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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.

Impaired rate-dependent depression of the Hoffman reflex (HRDD) is a potential biomarker of impaired spinal inhibition in patients with painful diabetic neuropathy. However, the optimum stimulus-response parameters that identify patients with spinal disinhibition are currently unknown. We systematically compared HRDD, performed using trains of 10 stimuli at five stimulation frequencies (0.3, 0.5, 1, 2 and 3 Hz), in 42 subjects with painful and 62 subjects with painless diabetic neuropathy with comparable neuropathy severity, and 34 healthy controls. HRDD was calculated using individual and mean responses compared to the initial response. At stimulation frequencies of 1, 2 and 3 Hz, HRDD was significantly impaired in patients with painful diabetic neuropathy compared to patients with painless diabetic neuropathy for all parameters and for most parameters when compared to healthy controls. HRDD was significantly enhanced in patients with painless diabetic neuropathy compared to controls for responses towards the end of the 1 Hz stimulation train. Receiver operating characteristic curve analysis in patients with and without pain showed that the area under the curve was greatest for response averages of stimuli 2-4 and 2-5 at 1 Hz, AUC = 0.84 (95%CI 0.76-0.92). Trains of 5 stimuli delivered at 1 Hz can segregate patients with painful diabetic neuropathy and spinal disinhibition, whereas longer stimulus trains are required to segregate patients with painless diabetic neuropathy and enhanced spinal inhibition.

Local meteorology over the Great Barrier Reef (GBR) can significantly influence ocean temperatures, which in turn impacts coral ecosystems. While El Niño–Southern Oscillation (ENSO) provides insight into the expected synoptic states, it lacks details of anticipated sub‐seasonal weather variability at local scales. This study explores the influence of the Madden‐Julian oscillation (MJO) on Australian tropical climate, both independently and in combination with ENSO, focusing on GBR impacts. We find that during El Niño periods, including the summer of 2009/10, faster propagating MJO patterns can disrupt background warm, dry conditions, and potentially provide cooling relief via increased cloud cover and stronger winds. In La Niña periods, such as the summer of 2021/22, the MJO tends to be prevented from passing the Maritime continent, forcing it to remain in a standing pattern in the Indian Ocean. This leads to decreased cloud cover and weaker winds over the GBR, generating warm ocean anomalies. Plain Language Summary: Bleaching is likely when tropical corals are exposed to ocean temperatures above a threshold for a prolonged period. In austral summer, tropical weather over the Great Barrier Reef (GBR) can vary from hot and sunny to stormy with rain and strong winds. During El Niño, summer weather over the GBR is typically warm, still, and dry, increasing the likelihood of coral bleaching due to increased exposure to solar radiation and decreased mixing. During La Niña, tropical storms, with cooling effects through increased rainfall and cloud cover, are more typical. The Madden‐Julian oscillation (MJO) is an eastward moving storm pattern near the equator that can also influence the background climate over the GBR. We find that the MJO can significantly influence the weather variability over the GBR, altering the expected states of El Niño and La Niña periods. Key Points: Composite maps show how the Madden‐Julian oscillation (MJO) can change meteorological patterns on the Great Barrier ReefCluster analysis is used to show the types of MJO propagation patterns likely to occur during El Niño and La Niña periodsOcean temperature variability is discussed with El Niño/La Niña phases as the background states and the MJO as a sub‐seasonal modulator [ABSTRACT FROM AUTHOR]

PURPOSE OF REVIEW:Neuropathic pain may arise from multiple mechanisms and locations. Efficacy of current treatments for painful diabetic neuropathy is limited to an unpredictable subset of patients, possibly reflecting diversity of pain generator mechanisms, and there is a lack of targeted treatments for individual patients. This review summarizes preclinical evidence supporting a role for spinal disinhibition in painful diabetic neuropathy, the physiology and pharmacology of rate-dependent depression (RDD) of the spinal H-reflex and the translational potential of using RDD as a biomarker of spinally mediated pain. RECENT FINDINGS:Impaired RDD occurs in animal models of diabetes and was also detected in diabetic patients with painful vs painless neuropathy. RDD status can be determined using standard neurophysiological equipment. Loss of RDD may provide a clinical biomarker of spinal disinhibition, thereby enabling a personalized medicine approach to selection of current treatment options and enrichment of future clinical trial populations.

