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Abstract Hereditary fructose intolerance (HFI) is a painful and potentially lethal genetic disease caused by a mutation in aldolase B resulting in accumulation of fructose-1-phosphate (F1P). No cure exists for HFI and treatment is limited to avoid exposure to fructose and sugar. Using aldolase B deficient mice, here we identify a yet unrecognized metabolic event activated in HFI and associated with the progression of the disease. Besides the accumulation of F1P, here we show that the activation of the purine degradation pathway is a common feature in aldolase B deficient mice exposed to fructose. The purine degradation pathway is a metabolic route initiated by adenosine monophosphate deaminase 2 (AMPD2) that regulates overall energy balance. We demonstrate that very low amounts of fructose are sufficient to activate AMPD2 in these mice via a phosphate trap. While blocking AMPD2 do not impact F1P accumulation and the risk of hypoglycemia, its deletion in hepatocytes markedly improves the metabolic dysregulation induced by fructose and corrects fat and glycogen storage while significantly increasing the voluntary tolerance of these mice to fructose. In summary, we provide evidence for a critical pathway activated in HFI that could be targeted to improve the metabolic consequences associated with fructose consumption.

A low-cost novel spectral camera able to be used for near infrared spectroscopy was made by using a Jetson Nano to synchronize a Sony IMX219 NOIR autofocus image sensor, an AMS AS7265x 18-channel spectral sensor and Osram SFH 4737 broadband infrared LED’s. Synchronizing an image sensor and spectral sensor augments a standard RGB image with light spectrum information; capturing the light distribution information normally lost in RGB image capture. Sutherland et al. [1] used this novel spectral camera to examine the dorsal surface of juvenile lobsters as a possible pre-moult detector. Having the image and spectrum in combination allowed the incomplete and unmineralized post-moult dorsal surface to be characterized with 86.7% accuracy for the first time. A proposed application for the spectral camera is to omit the local SFH 4737 light source and use the camera in daylight, effectively making a low-cost substitute hyperspectral snapshot camera. In this configuration the camera may have application for low-cost drone deployment for small scale agriculture.

Objective: Stable isotope studies have shown that hepatic de novo lipogenesis (DNL) plays an important role in the pathogenesis of intrahepatic lipid (IHL) deposition. Furthermore, previous research has demonstrated that fructose 1-phosphate (F1P) not only serves as a substrate for DNL, but also acts as a signalling metabolite that stimulates DNL from glucose. The aim of this study was to elucidate the mediators of F1P-stimulated DNL, with special focus on two key regulators of intrahepatic glucose metabolism, i.e., glucokinase regulatory protein (GKRP) and carbohydrate response element binding protein (ChREBP). Methods: Aldolase B deficient mice (Aldob−/−), characterized by hepatocellular F1P accumulation, enhanced DNL, and hepatic steatosis, were either crossed with GKRP deficient mice (Gckr−/−) or treated with short hairpin RNAs directed against hepatic ChREBP. Results: Aldob−/− mice showed higher rates of de novo palmitate synthesis from glucose when compared to wildtype mice (p

Abstract Pathogenic microorganisms contaminating potable water are a serious water quality concern because they have severe consequences for human and environmental health. Managing water contamination requires the availability of fast and highly sensitive point‐of‐use detection systems responsive to a wide concentration range. In the present work, this goal is achieved by realizing a cascade‐structured biosensor that exploits innovative stimuli‐responsive materials such as gold nanorods (AuNRs) and photosensitive nematic liquid crystals (NLCs). The cascade structure is fabricated by interfacing a glass substrate in a back‐to‐front arrangement, hosting an array of bioactivated AuNRs and an NLC cell. The AuNRs array integrates microfluidic channels, allowing direct water sampling and the analysis of reduced water volumes with high sensitivity. The biosensor combines in the same device two independent optical transducers: a bioactive AuNRs array (plasmonic biosensor), sensitive to refractive index alterations, and an NLC cell that detects the presence of pathogens by responding to light intensity variations. The plasmonic biosensor performs exceptionally well for very low concentrations of bacteria. In contrast, the NLC biosensor works for high‐concentration bacteria, thus providing a cascade‐like detection system able to detect bacteria in a wide concentration range from 10 to 109 CFU mL−1.

Challenges associated with cubozoan jellyfish detection and the limitations of current detection techniques limit the ability of scientists to fill critical knowledge gaps surrounding their ecology. Environmental DNA (eDNA), however, has proven useful as an ecological survey tool to detect and study these deadly jellyfish. This study aimed to leverage the power of eDNA to detect and explore the distribution of the Australian box jellyfish (Chironex fleckeri), encompassing both its medusae and polyp life history stages, within an open coastal bay (Horseshoe Bay) of Magnetic Island, Queensland, Australia. Our investigation focused on a hypothesis concerning the source locations of the jellyfish within Horseshoe Bay and, through a comparison of both life history stage distributions, aimed to determine potential population stock boundaries. eDNA results aligned with the predicted nearshore distribution of medusae. Further, the elusive benthic polyp stage was also detected. These findings confirmed Horseshoe Bay as a source location of the jellyfish. Moreover, our evidence supported a model that the area likely represents a population stock of the species. This adds to growing evidence suggesting some cubozoan jellyfish have population stocks of small spatial scales in both open and relatively closed ecosystems such as estuaries. In conclusion, this study serves as a notable example of eDNA’s ability to resolve critical knowledge gaps surrounding cubozoan ecology and to enhance the management ability of these deadly jellyfish to reduce envenomations.

Genomic prediction (GP) has emerged an effective tool for addressing the many shortcomings of traditional selective breeding, thereby enhancing the selection process. In this study, we optimized GP methods using 5-fold cross-validation to estimate genome-estimated breeding values for the weight traits of olive flounder (Paralichthys olivaceus). To accomplish our goal, we determined the parentage of the target broodstock and the ability of 11 prediction models to predict the weight traits of 1.8-year-old olive flounders, which were genotyped using a 70 K single nucleotide polymorphism (SNP) array. Moreover, our optimization efforts toward the predictive ability of genomic best linear unbiased prediction (GBLUP), Bayesian B (BB), and random forest (RF) methods encompassed changes in various aspects such as fixed effects, SNP quantity, population size, and phenotypic data collected at different fish ages. Additionally, we assessed the predictive ability for the total length and body depth of fish using GBLUP, BB, and RF. Among the 11 prediction methods used in this study, the BB (0.675), Elastic Net (0.679), and RF (0.698) methods exhibited the highest predictive abilities, whereas the GBLUP (0.637) method demonstrated the lowest. Incorporating information regarding fish sex as a fixed effect substantially improved the predictive ability of GBLUP and BB. For mean models, utilizing 3000–5000 random SNP markers resulted in a higher predictive ability, similar to that obtained using 50,000 SNPs. Increasing the population size reduced the standard deviation of the predictive ability. Notably, phenotypic records from 1.8-year-old fish exhibited a significantly higher predictive ability than those from the other age groups. Furthermore, GBLUP, BB, and RF provided higher predictive abilities for length (0.655–0.852) and body depth (0.665–0.861). These findings may significantly shape future olive flounder genomic selection programs and offer valuable insights into GP in aquaculture.

