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Marine heatwaves (MHWs) can severely impact marine biodiversity, fisheries, and aquaculture. Consequently, there is an increasing desire to understand the drivers of these events to inform their predictability so that proactive decisions may be made to reduce potential impacts. In the Tasman Sea (TS), several relatively intense and broad-scale MHWs have caused significant damage to marine fisheries and aquaculture industries. To assess the potential predictability of these events, we first determined the main driver of each MHW event in the TS from 1993 to 2021. We found that those MHWs driven by ocean advection – approximately 45% of all events – are generally longer in duration, less intense, and affected a smaller area compared with the remaining 55%, which are driven by air-sea heat fluxes, are shorter in duration, and more surface intense. As ocean advection-driven events in the TS have been closely studied and reported previously, we focus here on atmospherically driven MHWs. The predictability of these events is assessed by identifying the patterns of atmospheric pressure, winds, and air-sea heat fluxes in the southern hemisphere that coincide with MHWs in the Tasman Sea. We found that atmospherically driven MHWs in this region are more likely to occur during the positive phase of the asymmetric Southern Annular Mode (A-SAM) – which presents as an atmospheric zonal wave-3 pattern and is more likely to occur during La Niña years. These A-SAM events are linked to low wind speeds and increased downward solar radiation in the TS, which lead to increased surface ocean temperatures through the reduction of mixing.

We assess seasonally varying impacts of the Madden–Julian oscillation (MJO) on Australian maximum and minimum temperature anomalies and extremes, and their modulation by El Niño–Southern Oscillation (ENSO), for the period June 1974–May 2022. Our composite-based approach uses observed temperatures from the Australian Gridded Climate Data, and 850-hPa wind data from the NCEP–NCAR reanalysis, to show how relationships to temperature and circulation evolve over the eight-phase life cycle of the MJO, which we derive from the real-time multivariate MJO index. The MJO has significant impacts on Australian temperatures and winds in all parts of the country at various times throughout the year, and to varying degrees. Two of the most pronounced impacts are 1) daytime warming across southeastern Australia in MJO phase 3 during spring associated with a strong anomalous anticyclone and 2) nighttime cooling over Queensland in MJO phase 7 during winter associated with anomalous advection of cool dry continental air. La Niña acts to significantly lessen both of these impacts, while El Niño enhances both the phase 3 warming over southern Australia in spring and the phase 7 overnight cooling over southern Queensland in winter. We show how the MJO can combine with El Niño and La Niña to have strong compounding influences, thus highlighting the importance of understanding interactions between multiple modes of climate variability and how they relate to Australian temperatures and extremes.

This study first re-examines the impact of the Madden–Julian oscillation (MJO) on weekly rainfall probabilities and wind anomalies across Australia, motivated by the need for a contemporary understanding of the MJO’s influence on Australian rainfall, whether this has changed from a previous assessment published in 2009. With an extra 15 years of observations, we show that the strong impact of MJO phases 5 and 6 on northern Australia’s austral summer rainfall has weakened by around 5% over Australia’s Top End. In addition, austral spring has seen a weakening of the suppressed rainfall teleconnection with MJO phases 2 and 3 over southeast Australia. The weakened relationships make it a little harder to use the MJO to explain rainfall variations over northern Australia in summer and southeast Australia in spring in the current climate. The study’s second motivation is to further document the combined influence of El Niño–Southern Oscillation (ENSO) and the MJO on rainfall. In summer during El Niño, as compared with La Niña or neutral ENSO conditions, there are stronger reductions in rainfall probabilities over northern Australia associated with the dry MJO phases 8, 1, and 2, but the significantly increased rainfall probabilities in MJO phases 5 and 6 remain much the same. Indeed, the MJO dominates over ENSO in its influence on weekly rainfall probabilities in the north in summer. In contrast, ENSO tends to dominate across subtropical and southern Australia in spring. The updated probability maps are an important resource for estimating the intraseasonal influence of the MJO and ENSO on Australian rainfall. Significance Statement Accompanying forecasts of multiweek rainfall, the Australian Bureau of Meteorology provide average condition maps showing the long-term relationship between the Madden–Julian oscillation (MJO) and Australian weekly rainfall. Motivated by discussions with northern Australian beef producers, we updated the maps using high-resolution data and found that in the austral summer, the association between the MJO and northern rainfall has weakened in the past 15 years. Despite this, the MJO still dominates over El Niño–Southern Oscillation (ENSO) as a driver of changes in week-to-week rainfall over northern Australia in summer, although ENSO dominates farther south in spring. This study gives users an improved understanding of what to expect in terms of upcoming weekly weather when interpreting rainfall and MJO predictions.

The aim of this article was to study clinical and radiographic outcomes following treatment of bone healing disorders with a novel osteoinductive system that utilizes poly (ethyl acrylate), fibronectin and an ultra-low concentration of recombinant human bone morphogenetic protein-2. A case series of nine dogs and two cats were treated, and clinical records and radiographs were reviewed. Radiographs were scored by two blinded observers using the modified Radiographic Union Score for Tibial Fractures. Long-term follow-up was obtained using the Canine Orthopaedic Index and Feline Musculoskeletal Pain Index. Follow-up data were available for 11 treatments (10 cases). Complications: three minor, three major, one catastrophic (non-union requiring amputation). Lameness median 320 (range: 42–1,082) days postoperatively: ‘sound’ (three cases), ‘subtle’ (two), ‘mild’ (three), ‘moderate’ (one), and ‘non-weightbearing’ (one). The attending clinician judged 9 of 11 treatments achieved radiographic union; modified Radiographic Union Score for Tibial Fractures observers 1 and 2 agreed with the clinician in 8/9 and 5/9 treatments respectively. Long-term Canine Orthopaedic Index scores for five dogs median 650 (range: 544–1,724) days postoperatively: 15/64 (median) for four dogs with acceptable outcomes, 30/64 in one dog with a poor outcome. Feline Musculoskeletal Pain Index scores for two cats 433 and 751 days postoperatively: 48/60 and 60/60. Eight of 10 cases were sound or showed subtle or mild lameness in the short- or long-term, and radiographic union occurred in the majority of treatments.

