The effects of cardiovascular and orthopaedic surgery on vitamin concentrations: a narrative review of the literature and mechanisms of action.

Given the rise in worldwide chronic diseases, supplemented by an aging population, the volume of global major surgeries, encompassing cardiac and orthopedic procedures is anticipated to surge significantly. Surgical trauma can be accompanied by numerous postoperative complications and metabolic changes. The present review summarized the results from studies assessing the effects of orthopedic and cardiovascular surgery on vitamin concentrations, in addition to exploring the possible mechanisms associated with changes in concentrations. Studies have revealed a potentially severe depletion in plasma/serum concentrations of numerous vitamins following these surgeries acutely. Vitamins C, D and B1 appear particularly vulnerable to significant depletions, with vitamin C and D depletions consistently transpiring into inadequate and deficient concentrations, respectively. The possible multifactorial mechanisms impacting postoperative vitamin concentrations include changes in hemodilution and vitamin utilization, redistribution, circulatory transport and absorption. For a majority of vitamins, there has been a lack of investigation into the effects of both, cardiac and orthopedic surgery. Additionally, studies were predominantly restricted to short-term postoperative investigations, primarily performed within the first postoperative week of surgery. Overall, results indicated that further examination is necessary to determine the severity and clinical significance of the possible depletions in vitamin concentrations that ensue cardiovascular and orthopedic surgery.

Development and validation of retrospective electronic frailty index using operational data of aged care homes.

BACKGROUND: Although elderly population is generally frail, it is important to closely monitor their health deterioration to improve the care and support in residential aged care homes (RACs). Currently, the best identification approach is through time-consuming regular geriatric assessments. This study aimed to develop and validate a retrospective electronic frailty index (reFI) to track the health status of people staying at RACs using the daily routine operational data records. METHODS: We have access to patient records from the Royal Freemasons Benevolent Institution RACs (Australia) over the age of 65, spanning 2010 to 2021. The reFI was developed using the cumulative deficit frailty model whose value was calculated as the ratio of number of present frailty deficits to the total possible frailty indicators (32). Frailty categories were defined using population quartiles. 1, 3 and 5-year mortality were used for validation. Survival analysis was performed using Kaplan-Meier estimate. Hazard ratios (HRs) were estimated using Cox regression analyses and the association was assessed using receiver operating characteristic (ROC) curves. RESULTS: Two thousand five hundred eighty-eight residents were assessed, with an average length of stay of 1.2 ± 2.2 years. The RAC cohort was generally frail with an average reFI of 0.21 ± 0.11. According to the Kaplan-Meier estimate, survival varied significantly across different frailty categories (p < 0.01). The estimated hazard ratios (HRs) were 1.12 (95% CI 1.09-1.15), 1.11 (95% CI 1.07-1.14), and 1.1 (95% CI 1.04-1.17) at 1, 3 and 5 years. The ROC analysis of the reFI for mortality outcome showed an area under the curve (AUC) of ≥0.60 for 1, 3 and 5-year mortality. CONCLUSION: A novel reFI was developed using the routine data recorded at RACs. reFI can identify changes in the frailty index over time for elderly people, that could potentially help in creating personalised care plans for addressing their health deterioration.

The effects of surgery on plasma vitamin C concentrations and cognitive function: a protocol for a prospective, observational study.

BACKGROUND: Post-operative cognitive function has recently become an area of focus for researchers. The most commonly reported perioperative neurocognitive disorders include delirium and longer-lasting post-operative cognitive dysfunctions. The contributing pathophysiology to these complications remains unclear. A number of studies have systematically revealed a significant post-operative plasma vitamin C depletion. Recent insights have also exhibited a link between plasma vitamin C and numerous biological roles in brain function, with deficiencies potentially compromising cognitive function. AIM: The present prospective, observational study will investigate whether there is a possible link between post-operative plasma vitamin C depletion and cognitive dysfunction. METHODS: The cohort will consist of surgical patients, between the ages of 65 and 85 years, undergoing hip replacement surgery or a control group not exposed to surgical trauma. Participants will have their plasma vitamin C concentrations tested alongside a battery of computer-based cognitive assessments and paper and pen based cognitive tests. Further assessments will include dietary nutritional intake, serum vitamin B12 concentrations, cardiovascular biomarkers, wound healing, sleep quality, pain, mood and inflammatory cytokines. Participants will be tested at baseline (1-2 weeks prior to surgery) and subsequent testing sessions will be performed within 1 week, 4-6 weeks, 3 months and 6 months following surgery. CONCLUSIONS: Findings from this observational study will provide insight into whether there is a concomitant depletion in post-operative plasma vitamin C concentrations and cognition function. Extrapolated results may prompt future, extensive randomized controlled trials to assess whether vitamin C supplementation can alleviate or even prevent post-operative cognitive complications.

