Elevated Southern Hemisphere moisture availability during glacial periods.

Late Pleistocene ice-age climates are routinely characterized as having imposed moisture stress on low- to mid-latitude ecosystems1-5. This idea is largely based on fossil pollen evidence for widespread, low-biomass glacial vegetation, interpreted as indicating climatic dryness6. However, woody plant growth is inhibited under low atmospheric CO2 (refs. 7,8), so understanding glacial environments requires the development of new palaeoclimate indicators that are independent of vegetation9. Here we show that, contrary to expectations, during the past 350 kyr, peaks in southern Australian climatic moisture availability were largely confined to glacial periods, including the Last Glacial Maximum, whereas warm interglacials were relatively dry. By measuring the timing of speleothem growth in the Southern Hemisphere subtropics, which today has a predominantly negative annual moisture balance, we developed a record of climatic moisture availability that is independent of vegetation and extends through multiple glacial-interglacial cycles. Our results demonstrate that a cool-moist response is consistent across the austral subtropics and, in part, may result from reduced evaporation under cool glacial temperatures. Insofar as cold glacial environments in the Southern Hemisphere subtropics have been portrayed as uniformly arid3,10,11, our findings suggest that their characterization as evolutionary or physiological obstacles to movement and expansion of animal, plant and, potentially, human populations10 should be reconsidered.

Metabolic determinants of lupus pathogenesis.

The metabolism of healthy murine and more recently human immune cells has been investigated with an increasing amount of details. These studies have revealed the challenges presented by immune cells to respond rapidly to a wide variety of triggers by adjusting the amount, type, and utilization of the nutrients they import. A concept has emerged that cellular metabolic programs regulate the size of the immune response and the plasticity of its effector functions. This has generated a lot of enthusiasm with the prediction that cellular metabolism could be manipulated to either enhance or limit an immune response. In support of this hypothesis, studies in animal models as well as human subjects have shown that the dysregulation of the immune system in autoimmune diseases is associated with a skewing of the immunometabolic programs. These studies have been mostly conducted on autoimmune CD4+ T cells, with the metabolism of other immune cells in autoimmune settings still being understudied. Here we discuss systemic metabolism as well as cellular immunometabolism as novel tools to decipher fundamental mechanisms of autoimmunity. We review the contribution of each major metabolic pathway to autoimmune diseases, with a focus on systemic lupus erythematosus (SLE), with the relevant translational opportunities, existing or predicted from results obtained with healthy immune cells. Finally, we review how targeting metabolic programs may present novel therapeutic venues.

The retina-specific basigin isoform does not induce IL-6 expression in mouse monocytes.

Purpose: Basigin gene products are positioned on adjacent cell types in the neural retina and are thought to compose a lactate metabolon important for photoreceptor cell function. The Ig0 domain of basigin isoform 1 (basigin-1) is highly conserved throughout evolution, which suggests a conserved function. It has been suggested that the Ig0 domain has proinflammatory properties, and it is hypothesized to interact with basigin isoform 2 (basigin-2) for cell adhesion and lactate metabolon formation. Therefore, the purpose of the present study was to determine whether the Ig0 domain of basigin-1 binds to basigin-2 and whether the region of the domain used for binding is also used to stimulate interleukin-6 (IL-6) expression. Methods: Binding was assessed using recombinant proteins corresponding to the Ig0 domain of basigin-1 and endogenously expressed basigin-2 from mouse neural retina and brain protein lysates. The proinflammatory properties of the Ig0 domain were analyzed with exposure of the recombinant proteins to the mouse monocyte RAW 264.7 cell line and subsequent measurement of the IL-6 concentration in the culture medium via enzyme-linked immunosorbent assay (ELISA). Results: The data indicate that the Ig0 domain interacts with basigin-2 through a region within the amino half of the domain and that the Ig0 domain does not stimulate the expression of IL-6 in mouse cells in vitro. Conclusions: The Ig0 domain of basigin-1 binds to basigin-2 in vitro. In addition, contrary to previous reports, there was no evidence that the Ig0 domain potentiates IL-6 expression in a mouse monocyte cell line in vitro. However, it is possible that the Ig0 domain stimulates the expression of proinflammatory cytokines other than IL-6, or that the potential involvement of the Ig0 domain of basigin-1 in the acute inflammatory response is dependent on species.