Infectious zoonotic disease emergence, through spillover events, is of global concern and has the potential to cause significant harm to society, as recently demonstrated by COVID-19. More than 70% of the 400 infectious diseases that emerged in the past five decades have a zoonotic origin, including all recent pandemics. There have been several approaches used to predict the risk of spillover through some of the known or suspected infectious disease emergence drivers, largely using correlative approaches. Here, we predict the spatial distribution of spillover risk by approximating general transmission through animal and human interactions. These mass action interactions are approximated through the multiplication of the spatial distribution of zoonotic virus diversity and human population density. Although our results indicate higher risk in regions along the equator and in Southeast Asia where both virus diversity and human population density are high, it should be noted that this is primarily a conceptual exercise. We compared our spillover risk map to key factors, including the model inputs of zoonotic virus diversity estimate map, human population density map, and the spatial distribution of species richness. Despite the limitations of this approach, this viral spillover map is a step towards developing a more comprehensive spillover risk prediction system to inform global monitoring.

Abstract Global cerebral blood flow (gCBF) and cerebrovascular reactivity to hypercapnia (CVRCO2) are modulated by gonadal hormone activity, while insulin‐like growth factor 1 facilitates exercise‐mediated cerebral angiogenesis in adults. Whether critical periods of heightened hormonal and neural development during puberty represent an opportunity to further enhance gCBF and CVRCO2 is currently unknown. Therefore, we used duplex ultrasound to assess gCBF and CVRCO2 in n = 128 adolescents characterised as endurance‐exercise trained (males: n = 30, females: n = 36) or untrained (males: n = 29, females: n = 33). Participants were further categorised as pre‐ (males: n = 35, females: n = 33) or post‐ (males: n = 24, females: n = 36) peak height velocity (PHV) to determine pubertal or ‘maturity’ status. Three‐factor ANOVA was used to identify main and interaction effects of maturity status, biological sex and training status on gCBF and CVRCO2. Data are reported as group means (SD). Pre‐PHV youth demonstrated elevated gCBF and slower CVRCO2 mean response times than post‐PHV counterparts (both: P ≤ 0.001). gCBF was only elevated in post‐PHV trained males when compared to untrained counterparts (634 (43) vs. 578 (46) ml min−1; P = 0.007). However, CVRCO2 mean response time was faster in pre‐ (72 (20) vs. 95 (29) s; P ≤ 0.001), but not post‐PHV (P = 0.721) trained youth when compared to untrained counterparts. Cardiorespiratory fitness was associated with gCBF in post‐PHV youth (r2 = 0.19; P ≤ 0.001) and CVRCO2 mean response time in pre‐PHV youth (r2 = 0.13; P = 0.014). Higher cardiorespiratory fitness during adolescence can elevate gCBF while exercise training during childhood primes the development of cerebrovascular function, highlighting the importance of exercise training during the early stages of life in shaping the cerebrovascular phenotype.

Giant ichthyosaurs with body length estimates exceeding 20 m were present in the latest Triassic of the UK. Here we report on the discovery of a second surangular from the lower jaw of a giant ichthyosaur from Somerset, UK. The new find is comparable in size and morphology to a specimen from Lilstock, Somerset, described in 2018, but it is more complete and better preserved. Both finds are from the uppermost Triassic Westbury Mudstone Formation (Rhaetian), but the new specimen comes from Blue Anchor, approximately 10 km west along the coast from Lilstock. The more complete surangular would have been >2 m long, from an individual with a body length estimated at ~25 m. The identification of two specimens with the same unique morphology and from the same geologic age and geographic location warrants the erection of a new genus and species, Ichthyotitan severnensis gen. et sp. nov. Thin sections of the new specimen revealed the same histological features already observed in similar giant ichthyosaurian specimens. Our data also supports the previous suggestion of an atypical osteogenesis in the lower jaws of giant ichthyosaurs. The geological age and giant size of the specimens suggest shastasaurid affinities, but the material is too incomplete for a definitive referral. Ichthyotitan severnensis gen. et sp. nov., is the first-named giant ichthyosaur from the Rhaetian and probably represents the largest marine reptile formally described.

This study offers a comprehensive morpho-histological analysis of the gastrointestinal tract (GIT) of the Malabar red snapper. A comparison of its GIT morphology with that of the Asian seabass reveals similarities and differences between the two species. Additionally, the moisture content, crude protein, and ash in the fillets of Malabar red snapper and Asian seabass were slightly different, with Malabar red snapper exhibiting higher levels of essential fatty acids. Furthermore, higher levels of the polyunsaturated fatty acid (PUFA)/saturated fatty acid (SFA) ratio and docosahexaenoic acid (DHA)/eicosapentaenoic acid (EPA) ratio, and a lower omega-6/omega-3 ratio, were observed in Malabar red snapper compared to Asian seabass. The Malabar red snapper’s esophagus featured protective mechanisms such as simple columnar epithelial cells, mucous-secreting glands, and goblet cells that were predominantly stained for acid and neutral mucosubstances. Furthermore, its stomach, with mucus cells that were weakly stained for acid mucosubstances, exhibited distinct regions with varying glandular densities, with the pyloric region featuring few glands. The pyloric caeca of the fish were composed of five finger-like structures and few goblet cells. Several goblet cells gradually increased from the anterior to the posterior region of the intestine. These findings provide useful insights for the aquaculture sector, focusing on Malabar red snapper.

Tropical rock lobsters (Panulirus ornatus) are a highly cannibalistic species with intermoult animals predominantly attacking animals during ecdysis (moulting). Rapid, positive characterisation of pre-ecdysis lobsters may open a pathway to disrupt cannibalism. Ecdysial suture line development is considered for pre-ecdysis recognition with suture line definition compared for intermoult and pre-ecdysis lobsters emerged and immerged, using white, near ultraviolet (365 nm), near infrared (850 nm), and specialty SFH 4737 broadband IR LEDs against a reference of intermoult lobsters with no suture line development. Difficulties in acquiring suture line images prompted research into pre-ecdysis characterisation from the lobster’s dorsal carapace, due to its accessibility through a culture vessel’s surface. In this study, a novel low-cost spectral camera was developed by coordinating an IMX219 image sensor, an AS7265x spectral sensor, and four SFH 4737 broadband infrared LEDs through a single-board computer. Images and spectral data from the lobster’s dorsal carapace were acquired from intermoult, pre-ecdysis, and post-ecdysis lobsters. For the first time, suture line definition was found to be enhanced under 850 nm, 365 nm, and SFH 4737 LEDs for immerged lobsters, while the 850 nm LED achieved the best suture line definition of emerged lobsters. Although the spectral camera was unable to characterise pre-ecdysis, its development was validated when a least squares regression for binary classification decision boundary successfully separated 86.7% of post-ecdysis lobsters. Achieving post-ecdysis characterisation is the first time the dorsal carapace surface has been used to characterise a moult stage for palinurid lobsters.

Objective Patients with acute coronary syndrome (ACS) remain at high risk for recurrent ischaemic and bleeding events during follow-up. Our study aimed to quantify and compare the impact of these adverse events on quality of life (QoL).Methods Data from patients with ACS prospectively enrolled in the FORCE-ACS registry between January 2015 and December 2019 were used for this study. The primary ischaemic and bleeding events of interest were hospital readmission for ACS and Bleeding Academic Research Consortium type 2 or 3 bleeding during 12 months follow-up. QoL was measured using the EQ-5D Visual Analogue Scale (VAS) score and the 12-item Short Form Survey version 2 derived Physical Component Summary (PCS) and Mental Health Component Summary (MCS) scores at 12 months follow-up.Results In total, 3339 patients (mean age 66.8 years, 27.9% women) were included. During follow-up, ischaemic events occurred in 202 patients (6.0%) and bleeding events in 565 patients (16.9%). After adjustment for demographic and clinical characteristics, ischaemic events remained independently associated with lower QoL regardless of metric used. Bleeding was also independently associated with lower EQ-5D VAS and PCS scores, but not with a lower MCS score. The QoL decrement associated with ischaemic events was numerically larger than the decrement associated with bleeding.Conclusions Ischaemic and bleeding events remain prevalent and are independently associated with lower QoL at 12 months follow-up in patients previously admitted for ACS. The incidence and impact of these adverse events should be considered when balancing individual ischaemic and bleeding risks.

