Graph neural networks-enhanced relation prediction for ecotoxicology (GRAPE).

Exposure to toxic chemicals threatens species and ecosystems. This study introduces a novel approach using Graph Neural Networks (GNNs) to integrate aquatic toxicity data, providing an alternative to complement traditional in vivo ecotoxicity testing. This study pioneers the application of GNN in ecotoxicology by formulating the problem as a relation prediction task. GRAPE's key innovation lies in simultaneously modelling 444 aquatic species and 2826 chemicals within a graph, leveraging relations from existing datasets where informative species and chemical features are augmented to make informed predictions. Extensive evaluations demonstrate the superiority of GRAPE over Logistic Regression (LR) and Multi-Layer Perceptron (MLP) models, achieving remarkable improvements of up to a 30% increase in recall values. GRAPE consistently outperforms LR and MLP in predicting novel chemicals and new species. In particular, GRAPE showcases substantial enhancements in recall values, with improvements of ≥ 100% for novel chemicals and up to 13% for new species. Specifically, GRAPE correctly predicts the effects of novel chemicals (104 out of 126) and effects on new species (7 out of 8). Moreover, the study highlights the effectiveness of the proposed chemical features and induced network topology through GNN for accurately predicting metallic (74 out of 86) and organic (612 out of 674) chemicals, showcasing the broad applicability and robustness of the GRAPE model in ecotoxicological investigations. The code/data are provided at https://github.com/csiro-robotics/GRAPE.

Prokaryotic microbial ecology as an ecosurveillance tool for eukaryotic pathogen colonisation: Meiothermus and Naegleria fowleri.

Naegleria fowleri has been detected in drinking water distribution systems (DWDS) in Australia, Pakistan and the United States and is the causative agent of the highly fatal disease primary amoebic meningoencephalitis. Previous small scale field studies have shown that Meiothermus may be a potential biomarker for N. fowleri. However, correlations between predictive biomarkers in small sample sizes often breakdown when applied to larger more representative datasets. This study represents one of the largest and most rigorous temporal investigations of Naegleria fowleri colonisation in an operational DWDS in the world and measured the association of Meiothermus and N. fowleri over a significantly larger space and time in the DWDS. A total of 232 samples were collected from five sites over three-years (2016-2018), which contained 29 positive N. fowleri samples. Two specific operational taxonomic units assigned to M. chliarophilus and M. hypogaeus, were significantly associated with N. fowleri presence. Furthermore, inoculation experiments demonstrated that Meiothermus was required to support N. fowleri growth in field-collected biofilms. This validates Meiothermus as prospective biological tool to aid in the identification and surveillance of N. fowleri colonisable sites.

Realized impact of COVID-19 related disruptions on the National Bowel Cancer Screening Program.

BACKGROUND: Colorectal cancer is the second most common cause of cancer mortality in Australia (1). The National Bowel Cancer Screening Program (NBCSP) aims to reduce mortality through early detection with a biennial faecal occult blood test for Australians aged 50-74 years (2). Modelling predicted COVID-19 would reduce participation and delay colonoscopies despite the NBCSP continuing during the pandemic (3). This study analyses the realized impact of COVID-19 related disruptions on the NBCSP and the effect on mortality. METHODS: NBCSP participation, time to colonoscopy and annualized mortality were compared before and during COVID-19. The effect on mortality was determined using a validated microsimulation model (4, 5). RESULTS: From 1 January 2018 to 31 December 2019, 2 497 317 people participated in the NBCSP and 168 390 received a colonoscopy, compared to 2 490 265 and 162 573 from 1 January 2020 to 31 December 2021. Relative participation decreased 6 % and the proportion of colonoscopies performed within the recommended 120 days increased 14.5%. A disproportionally greater impact was observed outside major cities and in lower socioeconomic areas. An estimated 98-111 additional colorectal cancer deaths resulted from 3 % fewer colonoscopies performed during the pandemic. CONCLUSION: This study presents the most comprehensive analysis of the realized impact of COVID-19 on the NBCSP. Catch-up screening would be best targeted at Australians from rural and lower socioeconomic areas where participation remains low. Streamlined referral pathways and additional colonoscopy provisioning is required as less than two thirds of screen positive patients receive a colonoscopy within the recommended 120 days.