BackgroundAs the first point of contact in health care, primary care providers play an integral role in pandemic response. Despite this, primary care has been overlooked in previous pandemic plans, with a lack of emphasis on ways in which the unique characteristics of family practice could be leveraged to create a more effective response.AimTo explore family physicians’ perceptions of the integration of primary care in the COVID-19 pandemic response.Design and settingDescriptive qualitative approach examining family physician roles during the COVID-19 pandemic across four regions in Canada.MethodSemi-structured qualitative interviews were conducted with family physicians and participants were asked about their roles during each pandemic stage, as well as facilitators and barriers they experienced in performing these roles. Interviews were transcribed and a thematic analysis approach was employed to develop a unified coding template across the four regions and identify recurring themes.ResultsIn total, 68 family physicians completed interviews. Four priorities for integrating primary care in future pandemic planning were identified: 1) improve communication with family physicians; 2) prioritise community-based primary care; 3) leverage the longitudinal relationship between patients and family physicians; and 4) preserve primary care workforce capacity. Across all regions, family physicians felt that primary care was not well incorporated into the COVID-19 pandemic response.ConclusionFuture pandemic plans require greater integration of primary care to ensure the delivery of an effective and coordinated pandemic response. Strengthening pandemic preparedness requires a broader reconsideration and better understanding of the central role of primary care in health system functioning.

ACCESS-S2 is a major upgrade to the Australian Bureau of Meteorology’s multi-week to seasonal prediction system. It was made operational in October 2021, replacing ACCESS-S1. The focus of the upgrade is the addition of a new weakly coupled data assimilation system to provide initial conditions for atmosphere, ocean, land and ice fields. The model is based on the UK Met Office GloSea5-GC2 seasonal prediction system and is unchanged from ACCESS-S1, aside from minor corrections and enhancements. The performance of the assimilation system and the skill of the seasonal and multi-week forecasts have been assessed and compared to ACCESS-S1. There are improvements in the ACCESS-S2 initial conditions compared to ACCESS-S1, particularly for soil moisture and aspects of the ocean, notably the ocean currents. More realistic soil moisture initialisation has led to increased skill for forecasts over Australia, especially those of maximum temperature. The ACCESS-S2 system is shown to have increased skill of El Nino–Southern Oscillation forecasts over ACCESS-S1 during the challenging autumn forecast period. Analysis suggests that ACCESS-S2 will deliver improved operational forecast accuracy in comparison to ACCESS-S1. Assessments of the operational forecasts are underway. ACCESS-S2 represents another step forward in the development of seasonal forecast systems at the Bureau of Meteorology. However, key rainfall and sea surface temperature biases in ACCESS-S1 remain in ACCESS-S2, indicating where future efforts should be focused.

Since 2017, the Northern Australia Climate Program (NACP) has assisted the pastoral grazing industry to better manage drought risk and climate variability. The NACP funding is sourced from the beef cattle industry, government, and academia, representing the program’s broad range of aims and target beneficiaries. The program funds scientists in the United Kingdom and Australia, in addition to extension advisers called “Climate Mates” across a region that supports 15 million head of cattle. Many Climate Mates are employed in the cattle sector and have existing relationships in their communities and capacity to meaningfully engage with the program’s intended beneficiaries—red meat producers. The NACP is a prime example of a successful end-to-end program, integrating climate model improvements (research) with tailored forecast products (development), through to direct stakeholder engagement (extension), on-ground application of technologies (adoption), and improvement in industry and community resilience (impact). The climate information needs of stakeholders also feed back to the research and development components, ensuring the scientific research directly addresses end-user requirements. For any scientific research program, ensuring that research output has measurable real-world impact represents a key challenge. This is more difficult in cases where the scientific research is several steps away from the customer’s needs. This paper gives an overview of the NACP and research highlights, discussing how the end-to-end framework could be adapted and applied in other regions and industries. It seeks to provide a roadmap for other groups to follow to produce more targeted research with identifiable real-world benefits.

Pavement sealants are of environmental concern because of their complex petroleum-based chemistry and potential toxicity. Specifically, coal tar-derived sealants contain high concentrations of toxic/carcinogenic polycyclic aromatic hydrocarbons (PAHs) that, when weathered, can be transferred into the surrounding environment. Previous studies have demonstrated the effects of coal tar sealants on PAH concentration in nearby waterways and their harmful effects in aquatic ecosystems. Here, we investigate and compare the molecular composition of two different pavement sealants, petroleum asphalt- and coal tar-derived, and their photoproducts, by positive-ion (+) atmospheric pressure photoionization (APPI) and negative-ion (-) electrospray ionization (ESI) coupled with ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry to address species (high-boiling and/or high oxygen content) that lie outside the analytical window of other techniques due to ultra-high molecular complexity. In addition, we evaluate the toxicity of the water-soluble photoproducts by use of Microtox bioassay. The results demonstrate that the coal tar sealant contains higher amounts of PAHs and produces abundant water-soluble compounds, relative to unweathered materials, with a high abundance of PAH-like molecules of high toxicity. By comparison, the asphalt sealant produces fewer toxic water-soluble species, with molecular compositions that are consistent with natural dissolved organic matter. These results capture the mass, chemical diversity, toxicity, and source/photoproduct relationship of these compositionally complex emerging contaminants from the built environment.