Background Guidelines recommend prasugrel or ticagrelor for acute coronary syndrome (ACS) patients. However, these P2Y 12 inhibitors increase bleeding risk compared to clopidogrel. Although genotype-guided P2Y 12 -inhibitor selection has been shown to reduce bleeding risk, data on its clinical implementation is lacking. Methods The study included ACS patients receiving genotype-guided antiplatelet therapy, utilising either a point-of-care (POC) device or laboratory-based testing. We aimed to collect qualitative and quantitative data on genotyping, eligibility for de-escalation, physician adherence to genotype results, time to de-escalation and cost reduction. Results Of the 1,530 patients included in the ACS registry from 2021 to 2023, 738 ACS patients treated with ticagrelor received a CYP2C19 genotype test. The median turnover time of genotyping was 6.3 hours (interquartile range [IQR], 3.2-16.7), with 82.3% of the genotyping results known within 24 hours after admission. POC genotyping exhibited significantly shorter turnaround times compared to laboratory-based testing (with respective medians of 5.7 vs 47.8 hours; P

Absorption, reflection, and transmission coefficients of the hybrid structure formed by a metal film and a holographic polymer–liquid crystal grating (HPLCG) are theoretically studied in the spectral region of the HPLCG band gap. HPLCG cells consist of four alternating layers, two layers of polymer and two layers of the same liquid crystal (LC), but with different orientations of the LC director. The appearance of reflection, transmission, and absorption peaks in the HPLCG band gap due to the excitation of optical Tamm states (OTSs) at the metal film–HPLCG interface is investigated. The dependence of the spectral manifestation of OTSs on the parameters of the hybrid structure is also studied. A comparison is made with the corresponding results for the case when HPLCG cells of a hybrid structure consist of one polymer layer and one LC layer (two-layer HPLCG).

Shellfish allergy affects ~2.5% of the global population and is a type I immune response resulting from exposure to crustacean and/or molluscan proteins. The Australian Redclaw crayfish (Cherax quadricarinatus) is a freshwater species endemic to and farmed in northern Australia and is becoming an aquaculture species of interest globally. Despite being consumed as food, allergenic proteins from redclaw have not been identified or characterised. In addition, as different body parts are often consumed, it is conceivable that redclaw tissues vary in allergenicity depending on tissue type and function. To better understand food-derived allergenicity, this study characterised allergenic proteins in various redclaw body tissues (the tail, claw, and cephalothorax) and how the stability of allergenic proteins was affected through cooking (raw vs. cooked tissues). The potential of redclaw allergens to cross-react and cause IgE-binding in patients allergic to other shellfish (i.e., shrimp) was also investigated. Raw and cooked extracts were prepared from each body part. SDS-PAGE followed by immunoblotting was performed to determine allergen-specific antibody reactivity to sarcoplasmic calcium-binding protein and hemocyanin, as well as to identify redclaw proteins binding to IgE antibodies from individual and pooled sera of shrimp-allergic patients. Liquid chromatography-mass spectrometry (LC/MS) was utilised to identify proteins and to determine the proportion within extracts. Known crustacean allergens were found in all tissues, with a variation in tissue distribution (e.g., higher levels of hemocyanin in the claw and cephalothorax than in the tail). The proportion of some allergens as a percentage of remaining heat-stable proteins increased in cooked tissues. Previously described heat-stable allergens (i.e., hemocyanin and sarcoplasmic calcium-binding protein) were found to be partially heat-labile. Immunoblotting indicated that shrimp-allergic patients cross-react to redclaw allergens. IgE-binding bands, analysed by LC/MS, identified up to 11 known shellfish allergens. The findings of this study provide fundamental knowledge into the diagnostic and therapeutic field of shellfish allergy.

Summary: Background: Seizure risk forecasting could reduce injuries and even deaths in people with epilepsy. There is great interest in using non-invasive wearable devices to generate forecasts of seizure risk. Forecasts based on cycles of epileptic activity, seizure times or heart rate have provided promising forecasting results. This study validates a forecasting method using multimodal cycles recorded from wearable devices. Method: Seizure and heart rate cycles were extracted from 13 participants. The mean period of heart rate data from a smartwatch was 562 days, with a mean of 125 self-reported seizures from a smartphone app. The relationship between seizure onset time and phases of seizure and heart rate cycles was investigated. An additive regression model was used to project heart rate cycles. The results of forecasts using seizure cycles, heart rate cycles, and a combination of both were compared. Forecasting performance was evaluated in 6 of 13 participants in a prospective setting, using long-term data collected after algorithms were developed. Findings: The results showed that the best forecasts achieved a mean area under the receiver-operating characteristic curve (AUC) of 0.73 for 9/13 participants showing performance above chance during retrospective validation. Subject-specific forecasts evaluated with prospective data showed a mean AUC of 0.77 with 4/6 participants showing performance above chance. Interpretation: The results of this study demonstrate that cycles detected from multimodal data can be combined within a single, scalable seizure risk forecasting algorithm to provide robust performance. The presented forecasting method enabled seizure risk to be estimated for an arbitrary future period and could be generalised across a range of data types. In contrast to earlier work, the current study evaluated forecasts prospectively, in subjects blinded to their seizure risk outputs, representing a critical step towards clinical applications. Funding: This study was funded by an Australian Government National Health & Medical Research Council and BioMedTech Horizons grant. The study also received support from the Epilepsy Foundation of America's ‘My Seizure Gauge’ grant.

Abstract Characterising crustacean behaviour in response to conspecific chemical cues contributes to our evolving knowledge of the drivers of their social behaviour. There is particular interest in understanding the chemical and behavioural mechanisms contributing to cannibalism at ecdysis, as this behaviour substantially limits culture productivity of several commercially important crustaceans. Before investigating the role of chemoreception in cannibalism of moulting crustaceans, we must investigate its role in detecting moulting conspecifics. Here we use a two-current choice flume to observe juvenile tropical rock lobster (Panulirus ornatus) behavioural response to conspecific moulting cues and identifying attracted and avoidant behaviours correlating to moult stage and social relationship. Observed cue preferences show inter-moult juveniles are attracted to the moulting cues of lobsters to which they are socially naïve. In contrast, post-moult and inter-moult juveniles avoid the moulting cues of individuals whom they are socially familiar with. Average speed and total distance travelled by lobsters increases in response to conspecific moulting cues. This study demonstrates the suitability of a two-current choice flume for behavioural assays in P. ornatus and characterises clear behavioural patterns in juveniles exposed to conspecific moulting cues. This provides important framework for understanding the role of chemical communication in eliciting cannibalism.

In 2019, the first cases of SARS-CoV-2 were detected in Wuhan, China, and by early 2020 the first cases were identified in the United States. SARS-CoV-2 infections increased in the US causing many states to implement stay-at-home orders and additional safety precautions to mitigate potential outbreaks. As policies changed throughout the pandemic and restrictions lifted, there was an increase in demand for COVID-19 testing which was costly, difficult to obtain, or had long turn-around times. Some academic institutions, including Boston University (BU), created an on-campus COVID-19 screening protocol as part of a plan for the safe return of students, faculty, and staff to campus with the option for in-person classes. At BU, we put together an automated high-throughput clinical testing laboratory with the capacity to run 45,000 individual tests weekly by Fall of 2020, with a purpose-built clinical testing laboratory, a multiplexed reverse transcription PCR (RT-qPCR) test, robotic instrumentation, and trained staff. There were many challenges including supply chain issues for personal protective equipment and testing materials in addition to equipment that were in high demand. The BU Clinical Testing Laboratory (CTL) was operational at the start of Fall 2020 and performed over 1 million SARS-CoV-2 PCR tests during the 2020-2021 academic year.

