Type 2 diabetes mellitus (T2DM) is a major disease worldwide, causing significant mortality and morbidity. Currently, in Aotearoa, New Zealand, there is a high prevalence of T2DM, with a disproportionate impact on Māori and Pacific populations(1). Moreover, it has been predicted that the prevalence will continually increase. Research has shown that insulin resistance (IR) has been reported to play a critical role in the development of T2DM and other related cardiometabolic diseases(2). Therefore, managing IR is crucial to reducing the development of T2DM. Notably, bioactive compounds in various diets are known to modify the risk of T2DM by regulating IR. Among such dietary compounds include kawakawa (Piper excelsum), an indigenous species used by Māori in traditional medicine (Rongoā). Kawakawa is shown to contain several bioactive compounds that are shown to have insulin-sensitising effects. Research by our group has recently shown kawakawa to have potential anti-diabetic and anti-inflammatory effects in healthy human volunteers(3,4). However, how Kawakawa exerts these effects on insulin signalling and glucose uptake remains unknown. We hypothesise that kawakawa will enhance the glucose uptake in the treated cells and will differentially regulate key genes involved in insulin signalling pathways, including GLUT2, IRS-1, PPAR-γ, and PI3K/Akt, across various tissues. To test our hypothesis, we aim to investigate the mechanistic action of kawakawa extract on insulin signalling pathways in different cell models from metabolically active organs. We will use the same kawakawa powder sample shown to improve postprandial insulin in a healthy population. Cell models representing different insulin-responsive organs: liver (HepG2), skeletal muscle (L6-GLUT4myc), pancreas (MIN6), and adipose (3T3-L1) will be used. The cells will be treated with different doses of kawakawa extract, and glucose uptake will be measured. Key signalling pathways, including GLUT2, IRS-1, PPAR-γ, and PI3K/Akt, will be monitored using western blot and quantitative polymerase chain reaction (qPCR) analysis. The findings of this study have the potential to identify key targets of kawakawa action on insulin signalling in metabolically active organs. These outcomes will inform future research with kawakawa in clinical settings in people with cardiometabolic diseases such as T2DM and can form the basis for developing a dietary intervention for individuals at risk of these diseases. Additionally, Rongoā is an acceptable intervention by Māori, integrating this knowledge with evidence-based scientific interventions would aid in creating a holistic health paradigm that resonates within Māori communities.

Astrobiology is a scientific field that is very interdisciplinary and developing very fast, with many new discoveries generating a high level of attention in both the scientific community and the public. A central goal of astrobiology is to discover life beyond Earth which is, with our current instrumentation and knowledge, arguably within our reach. However, knowledge exchange crossing disciplinary boundaries is becoming increasingly challenging due to different usage of nomenclature and scientific controversies often limited to subdisciplines. There have been some efforts to compile organized databases of terms, concepts and other relevant material within some of the subfields contributing to astrobiology, for example through manually curated online portals designed to benefit students, teachers and practitioners of astrobiology-related research. However, the developments within the subfields and the potentially premature communication of research findings are too fast for objective research portals to remain reliable and up-to-date enough to enable well-informed scientific discussions. We suggest here a novel strategy for developing an online tracers portal as a self-maintaining and self-updating information platform, that would allow not only for a relatively unbiased selection of research results, but also provide fast access to latest scientific discoveries together with potential controversies, such that users of the tracers portal can form their own opinion on all available data rather than obtaining an already filtered and potentially biased selection of information.

Recent changes to US research funding are having far-reaching consequences that imperil the integrity of science and the provision of care to vulnerable populations. Resisting these changes, the BJPsych Portfolio reaffirms its commitment to publishing mental science and advancing psychiatric knowledge that improves the mental health of one and all.

