OBJECTIVES/GOALS: This study aims to develop objectively scored histological characteristics of early oral leukoplakia, which may be correlated with molecular pathways predictive of progression into proliferative verrucous leukoplakia (PVL). The secondary aim is to develop a biomarker profile to be used in diagnosis, staging, and management of PVL. METHODS/STUDY POPULATION: Clinical and pathology records of 120 patients with oral leukoplakia and/or PVL were reviewed. Eight patients were selected—all had serial biopsies over time leading to PVL suspicion. Specimens were deidentified and subjected to blinded examination by a board certified oral pathologist, then scored relative to the extent of each of the commonly accepted histologic characteristics of PVL: hyperkeratosis, acanthosis, blunt rete ridges, hyperchromatic nuclei, increased nuclear-cytoplasmic ratio, dyskeratosis, and surface corrugation. Given these results, a larger subset of patient samples will be labeled and assayed for expression of epidermal growth factor receptor tyrosine kinases and downstream pro-oncogenic signaling mediators. Expression of these factors will be tested against progression to PVL. RESULTS/ANTICIPATED RESULTS: Histologically, in scoring the specimens from eight subjects, the characteristics of acanthosis, dyskeratosis, and blunted rete ridges had the strongest correlation with eventual progression to PVL. These criteria will therefore be recommended as an objective histopathologic method of identification of patients with high risk of development of PVL, and therefore malignant potential. We expect the results of the biomarker assay to provide a molecular basis for predicting PVL pathogenesis. Particularly, we anticipate pro-oncogenic targets such as EGFR, PI3K, Akt, and mTOR pathways will show increased expression as leukoplakic lesions progress. These results would then provide the basis for testing patient samples for expression of these markers in a longitudinal study of PVL emergence and progression. DISCUSSION/SIGNIFICANCE: The aggressive nature of PVL, with a rate of malignant transformation of 61% and mortality rate of 40%, requires close clinical monitoring in order to improve patient outcomes. Therefore, well defined objective clinical, histologic, and molecular criteria are critical for early detection of sites likely to progress to PVL and subsequent malignancy.

Optimum nutrition plays a major role in the achievement and maintenance of good health. The Nutrition Society of the UK and Ireland and the Sabri Ülker Foundation, a charity based in Türkiye and focused on improving public health, combined forces to highlight this important subject. A hybrid conference was held in Istanbul, with over 4000 delegates from sixty-two countries joining the proceedings live online in addition to those attending in person. The primary purpose was to inspire healthcare professionals and nutrition policy makers to better consider the role of nutrition in their interactions with patients and the public at large to reduce the prevalence of non-communicable diseases such as obesity and type 2 diabetes. The event provided an opportunity to share and learn from different approaches in the UK, Türkiye and Finland, highlighting initiatives to strengthen research in the nutritional sciences and translation of that research into nutrition policy. The presenters provided evidence of the links between nutrition and disease risk and emphasised the importance of minimising risk and implementing early treatment of diet-related disease. Suggestions were made including improving health literacy and strengthening policies to improve the quality of food production and dietary behaviour. A multidisciplinary approach is needed whereby Governments, the food industry, non-governmental groups and consumer groups collaborate to develop evidence-based recommendations and appropriate joined-up policies that do not widen inequalities. This summary of the proceedings will serve as a gateway for those seeking to access additional information on nutrition and health across the globe.

This article is based on an EAA session in Kiel in 2021, in which thirteen contributors provide their response to Robb and Harris's (2018) overview of studies of gender in the European Neolithic and Bronze Age, with a reply by Robb and Harris. The central premise of their 2018 article was the opposition of ‘contextual Neolithic gender’ to ‘cross-contextual Bronze Age gender’, which created uneasiness among the four co-organizers of the Kiel meeting. Reading Robb and Harris's original article leaves the impression that there is an essentialist ‘Neolithic’ and ‘Bronze Age’ gender, the former being under-theorized, unclear, and unstable, the latter binary, unchangeable, and ideological. While Robb and Harris have clearly advanced the discussion on gender, the perspectives and case studies presented here, while critical of their views, take the debate further, painting a more complex and diverse picture that strives to avoid essentialism.

