Automated analysis and detection of epileptic seizures in video recordings using artificial intelligence.

Introduction: Automated seizure detection promises to aid in the prevention of SUDEP and improve the quality of care by assisting in epilepsy diagnosis and treatment adjustment. Methods: In this phase 2 exploratory study, the performance of a contactless, marker-free, video-based motor seizure detection system is assessed, considering video recordings of patients (age 0-80 years), in terms of sensitivity, specificity, and Receiver Operating Characteristic (ROC) curves, with respect to video-electroencephalographic monitoring (VEM) as the medical gold standard. Detection performances of five categories of motor epileptic seizures (tonic-clonic, hyperkinetic, tonic, unclassified motor, automatisms) and psychogenic non-epileptic seizures (PNES) with a motor behavioral component lasting for >10 s were assessed independently at different detection thresholds (rather than as a categorical classification problem). A total of 230 patients were recruited in the study, of which 334 in-scope (>10 s) motor seizures (out of 1,114 total seizures) were identified by VEM reported from 81 patients. We analyzed both daytime and nocturnal recordings. The control threshold was evaluated at a range of values to compare the sensitivity (n = 81 subjects with seizures) and false detection rate (FDR) (n = all 230 subjects). Results: At optimal thresholds, the performance of seizure groups in terms of sensitivity (CI) and FDR/h (CI): tonic-clonic- 95.2% (82.4, 100%); 0.09 (0.077, 0.103), hyperkinetic- 92.9% (68.5, 98.7%); 0.64 (0.59, 0.69), tonic- 78.3% (64.4, 87.7%); 5.87 (5.51, 6.23), automatism- 86.7% (73.5, 97.7%); 3.34 (3.12, 3.58), unclassified motor seizures- 78% (65.4, 90.4%); 4.81 (4.50, 5.14), and PNES- 97.7% (97.7, 100%); 1.73 (1.61, 1.86). A generic threshold recommended for all motor seizures under study asserted 88% sensitivity and 6.48 FDR/h. Discussion: These results indicate an achievable performance for major motor seizure detection that is clinically applicable for use as a seizure screening solution in diagnostic workflows.

Welfare Implications for Tigers in Travelling Circuses.

There are very few studies that have focused on species-specific welfare implications for tigers in a travelling circus. The absence of scientific evidence to inform nationwide legislation means that tigers are still commonly used in travelling circuses across the world. A systematic review of relevant published studies was conducted using the bibliographic databases Web of Science and Scopus, supplemented by a narrative search. In total, 42 relevant studies were identified that assessed the welfare of tigers in captivity, including circuses and zoos. Only eight papers assessed the welfare implications for tigers in circuses directly, evidencing the lack of research in this area. Given that circuses provide a sub-optimal environment compared to zoos, implications for tiger welfare were also inferred from zoo research, within the Five Domains framework. Collectively, these papers infer that the travelling nature of a circus often negatively impacts the welfare domains of nutrition, physical environment, health, and mental state. This is due to limitations in enclosure size, as well as in both environmental and behavioural enrichment. There is also often difficulty in sourcing appropriate food and specialised routine veterinary care. The literature is divided concerning behavioural interactions, specifically whether training can improve welfare by offering mental stimulation. However, circus performances are often associated with negative welfare due to noise disruption from spectators. The collective scientific evidence indicates that tigers are not well suited to circus living, due to the inability of a travelling circus to provide for their species-specific psychological, physiological, and behavioural needs.

Utilisation of Chronic Disease and Mental Health Management Services and Cardioprotective Medication Prescriptions in Primary Care for Patients With Cardiovascular Diseases and Cancer: A Cross-Sectional Study.