Objectives/Goals: The never in mitosis kinase (NEK) family regulates vital processes, namely cell cycle progression, but their potential as therapeutic targets in TNBC has not been fully explored. Our studies aim to develop a toolkit to investigate the functional roles of NEKs in pathologies including carcinogenesis. Methods/Study Population: To assess differential NEK expression in normal and tumor tissues and correlation of gene expression with patient survival, we used Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan–Meier Plotter (KMPlot) pan-cancer analysis, respectively. Basal NEK protein levels were determined by immunoblot across a panel of cell lines, including breast cancer, osteosarcoma, hepatocellular carcinoma, and non-cancerous cells, to identify appropriate systems for evaluation of NEK function. Doxycycline-inducible cell lines were generated by transduction with lentiviral stocks of NEK shRNA and overexpression constructs and antibiotic selection. Expression was analyzed by qPCR and immunoblot. Results/Anticipated Results: Expression of NEK2, 4, 5, 6, 8, and 11 was higher in breast tumors compared to normal tissue by GEPIA analysis. Further examination using KMPlot showed a correlation between elevated NEK6 expression and decreased overall survival in patients with aggressive cancers. As an initial proof-of-concept study, we analyzed NEK6 protein expression in breast cancer cells. Levels of NEK6 were elevated in TNBC cells (MDA-MB-231) compared to hormone receptor positive (HR+) breast cancer cells (MCF7). Using complementary approaches to investigate the functional role of NEK6 in breast cancer, we depleted NEK6 expression using shRNAs in TNBC cells and expressed NEK6 in HR+ cells Discussion/Significance of Impact: Because kinase dysregulation promotes oncogenesis and metastasis, targeting kinases is a key strategy in therapeutic development. A NEK-specific molecular toolkit allows researchers to elucidate NEK functions and contributions to carcinogenesis, promoting advancement of novel therapies.

We study the planar FitzHugh–Nagumo system with an attracting periodic orbit that surrounds a repelling focus equilibrium. When the associated oscillation of the system is perturbed, in a given direction and with a given amplitude, there will generally be a change in phase of the perturbed oscillation with respect to the unperturbed one. This is recorded by the phase transition curve (PTC), which relates the old phase (along the periodic orbit) to the new phase (after perturbation). We take a geometric point of view and consider the phase-resetting surface comprising all PTCs as a function of the perturbation amplitude. This surface has a singularity when the perturbation maps a point on the periodic orbit exactly onto the repelling focus, which is the only point that does not return to stable oscillation. We also consider the PTC as a function of the direction of the perturbation and present how the corresponding phase-resetting surface changes with increasing perturbation amplitude. In this way, we provide a complete geometric interpretation of how the PTC changes for any perturbation direction. Unlike other examples discussed in the literature so far, the FitzHugh–Nagumo system is a generic example and, hence, representative for planar vector fields.

This paper reports an expansion of the English as a second language (L2) component of the Multilingual Eye Movement Corpus (MECO L2), an international database of eye movements during text reading. While the previous Wave 1 of the MECO project (Kuperman et al., 2023) contained English as a L2 reading data from readers with 12 different first language (L1) backgrounds, the newly collected dataset adds eye-tracking data on English text reading from 13 distinct L1 backgrounds (N = 660) as well as participants’ scores on component skills of English proficiency and information about their demographics and language background and use. The paper reports reliability estimates, descriptive statistics, and correlational analyses as means to validate the expansion dataset. Consistent with prior literature and the MECO Wave 1, trends in the MECO Wave 2 data include a weak correlation between reading comprehension and oculomotor measures of reading fluency and a greater L1-L2 contrast in reading fluency than reading comprehension. Jointly with Wave 1, the MECO project includes English reading data from more than 1,200 readers representing a diversity of native writing systems (logographic, abjad, abugida, and alphabetic) and 19 distinct L1 backgrounds. We provide multiple pointers to new venues of how L2 reading researchers can mine this rich publicly available dataset.

In this manuscript, we highlight current literature on environmental hygiene techniques to combat reservoirs of antibiotic resistant organisms in the healthcare environment. We discuss several topics for each strategy, including mechanism of action, assessment of effectiveness based on studies, cost, and real-world translatability. The techniques and topics summarized here are not inclusive of all available environmental hygiene techniques but highlight some of the more popular and investigated strategies. We focus on the following: Ultraviolet radiation, hydrogen peroxide vapor, copper-coated surfaces, phages, interventions involving sinks, and educational initiatives.

