Efficient High-Order Space-Angle-Energy Polytopic Discontinuous Galerkin Finite Element Methods for Linear Boltzmann Transport.

We introduce an hp-version discontinuous Galerkin finite element method (DGFEM) for the linear Boltzmann transport problem. A key feature of this new method is that, while offering arbitrary order convergence rates, it may be implemented in an almost identical form to standard multigroup discrete ordinates methods, meaning that solutions can be computed efficiently with high accuracy and in parallel within existing software. This method provides a unified discretisation of the space, angle, and energy domains of the underlying integro-differential equation and naturally incorporates both local mesh and local polynomial degree variation within each of these computational domains. Moreover, general polytopic elements can be handled by the method, enabling efficient discretisations of problems posed on complicated spatial geometries. We study the stability and hp-version a priori error analysis of the proposed method, by deriving suitable hp-approximation estimates together with a novel inf-sup bound. Numerical experiments highlighting the performance of the method for both polyenergetic and monoenergetic problems are presented.

"An excellent servant but a terrible master": Understanding the value of wearables for self-management in people with cystic fibrosis and their healthcare providers - A qualitative study.

BACKGROUND: Wearables hold potential to improve chronic disease self-management in conditions like cystic fibrosis (CF) through remote monitoring, early detection of illness and motivation. Little is known about the acceptability and sustainability of integrating wearables into routine care from the perspectives of people with CF (pwCF) and their treating clinicians. METHODS: A cross-sectional qualitative study involving semi-structured interviews with adult pwCF and focus groups comprising members of a CF multidisciplinary team (MDT) were conducted at a specialist CF centre in Australia. A phenomenological orientation underpinned the study. Inductive thematic analysis was performed using the Framework method. The study adhered to the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist. RESULTS: Nine pwCF and eight members of a CF MDT, representing six clinical disciplines, participated in the study. Eight themes were inductively generated from the data, of which four were identified from each group. PwCF valued wearables for providing real-time data to motivate healthy behaviours and support shared goal-setting with healthcare providers. Wearables did not influence adherence to CF-specific self-management practices and had some hardware limitations. Members of the CF MDT recognised potential benefits of remote monitoring and shared goal-setting, but advised caution regarding data accuracy, generating patient anxiety in certain personality traits, and lack of evidence supporting use in CF self-management. CONCLUSIONS: Perspectives on integrating wearables into CF care were cautiously optimistic, with emerging risks related to patient anxiety and lack of evidence moderating acceptance.

Detection and Exclusion of False-Positive Molecular Formula Assignments via Mass Error Distributions in UHR Mass Spectra of Natural Organic Matter.

Ultrahigh resolution mass spectrometry (UHRMS) routinely detects and identifies thousands of mass peaks in complex mixtures, such as natural organic matter (NOM) and petroleum. The assignment of several chemically plausible molecular formulas (MFs) for a single accurate mass still poses a major problem for the reliable interpretation of NOM composition in a biogeochemical context. Applying sensible chemical rules for MF validation is often insufficient to eliminate multiple assignments (MultiAs)─especially for mass peaks with low abundance or if ample heteroatoms or isotopes are included - and requires manual inspection or expert judgment. Here, we present a new approach based on mass error distributions for the identification of true and false assignments among MultiAs. To this end, we used the mass error in millidalton (mDa), which was superior to the commonly used relative mass error in ppm. We developed an automatic workflow to group MultiAs based on their shared formula units and Kendrick mass defect values and to evaluate the mass error distribution. In this way, the number of valid assignments of chlorinated disinfection byproducts was increased by 8-fold as compared to only applying 37Cl/35Cl isotope ratio filters. Likewise, phosphorus-containing MFs can be differentiated against chlorine-containing MFs with high confidence. Further, false assignments of highly aromatic sulfur-containing MFs ("black sulfur") to sodium adducts in negative ionization mode can be excluded by applying our approach. Overall, MFs for mass peaks that are close to the detection limit or where naturally occurring isotopes are rare (e.g., 15N) or absent (e.g., P and F) can now be validated, substantially increasing the reliability of MF assignments and broadening the applicability of UHRMS analysis to even more complex samples and processes.