Impact of obesity on patients undergoing surgery for rectal cancer in Australia and New Zealand.

PURPOSE: Patients with obesity undergoing rectal cancer surgery may have an increased risk of developing complications, though evidence is inconclusive. The aim of this study was to determine the direct impact of obesity on postoperative outcomes using data from a large clinical registry. METHOD: The Binational Colorectal Cancer Audit registry was used to identify patients who underwent rectal cancer surgery in Australia and New Zealand from 2007-2021. Primary outcomes were inpatient surgical and medical complications. Logistic regression models were developed to describe the association between body-mass index (BMI) and outcomes. RESULTS: Among 3,708 patients (median age 66 years [IQR 56.75-75], 65.0% male), 2.0% had a BMI < 18.5 kg/m2, 35.4% had a BMI of 18.5-24.9 kg/m2, 37.6% had a BMI of 25.0-29.9 kg/m2, 16.7% had a BMI of 30.0-34.9 kg/m2, and 8.2% had a BMI ≥ 35.0 kg/m2. Surgical complications occurred in 27.7% of patients with a BMI of 18.5-24.9 kg/m2, 26.6% of patients with a BMI of 25.0-29.9 kg/m2 (OR 0.91, 95% CI 0.76-1.10), 28.5% with a BMI of 30.0-34.9 kg/m2 (OR 0.96, 95% CI 0.76-1.21), and 33.2% with a BMI ≥ 35.0 kg/m2 (OR 1.27, 95% CI 0.94-1.71). Modelling BMI as a continuous variable confirmed a J-shaped relationship. The association between BMI and medical complications was more linear. CONCLUSION: Risk of postoperative complications is increased in patients with obesity undergoing rectal cancer surgery.

Pelvic floor training improves faecal incontinence and obstructed defaecation despite the presence of rectal intussusception.

BACKGROUND: Rectal intussusception is often observed in patients with faecal incontinence and obstructed defaecation. The aim of this study is to assess if pelvic floor training improves faecal incontinence and obstructed defaecation in patients with rectal intussusception. METHODS: Case notes of all patients referred to Bankstown Hospital Pelvic Floor Clinic between 2013 and 2018 for the management of faecal incontinence and obstructed defaecation and rectal intussusception were retrospectively reviewed using a prospectively maintained database. St Mark's faecal incontinence and Cleveland clinic constipation scores were obtained from patients before and after they underwent pelvic floor training. RESULTS: One hundred and thirty-one patients underwent pelvic floor training at Bankstown Hospital Pelvic Floor Clinic between 2013 and 2018. Sixty-one patients had rectal intussusception (22 low-grade and 39 high-grade). Median St Marks score improved following pelvic floor training from 8 to 1 (P < 0.001). Median Cleveland Clinic constipation score improved from 8 to 5 (P < 0.001). In patients with low grade rectal intussusception, pelvic floor training improved median St Mark's score from 3 to 0 (P = 0.003), whereas Cleveland Clinic constipation score improved from 9 to 7 (P < 0.001). In patients with high-grade rectal intussusception, pelvic floor training improved median St Mark's score from 9 to 2 (P < 0.001), whereas median Cleveland Clinic constipation score improved from 8 to 4 (P < 0.001). CONCLUSION: Pelvic floor training without biofeedback therapy improves faecal incontinence and obstructed defaecation. Improvement in symptoms is unrelated to rectal intussusception observed on proctography or at examination under anaesthesia in these patients.

Robotic-assisted versus laparoscopic rectal surgery in obese and morbidly obese patients: ACS-NSQIP analysis.

