Distinguishing early domesticates from their wild progenitors presents a significant obstacle for understanding human-mediated effects in the past. The origin of dogs is particularly controversial because potential early dog remains often lack corroborating evidence that can provide secure links between proposed dog remains and human activity. The Tumat Puppies, two permafrost-preserved Late Pleistocene canids, have been hypothesized to have been littermates and early domesticates due to a physical association with putatively butchered mammoth bones. Through a combination of osteometry, stable isotope analysis, plant macrofossil analysis, and genomic and metagenomic analyses, this study exploits the unique properties of the naturally mummified Tumat Puppies to examine their familial relationship and to determine whether dietary information links them to human activities. The multifaceted analysis reveals that the 14,965–14,046 cal yr BP Tumat Puppies were littermates who inhabited a dry and relatively mild environment with heterogeneous vegetation and consumed a diverse diet, including woolly rhinoceros in their final days. However, because there is no evidence of mammoth consumption, these data do not establish a link between the canids and ancient humans.

We present a mathematical model to investigate heat transfer and mass transport dynamics in the wave-driven free-surface boundary layer of the ocean under the influence of long-crested progressive surface gravity waves. The continuity, momentum and convection–diffusion equations for fluid temperature are solved within a Lagrangian framework. We assume that eddy viscosity and thermometric conductivity are dependent on Lagrangian coordinates, and derive a new form of the second-order Lagrangian mass transport velocity, applicable across the entire finite water depth. We then analyse the convective heat dynamics influenced by the free-surface boundary layer. Rectangular distributions of free-surface temperature (i.e. a Dirichlet boundary condition) are considered, and analytical solutions for thermal boundary layer temperature fields are provided to offer insights into free-surface heat transfer mechanisms affected by ocean waves. Our results suggest the need to improve existing models that neglect the effects of free-surface waves and the free-surface boundary layer on ocean mass transport and heat transfer.

Reducing antimicrobial use (AMU) in livestock may be one of the keys to limit the emergence of antimicrobial resistance (AMR) in bacterial populations, including zoonotic pathogens. This study assessed the temporal association between AMU in livestock and AMR among Campylobacter isolates from human infections in the Netherlands between 2004 – 2020. Moreover, the associations between AMU and AMR in livestock and between AMR in livestock and AMR in human isolates were assessed. AMU and AMR data per antimicrobial class (tetracyclines, macrolides and fluoroquinolones) for Campylobacter jejuni and Campylobacter coli from poultry, cattle, and human patients were retrieved from national surveillance programs. Associations were assessed using logistic regression and the Spearman correlation test. Overall, there was an increasing trend in AMR among human C. jejuni/coli isolates during the study period, which contrasted with a decreasing trend in livestock AMU. In addition, stable trends in AMR in broilers were observed. No significant associations were observed between AMU and AMR in domestically produced broilers. Moderate to strong positive correlations were found between the yearly prevalence of AMR in broiler and human isolates. Reducing AMU in Dutch livestock alone may therefore not be sufficient to tackle the growing problem of AMR in Campylobacter among human cases in the Netherlands. More insight is needed regarding the population genetics and the evolutionary processes involved in resistance and fitness among Campylobacter.

The United States Government (USG) public-private partnership “Accelerating COVID-19 Treatment Interventions and Vaccines” (ACTIV) was launched to identify safe, effective therapeutics to treat patients with Coronavirus Disease 2019 (COVID-19) and prevent hospitalization, progression of disease, and death. Eleven original master protocols were developed by ACTIV, and thirty-seven therapeutic agents entered evaluation for treatment benefit. Challenges encountered during trial implementation led to innovations enabling initiation and enrollment of over 26,000 participants in the trials. While only two ACTIV trials continue to enroll, the recommendations here reflect information from all the trials as of May 2023. We review clinical trial implementation challenges and corresponding lessons learned to inform future therapeutic clinical trials implemented in response to a public health emergency and the conduct of complex clinical trials during “peacetime,” as well.

Accurately quantifying all the components of the surface energy balance (SEB) is a prerequisite for the reliable estimation of surface melt and the surface mass balance over ice and snow. This study quantifies the SEB closure by comparing the energy available for surface melt, determined from continuous measurements of radiative fluxes and turbulent heat fluxes, to the surface ablation measured on the Greenland ice sheet between 2003 and 2023. We find that the measured daily energy available for surface melt exceeds the observed surface melt by on average 18 ± 30 W m−2 for snow and 12 ± 54 W m−2 for ice conditions (mean ± SD), which corresponds to 46 and 10% of the average energy available for surface melt, respectively. When the surface is not melting, the daily SEB is on average closed within 5 W m−2. Based on the inter-comparison of different ablation sensors and radiometers installed on different stations, and on the evaluation of modelled turbulent heat fluxes, we conclude that measurement uncertainties prevent a better daily to sub-daily SEB closure. These results highlight the need and challenges in obtaining accurate long-term in situ SEB observations for the proper evaluation of climate models and for the validation of remote sensing products.