A Mitochondrial Basis for Heart Failure Progression.

In health, the human heart is able to match ATP supply and demand perfectly. It requires 6 kg of ATP per day to satisfy demands of external work (mechanical force generation) and internal work (ion movements and basal metabolism). The heart is able to link supply with demand via direct responses to ADP and AMP concentrations but calcium concentrations within myocytes play a key role, signalling both inotropy, chronotropy and matched increases in ATP production. Calcium/calmodulin-dependent protein kinase (CaMKII) is a key adapter to increased workload, facilitating a greater and more rapid calcium concentration change. In the failing heart, this is dysfunctional and ATP supply is impaired. This review aims to examine the mechanisms and pathologies that link increased energy demand to this disrupted situation. We examine the roles of calcium loading, oxidative stress, mitochondrial structural abnormalities and damage-associated molecular patterns.

Genetic factors associated with hidradenitis suppurativa, a literature review.

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by deep-seated, painful lesions most frequently occurring in intertriginous areas of the skin. HS leads to poor quality of life in affected individuals and is difficult to diagnose and treat. Objective: Understanding the genetics associated with familial inheritance may lead to a better understanding of the pathogenesis of this debilitating disease. Methods: Articles published until March 9, 2023, were identified in PubMed using the following search terms: hidradenitis suppurativa and gene* or acne inversa and gene*. Results: The rate of monogenic mutations associated with HS is less than 7%, with the most common genetic mutations reported in sporadic and familial HS cases being in NCSTN and less frequently in PSENEN. Individuals with mutations in the gamma-secretase complex tended to have more severe HS and an early age of onset. Limitations: This study was limited to the case studies available in PubMed, the majority of which used targeted gene panels to detect genetic mutations. Conclusion: Approximately 30% of individuals diagnosed with HS report having a positive family history; however, very few studies demonstrate monogenic familial transmission of HS. The case studies of syndromic HS reported a variety of genetic mutations associated with HS, some of which were familial, while others were sporadic, suggesting that other pathways may be involved in the pathogenesis of HS and other potential mutations that have yet to be evaluated. More research is needed to understand the genetic mutations in HS.

Patterns of health service use for children with mental disorders in an Australian state population cohort.

OBJECTIVES: The rate of mental health services provided to children and young people is increasing worldwide, including in Australia. The aim of this study was to describe patterns of hospital and ambulatory mental health service use among a large population cohort of adolescents followed from birth, with consideration of variation by age, sex and diagnosis. METHODS: Characteristics of services provided for children with mental disorder diagnoses between birth and age 17.5 years were ascertained for a population cohort of 85,642 children (52.0% male) born between 2002 and 2005, from 'Admitted Patients', 'Emergency Department' and 'Mental Health Ambulatory' records provided by the New South Wales and Australian Capital Territory Health Departments. RESULTS: A total of 11,205 (~13.1%) children received at least one hospital or ambulatory health occasion of service for a mental health condition in the observation period. More than two-fifths of children with mental disorders had diagnoses spanning multiple categories of disorder over time. Ambulatory services were the most heavily used and the most common point of first contact. The rate of mental health service contact increased with age across all services, and for most categories of mental disorder. Girls were more likely to receive services for mental disorders than boys, but boys generally had an earlier age of first service contact. Finally, 3.1% of children presenting to mental health services experienced involuntary psychiatric inpatient admission. CONCLUSIONS: The extent of hospital and ambulatory-based mental healthcare service among children emphasises the need for primary prevention and early intervention.

Similarities and differences between post-traumatic stress disorder and major depressive disorder: Evidence from task-evoked functional magnetic resonance imaging meta-analysis.