Data Integration Using Advances in Machine Learning in Drug Discovery and Molecular Biology.

While the term artificial intelligence and the concept of deep learning are not new, recent advances in high-performance computing, the availability of large annotated data sets required for training, and novel frameworks for implementing deep neural networks have led to an unprecedented acceleration of the field of molecular (network) biology and pharmacogenomics. The need to align biological data to innovative machine learning has stimulated developments in both data integration (fusion) and knowledge representation, in the form of heterogeneous, multiplex, and biological networks or graphs. In this chapter we briefly introduce several popular neural network architectures used in deep learning, namely, the fully connected deep neural network, recurrent neural network, convolutional neural network, and the autoencoder. Deep learning predictors, classifiers, and generators utilized in modern feature extraction may well assist interpretability and thus imbue AI tools with increased explication, potentially adding insights and advancements in novel chemistry and biology discovery.The capability of learning representations from structures directly without using any predefined structure descriptor is an important feature distinguishing deep learning from other machine learning methods and makes the traditional feature selection and reduction procedures unnecessary. In this chapter we briefly show how these technologies are applied for data integration (fusion) and analysis in drug discovery research covering these areas: (1) application of convolutional neural networks to predict ligand-protein interactions; (2) application of deep learning in compound property and activity prediction; (3) de novo design through deep learning. We also: (1) discuss some aspects of future development of deep learning in drug discovery/chemistry; (2) provide references to published information; (3) provide recently advocated recommendations on using artificial intelligence and deep learning in -omics research and drug discovery.

Bayesian analysis of meta-analytic models incorporating dependency: new approaches for the hierarchical Bayesian delta-splitting model.

Dependence between studies in meta-analysis is an assumption which is imposed on the structure of hierarchical Bayesian meta-analytic models. Dependence in meta-analysis can occur as a result of study reports using the same data or from the same authors. In this paper, the hierarchical Bayesian delta-splitting (HBDS) model (Steven and Taylor, 2009), which allows for dependence between studies and sub-studies by introducing dependency at the sampling and hierarchical levels, is developed using Bayesian approaches. Parameter estimation obtained from the joint posterior distributions of all parameters for the HBDS model was conducted using the Metropolis within Gibbs algorithm. The estimation of parameters for simulation studies using R code confirmed the consistency of the model parameters. These parameters were then tested successfully on studies to assess the effects of native-language vocabulary aids on second language reading as a case study.

The Contribution of Plasma and Brain Vitamin C on Age and Gender-Related Cognitive Differences: A Mini-Review of the Literature.

There is increasing evidence that sex differences in the brain may contribute to gender-related behavioral differences, including cognitive function. Literature has revealed gender dimorphisms in cognitive function between males and females. Additionally, several risk factors associated with cognitive decline depend on chronological age. It is well recognized that the process of aging is associated with a decline in cognitive ability and brain function. Various explanations may account for these gender-related cognitive differences and age-associated cognitive changes. Recent investigations have highlighted the importance of vitamin C in maintaining brain health and its association with cognitive function in both cognitively intact and impaired cohorts. The present review explores previous literature that has evaluated differences in plasma/brain vitamin C between genders and during aging. It then assesses whether these age and gender-related differences may affect the relationship between plasma/brain vitamin C and cognition. The purpose of this review was to examine the evidence for a link between plasma/brain vitamin C and cognition and the impact of gender and age on this relationship. Epidemiological studies have frequently shown higher vitamin C plasma concentrations in women. Similarly, aging has been systematically associated with reductions in plasma vitamin C levels. A range of animal studies has demonstrated potential gender and age-related differences in vitamin C brain distribution and utilization. The reviewed literature suggests that gender differences in plasma and brain vitamin C may potentially contribute to differences in gender-associated cognitive ability, particularly while females are pre-menopausal. Additionally, we can propose that age-associated differences in plasma and brain vitamin C may be potentially linked to age-associated cognitive differences, with older cohorts appearing more vulnerable to experience declines in plasma vitamin C concentrations alongside compromised vitamin C brain regulation. This review encourages future investigations to take into account both gender and age when assessing the link between plasma vitamin C concentrations and cognitive function. Further large scale investigations are required to assess whether differences in cognitive function between genders and age groups may be causally attributed to plasma vitamin C status and brain distribution and utilization.