Cable bacteria encompass at least two genera, and they are known to vary greatly in habitat preferences and filament thickness. We systematically investigated variations and similarities in cellular structures and electrical properties of different cable bacteria strains. Using SEM, TEM, STEM-EDX and ToF-SIMS, we characterized shared features of cable bacteria, such as inner and outer membranes, surface layer and cell junction architecture, as well as strain specific features, like the number and size of periplasmic conductive fibers (PCFs). Our data indicates that the PCFs are organized as loose stranded rope-like structures. With spatially resolved elemental analysis we detected nickel-containing co-factors within the PCF of cable bacteria strains in both genera suggesting a conserved conduction mechanism. Electrical conductivity of different cable bacteria strains showed a range of values covering three orders of magnitude indicating an unknown metabolic adaptation. Using cryogenic electron tomography we discovered multiple polar chemosensory arrays, abundant cytoplasmic inner membrane-attached vesicles (IMVs), polysomes and inner membrane invaginations that shed light on cable bacteria metabolism including complex motility control mechanisms, localized protein synthesis, and membrane remodeling. We propose that the IMVs discovered in this work are novel metabolic hubs closely connected to the unique conductive fiber structure of cable bacteria.

The Sorting and Assembly Machinery (SAM) Complex functions in the assembly of β-barrel in the mitochondrial membrane. The SAM complex is made up of three subunits, Sam35, Sam37, and Sam50. While both Sam35 and Sam37 are peripheral membrane proteins that are not required for survival, Sam50 interacts with the MICOS complex to connect the inner and outer mitochondrial membranes and forms the mitochondrial intermembrane space bridging (MIB) complex. Specifically, Sam50 stabilizes the MIB complex for protein transport, respiratory chain complex assembly, and cristae integrity regulation. To structurally form and sustain the cristae, the MICOS complex assembles at the cristae junction and binds directly to Sam50. However, the role of Sam50 in overall mitochondrial structure and metabolism in skeletal muscle remains unclear. Here, we use SBF-SEM and Amira software perform 3D renderings of mitochondria and autophagosomes in human myotubes. Beyond this, Gas Chromatography-Mass Spectrometry-based metabolomics was utilized to interrogate differential changes of the metabolites in wild-type (WT) andSam50deficient myotubes. Ablation ofSam50, revealed increases in ß-Alanine, propanoate, and phenylalanine, and tyrosine metabolism. Additionally, we observed that mitochondrial fragmentation and autophagosome formation was increased inSam50-deficient myotubes compared to control myotubes. Beyond this, the metabolomic analysis revealed an increase in amino acid metabolism and fatty acid metabolism. XF24 Seahorse Analyzer shows that oxidative capacity is further impaired upon ablation ofSam50in both murine and human myotubes. Together, these data suggest Sam50 is critical for establishing and maintaining mitochondria, mitochondrial cristae structure, and mitochondrial metabolism.

SummaryOPA1 is a dynamin-related GTPase that modulates various mitochondrial functions and is involved in mitochondrial morphology. There are eight different isoforms of OPA1 in humans that are expressed as short or long-form isoforms. These isoforms contribute to OPA1’s ability to control mitochondrial functions. However, isolating OPA1 isoforms through western blot has been a difficult task. To address this issue, we outline an optimized western blot protocol to isolate different isoforms of OPA1 on the basis of different antibodies. This protocol can be used to study changes in mitochondrial structure and function.Tweetable AbstractWestern blot protocol optimization to visualize OPA1 isoforms.HighlightsProtocol for isolating OPA1 isoforms in skeletal muscle tissueSteps for running isolated skeletal muscle cells from muscle tissue on a gelHow to collect samples in preparation for western blottingDetection of OPA1 isoformsGraphical AbstractKey Resources TableMethod SummarySamples for western blot analysis are isolated from lysed cells, loaded onto a gel, and ran using optimized conditions to better isolate OPA1 isoforms. Samples are transferred to a membrane to for incubation and protein detection using OPA1 antibodies.

Isolation of skeletal muscles allows for the exploration of many complex diseases. Fibroblasts and myoblast play important roles in skeletal muscle morphology and function. However, skeletal muscles are complex and made up of many cellular populations and validation of these populations is highly important. Therefore, in this article, we discuss a comprehensive method to isolate mice skeletal muscle, create satellite cells for tissue culture, and use immunofluorescence to validate our approach.Novel imaging technology is increasing our ability to visualize and analyze cellular organelles and compartments.Tweetable AbstractProper antibody validation of cellular populations within isolated skeletal muscle can lead to better elucidation of skeletal muscle structure and function, and their roles in complex diseases.Graphical AbstractMethod SummaryMyoblasts are isolated from mouse limb muscles. They are plated for immunofluorescence-based validation using confocal microscopy. This method demonstrates the need for reliable antibodies to correctly determine and differentiate between cellular populations within isolated skeletal muscles.

SummaryProximity ligation assays (PLA) use specific antibodies to detect endogenous protein-protein interactions. PLA is a highly useful biochemical technique that allows two proteins within close proximity to be visualized with fluorescent probes amplified by PCR. While this technique has gained prominence, the use of PLA in mouse skeletal muscle (SkM) is novel. In this article, we discuss how the PLA method can be used in SkM to study the protein-protein interactions within mitochondria-endoplasmic reticulum contact sites (MERCs).Tweetable AbstractProximity Ligation Assays can be used in skeletal muscle tissue and myoblasts to explore the protein-protein interactions involved in MERC sites.HighlightsSkeletal muscle tissue and cells are plated on glass coverslips for evaluation by proximity ligation assay (PLA).Following fixation, cells are probed and stained for Mfn1, Mfn2, mitochondria, and ER and imaged using fluorescence confocal microscopy.This method shows that PLA can be used in mouse SkM and is adaptable to other models.Protocol for detection of protein-protein interactions using PLA.Graphical AbstractKey Resources Table