BACKGROUND: Post-traumatic stress disorder (PTSD) and major depressive disorder (MDD) are psychiatric disorders that can present with overlapping symptoms and shared risk factors. However, the extent to which these disorders share common underlying neuropathological mechanisms remains unclear. To investigate the similarities and differences in task-evoked brain activation patterns between patients with PTSD and MDD. METHODS: A coordinate-based meta-analysis was conducted across 35 PTSD studies (564 patients and 543 healthy controls) and 125 MDD studies (4049 patients and 4170 healthy controls) using anisotropic effect-size signed differential mapping software. RESULTS: Both PTSD and MDD patients exhibited increased neural activation in the bilateral inferior frontal gyrus. However, PTSD patients showed increased neural activation in the right insula, left supplementary motor area extending to median cingulate gyrus and superior frontal gyrus (SFG), and left fusiform gyrus, and decreased neural activation in the right posterior cingulate gyrus, right middle temporal gyrus, right paracentral lobule, and right inferior parietal gyrus relative to MDD patients. CONCLUSION: Our meta-analysis suggests that PTSD and MDD share some similar patterns of brain activation, but also have distinct neural signatures. These findings contribute to our understanding of the potential neuropathology underlying these disorders and may inform the development of more targeted and effective treatment and intervention strategies. Moreover, these results may provide useful neuroimaging targets for the differential diagnosis of MDD and PTSD.

The effects of a Teddybear Hospital project on prescool childrens' knowledge and medical students' professionalism: a prospective cohort study.

BACKGROUND: The Teddybear Hospital (TH) Project is an effort to increase children's knowledge and decrease their anxiety. It is also intended to improve medical students' pediatric communication skills. This study evaluated the educational effects on participating preschool children and medical students. METHODS: Preschool children were offered to bring their stuffed toys to the TH at our tertiary academic medical center. Medical students who had completed the pediatric surgery rotation staffed the TH, performed examinations, and interacted with the children. The children's knowledge of anatomy, medical equipment, and healthy lifestyle, along with their level of anxiety towards hospitalization, was assessed using pre- and post-interventional validated survey tools. Preschool peers who did not participate in the TH served as controls. Participating medical students were tested on professionalism and pediatric surgical knowledge during, and 3 weeks after the intervention, and compared to their non-participating peers. RESULTS: A total of 131 children (63 intervention, 68 control) and 48 medical students (16 intervention, 32 control) participated in the study. Children's state anxiety decreased by 0.98 points (95% Confidence Interval [CI] -0.3 to -1.8, P<0.001), while knowledge increased significantly on "healthy lifestyle" by 1.4 points (95% CI 1.01 to 1.79, P<0.05), on "medical equipment" by 4.5 points (95% CI 3.8 to 5.2, P <0.0001), and on "anatomy" by 5.05 points (95% CI 4.73 to 5.73, P<0.01). No changes were detected in any of the outcome measures in the control group. Medical students' objective professionalism increased by 4.2 points (95% CI 1.58 to 6.80, P<0.01) compared to non-participant medical students. The tests did not show an increase in the medical students' pediatric surgical knowledge. CONCLUSIONS: Preschool participation in a TH increased knowledge and decreased anxiety regarding hospitalization and medical personnel. It also helped medical students to playfully acquire medical professionalism.

Myths and Methodologies: Standardisation in Human Physiology Research-Should We Control the Controllables?

The premise of research in human physiology is to explore a multifaceted system whilst identifying one or a few outcomes of interest. Therefore, the control of potentially confounding variables requires careful thought regarding the extent of control and complexity of standardisation. One common factor to control prior to testing is diet, as food and fluid provision may deviate from participants' habitual diets, yet a self-report and replication method can be flawed by under-reporting. Researchers may also need to consider standardisation of physical activity, whether it be through familiarisation trials, wash-out periods, or guidance on levels of physical activity to be achieved before trials. In terms of pharmacological agents, the ethical implications of standardisation require researchers to carefully consider how medications, caffeine consumption and oral contraceptive prescriptions may affect the study. For research in females, it should be considered whether standardisation between- or within-participants in regards to menstrual cycle phase is most relevant. The timing of measurements relative to various other daily events is relevant to all physiological research and so it can be important to standardise when measurements are made. This review summarises the areas of standardisation which we hope will be considered useful to anyone involved in human physiology research, including when and how one can apply standardisation to various contexts.