Background: We evaluated vorasidenib (VOR), a dual inhibitor of mIDH1/2, in patients with mIDH1/2 glioma (Phase 3; NCT04164901). Methods: Patients with residual/recurrent grade 2 mIDH1/2 oligodendroglioma or astrocytoma were enrolled (age ≥12; Karnofsky Performance Score ≥80; measurable non-enhancing disease; surgery as only prior treatment; not in immediate need of chemoradiotherapy). Patients were stratified by 1p19q status and baseline tumor size and randomized 1:1 to VOR 40 mg or placebo (PBO) daily in 28-day cycles. Endpoints included imaging-based progression-free survival (PFS), time to next intervention (TTNI), tumor growth rate (TGR), health-related quality of life (HRQoL), neurocognition and seizure activity. Results: 331 patients were randomized (VOR, 168; PBO, 163). The median age was 40.0 years. 172 and 159 patients had histologically confirmed oligodendroglioma and astrocytoma, respectively. Treatment with VOR significantly improved PFS and TTNI. Median PFS: VOR, 27.7 mos; PBO, 11.1 mos (P=0.000000067). Median TTNI: VOR, not reached; PBO, 17.8 mos (P=0.000000019). Treatment with VOR resulted in shrinkage of tumor volume. Post-treatment TGR: VOR, -2.5% (95% CI: -4.7, -0.2); PBO, 13.9% (95% CI: 11.1, 16.8). HRQoL and neurocognition were preserved and seizure control was maintained. VOR had a manageable safety profile. Conclusions: VOR was effective in mIDH1/2 diffuse glioma not in immediate need of chemoradiotherapy.

The comprehensive overview of Neogene lithostratigraphy in the eastern Netherlands dates back to the mid-1970s. In the present study, continuous gamma-ray logs and in situ sediment core samples from six boreholes in the area allowed palynological and mollusc analyses and wireline log-based correlation. These investigations were aimed at updating and revising the existing Neogene lithostratigraphy within the Stratigraphic Nomenclature of the Netherlands by integrating litho-, bio-, and sequence-stratigraphic approaches. The analytical results yielded the establishment of new holo- and lectostratotype sections, together with cross-border interregional correlation. The lithostratigraphic revision resulted in the modified definition of the Aalten, Eibergen and Delden members and the definition of two new proposed members: the Dale and Doetinchem members. The Ticheloven bed, removed in earlier studies, is proposed to be reinstated, and the Stemerdink Bed is upgraded in its hierarchical status to the Stemerdink member. All lithostratigraphic units are included in the present Miocene subdivision of the Groote Heide and Diessen formations, which include three recognisable unconformities: the Early-Miocene Unconformity (EMU), Mid-Miocene Unconformity (MMU) and Late-Miocene Unconformity (LMU). The new, revised, reintroduced and existing local lithostratigraphic units and sequences are discussed with their counterparts in the south and southeast of the Netherlands, in Germany and Belgium, and from this a regionally consistent framework has emerged of the regional Neogene lithostratigraphy.

Deep-water surface wave breaking affects the transfer of mass, momentum, energy and heat between the air and sea. Understanding when and how the onset of wave breaking will occur remains a challenge. The mechanisms that form unforced steep waves, i.e. nonlinearity or dispersion, are thought to have a strong influence on the onset of wave breaking. In two dimensions and in deep water, spectral bandwidth is the main factor that affects the roles these mechanism play. Existing studies, in which the relationship between spectral bandwidth and wave breaking onset is investigated, present varied and sometimes conflicting results. We perform potential-flow simulations of two-dimensional focused wave groups on deep water to better understand this relationship, with the aim of reconciling existing studies. We show that the way in which steepness is defined may be the main source of confusion in the literature. Locally defined steepness at breaking onset reduces as a function of bandwidth, and globally defined (spectral) steepness increases. The relationship between global breaking onset steepness and spectral shape (using the parameters bandwidth and spectral skewness) is too complex to parameterise in a general way. However, we find that the local surface slope of maximally steep non-breaking waves, of all spectral bandwidths and shapes that we simulate, approaches a limit of $1/\tan ({\rm \pi} /3)\approx 0.5774$. This slope-based threshold is simple to measure and may be used as an alternative to existing kinematic breaking onset thresholds. There is a potential link between slope-based and kinematic breaking onset thresholds, which future work should seek to better understand.