Impaired rate-dependent depression (RDD) of the Hoffman reflex is associated with reduced dorsal spinal cord potassium chloride cotransporter expression and impaired spinal γ-aminobutyric acid type A receptor function, indicative of spinal inhibitory dysfunction. We have investigated the pathogenesis of impaired RDD in diabetic rodents exhibiting features of painful neuropathy and the translational potential of this marker of spinal inhibitory dysfunction in human painful diabetic neuropathy. Impaired RDD and allodynia were present in type 1 and type 2 diabetic rats but not in rats with type 1 diabetes receiving insulin supplementation that did not restore normoglycemia. Impaired RDD in diabetic rats was rapidly normalized by spinal delivery of duloxetine acting via 5-hydroxytryptamine type 2A receptors and temporally coincident with the alleviation of allodynia. Deficits in RDD and corneal nerve density were demonstrated in patients with painful diabetic neuropathy compared with healthy control subjects and patients with painless diabetic neuropathy. Spinal inhibitory dysfunction and peripheral small fiber pathology may contribute to the clinical phenotype in painful diabetic neuropathy. Deficits in RDD may help identify patients with spinally mediated painful diabetic neuropathy who may respond optimally to therapies such as duloxetine.

Aims: We investigate the associations between major Australian climate drivers and extreme weekly fire danger throughout the year. Methods: We use a composite-based approach, relating the probability of top-decile observed potential fire intensity to the positive and negative modes of the El Niño Southern Oscillation, Indian Ocean Dipole, Madden–Julian Oscillation, Southern Annular Mode, split-flow blocking and Subtropical Ridge Tasman Highs, both concurrently and at a variety of lag times. Key results: The chance of extreme fire danger increases over broad regions of the continent in response to El Niño and positive Indian Ocean Dipole events, the negative mode of the Southern Annular Mode, split-flow Blocking Index and Subtropical Ridge Tasman High, and Madden–Julian Oscillation phases 5, 6, 2 and 8 in Austral summer, autumn, winter and spring respectively. These relationships exist not only concurrently, but also when a climate event occurs up to 6 months ahead of the season of interest. Conclusions: These findings highlight the importance of considering the influence of diverse climate drivers, at a range of temporal lag periods, in understanding and predicting extreme fire danger. Implications: The results of this study may aid in the development of effective fire management strategies and decision-making processes to mitigate the impacts of fire events in Australia. This paper explores the relationships between the major forces influencing Australian weather and climate, and the chance of severe fire seasons. The findings could be valuable in decision making and preparation for upcoming fire seasons to avoid more seasons with devastating outcomes such as the 2019–2020 Black Summer. This article belongs to the Collection Fire and Climate. [ABSTRACT FROM AUTHOR]

Extended warning of above‐average and extreme precipitation is valuable to a wide range of stakeholders. However, the sporadic nature of precipitation makes it difficult to forecast skilfully beyond one week. Subseasonal forecasting is a growing area of science that aims to predict average weather conditions multiple weeks in advance using dynamical models. Building on recent work in this area, we test the hypothesis that using large‐scale horizontal moisture transport as a predictor for precipitation may increase the forecast skill of the above‐median and high‐precipitation weeks on subseasonal time‐scales. We analysed retrospective forecast (hindcast) sets from the Australian Bureau of Meteorology's latest operational subseasonal‐to‐seasonal forecasting model, ACCESS‐S2, to compare the forecast skill of precipitation using integrated water vapour transport (IVT) as a proxy, compared to using precipitation forecasts directly. We show that ACCESS‐S2 precipitation generally produces more skilful forecasts, except over some regions where IVT could be a useful additional diagnostic for warning of heavy precipitation events. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "A Statistical Forecasting Model for Extremes of the Fire Behaviour Index in Australia." The correction addresses errors in Figure 5 and Table 5 of the original publication. The corrected figure shows the forecast probability of extreme fire behavior index (FBI) using three ensemble members at two- and three-week hindcast lead times. The corrected table compares the accuracy, probability of detection, and false alarm ratio of the dynamical and statistical models. The correction emphasizes the importance of using multiple forecasting methods for fire danger forecasts. The scientific conclusions of the article remain unaffected. [Extracted from the article]