Making Predictions Using Poorly Identified Mathematical Models.

Many commonly used mathematical models in the field of mathematical biology involve challenges of parameter non-identifiability. Practical non-identifiability, where the quality and quantity of data does not provide sufficiently precise parameter estimates is often encountered, even with relatively simple models. In particular, the situation where some parameters are identifiable and others are not is often encountered. In this work we apply a recent likelihood-based workflow, called Profile-Wise Analysis (PWA), to non-identifiable models for the first time. The PWA workflow addresses identifiability, parameter estimation, and prediction in a unified framework that is simple to implement and interpret. Previous implementations of the workflow have dealt with idealised identifiable problems only. In this study we illustrate how the PWA workflow can be applied to both structurally non-identifiable and practically non-identifiable models in the context of simple population growth models. Dealing with simple mathematical models allows us to present the PWA workflow in a didactic, self-contained document that can be studied together with relatively straightforward Julia code provided on GitHub . Working with simple mathematical models allows the PWA workflow prediction intervals to be compared with gold standard full likelihood prediction intervals. Together, our examples illustrate how the PWA workflow provides us with a systematic way of dealing with non-identifiability, especially compared to other approaches, such as seeking ad hoc parameter combinations, or simply setting parameter values to some arbitrary default value. Importantly, we show that the PWA workflow provides insight into the commonly-encountered situation where some parameters are identifiable and others are not, allowing us to explore how uncertainty in some parameters, and combinations of parameters, regardless of their identifiability status, influences model predictions in a way that is insightful and interpretable.

Liver Fibrosis Assessed Via Noninvasive Tests is Associated With Incident Heart Failure in a General Population Cohort.

BACKGROUND & AIMS: The aim of this study was to determine whether liver fibrosis is associated with heart failure in a general population cohort, and if genetic polymorphisms (PNPLA3 rs738409; TM6SF2 rs58542926), linked to increased risk of liver fibrosis and decreased risk of coronary artery disease, modify this association. METHODS: Using UK Biobank data, we prospectively examined the relationship between noninvasive fibrosis markers (nonalcoholic fatty liver disease [NAFLD] fibrosis score [NFS], Fibrosis-4 [FIB-4] and aspartate transaminase [AST] to platelet ratio index [APRI]) and incident hospitalization/death from heart failure (n = 413,860). Cox-regression estimated hazard ratios (HRs) for incident heart failure. Effects of PNPLA3 and TM6SF2 on the association between liver fibrosis and heart failure were estimated by stratifying for genotype and testing for an interaction between genotype and liver fibrosis using a likelihood ratio test. RESULTS: A total of 12,527 incident cases of heart failure occurred over a median of 10.7 years. Liver fibrosis was associated with an increased risk of hospitalization or death from heart failure (multivariable adjusted high-risk NFS score HR, 1.59; 95% confidence interval [CI],1.47-1.76; P < .0001; FIB-4 HR, 1.69; 95% CI, 1.55-1.84; P < .0001; APRI HR, 1.85; 95% CI, 1.56-2.19; P < .0001; combined fibrosis scores HR, 1.90; 95% CI, 1.44-2.49; P < .0001). These associations persisted for people with metabolic dysfunction-associated steatotic liver disease (MASLD), MASLD with alcohol consumption (Met-ALD), and harmful alcohol consumption. PNPLA3 rs738409 GG and TM6SF2 rs58542926 TT did not attenuate the positive association between fibrosis markers and heart failure. For PNPLA3, a statistically significant interaction was found between PNPLA3 rs738409, FIB-4, APRI score, and heart failure. CONCLUSION: In the general population, serum markers of liver fibrosis are associated with increased hospitalization/death from heart failure. Genetic polymorphisms associated with liver fibrosis were not positively associated with elevated heart failure risk.

Reward Sensitivity and Noise Contribute to Negative Affective Bias: A Learning Signal Detection Theory Approach in Decision-Making.