Mitochondria are required for energy production and even give brown adipose tissue (BAT) its characteristic color due to their high iron content and abundance The physiological function and bioenergetic capacity of mitochondria are connected to the structure, folding, and organization of its inner-membrane cristae. During the aging process, mitochondrial dysfunction is observed, and the regulatory balance of mitochondrial dynamics is often disrupted, leading to increased mitochondrial fragmentation in aging cells. Therefore, we hypothesized that the morphological changes in BAT mitochondria and cristae observed across aging would reflect alterations to energy dynamics. We developed a quantitative three-dimensional (3D) electron microscopy approach to map cristae network organization in mouse BAT to test this hypothesis. Using this methodology, we investigated the 3D morphology of mitochondrial cristae in adult (3-month) and aged (2-year) murine BAT tissue via serial block face-scanning electron microscopy (SBF-SEM) and3D reconstruction software for manual segmentation, analysis, and quantification. Upon investigation, we found increases in mitochondrial volume, surface area, and complexity and decreased sphericity in aged BAT. Cristae examination revealed decreased cristae volume, perimeter, and complexity, with cristate appearing more heterogeneous. Overall, these data define the nature of the mitochondrial structure in BAT, showing loss of cristae definition across aging, suggesting alterations in functionality and bioactivity.Graphical AbstractWorkflow overview of serial block facing-scanning electron microscopy (SBF-SEM), data segmentation, and 3D analysis of mitochondria using Amira software in murine BAT.

IntroductionMany studies in mice have demonstrated that cardiac-specific innate immune signaling pathways can be reprogrammed to modulate inflammation in response to myocardial injury and improve outcomes. While the echocardiography standard parameters of left ventricular (LV) ejection fraction, fractional shortening, end-diastolic diameter, and others are used to assess cardiac function, their dependency on loading conditions somewhat limits their utility in completely reflecting the contractile function and global cardiovascular efficiency of the heart. A true measure of global cardiovascular efficiency should include the interaction between the ventricle and the aorta (ventricular-vascular coupling, VVC) as well as measures of aortic impedance and pulse wave velocity.MethodsWe measured cardiac Doppler velocities, blood pressures, along with VVC, aortic impedance, and pulse wave velocity to evaluate global cardiac function in a mouse model of cardiac-restricted low levels of TRAF2 overexpression that conferred cytoprotection in the heart.ResultsWhile previous studies reported that response to myocardial infarction and reperfusion was improved in the TRAF2 overexpressed mice, we found that TRAF2 mice had significantly lower cardiac systolic velocities and accelerations, diastolic atrial velocity, aortic pressures, rate-pressure product, LV contractility and relaxation, and stroke work when compared to littermate control mice. Also, we found significantly longer aortic ejection time, isovolumic contraction and relaxation times, and significantly higher mitral early/atrial ratio, myocardial performance index, and ventricular vascular coupling in the TRAF2 overexpression mice compared to their littermate controls. We found no significant differences in the aortic impedance and pulse wave velocity.DiscussionWhile the reported tolerance to ischemic insults in TRAF2 overexpression mice may suggest enhanced cardiac reserve, our results indicate diminished cardiac function in these mice.

Introduction Proteomic analysis of human plasma by LC–ESI–MS/MS has discovered a limited number of new cellular protein biomarkers that may be confirmed by independent biochemical methods. Analysis of COVID-19 plasma has indicated the re-purposing of known biomarkers that might be used as prognostic markers of COVID-19 infection. However, multiple molecular approaches have previously indicated that the SARS-COV2 infection cycle is linked to the biology of mitochondria and that the response to infections may involve the action of heme containing oxidative enzymes. Methods Human plasma from COVID-19 and ICU-ARDS was analyzed by classical analytical biochemistry techniques and classical frequency-based statistical approaches to look for prognostic markers of severe COVID-19 lung damage. Plasma proteins from COVID-19 and ICU-ARDS were identified and enumerated versus the controls of normal human plasma (NHP) by LC–ESI–MS/MS. The observation frequency of proteins detected in COVID-19 and ICU-ARDS patients were compared to normal human plasma, alongside random and noise MS/MS spectra controls, using the Chi Square (χ2) distribution. Results PCR showed the presence of MT-ND1 DNA in the plasma of COVID-19, ICU-ARDS, as well as normal human plasma. Mitochondrial proteins such as MRPL, L2HGDH, ATP, CYB, CYTB, CYP, NDUF and others, were increased in COVID-19 and ICU-ARDS plasma. The apparent activity of the cytochrome components were tested alongside NHP by dot blotting on PVDF against a purified cytochrome c standard preparation for H2O2 dependent reaction with luminol as measured by enhanced chemiluminescence (ECL) that showed increased activity in COVID-19 and ICU-ARDS patients. Discussion The results from PCR, LC–ESI–MS/MS of tryptic peptides, and cytochrome ECL assays confirmed that mitochondrial components were present in the plasma, in agreement with the established central role of the mitochondria in SARS-COV-2 biology. The cytochrome activity assay showed that there was the equivalent of at least nanogram amounts of cytochrome(s) in the plasma sample that should be clearly detectable by LC–ESI–MS/MS. The release of the luminol oxidase activity from cells into plasma forms the basis of a simple and rapid test for the severity of cell damage and lung injury in COVID-19 infection and ICU-ARDS. Graphical Abstract

Cable bacteria are centimeter-long filamentous bacteria that conduct electrons via internal wires, thus coupling sulfide oxidation in deeper, anoxic sediment with oxygen reduction in surface sediment. This activity induces geochemical changes in the sediment, and other bacterial groups appear to benefit from the electrical connection to oxygen. Here, we report that diverse bacteria swim in a tight flock around the anoxic part of oxygen-respiring cable bacteria and disperse immediately when the connection to oxygen is disrupted (by cutting the cable bacteria with a laser). Raman microscopy shows that flocking bacteria are more oxidized when closer to the cable bacteria, but physical contact seems to be rare and brief, which suggests potential transfer of electrons via unidentified soluble intermediates. Metagenomic analysis indicates that most of the flocking bacteria appear to be aerobes, including organotrophs, sulfide oxidizers, and possibly iron oxidizers, which might transfer electrons to cable bacteria for respiration. The association and close interaction with such diverse partners might explain how oxygen via cable bacteria can affect microbial communities and processes far into anoxic environments.