Multiplexed Prostate Cancer Companion Diagnostic Devices.

Prostate cancer (PCa) remains one of the most prominent forms of cancer for men. Since the early 1990s, Prostate-Specific Antigen (PSA) has been a commonly recognized PCa-associated protein biomarker. However, PSA testing has been shown to lack in specificity and sensitivity when needed to diagnose, monitor and/or treat PCa patients successfully. One enhancement could include the simultaneous detection of multiple PCa-associated protein biomarkers alongside PSA, also known as multiplexing. If conventional methods such as the enzyme-linked immunosorbent assay (ELISA) are used, multiplexed detection of such protein biomarkers can result in an increase in the required sample volume, in the complexity of the analytical procedures, and in adding to the cost. Using companion diagnostic devices such as biosensors, which can be portable and cost-effective with multiplexing capacities, may address these limitations. This review explores recent research for multiplexed PCa protein biomarker detection using optical and electrochemical biosensor platforms. Some of the novel and potential serum-based PCa protein biomarkers will be discussed in this review. In addition, this review discusses the importance of converting research protocols into multiplex point-of-care testing (xPOCT) devices to be used in near-patient settings, providing a more personalized approach to PCa patients' diagnostic, surveillance and treatment management.

More extreme swings of the South Pacific convergence zone due to greenhouse warming.

The South Pacific convergence zone (SPCZ) is the Southern Hemisphere's most expansive and persistent rain band, extending from the equatorial western Pacific Ocean southeastward towards French Polynesia. Owing to its strong rainfall gradient, a small displacement in the position of the SPCZ causes drastic changes to hydroclimatic conditions and the frequency of extreme weather events--such as droughts, floods and tropical cyclones--experienced by vulnerable island countries in the region. The SPCZ position varies from its climatological mean location with the El Niño/Southern Oscillation (ENSO), moving a few degrees northward during moderate El Niño events and southward during La Niña events. During strong El Niño events, however, the SPCZ undergoes an extreme swing--by up to ten degrees of latitude toward the Equator--and collapses to a more zonally oriented structure with commensurately severe weather impacts. Understanding changes in the characteristics of the SPCZ in a changing climate is therefore of broad scientific and socioeconomic interest. Here we present climate modelling evidence for a near doubling in the occurrences of zonal SPCZ events between the periods 1891-1990 and 1991-2090 in response to greenhouse warming, even in the absence of a consensus on how ENSO will change. We estimate the increase in zonal SPCZ events from an aggregation of the climate models in the Coupled Model Intercomparison Project phases 3 and 5 (CMIP3 and CMIP5) multi-model database that are able to simulate such events. The change is caused by a projected enhanced equatorial warming in the Pacific and may lead to more frequent occurrences of extreme events across the Pacific island nations most affected by zonal SPCZ events.

Dietary tryptophan and genetic susceptibility expand gut microbiota that promote systemic autoimmune activation.

Tryptophan modulates disease activity and the composition of microbiota in the B6.Sle1.Sle2.Sle3 (TC) mouse model of lupus. To directly test the effect of tryptophan on the gut microbiome, we transplanted fecal samples from TC and B6 control mice into germ-free or antibiotic-treated non-autoimmune B6 mice that were fed with a high or low tryptophan diet. The recipient mice with TC microbiota and high tryptophan diet had higher levels of immune activation, autoantibody production and intestinal inflammation. A bloom of Ruminococcus gnavus (Rg), a bacterium associated with disease flares in lupus patients, only emerged in the recipients of TC microbiota fed with high tryptophan. Rg depletion in TC mice decreased autoantibody production and increased the frequency of regulatory T cells. Conversely, TC mice colonized with Rg showed higher autoimmune activation. Overall, these results suggest that the interplay of genetic and tryptophan can influence the pathogenesis of lupus through the gut microbiota.

A randomized maternal evaluation of epinephrine autoinjection devices.