In patients with mood disorders, negative affective biases - systematically prioritising and interpreting information negatively - are common. A translational cognitive task testing this bias has shown that depressed patients have a reduced preference for a high reward under ambiguous decision-making conditions. The precise mechanisms underscoring this bias are, however, not yet understood. We therefore developed a set of measures to probe the underlying source of the behavioural bias by testing its relationship to a participant's reward sensitivity, value sensitivity and reward learning rate. One-hundred-forty-eight participants completed three online behavioural tasks: the original ambiguous-cue decision-making task probing negative affective bias, a probabilistic reward learning task probing reward sensitivity and reward learning rate, and a gambling task probing value sensitivity. We modelled the learning task through a dynamic signal detection theory model and the gambling task through an expectation-maximisation prospect theory model. Reward sensitivity from the probabilistic reward task (ß = 0.131, p = 0.024) and setting noise from the probabilistic reward task (ß = -0.187, p = 0.028) both predicted the affective bias score in a logistic regression. Increased negative affective bias, at least on this specific task, may therefore be driven in part by a combination of reduced sensitivity to rewards and more variable responses.

Post column infusion of an internal standard into LC-FT-ICR MS enables semi-quantitative comparison of dissolved organic matter in original samples.

Ultrahigh resolution mass spectrometry hyphenated with liquid chromatography (LC) is an emerging tool to explore the isomeric composition of dissolved organic matter (DOM). However, matrix effects limit the potential for semi-quantitative comparison of DOM molecule abundances across samples. We introduce a post-column infused internal standard (PCI-IS) for reversed-phase LC-FT-ICR MS measurements of DOM and systematically evaluate matrix effects, detector linearity and the precision of mass peak intensities. Matrix effects for model compounds spiked into freshwater DOM samples ranging from a headwater stream to a major river were reduced by 5-10% for PCI-IS corrected mass peak intensities as compared to raw (i.e., untransformed) intensities. A linear regression of PCI-IS corrected DOM mass peak intensities across a typical DOM concentration range (2-15 mg dissolved organic carbon L-1) in original, non-extracted freshwater samples demonstrates excellent linearity of the detector response (r2 > 0.9 for 98% of detected molecular formulas across retention times). Importantly, PCI-IS could compensate for 80% of matrix effects across an environmental gradient of DOM composition from groundwater to surface water. This enabled studying the ionization efficiency of DOM isomers and linking the observed differences to the biogeochemical sources. With PCI-IS original, non-extracted DOM samples can be analysed by LC-FT-ICR MS without carbon load adjustment, and mass peak intensities can be reliably used to semi-quantitatively compare isomer abundances between compositionally similar DOM samples.

Indian Ocean temperature anomalies predict long-term global dengue trends.

Despite identifying El Niño events as a factor in dengue dynamics, predicting the oscillation of global dengue epidemics remains challenging. Here, we investigate climate indicators and worldwide dengue incidence from 1990 to 2019 using climate-driven mechanistic models. We identify a distinct indicator, the Indian Ocean basin-wide (IOBW) index, as representing the regional average of sea surface temperature anomalies in the tropical Indian Ocean. IOBW is closely associated with dengue epidemics for both the Northern and Southern hemispheres. The ability of IOBW to predict dengue incidence likely arises as a result of its effect on local temperature anomalies through teleconnections. These findings indicate that the IOBW index can potentially enhance the lead time for dengue forecasts, leading to better-planned and more impactful outbreak responses.

Increased α2,3-sialyl N-glycosylated prostate-specific membrane antigen (PSMA) in post-DRE urine is associated with high grade group prostate cancer.