Laparoscopic rectal surgery within the confines of a narrow pelvis may be associated with a high rate of open conversion. In the obese and morbidly obese patient, the complexity of laparoscopic surgery increases substantially. Robotic technology is known to reduce the risk of conversion, but it is unclear if it can overcome the technical challenges associated with obesity. The ACS NSQIP database was used to identify obese patients who underwent elective laparoscopic or robotic-assisted rectal resection from 2015 to 2016. Obesity was defined as a body mass index (BMI) greater than or equal to 30 kg/m2. Morbid obesity was defined as a BMI greater than or equal to 35 kg/m2. The primary outcome was unplanned conversions to open. Other outcomes measures assessed included anastomotic leak, operative time, surgical site infections, length of hospital stay, readmissions and mortality. Statistical analyses were performed using SPSS 22.0 (IBM SPSS, USA). 1490 patients had robotic-assisted and 4967 patients had laparoscopic rectal resections between 2015 and 2016. Of those patients, 561 obese patients had robotic-assisted rectal resections and 1824 patients underwent laparoscopic rectal surgery. In the obese cohort, the rate of unplanned conversion to open in the robotic group was 14% compared to 24% in the laparoscopic group (P < 0.0001). Median operative time was significantly longer in the robotic group (248 min vs. 215 min, P < 0.0001). There was no difference in anastomotic leak or systemic sepsis between the laparoscopic and robotic rectal surgery groups. In morbidly obese patients (BMI ≥ 35 kg/m2), the rate of unplanned conversion to open in the robotic group was 19% compared to 26% in the laparoscopic group (P < 0.027). There was no difference in anastomotic leak, systemic sepsis or surgical site infection rates between robotic and laparoscopic rectal resection. Multivariate analysis showed that robotic-assisted surgery was associated with fewer unplanned conversions to open (OR 0.28, P < 0.0001). Robotic-assisted surgery is associated with a decreased risk of conversion to open in obese and morbidly obese patients when compared to conventional laparoscopic surgery. However, robotic surgery was associated with longer operative time and despite improvement in the rate of conversion to open, there was no difference in complications or length of stay. Our findings are limited by the retrospective non-randomised nature of the study, demographic differences between the two groups, and the likely difference in surgeon experience between the two groups. Large randomised controlled studies are needed to further explore the role of robotic rectal surgery in obese and morbidly obese patients.

The role of predicted chemotactic and hydrocarbon degrading taxa in natural source zone depletion at a legacy petroleum hydrocarbon site.

Petroleum hydrocarbon contamination is a global problem which can cause long-term environmental damage and impacts water security. Natural source zone depletion (NSZD) is the natural degradation of such contaminants. Chemotaxis is an aspect of NSZD which is not fully understood, but one that grants microorganisms the ability to alter their motion in response to a chemical concentration gradient potentially enhancing petroleum NSZD mass removal rates. This study investigates the distribution of potentially chemotactic and hydrocarbon degrading microbes (CD) across the water table of a legacy petroleum hydrocarbon site near Perth, Western Australia in areas impacted by crude oil, diesel and jet fuel. Core samples were recovered and analysed for hydrocarbon contamination using gas chromatography. Predictive metagenomic profiling was undertaken to infer functionality using a combination of 16 S rRNA sequencing and PICRUSt2 analysis. Naphthalene contamination was found to significantly increase the occurrence of potential CD microbes, including members of the Comamonadaceae and Geobacteraceae families, which may enhance NSZD. Further work to explore and define this link is important for reliable estimation of biodegradation of petroleum hydrocarbon fuels. Furthermore, the outcomes suggest that the chemotactic parameter within existing NSZD models should be reviewed to accommodate CD accumulation in areas of naphthalene contamination, thereby providing a more accurate quantification of risk from petroleum impacts in subsurface environments, and the scale of risk mitigation due to NSZD.

Non-additive gene interactions underpin molecular and phenotypic responses in honey bee larvae exposed to imidacloprid and thymol.

Understanding the cumulative risk of chemical mixtures at environmentally realistic concentrations is a key challenge in honey bee ecotoxicology. Ecotoxicogenomics, including transcriptomics, measures responses in individual organisms at the molecular level which can provide insights into the mechanisms underlying phenotypic responses induced by one or more stressors and link impacts on individuals to populations. Here, fifth instar honey bee larvae were sampled from a previously reported field experiment exploring the phenotypic impacts of environmentally realistic chronic exposures of the pesticide imidacloprid (5 µg.kg-1 for six weeks) and the acaricide thymol (250 g.kg-1 applied via Apiguard gel in-hive for four weeks), both separately and in combination. RNA-seq was used to discover individual and interactive chemical effects on larval gene expression and to uncover molecular mechanisms linked to reported adult and colony phenotypes. The separate and combined treatments had distinct gene expression profiles which represented differentially affected signaling and metabolic pathways. The molecular signature of the mixture was characterised by additive interactions in canonical stress responses associated with oxidative stress and detoxification, and non-additive interactions in secondary responses including developmental, neurological, and immune pathways. Novel emergent impacts on eye development genes correlated with long-term defects in visual learning performance as adults. This is consistent with these chemicals working through independent modes of action that combine to impact common downstream pathways, and highlights the importance of establishing mechanistic links between molecular and phenotypic responses when predicting effects of chemical mixtures on ecologically relevant population outcomes.