The apicomplexan parasite Cyclospora cayetanensis causes seasonal foodborne outbreaks of the gastrointestinal illness cyclosporiasis. Prior to the coronavirus disease-2019 pandemic, annually reported cases were increasing in the USA, leading the US Centers for Disease Control and Prevention to develop a genotyping tool to complement cyclosporiasis outbreak investigations. Thousands of US isolates and 1 from China (strain CHN_HEN01) were genotyped by Illumina amplicon sequencing, revealing 2 lineages (A and B). The allelic composition of isolates was examined at each locus. Two nuclear loci (CDS3 and 360i2) distinguished lineages A and B. CDS3 had 2 major alleles: 1 almost exclusive to lineage A and the other to lineage B. Six 360i2 alleles were observed – 2 exclusive to lineage A (alleles A1 and A2), 2 to lineage B (B1 and B2) and 1 (B4) was exclusive to CHN_HEN01 which shared allele B3 with lineage B. Examination of heterozygous genotypes revealed that mixtures of A- and B-type 360i2 alleles occurred rarely, suggesting a lack of gene flow between lineages. Phylogenetic analysis of loci from whole-genome shotgun sequences, mitochondrial and apicoplast genomes, revealed that CHN_HEN01 represents a distinct lineage (C). Retrospective examination of epidemiologic data revealed associations between lineage and the geographical distribution of US infections plus strong temporal associations. Given the multiple lines of evidence for speciation within human-infecting Cyclospora, we provide an updated taxonomic description of C. cayetanensis, and describe 2 novel species as aetiological agents of human cyclosporiasis: Cyclospora ashfordi sp. nov. and Cyclospora henanensis sp. nov. (Apicomplexa: Eimeriidae).

The magnitude and azimuth of horizontal ice flow at Camp Century, Greenland have been measured several times since 1963. Here, we provide a further two independent measurements over the 2017–21 period. Our consensus estimate of horizontal ice flow from four independent satellite-positioning solutions is 3.65 ± 0.13 m a−1 at an azimuth of 236 ± 2°. A portion of the small, but significant, differences in ice velocity and azimuth reported between studies likely results from spatial gradients in ice flow. This highlights the importance of restricting inter-study comparisons of ice flow estimates to measurements surveyed within a horizontal distance of one ice thickness from each other. We suggest that ice flow at Camp Century is stable on seasonal to multi-decadal timescales. The airborne and satellite laser altimetry record indicates an ice thickening trend of 1.1 ± 0.3 cm a−1 since 1994. This thickening trend is qualitatively consistent with previously inferred ongoing millennial-scale ice thickening at Camp Century. The ice flow divide immediately north of Camp Century may now be migrating southward, although the reasons for this divide migration are poorly understood. The Camp Century flowlines presently terminate in the vicinity of Innaqqissorsuup Oqquani Sermeq (Gade Gletsjer) on the Melville Bay coast.

In the US Southwest and Northwest Mexico, people and turkeys (Meleagris gallopavo) have had a reciprocal relationship for millennia; turkeys supplied feathers, meat, and other resources, whereas people provided food, shelter, and care. To investigate how turkeys fit within subsistence, economic production, sociopolitical organization, and religious and ritual practice in the Mimbres Valley of southwestern New Mexico, we report on genetic (mtDNA) and stable isotope (δ13C, δ15N) data from turkeys recovered from Mimbres Classic period (AD 1000–1130) sites. Results indicate that Mimbres aviculturists had haplogroup H1 and H2 turkeys, and most ate maize-based diets similar to humans, but some ate nonmaize and mixed diets. We contextualize these data to other turkey studies from the northern Southwest and discuss how the human-turkey relationship began, the evidence for pens and restricting turkey movement, and the socioecological factors related to turkey management during the Classic period, particularly the challenges associated with providing maize to turkeys during times of environmental stress. This study has broad relevance to places where people managed wild, tame, and domestic animals, and we offer new insights into how prehispanic, small-scale, middle-range agricultural societies managed turkeys for ritual and utilitarian purposes.