BACKGROUND: Intramuscular epinephrine (adrenaline) is the first-line therapy for anaphylaxis and prompt administration improves outcome. In 2011, two epinephrine autoinjectors existed in the United Kingdom, differing in their users' administration method: EpiPen(®) and Anapen(®) . We routinely train all families who receive these devices. AIM: To evaluate: Maternal competence in using epinephrine autoinjectors following our standard anaphylaxis training package. Which device mothers found easier to use. METHODS: Mothers with no previous epinephrine autoinjector experience were approached to participate. One clinician provided a standardized demonstration on using a randomly assigned autoinjector device. She immediately evaluated the mothers' performance using ten predetermined criteria. Four criteria were device specific and six were common criteria to both devices. RESULTS: One hundred mothers participated: 50 EpiPen(®) and 50 Anapen(®) . A substantial proportion of mothers (15% overall) were not able to successfully 'fire' these training devices: Anapen(®) 4% and EpiPen(®) 26% (OR 8.43, p = 0.005). Only 22% of mothers overall were able to perform all ten procedures completely successfully: Anapen(®) 32% and EpiPen(®) 12%. Chi-squared analysis showed a significantly higher proportion of mothers correctly performing all Anapen(®) specific procedures than EpiPen(®) (OR 14.24, p < 0.0001). CONCLUSION: It is concerning that 15% of mothers overall could not 'fire' these devices correctly despite a one-to-one demonstration, identifying a need for more user friendly devices and training. Mothers found the Anapen(®) device significantly easier to use, which may have implications for future prescribing. Evaluation of the next generation of autoinjectors and their training packages needs to be performed as important practical differences may be found.

TLR7/TLR8 activation and susceptibility genes synergize to breach gut barrier in a mouse model of lupus.

Background: Mounting evidence suggests that increased gut permeability, or leaky gut, and the resulting translocation of pathobionts or their metabolites contributes to the pathogenesis of Systemic Lupus Erythematosus. However, the mechanisms underlying the induction of gut leakage remain unclear. In this study, we examined the effect of a treatment with a TLR7/8 agonist in the B6.Sle1.Sle2.Sle3 triple congenic (TC) mouse, a spontaneous mouse model of lupus without gut leakage. Materials and methods: Lupus-prone mice (TC), TC.Rag1-/- mice that lack B and T cells, and congenic B6 healthy controls were treated with R848. Gut barrier integrity was assessed by measuring FITC-dextran in the serum following oral gavage. Claudin-1 and PECAM1 expression as well as the extent of CD45+ immune cells, B220+ B cells, CD3+ T cells and CD11b+ myeloid cells were measured in the ileum by immunofluorescence. NKp46+ cells were measured in the ileum and colon by immunofluorescence. Immune cells in the ileum were also analyzed by flow cytometry. Results: R848 decreased gut barrier integrity in TC but not in congenic control B6 mice. Immunofluorescence staining of the ileum showed a reduced expression of the tight junction protein Claudin-1, endothelial cell tight junction PECAM1, as well as an increased infiltration of immune cells, including B cells and CD11b+ cells, in R848-treated TC as compared to untreated control mice. However, NKp46+ cells which play critical role in maintaining gut barrier integrity, had a lower frequency in treated TC mice. Flow cytometry showed an increased frequency of plasma cells, dendritic cells and macrophages along with a decreased frequency of NK cells in R848 treated TC mice lamina propria. In addition, we showed that the R848 treatment did not induce gut leakage in TC.Rag1-/- mice that lack mature T and B cells. Conclusions: These results demonstrate that TLR7/8 activation induces a leaky gut in lupus-prone mice, which is mediated by adaptive immune responses. TLR7/8 activation is however not sufficient to breach gut barrier integrity in non-autoimmune mice.

Pharmacologic inhibition of glycolysis prevents the development of lupus by altering the gut microbiome in mice.

Gut dysbiosis has been associated with lupus pathogenesis, and fecal microbiota transfers (FMT) from lupus-prone mice shown to induce autoimmune activation into healthy mice. The immune cells of lupus patients exhibit an increased glucose metabolism and treatments with 2-deoxy-D-glucose (2DG), a glycolysis inhibitor, are therapeutic in lupus-prone mice. Here, we showed in two models of lupus with different etiologies that 2DG altered the composition of the fecal microbiome and associated metabolites. In both models, FMT from 2DG-treated mice protected lupus-prone mice of the same strain from the development of glomerulonephritis, reduced autoantibody production as well as the activation of CD4+ T cells and myeloid cells as compared to FMT from control mice. Thus, we demonstrated that the protective effect of glucose inhibition in lupus is transferable through the gut microbiota, directly linking alterations in immunometabolism to gut dysbiosis in the hosts.