Genomics and transcriptomics yields a system-level view of the biology of the pathogen Naegleria fowleri.

BACKGROUND: The opportunistic pathogen Naegleria fowleri establishes infection in the human brain, killing almost invariably within 2 weeks. The amoeba performs piece-meal ingestion, or trogocytosis, of brain material causing direct tissue damage and massive inflammation. The cellular basis distinguishing N. fowleri from other Naegleria species, which are all non-pathogenic, is not known. Yet, with the geographic range of N. fowleri advancing, potentially due to climate change, understanding how this pathogen invades and kills is both important and timely. RESULTS: Here, we report an -omics approach to understanding N. fowleri biology and infection at the system level. We sequenced two new strains of N. fowleri and performed a transcriptomic analysis of low- versus high-pathogenicity N. fowleri cultured in a mouse infection model. Comparative analysis provides an in-depth assessment of encoded protein complement between strains, finding high conservation. Molecular evolutionary analyses of multiple diverse cellular systems demonstrate that the N. fowleri genome encodes a similarly complete cellular repertoire to that found in free-living N. gruberi. From transcriptomics, neither stress responses nor traits conferred from lateral gene transfer are suggested as critical for pathogenicity. By contrast, cellular systems such as proteases, lysosomal machinery, and motility, together with metabolic reprogramming and novel N. fowleri proteins, are all implicated in facilitating pathogenicity within the host. Upregulation in mouse-passaged N. fowleri of genes associated with glutamate metabolism and ammonia transport suggests adaptation to available carbon sources in the central nervous system. CONCLUSIONS: In-depth analysis of Naegleria genomes and transcriptomes provides a model of cellular systems involved in opportunistic pathogenicity, uncovering new angles to understanding the biology of a rare but highly fatal pathogen.

Using Simulation Modeling to Guide the Design of the Girl Scouts Fierce & Fit Program.

OBJECTIVE: The study aim was to help the Girl Scouts of Central Maryland evaluate, quantify, and potentially modify the Girl Scouts Fierce & Fit program. METHODS: From 2018 to 2019, our Public Health Informatics, Computational, and Operations Research team developed a computational simulation model representing the 250 adolescent girls participating in the Fierce & Fit program and how their diets and physical activity affected their BMI and subsequent outcomes, including costs. RESULTS: Changing the Fierce & Fit program from a 6-week program meeting twice a week, with 5 minutes of physical activity each session, to a 12-week program meeting twice a week with 30 minutes of physical activity saved an additional $84,828 ($80,130-$89,526) in lifetime direct medical costs, $81,365 ($76,528-$86,184) in lifetime productivity losses, and 7.85 (7.38-8.31) quality-adjusted life-years. The cost-benefit of implementing this program was $95,943. Based on these results, the Girl Scouts of Central Maryland then implemented these changes in the program. CONCLUSIONS: This is an example of using computational modeling to help evaluate and revise the design of a program aimed at increasing physical activity among girls.

Investigation into the microbial communities and associated crude oil-contamination along a Gulf War impacted groundwater system in Kuwait.