The effects of knee arthroplasty on plasma vitamin C concentrations and cognitive function: a case study.

Post-operative neurocognitive disorders are becoming well-documented conditions, with their pathogenesis remaining unclear. Vitamin C is a molecule that has recently demonstrated both a potential link with cognitive function and a significant post-operative decline. Here, we present a case study of a 72-year-old male who underwent total knee replacement surgery. The patient demonstrated a substantial decline in plasma vitamin C concentrations, indicative of a severe deficiency, during the first post-operative week (post-operative Days 3 and 7). Similarly, at these time points, a number of validated paper and pen tests revealed a substantial decline in cognition on tasks relating to total recall, delayed recall, motor speed, recognition and motor speed, with no signs of delirium. These results provide the justification for larger, cohort studies to determine whether post-operative plasma vitamin C depletions could contribute to cognitive deficits post-operatively.

Gender Differences in Plasma Vitamin C Concentrations and Cognitive Function: A Pilot Cross-Sectional Study in Healthy Adults.

BACKGROUND: A number of investigations have highlighted the importance of vitamin C in maintaining brain health. Biologically, vitamin C has exhibited roles in neuromodulation, neurodevelopment, vascular support, and neuroprotection. Vitamin C's contribution to cognitive function in both cognitively intact and impaired cohorts has previously been assessed, with little focus on gender variability. OBJECTIVE: The present study explored the interaction between gender and plasma vitamin C on cognitive performance, and the effect of different amounts of plasma vitamin C (adequate/inadequate) on various cognitive tasks by gender. METHODS: This retrospective analysis was conducted in healthy adults (n = 80, female = 52, male = 28, 24-96 y) with a range of blood plasma vitamin C concentrations. Cognitive assessments included the Swinburne University Computerized Cognitive Assessment Battery (SUCCAB) and 2 pen-and-paper tests, the Symbol Digits Modalities Test (SDMT) and the Hopkins Verbal Learning Test-Revised (HVLT-R). Food-frequency questionnaires were used to elucidate dietary consumption. RESULTS: After adjusting for a number of potential covariates such as age, number of prescribed medications and dose of vitamin C supplementation, results indicated a significant interaction (P < 0.001) between plasma vitamin C and gender on cognitive function, on both the computerized and pen-and-paper assessments. A novel finding was that the performance of males with inadequate plasma vitamin C was poorer on tasks involving components of memory (short/delayed), inhibition, and visual perception, whereas females presenting with inadequate vitamin C were more compromised on tasks involving psychomotor performance/motor speed. Additionally, females with adequate vitamin C concentrations exhibited higher performance than males on tasks involving recall, recognition, attention, and focus. CONCLUSIONS: Further larger-scale investigations are required to establish a cause-and-effect relation and to elucidate whether differences in cognitive function between genders may be attributed to plasma vitamin C status.This trial was registered at https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=369440&isReview=true as ACTRN12615001140549.

A Modified Reach-to-Grasp Task in a Supine Position Shows Coordination Between Elbow and Hand Movements After Stroke.