BACKGROUND: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality among cancer survivors. Mental health is considered an important risk factor affecting the treatment of cardiovascular disease. However, little is known about the use of secondary prevention strategies for CVD in patients with both cancer and CVD. This study aimed to compare the utilisation of primary care chronic disease management plans, mental health care and guideline-indicated cardioprotective medications among CVD patients with and without cancer. METHODS: Retrospective cross-sectional study utilising clinical data of patients with CVD from 50 Australian primary care practices. Outcomes included the use of chronic disease management plans, mental health care, guideline-indicated cardioprotective medications and influenza vaccination. Logistic regression, accounting for demographic and clinical covariates and clustering effects by practices, was used to compare the two groups. RESULTS: Of the 15,040 patients with CVD, 1,486 patients (9.9%) concurrently had cancer. Patients with cancer, compared to those without, were older (77.6 vs 71.8 years, p<0.001), more likely to drink alcohol (62.6% vs 55.7%, p<0.001), have lower systolic (130.3±17.8 vs 132.5±21.1 mmHg, p<0.001) and diastolic (72.2±11 vs 75.3±34 mmHg, p<0.001) blood pressure. Although suboptimal for both groups, patients with cancer were significantly more likely to have general practice management plans (GPMPs) (51.4% vs 43.2%, p<0.001), coordination of team care arrangements (TCAs) (46.2% vs 37.0%, p<0.001), have a review of either GPMP or TCA (42.8% vs 34.7%, p<0.001), have a mental health treatment consultation (15.4% vs 10.5%, p=0.004) and be prescribed blood pressure-lowering medications (70.1% vs 66.0%, p=0.002). However, there were no statistical differences in the prescription of lipid-lowering or antiplatelet medications. After adjustments for covariates and multiple testing, patients with cancer did not show a difference in GPMPs, TCAs, and a review of either, but were more likely to receive mental health treatment consultations than those without cancer (odds ratio 1.76; 95% confidence interval 1.42-2.19). CONCLUSIONS: Less than half of patients with CVD had a GPMP, TCA or review of either. Although those patients with cancer were more likely to receive these interventions, still around half the patients did not. Medicare-funded GPMPs, TCAs and a review of either GPMP or TCA were underutilised, and future studies should seek to identify ways of improving access to these services.

From the Backyard to Our Beds: The Spectrum of Care, Attitudes, Relationship Types, and Welfare in Non-Commercial Chicken Care.

Non-commercial chickens may be the third most numerous pets in Western countries. Yet, to date, there is limited research into their welfare or the care-taking practices and attitudes of their guardians. Using a quantitative questionnaire, this study investigated non-commercial chicken owners' care-taking practices, attitudes, and relationship types with their chickens. Additionally, the study investigated barriers to optimizing non-commercial chicken welfare. Specific questions were asked regarding niche care-taking practices, including the use of Suprelorin® implants. With 2000+ responses, this study found variable care-taking practices, yet largely positive attitudes towards chickens, and a "personal" (though not "close personal") owner-chicken relationship, as defined by the Owner-Bird Relationship Scale. The Chicken Attitude Scale, Owner-Bird Relationship Scale, and Care Series scores were found to be correlated with each other, with coefficients ranging from 0.176 to 0.543 (p < 0.001). "Preventing commercial chickens from going to slaughter" was a key motive for chicken care by 56.1% of respondents, with 69.6% of respondents stating they cared for ex-commercial chickens. This study found a higher prevalence of reported poor health conditions and number of deaths relative to prior studies, and egg yolk peritonitis emerged as a leading health condition and cause of death. Moreover, 68.0% had not heard of Suprelorin® implants, and only 6.3% used implants. Most (76.4%) chicken carers followed an omnivorous diet that includes chicken meat/eggs. The results reinforced previous findings concerning a need for more avian-specialist, locally available, and affordable veterinary care for chickens. Research into Suprelorin® implants, rooster-specific care, and tailored requirements of caring for ex-commercial chickens is recommended.

Artificial intelligence in epilepsy phenotyping.

Artificial intelligence (AI) allows data analysis and integration at an unprecedented granularity and scale. Here we review the technological advances, challenges, and future perspectives of using AI for electro-clinical phenotyping of animal models and patients with epilepsy. In translational research, AI models accurately identify behavioral states in animal models of epilepsy, allowing identification of correlations between neural activity and interictal and ictal behavior. Clinical applications of AI-based automated and semi-automated analysis of audio and video recordings of people with epilepsy, allow significant data reduction and reliable detection and classification of major motor seizures. AI models can accurately identify electrographic biomarkers of epilepsy, such as spikes, high-frequency oscillations, and seizure patterns. Integrating AI analysis of electroencephalographic, clinical, and behavioral data will contribute to optimizing therapy for patients with epilepsy.

Automatic classification of hyperkinetic, tonic, and tonic-clonic seizures using unsupervised clustering of video signals.