Redox Homeostasis Involvement in the Pharmacological Effects of Metformin in Systemic Lupus Erythematosus.

Significance: Metformin has been proposed as a treatment for systemic lupus erythematosus (SLE). The primary target of metformin, the electron transport chain complex I in the mitochondria, is associated with redox homeostasis in immune cells, which plays a critical role in the pathogenesis of autoimmune diseases. This review addresses the evidence and knowledge gaps on whether a beneficial effect of metformin in lupus may be due to a restoration of a balanced redox state. Recent Advances: Clinical trials in SLE patients with mild-to-moderate disease activity and preclinical studies in mice have provided encouraging results for metformin. The mechanism by which this therapeutic effect was achieved is largely unknown. Metformin regulates redox homeostasis in a context-specific manner. Multiple cell types contribute to SLE, with evidence of increased mitochondrial oxidative stress in T cells and neutrophils. Critical Issues: The major knowledge gaps are whether the efficacy of metformin is linked to a restored redox homeostasis in the immune system, and if it does, in which cell types it occurs? We also need to know which patients may have a better response to metformin, and whether it corresponds to a specific mechanism? Finally, the identification of biomarkers to predict treatment outcomes would be of great value. Future Directions: Mechanistic studies must address the context-dependent pharmacological effects of metformin. Multiple cell types as well as a complex disease etiology should be considered. These studies must integrate the rapid advances made in understanding how metabolic programs direct the effector functions of immune cells. Antioxid. Redox Signal. 36, 462-479.

Microbiota-mediated skewing of tryptophan catabolism modulates CD4+ T cells in lupus-prone mice.

A skewed tryptophan metabolism has been reported in patients with lupus. Here, we investigated the mechanisms by which it occurs in lupus-susceptible mice, and how tryptophan metabolites exacerbate T cell activation. Metabolomic analyses demonstrated that tryptophan is differentially catabolized in lupus mice compared to controls and that the microbiota played a role in this skewing. There was no evidence for differential expression of tryptophan catabolic enzymes in lupus mice, further supporting a major contribution of the microbiota to skewing. However, isolated lupus T cells processed tryptophan differently, suggesting a contribution of T cell intrinsic factors. Functionally, tryptophan and its microbial product tryptamine increased T cell metabolism and mTOR activation, while kynurenine promoted interferon gamma production, all of which have been associated with lupus. These results showed that a combination of microbial and T cell intrinsic factors promotes the production of tryptophan metabolites that enhance inflammatory phenotypes in lupus T cells.

Intranasal Carnosine Mitigates α-Synuclein Pathology and Motor Dysfunction in the Thy1-aSyn Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) is a debilitating neurodegenerative disorder. Early symptoms include motor dysfunction and impaired olfaction. Toxic aggregation of α-synuclein (aSyn) in the olfactory bulb (OB) and substantia nigra pars compacta (SNpc) is a hallmark of PD neuropathology. Intranasal (IN) carnosine (2 mg/d for 8 weeks) was previously demonstrated to improve motor behavior and mitochondrial function in Thy1-aSyn mice, a model of PD. The present studies evaluated the efficacy of IN carnosine at a higher dose in slowing progression of motor deficits and aSyn accumulation in Thy1-aSyn mice. After baseline neurobehavioral assessments, IN carnosine was administered (0.0, 2.0, or 4.0 mg/day) to wild-type and Thy1-aSyn mice for 8 weeks. Olfactory and motor behavioral measurements were repeated prior to end point tissue collection. Brain sections were immunostained for aSyn and tyrosine hydroxylase (TH). Immunopositive cells were counted using design-based stereology in the SNpc and OB mitral cell layer (MCL). Behavioral assessments revealed a dose-dependent improvement in motor function with increasing carnosine dose. Thy1-aSyn mice treated with 2.0 or 4.0 mg/d IN carnosine exhibited fewer aSyn-positive (aSyn(+)) cell bodies in the SNpc compared to vehicle-treated mice. Moreover, the number of aSyn(+) cell bodies in carnosine-treated Thy1-aSyn mice was reduced to vehicle-treated wild-type levels in the SNpc. Carnosine treatment did not affect the number of aSyn(+) cell bodies in the OB-MCL or the number of TH(+) cells in the SNpc. In summary, intranasal carnosine treatment decreased aSyn accumulation in the SNpc, which may underlie its mitigation of motor deficits in the Thy1-aSyn mice.

