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Plant biosecurity and One Health: government and industry roles as risk creators and mitigators.
No full textThe One Health concept highlights the interconnectedness of human, animal, and environmental health and places significant importance on plant biosecurity. This is due to the profound impact of plant biosecurity on food safety and security for animals and people, biodiversity, and the economy. This narrative review examines the roles of government and industry as risk creators and mitigators in plant biosecurity within a One Health framework, focusing on how their collaboration can strengthen surveillance, enhance regulatory policies, and mitigate the spread of plant pests and diseases. Plant biosecurity, which encompasses the measures to safeguard plant biosecurity and life in the same way that animal biosecurity safeguards animal and human health and life, is a critical component of One Health. Measures include a range of policies, regulations, strategies and activities to protect plants from exotic and established pests and diseases. Government, industry, and community actions are critical elements of plant biosecurity. These include pest surveillance and the establishment and maintenance of pest-free areas. Government agencies and industry professionals play a central and pivotal role in shaping plant biosecurity by implementing policies and regulations and developing innovative strategies. These actions can have a dual effect on plant biosecurity: they can either mitigate risks by preventing the introduction and spread of pests or create risks if regulations are inadequate or poorly enforced. The success of plant biosecurity efforts depends on how well government policies align with One Health principles, which require a careful balance between economic, environmental, social and health-related technical/scientific considerations. Pest surveillance, a foundational element of plant biosecurity, provides the tools for early detection and rapid response to pest outbreaks, essential for protecting plant biosecurity. Surveillance programs enable continuous monitoring of pest populations and the detection of emerging threats, which is critical for maintaining pest-free areas. The benefits of pest surveillance are numerous and extend beyond plant biosecurity, contributing to broader One Health objectives by reducing the risk of zoonotic diseases and preserving the ecological integrity of ecosystems. It underpins important economic and trade objectives by projecting confidence in the safety and health of Australia's agricultural products to international trading partners. Strategies to achieve and maintain pest-free areas include stringent quarantine measures, continuous surveillance, and effective rapid response protocols. The interconnectedness of plant biosecurity with One Health is evident in these efforts, as maintaining pest-free areas supports ecosystem health, minimises the need for chemical interventions and consequent pressure on antimicrobial resistance, and promotes sustainable agricultural practices. Government actions, pest surveillance, and the maintenance of pest-free regions are essential components of a robust plant biosecurity strategy. By aligning these measures with One Health principles, it is possible to protect plant biosecurity, enhance environmental sustainability, and contribute to global health outcomes. This holistic approach highlights the importance of cross-sector collaboration and the need for solid biosecurity frameworks to safeguard plant biosecurity in an increasingly interconnected world
Feasibility, acceptability and preliminary clinical outcomes of a brief coping-focused intervention for delusions blended with smartphone-based ecological momentary assessment and intervention in persons with schizophrenia spectrum disorders: A pilot single-arm trial
No full textDelusions are one of the core symptoms of schizophrenia spectrum disorders (SSD), associated with distress and impaired functioning. Traditional Cognitive Behavioral Therapy (CBT) approaches are less effective for delusions, require significant resources, and specialized staff training. Symptom-specific therapy approaches, which target factors involved in the development and maintenance of psychotic symptoms, provide a valid alternative. Recent research demonstrates the efficacy of coping strategies as an intervention element, however, so far, only in the context of auditory hallucinations. Digital technologies, such as ecological momentary assessment (EMA) and ecological momentary intervention (EMI), are gaining attention in mental health, providing enhanced assessment and intervention opportunities. The present single-arm trial aimed to investigate the feasibility, acceptability, and preliminary outcomes of a smartphone-based blended EMA/I psychological therapy approach focusing on improving coping strategies for delusions in SSD. In total, N = 10 participants received four face-to-face therapy sessions alongside German university-level treatment-as-usual over an intervention period of four to six weeks. Feasibility was assessed by completion rates of the EMA/I questionnaires, use of the application between sessions and recruitment rates. Acceptability was assessed