Marsupials give birth to immunologically naïve young after a relatively short gestation period compared to eutherians. Consequently, the joey significantly relies on maternal protection, which is the focus of the present review. The milk and the pouch environment are essential contributors to maternal protection for the healthy development of joeys. In this review, we discuss bioactive components found in the marsupial pouch and milk that form cornerstones of maternal protection. These bioactive components include immune cells, immunoglobulins, the s100 family of calcium-binding proteins, lysozymes, whey proteins, antimicrobial peptides and other immune proteins. Furthermore, we investigated the possibility of the presence of plurifunctional components in milk and pouches that are potentially bioactive. These compounds include caseins, vitamins and minerals, oligosaccharides, lipids, and microRNAs. Where applicable, this review addresses variability in bioactive components during different phases of lactation, designed to fulfil the immunological needs of the growing pouch young. Yet there are numerous additional research opportunities to pursue, including uncovering novel bioactive components, investigating their mode of action, dynamics, stability, and ability to penetrate the gut epithelium ensuring systemic actions.

Herbert Mehrtens‘ work and the implications of the historical ideas he advanced went beyond the history of any single discipline. The article therefore addresses three broad issues: (1) Mehrtens‘ reconceptualization of mathematical modernism, in his field-changing book Moderne—Sprache—Mathematik (1990) and other works, as an epistemic and cultural phenomenon in a way that could potentially reach across and also beyond the sciences and also link scientific and cultural modernisms; (2) the extension of his work to the history of modernity itself via the concept of “technocratic modernism”; (3) his seminal contributions to the historiography of the sciences and technology during the National Socialist period, focusing on his critique of claims that mathematics, the natural sciences and technology were morally or politically “neutral” during or after the Nazi era, and on his counter-claim that mathematicians and other scientists had in fact mobilized themselves and their knowledge in support of Nazism’s central political projects. Taken as a guide for understanding science-politics relations in general, Mehrtens‘ work was and remains a counterweight to the political abstinence adopted by many who have followed the “cultural turn” in history of science and technology. In the broadest sense, the article is a plea for the culturally relevant and politically engaged historiography of the sciences and humanities that Mehrtens himself pursued.

Bentonites are readily available clays used in the livestock industry as feed additives to reduce aflatoxin (AF) exposure; their potential interaction with nutrients is the main concern limiting their use, however. The objective of the present study was to determine the safety of a dietary sodium-bentonite (Na-bentonite) supplement as a potential AF adsorbent, using juvenile Sprague Dawley (SD) rats as a research model. Animals were fed either a control diet or a diet containing Na-bentonite at 0.25% and 2% (w/w) inclusion rate. Growth, serum, and blood biochemical parameters, including selected serum vitamins (A and E) and elements such as calcium (Ca), potassium (K), iron (Fe), and zinc (Zn) were measured. The mineral characteristics and the aflatoxin B1 sorption capacity of Na-bentonite were also determined. By the end of the study, males gained more weight than females in control and Na-bentonite groups (p ≤ 0.0001); the interaction between treatment and sex was not significant (p = 0.6780), however. Some significant differences between the control group and bentonite treatments were observed in serum biochemistry and vitamin and minerals measurements; however, parameters fell within reference clinical values reported for SD rats and no evidence of dose-dependency was found. Serum Na and Na/K ratios were increased, while K levels were decreased in males and females from Na-bentonite groups. Serum Zn levels were decreased only in males from Na-bentonite treatments. Overall, results showed that inclusion of Na-bentonite at 0.25% and 2% did not cause any observable toxicity in a 3-month rodent study.

Obesity is one of the major contributors to the excess mortality seen in people with severe mental illness (SMI) and in low- and middle-income countries people with SMI may be at an even greater risk. In this study, we aimed to determine the prevalence of obesity and overweight in people with SMI and investigate the association of obesity and overweight with sociodemographic variables, other physical comorbidities, and health-risk behaviours. This was a multi-country cross-sectional survey study where data were collected from 3989 adults with SMI from three specialist mental health institutions in Bangladesh, India, and Pakistan. The prevalence of overweight and obesity was estimated using Asian BMI thresholds. Multinomial regression models were then used to explore associations between overweight and obesity with various potential determinants. There was a high prevalence of overweight (17·3 %) and obesity (46·2 %). The relative risk of having obesity (compared to normal weight) was double in women (RRR = 2·04) compared with men. Participants who met the WHO recommendations for fruit and vegetable intake had 2·53 (95 % CI: 1·65–3·88) times greater risk of having obesity compared to those not meeting them. Also, the relative risk of having obesity in people with hypertension is 69 % higher than in people without hypertension (RRR = 1·69). In conclusion, obesity is highly prevalent in SMI and associated with chronic disease. The complex relationship between diet and risk of obesity was also highlighted. People with SMI and obesity could benefit from screening for non-communicable diseases, better nutritional education, and context-appropriate lifestyle interventions.