Low birthweight is a risk factor for type 2 diabetes. We hypothesised that differential associations between birthweight and clinical characteristics in persons with and without type 2 diabetes may provide novel insights into the role of birthweight in type 2 diabetes and its progression. We analysed UK Biobank data from 9,442 persons with and 254,446 without type 2 diabetes. Associations between birthweight, clinical traits, and genetic predisposition were assessed using adjusted linear and logistic regression, comparing the lowest and highest 25% of birthweight to the middle 50%. Each kg increase in birthweight was associated with higher BMI, waist, and hip circumference, with stronger effects in persons with versus without type 2 diabetes (BMI: 0.74 [0.58, 0.90] vs. 0.21 [0.18, 0.24] kg/m2; waist: 2.15 [1.78, 2.52] vs. 1.04 [0.98, 1.09] cm; hip: 1.65 [1.33, 1.97] vs. 1.04 [1.04, 1.09] cm). Family history of diabetes was associated with higher birthweight regardless of diabetes status, albeit with a twofold higher effect estimate in type 2 diabetes. Low birthweight was further associated with prior myocardial infarction regardless of type 2 diabetes status (OR 1.33 [95% CI 1.11, 1.60] for type 2 diabetes; 1.23 [95% CI 1.13, 1.33] without), and hypertension (OR 1.25 [1.23, 1.28] and stroke 1.24 [1.14, 1.34]) only among persons without type 2 diabetes. Differential associations between birthweight and cardiometabolic traits in persons with and without type 2 diabetes illuminate potential causal inferences reflecting the roles of pre- and postnatal environmental versus genetic aetiologies and disease mechanisms.

North Carolina growers have long struggled to control Italian ryegrass, and recent research has confirmed that some Italian ryegrass biotypes have become resistant to nicosulfuron, glyphosate, clethodim, and paraquat. Integrating alternative management strategies is crucial to effectively control such biotypes. The objectives of this study were to evaluate Italian ryegrass control with cover crops and fall-applied residual herbicides and investigate cover crop injury from residual herbicides. This study was conducted during the fall/winter of 2021–22 in Salisbury, NC, and fall/winter of 2021–22 and 2022–23 in Clayton, NC. The study was designed as a 3 × 5 split-plot in which the main plot consisted of three cover crop treatments (no-cover, cereal rye at 80 kg ha−1, and crimson clover at 18 kg ha−1), and the subplots consisted of five residual herbicide treatments (S-metolachlor, flumioxazin, metribuzin, pyroxasulfone, and nontreated). In the 2021–22 season at Clayton, metribuzin injured cereal rye and crimson clover 65% and 55%, respectively. However, metribuzin injured both cover crops ≤6% in 2022–23. Flumioxazin resulted in unacceptable crimson clover injury of 50% and 38% in 2021–22 and 2022–23 in Clayton and 40% in Salisbury, respectively. Without preemergence herbicides, cereal rye controlled Italian ryegrass by 85% and 61% at 24 wk after planting in 2021–22 and 2022–23 in Clayton and 82% in Salisbury, respectively. In 2021–22, Italian ryegrass seed production was lowest in cereal rye plots at both locations, except when it was treated with metribuzin. For example, in Salisbury, cereal rye plus metribuzin resulted in 39,324 seeds m–2, compared to ≤4,386 seeds m–2 from all other cereal rye treatments. In 2022–23, Italian ryegrass seed production in cereal rye was lower when either metribuzin or pyroxasulfone were used preemergence (2,670 and 1,299 seeds m–2, respectively) compared with cereal rye that did not receive an herbicide treatment (5,600 seeds m–2). cereal rye (Secale cereale L.) and crimson clover (Trifolium incarnatum L.)

Pirrie v McFarlane remains an enigmatic case. Decided a few years after the landmark decision of Engineers it reflected an application of the reciprocal nature of the principle applied in that case. The thrust of the decision in Engineers was that the Commonwealth Parliament had power under s 51(xxxv) to make laws binding on the States. In the course of judgment the majority judges had also observed as follows:

Coming so soon after Engineers, the decision in Pirrie v McFarlane is clearly consistent with this observation of the majority judges. However, given the subsequent developments in cases such as Cigamatic and Bogle, the authority of Pirrie v McFarlane has been questioned.