The dominant sensory phenotype in patients with diabetic polyneuropathy and neuropathic pain is a loss of function. This raises questions as to which mechanisms underlie pain generation in the face of potentially reduced afferent input. One potential mechanism is spinal disinhibition, whereby a loss of spinal inhibition leads to increased ascending nociceptive drive due to amplification of, or a failure to suppress, incoming signals from the periphery. We aimed to explore whether a putative biomarker of spinal disinhibition, impaired rate-dependent depression of the Hoffmann reflex, is associated with a mechanistically appropriate and distinct pain phenotype in patients with painful diabetic neuropathy. In this cross-sectional study, 93 patients with diabetic neuropathy underwent testing of Hoffmann reflex rate-dependent depression and detailed clinical and sensory phenotyping, including quantitative sensory testing. Compared to neuropathic patients without pain, patients with painful diabetic neuropathy had impaired Hoffmann reflex rate-dependent depression at 1, 2 and 3 Hz (P ≤ 0.001). Patients with painful diabetic neuropathy exhibited an overall loss of function profile on quantitative sensory testing. However, within the painful diabetic neuropathy group, cluster analysis showed evidence of greater spinal disinhibition associated with greater mechanical pain sensitivity, relative heat hyperalgesia and higher ratings of spontaneous burning pain. These findings support spinal disinhibition as an important centrally mediated pain amplification mechanism in painful diabetic neuropathy. Furthermore, our analysis indicates an association between spinal disinhibition and a distinct phenotype, arguably akin to hyperpathia, with combined loss and relative gain of function leading to increasing nociceptive drive.

We describe changes in the comprehensiveness of services delivered by family physicians in 4 Canadian provinces (British Columbia, Manitoba, Ontario, Nova Scotia) during the periods 1999-2000 and 2017-2018 and explore if changes differ by years in practice. We measured comprehensiveness using province-wide billing data across 7 settings (home, long-term care, emergency department, hospital, obstetrics, surgical assistance, anesthesiology) and 7 service areas (pre/postnatal care, Papanicolaou [Pap] testing, mental health, substance use, cancer care, minor surgery, palliative home visits). Comprehensiveness declined in all provinces, with greater changes in number of service settings than service areas. Decreases were no greater among new-to-practice physicians.

Cable bacteria are centimeters-long filamentous bacteria that oxidize sulfide in anoxic sediment layers and reduce oxygen at the oxic-anoxic interface, connecting these reactions via electron transport. The ubiquitous cable bacteria have a major impact on sediment geochemistry and microbial communities. This includes diverse bacteria swimming around cable bacteria as dense flocks in the anoxic zone, where the cable bacteria act as chemotactic attractant. We hypothesized that flocking only appears when cable bacteria are highly abundant and active. We set out to discern the timing and drivers of flocking over 81 days in an enrichment culture of the freshwater cable bacterium Candidatus Electronema aureum GS by measuring sediment microprofiles of pH, oxygen, and electric potential as a proxy of cable bacteria activity. Cable bacterial relative abundance was quantified by 16S rRNA amplicon sequencing, and microscopy observations to determine presence of flocking. Flocking was always observed at some cable bacteria, irrespective of overall cable bacteria rRNA abundance, activity, or sediment pH. Diverse cell morphologies of flockers were observed, suggesting that flocking is not restricted to a specific, single bacterial associate. This, coupled with their consistent presence supports a common mechanism of interaction, likely interspecies electron transfer via electron shuttles. Flocking appears exclusively linked to the electron conducting activity of the individual cable bacteria.

Hemoglobinopathies are one of the most prevalent genetic disorders, affecting millions throughout the world. These are caused by pathogenic variants in genes that control the production of hemoglobin (Hb) subunits. As the number of known Hb variants has increased, it has become more challenging to obtain unambiguous results from routine chromatographic assays employed in the clinical laboratory. Top-down proteomic analysis of Hb by mass spectrometry is a definitive method to directly characterize the sequences of intact subunits. Here, we apply "chimeric ion loading" to characterize Hb β subunit variants. In this technique, product ions derived from complementary dissociation techniques are accumulated in a multipole storage device before delivery to a 21 T Fourier-transform ion cyclotron resonance mass spectrometer for simultaneous detection. To further improve the efficiency of identification of Hb variants and localization of the mutation site(s), we developed an R programming script, "Variants Identifier", to search top-down data against a database containing accurate intact mass differences and diagnostic ions from investigated Hb variants. A second R script, "PredictDiag", was developed and employed to determine relevant diagnostic ions for additional Hb variants with known sequences. These two R scripts were successfully applied to the identification of a Hb δ-β fusion protein and other Hb variants. The combination of chimeric ion loading and the above R scripts enables rapid and reliable interpretation of top-down mass spectrometry data, regardless of activation type, for Hb variant identification.

