This manuscript summarizes a presentation delivered by the first author at the 2024 symposium for the Calvin Schwabe Award for Lifetime Achievement in Veterinary Epidemiology and Preventive Medicine, which was awarded to Dr. Jan Sargeant. Epidemiologic research plays a crucial role in understanding the complex relationships between exposures and health outcomes. However, the accuracy of the conclusions drawn from these investigations relies upon the meticulous selection and measurement of exposure variables. Appropriate exposure variable selection is crucial for understanding disease etiologies, but it is often the case that we are not able to directly measure the exposure variable of interest and use proxy measures to assess exposures instead. Inappropriate use of proxy measures can lead to erroneous conclusions being made about the true exposure of interest. These errors may lead to biased estimates of associations between exposures and outcomes. The consequences of such biases extend beyond research concerns as health decisions can be made based on flawed evidence. Recognizing and mitigating these biases are essential for producing reliable evidence that informs health policies and interventions, ultimately contributing to improved population health outcomes. To address these challenges, researchers must adopt rigorous methodologies for exposure variable selection and validation studies to minimize measurement errors.

A resurgence of panpsychism and dualism is a matter of ongoing debate in modern neuroscience. Although metaphysically hostile, panpsychism and dualism both persist in the science of consciousness because the former is proposed as a straightforward answer to the problem of integrating consciousness into the fabric of physical reality, whereas the latter proposes a simple solution to the problem of free will by endowing consciousness with causal power as a prerequisite for moral responsibility. I take the Integrated Information Theory (IIT) as a paradigmatic exemplar of a theory of consciousness (ToC) that makes its commitments to panpsychism and dualism within a unified framework. These features are not, however, unique for IIT. Many ToCs are implicitly prone to some degree of panpsychism whenever they strive to propose a universal definition of consciousness, associated with one or another known phenomenon. Yet, those ToCs that can be characterized as strongly emergent are at risk of being dualist. A remedy against both covert dualism and uncomfortable corollaries of panpsychism can be found in the evolutionary theory of life, called here \"bioprotopsychism\" and generalized in terms of autopoiesis and the free energy principle. Bioprotopsychism provides a biologically inspired basis for a minimalist approach to consciousness via the triad \"chemotaxis-efference copy mechanism-counterfactual active inference\" by associating the stream of weakly emergent conscious states with an amount of information (best guesses) of the brain, engaged in unconscious predictive processing.

Asbestos is a carcinogen that can cause lung cancer. The suspicion that a lung cancer diagnosis may be associated with exposure to asbestos has no bearing on treatment. However, attributing an individual\'s lung cancer to asbestos exposure has important medicolegal implications and may impact public health measures and policy. Simultaneous exposure(s) to other carcinogens (such as tobacco smoke, silica and many others) adds complexity while trying to answer the causation question. The Helsinki criteria were formulated to assist attributing lung cancer to previous asbestos exposure. Surrogate markers can be used and include signs of asbestosis and pleural plaques. The most widely used criterion for the presence of asbestosis is interstitial fibrosis in conjunction with 2 or more asbestos bodies/1 cm2 tissue section by light microscopy. Identification of asbestos bodies ty light pr electron microscopy provides an important element for asbestos diagnosis. However, fibrosis may be subtle, and the distribution of asbestos bodies is not uniform throughout the lungs, some types of asbestos fibres have low biopersistence, and not all types of asbestos readily form asbestos bodies. Additional criteria require knowledge of exposure history, which is often unknown to pathologists, but reliance on morphology in isolation may lead to mis-classification of interstitial lung disease as idiopathic. While a smoking-related lung cancer signature has emerged, an asbestos-related lung cancer signature has not yet been identified. In this review we will discuss practice points for the surgical pathologist.

Seaweeds play a strong ecological and economical role along the world\'s coastlines, where they support industries (e.g., aquaculture, bioproducts) and essential ecosystem services (e.g., biodiversity, fisheries, carbon capture). Evidence from wild and cultured seaweeds suggests that microorganisms play crucial roles in their health and functioning, prompting the need for considering seaweeds and their microbiome as a coherent entity or \"holobiont.\" Here we show that the number of studies investigating seaweed hosts and their microbiome have increased in the last two decades. This likely reflects the increase in the appreciation of the importance of microbiomes for eukaryotic hosts, improved molecular approaches used to characterize their interactions, and increasing interest in commercial use of seaweeds. However, although increasing, most studies of seaweed holobionts have focused on (i) a few seaweed species of ecological or commercial significance, (ii) interactions involving only bacteria, and (iii) descriptive rather than experimental approaches. The relatively few experimental studies have mostly focused on manipulating abiotic factors to examine responses of seaweeds and their microbiome. Of the few studies that directly manipulated microorganisms to investigate their effects on seaweeds, most were done in laboratory or aquaria. We emphasize the need to move beyond the descriptions of patterns to experimental approaches for understanding causation and mechanisms. We argue that such experimental approaches are necessary for a better understanding of seaweed holobionts, for management actions for wild and cultivated seaweeds, and to better integrate studies of seaweed holobionts with the broader fields of seaweed ecology and biology, which are strongly experimental.