Abstract Environmental DNA (eDNA) methods are increasingly applied in the marine environment to identify species and community structure. To establish widely applicable eDNA techniques for elasmobranchs, we used the Critically Endangered largetooth sawfish (Pristis pristis Linnaeus, 1758) as a model species for: (1) assessing eDNA particle size distribution; (2) assessing the efficiency of long‐term preservation of water samples; and (3) comparing the efficiency and detection sensitivity of filtration and precipitation methods. Water samples (1 L) collected from a tank containing one largetooth sawfish specimen were sequentially filtered through five filter membranes of decreasing pore size (20, 10, 5, 1.2, and 0.45 μm). The proportion of sawfish eDNA retained within each size class was determined through quantitative real‐time PCR (qPCR) using a species‐specific TaqMan probe assay. A linear mixed‐effects model (lme) showed that the 1.2 and 20 µm filters captured most of the eDNA particles present in the sampled water. Additionally, whole water samples (0.375 L) were preserved in Longmire's buffer, stored at tropical ambient temperatures (26.3°C ± 3.0 SD) and extracted at five time points: immediately, one, two, and three months after collection, as well as frozen and extracted three months later, to assess the preservation efficiency of Longmire's buffer via qPCR analysis. A linear mixed‐effects model showed that samples maintained maximal eDNA yield for at least three months after collection at ambient storage. Lastly, when comparing the filtration and precipitation methods, filtration using 0.45 µm pore size was more sensitive to capture of largetooth sawfish eDNA than filtration with 20 µm filter or water precipitation. However, water precipitation was more efficient when accounting for volume of water processed. These results provide options for best capture and preservation of elasmobranch eDNA.

Excessive intake of sugar, and particularly fructose, is closely associated with the development and progression of metabolic syndrome in humans and animal models. However, genetic disorders in fructose metabolism have very different consequences. While the deficiency of fructokinase, the first enzyme involved in fructose metabolism, is benign and somewhat desirable, missense mutations in the second enzyme, aldolase B, causes a very dramatic and sometimes lethal condition known as hereditary fructose intolerance (HFI). To date, there is no cure for HFI, and treatment is limited to avoiding fructose and sugar. Because of this, for subjects with HFI, glucose is their sole source of carbohydrates in the diet. However, clinical symptoms still occur, suggesting that either low amounts of fructose are still being consumed or, alternatively, fructose is being produced endogenously in the body. Here, we demonstrate that as a consequence of consuming high glycemic foods, the polyol pathway, a metabolic route in which fructose is produced from glucose, is activated, triggering a deleterious mechanism whereby glucose, sorbitol and alcohol induce severe liver disease and growth retardation in aldolase B knockout mice. We show that generically and pharmacologically blocking this pathway significantly improves metabolic dysfunction and thriving and increases the tolerance of aldolase B knockout mice to dietary triggers of endogenous fructose production.

This work presents models for homogenizing or finding the effective transport or mechanical properties of microscale composites formed from highly contrasting phases described on a grid. The methods developed here are intended for engineering applications where speed and geometrical flexibility are a premium. A canonical case that is mathematically challenging and yet can be applied to many realistic materials is a 4-phase 2-dimensional periodic checkerboard or tiling. While analytic solutions for calculating effective properties exist for some cases, versatile methods are needed to handle anisotropic and non-square grids. A reinterpretation and extension of an existing analytic solution that utilizes equivalent circuits is developed. The resulting closed-form expressions for effective conductivity are shown to be accurate within a few percent or better for multiple cases of interest. Secondly a versatile and efficient spectral method is presented as a solution to the 4-phase primitive cell with a variety of external boundaries. The spectral method expresses the solution to effective conductivity in terms of analytically derived eigenfunctions and numerically determined spectral coefficients. The method is validated by comparing to known solutions and can allow extensions to cases with no current analytic solution.

Bremsstrahlung x rays generated in laser-solid interactions can be used as light sources for high-energy-density science. We present electron and x-ray spectra from multidimensional kinetic simulations with varying laser pulse intensity and duration at fixed energy of 200J. A phenomenological model for the transition from superponderomotive to ponderomotive temperatures is described, yielding a temperature scaling that depends on pulse duration and density scale length. The shortest pulses create low-divergence electron beams before self-generated magnetic fields evolve, yielding 1–5-MeV forward-going x rays containing ∼0.5% of the laser energy.

Abstract The significant mortality rate and prolonged ventilator days associated with invasive mechanical ventilation (IMV) in patients with severe COVID-19 have incited a debate surrounding the use of noninvasive respiratory support (NIRS) (i.e., HFNC, CPAP, NIV) as a potential treatment strategy. Central to this debate is the role of NIRS in preventing intubation in patients with mild respiratory disease and the potential beneficial effects on both patient outcome and resource utilization. However, there remains valid concern that use of NIRS may prolong time to intubation and lung protective ventilation in patients with more advanced disease, thereby worsening respiratory mechanics via self-inflicted lung injury. In addition, the risk of aerosolization with the use of NIRS has the potential to increase healthcare worker (HCW) exposure to the virus. We review the existing literature with a focus on rationale, patient selection and outcomes associated with the use of NIRS in COVID-19 and prior pandemics, as well as in patients with acute respiratory failure due to different etiologies (i.e., COPD, cardiogenic pulmonary edema, etc.) to understand the potential role of NIRS in COVID-19 patients. Based on this analysis we suggest an algorithm for NIRS in COVID-19 patients which includes indications and contraindications for use, monitoring recommendations, systems-based practices to reduce HCW exposure, and predictors of NIRS failure. We also discuss future research priorities for addressing unanswered questions regarding NIRS use in COVID-19 with the goal of improving patient outcomes.

This registry assessed the impact of conservative and invasive strategies on major adverse clinical events (MACE) in elderly patients with non-ST-elevation myocardial infarction (NSTEMI). Patients aged ≥75 years with NSTEMI were prospectively registered from European centers and followed up for one year. Outcomes were compared between conservative and invasive groups in the overall population and a propensity score-matched (PSM) cohort. MACE included cardiovascular death, acute coronary syndrome, and stroke. The study included 1190 patients (median age 80 years, 43% female). CAG was performed in 67% (N = 798), with two-thirds undergoing revascularization. Conservatively treated patients had higher baseline risk. After propensity score matching, 319 patient pairs were successfully matched. MACE occurred more frequently in the conservative group (total population 20% vs. 12%, adjHR 0.53, 95% CI 0.37–0.77, p = 0.001), remaining significant in the PSM cohort (18% vs. 12%, adjHR 0.50, 95% CI 0.31–0.81, p = 0.004). In conclusion, an early invasive strategy was associated with benefits over conservative management in elderly patients with NSTEMI. Risk factors associated with ischemia and bleeding should guide strategy selection rather than solely relying on age.