We recently reported on the radio-frequency attenuation length of cold polar ice at Summit Station, Greenland, based on bi-static radar measurements of radio-frequency bedrock echo strengths taken during the summer of 2021. Those data also allow studies of (a) the relative contributions of coherent (such as discrete internal conducting layers with sub-centimeter transverse scale) vs incoherent (e.g. bulk volumetric) scattering, (b) the magnitude of internal layer reflection coefficients, (c) limits on signal propagation velocity asymmetries (‘birefringence’) and (d) limits on signal dispersion in-ice over a bandwidth of ~100 MHz. We find that (1) attenuation lengths approach 1 km in our band, (2) after averaging 10 000 echo triggers, reflected signals observable over the thermal floor (to depths of ~1500 m) are consistent with being entirely coherent, (3) internal layer reflectivities are ≈–60$\to$–70 dB, (4) birefringent effects for vertically propagating signals are smaller by an order of magnitude relative to South Pole and (5) within our experimental limits, glacial ice is non-dispersive over the frequency band relevant for neutrino detection experiments.

Lacquerwork technologies comprise multiple techniques depending on countries, time, and traditions. Carved Asian lacquers applied on wooden objects consist of multiple thin uncolored or pigmented layers spread over the surface. To radiocarbon (14C) date these types of objects, often only the wooden structure is used. Here we report on a set of carved lacquered objects that were dated based on stylistic form, 14C dating of the wooden structure and of the Asian lacquers. THM-Py-GC-MS and micro-Raman spectroscopy were used to confirm the molecular composition of the lacquers and helped assessing the pretreatment protocol. The lacquers analyzed contained between 20 and 50% wt carbon, thus 2–5 mg of sample were necessary for 14C dating. The dates obtained on wood and lacquers showed a reliable correlation. The results suggest that, in most cases, it is sufficient to sample a part of the lacquer layers to date an object. We advise to perform an acid pretreatment followed by a successive solvent immersion with an increasing polarity. Dating different components of a lacquered object can also help to understand previous restoration interventions that frequently occur for ancient lacquered objects. Ceramic, metallic, and other objects covered with Asian lacquers can also be dated using this approach.

An increased number of rogue waves, relative to standard distributions, can be induced by unidirectional waves passing over abrupt decreases in water depth. We investigate this phenomenon in a more general setting of multidirectional waves. We examine the influence of the directionality on the occurrence probability of rogue waves using laboratory experiments and fully nonlinear potential flow simulations. Based on the analysis of the statistics of random waves, we find that directional spreading reduces the formation probability of rogue waves relative to unidirectional seas. Nevertheless, for typical values of directional spreading in the ocean ($15^{\circ }\unicode{x2013}30^{\circ }$), our numerical results suggest that there is still a significant enhancement to the number of rogue waves just beyond the top of a depth discontinuity.

Trauma exposure is prevalent globally and is a defining event for the development of posttraumatic stress disorder (PTSD), characterised by intrusive thoughts, avoidance behaviours, hypervigilance and negative alterations in cognition and mood. Exposure to trauma elicits a range of physiological responses which can interact with environmental factors to confer relative risk or resilience for PTSD. This systematic review summarises the findings of longitudinal studies examining biological correlates predictive of PTSD symptomology. Databases (Pubmed, Scopus and Web of Science) were systematically searched using relevant keywords for studies published between 1 January 2021 and 31 December 2022. English language studies were included if they were original research manuscripts or meta-analyses of cohort investigations that assessed longitudinal relationships between one or more molecular-level measures and either PTSD status or symptoms. Eighteen of the 1,042 records identified were included. Studies primarily included military veterans/personnel, individuals admitted to hospitals after acute traumatic injury, and women exposed to interpersonal violence or rape. Genomic, inflammation and endocrine measures were the most commonly assessed molecular markers and highlighted processes related to inflammation, stress responding, and learning and memory. Quality assessments were done using the Systematic Appraisal of Quality in Observational Research, and the majority of studies were rated as being of high quality, with the remainder of moderate quality. Studies were predominantly conducted in upper-income countries. Those performed in low- and middle-income countries were not broadly representative in terms of demographic, trauma type and geographic profiles, with three out of the four studies conducted assessing only female participants, rape exposure and South Africa, respectively. They also did not generate multimodal data or use machine learning or multilevel modelling, potentially reflecting greater resource limitations in LMICs. Research examining molecular contributions to PTSD does not adequately reflect the global burden of the disorder.