising. Only a basic safety profile can be assessed based on this pilot study. Further study with a PCSK-9 inhibitor in septic or septic shock patients is required to further determine its benefit in ICU patients.

Introduction: The accuracy of urine culture results can be affected by pre-analytical factors such as transport delays and storage conditions. The objectives of this study were to analyze urine collection practices and assess the impact of introducing boric acid tubes for urine collection on quantitative urinary bacterial cultures of hospitalized patients in medical wards., Methods: A quasi-experimental pre-post study conducted in an acute care facility. In the pre-intervention phase (2020-2021), urine samples were transported without preservatives at room temperature. In 2022 (post-intervention), we transitioned to boric acid transport tubes, evaluating its effect on significant bacterial growth (≥ 105 CFU/ml). Bivariate and multivariate analyses identified predictors of culture positivity., Results: Throughout the duration of the study, a total of 12,660 urine cultures were analyzed. Date and time documentation was complete for 38.3% of specimens. Culture positivity was higher with longer processing times: positivity was 21.3% (220/1034) when specimens were processed within 4 h, 28.4% (955/3364) when processed in 4-24 h, and 32.9% (137/417) when processed after 24 h (p < 0.0001). For 4-24-hour processing, positivity decreased from 30.4% (704/2317) pre-intervention to 24.0% (251/1047) post-intervention (p < 0.001), with no significant changes in < 4 or ≥ 24-hour specimens. Stratified analysis by processing time revealed that the intervention was associated with reduced positivity only in cultures processed within 4-24 h (OR 0.80, 95% CI 0.67-0.94; p = 0.008)., Conclusion: The introduction of boric acid transport tubes predominantly influenced cultures transported within a 4-24-hour window. This presents an opportunity to improve urine tract infection diagnostic practices in healthcare settings., (© 2024. The Author(s).)

Objective: Burkholderia pseudomallei, the etiological cause of melioidosis, is a soil saprophyte endemic in South-East Asia, where it constitutes a public health concern of high-priority. Melioidosis cases are sporadically identified in nonendemic areas, usually associated with travelers or import of goods from endemic regions. Due to extensive intercontinental traveling and the anticipated climate change-associated alterations of the soil bacterial flora, there is an increasing concern for inadvertent establishment of novel endemic areas, which may expand the global burden of melioidosis. Rapid diagnosis, isolation and characterization of B. pseudomallei isolates is therefore of utmost importance particularly in non-endemic locations., Data Description: We report the genome sequences of two novel clinical isolates (MWH2021 and MST2022) of B. pseudomallei identified in distinct acute cases of melioidosis diagnosed in two individuals arriving to Israel from India and Thailand, respectively. The data includes preliminary genetic analysis of the genomes determining their phylogenetic classification in rapport to the genomes of 131 B. pseudomallei strains documented in the NCBI database. Inspection of the genomic data revealed the presence or absence of loci encoding for several documented virulence determinants involved in the molecular pathogenesis of melioidosis. Virulence analysis in murine models of acute or chronic melioidosis established that both strains belong to the highly virulent class of B. pseudomalleii., (© 2024. The Author(s).)

Nitrogen vacancy (NV) center-based magnetometry has been proven to be a versatile sensor for various classes of magnetic materials in broad temperature and frequency ranges. Here, we use the longitudinal relaxation time T 1 of single NV centers to investigate the spin dynamics of nanometer-thin flakes of α-RuCl 3 at room temperature. We observe a significant reduction in the T 1 in the presence of α-RuCl 3 in the proximity of NVs, which we attribute to paramagnetic spin noise confined in the 2D hexagonal planes. Furthermore, the T 1 time exhibits a monotonic increase with an applied magnetic field. We associate this trend with the alteration of the spin and charge noise in α-RuCl 3 under an external magnetic field. These findings suggest that the influence of the spin dynamics of α-RuCl 3 on the T 1 of the NV center can be used to gain information about the material itself and the technique to be used on other 2D materials.

Introduction: Bloodstream Infections (BSI) are a major cause of death and hospitalization among hemodialysis (HD) patients. The rates of BSI among HD patients vary and are influenced by local patient and pathogen characteristics. Modifications in local infection prevention protocols in light of active surveillance of BSI has been shown to improve clinical outcomes. The aim of this study was to further explore factors associated with BSI in a contemporary cohort of HD patients at a public teaching hospital dialysis center in Israel., Methods: This was a retrospective cohort study of HD patients with a BSI in the years 2014 to 2018. The primary outcome was the occurrence of BSI. Secondary outcomes were to describe the causative pathogens of BSI, and to assess for risk factors for BSI, and mortality., Results: Included were 251 patients. The mean age was 68.5 ± 13.4 years, 66.9% were male. The mean time from initiation of dialysis was 34.76 ± 40.77 months, interquartile range (IQR) 1-47.5 months and the follow up period of the cohort was 25.17 ± 15.9 months. During the observation period, 44 patients (17.5%) developed 54 BSI events, while 10 of them (3.9% of the whole cohort) developed recurrent BSI events. Gram-negative microorganisms caused 46.3% of all BSI events. 31.4% of these BSI were caused by resistant bacteria. In a multivariate logistic regression analysis, patients receiving dialysis through a central line had a significantly increased risk for BSI adjusted Odds Ratio (aOR) 3.907, p = 0.005, whereas patients' weight was mildly protective (aOR 0.971, p = 0.024)., Conclusions: We noted an increased prevalence of gram-negative pathogens in the etiology of BSI in HD patients. Based on our findings, additional empirical antibiotics addressing gram negative bacteria have been added to our empirical treatment protocol. Our findings highlight the need to follow local epidemiology for implementing appropriate preventative measures and for tailoring appropriate empiric antibiotic therapy., (© 2023. The Author(s).)