INTRODUCTION: Aberrant glycosylation of proteins is an important hallmark in multiple cancers. Prostate-specific membrane antigen (PSMA), a highly glycosylated protein with 10 N-linked glycosylation sites, is an Food and Drug Administration approved theranostic for prostate cancer. However, glycosylation changes in PSMA that are associated with prostate cancer disease progression have not been fully characterized. METHODS: We investigated whether urinary PSMA sialylation correlate with high-grade prostate cancer. Urine samples were collected from men after digital rectal examination (DRE) before prostate biopsy. Lectin-antibody enzyme-linked immunoassay was used to quantify α2,3-sialyl PSMA in post-DRE urine samples from subjects with benign prostate tumors, Grade Group 1 prostate cancer and those with Grade Group ≥2 disease. RESULTS: There are significant increases in α2,3-sialylated PSMA in patients with Grade Group ≥2 disease compared to benign (p = 0.0009) and those with Grade Group 1 disease (p = 0.0063). There were no significant differences in α2,3-sialyl PSMA levels between Grade Group 1 and benign prostate tumors (p = 0.7947). CONCLUSIONS: Our study shows that there are significant differences in the abundance of α2,3-sialylated PSMA in post-DRE urines from disease stratified prostate cancer patients, and the increase is correlated with progression and disease severity. The detection of increased PSMA sialyation in post-DRE urines from patients with higher Grade Group ≥2 disease states provides novel untapped potential for the development of prognostic biomarkers for prostate cancer. Specifically, quantitation of α2,3-sialylated PSMA shows potential for discriminating between benign to intermediate grade disease, which is a significant clinical challenge in staging and risk stratification of prostate cancer.

Antigen-level resolution of commensal-specific B cell responses can be enabled by phage display screening coupled with B cell tetramers.

Induction of commensal-specific immunity contributes to tissue homeostasis, yet the mechanisms underlying induction of commensal-specific B cells remain poorly understood in part due to a lack of tools to identify these cells. Using phage display, we identified segmented filamentous bacteria (SFB) antigens targeted by serum and intestinal antibodies and generated B cell tetramers to track SFB-specific B cells in gut-associated lymphoid tissues. We revealed a compartmentalized response in SFB-specific B cell activation, with a gradient of immunoglobulin A (IgA), IgG1, and IgG2b isotype production along Peyer's patches contrasted by selective production of IgG2b within mesenteric lymph nodes. V(D)J sequencing and monoclonal antibody generation identified somatic hypermutation driven affinity maturation to SFB antigens under homeostatic conditions. Combining phage display and B cell tetramers will enable investigation of the ontogeny and function of commensal-specific B cell responses in tissue immunity, inflammation, and repair.

Prospective validation of clinical deterioration predictive models prior to intensive care unit transfer among patients admitted to acute care cardiology wards.

Objective. Very few predictive models have been externally validated in a prospective cohort following the implementation of an artificial intelligence analytic system. This type of real-world validation is critically important due to the risk of data drift, or changes in data definitions or clinical practices over time, that could impact model performance in contemporaneous real-world cohorts. In this work, we report the model performance of a predictive analytics tool developed before COVID-19 and demonstrate model performance during the COVID-19 pandemic.Approach. The analytic system (CoMETⓇ, Nihon Kohden Digital Health Solutions LLC, Irvine, CA) was implemented in a randomized controlled trial that enrolled 10 422 patient visits in a 1:1 display-on display-off design. The CoMET scores were calculated for all patients but only displayed in the display-on arm. Only the control/display-off group is reported here because the scores could not alter care patterns.Main results.Of the 5184 visits in the display-off arm, 311 experienced clinical deterioration and care escalation, resulting in transfer to the intensive care unit, primarily due to respiratory distress. The model performance of CoMET was assessed based on areas under the receiver operating characteristic curve, which ranged from 0.725 to 0.737.Significance.The models were well-calibrated, and there were dynamic increases in the model scores in the hours preceding the clinical deterioration events. A hypothetical alerting strategy based on a rise in score and duration of the rise would have had good performance, with a positive predictive value more than 10-fold the event rate. We conclude that predictive statistical models developed five years before study initiation had good model performance despite the passage of time and the impact of the COVID-19 pandemic.

Human movement and environmental barriers shape the emergence of dengue.