The clinical field of depression and other mood disorders is characterised by the vast heterogeneity between those who present for care, and the highly variable degree of response to the range of psychological, pharmacological and physical treatments currently provided. These individual differences likely have a genetic component, and leveraging genetic risk is appealing because genetic risk factors point to causality. The possibility that individual genotyping at entry to health care may be a key way forward is worthy of discussion (Torkamani et al., 2018).

Coconut farming contributes to the livelihoods of millions of people in tropical countries but is less frequently considered as a threat to biodiversity compared to other palm commodities such as oil palm. The expansion of coconut farming alongside other smallholder agriculture in Sulawesi, Indonesia, is of potential concern as the region is a centre of species endemism. We studied bird diversity and community structure in forests, coconut palm plantations and mixed farmland in Gorontalo Province, northern Sulawesi. Forest and non-forest sites supported similar numbers of species overall, but compared to agricultural areas, forest sites had communities that were more diverse and more even (i.e. different species were present at similar abundances). We found far fewer endemic species in agricultural areas compared to forests, and the communities in palm plantations and mixed farmland sites were dominated by generalist birds, with few indicator taxa. Nevertheless, there was a higher number of endemic species in coconut palm plantations than in mixed farmland sites. These findings mirror patterns of biotic homogenization documented elsewhere in the Wallacea centre of endemism, and imply that coconut palm plantations have comparable biodiversity value to other farmland systems. Increased protection of lowland forests and improved management of coconut farms could be important for supporting the conservation of the endemic birds of Sulawesi in the long term, but this warrants further study.

The recruitment of participants for research studies may be subject to bias. The Prospective Imaging Study of Ageing (PISA) aims to characterize the phenotype and natural history of healthy adult Australians at high future risk of Alzheimer’s disease (AD). Participants approached to take part in PISA were selected from existing cohort studies with available genomewide genetic data for both successfully and unsuccessfully recruited participants, allowing us to investigate the genetic contribution to voluntary recruitment, including the genetic predisposition to AD. We use a polygenic risk score (PRS) approach to test to what extent the genetic risk for AD, and related risk factors predict participation in PISA. We did not identify a significant association of genetic risk for AD with study participation, but we did identify significant associations with PRS for key causal risk factors for AD, IQ, household income and years of education. We also found that older and female participants were more likely to take part in the study. Our findings highlight the importance of considering bias in key risk factors for AD in the recruitment of individuals for cohort studies.

In this paper, we investigate the thermal evolution in a one-dimensional bagasse stockpile. The mathematical model involves four unknowns: the temperature, oxygen content, liquid water content and water vapour content. We first nondimensionalize the model to identify dominant terms and so simplify the system. We then calculate solutions for the approximate and full system. It is shown that under certain conditions spontaneous combustion will occur. Most importantly, we show that spontaneous combustion can be avoided by sequential building. To be specific, in a situation where, say, a $4.7\,$m stockpile can spontaneously combust, we could construct a $3\,$m pile and then some days later add another $1.7\,$m to produce a stable $4.7\,$m pile.

Background: Our aim was to develop a National Quality Indicators Set for the Care of Adults Hospitalized for Neurological Problems, to serve as a foundation to build regional or national quality initiatives in Canadian neurology centres. Methods: We used a national eDelphi process to develop a suite of quality indicators and a parallel process of surveys and patient focus groups to identify patient priorities. Canadian content and methodology experts were invited to participate. To be included, >70% of participants had to rate items as critical and <15% had to rate it as not important. Two rounds of surveys and consensus meetings were used identify and rank indicators, followed by national consultation with members of the Canadian Neurological Society. Results: 38 neurologists and methodologists and 56 patients/caregivers participated in this project. An initial list of 91 possible quality indicators was narrowed to 40 indicators across multiple categories of neurological conditions. 21 patient priorities were identified. Conclusions: This quality indicators suite can be used regionally or nationally to drive improvement initiatives for inpatient neurology care. In addition, we identified multiple opportunities for further research where evidence was lacking or patient and provider priorities did not align.