Abstract Background There is strong evidence that noninvasive ventilation (NIV) improves the outcomes of patients hospitalized with severe COPD exacerbation, and NIV is recommended as the first-line therapy for these patients. Yet, several studies have demonstrated substantial variation in NIV use across hospitals, leading to preventable morbidity and mortality. In addition, prior studies suggested that efforts to increase NIV use in COPD need to account for the complex and interdisciplinary nature of NIV delivery and the need for team coordination. Therefore, our initial project aimed to compare two educational strategies: online education (OLE) and interprofessional education (IPE), which targets complex team-based care in NIV delivery. Due to the impact of the COVID-19 pandemic on recruitment and planned intervention, we had made several changes in the study design, statistical analysis, and implementation strategies delivery as outlined in the methods. Methods We originally proposed a two-arm, pragmatic, cluster, randomized hybrid implementation-effectiveness trial comparing two education strategies to improve NIV uptake in patients with severe COPD exacerbation in 20 hospitals with a low baseline rate of NIV use. Due to logistical constrains and slow recruitment, we changed the study design to an opened cohort stepped-wedge design with three steps which will allow the institutions to enroll when they are ready to participate. Only the IPE strategy will be implemented, and the education will be provided in an online virtual format. Our primary outcome will be the hospital-level risk-standardized NIV proportion for the period post-IPE training, along with the change in rate from the period prior to training. Aim 1 will compare the change over time of NIV use among patients with COPD in the step-wedged design. Aim 2 will explore the mediators’ role (respiratory therapist autonomy and team functionality) on the relationship between the implementation strategies and effectiveness. Finally, in Aim 3, through interviews with providers, we will assess the acceptability and feasibility of the educational training. Conclusion The changes in study design will result in several limitation. Most importantly, the hospitals in the three cohorts are not randomized as they enroll based on their readiness. Second, the delivery of the IPE is virtual, and it is not known if remote education is conducive to team building. However, this study will be among the first to test the impact of IPE in the inpatient setting carefully and may generalize to other interventions directed to seriously ill patients. Trial registration ClinicalTrials.gov NCT04206735 . Registered on December 20, 2019;

Abstract The ability to forecast seizures minutes to hours in advance of an event has been verified using invasive EEG devices, but has not been previously demonstrated using noninvasive wearable devices over long durations in an ambulatory setting. In this study we developed a seizure forecasting system with a long short-term memory (LSTM) recurrent neural network (RNN) algorithm, using a noninvasive wrist-worn research-grade physiological sensor device, and tested the system in patients with epilepsy in the field, with concurrent invasive EEG confirmation of seizures via an implanted recording device. The system achieved forecasting performance significantly better than a random predictor for 5 of 6 patients studied, with mean AUC-ROC of 0.80 (range 0.72–0.92). These results provide the first clear evidence that direct seizure forecasts are possible using wearable devices in the ambulatory setting for many patients with epilepsy.

Aims: To determine the clinical efficacy, adverse events and side-effect dyspnea of CYP3A4*22 and CYP3A5 expressor status in ticagrelor treated patients.Methods and results: Ticagrelor treated patients from the POPular Genetics randomized controlled trial were genotyped for CYP3A4*22 and CYP3A5*3 alleles. Patients were divided based on their genotype. In total 1,281 patients with ST-segment elevation myocardial infarction (STEMI) were included. CYP3A4*22 carriers (n = 152) versus CYP3A4*22 non-carrier status (n = 1,129) were not found to have a significant correlation with the primary thrombotic endpoint: cardiovascular death, myocardial infarction, definite stent thrombosis and stroke [1.3% vs. 2.5%, adjusted hazard ratio 1.81 (0.43–7.62) p = 0.42], or the primary bleeding endpoint: PLATO major and minor bleeding [13.2% vs. 11.3%, adjusted hazard ratio 0.93 (0.58–1.50) p = 0.77]. Among the CYP3A4*1/*1 patients, CYP3A5 expressors (n = 196) versus non-expressors (n = 926) did not show a significant difference for the primary thrombotic [2.6% vs. 2.5%, adjusted hazard ratio 1.03 (0.39–2.71) p = 0.95], or the primary bleeding endpoint [12.8% vs. 10.9%, adjusted hazard ratio 1.13 (0.73–1.76) p = 0.58]. With respect to dyspnea, no significant difference was observed between CYP3A4*22 carriers versus CYP3A4*22 non-carriers [44.0% vs. 45.0%, odds ratio 1.04 (0.45–2.42) p = 0.93], or in the CYP3A4*1/*1 group, CYP3A5 expressors versus CYP3A5 non-expressors [35.3% vs. 47.8%, odds ratio 0.60 (0.27–1.30) p = 0.20].Conclusion: In STEMI patients treated with ticagrelor, neither the CYP3A4*22 carriers, nor the CYP3A5 expressor status had a statistical significant effect on thrombotic and bleeding event rates nor on dyspnea.Clinical Trial Registration:ClinicalTrials.gov, identifier NCT01761786.

The first complete ichthyosaur skeleton was introduced to the scientific community in 1819 by Sir Everard Home, and given the name Proteosaurus, although the name was subsequently replaced by ‘Ichthyosaurus’. The skeleton is from Lyme Regis and was probably collected by Mary Anning as it was in the collection of Colonel Birch. The specimen ultimately ended up in the collection of the Royal College of Surgeons, London, where it was destroyed in a bombing raid during World War II. We have discovered two plaster casts of the specimen, although no record exists of casts ever being made. The casts are at the Peabody Museum, Yale University, USA and the Museum für Naturkunde, Berlin, Germany. Significantly, these verify the accuracy of the published drawing of the specimen, and clarify morphologies of some of the bones. Discrepancies between the drawing and the casts are mainly in the details of the forefins and hindfins. The specimen can be assigned to Ichthyosaurus, but the species cannot be determined. This case illustrates the importance of old casts in museum collections. Additional, yet unrecognized casts of this specimen might exist in the UK or elsewhere.

Neural processes are complex and difficult to image. This paper presents a new space-time resolved brain imaging framework, called Neurophysiological Process Imaging (NPI), that identifies neurophysiological processes within cerebral cortex at the macroscopic scale. By fitting uncoupled neural mass models to each electromagnetic source time-series using a novel nonlinear inference method, population averaged membrane potentials and synaptic connection strengths are efficiently and accurately inferred and imaged across the whole cerebral cortex at a resolution afforded by source imaging. The efficiency of the framework enables return of the augmented source imaging results overnight using high performance computing. This suggests it can be used as a practical and novel imaging tool. To demonstrate the framework, it has been applied to resting-state magnetoencephalographic source estimates. The results suggest that endogenous inputs to cingulate, occipital, and inferior frontal cortex are essential modulators of resting-state alpha power. Moreover, endogenous input and inhibitory and excitatory neural populations play varied roles in mediating alpha power in different resting-state sub-networks. The framework can be applied to arbitrary neural mass models and has broad applicability to image neural processes of different brain states.