Understanding how emerging infectious diseases spread within and between countries is essential to contain future pandemics. Spread to new areas requires connectivity between one or more sources and a suitable local environment, but how these two factors interact at different stages of disease emergence remains largely unknown. Further, no analytical framework exists to examine their roles. Here we develop a dynamic modelling approach for infectious diseases that explicitly models both connectivity via human movement and environmental suitability interactions. We apply it to better understand recently observed (1995-2019) patterns as well as predict past unobserved (1983-2000) and future (2020-2039) spread of dengue in Mexico and Brazil. We find that these models can accurately reconstruct long-term spread pathways, determine historical origins, and identify specific routes of invasion. We find early dengue invasion is more heavily influenced by environmental factors, resulting in patchy non-contiguous spread, while short and long-distance connectivity becomes more important in later stages. Our results have immediate practical applications for forecasting and containing the spread of dengue and emergence of new serotypes. Given current and future trends in human mobility, climate, and zoonotic spillover, understanding the interplay between connectivity and environmental suitability will be increasingly necessary to contain emerging and re-emerging pathogens.

Myths and Methodologies: Standardisation in human physiology research-should we control the controllables?

The premise of research in human physiology is to explore a multifaceted system whilst identifying one or a few outcomes of interest. Therefore, the control of potentially confounding variables requires careful thought regarding the extent of control and complexity of standardisation. One common factor to control prior to testing is diet, as food and fluid provision may deviate from participants' habitual diets, yet a self-report and replication method can be flawed by under-reporting. Researchers may also need to consider standardisation of physical activity, whether it be through familiarisation trials, wash-out periods, or guidance on levels of physical activity to be achieved before trials. In terms of pharmacological agents, the ethical implications of standardisation require researchers to carefully consider how medications, caffeine consumption and oral contraceptive prescriptions may affect the study. For research in females, it should be considered whether standardisation between- or within-participants in regards to menstrual cycle phase is most relevant. The timing of measurements relative to various other daily events is relevant to all physiological research and so it can be important to standardise when measurements are made. This review summarises the areas of standardisation which we hope will be considered useful to anyone involved in human physiology research, including when and how one can apply standardisation to various contexts.

Spatial distribution of settlement of Diadema antillarum around Saba, Dutch Caribbean.

The mass mortality event of the herbivorous sea urchin Diadema antillarum in 1983-1984 has been a major contributor to the diminished resilience of coral reefs throughout the Caribbean. The reduction in grazing pressure resulted in algae proliferation, which inhibited coral recruitment after disturbances such as disease, hurricanes, pollution and climatic change induced marine heat waves. Natural recovery of D. antillarum after the 1983-1984 die-off has been slow. However, the few locations with recovered populations exhibit signs of improvement in coral reef health, prompting interest in D. antillarum restoration. Current restoration strategies include translocation of wild individuals, the restocking of juveniles that are either cultured from gametes or collected as settlers and head-started in a nursery, and assisted natural recovery by providing suitable settlement substrate. Both the collection of wild settlers and assisted natural recovery necessitate an understanding of the local, spatiotemporal trends in settlement. In this study, which was carried out on the Dutch Caribbean Island of Saba, artificial turf settlement collectors were deployed at nine locations around the island and monitored from June 2019 till July 2020 (13 months). The primary objective was to identify trends in larval settlement in space and time, to be able to optimize restoration efforts. Additionally, the small size of Saba allowed us to deploy settlement collectors around the island and compare D. antillarum settlement between windward and leeward sides. Our study showed that on Saba, D. antillarum settlement peaked in June and July, following similar seasonal trends observed around other islands in the Northeastern Caribbean. By far the most settlement occurred at the leeward side of the island, suggesting that hydrodynamic forces entrained D. antillarum larvae in the lee of Saba and/or calmer waters facilitated settlement. Limited settlement occurred on the more exposed windward locations. The identified high settlement locations are candidates for settler collection and restoration attempts. Continued monitoring of D. antillarum settlement, especially in light of the 2022 D. antillarum die-off, holds significance as it can provide insights into the potential of natural recovery.