Objective: A modified reach-to-grasp task has been developed for the purpose of investigating arm-hand coordination in a supine position in the functional magnetic resonance imaging environment. The objective of this study was to investigate the kinematics of the reach-to-grasp task, in stroke and healthy participants. Design: Observational cohort study. Setting: Movement laboratory. Participants: Ten stroke participants and 10 age-matched healthy participants performed 10 repetitions of the modified reach-to-grasp task in two conditions-a natural condition and a standardized condition in a splint. Intervention: Not applicable. Main Outcome Measures: Kinematic variables of start time of transport, start time of aperture, movement duration, time of peak velocity (PV), percentage time of PV, peak deceleration (PD), percentage time of PD, peak aperture (PA), time of PA, and percentage time of PA were recorded. The correlation between key events in the grasp and transport trajectories were investigated. Performance between conditions and groups were compared. Results: Both groups demonstrated a significant correlation between the start time of aperture and the start time of transport and between the time of PA and PV in both conditions. A significant correlation was found between the time of PA and the PD in both conditions for the healthy group, but in neither condition for the stroke group. Movements by participants with stroke had a significantly longer movement duration, a smaller PV, and an earlier absolute time of PV and PD, and an earlier percentage time of PV and PD. They also had a smaller aperture than healthy participants. Wearing the splint resulted in a significantly higher PV, later absolute and percentage time of PV, PD, and PA, and a smaller PA compared to moving without the splint. The timing of transport variables time to peak velocity and time to peak deceleration, were strongest determinants of movement duration. Conclusion: The modified reach-to-grasp movement performed without the constraint of the splint, demonstrates similar motor control and coordination between the grasp and transport components of reach-to-grasp as in seated reach-to-grasp. This provides a new task that may be used to explore reach-to-grasp in the fMRI environment.

Plasma Vitamin C Concentrations and Cognitive Function: A Cross-Sectional Study.

Vitamin-C is a water soluble molecule that humans have lost the ability to produce. Vitamin-C plays a role in CNS functions such as neuronal differentiation, maturation, myelin formation and modulation of the catecholaminergic systems. A recent systematic review by our team indicated the need for further research into the relationship between plasma vitamin C and cognition in cognitively intact participants using plasma vitamin C concentrations instead of estimates derived from food-frequency-questionnaires (FFQ), and more sensitive cognitive assessments suitable for cognitive abilities vulnerable to aging. It was hypothesized that higher plasma vitamin C concentrations would be linked with higher cognitive performance. This cross-sectional trial was conducted on healthy adults (n = 80, Female = 52, Male = 28, 24-96 years) with a range of plasma Vitamin C concentrations. Cognitive assessments included The Swinburne-University-Computerized-Cognitive-Assessment-Battery (SUCCAB) and two pen and paper tests, the Symbol-Digits-Modalities-Test (SDMT) and Hopkins-Verbal-Learning-Test-Revised (HVLT-R). The pen and paper assessments were conducted to establish whether their scores would correlate with the computerized tasks. Plasma-Vitamin C concentrations were measured using two biochemical analyses. Participants were grouped into those with plasma vitamin-C concentrations of adequate level (≥28 µmol/L) and deficient level (<28 µmol/L). The SUCCAB identified a significantly higher performance ratio (accuracy/reaction-time) in the group with adequate vitamin-C levels vs. deficient vitamin-C on the choice reaction time (M = 188 ± 4 vs. 167 ± 9, p = 0.039), immediate recognition memory (M = 81 ± 3 vs. 68 ± 6, p = 0.03), congruent Stroop (M = 134 ± 3 vs. 116 ± 7, p = 0.024), and delayed recognition tasks (M = 72 ± 2 vs. 62 ± 4, p = 0.049), after adjusting for age (p < 0.05). Significantly higher scores in immediate recall on the HVLT-R (M = 10.64 ± 0.16 vs. 9.17 ± 0.37, p = 0.001), delayed recall (M = 9.74 ± 0.22 vs. 7.64 ± 0.51, p < 0.001), total recall (M = 27.93 ± 0.48 vs. 24.19 ± 1.11, p = 0.003) were shown in participants with adequate plasma Vitamin-C concentrations, after adjusting for vitamin-C supplementation dose (p < 0.05). Similarly, higher SDMT scores were observed in participants with adequate plasma Vitamin-C concentrations (M = 49.73 ± 10.34 vs. 41.38 ± 5.06, p = 0.039), after adjusting for age (p < 0.05). In conclusion there was a significant association between vitamin-C plasma concentrations and performance on tasks involving attention, focus, working memory, decision speed, delayed and total recall, and recognition. Plasma vitamin C concentrations obtained through vitamin C supplementation did not affect cognitive performance differently to adequate concentrations obtained through dietary intake. Clinicaltrials.gov Unique Identifier: ACTRN 12615001140549, URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=369440.