Black tiger shrimp (Penaeus monodon) is the second most important aquaculture species of shrimp in the world. In addition to growth traits, uncooked and cooked body color of shrimp are traits of significance for profitability and consumer acceptance. This study investigated for the first time, the phenotypic and genetic variances and relationships for body weight and body color traits, obtained from image analyses of 838 shrimp, representing the progeny from 55 sires and 52 dams. The color of uncooked shrimp was subjectively scored on a scale from 1 to 4, with “1” being the lightest/pale color and “4” being the darkest color. For cooked shrimp color, shrimp were graded firstly by subjective scoring using a commercial grading score card, where the score ranged from 1 to 12 representing light to deep coloration which was subsequently found to not be sufficiently reliable with poor repeatability of measurement (r = 0.68–0.78) Therefore, all images of cooked color were regraded on a three-point scale from brightest and lightest colored cooked shrimp, to darkest and most color-intense, with a high repeatability (r = 0.80–0.92). Objective color of both cooked and uncooked color was obtained by measurement of RGB intensities (values range from 0 to 255) for each pixel from each shrimp. Using the “convertColor” function in “R”, the RGB values were converted to L*a*b* (CIE Lab) systems of color properties. This system of color space was established in 1976, by the International Commission of Illumination (CIE) where “L*” represents the measure of degree of lightness, values range from 0 to 100, where 0 = pure black and 100 = pure white. The value “a*” represents red to green coloration, where a positive value represents the color progression towards red and a negative value towards green. The value “b*” represents blue to yellow coloration, where a positive value refers to more yellowish and negative towards the blue coloration. In total, eight color-related traits were investigated. An ordinal mixed (threshold) model was adopted for manually (subjectively) scored color phenotypes, whereas all other traits were analyzed by linear mixed models using ASReml software to derive variance components and estimated breeding values (EBVs). Moderate to low heritability estimates (0.05–0.35) were obtained for body color traits. For subjectively scored cooked and uncooked color, EBV-based selection would result in substantial genetic improvement in these traits. The genetic correlations among cooked, uncooked and body weight traits were high and ranged from −0.88 to 0.81. These suggest for the first time that 1) cooked color can be improved indirectly by genetic selection based on color of uncooked/live shrimp, and 2) intensity of coloration is positively correlated with body weight traits and hence selection for body weight will also improve color traits in this population.

Abstract Viruses that infect bacteria (phages) are increasingly recognized for their importance in diverse ecosystems but identifying and annotating them in large-scale sequence datasets is still challenging. Although efficient scalable virus identification tools are emerging, defining the exact ends (termini) of phage genomes is still particularly difficult. The proper identification of termini is crucial, as it helps in characterizing the packaging mechanism of bacteriophages and provides information on various aspects of phage biology. Here, we introduce PhageTermVirome (PTV) as a tool for the easy and rapid high-throughput determination of phage termini and packaging mechanisms using modern large-scale metagenomics datasets. We successfully tested the PTV algorithm on a mock virome dataset and then used it on two real virome datasets to achieve the rapid identification of more than 100 phage termini and packaging mechanisms, with just a few hours of computing time. Because PTV allows the identification of free fully formed viral particles (by recognition of termini present only in encapsidated DNA), it can also complement other virus identification softwares to predict the true viral origin of contigs in viral metagenomics datasets. PTV is a novel and unique tool for high-throughput characterization of phage genomes, including phage termini identification and characterization of genome packaging mechanisms. This software should help researchers better visualize, map and study the virosphere. PTV is freely available for downloading and installation at https://gitlab.pasteur.fr/vlegrand/ptv .

Epoxide hydrolases catalyze the conversion of epoxides to vicinal diols in a range of cellular processes such as signaling, detoxification, and virulence. These enzymes typically utilize a pair of tyrosine residues to orient the substrate epoxide ring in the active site and stabilize the hydrolysis intermediate. A new subclass of epoxide hydrolases that utilize a histidine in place of one of the tyrosines was established with the discovery of the CFTR Inhibitory Factor (Cif) from Pseudomonas aeruginosa. Although the presence of such Cif-like epoxide hydrolases was predicted in other opportunistic pathogens based on sequence analyses, only Cif and its homolog aCif from Acinetobacter nosocomialis have been characterized. Here we report the biochemical and structural characteristics of Cfl1 and Cfl2, two Cif-like epoxide hydrolases from Burkholderia cenocepacia. Cfl1 is able to hydrolyze xenobiotic as well as biological epoxides that might be encountered in the environment or during infection. In contrast, Cfl2 shows very low activity against a diverse set of epoxides. The crystal structures of the two proteins reveal quaternary structures that build on the well-known dimeric assembly of the α/β hydrolase domain, but broaden our understanding of the structural diversity encoded in novel oligomer interfaces. Analysis of the interfaces reveals both similarities and key differences in sequence conservation between the two assemblies, and between the canonical dimer and the novel oligomer interfaces of each assembly. Finally, we discuss the effects of these higher-order assemblies on the intra-monomer flexibility of Cfl1 and Cfl2 and their possible roles in regulating enzymatic activity.

Objectives To validate the Global Registry of Acute Coronary Events (GRACE) risk score and examine the extent and impact of the risk–treatment paradox in contemporary patients with acute coronary syndrome (ACS).Methods Data from 5015 patients with ACS enrolled in the FORCE-ACS registry between January 2015 and December 2019 were used for model validation. The performance of the GRACE risk score for predicting in-hospital and 1-year mortality was evaluated based on indices of model discrimination and calibration. Differences in the delivery of guideline-recommended care among patients who survived hospitalisation (n=4911) per GRACE risk stratum were assessed and the association with postdischarge mortality was examined.Results Discriminative power of the GRACE risk score was good for predicting in-hospital (c-statistic: 0.86; 95% CI: 0.83 to 0.90) and 1-year mortality (c-statistic: 0.82; 95% CI: 0.79 to 0.84). However, the GRACE risk score overestimated the absolute in-hospital and 1-year mortality risk (Hosmer-Lemeshow goodness-of-fit test p

AbstractShrimp are a valuable aquaculture species globally; however, disease remains a major hindrance to shrimp aquaculture sustainability and growth. Mechanisms mediated by endogenous viral elements have been proposed as a means by which shrimp that encounter a new virus start to accommodate rather than succumb to infection over time. However, evidence on the nature of such endogenous viral elements and how they mediate viral accommodation is limited. More extensive genomic data on Penaeid shrimp from different geographical locations should assist in exposing the diversity of endogenous viral elements. In this context, reported here is a PacBio Sequel-based draft genome assembly of an Australian black tiger shrimp (Penaeus monodonP. monodon

Background: Point-of-care (POC) testing equipment is commonly utilized in outpatient clinics. Our institution recently interfaced POC chemistry and hematology devices at two outpatient clinics via middleware software to the central electronic health record (EHR), facilitating a comparison of manual transcription versus automatic reporting via interface. This allowed for estimation of serious/obvious error rates and manual time savings. Additional goals were to develop autoverification rules and analyze broad trends of results in response to common clinician complaints on the POC testing. Material and Methods: Data were obtained from two satellite clinic sites providing both primary and urgent care within an academic health system. Interface of devices was accomplished via Instrument Manager middleware software and occurred approximately halfway through the 38 month retrospective timeframe. Laboratory results for three testing POC chemistry and hematology panels were extracted with EHR tools. Results: Nearly 100,000 lab values were analyzed and revealed that the rate of laboratory values outside reference range was essentially unchanged before and after interface of POC testing devices (2.0–2.1%). Serious/obvious errors, while rare overall, declined significantly, with none recorded after the interface with autoverified results and only three related to manual edits of results that failed autoverification. Fewer duplicated test results were identified after the interface, most notably with the hematology testing. Anion gap values of less than zero were observed more frequently in POC device tests when compared to central laboratory tests and are attributed to a higher proportion of Cl values greater than 110 mEq/L and CO2 values greater than 30 mEq/L with POC results. Time savings of eliminating manual data entry were calculated to be 21.6 employee hours per month. Conclusions: In a switch from manual entry to automatic interface for POC chemistry and hematology, the most notable changes were reduction of serious/obvious errors and duplicate results. Significant time employee time savings highlight an additional benefit of instrument interfacing. Lastly, a difference between POC and central laboratory instruments is a higher rate of high Cl and CO2 values relative to the central laboratory.