by a satisfaction questionnaire, open feedback, and analysis of adverse effects. Clinical outcomes included self-rated and rater-based intensity and distress of delusions and comorbid symptoms at pre- and post-intervention. Findings supported the feasibility and acceptability of the DICE (DICE - Delusion Ideation in the Context of Everyday life intervention) intervention, with high retention (10/13 participants, 77 %) and completion rates for the EMA- (59 %) and EMI-questionnaires (72 %), as well as a high protocol adherence (90–97 %), exceeding all predefined benchmarks. Open feedback indicated good satisfaction, with all participants using the application between sessions, reflecting a high engagement level. Clinical outcomes displayed relevant changes in ameliorating the intensity of delusions when being measured by the Psychotic Symptom Rating Scales as well as by the Green Paranoid Thought Scale, and self-rated improvements in distress and depressive symptoms. Changes in the intensity and distress of delusions might be explained by improved coping behaviour. Further research with control conditions is needed to validate findings and analyze the efficacy as well as mechanisms of actions of the intervention in a fully powered trial
Receptor deorphanization in starfish reveals the evolution of relaxin signaling as a regulator of reproduction
No full textBackground: Relaxins are a family of peptides that regulate reproductive physiology in vertebrates. Evidence that this is an evolutionarily ancient role of relaxins has been provided by the discovery of two relaxin-like gonad-stimulating peptides (RGP1 and RGP2) that trigger spawning in starfish. The main aim of this study was to identify the receptor(s) that mediate(s) the effects of RGP1 and RGP2 in starfish. Results: Here we show that RGP1 and RGP2 belong to a family of peptides that include vertebrate relaxins, Drosophila insulin-like peptide 8 (Dilp8), and other relaxin-like peptides in several protostome taxa. An ortholog of the human relaxin receptors RXFP1 and RXFP2 and the Drosophila receptor LGR3 was identified in starfish (RXFP/LGR3). In Drosophila, but not in humans and other vertebrates, there is a paralog of LGR3 known as LGR4, and here an LGR4-type receptor was also identified in starfish. In vitro pharmacological experiments revealed that both RGP1 and RGP2 act as ligands for RXFP/LGR3 in the starfish Acanthaster cf. solaris and Asterias rubens, but neither peptide acts as a ligand for LGR4 in these species. Conclusions: Discovery of the RXFP/LGR3-type receptor for RGP1 and RGP2 in starfish provides a new insight into the evolution of relaxin-type signaling as a regulator of reproductive processes. Furthermore, our findings indicate that RXFP/LGR3-type receptors have been lost in several phyla, including urochordates, mollusks, bryozoans, platyhelminthes, and nematodes
Designing theranostics to target the oncoprotein ROR1
No full text© 2025 Joseph Nicholas Van De GardeIntroduction
Peptide-based theranostics possess an unparalleled capacity to non-invasively detect and treat malignant disease through the specific targeting of receptors that are aberrantly expressed in cancer. Their modular structure allows for the integration of both imaging and therapeutic functionalities into a single molecule. However, their development is tightly constrained by the inherent difficulty in identifying ligands that not only bind with high affinity, but also possess the required physiochemical properties such as stability, solubility, and specificity.
Theranostics targeting the tyrosine-protein kinase transmembrane receptor ROR1 represent a particularly exciting opportunity, as ROR1 is selectively expressed in many aggressive and treatment-resistant cancers while largely absent from normal adult tissues. This makes it an ideal molecular target for selective cancer imaging and therapy. This study presents a streamlined, rational methodology for the discovery and development of peptide-based radiopharmaceuticals, establishing a platform for the creation of first-in-class ROR1 theranostic agents.
Methodology
Random nonstandard Peptide Integrated Discovery, an innovative in vitro selection platform based on mRNA display, was employed to discover lead peptide candidates. This method enables the ultra-high-throughput screening of over 10^12 macrocyclic peptide sequences, incorporating noncanonical amino acids to enhance stability and target engagement.
Peptides that exhibited strong enrichment after five iterative biopanning cycles against
recombinant ROR1 were selected for further evaluation. These enriched sequences were
chemically synthesised using solid phase peptide synthesis protocols optimised for
macrocycles. Binding affinities were quantified using Surface Plasmon Resonance, and peptides exhibiting high affinity particularly those with dissociation constants less than 1 nM were subsequently conjugated with the DOTA chelator to enable radiolabelling with Gallium-68 and Lutetium-177. To ensure that the DOTA conjugation did not compromise ROR1 binding, secondary SPR analyses were performed. Additionally, radiolabelled peptides were evaluated in cell-based saturation assays using 22RV1 prostate cancer cells and OVCAR4 Ovarian cancer cells engineered to overexpress ROR1.