OBJECTIVES/GOALS: Glioblastomas (GBMs) are heterogeneous, treatment-resistant tumors that are driven by populations of cancer stem cells (CSCs). In this study, we perform an epigenetic-focused functional genomics screen in GBM organoids and identify WDR5 as an essential epigenetic regulator in the SOX2-enriched, therapy resistant cancer stem cell niche. METHODS/STUDY POPULATION: Despite their importance for tumor growth, few molecular mechanisms critical for CSC population maintenance have been exploited for therapeutic development. We developed a spatially resolved loss-of-function screen in GBM patient-derived organoids to identify essential epigenetic regulators in the SOX2-enriched, therapy resistant niche. Our niche-specific screens identified WDR5, an H3K4 histone methyltransferase responsible for activating specific gene expression, as indispensable for GBM CSC growth and survival. RESULTS/ANTICIPATED RESULTS: In GBM CSC models, WDR5 inhibitors blocked WRAD complex assembly and reduced H3K4 trimethylation and expression of genes involved in CSC-relevant oncogenic pathways. H3K4me3 peaks lost with WDR5 inhibitor treatment occurred disproportionally on POU transcription factor motifs, required for stem cell maintenance and including the POU5F1(OCT4)::SOX2 motif. We incorporated a SOX2/OCT4 motif driven GFP reporter system into our CSC cell models and found that WDR5 inhibitor treatment resulted in dose-dependent silencing of stem cell reporter activity. Further, WDR5 inhibitor treatment altered the stem cell state, disrupting CSC in vitro growth and self-renewal as well as in vivo tumor growth. DISCUSSION/SIGNIFICANCE: Our results unveiled the role of WDR5 in maintaining the CSC state in GBM and provide a rationale for therapeutic development of WDR5 inhibitors for GBM and other advanced cancers. This conceptual and experimental framework can be applied to many cancers, and can unmask unique microenvironmental biology and rationally designed combination therapies.

Albedo is a key factor in modulating the absorption of solar radiation on ice surfaces. Satellite measurements have shown a general reduction in albedo across the Greenland ice sheet over the past few decades, particularly along the western margin of the ice sheet, a region known as the Dark Zone (albedo < 0.45). Here we chose a combination of Landsat 4–8 and Sentinel 2 imagery to enable us to derive the longest record of albedo variations in the Dark Zone, running from 1984 to 2020. We developed a simple, pragmatic and efficient sensor transformation to provide a long time series of consistent, harmonized satellite imagery. Narrow to broadband conversion algorithms were developed from regression models of harmonized satellite data and in situ albedo from the Program for Monitoring of the Greenland Ice Sheet (PROMICE) automatic weather stations. The albedo derived from the harmonized Landsat and Sentinel 2 data shows that the maximum extent of the Dark Zone expanded rapidly between 2005 and 2007, increasing to ~280% of the average annual maximum extent of 2900 km2 to ~8000 km2 since. The Dark Zone is continuing to darken slowly, with the average annual minimum albedo decreasing at a rate of $\sim \!-0.0006 \pm 0.0004 \, {\rm a}^{-1}$ (p = 0.16, 2001–2020).

Recent theoretical models have posited that increases in self-injurious thoughts and behaviors (SITBs) during adolescence may be linked to failures in biological stress regulation in contexts of social stress. However, there is a lack of data examining this hypothesis during the transition to adolescence, a sensitive period of development characterized by changes across socioaffective and psychophysiological domains. Building on principles from developmental psychopathology and the RDoC framework, the present study used a longitudinal design in a sample of 147 adolescents to test whether interactions among experiences of social (i.e., parent and peer) conflict and cardiac arousal (i.e., resting heart rate) predicted adolescents’ engagement in SITBs (i.e., nonsuicidal self-injury, NSSI; and suicidal ideation; SI) across 1-year follow-up. Prospective analyses revealed that adolescents experiencing a combination of greater peer, but not family, conflict and higher cardiac arousal at baseline showed significant longitudinal increases in NSSI. In contrast, social conflict did not interact with cardiac arousal to predict future SI. Findings indicate that greater peer-related interpersonal stress in adolescents may increase risk for future NSSI among youth with physiological vulnerabilities (i.e., higher resting heart rate) that may be markers of maladaptive stress responses. Future research should examine these processes at finer timescales to elucidate whether these factors are proximal predictors of within-day SITBs.

In 2017 the Scottish Government passed the Child Poverty (Scotland) Act with the commitment to significantly reduce the relative child poverty rate from the current prevailing level of around 25% to 10% by 2030/31. In response, the government introduced the Scottish Child Payment (SCP) that provides a direct transfer to households at a fixed rate per eligible child – currently £25 per week. In this paper we explore, using a micro to macro modelling approach, the effectiveness of using the SCP to achieve the Scottish child poverty targets. While we find that the ambitious child poverty targets can technically be met solely using the SCP, the necessary payment of £165 per week amounting to a total government cost of £3 billion per year, makes the political and economy-wide barriers significant. A key issue with only using the SCP is the non-linearity in the response to the payment; as the payment increases, the marginal gain in the reduction of child poverty decreases – this is particularly evident after payments of £80 per week. A ‘policy-mix’ option combining the SCP, targeted cash transfers and other policy levels (such as childcare provision) seems the most promising approach to reaching the child poverty targets.

In recent years there has been an upsurge in what has come to be called “quantitative history.” Despite the enthusiasm for this approach, however, some of its critics have validly claimed that its payoffs have all too often failed to live up to its promises of new and more accurate findings. Perhaps a central reason for this criticism is that although the quantitative historian may have been sufficiently thorough in collecting his data, he has often failed to apply to them the sensitive techniques of modern data analysis. Rather, he has continued to rely on more traditional methods of description such as means and percentages. As a result, quantitative works are often long on tables and short on analysis.