Tripeptide analogues of MG132 as protease inhibitors.

The 26S proteasome and calpain are linked to a number of important human diseases. Here, we report a series of analogues of the prototypical tripeptide aldehyde inhibitor MG132 that show a unique combination of high activity and selectivity for calpains over proteasome. Tripeptide aldehydes (1-3) with an aromatic P3 substituent show enhanced activity and selectivity against ovine calpain 2 relative to chymotrypsin-like activity of proteasome. Docking studies reveal the key contacts between inhibitors and calpain to confirm the importance of the S3 pocket with respect to selectivity between calpains 1 and 2 and the proteasome.

Vitamin C Status and Cognitive Function: A Systematic Review.

Vitamin C plays a role in neuronal differentiation, maturation, myelin formation and modulation of the cholinergic, catecholinergic, and glutaminergic systems. This review evaluates the link between vitamin C status and cognitive performance, in both cognitively intact and impaired individuals. We searched the PUBMED, SCOPUS, SciSearch and the Cochrane Library from 1980 to January 2017, finding 50 studies, with randomised controlled trials (RCTs, n = 5), prospective (n = 24), cross-sectional (n = 17) and case-control (n = 4) studies. Of these, 36 studies were conducted in healthy participants and 14 on cognitively impaired individuals (including Alzheimer's and dementia). Vitamin C status was measured using food frequency questionnaires or plasma vitamin C. Cognition was assessed using a variety of tests, mostly the Mini-Mental-State-Examination (MMSE). In summary, studies demonstrated higher mean vitamin C concentrations in the cognitively intact groups of participants compared to cognitively impaired groups. No correlation between vitamin C concentrations and MMSE cognitive function was apparent in the cognitively impaired individuals. The MMSE was not suitable to detect a variance in cognition in the healthy group. Analysis of the studies that used a variety of cognitive assessments in the cognitively intact was beyond the scope of this review; however, qualitative assessment revealed a potential association between plasma vitamin C concentrations and cognition. Due to a number of limitations in these studies, further research is needed, utilizing plasma vitamin C concentrations and sensitive cognitive assessments that are suitable for cognitively intact adults.

Sleep Difficulty and Disease in a Cohort of Very Old Women.

OBJECTIVE: The objective of this study was to investigate the association between chronic diseases and sleep difficulty in older women. METHOD: A total of 10,721 women from The Australian Longitudinal Study on Women's Health, aged 70 to 75 years at baseline (1996), who answered sleep questionnaire data over 15 years follow-up, were surveyed. Longitudinal sleep difficulty class was regressed on baseline diseases. RESULTS: Arthritis and heart disease were the strongest predictors of sleep difficulty; odds ratios for belonging to the greatest sleep difficulty class were 2.27 (95% confidence interval [CI] = [1.98, 2.61]) and 1.8 (95% CI [1.5, 2.16], respectively. Bronchitis/emphysema, osteoporosis, asthma, diabetes, and hypertension also predicted greater sleep difficulty. CONCLUSION: Older women diagnosed with the aforementioned significant diseases may also be at greater risk of sleep difficulty. These women may need counseling or treatment for their sleep difficulty, to prevent depression, cognitive function decline, falls, frailty, and increased mortality, as well as greater risk of nursing home placement, well known to be reinforced by sleep trouble, and the associated health care costs and societal impacts poor sleep quality has for older adults.

Sleeping difficulty, disease and mortality in older women: a latent class analysis and distal survival analysis.