Results
The RaPID platform successfully identified three cyclic peptides with subnanomolar affinity for recombinant ROR1, as well as five additional candidates with affinity below 5 nM. The top three ligands were radiolabelled with Gallium-68 and Lutetium-177, achieving high radiochemical purity (greater than 97%) and exhibiting robust binding to ROR1 in vitro. Notably, SPR analyses of their nonradioactive analogues confirmed that conjugation with DOTA and subsequent radiolabelling were well tolerated, preserving their high binding affinity.
Conclusion
This study demonstrates the successful application of RaPID in identifying cyclic peptides with low and subnanomolar affinity for ROR1. These ligands represent promising scaffolds for the development of radiopharmaceuticals targeting ROR1, and importantly, maintain high binding affinity following DOTA conjugation and radiolabelling. Cell saturation studies confirmed their high specificity for ROR1, while in vivo imaging in prostate cancer xenograft models validated their ability to selectively detect ROR1 expression. Further biodistribution and metabolic stability studies have laid the groundwork for their continued development as targeted imaging and therapeutic agents in ROR1-positive malignancies
The Commercial Determinants of Nonalcoholic Beer: Redemption, Revenue, or Men’s Harm Reduction?
No full textPublic awareness about the connections between men’s alcohol use and poor health outcomes, including increased male suicide risk, has led to reduced consumption and increased use of nonalcoholic beverages—most prominently nonalcoholic beer (NAB). Marketed as a healthy substitution option (i.e., periodically switching to an NAB rather than abstaining from alcoholic beer), the rapidly growing NAB sector might be somewhat redemptive, wherein the alcoholic beer industry (as the predominant producers of NAB) is selling harm reduction to men, albeit for profit. The commercial determinants of NAB are, however, complex and have significant implications for legislation and policy. For example, in Canada, NAB is exempt from alcoholic beer excise duty but considered beer for the goods and services and harmonized sales taxes. Coupled with industry production costs and profit margins, these taxes contribute to NAB and alcoholic beer retail price parity. From a public health perspective, there are also concerns about increasing alcoholic beer brand recognition and sales revenue by extending NAB visibility in more places (e.g., supermarkets), contexts (e.g., taking medication), and activities (e.g., driving). The current article highlights (1) the connections between men’s alcohol use and health risks, ahead of discussing, (2) the rise of NAB, and mapping (3) NAB legislation and policy implications. We conclude with a discussion about the redemption, revenue, and men’s harm reduction potentials, pragmatically arguing the need to both regulate and incentivize NAB. Proposed are promising directions for future research with the goal of reducing men’s alcohol use and associated harms
Exploring epidemiological risk factors for cerebral amyloid angiopathy: Considerations for monoclonal antibody therapy in people with Alzheimer's disease
No full textINTRODUCTION: Cerebral amyloid angiopathy (CAA) increases the risk of amyloid-related imaging abnormalities in Alzheimer's disease (AD) patients receiving anti-amyloid-beta therapies, emphasizing the need to identify its risk factors. METHODS: Data were collected from three cohort studies, and a machine learning model was developed to predict CAA occurrence using the selected risk factors. RESULTS: The AD neuropathologic changes (ADNC)-CAA association was significantly positive in the cross-sectional analysis. When stratified by selected risk factors, this association was generally stronger among females, smokers, people with a history of stroke/memory complaints, apolipoprotein E (APOE)-ε4 carriers, and those without diabetes/heart conditions. In the longitudinal analysis of the association between potential risk factors and CAA, a higher risk of CAA was observed among males, older individuals, smokers, people with diabetes/heart conditions, lower Mini-Mental State Examination (MMSE) scores, and APOE-ε4 carriers compared to their respective reference groups. DISCUSSION: Our study identified risk factors for cerebral amyloid angiopathy, informing potential prevention strategies. Highlights: ADNC were significantly positively associated with the risk of CAA. The ADNC-CAA association was generally stronger among females, smokers, people with a history of stroke/memory complaints, APOE-ε4 carriers, and those without diabetes or heart conditions. Longitudinally, higher CAA risk was observed among males, older individuals, smokers, people with diabetes/heart conditions/lower MMSE scores, and APOE-ε4 carriers compared to their reference groups
What does memory retrieval leave on the table? Modelling the Cost of Semi-Compositionality with MINERVA2 and sBERT