During the First Gulf War (1991) a large number of oil wells were destroyed and oil fires subsequently extinguished with seawater. As a result Kuwait's sparse fresh groundwater resources were severely contaminated with crude oil. Since then limited research has focused on the microbial community ecology of the groundwater and their impact on the associated contamination. Here, the microbial community ecology (bacterial, archaeal and eukaryotic) and how it relates to the characteristics of the hydrocarbon contaminants were examined for the first time since the 1991 event. This study was conducted using 15 wells along the main groundwater flow direction and detected several potential hydrocarbon degrading microorganisms such as Hyphomicrobiaceae, Porphyromonadaceae and Eurotiomycetes. The beta diversity of the microbial communities correlated significantly with total petroleum hydrocarbon (TPH) concentrations and salinity. The TPH consisted mainly of polar compounds present as an unresolved complex mixture (UCM) of a highly recalcitrant nature. Based on the proportions of TPH to dissolved organic carbon (DOC), the results indicate that some minor biodegradation has occurred within highly contaminated aquifer zones. However, overall the results from this study suggest that the observed variations in TPH concentrations among the sampled wells are mainly induced by mixing/dilution with pristine groundwater rather than by biodegradation of the contaminants. The findings make an important contribution to better understand the fate of the groundwater pollution in Kuwait, with important implications for the design of future remediation efforts.

Biodegradability of legacy crude oil contamination in Gulf War damaged groundwater wells in Northern Kuwait.

During the 1991 Gulf War, oil wells in the oil fields of Kuwait were set aflame and destroyed. This resulted in severe crude oil pollution of the countries only fresh water aquifers. Here, for the first time the natural attenuation and biodegradation of the persisting groundwater contamination was investigated to assess potential processes in the aquifer. Biodegradation experiments were conducted under aerobic and multiple anaerobic conditions using microcosms of the contaminated groundwater from Kuwait. Under the conditions tested, a portion of the total petroleum hydrocarbon (TPH) component was degraded, however there was only a slight change in the bulk concentration of the contaminant measured as dissolved organic carbon (DOC), suggesting the presence of a recalcitrant pollutant. Changes in the associated microbial community composition under different reduction-oxidation conditions were observed and known hydrocarbon degraders identified. The results of this study indicate that lingering contaminant still persists in the groundwater and is recalcitrant to further biodegradation, which presents challenges for future remediation plans.

Discrepancy between true distance of tibial tuberosity advancement and cage size: An ex vivo study.

OBJECTIVE: To determine the discrepancy between true distance of tibial tuberosity advancement (tTTA) and the most commonly used cages. The null hypothesis was that tTTA would be within 1.5 mm difference of the cage size. STUDY DESIGN: Ex vivo study. SAMPLE POPULATION: Eight foam cortical shell specimens modeled from canine tibias. METHODS: Modified tibial tuberosity advancement (TTA) was performed to allow repeated measurement of the tTTA. The Pearson correlation test was used to evaluate the relationships of tTTA and cage sizes (P < .05). The difference between tTTA and cage size was calculated to establish the degree of underadvancement during the TTA. RESULTS: Two hundred forty tTTA measurements were recorded. The tTTA was less than each corresponding cage size (P < .001). Four cage sizes resulted in a difference greater than 1.5 mm (P < .001-.04). The 6-mm cage resulted in median tTTA of 4.3 mm, which did not differ significantly from 4.5 mm (range, 3.2-6.65). The median underadvancement ranged from 1.7 to 2.5 mm for the tested cage sizes. The percentage underadvancement ranged from 21% to 28% for the tested cage sizes. CONCLUSION: The tTTA was less than the corresponding cage sizes by at least 1.5 mm in all except the 6-mm cage. CLINICAL SIGNIFICANCE: Selection of a larger cage size during the TTA may be advantageous to compensate for underadvancement and to minimize the risk of residual cranial tibial translation.

Biodegradability of polar compounds formed from weathered diesel.

Once released into the environment, petroleum is exposed to biological and physical weathering processes which can lead to the formation and accumulation of highly recalcitrant polar compounds. These polar compounds are often challenging to analyse and can be present as an "unresolved complex mixture" (UCM) in total petroleum hydrocarbon (TPH) analyses and can be mistaken for natural organic matter. Existing research on UCMs comprised of polar compounds is limited, with a majority of the compounds remaining unidentified and their long-term persistence unknown. Here, we investigated the potential biodegradation of these recalcitrant polar compounds isolated from weathered diesel contaminant, and the changes in the microbial community composition associated with the biodegradation process. Microcosms were used to study the biodegradability of the polar compounds under various aerobic and anaerobic conditions and the results compared against the biodegradation of fresh diesel. Under all conditions tested, the majority of the polar UCM contaminant remained recalcitrant to biodegradation. The degradation was limited to the TPH portion of the polar UCM, which represented a minor fraction of the total polar UCM concentration. Changes in microbial community composition were observed under different redox conditions and in the presence of different contaminants. This work furthers the understanding of the biodegradation and long-term recalcitrance of polar compounds formed through weathering at contaminated legacy sites.