Introduction: This study evaluated the accuracy of motion signals extracted from video monitoring data to differentiate epileptic motor seizures in patients with drug-resistant epilepsy. 3D near-infrared video was recorded by the Nelli® seizure monitoring system (Tampere, Finland). Methods: 10 patients with 130 seizures were included in the training dataset, and 17 different patients with 98 seizures formed the testing dataset. Only seizures with unequivocal hyperkinetic, tonic, and tonic-clonic semiology were included. Motion features from the catch22 feature collection extracted from video were explored to transform the patients' videos into numerical time series for clustering and visualization. Results: Changes in feature generation provided incremental discrimination power to differentiate between hyperkinetic, tonic, and tonic-clonic seizures. Temporal motion features showed the best results in the unsupervised clustering analysis. Using these features, the system differentiated hyperkinetic, tonic and tonic-clonic seizures with 91, 88, and 45% accuracy after 100 cross-validation runs, respectively. F1-scores were 93, 90, and 37%, respectively. Overall accuracy and f1-score were 74%. Conclusion: The selected features of motion distinguished semiological differences within epileptic seizure types, enabling seizure classification to distinct motor seizure types. Further studies are needed with a larger dataset and additional seizure types. These results indicate the potential of video-based hybrid seizure monitoring systems to facilitate seizure classification improving the algorithmic processing and thus streamlining the clinical workflow for human annotators in hybrid (algorithmic-human) seizure monitoring systems.

Proposed solutions to anthropogenic climate change: A systematic literature review and a new way forward.

Humanity is now facing what may be the biggest challenge to its existence: irreversible climate change brought about by human activity. Our planet is in a state of emergency, and we only have a short window of time (7-8 years) to enact meaningful change. The goal of this systematic literature review is to summarize the peer-reviewed literature on proposed solutions to climate change in the last 20 years (2002-2022), and to propose a framework for a unified approach to solving this climate change crisis. Solutions reviewed include a transition toward use of renewable energy resources, reduced energy consumption, rethinking the global transport sector, and nature-based solutions. This review highlights one of the most important but overlooked pieces in the puzzle of solving the climate change problem - the gradual shift to a plant-based diet and global phaseout of factory (industrialized animal) farming, the most damaging and prolific form of animal agriculture. The gradual global phaseout of industrialized animal farming can be achieved by increasingly replacing animal meat and other animal products with plant-based products, ending government subsidies for animal-based meat, dairy, and eggs, and initiating taxes on such products. Failure to act will ultimately result in a scenario of irreversible climate change with widespread famine and disease, global devastation, climate refugees, and warfare. We therefore suggest an "All Life" approach, invoking the interconnectedness of all life forms on our planet. The logistics for achieving this include a global standardization of Environmental, Social, and Governance (ESG) or similar measures and the introduction of a regulatory body for verification of such measures. These approaches will help deliver environmental and sustainability benefits for our planet far beyond an immediate reduction in global warming.

Identification of SKOR2 IgG as a novel biomarker of paraneoplastic neurologic syndrome.

Introduction: The development of new autoantigen discovery techniques, like programmable phage immunoprecipitation sequencing (PhIP-Seq), has accelerated the discovery of neural-specific autoantibodies. Herein, we report the identification of a novel biomarker for paraneoplastic neurologic syndrome (PNS), Sloan-Kettering-Virus-Family-Transcriptional-Corepressor-2 (SKOR2)-IgG, utilizing PhIP-Seq. We have also performed a thorough clinical validation using normal, healthy, and disease/cancer control samples. Methods: Stored samples with unclassified staining at the junction of the Purkinje cell and the granule cell layers were analyzed by PhIP-Seq for putative autoantigen identification. The autoantigen was confirmed by recombinant antigen-expressing cell-based assay (CBA), Western blotting, and tissue immunofluorescence assay colocalization. Results: PhIP-Seq data revealed SKOR2 as the candidate autoantigen. The target antigen was confirmed by a recombinant SKOR-2-expressing, and cell lysate Western blot. Furthermore, IgG from both patient samples colocalized with a commercial SKOR2-specific IgG on cryosections of the mouse brain. Both SKOR2 IgG-positive patients had central nervous system involvement, one presenting with encephalitis and seizures (Patient 1) and the other with cognitive dysfunction, spastic ataxia, dysarthria, dysphagia, and pseudobulbar affect (Patient 2). They had a refractory progressive course and were diagnosed with adenocarcinoma (Patient 1: lung, Patient 2: gallbladder). Sera from adenocarcinoma patients without PNS (n=30) tested for SKOR2-IgG were negative. Discussion: SKOR2 IgG represents a novel biomarker for PNS associated with adenocarcinoma. Identification of additional SKOR2 IgG-positive cases will help categorize the associated neurological phenotype and the risk of underlying malignancy.