No full textDespite being ubiquitous in natural language, collocations (e.g., kick+habit) incur a unique processing cost, compared to compositional phrases (kick+door) and idioms (kick+bucket). We confirm this cost with behavioural data as well as MINERVA2, a memory model, suggesting that collocations constitute a distinct linguistic category. While the model fails to fully capture the observed human processing patterns, we find that below a specific item frequency threshold, the model’s retrieval failures align with human reaction times across conditions. This suggests an alternative processing mechanism that activates when memory retrieval fails
Change in willingness for surgery and risk of joint replacement after an education and exercise program for hip/knee osteoarthritis: A longitudinal cohort study of 55,059 people
No full textBACKGROUND: Numerous studies report that education and exercise interventions can shift people's willingness to undergo joint replacement surgery for osteoarthritis. We aimed to investigate whether becoming unwilling to undergo surgery following an education and exercise intervention for hip and knee osteoarthritis is associated with lower probability of receiving actual surgery. METHODS AND FINDINGS: This was a register-based cohort study including people from the Swedish Osteoarthritis Register who underwent a 3-month education and exercise intervention for knee or hip osteoarthritis. Participants self-reported their willingness to have joint replacement surgery ('yes' or 'no') and were grouped based on their response pre- and post-intervention (always willing for surgery; became unwilling for surgery; never willing for surgery; became willing for surgery). Data on joint replacement surgery was obtained through the Swedish Arthroplasty Register. The probability and hazard of surgery occurring, as well as the mean time without surgery was calculated up to 5-years (primary outcome) and 9-years (secondary outcome) post-intervention. We adjusted for age, sex, body mass index (BMI), education, joint pain, quality of life, walking difficulties, number of prior visits with an orthopedic surgeon, prior joint surgeries in the knee or hip (other than joint replacement), and comorbidities. 55,059 people were included, 69% were female (N = 37,739), with a mean age 66years (standard deviation [SD] = 9.3), and a BMI of 27.5 (SD = 4.9). In total, 70% (N = 38,386) were never willing for surgery, 14% (N = 7,736) were always willing for surgery, 10% (N = 5,649) became unwilling for surgery, and 6% (N = 3,288) became willing for surgery. Compared to those who were always willing for surgery, participants who became unwilling had a 20% (95% confidence interval [CI]: 18, 22%) lower probability of having surgery by 5-years post-intervention. This corresponded to delaying surgery by 1.1 (95% CI: 1.0, 1.1) years. Compared to those who were always willing for surgery, the hazard of surgery occurring at 1-year post-intervention was lower in those who became unwilling (hazard ratio (HR) 0.5 [95% CI: 0.4, 0.5]), though was then higher at 5-years (HR 1.4 [95% CI: 1.2, 1.7]). Estimates remained stable from 5 to 9 years. Limitations of our study include the inability to account for all potential confounders, and to infer the contribution of the intervention to change in willingness for surgery due to the absence of a control group. Data were collected in Sweden, generalisability to other countries may be limited. CONCLUSIONS: Becoming unwilling for joint replacement surgery following an education and exercise program for hip and knee osteoarthritis could reduce the number of joint replacement surgeries by 20% at 5 years post-intervention, with the possibility of maintaining most of this reduction up to 9 years post-intervention. Interventions that can shift willingness to undergo surgery may thus result in relevant delays and reductions in future joint replacements
Canonical-Inflow Adverse Pressure Gradient Turbulent Boundary Layers at High Reynolds Numbers
No full text© 2025 Luka LindicThis thesis investigates high Reynolds number turbulent boundary layer (TBL) flows
subjected to canonical-inflow adverse pressure gradients (APG) in a unique wind tunnel
experimental setup. The study is motivated by the necessity to understand the influence
of APG on turbulence structure and energy transfer mechanisms, which are pertinent to
various engineering applications, such as turbine cascades, ship hulls, and aircraft wings.
These applications often involve complex aerodynamic environments where controlling
drag and enhancing flow stability are of critical importance.
The experimental campaign was conducted in a high Reynolds number turbulent bound-
ary layer wind tunnel facility, designed to minimize upstream history effects. In this fa-
cility, carefully controlled canonical-inflow APG conditions were generated by blocking
the outlet section and incorporating open slots in the tunnel ceiling. This setup enabled
the investigation of both smooth and rough wall conditions to comprehensively assess
the interaction between surface roughness and adverse pressure gradients, particularly
at high Reynolds numbers.