The aim of this study is to identify patterns of sleep difficulty in older women, to investigate whether sleep difficulty is an indicator for poorer survival, and to determine whether sleep difficulty modifies the association between disease and death. Data were from the Australian Longitudinal Study on Women's Health, a 15-year longitudinal cohort study, with 10 721 women aged 70-75 years at baseline. Repeated-measures latent class analysis identified four classes of persistent sleep difficulty: troubled sleepers (N = 2429, 22.7%); early wakers (N = 3083, 28.8%); trouble falling asleep (N = 1767, 16.5%); and untroubled sleepers (N = 3442, 32.1%). Sleep difficulty was an indicator for mortality. Compared with untroubled sleepers, hazard ratios and 95% confidence intervals for troubled sleepers, early wakers, and troubled falling asleep were 1.12 (1.03, 1.23), 0.81 (0.75, 0.91) and 0.89 (0.79, 1.00), respectively. Sleep difficulty may modify the prognosis of women with chronic diseases. Hazard ratios (and 95% confidence intervals) for having three or more diseases (compared with 0 diseases) were enhanced for untroubled sleepers, early wakers and trouble falling asleep [hazard ratio = 1.86 (1.55, 2.22), 1.91 (1.56, 2.35) and 1.98 (1.47, 2.66), respectively], and reduced for troubled sleepers [hazard ratio = 1.57 (1.24, 1.98)]. Sleep difficulty in older women is more complex than the presence or absence of sleep difficulty, and should be considered when assessing the risk of death associated with disease.

Global trends and projections for tobacco use, 1990-2025: an analysis of smoking indicators from the WHO Comprehensive Information Systems for Tobacco Control.

BACKGROUND: Countries have agreed on reduction targets for tobacco smoking stipulated in the WHO global monitoring framework, for achievement by 2025. In an analysis of data for tobacco smoking prevalence from nationally representative survey data, we aimed to provide comprehensive estimates of recent trends in tobacco smoking, projections for future tobacco smoking, and country-level estimates of probabilities of achieving tobacco smoking targets. METHODS: We used a Bayesian hierarchical meta-regression modelling approach using data from the WHO Comprehensive Information Systems for Tobacco Control to assess trends from 1990 to 2010 and made projections up to 2025 for current tobacco smoking, daily tobacco smoking, current cigarette smoking, and daily cigarette smoking for 173 countries for men and 178 countries for women. Modelling was implemented in Python with DisMod-MR and PyMC. We estimated trends in country-specific prevalence of tobacco use, projections for future tobacco use, and probabilities for decreased tobacco use, increased tobacco use, and achievement of targets for tobacco control from posterior distributions. FINDINGS: During the most recent decade (2000-10), the prevalence of tobacco smoking in men fell in 125 (72%) countries, and in women fell in 156 (88%) countries. If these trends continue, only 37 (21%) countries are on track to achieve their targets for men and 88 (49%) are on track for women, and there would be an estimated 1·1 billion current tobacco smokers (95% credible interval 700 million to 1·6 billion) in 2025. Rapid increases are predicted in Africa for men and in the eastern Mediterranean for both men and women, suggesting the need for enhanced measures for tobacco control in these regions. INTERPRETATION: Our findings show that striking between-country disparities in tobacco use would persist in 2025, with many countries not on track to achieve tobacco control targets and several low-income and middle-income countries at risk of worsening tobacco epidemics if these trends remain unchanged. Immediate, effective, and sustained action is necessary to attain and maintain desirable trajectories for tobacco control and achieve global convergence towards elimination of tobacco use. FUNDING: Ministry of Health, Labour and Welfare, Japan; Ministry of Education, Culture, Sports and Technology, Japan; Department of Health, Australia; Bloomberg Philanthropies.

Environmental and Anthropogenic Impacts on Avifaunal Assemblages in an Urban Parkland, 1976 to 2007.

Urban environments are unique, rapidly changing habitats in which almost half of the world's human population resides. The effects of urbanisation, such as habitat (vegetation) removal, pollution and modification of natural areas, commonly cause biodiversity loss. Long-term ecological monitoring of urban environments is vital to determine the composition and long-term trends of faunal communities. This paper provides a detailed view of long-term changes in avifaunal assemblages of the Adelaide City parklands and discusses the anthropogenic and environmental factors that contributed to the changes between 1976 and 2007. The Adelaide City parklands (ACP) comprise 760 ha of land surrounding Adelaide's central business district. Naturalist Robert Whatmough completed a 32-year survey of the ACP to determine the structure of the urban bird community residing there. Annual species richness and the abundance of birds in March and September months were analysed. Linear regression analysis was applied to species richness and abundance data of each assemblage. Resident parkland birds demonstrated significant declines in abundance. Native and introduced species also exhibited long-term declines in species richness and abundance throughout the 32-year period. Cycles of varying time periods indicated fluctuations in avian biodiversity demonstrating the need for future monitoring and statistical analyses on bird communities in the Adelaide City parklands.

