The biopsychosocial model remains a key paradigm for healthcare, despite widely recognised scientific and philosophical shortcomings. Here we report on recent updates integrating evolutionary theory with the biopsychosocial model to provide a more comprehensive and scientifically complete approach to understanding the multiple relevant levels of causation of medical and psychiatric problems.

α-Lactalbumin (α-LA) and β-lactoglobulin (β-LG) are major whey proteins in bovine milk. We studied the effects of these molecules on the intestinal cell response by comparing the native form with the denatured form containing oligomers obtained by treatment with 2,2,2-trifluoroethanol (TFE). We previously reported that proteins in native and TFE-treated forms exhibited cell growth stimulation and cytotoxicity, respectively, in undifferentiated rat crypt IEC-6 and human colon Caco-2 cells. However, neither whey protein showed cytotoxicity even in the TFE-treated form in differentiated Caco-2 cells. Only undifferentiated immature intestinal cells can distinguish between these native and denatured proteins. Moreover, α-LA and β-LG exhibited different oligomer formation characteristics during the TFE treatment. In the present study, we compared the effects of native and TFE-treated whey proteins on IEC-6 cells in more detail. The native forms of both whey proteins exhibited cell proliferative effects in a concentration-dependent manner. For the TFE-treated forms, α-LA showed rapid and potent cytotoxicity, whereas β-LG altered cell responses depending on its concentration and exposure time; lower concentration/shorter exposure and higher concentration/longer exposure induced cell growth stimulation and cytotoxicity, respectively. Pre-treatment of the cell membrane with cholesterol suppressed the effects on the cell response only in TFE-treated β-LG (TFE-β-LG). In a preliminary examination using inhibitors of signal transduction, TFE-treated α-LA acted on the intrinsic apoptosis pathway via Bcl-2-associated X and p53, whereas the action of TFE-LG did not require this pathway. Tyrosine phosphorylation is necessary for the cell proliferation effect of both native whey proteins; however, native α-LA, but not native β-LG, also required activation of the pathway with selective epidermal growth factor receptor tyrosine kinase and Janus kinase 2/3. In summary, the two major bovine milk whey proteins induced similar yet discrete responses in undifferentiated intestinal cells. Even when oligomers are formed, β-LG may be much less hazardous to immature intestinal cells than α-LA.

The bucolic poems of Martius Valerius, first published in 1946, used to be dated to the twelfth century, but thanks to the work of François Dolbeau and Justin Stover, they are now securely dated to the sixth. In this article, I demonstrate that Martius’ fourth eclogue draws extensively on two of the logical works of Boethius, the introduction to the second edition of the commentary on Porphyry's Isagoge and the translation of Aristotle's Peri hermeneias, both from the mid 510s. These works were well known in the twelfth century, but I corroborate the sixth-century dating first by connecting Martius Valerius with Martius Novatus Renatus, editor of a corpus of Boethius’ logical monographs in the 520s, and secondly by arguing that Martius Valerius belonged to a circle of students in Rome who attached themselves to leading senators, including Boethius. I end by considering Martius’ career as quaestor and consul.

Researchers often aim to assess whether repeated measures of an exposure are associated with repeated measures of an outcome. A question of particular interest is how associations between exposures and outcomes may differ over time. In other words, researchers may seek the best form of a temporal model. While several models are possible, researchers often consider a few key models. For example, researchers may hypothesize that an exposure measured during a sensitive period may be associated with repeated measures of the outcome over time. Alternatively, they may hypothesize that the exposure measured immediately before the current time period may be most strongly associated with the outcome at the current time. Finally, they may hypothesize that all prior exposures are important. Many analytic methods cannot compare and evaluate these alternative temporal models, perhaps because they make the restrictive assumption that the associations between exposures and outcomes remains constant over time. Instead, we provide a tutorial describing four temporal models that allow the associations between repeated measures of exposures and outcomes to vary, and showing how to test which temporal model is best supported by the data. By finding the best temporal model, developmental psychopathology researchers can find optimal windows for intervention.

A new observatory site should be investigated for its local climate conditions to see its potential and limitations. In this respect, we examine several meteorological parameters at the site of Timau National Observatory, Indonesia using the ERA5 dataset from 2002 to 2021. Based on this dataset, we conclude that the surface temperature at Timau is around $18.9^{\circ}$C with relatively small temperature variation ($\sim$$1.5^{\circ}$C) over the day. This temperature stability is expected to give advantages to the observatory. In terms of humidity and water vapour, Timau is poor for infrared observations as the median precipitable water vapour exceeds 18 mm, even during the dry season. However, near-infrared observations are feasible. Even though our cloud cover analysis confirms the span of the observing season in the region, we find a significant discrepancy between the clear sky fraction derived from the ERA5 dataset and the one estimated using satellite imagery. Aside from the indicated bias, our results provide insights and directions for the operation and future development of the observatory.