Abstract Background Restrictions to gene flow, genetic drift, and divergent selection associated with different environments are significant drivers of genetic differentiation. The black tiger shrimp (Penaeus monodon), is widely distributed throughout the Indian and Pacific Oceans including along the western, northern and eastern coastline of Australia, where it is an important aquaculture and fishery species. Understanding the genetic structure and the influence of environmental factors leading to adaptive differences among populations of this species is important for farm genetic improvement programs and sustainable fisheries management. Results Based on 278 individuals obtained from seven geographically disparate Australian locations, 10,624 high-quality SNP loci were used to characterize genetic diversity, population structure, genetic connectivity, and adaptive divergence. Significant population structure and differentiation were revealed among wild populations (average F ST = 0.001–0.107; p

Abstract Background The development of genome-wide genotyping resources has provided terrestrial livestock and crop industries with the unique ability to accurately assess genomic relationships between individuals, uncover the genetic architecture of commercial traits, as well as identify superior individuals for selection based on their specific genetic profile. Utilising recent advancements in de-novo genome-wide genotyping technologies, it is now possible to provide aquaculture industries with these same important genotyping resources, even in the absence of existing genome assemblies. Here, we present the development of a genome-wide SNP assay for the Black Tiger shrimp (Penaeus monodon) through utilisation of a reduced-representation whole-genome genotyping approach (DArTseq). Results Based on a single reduced-representation library, 31,262 polymorphic SNPs were identified across 650 individuals obtained from Australian wild stocks and commercial aquaculture populations. After filtering to remove SNPs with low read depth, low MAF, low call rate, deviation from HWE, and non-Mendelian inheritance, 7542 high-quality SNPs were retained. From these, 4236 high-quality genome-wide loci were selected for baits-probe development and 4194 SNPs were included within a finalized target-capture genotype-by-sequence assay (DArTcap). This assay was designed for routine and cost effective commercial application in large scale breeding programs, and demonstrates higher confidence in genotype calls through increased call rate (from 80.2 ± 14.7 to 93.0% ± 3.5%), increased read depth (from 20.4 ± 15.6 to 80.0 ± 88.7), as well as a 3-fold reduction in cost over traditional genotype-by-sequencing approaches. Conclusion Importantly, this assay equips the P. monodon industry with the ability to simultaneously assign parentage of communally reared animals, undertake genomic relationship analysis, manage mate pairings between cryptic family lines, as well as undertake advance studies of genome and trait architecture. Critically this assay can be cost effectively applied as P. monodon breeding programs transition to undertaking genomic selection.

Abstract Obesity and metabolic syndrome are strongly associated with cancer, and these disorders may share a common mechanism. Recently, fructose has emerged as a driving force to develop obesity and metabolic syndrome. Thus, we assume that fructose may be the mechanism to explain why obesity and metabolic syndrome are linked with cancer. Clinical and experimental evidence showed that fructose intake was associated with cancer growth and that fructose transporters are upregulated in various malignant tumors. Interestingly, fructose metabolism can be driven under low oxygen conditions, accelerates glucose utilization, and exhibits distinct effects as compared to glucose, including production of uric acid and lactate as major byproducts. Fructose promotes the Warburg effect to preferentially downregulate mitochondrial respiration and increases aerobic glycolysis that may aid metastases that initially have low oxygen supply. In the process, uric acid may facilitate carcinogenesis by inhibiting the TCA cycle, stimulating cell proliferation by mitochondrial ROS, and blocking fatty acid oxidation. Lactate may also contribute to cancer growth by suppressing fat oxidation and inducing oncogene expression. The ability of fructose metabolism to directly stimulate the glycolytic pathway may have been protective for animals living with limited access to oxygen, but may be deleterious toward stimulating cancer growth and metastasis for humans in modern society. Blocking fructose metabolism may be a novel approach for the prevention and treatment of cancer.

Critical slowing (associated with increased variance and autocorrelation) can precede critical state transitions. Here, the authors show critical slowing can be used as a marker in seizure forecasting algorithms.

Analyzing historical maps and Landsat imagery indicates that coastal glaciers in the western Prince William Sound (PWS) have retreated since the end of the Little Ice Age, exhibiting accelerated retreat after the mid-2000s. A multitemporal inventory of 43 glaciers was developed using historical field observations, topographic maps, and Landsat imagery. Area and length measurements are derived from digitized outlines, and center lines are derived from a semi-automatic, geographic information systems (GIS)-based algorithm. Land-based glaciers retreated at a peak rate of 48 m a−1 from the mid-2000s to 2018, more than doubling the average rate of retreat (22 m a−1) for the preceding fifty-year period. From ~1950 to 2018, the total area of land-based glaciers decreased by 228 km2, with 36 percent of the glacier loss occurring after the mid-2000s. Simple upscaling of area and volume changes to unmeasured glaciers across the entire PWS resulted in an estimated aggregate glacier mass loss of 379 Gt, equivalent to a 1.047 mm rise in sea level from the 1950s to 2018. Tidewater glaciers respond asynchronously with differing periods of peak area and length loss and lower average rate of retreat compared to land-based glaciers. Glacier retreat correlates with increased summer and winter temperatures and decreased winter precipitation.

Background: Circadian and multiday rhythms are found across many biological systems, including cardiology, endocrinology, neurology, and immunology. In people with epilepsy, epileptic brain activity and seizure occurrence have been found to follow circadian, weekly, and monthly rhythms. Understanding the relationship between these cycles of brain excitability and other physiological systems can provide new insight into the causes of multiday cycles. The brain-heart link has previously been considered in epilepsy research, with potential implications for seizure forecasting, therapy, and mortality (i.e., sudden unexpected death in epilepsy). Methods: We report the results from a non-interventional, observational cohort study, Tracking Seizure Cycles. This study sought to examine multiday cycles of heart rate and seizures in adults with diagnosed uncontrolled epilepsy (N=31) and healthy adult controls (N=15) using wearable smartwatches and mobile seizure diaries over at least four months (M=12.0, SD=5.9; control M=10.6, SD=6.4). Cycles in heart rate were detected using a continuous wavelet transform. Relationships between heart rate cycles and seizure occurrence were measured from the distributions of seizure likelihood with respect to underlying cycle phase. Findings: Heart rate cycles were found in all 46 participants (people with epilepsy and healthy controls), with circadian (N=46), about-weekly (N=25) and about-monthly (N=13) rhythms being the most prevalent. Of the participants with epilepsy, 19 people had at least 20 reported seizures, and 10 of these had seizures significantly phase locked to their multiday heart rate cycles. Interpretation: Heart rate cycles showed similarities to multiday epileptic rhythms and may be comodulated with seizure likelihood. The relationship between heart rate and seizures is relevant for epilepsy therapy, including seizure forecasting, and may also have implications for cardiovascular disease. More broadly, understanding the link between multiday cycles in the heart and brain can shed new light on endogenous physiological rhythms in humans. Funding: This research received funding from the Australian Government National Health and Medical Research Council (investigator grant 1178220), the Australian Government BioMedTech Horizons program, and the Epilepsy Foundation of America's ‘My Seizure Gauge’ grant.

A recent workshop titled “Developing Models to Study Polymicrobial Infections,” sponsored by the Dartmouth Cystic Fibrosis Center (DartCF), explored the development of new models to study the polymicrobial infections associated with the airways of persons with cystic fibrosis (CF). The workshop gathered 35+ investigators over two virtual sessions.