Use of smart directional antennas in handheld devices to generate a narrow beam in different directions for mmWave/TeraHertz communications present significant challenges. Devices using such antennas may have to scan several different directions in three-dimensional (3D) space to discover another user or an access point, a process that can result in problematic delays. Moreover, small movements of a user/device in the form of rotation and/or displacement may cause the discovered link to be lost. This paper proposes adaptive link discovery algorithms for devices in both infrastructure/ad hoc networks and evaluates their performance in terms of time-to-discovery. We show that one of the two proposed methods provides guaranteed discovery. We use an inertial measurement unit sensor to help intelligently rediscover a lost/degraded link. We propose sensor assisted link prediction methods for low-latency rediscovery in 3D space. We evaluate the effectiveness of our prediction-based rediscovery methods by testing them with real datasets representing various user/device 3D rotation patterns. We show that the smoothing based rediscovery can reach the prediction accuracy to 100% when two antenna sectors are searched, and it reduces the time-to-rediscovery by up to Sx (S times) as compared to the time-to-discovery, where S is the number of antenna sectors.

Age-associated neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and Alzheimer's disease (AD) are an unmet health need, with significant economic and societal implications, and an ever-increasing prevalence. Membrane lipid rafts (MLRs) are specialised plasma membrane microdomains that provide a platform for intracellular trafficking and signal transduction, particularly within neurons. Dysregulation of MLRs leads to disruption of neurotrophic signalling and excessive apoptosis which mirrors the final common pathway for neuronal death in ALS, PD and AD. Sphingomyelinase (SMase) and phospholipase (PL) enzymes process components of MLRs and therefore play central roles in MLR homeostasis and in neurotrophic signalling. We review the literature linking SMase and PL enzymes to ALS, AD and PD with particular attention to attractive therapeutic targets, where functional manipulation has been successful in preclinical studies. We propose that dysfunction of these enzymes is upstream in the pathogenesis of neurodegenerative diseases and to support this we provide new evidence that ALS risk genes are enriched with genes involved in ceramide metabolism (P=0.019, OR = 2.54, Fisher exact test). Ceramide is a product of SMase action upon sphingomyelin within MLRs, and it also has a role as a second messenger in intracellular signalling pathways important for neuronal survival. Genetic risk is necessarily upstream in a late age of onset disease such as ALS. We propose that manipulation of MLR structure and function should be a focus of future translational research seeking to ameliorate neurodegenerative disorders.

Influenza, an acute viral respiratory disease that is currently causing severe financial and resource strains worldwide. With the recent COVID-19 pandemic exceeding 153 million cases worldwide, there is a need for a low-cost and contactless surveillance system to detect symptomatic individuals, more so in counties with limited healthcare resources. As with many diseases, there are bio-clinical signals relating to the physical symptoms. The main objective of this study was to develop FluNet, a novel, proof-of-concept, low-cost and contactless device for the detection of high-risk individuals. The system passively conducts face detection in the longwave infrared domain with a precision rating of 0.9798 and mean intersection over union of 0.7386 while sequentially taking the temperature trend of faces with a thermal accuracy of ± 1 K. While in parallel determining if someone in audible proximity is coughing by using a custom deep convolutional neural network with a precision rating of 0.9519. In addition to presenting FluNet, two datasets have been constructed, one for face detection in the longwave infrared domain consisting of 250 images of 20 participants’ faces at various rotations and coverings, including face masks. The other for the real-time detection of cough patterns comprised of a sizeable dataset of 40,482 cough / not cough sounds, coupled with a new lightweight artificial neural network architecture for the classification of cough spectrograms. These findings could be helpful for future low-cost edge computing applications for influenza-like monitoring.

BACKGROUND Risk factors, virological parameters, and outcomes associated with HHV-6 viremia in high-risk donor CMV-seropositive and recipient CMV-seronegative (D+R-) liver transplant recipients in the current era are incompletely defined. METHODS The study population consisted of patients in the preemptive therapy (PET) arm of a randomized, controlled trial of PET versus valganciclovir prophylaxis for CMV prevention in D+R- liver transplant recipients. Weekly blood samples through 100 d in the PET group were tested for HHV-6 viremia using a real-time quantitative polymerase chain reaction. Assessments included virological characteristics and relationship with CMV, risk factors, and impact of HHV-6 viremia with outcomes through 12 mo posttransplant. RESULTS HHV-6 viremia at any level developed in 42% (40 of 96). Older patient age (P = 0.03), longer hospitalization (P = 0.015), and ICU stay at transplantation (P = 0.029) were significantly associated with high-grade viremia. Concurrent HHV-6 and CMV viremia was associated with earlier onset of HHV-6 viremia (P = 0.004), higher HHV-6 area under the curve (P = 0.043), and higher peak HHV-6 viral load (P = 0.006) versus HHV-6 viremia alone. High-grade viremia was independently associated with biopsy-proven rejection within 12 mo (P = 0.045) posttransplant. CONCLUSIONS Among D+R- liver transplant recipients receiving valganciclovir as PET, high-grade HHV-6 viremia was associated with increased age and critical illness in ICU at time of transplant and was independently associated with allograft rejection.

International audience; Recent advances in instrumentation for high-field Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) have enabled access to ∼70 »000 unique molecular formulas in broadband mass spectral characterization of unfractionated/whole asphaltenes. The results accumulated over a decade highlight the need for an asphaltene molecular model that acknowledges the coexistence of (1) monofunctional and polyfunctional species; (2) island and archipelago structural motifs; and (3) heteroatom-depleted/highly aromatic compounds, as well as atypical species with low aromaticity but increased heteroatom content. Collectively, results from FT-ICR MS, preparatory-scale separations (extrography/interfacial material), gel permeation chromatography, precipitation behavior in heptane:toluene, thermal decomposition, and aggregate microstructure by atomic force microscopy (among other techniques), suggest that the strong aggregation of asphaltenes results from the synergy between several intermolecular forces: π-stacking, hydrogen bonding, London forces, and acid/base interactions. This review presents general features of asphaltene molecular composition reported over the past five decades. We focus on mass spectrometry characterization and expose the reasons why early results supported the dominance of single-core motifs. Then, the discussion shifts to recent advances in instrumentation for high-field FT-ICR MS, which have enabled the detection of thousands of species in asphaltene samples, whose molecular composition and fragmentation behavior in ultrahigh vacuum agree with the coexistence of single-core and multicore structural motifs. Furthermore, evidence that highlights the limitations of commercially available/custom-built ion sources and selective ionization effects is presented. Consequently, the limitations require separations (e.g., chromatography, extrography) to gain more-comprehensive molecular-level insights into the composition of these complex organic mixtures. The final sections present evidence for the role of aggregation in selective ionization and suggest that advanced characterization by both thermal desorption/decomposition and liquid chromatography with online FT-ICR MS detection can be employed to mitigate the effects of aggregation and provide unique insights in molecular composition/structure.