Previous L2 studies used binary Truth-Value-Judgment (TVJ) tasks to investigate L1–L2 differences in scalar implicature derivation (some X implicates some but not all X). They examined participants’ judgments of sentences with weak scalar expressions (“Timothy ate some of the pretzels”) when stronger ones are true (“Timothy ate all of the pretzels”). Some studies indicate adult L2 learners are less likely than L1 users to accept such statements while others found the opposite, concluding that implicature derivation is “costly” for L2 learners, rendering them less pragmatically competent than L1 users. Importantly, related L1 research suggests that TVJ tasks only capture sensitivity to under-informativeness. This sensitivity might be completely overridden by metalinguistic attitudes in binary tasks, whereas graded tasks reveal nuanced judgment patterns. Exploring L2 response behaviors, we tested English L1 speakers and competent German L2 English learners using binary and graded tasks. In both tasks, we found evidence of pragmatic responding with no evidence of differences between groups. Bayes factor analyses of the graded data favored H0 over the hypotheses that L2 learners provide fewer or more rejections to under-informative input than L1 learners. We explore implications for L2 learners’ pragmatic abilities, differences with previous studies, and the role of TVJ tasks in under-informative contexts.

The malicious use of artificial intelligence is growing rapidly, creating major security threats for individuals and the healthcare sector. Individuals with mental illness may be especially vulnerable. Healthcare provider data are a prime target for cybercriminals. There is a need to improve cybersecurity to detect and prevent cyberattacks against individuals and the healthcare sector, including the use of artificial intelligence predictive tools.

Gender and age are central organising principles of social relations, with socially constructed gendered and age-based norms influencing patterns of social behaviour, power and inequality. Despite recent literature highlighting the importance of subjective measures of equality, including as a significant predictor of wellbeing, there is a gap in studies focused on subjective equality in research on ageing. Drawing on an equality ranking exercise and life herstory interviews with 20 older-aged women (65+) in Aotearoa New Zealand, this article focuses on the intersectionality of age and gender, analysing the ways in which participants constructed their experiences of equality over the lifecourse from their standpoint as older-aged women. The analysis reveals a significant rise in subjective equality from childhood to older age, with more varied responses in childhood and a convergence of responses from adolescence onwards. Participants’ constructions of equality differed: age was the dominant construct of equality women ascribed to their childhood years, while gender inequality came to the fore during their teenage years. In early to mid-adulthood, women found ways to navigate gendered inequality in various life domains, while in older adulthood equality was constructed as freedom and life satisfaction. This trajectory suggests that the frames individuals use to make sense of equality and their personal experiences are not fixed; they are fluid and shift throughout the lifecourse.

Folate, vitamin B12, vitamin B6 and riboflavin interact by functioning as cofactors within one-carbon metabolism (OCM), a network of interrelated cellular pathways essential for numerous biological processes, including the biosynthesis of DNA, amino acid interconversions and methylation reactions. The pathways of OCM are influenced by endocrine signals and genetic polymorphisms and are particularly responsive to relevant B-vitamin intakes. Physiological changes in healthy pregnancy, leading to a steady decline in B-vitamin status, add another layer of complexity to the regulation of OCM. Although significant advances have been made to improve our understanding of these pregnancy-related changes, no specific reference ranges yet exist for B-vitamin biomarkers in pregnancy to support normal fetal growth without depleting maternal stores. The lack of pregnancy-related criteria for adequacy of B-vitamin status is in turn a major limitation in identifying pregnant women most at risk of B-vitamin deficiency. Another challenge is that the evidence is very limited to provide a basis for establishing pregnancy-specific dietary recommendations for B-vitamins to support successful pregnancy outcomes. In terms of preventing adverse outcomes, periconceptional folic acid supplementation has a proven role, established more than 30 years ago, in protecting against neural tube defect-affected pregnancies and this has been the major focus of public health policy worldwide. This review evaluates the emerging evidence for the less well recognised role of B-vitamins in preventing hypertensive disorders in pregnancy and the intergenerational effects of B-vitamins on offspring neurodevelopment and cognitive performance during childhood. We also consider the underlying biological mechanisms.

I propose that meta-learned models, and in particular the situation-aware deployment of “learning-to-infer” modules can be advantageously extended to domains commonly thought to lie outside the cognitive, such as motivations and preferences on one hand, and the effectuation of micro- and coping-type behaviors.