Continental scale analysis of bird migration timing: influences of climate and life history traits-a generalized mixture model clustering and discriminant approach.

There is substantial evidence of climate-related shifts to the timing of avian migration. Although spring arrival has generally advanced, variable species responses and geographical biases in data collection make it difficult to generalise patterns. We advance previous studies by using novel multivariate statistical techniques to explore complex relationships between phenological trends, climate indices and species traits. Using 145 datasets for 52 bird species, we assess trends in first arrival date (FAD), last departure date (LDD) and timing of peak abundance at multiple Australian locations. Strong seasonal patterns were found, i.e. spring phenological events were more likely to significantly advance, while significant advances and delays occurred in other seasons. However, across all significant trends, the magnitude of delays exceeded that of advances, particularly for FAD (+22.3 and -9.6 days/decade, respectively). Geographic variations were found, with greater advances in FAD and LDD, in south-eastern Australia than in the north and west. We identified four species clusters that differed with respect to species traits and climate drivers. Species within bird clusters responded in similar ways to local climate variables, particularly the number of raindays and rainfall. The strength of phenological trends was more strongly related to local climate variables than to broad-scale drivers (Southern Oscillation Index), highlighting the importance of precipitation as a driver of movement in Australian birds.

Using Self-Organising Maps (SOMs) to assess synchronies: an application to historical eucalypt flowering records.

Self-Organising Map (SOM) clustering methods applied to the monthly and seasonal averaged flowering intensity records of eight Eucalypt species are shown to successfully quantify, visualise and model synchronisation of multivariate time series. The SOM algorithm converts complex, nonlinear relationships between high-dimensional data into simple networks and a map based on the most likely patterns in the multiplicity of time series that it trains. Monthly- and seasonal-based SOMs identified three synchronous species groups (clusters): E. camaldulensis, E. melliodora, E. polyanthemos; E. goniocalyx, E. microcarpa, E. macrorhyncha; and E. leucoxylon, E. tricarpa. The main factor in synchronisation (clustering) appears to be the season in which flowering commences. SOMs also identified the asynchronous relationship among the eight species. Hence, the likelihood of the production, or not, of hybrids between sympatric species is also identified. The SOM pattern-based correlation values mirror earlier synchrony statistics gleaned from Moran correlations obtained from the raw flowering records. Synchronisation of flowering is shown to be a complex mechanism that incorporates all the flowering characteristics: flowering duration, timing of peak flowering, of start and finishing of flowering, as well as possibly specific climate drivers for flowering. SOMs can accommodate for all this complexity and we advocate their use by phenologists and ecologists as a powerful, accessible and interpretable tool for visualisation and clustering of multivariate time series and for synchrony studies.

Modeling and control of the agitation-sedation cycle for critical care patients.

Agitation-sedation cycling in critically ill patients, characterized by oscillations between states of agitation and over-sedation, is damaging to patient health, and increases length of stay and healthcare costs. The mathematical model presented captures the essential dynamics of the agitation-sedation system for the first time, and is statistically validated using recorded infusion data for 37 patients. Constant patient-specific patient parameters are used, illustrating the commonality of these fundamental dynamics over a broad range of patients. The validated model serves as a basis for comparison of sedation administration methods, devices, therapeutics and protocols. Heavy derivative feedback control is shown to be an effective means of managing agitation, given consistent agitation measurement. The improved agitation management reduces the modeled mean and peak agitation levels 68.4% and 52.9% on average, respectively. Some patients showed over 90% reduction in mean agitation level through increased control gains. This improved agitation management is achieved via heavy derivative feedback control of sedation administration, which provides an essentially bolus-driven management approach, aligned with recent sedation practices.