Comparison of TPLO tibial tuberosity fractures with and without an in situ rotational pin.

OBJECTIVE: Cranial cruciate ligament (CCL) rupture is a common cause of pelvic limb lameness in dogs. The tibial plateau leveling osteotomy (TPLO) is a well-described surgical procedure that treats CCL ruptures. The objective of this study was to compare the risk of tibial tuberosity fractures from TPLO procedures using a TPLO reduction pin in situ versus patients with a TPLO reduction pin removed at the time of surgery. Our hypothesis is that patients with a TPLO reduction pin left in situ will have a decreased incidence of tibial tuberosity fractures. RESULTS: A total of 400 dogs that fitted the criteria of 200 consecutive TPLO surgeries performed with each group were included in the study. The Student's t-test revealed a statistically significant difference in fractures observed in group 1 (in situ pin) and group 2 (no pin). In univariate logistic regression analysis, only the covariate for the presence of the reduction pin was associated with a statistically significant reduction in the likelihood of tibial tuberosity fracture. In the multivariate model, the presence of the reduction pin was associated with an approximate 92% reduction in the likelihood of tibial tuberosity fracture.

Preferential feeding in Naegleria fowleri; intracellular bacteria isolated from amoebae in operational drinking water distribution systems.

The amoeba Naegleria fowleri is the causative agent of the highly fatal disease, primary amoebic meningoencephalitis, and estimated to cause 16 deaths per year in the United States alone. Colonisation of drinking water distribution systems (DWDSs) by the N. fowleri is a significant public health issue. Understanding the factors which enable this pathogen to colonise and thrive in DWDSs is critical for proper management. The microbial ecology within DWDSs may influence the ability of N. fowleri to colonise DWDSs by facilitating the availability of an appropriate food source. Using biofilm samples obtained from operational DWDSs, 16S rRNA amplicon metabarcoding was combined with genus-specific PCR and Sanger sequencing of intracellular associated bacteria from isolated amoeba and their parental biofilms to identify Meiothermus chliarophilus as a potential food source for N. fowleri. Meiothermus was confirmed as a food source for N. fowleri following successful serial culturing of axenic N. fowleri with M. chliarophilus or M. ruber as the sole food source. The ability to identify environmental and ecological conditions favourable to N. fowleri colonisation, including the detection of appropriate food sources such as Meiothermus, could provide water utilities with a predictive tool for managing N. fowleri colonisation within the DWDS.

Evaluation of tumor volume reduction of nasal carcinomas versus sarcomas in dogs treated with definitive fractionated megavoltage radiation: 15 cases (2010-2016).

OBJECTIVE: Local control is a major challenge in treating canine nasal tumors, and cytoreduction following radiation therapy has been recommended to extend survival and to delay local recurrence. Our objective was to compare the effect of definitive radiotherapy on the tumor volume of intranasal carcinomas compared to sarcomas. We evaluated 15 dogs that received radiotherapy within 1 month of initial CT scan, and post radiation CT scans performed within 3 months of completing full course definitive megavoltage radiation. Tumor reduction volume based on CT scans were obtained and compared between carcinoma and sarcoma groups. RESULTS: The following tumor types were treated; carcinoma (8/15), sarcoma (7/15). The mean nasal tumor size before radiation therapy was 24.5 cm3 and tumor size after radiation therapy was 13.5 cm3 resulting in a mean reduction of 55.1% reduction in tumor size for both carcinomas and sarcomas. The carcinoma group displayed a volume reduction of 67.1% (SD ± 16.9) and the sarcoma group displayed a volume reduction of 21.3% (SD ± 39.7). Within the study period carcinomas were more responsive in the reduction of volume than sarcomas with fractionated megavoltage radiation.