Much of today’s academic scholarship of international cultural heritage law circles around cultural heritage’s protection for the benefit of future generations. Despite this, the efforts to systematically examine the concept in more detail are scarcer. This paper seeks to fill this gap by taking a closer look at the ways in which the notion of future generations features in the body of international cultural heritage law. This contribution firstly illustrates how central the idea of protecting cultural heritage for the benefit of future generations is in international cultural heritage law. Despite this centrality, evidenced by an extensive analysis of international and regional hard and soft law, national law, case law, and policy options, its precisely contours the second argument of this paper, is that they remain elusive. Finally, skepticism is voiced over the concept’s potential ambivalent use with respect to the protection of cultural heritage.

This paper develops a monetary R&D-driven endogenous growth model featuring endogenous innovation scales and the price-marginal cost markup. To endogenize the step size of quality improvement, we propose a tradeoff mechanism between the risk of innovation failure and the benefit of innovation success in R&D firms. Several findings emerge from the analysis. First, a rise in the nominal interest rate decreases economic growth; however, its relationship with social welfare is ambiguous. Second, either strengthening patent protection or raising the professional knowledge of R&D firms leads to an ambiguous effect on economic growth. Third, the Friedman rule of a zero nominal interest rate fails to be optimal in view of the social welfare maximum. Finally, our numerical analysis indicates that the extent of patent protection and the level of an R&D firm’s professional knowledge play a crucial role in determining the optimal interest rate.

The operation of the ANU 2.3 m telescope transitioned from classically scheduled remote observing to fully autonomous queue scheduled observing in March 2023. The instrument currently supported is WiFeS, a visible-light low-resolution image-slicing integral field spectrograph with a $25^{\prime\prime}\,\times38^{\prime\prime}$ field of view (offering precision spectrophotometry free from aperture effects). It is highly suitable for rapid spectroscopic follow-up of astronomical transient events and regular cadence observations. The new control system implements flexible queue scheduling and supports rapid response override for target-of-opportunity observations. The ANU 2.3 m is the largest optical telescope to have been retro-fitted for autonomous operation to date, and it remains a national facility servicing a broad range of science cases. We present an overview of the automated control system and report on the first six months of continuous operation.

In the global economy, the international strategies of family firms, influenced by family ownership and management, remain underexplored. Bridging the family business and international business fields, we use the socioemotional wealth lens to examine 1,236 international expansions from 2007 to 2013. Categorizing firms into pure family, nearly pure family, borderline family, and non-family typologies, we assess the influence of internal (experience, knowledge) and external (country risk) factors on their entry modes. Results indicate that higher family involvement in ownership/management increases the preference for greenfield investments over acquisitions or equity alliances, a relationship further moderated by international experience and country risk. This study provides nuanced insights into the international behaviors of family firms.

The omnipresence of change has been singled out as posing an important challenge to law, both in theory and in practice, throughout its history. Arguably, the most efficient method of adapting the law to constant changes is legal education. Recent changes in the global arena have added to the complexity of the expected role of future legal talents, requiring them to acquire not only a profound knowledge of local and global laws but also a variety of legal as well as non-legal skills. This article presents some of the principal challenges faced by law schools and legal education in the world of today. These challenges are then explored using the example of a new Bachelor of Laws (LL.B.) degree programme in Chinese Law and Global Legal Studies in the English Language that will be offered by the Faculty of Law of the University of Macau in Macao, China.

In this paper, we construct an elaborate general equilibrium model with a continuum of production fragments for an intermediate good, then incorporate it in a growth model to address the effects of global production fragmentation, vertical specialization, and trade on growth and inequality for a small developing country. Among other things, we show that a small developing economy grows faster than the rest of the world as a result of global fragmentation and trade in intermediates if it is skilled-labor scarce. We further address the effects of such a trade opening on wage inequality.

Recent research has shed light on the impact of pre-electoral coalitions on government formation in presidential democracies. However, the fact that pre-electoral coalitions are not automatically transformed into coalition cabinets has often gone under the radar. In this article, I argue that the importance of pre-electoral pacts for government formation depends on the degree of legislative polarization. When parties are distant from one another in the ideological spectrum, presidents face more difficulties in breaking away from the pre-electoral pact and rearranging their multiparty alliances. Conversely, when polarization is not pervasive, presidents have more leeway to build coalition cabinets different from the ones prescribed by pre-electoral coalitions. Drawing on a dataset of 13 Latin American countries, the results support my claim and suggest that the relationship between government formation and the concession of office benefits for pre-electoral coalition members is more nuanced than previously assumed.