Previous work has suggested a potential structural dependence for the formation of oil- and water-soluble photoproducts from the simulated solar irradiation of petroleum. Aromatic species in petrol...

The austral spring climate of 2020 was characterised by the occurrence of La Niña, which is the most predictable climate driver of Australian springtime rainfall. Consistent with this La Niña, the Bureau of Meteorology’s dynamical sub-seasonal to seasonal forecast system, ACCESS-S1, made highly confident predictions of wetter-than-normal conditions over central and eastern Australia for spring when initialised in July 2020 and thereafter. However, many areas of Australia received near average to severely below average rainfall, particularly during November. Possible causes of the deviation of rainfall from its historical response to La Niña and causes of the forecast error are explored with observational and reanalysis data for the period 1979–2020 and real-time forecasts of ACCESS-S1 initialised in July to November 2020. Several compounding factors were identified as key contributors to the drier-than-anticipated spring conditions. Although the ocean surface to the north of Australia was warmer than normal, which would have acted to promote rainfall over northern Australia, it was not as warm as expected from its historical relationship with La Niña and its long-term warming trend. Moreover, a negative phase of the Indian Ocean Dipole mode, which typically acts to increase spring rainfall in southern Australia, decayed earlier than normal in October. Finally, the Madden–Julian Oscillation activity over the equatorial Indian Ocean acted to suppress rainfall across northern and eastern Australia during November. While ACCESS-S1 accurately predicted the strength of La Niña over the Niño3.4 region, it over-predicted the ocean warming to the north of Australia and under-predicted the strength of the November MJO event, leading to an over-prediction of the Australian spring rainfall and especially the November-mean rainfall.

We assess the ability of the Bureau of Meteorology’s ACCESS-S1 dynamical forecast system to simulate and predict extreme fire weather over Australia during austral spring (SON) and summer (DJF) on subseasonal timescales. Specifically, we focus on the roles of the El Nino-Southern Oscillation (ENSO), Indian Ocean Dipole (IOD), Southern Annular Mode (SAM), Madden–Julian Oscillation (MJO), and two modes of persistent high-pressure in the Australian region characterised as (i) split-flow blocking highs and (ii) subtropical ridge Tasman highs (STRH). The observed likelihood of extreme fire weather increases over most of Australia in association with El Nino, the positive IOD, negative SAM and low split-flow blocking, in both seasons. These increases are generally largest in SON over the southeast. Notable increases in the likelihood of extreme fire weather also occur north of 30° S during low STRH activity, and over the southeast during MJO phase 3. Using retrospective forecasts at lead times of 2–3 weeks for the period 1990–2012, we show that ACCESS-S1 simulates reasonably well the observed modulation of extreme weekly-mean fire weather by each climate driver, however the simulated changes in probabilities are often weaker than those observed. Each climate driver plays an important role in providing predictive skill for regions where ACCESS-S1 captures a high likelihood of experiencing extreme fire weather conditions. The results of this study highlight windows of forecast opportunity during active climate driver phases that can be useful to regional users in fire management, emergency services, health, national park management, and the agriculture and energy sectors.

An invasive population of the coconut rhinoceros beetle (Oryctes rhinoceros; CRB) was discovered in Honiara, Guadalcanal, Solomon Islands in 2015. The beetle has caused severe damage to coconut palms in the outbreak area and its continued spread threatens the food security and livelihood of thousands of smallholder farmers in the region. Spread and abundance of the beetle were monitored using bucket traps baited with the aggregation pheromone, ethyl-4 methyloctanoate. Beetles were collected from traps approximately bi-weekly for two periods; one during 2017–18 and the other during 2019–2020. Trap catches showed that CRB was present throughout the whole survey region with significantly higher numbers of female CRB trapped than males. Results indicate a significant 1.5-fold increase in CRB trap catch numbers from 2017–2018 to 2019–2020 despite control efforts. The number of CRB adults trapped also varied between sites and months during both time periods but with no clear patterns. Removal of breeding sites along with strong local quarantine should remain the top priority of the local government to contain CRB expansion within Solomon Islands and beyond.

Radio frequency fingerprint identification (RFFI) is an emerging device authentication technique that relies on the intrinsic hardware characteristics of wireless devices. This paper designs a deep learning-based RFFI scheme for Long Range (LoRa) systems. Firstly, the instantaneous carrier frequency offset (CFO) is found to drift, which could result in misclassification and significantly compromise the stability of the deep learning-based RFFI system. CFO compensation is demonstrated to be effective mitigation. Secondly, three signal representations for deep learning-based RFFI are investigated in time, frequency, and time-frequency domains, namely in-phase and quadrature (IQ) samples, fast Fourier transform (FFT) results and spectrograms, respectively. For these signal representations, three deep learning models are implemented, i.e., multilayer perceptron (MLP), long short-term memory (LSTM) network and convolutional neural network (CNN), in order to explore an optimal framework. Finally, a hybrid classifier that can adjust the prediction of deep learning models with the estimated CFO is designed to further increase the classification accuracy. The CFO will not change dramatically over several continuous days, hence it can be used to correct predictions when the estimated CFO is much different from the reference one. Experimental evaluation is performed in real wireless environments involving 25 LoRa devices and a Universal Software Radio Peripheral (USRP) N210 platform. The spectrogram-CNN model is found to be optimal for classifying LoRa devices which can reach an accuracy of 96.40% with the least complexity and training time.