The relative benefits for environmental sustainability of vegan diets for dogs, cats and people.

Environmental impacts of the livestock sector are proportional to consumption levels. To assess the relative consumption of livestock animals within the diets of dogs, cats and people, this study examined their dietary energy needs within the US in 2020, and globally in 2018. Also studied were US pet food ingredients, and environmental sustainability indicators for plant- and animal-based foods consumed globally. Relative consumptions of average livestock animals were: US: dogs- 17.7%, cats- 2.3%, humans- 80.0%; and globally: dogs- 7.7%, cats- 1.2%, humans- 91.1%. Full transition to nutritionally-sound vegan diets would spare from slaughter the following numbers of terrestrial livestock animals annually (billions): US: dogs- 1.7, cats- 0.2, humans- 7.8, and globally: dogs- 6.0, cats- 0.9, humans- 71.3, as well as billions of aquatic animals in all dietary groups. Very large impact reductions were also associated with land and water use, emissions of greenhouse gases (GHGs), acidifying and eutrophifying gases, and biocide use, in all dietary groups. If implemented globally, nutritionally-sound vegan diets would free up land larger than the following nations: dogs-Saudi Arabia or Mexico, cats-Japan or Germany, humans-Russia-the world's largest country-combined with India. Such diets would save freshwater volumes greater than all renewable freshwater in the following nations: dogs-Denmark, cats-Jordan, humans-Cuba. Such diets would reduce GHGs by amounts greater than all GHG emissions from following nations: dogs-South Africa or the UK, cats-Israel or New Zealand, humans-India or the entire EU. The numbers of additional people who could be fed using food energy savings associated with vegan diets exceeded the 2018 human populations of the following nations: dogs-the entire European Union, cats-France or the UK, humans-every single nation or collective region on Earth, as defined by the World Bank. All of these estimates are conservative.

Vegan versus meat-based cat food: Guardian-reported health outcomes in 1,369 cats, after controlling for feline demographic factors.

Increasing concerns about environmental sustainability, farmed animal welfare and competition for traditional protein sources, are driving considerable development of alternative pet foods. These include raw meat diets, in vitro meat products, and diets based on novel protein sources including terrestrial plants, insects, yeast, fungi and potentially seaweed. To study health outcomes in cats fed vegan diets compared to those fed meat, we surveyed 1,418 cat guardians, asking about one cat living with them, for at least one year. Among 1,380 respondents involved in cat diet decision-making, health and nutrition was the factor considered most important. 1,369 respondents provided information relating to a single cat fed a meat-based (1,242-91%) or vegan (127-9%) diet for at least a year. We examined seven general indicators of illness. After controlling for age, sex, neutering status and primary location via regression models, the following risk reductions were associated with a vegan diet for average cats: increased veterinary visits- 7.3% reduction, medication use- 14.9% reduction, progression onto therapeutic diet- 54.7% reduction, reported veterinary assessment of being unwell- 3.6% reduction, reported veterinary assessment of more severe illness- 7.6% reduction, guardian opinion of more severe illness- 22.8% reduction. Additionally, the number of health disorders per unwell cat decreased by 15.5%. No reductions were statistically significant. We also examined the prevalence of 22 specific health disorders, using reported veterinary assessments. Forty two percent of cats fed meat, and 37% of those fed vegan diets suffered from at least one disorder. Of these 22 disorders, 15 were most common in cats fed meat, and seven in cats fed vegan diets. Only one difference was statistically significant. Considering these results overall, cats fed vegan diets tended to be healthier than cats fed meat-based diets. This trend was clear and consistent. These results largely concur with previous, similar studies.

Correction: Vegan versus meat-based dog food: Guardian-reported indicators of health.