The COVID-19 pandemic has harmed many people's mental health globally. Whilst the evidence generated thus far from high-income countries regarding the pandemic's impact on suicide rates is generally reassuring, we know little about its influence on this outcome in lower- and middle-income countries or among marginalised and disadvantaged people. There are some signals for concern regarding the pandemic's potentially unequal impact on suicide rates, with some of the affected demographic subgroups and regions being at elevated risk before the pandemic began. However, the evidence-base for this topic is currently sparse, and studies conducted to date have generally not taken account of pre-pandemic temporal trends. The collection of accurate, complete and comparable data on suicide rate trends in ethnic minority and low-income groups should be prioritised. The vulnerability of low-income groups will likely be exacerbated further by the current energy supply and cost-of-living crises in many countries. It is therefore crucial that reassuring messaging highlighting the stability of suicide rates during the pandemic does not lead to complacency among policymakers.

Bustards comprise a highly threatened family of birds and, being relatively fast, heavy fliers with very limited frontal visual fields, are particularly susceptible to mortality at powerlines. These infrastructures can also displace them from immediately adjacent habitat and act as barriers, fragmenting their ranges. With geographically ever wider energy transmission and distribution grids, the powerline threat to bustards is constantly growing. Reviewing the published and unpublished literature up to January 2021, we found 2,774 records of bustard collision with powerlines, involving 14 species. Some studies associate powerline collisions with population declines. To avoid mortalities, the most effective solution is to bury the lines; otherwise they should be either routed away from bustard-frequented areas, or made redundant by local energy generation. When possible, new lines should run parallel to existing structures and wires should preferably be as low and thick as possible, with minimal conductor obstruction of vertical airspace, although it should be noted that these measures require additional testing. A review of studies finds limited evidence that ‘bird flight diverters’ (BFDs; devices fitted to wires to induce evasive action) achieve significant reductions in mortality for some bustard species. Nevertheless, dynamic BFDs are preferable to static ones as they are thought to perform more effectively. Rigorous evaluation of powerline mortalities, and effectiveness of mitigation measures, need systematic carcass surveys and bias corrections. Whenever feasible, assessments of displacement and barrier effects should be undertaken. Following best practice guidelines proposed with this review paper to monitor impacts and mitigation could help build a reliable body of evidence on best ways to prevent bustard mortality at powerlines. Research should focus on validating mitigation measures and quantifying, particularly for threatened bustards, the population effects of powerline grids at the national scale, to account for cumulative impacts on bustards and establish an equitable basis for compensation measures.

Negative emotionality (NE) was evaluated as a candidate mechanism linking prenatal maternal affective symptoms and offspring internalizing problems during the preschool/early school age period. The participants were 335 mother–infant dyads from the Maternal Adversity, Vulnerability and Neurodevelopment project. A Confirmatory Bifactor Analysis (CFA) based on self-report measures of prenatal depression and pregnancy-specific anxiety generated a general factor representing overlapping symptoms of prenatal maternal psychopathology and four distinct symptom factors representing pregnancy-specific anxiety, negative affect, anhedonia and somatization. NE was rated by the mother at 18 and 36 months. CFA based on measures of father, mother, child-rated measures and a semistructured interview generated a general internalizing factor representing overlapping symptoms of child internalizing psychopathology accounting for the unique contribution of each informant. Path analyses revealed significant relationships among the general maternal affective psychopathology, the pregnancy- specific anxiety, and the child internalizing factors. Child NE mediated only the relationship between pregnancy-specific anxiety and the child internalizing factors. We highlighted the conditions in which prenatal maternal affective symptoms predicts child internalizing problems emerging early in development, including consideration of different mechanistic pathways for different maternal prenatal symptom presentations and child temperament.

Given the growing use of Artificial intelligence (AI) and machine learning (ML) methods across all aspects of environmental sciences, it is imperative that we initiate a discussion about the ethical and responsible use of AI. In fact, much can be learned from other domains where AI was introduced, often with the best of intentions, yet often led to unintended societal consequences, such as hard coding racial bias in the criminal justice system or increasing economic inequality through the financial system. A common misconception is that the environmental sciences are immune to such unintended consequences when AI is being used, as most data come from observations, and AI algorithms are based on mathematical formulas, which are often seen as objective. In this article, we argue the opposite can be the case. Using specific examples, we demonstrate many ways in which the use of AI can introduce similar consequences in the environmental sciences. This article will stimulate discussion and research efforts in this direction. As a community, we should avoid repeating any foreseeable mistakes made in other domains through the introduction of AI. In fact, with proper precautions, AI can be a great tool to help reduce climate and environmental injustice. We primarily focus on weather and climate examples but the conclusions apply broadly across the environmental sciences.