The well known writings and other contributions of Professor Zines on the High Court's interpretation of Australia’s Constitution and public law generally have justly earned him the admiration and deep respect of eminent jurists both within Australia and abroad. His interests extended to courts in other western liberal democracies.

In a book based on a series of lectures delivered at the University of Cambridge under the auspices of the Smuts Memorial Fund, Professor Leslie Zines ventured into a comparative study of, inter alia, the role of the courts in the United Kingdom, Canada, Australia and New Zealand. He noted that Canada, Australia and New Zealand share the common feature of the perplexing difficulty of pin-pointing an exact date when these countries obtained their independence from Britain. In other countries which were former British colonies, the date of independence could largely be identified by the date when the Union Jack was lowered and a new national flag was unfurled.

In a federal system there is a constant need to resolve problems created by conflicting provisions of laws enacted by. the federal legislature and those enacted by a state or provincial legislature. In the case of a unitary system it is merely the question of a later statute conflicting with an earlier statute enacted by the same legislature, and in such an instance, the conflict is resolved by regarding the earlier law as having been impliedly repealed by the later law.

In the Australian federal system the conflict is resolved by resorting to the express provisions of s 109 of the Commonwealth Constitution, which reads as follows:

When a law of a State is inconsistent with a law of the Commonwealth, the latter shall prevail, and the former shall, to the extent of the inconsistency, be invalid.

Two studies were conducted in 2022 and 2023 near Rocky Mount and Clayton, NC, to determine the optimal granular ammonium sulfate (AMS) rate and application timing for pyroxasulfone-coated AMS. In the rate study, AMS rates included 161, 214, 267, 321, 374, 428, and 481 kg ha−1, equivalent to 34, 45, 56, 67, 79, 90, and 101 kg N ha−1, respectively. All rates were coated with pyroxasulfone at 118 g ai ha−1 and topdressed onto 5- to 7-leaf cotton. In the timing study, pyroxasulfone (118 g ai ha−1) was coated on AMS and topdressed at 321 kg ha−1 (67 kg N ha−1) onto 5- to 7-leaf, 9- to 11-leaf, and first bloom cotton. In both studies, weed control and cotton tolerance to pyroxasulfone-coated AMS were compared to pyroxasulfone applied POST and POST-directed. The check in both studies received non-herbicide-treated AMS (321 kg ha−1). Before treatment applications, all plots (including the check) were maintained weed-free with glyphosate and glufosinate. In both studies, pyroxasulfone applied POST was most injurious (8% to 16%), while pyroxasulfone-coated AMS resulted in ≤4% injury. Additionally, no differences in cotton lint yield were observed in either study. With the exception of the lowest rate of AMS (161 kg ha−1; 79%), all AMS rates coated with pyroxasulfone controlled Palmer amaranth ≥83%, comparably to pyroxasulfone applied POST (92%) and POST-directed (89%). In the timing study, the application method did not affect Palmer amaranth control; however, applications made at the mid- and late timings outperformed early applications. These results indicate that pyroxasulfone-coated AMS can control Palmer amaranth comparably to pyroxasulfone applied POST and POST-directed, with minimal risk of cotton injury. However, the application timing could warrant additional treatment to achieve adequate late-season weed control.

Graphical models have received an increasing amount of attention in network psychometrics as a promising probabilistic approach to study the conditional relations among variables using graph theory. Despite recent advances, existing methods on graphical models usually assume a homogeneous population and focus on binary or continuous variables. However, ordinal variables are very popular in many areas of psychological science, and the population often consists of several different groups based on the heterogeneity in ordinal data. Driven by these needs, we introduce the finite mixture of ordinal graphical models to effectively study the heterogeneous conditional dependence relationships of ordinal data. We develop a penalized likelihood approach for model estimation, and design a generalized expectation-maximization (EM) algorithm to solve the significant computational challenges. We examine the performance of the proposed method and algorithm in simulation studies. Moreover, we demonstrate the potential usefulness of the proposed method in psychological science through a real application concerning the interests and attitudes related to fan avidity for students in a large public university in the United States.