[This corrects the article DOI: 10.1371/journal.pone.0265662.].

Expression of lymphoid structure-associated cytokine/chemokine gene transcripts in tumor and protein in serum are prognostic of melanoma patient outcomes.

Background: Proinflammatory chemokines/cytokines support development and maturation of tertiary lymphoid structures (TLS) within the tumor microenvironment (TME). In the current study, we sought to investigate the prognostic value of TLS-associated chemokines/cytokines (TLS-kines) expression levels in melanoma patients by performing serum protein and tissue transcriptomic analyses, and to then correlate these data with patients clinicopathological and TME characteristics. Methods: Levels of TLS-kines in patients' sera were quantitated using a custom Luminex Multiplex Assay. The Cancer Genomic Atlas melanoma cohort (TCGA-SKCM) and a Moffitt Melanoma cohort were used for tissue transcriptomic analyses. Associations between target analytes and survival outcomes, clinicopathological variables, and correlations between TLS-kines were statistically analyzed. Results: Serum of 95 patients with melanoma were evaluated; 48 (50%) female, median age of 63, IQR 51-70 years. Serum levels of APRIL/TNFSF13 were positively correlated with levels of both CXCL10 and CXCL13. In multivariate analyses, high levels of serum APRIL/TNFSF13 were associated with improved event-free survival after adjusting for age and stage (HR = 0.64, 95% CI 0.43-0.95; p = 0.03). High expression of APRIL/TNFSF13 tumor transcripts was significantly associated with improved OS in TCGA-SKCM (HR = 0.69, 95% CI 0.52-0.93; p = 0.01) and in Moffitt Melanoma patients (HR = 0.51, 95% CI: 0.32-0.82; p = 0.006). Further incorporation of CXCL13 and CXCL10 tumor transcript levels in a 3-gene index revealed that high APRIL/CXCL10/CXCL13 expression was associated with improved OS in the TCGA SKCM cohort (HR = 0.42, 95% CI 0.19-0.94; p = 0.035). Melanoma differentially expressed genes positively associated with high APRIL/CXCL10/CXCL13 tumor expression were linked to tumor infiltration by a diverse array of proinflammatory immune cell types. Conclusion: Serum protein and tumor transcript levels of APRIL/TNFSF13 are associated with improved survival outcomes. Patients exhibiting high coordinate expression of APRIL/CXCL10/CXCL13 transcripts in their tumors displayed superior OS. Further investigation of TLS-kine expression profiles related to clinical outcomes in larger cohort studies is warranted.

The Integrated Effect of Environmental Conditions and Human Presence on the Behaviour of a Pair of Zoo-Housed Asian Small-Clawed Otters.

Zoos and aquaria have the ethical responsibility to provide animals under their care with conditions that promote good welfare. This study evaluated the combined influence of human presence and environmental factors on the behaviour of zoo-housed Asian small-clawed otters (Aonyx cinereus). Data collection was conducted on a pair hosted at Pistoia Zoo (Italy). Data were collected from July to September 2020 (over 14 days). We video-recorded the otters' behaviours, using the continuous focal animal sampling, obtaining 42 h of observation per subject. The otters displayed a wide array of species-specific behaviours. Compared to previous captive studies, the subjects engaged less in locomotion, food-related and affiliative behaviours, and more in vigilance. Human-animal interactions were limited, and mostly elicited neutral or positive responses, except for begging behaviours performed towards caregivers. Time of day and animal identity were the main significant predictors for behaviours. No effects of visitor presence or background noise were detected. Nonetheless, increasing enrichment use could stimulate food-related behaviours, and reduce vigilance and begging. This study confirms the importance of applying an integrated approach to analyse the complexity of otters' experiences, and provides insights to guide husbandry improvements.

Immunotherapy in Melanoma: Recent Advances and Future Directions.