The primary objective of this research is to utilize this facility to address critical ques-
tions regarding APG behavior at high Reynolds numbers, with a specific focus on the
outer region, where the turbulent/non-turbulent interface significantly affects energy
distribution, and where production and dissipation terms are most dominant. The
outer region dynamics were examined using high-resolution two-dimensional Particle
Image Velocimetry (2D-PIV), which enabled detailed visualization and quantification
of turbulence structures. Additionally, hot-wire anemometry was employed to acquire
turbulence statistics with high temporal and spatial resolution.
A key contribution of this thesis is the detailed characterization of turbulence statis-
tics—including mean velocity profiles, turbulence intensities, energy spectra, and the
turbulent kinetic energy budget—in both smooth- and rough-wall TBLs under APG
conditions. The experimental results demonstrate that APG significantly modifies the
outer region turbulence structures, particularly at high Reynolds numbers. The find-
ings indicate that turbulence intensities and spectral energy content of the streamwise
velocity are markedly increased in the presence of APG, emphasizing the necessity for
improved scaling laws that account for both Reynolds number effects and pressure gra-
dient influences. Notably, when compared to low Reynolds number numerical simulation
data, significant insights were obtained for the turbulent kinetic energy budget at high
Reynolds numbers.
Furthermore, the analysis of the turbulent/non-turbulent interface (TNTI) revealed that
APG conditions enhance mixing and momentum exchange in the outer region. High-
resolution PIV facilitated the detection of fine-scale structures, which are typically chal-
lenging to capture with conventional measurement techniques. To detect the TNTI,
both the Local Kinetic Energy (LKE) and spanwise vorticity methods were employed,
with Joint Probability Density Functions (JPDFs) for LKE/vorticity and wall-normal
distance used to determine the respective thresholds and estimate corresponding TNTI
heights. A sensitivity analysis of the mean TNTI height with respect to the thresh-
old was conducted for both methods, revealing that the LKE method exhibits lower
sensitivity compared to vorticity. The results indicate the limitations of using in-plane
vorticity for the current experimental data, while also identifying constraints within the
LKE method.
The findings suggest that, based on relatively small thresholds, the normalized TNTI
height decreases with increasing adverse pressure gradients at high Reynolds numbers
(Friction Reynolds number >8000), aligning with previous results obtained at lower Reynolds numbers (Friction Reynolds number<1000). Additionally, conditional averaging analysis of the instantaneous streamwise and wall-normal velocities, based on TNTI height, revealed that the outer wake region in the APG flow significantly differs from the zero pressure gradient (ZPG) case. In particular, the APG flow shows a greater spread in the conditional averaged velocity curves compared to the ZPG case, with the onset of deviation from the mean velocity profile occurring closer to the normalized position from the wall.
The outcomes of this thesis provide insights into the complex interactions between ZPG
and APG TBL flows. These insights are essential for enhancing turbulence modeling
in computational fluid dynamics (CFD) and for optimizing engineering designs that
operate within APG-dominated environments. The refined scaling laws and turbulence
statistics obtained from this study offer guidance for future experimental and numerical
investigations of APG turbulent boundary layers at high Reynolds numbers.
In conclusion, this work advances the understanding of outer region turbulence char-
acteristics in high Reynolds number TBLs, subjected to adverse pressure gradients,
with significant implications for aerodynamic drag reduction strategies, wind turbine
efficiency improvements, and flow control applications in both industrial and aerospace
engineering
Addressing the COVID-induced healthcare backlog: How can we balance the interests of people and nature?
No full textThe COVID-19 pandemic created healthcare backlogs of routine primary and preventive care, elective procedures, dental care, and mental healthcare appointments across the world. So far, governments are responding by enacting pandemic recovery policies that expand their healthcare sector activity, without much, if any, consideration of its effects on the environmental crisis that is (among other things) worsening human health and health equity. This paper argues that, as a matter of health and social justice, governments have an ethical responsibility to equitably reduce the backlog with minimal environmental damage. To do so, a first key action is to give priority to policy options that minimise negative human impacts on the environment. Yet these policies alone will not be sufficient to address the backlog, particularly in relation to elective procedures. The paper therefore contends that a second key action for governments is to enact the policy options that are best able to equitably reduce the remainder of the backlog, while accelerating the transition to sustainable health care in ways that are best able to reduce the specific environmental costs of those policy options. It concludes by considering whether limits apply to governments' ethical responsibilities that ultimately mean accelerating the transition to sustainable health care is not required when addressing the backlog