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BACKGROUND: Both psoriasis and vitiligo are autoimmune skin diseases. Previous observational studies have indicated a relationship between the two conditions, and simultaneous onset of both diseases poses increased health risks to patients. However, limited research has explored the causal relationship between psoriasis and vitiligo.
OBJECTIVE: To investigate whether a causal association exists between psoriasis and vitiligo.
METHODS: A case of Chinese patients diagnosed with psoriasis and vitiligo has been reported. Transcriptome sequencing was performed on normal, psoriasis, vitiligo, and co-morbid skin tissues of the patients, and single-cell transcriptome sequencing was conducted on the co-morbid skin tissues. A comprehensive Mendelian randomization analysis of Genome-wide association studies (GWAS) was performed on a cohort of 261 018 European individuals with psoriasis from the IEU Open GWAS Project and vitiligo from the National Institutes of Health (NIH) Database of Genotypes and Phenotypes.
RESULTS: Case report and transcriptome results showed that skin tissue with vitiligo combined with psoriasis exhibited both vitiligo and psoriasis. Single-cell transcriptome sequencing results showed that in comparison to normal skin and psoriatic skin, the proportions of CD8+ T cells, natural killer cells, naive T cells, T helper cells 17, regulatory T cells, conventional type 1 dendritic cells, Conventional type 2 dendritic cells, and plasmacytoid dendritic cells were all increased in skin tissue with vitiligo combined with psoriasis. Mendelian randomization analysis included 4510 patients with psoriasis and 4680 patients with vitiligo. The results showed no causal relationship between vitiligo and psoriasis in the forward direction (p = 0.192; odds ratio [OR], 1.059; 95% confidence interval [CI], 0.971-1.155) or in the reverse direction (p = 0.459; OR, 0.927; 95% CI, 0.757-1.134).
CONCLUSIONS: This study suggests that the association between psoriasis and vitiligo may be closely related to immunity, however, Mendelian randomization studies do not support a causal relationship. These findings hold significant implications for clinicians aiming to enhance their understanding and treatment approaches for psoriasis and vitiligo.

UNASSIGNED: Observational studies have reported positive associations between glaucoma and stroke; however, controversial results exist. Importantly, the nature of the relationship remains unknown since previous studies were not designed to test causality. Therefore, we aimed to investigate the possible causal relationships between glaucoma and stroke.
UNASSIGNED: Our two-sample Mendelian randomization (MR) encompassed multi-ethnic large-scale genome-wide association studies with more than 20000 cases and 260000 controls for glaucoma, and more than 80000 cases and 630000 controls for stroke. Individual effect estimates for each SNP were combined using the inverse-variance weighted (IVW) method. To avoid potential pleiotropic effects, we adjusted the main results by excluding genetic variants associated with metabolic factors. The weighted median and MR-Egger methods were also used for the sensitivity analysis.
UNASSIGNED: Our MR analysis revealed that glaucoma and its subtypes, including primary open-angle glaucoma and primary angle-closure glaucoma, exhibited no causal role in relation to any stroke (AS), any ischemic stroke (AIS), large-artery atherosclerotic stroke (LAS), small-vessel stroke (SVS), or cardioembolic stroke (CES) across MR analyses (all P ​> ​0.05). The null associations remained robust even after adjusting for metabolic-related traits and were consistent in both the European and Asian populations. Furthermore, reverse MR analyses also did not indicate any significant causal effects of AS, AIS, LAS, or CES on glaucoma risk.
UNASSIGNED: Evidence from our series of causal inference approaches using large-scale population-based MR analyses did not support causal effects between glaucoma and stroke. These findings suggest that the relationship of glaucoma management and stroke risk prevention should be carefully evaluated in future studies. In turn, stroke diagnosis should not be simply applied to glaucoma risk prediction.

BACKGROUND: Evidence-based practice is the principle governing a range of healthcare practices and beyond. However, it has suffered from a lack of philosophical rigour. This paper sets out to analyse the epistemological basis of evidence-based practice.
METHODS: The paper uses a conceptual analysis. First, it describes the implicit epistemology at work in evidence-based practice. Second, it evaluates the implicit epistemological basis.
RESULTS: The analysis indicates that evidence-based practice lacks an explicit epistemological basis. It shows, moreover, that the implicit epistemological basis is untenable.
CONCLUSIONS: There is a need to re-think the epistemological basis for evidence-based practice. Evidence-based practice is out of touch with developments within philosophy of science.

This review explores the relationship between lithium in drinking water and mental health, a subject that has garnered increasing attention in investigations. Lithium, a metal with a well-established role in psychiatric medications, is found in trace amounts in drinking water, and studies suggest its potential correlations with lower rates of suicide and certain psychiatric disorders. However, these correlations do not imply causation, necessitating an examination of the underlying mechanisms. Lithium concentrations in drinking water vary globally, presenting challenges in establishing a universal threshold for \"high\" or \"low\" levels. Additionally, the optimal dosage for potential mental health benefits remains uncertain. Lithium is not considered an essential nutrient, and supplementation should be approached with caution due to possible toxicity risks, emphasizing the importance of medical supervision. The lack of causation and ongoing need for further investigation underscores the importance of cautious interpretation and transparent communication in navigating this evolving field.

Recent media coverage of high-profile cases of cervical artery dissection (CAD) has ignited the discussion about the role of cervical spine manipulation (CSM) in causing cervical artery dissection. However, research does not support a causal association between cervical spine manipulation and cervical artery dissection in a healthy cervical spine. The objective of this study was to review the 10 most recent case reports of cervical spine manipulation and cervical artery dissection for convincing evidence of the causation of cervical artery dissection by cervical spine manipulation. Nine of 10 case reports showed no convincing evidence of a causal relationship between cervical spine manipulation and cervical artery dissection. The 10th case report was exceptional as the CSM was contraindicated by pre-existing cervical spine pathology. We conclude that these 10 case reports provide no convincing evidence of the causation of cervical artery dissection by cervical spine manipulation in a healthy cervical spine. One case report demonstrated that cervical spine manipulation can cause cervical artery dissection when performed in the presence of pre-existing cervical spine pathology. Therefore, we conclude that practitioners should exclude cervical spine pathology before performing cervical spine manipulation.