The use of immunotherapy in the treatment of advanced and high-risk melanoma has led to a striking improvement in outcomes. Although the incidence of melanoma has continued to rise, median survival has improved from approximately 6 months to nearly 6 years for patients with advanced inoperable stage IV disease. Recent understanding of the tumor microenvironment and its interplay with the immune system has led to the explosive development of novel immunotherapy treatments. Since the approval of the therapeutic cytokines interleukin-2 and interferon alfa-2 in the 1990s, the development of novel immune checkpoint inhibitors (ICIs), oncolytic virus therapy, and modulators of the tumor microenvironment have given way to a new era in melanoma treatment. Monoclonal antibodies directed at programmed cell death protein 1 receptor (PD-1) and its ligand (PDL-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and lymphocyte-activation gene 3 (LAG-3) have provided robust activation of the adaptive immune system, restoring immune surveillance leading to host tumor recognition and destruction. Multiple other immunomodulatory therapeutics are under investigation to overcome resistance to ICI therapy, including the toll-like receptor-9 (TLR-9) and 7/8 (TLR-7/8) agonists, stimulator of interferon genes (STING) agonists, and fecal microbiota transplantation. In this review, we focus on the recent advances in immunotherapy for the treatment of melanoma and provide an update on novel therapies currently under investigation.

Development of a Screencast-Based Flipped Classroom to Enrich Learning and Reduce Faculty Time Requirements in an Animal Welfare Master's Degree.

A new distance learning Master of Science (MSc) degree in Animal Welfare Science, Ethics and Law was established in 2016 within the Centre for Animal Welfare at the University of Winchester, UK. Our program recruited students worldwide, with enrollments increasing dramatically since its inception in 2016. However, despite rapid growth, our MSc has had only one full-time equivalent faculty member. With further projected sharp increases in student numbers, significant programmatic change was required for the MSc to remain viable. After consultation with our students and program team, we decided to transition to a flipped classroom teaching model. Piloting a screencast-based flipped classroom in one course, our objectives were to provide a more enriched, engaging, and effective student learning experience and to increase student satisfaction while concurrently saving staff time in future years. We aimed to provide a series of enriched screencast videos of short (∼20-minute) durations, with contents clearly signposted. The new teaching model was well received. Within our 2021 program survey, 100% of respondents expressed a wish to see our screencast-based flipped classroom approach continued, and 71%-86% wished to see it implemented in various additional courses. This model has greatly enriched students' learning experiences, increasing student engagement and satisfaction while also freeing staff time to engage in discussion fora and additional live sessions. Learning and achievement outcomes also appear positive. We plan to steadily integrate this model across additional courses, although initial time investment will be significant. Hence, this new model will be implemented over several semesters.

Multiple primary melanoma in association with other personal and familial cancers.

BACKGROUND: Multiple primary melanoma (MPM) is known to be associated with familial melanoma. However, the association between MPM and other personal and familial cancers is not well documented. The objective of this study was to evaluate the association between MPM and personal history of other cancers or cancer history among first-degree relatives (FDRs). METHODS: We performed a retrospective case-control study including cases with gender-matched MPM and single primary melanoma (SPM) at a 1:2 ratio from the University of Pittsburgh Cancer Institute Melanoma Center Biological Sample and Nevus Bank. The associations between MPM and other cancers were evaluated using univariable and multivariable logistic regression models. RESULTS: In total, 378 patients (44.2% men; median age 52 years) were enrolled, including 252 with SPM and 126 with MPM. In comparison to patients with SPM, patients with MPM were more likely to have squamous cell carcinoma (odds ratio [OR] 1.95, 95% confidence interval [CI] 1.001-3.79, p = 0.047) and prostate cancer (OR 2.72, 95% CI 1.07-7.01, p = 0.034). FDRs of patients with MPM had higher prevalence of melanoma (OR 2.37, 95% CI 1.31-4.28, p = 0.004) and prostate cancer (OR 2.92, 95% CI 1.47-6.14, p = 0.002) but not other cancers. In multivariable analysis, the association remained significant between MPM and squamous cell carcinoma (OR 2.18, 95% CI 1.08-4.39, p = 0.028), prostate cancer (OR 2.85, 95% CI 1.09-7.54, p = 0.032), FDR history of melanoma (OR 2.37, 95% CI 1.31-4.29, p = 0.004), and FDR history of prostate cancer (OR 3.26, 95% CI 1.59-6.83, p = 0.001). CONCLUSIONS: Patients with MPM have a higher prevalence of personal and FDR histories of nonmelanoma skin cancers and prostate cancer.

The Impacts of Colony Cages on the Welfare of Chickens Farmed for Meat.