We assessed the ability of the Bureau of Meteorology’s ACCESS-S1 dynamical forecast system to simulate and predict high rainfall extremes for each season over Australia, especially focusing on the role of the Madden-Julian Oscillation (MJO). Using retrospective forecasts for the period 1990–2012, we show that ACCESS-S1 simulated the observed modulation of extreme weekly mean rainfall by each phase of the MJO reasonably well; however the simulated changes in probabilities tended to be weaker than those observed, especially across the far north during the austral summer season. The ability of the model to (i) simulate the observed modulation of extreme rainfall and (ii) predict the MJO to a lead time of four weeks, translated to enhanced forecast skill for predicting the occurrence of extreme weekly mean rainfall across much of Australia at times when the MJO was strong, compared to when the MJO was weak, during the austral spring and summer seasons in weeks 2 and 3. However, skill reduced across the central far north during the summer when the MJO was strong, suggesting the model is not good at depicting the MJO’s convective phases as it protrudes southward over northern Australia. During autumn and winter, there was little indication of changes in forecast skill, depending on the strength of the MJO. The results of this study will be useful for regional applications when the MJO is forecast to be strong during spring and summer, particularly where the swing in probability of extreme rainfall is large for specific phases of the MJO.

Many studies in mice have demonstrated that cardiac-specific innate immune signaling pathways can be reprogrammed to modulate inflammation in response to myocardial injury and improve outcomes. While the echocardiography standard parameters of left ventricular (LV) ejection fraction, fractional shortening, and end-diastolic diameter, and others, are used to assess cardiac function, their dependency on loading conditions somewhat limit their utility in completely reflecting the contractile function and global cardiovascular efficiency of the heart. A true measure of global cardiovascular efficiency should include of the interaction between the ventricle and the aorta (ventriculo-vascular coupling, VVC) as well as measures of aortic impedance and pulse wave velocity. We measured cardiac Doppler velocities, blood pressures, along with VVC, aortic impedance, and pulse wave velocity to evaluate global cardiac function in mouse model of cardiac-restricted low levels TRAF2 overexpression that conferred cytoprotection in the heart. While previous studies reported that response to myocardial infraction and reperfusion was improved in the TRAF2 overexpressed mice, we found that TRAF2 mice had significantly lower cardiac systolic velocities and accelerations, diastolic atrial velocity, lower aortic pressures and rate-pressure product, lower LV contractility and relaxation, and lower stroke work when compared to littermate control mice. Also, we found significantly longer aortic ejection time, isovolumic contraction and relaxation times, and significantly higher mitral early/atrial ratio, myocardial performance index, and ventricular vascular coupling in the TRAF2 overexpression mice compared to their littermate controls. We found no significant differences in the aortic impedance and pulse wave velocity. While the reported tolerance to ischemic insults in TRAF2 overexpression mice may suggest enhanced cardiac reserve, our results indicate a diminished cardiac function in these mice.

We describe the characterisation of a variable number tandem repeat (VNTR) domain within intron 1 of the amyotrophic lateral sclerosis (ALS) risk gene CFAP410 (Cilia and flagella associated protein 410) (previously known as C21orf2), providing insight into how this domain could support differential gene expression and thus be a modulator of ALS progression or risk. We demonstrated the VNTR was functional in a reporter gene assay in the HEK293 cell line, exhibiting both the properties of an activator domain and a transcriptional start site, and that the differential expression was directed by distinct repeat number in the VNTR. These properties embedded in the VNTR demonstrated the potential for this VNTR to modulate CFAP410 expression. We extrapolated these findings in silico by utilisation of tagging SNPs for the two most common VNTR alleles to establish a correlation with endogenous gene expression. Consistent with in vitro data, CFAP410 isoform expression was found to be variable in the brain. Furthermore, although the number of matched controls was low, there was evidence for one specific isoform being correlated with lower expression in those with ALS. To address if the genotype of the VNTR was associated with ALS risk, we characterised the variation of the CFAP410 VNTR in ALS cases and matched controls by PCR analysis of the VNTR length, defining eight alleles of the VNTR. No significant difference was observed between cases and controls, we noted, however, the cohort was unlikely to contain sufficient power to enable any firm conclusion to be drawn from this analysis. This data demonstrated that the VNTR domain has the potential to modulate CFAP410 expression as a regulatory element that could play a role in its tissue-specific and stimulus-inducible regulation that could impact the mechanism by which CFAP410 is involved in ALS.

The sediments under the Oxygen Minimum Zone of the Eastern Boundary Current System (EBCS) along Central-South Peru and North-Central Chile, known as Humboldt Sulfuretum (HS), is an organic-matter-rich benthic habitat, where bacteria process a variety of sulfur compounds under low dissolved-oxygen concentrations, and high sulfide and nitrate levels. This study addressed the structure, diversity and spatial distribution patterns of the HS bacterial community along Northern and South-Central Chile using 16S rRNA gene amplicon sequencing. The results show that during the field study period, the community was dominated by sulfur-associated bacteria. Indeed, the most abundant phylum was Desulfobacterota, while Sva0081 sedimentary group, of the family Desulfosarcinaceae (the most abundant family), which includes sulfate-reducer and H2 scavenger bacteria, was the most abundant genus. Furthermore, a spatial pattern was unveiled along the study area to which the family Desulfobulbaceae contributed the most to the spatial variance, which encompasses 42 uncharacterized amplicon sequence variants (ASVs), three assigned to Ca. Electrothrix and two to Desulfobulbus. Moreover, a very high microdiversity was found, since only 3.7% of the ASVs were shared among localities, reflecting a highly diverse and mature community.