Cubozoan jellyfish pose a risk of envenomation to humans and a threat to many businesses, yet crucial gaps exist in determining threats to stakeholders and understanding their ecology. Environmental DNA (eDNA) provides a cost-effective method for detection that is less labour intensive and provides a higher probability of detection. The objective of this study was to develop, optimise and trial the use of eDNA to detect the Australian box jellyfish, Chironex fleckeri. This species was the focus of this study as it is known to have the strongest venom of any cubozoan; it is responsible for more than 200 recorded deaths in the Indo-Pacific region. Further, its ecology is poorly known. Herein, a specific and sensitive probe-based assay, multiplexed with an endogenous control assay, was developed, and successfully utilised to detect the deadly jellyfish species and differentiate them from closely related taxa. A rapid eDNA decay rate of greater than 99% within 27 h was found with no detectable influence from temperature. The robustness of the technique indicates that it will be of high utility for detection and to address knowledge gaps in the ecology of C. fleckeri; further, it has broad applicability to other types of zooplankton.

Accurate identification of seizure activity, both clinical and subclinical, has important implications in the management of epilepsy. Accurate recognition of seizure activity is essential for diagnostic, management and forecasting purposes, but patient-reported seizures have been shown to be unreliable. Earlier work has revealed accurate capture of electrographic seizures and forecasting is possible with an implantable intracranial device, but less invasive electroencephalography (EEG) recording systems would be optimal. Here, we present preliminary results of seizure detection and forecasting with a minimally invasive sub-scalp device that continuously records EEG. Five participants with refractory epilepsy who experience at least two clinically identifiable seizures monthly have been implanted with sub-scalp devices (Minder®), providing two channels of data from both hemispheres of the brain. Data is continuously captured via a behind-the-ear system, which also powers the device, and transferred wirelessly to a mobile phone, from where it is accessible remotely via cloud storage. EEG recordings from the sub-scalp device were compared to data recorded from a conventional system during a 1-week ambulatory video-EEG monitoring session. Suspect epileptiform activity (EA) was detected using machine learning algorithms and reviewed by trained neurophysiologists. Seizure forecasting was demonstrated retrospectively by utilizing cycles in EA and previous seizure times. The procedures and devices were well-tolerated and no significant complications have been reported. Seizures were accurately identified on the sub-scalp system, as visually confirmed by periods of concurrent conventional scalp EEG recordings. The data acquired also allowed seizure forecasting to be successfully undertaken. The area under the receiver operating characteristic curve (AUC score) achieved (0.88), which is comparable to the best score in recent, state-of-the-art forecasting work using intracranial EEG.

Barramundi, Lates calcarifer, are protandrous hermaphrodites where individuals first sexually mature as male at 3−5 years of age, before reorganizing gonadal tissue to change to female several years later when they reach around 70 cm in total length (∼4−5 kg). However, recent anecdotal evidence suggests that in populations farmed in Singapore, this sex change may be occurring much earlier than previously recorded, thus posing challenges for hatcheries to select and maintain male fish for breeding purposes. This study examined the gonadal sex and maturation status of barramundi from a commercial sea-cage farm located in the southern waters of Singapore and confirmed this precocious sex change phenomenon. Barramundi (n = 173) harvested between 2 and 3 years old were individually measured (mean ± SE); total length (70.3 ± 7.3 cm), weighed (4.7 ± 1.4 kg), and had their gonads dissected for sex identification through histological analyses. Histology showed that only 19 % were still male, 8% were in transitional stages of sex change and 73 % of fish were female. In this precocious farmed population, females as small as 2 kg were found, with the proportion of males in the population decreasing to less than 50 % from 2.5 to 3 kg (55∼60 cm). Above 3 kg and 5 kg, 70 % and 90 % of sampled individuals were females, respectively. Comparative farm studies from French Polynesia and in wild Australian stocks indicate that the farmed population in our study is changing sex at body weights approximately half that of what was previously known. The findings of this study are important for local breeders to make decisions of when, and at what size to select candidate L. calcarifer broodstock in Singaporean waters so that the recommended 2:1 male-to-female spawning ratio can be achieved. The exact causes for this early sex change are still unknown and deserve further investigation.

To enable cumulative increases in aquaculture productivity, structured and efficient selective breeding programs are required. These are contingent on the management of genetic resources within the breeding population though the attainment of accurate pedigree information which can be provided by DNA-based parentage analysis. This study developed a SNP panel for greenlip abalone, Haliotis laevigata, from DArTSeq data produced from a genetic audit of greenlip abalone (n = 336) from five farms. The initial dataset consisted of 15,320 SNPs. Strict filtering on SNP quality control metrics was conducted to select the most informative 1,004 SNPs for the design of a DArTag™ genotyping panel for greenlip abalone. Sixteen broodstock and 1035 hatchery produced progeny were genotyped using the 1,004 SNP DArTag™ panel. The resulting genotypes were filtered, to produce 705 high performing SNPs. In silico parentage analysis using subsets of these SNPs (highest ranked by polymorphic information content) revealed that the inclusion of < 50 SNPs were satisfactory to resolve parentage for 10,000 simulated progeny to up to 200 candidate parents. The resolving power of the panel was also assessed under high levels of inbreeding (0–50 %) and relatedness (0–50 %) between candidate parents, and conditions of missing parental genotypes (10–50 %) in silico. Under all levels of inbreeding, relatedness and missing parental genotypes simulated, the panel was able to accurately assign parental pairs to the offspring. To validate these in silico results, parentage analysis of the hatchery produced progeny of the 16 candidate broodstock was conducted using both CERVUS and APIS. Complete parentage was assigned to all experimental progeny, with 100 % consensus between the two methods used. This study indicates this panel will serve as an efficient and cost-effective tool for accurate pedigree establishment for greenlip abalone.

It is a major challenge in clinical epilepsy to diagnose and treat a disease characterized by infrequent seizures based on patient or caregiver reports and limited duration clinical testing. The poor reliability of self-reported seizure diaries for many people with epilepsy is well-established, but these records remain necessary in clinical care and therapeutic studies. A number of wearable devices have emerged, which may be capable of detecting seizures, recording seizure data, and alerting caregivers. Developments in non-invasive wearable sensors to measure accelerometry, photoplethysmography (PPG), electrodermal activity (EDA), electromyography (EMG), and other signals outside of the traditional clinical environment may be able to identify seizure-related changes. Non-invasive scalp electroencephalography (EEG) and minimally invasive subscalp EEG may allow direct measurement of seizure activity. However, significant network and computational infrastructure is needed for continuous, secure transmission of data. The large volume of data acquired by these devices necessitates computer-assisted review and detection to reduce the burden on human reviewers. Furthermore, user acceptability of such devices must be a paramount consideration to ensure adherence with long-term device use. Such devices can identify tonic–clonic seizures, but identification of other seizure semiologies with non-EEG wearables is an ongoing challenge. Identification of electrographic seizures with subscalp EEG systems has recently been demonstrated over long (>6 month) durations, and this shows promise for accurate, objective seizure records. While the ability to detect and forecast seizures from ambulatory intracranial EEG is established, invasive devices may not be acceptable for many individuals with epilepsy. Recent studies show promising results for probabilistic forecasts of seizure risk from long-term wearable devices and electronic diaries of self-reported seizures. There may also be predictive value in individuals' symptoms, mood, and cognitive performance. However, seizure forecasting requires perpetual use of a device for monitoring, increasing the importance of the system's acceptability to users. Furthermore, long-term studies with concurrent EEG confirmation are lacking currently. This review describes the current evidence and challenges in the use of minimally and non-invasive devices for long-term epilepsy monitoring, the essential components in remote monitoring systems, and explores the feasibility to detect and forecast impending seizures via long-term use of these systems.