There is growing interest in keeping meat chickens in modern colony cages (CCs) rather than conventional litter-floor barns. Suggested welfare improvements for chickens in such systems include reduced bodily lesions due to lower contact with flooring contaminated with faeces and urine, due to slatted flooring and automated faeces removal. This systematic review sought to determine the animal welfare impacts of CCs using slatted flooring, in comparison to litter-based non-cage systems. Overall, 23 relevant studies were retrieved. From one perspective, the extant research appeared mixed. Fifteen (65%) of these 23 studies identified some form of welfare concern about slatted floors, and thus CCs. Yet, when considering actual welfare indicators assessed, the tallies generated in favour of each housing system were similar. Crucially however, there were incomplete behavioural welfare measures in 100% of the empirical studies reviewed. Accordingly, significant welfare concerns exist about CCs, centring around behavioural deprivation. Given that over 70 billion chickens are farmed then slaughtered each year globally, widespread implementation of CCs would create a major animal welfare concern. Instead of implementing such CC systems, research and development is recommended into improving welfare outcomes of conventional litter barns using different forms of commercially feasible enrichment. As a minimum, a full behavioural analysis, as detailed in the Welfare Quality Assessment protocols, should form a mandatory part of any future studies aimed at assessing the welfare impacts of housing systems on farmed chickens.

Sentinel Lymph Node Gene Expression Signature Predicts Recurrence-Free Survival in Cutaneous Melanoma.

We sought to develop a sentinel lymph node gene expression signature score predictive of disease recurrence in patients with cutaneous melanoma. Gene expression profiling was performed on SLN biopsies using U133A 2.0 Affymetrix gene chips. The top 25 genes associated with recurrence-free survival (RFS) were selected and a penalized regression function was used to select 12 genes with a non-zero coefficient. A proportional hazards regression model was used to evaluate the association between clinical covariates, gene signature score, and RFS. Among the 45 patients evaluated, 23 (51%) had a positive SLN. Twenty-one (46.7%) patients developed disease recurrence. For the top 25 differentially expressed genes (DEG), 12 non-zero penalized coefficients were estimated (CLGN, C1QTNF3, ADORA3, ARHGAP8, DCTN1, ASPSCR1, CHRFAM7A, ZNF223, PDE6G, CXCL3, HEXIM1, HLA-DRB). This 12-gene signature score was significantly associated with RFS (p < 0.0001) and produced a bootstrap C index of 0.888. In univariate analysis, Breslow thickness, presence of primary tumor ulceration, SLN positivity were each significantly associated with RFS. After simultaneously adjusting for these prognostic factors in relation to the gene signature, the 12-gene score remained a significant independent predictor for RFS (p < 0.0001). This SLN 12-gene signature risk score is associated with melanoma recurrence regardless of SLN status and may be used as a prognostic factor for RFS.

Age-Related Variation in the Provision of Primary Care Services and Medication Prescriptions for Patients with Cardiovascular Disease.

As population aging progresses, demands of patients with cardiovascular diseases (CVD) on the primary care services is inevitably increased. However, the utilisation of primary care services across varying age groups is unknown. The study aims to explore age-related variations in provision of chronic disease management plans, mental health care, guideline-indicated cardiovascular medications and influenza vaccination among patients with CVD over differing ages presenting to primary care. Data for patients with CVD were extracted from 50 Australian general practices. Logistic regression, accounting for covariates and clustering effects by practices, was used for statistical analysis. Of the 14,602 patients with CVD (mean age, 72.5 years), patients aged 65-74, 75-84 and ≥85 years were significantly more likely to have a GP management plan prepared (adjusted odds ratio (aOR): 1.6, 1.88 and 1.55, respectively, p < 0.05), have a formal team care arrangement (aOR: 1.49, 1.8, 1.65, respectively, p < 0.05) and have a review of either (aOR: 1.63, 2.09, 1.93, respectively, p < 0.05) than those < 65 years. Patients aged ≥ 65 years were more likely to be prescribed blood-pressure-lowering medications and to be vaccinated for influenza. However, the adjusted odds of being prescribed lipid-lowering and antiplatelet medications and receiving mental health care were significantly lowest among patients ≥ 85 years. There are age-related variations in provision of primary care services and pharmacological therapy. GPs are targeting care plans to older people who are more likely to have long-term conditions and complex needs.