Background: It is unknown whether convalescent immunoglobulins (cIgGs) are better than convalescent plasma (CP) for patients with coronavirus 2019 (COVID-19)., Methods: In this randomized controlled trial, we assigned high risk COVID-19 patients with ≤10 days of symptoms, to receive cIgGs or CP. The primary endpoint was improvement on day 14 according to the World Health Organization scale. Secondary endpoints were survival on day 14, and improvement, survival, and percent of ventilated patients on day 28, and treatment response in unvaccinated and vaccinated patients., Results: A total of 319 patients were included: 166 received cIgGs and 153 CP. Median age was 64 to 66 years. A total of 112 patients (67.5%) in the cIgG group and 103 patients (67.3%) in the CP group reached the primary endpoint. Difference between groups was 0.1 (95% confidence interval, -10.1 to 10.4; P = .026), failing to reach noninferiority. More patients receiving cIgG improved by day 28 (136 patients [81.9%] and 108 patients [70.6%], respectively; 95% confidence interval, 1.9-20.7; P < .001; for superiority P = .018). Seventeen patients in the cIgG group (10.2%) and 25 patients (16.3%) in the CP group required mechanical ventilation (P = .136). Sixteen (9.6%) and 23 (15%) patients, respectively, died (P = .172). More unvaccinated patients improved by day 28 in the cIgG group (84.1% vs 66.1%; P = .024), and survival was better in the cIgG group (89.9% vs 77.4%; P = .066)., Conclusions: cIgGs failed to reach the primary noninferiority endpoint on day 14 but was superior to CP on day 28. Survival and improvement by day 28 in unvaccinated patients treated with cIgGs were better. In the face of new variants, cIgGs are a viable option for treating COVID-19., Trial Registration Number: My Trials MOH&#95;2021-01-14&#95;009667., Competing Interests: Potential conflicts of interest . Y. M. was a primary investigator on a grant received from KAMADA supporting this study. She also received honoraria for participation in advisory boards from KAMADA and MSD and received honoraria for lectures or writing services from MSD, Pfizer, Medison, and Maccabi health services (paid to author); travel grants from Pfizer (paid to institution); unpaid roles on Israeli Ministry of Health's epidemic preparedness committee and infectious disease and vaccine committee, and as Treasurer to Society for Research and Prevention of Sexually Transmitted Diseases. T. B. N. reports consulting fees from AstraZeneca and MSD; honoraria for participation in advisory boards from AstraZeneca and MSD; and honoraria for lectures and travel grants from AstraZeneca, MSD, and Medison. N. A. is an employee of Kamada and holds Kamada stock options. S. C. is an employee of Kamada and holds Kamada stock options. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Although cooking is regarded as a key element in the evolutionary success of the genus Homo, impacting various biological and social aspects, when intentional cooking first began remains unknown. The early Middle Pleistocene site of Gesher Benot Ya'aqov, Israel (marine isotope stages 18-20; ~0.78 million years ago), has preserved evidence of hearth-related hominin activities and large numbers of freshwater fish remains (>40,000). A taphonomic study and isotopic analyses revealed significant differences between the characteristics of the fish bone assemblages recovered in eight sequential archaeological horizons of Area B (Layer II-6 levels 1-7) and natural fish bone assemblages (identified in Area A). Gesher Benot Ya'aqov archaeological horizons II-6 L1-7 exhibited low fish species richness, with a clear preference for two species of large Cyprinidae (Luciobarbus longiceps and Carasobarbus canis) and the almost total absence of fish bones in contrast to the richness of pharyngeal teeth (>95%). Most of the pharyngeal teeth recovered in archaeological horizons II-6 L1-7 were spatially associated with 'phantom' hearths (clusters of burnt flint microartifacts). Size-strain analysis using X-ray powder diffraction provided evidence that these teeth had been exposed to low temperature (<500 °C), suggesting, together with the archaeological and taphonomic data, that the fish from the archaeological horizons of Area B had been cooked and consumed on site. This is the earliest evidence of cooking by hominins., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The aim of this study was to compare short- and long-term mortality among patients with urosepsis caused by Escherichia coli susceptibile (EC-SC) and resistant (EC-RC) to 3rd generation cephalosporins., Methods: A retrospective cohort study that included all patients with E. coli urosepsis admitted to a 700-bed hospital from January 2014 until December 2019. Mortality up to 30 days, 6 months and 1 year was assessed using logistic multivariate regression analysis and Cox regression analysis., Results: A total of 313 adult were included, 195 with EC-SC and 118 patients with EC-RC. 205 were females (74%), mean age was 79 (SD 12) years. Mean Charlson score was 4.93 (SD 2.18) in the EC-SC group and 5.74 (SD 1.92) in the EC-RC group. Appropriate empiric antibiotic therapy was initiated in 245 (78.3%) patients, 100% in the EC-SC group but only 42.5% in the EC-RC group. 30-day mortality occurred in 12 (6.3%) of EC-SC group and 15 (12.7%) in the EC-RC group. Factors independently associated with 30-day mortality were Charlson score, Pitt bacteremia score, fever upon admission and infection with a EC-RC. Appropriate antibiotic therapy was not independently associated with 30-day mortality. Differences in mortality between groups remained significant one year after the infection and were significantly associated with the Charlson co-morbidity score., Conclusions: Mortality in patients with urosepsis due to E. coli is highly affected by age and comorbidities. Although mortality was higher in the EC-RC group, we could not demonstrate an association with inappropriate empirical antibiotic treatment. Mortality remained higher at 6 months and 1 year long after the infection resolved but was associated mainly with co-morbidity., (© 2022. The Author(s).)