Influence of the 2015-2016 El Niño on the record-breaking mangrove dieback along northern Australia coast.

This study investigates the underlying climate processes behind the largest recorded mangrove dieback event along the Gulf of Carpentaria coast in northern Australia in late 2015. Using satellite-derived fractional canopy cover (FCC), variation of the mangrove canopies during recent decades are studied, including a severe dieback during 2015-2016. The relationship between mangrove FCC and climate conditions is examined with a focus on the possible role of the 2015-2016 El Niño in altering favorable conditions sustaining the mangroves. The mangrove FCC is shown to be coherent with the low-frequency component of sea level height (SLH) variation related to the El Niño Southern Oscillation (ENSO) cycle in the equatorial Pacific. The SLH drop associated with the 2015-2016 El Niño is identified to be the crucial factor leading to the dieback event. A stronger SLH drop occurred during austral autumn and winter, when the SLH anomalies were about 12% stronger than the previous very strong El Niño events. The persistent SLH drop occurred in the dry season of the year when SLH was seasonally at its lowest, so potentially exposed the mangroves to unprecedented hostile conditions. The influence of other key climate factors is also discussed, and a multiple linear regression model is developed to understand the combined role of the important climate variables on the mangrove FCC variation.

Lupus susceptibility gene Esrrg modulates regulatory T cells through mitochondrial metabolism.

Estrogen-related receptor γ (Esrrg) is a murine lupus susceptibility gene associated with T cell activation. Here, we report that Esrrg controls Tregs through mitochondria homeostasis. Esrrg deficiency impaired the maintenance and function of Tregs, leading to global T cell activation and autoimmunity in aged mice. Further, Esrrg-deficient Tregs presented an impaired differentiation into follicular Tregs that enhanced follicular helper T cells' responses. Mechanistically, Esrrg-deficient Tregs presented with dysregulated mitochondria with decreased oxygen consumption as well as ATP and NAD+ production. In addition, Esrrg-deficient Tregs exhibited decreased phosphatidylinositol and TGF-ß signaling pathways and increased mTOR complex 1 activation. We found that the expression of human ESRRG, which is high in Tregs, was lower in CD4+ T cells from patients with lupus than in healthy controls. Finally, knocking down ESRRG in Jurkat T cells decreased their metabolism. Together, our results reveal a critical role of Esrrg in the maintenance and metabolism of Tregs, which may provide a genetic link between lupus pathogenesis and mitochondrial dysfunction in T cells.

Intestinal Dysbiosis and Tryptophan Metabolism in Autoimmunity.

The development of autoimmunity involves complex interactions between genetics and environmental triggers. The gut microbiota is an important environmental constituent that can heavily influence both local and systemic immune reactivity through distinct mechanisms. It is therefore a relevant environmental trigger or amplifier to consider in autoimmunity. This review will examine recent evidence for an association between intestinal dysbiosis and autoimmune diseases, and the mechanisms by which the gut microbiota may contribute to autoimmune activation. We will specifically focus on recent studies connecting tryptophan metabolism to autoimmune disease pathogenesis and discuss evidence for a microbial origin. This will be discussed in the context of our current understanding of how tryptophan metabolites regulate immune responses, and how it may, or may not, be applicable to autoimmunity.

Supplemental taurine during adolescence and early adulthood has sex-specific effects on cognition, behavior and neurotransmitter levels in C57BL/6J mice dependent on exposure window.

The mammalian brain goes through final maturation during late adolescence and early adulthood with sex differences in timing. The key cellular processes, including changes in neurotransmitter receptor density and synaptic pruning, make this age uniquely vulnerable to neurotoxic insults. Teenagers and young adults are the major consumers of energy drinks, which contain high levels of taurine and caffeine. Taurine is one of the most abundant amino acids in the central nervous system, but the effects of supplemental taurine consumption during adolescence has not been well studied. We conducted an initial short-term exposure study with 0.12% taurine in drinking water and a long-term exposure dose-response study using 0.06 and 0.12% taurine in male and female C57BL/6J mice. We examined a broad range of cognitive functions and behaviors and measured neurotransmitter levels. We found no significant differences in anxiety, open field locomotor activity, or sensorimotor gating. However, we found impairments in novel object recognition and sex differences in Morris water maze. When taurine treatment stopped before behavioral experiments began, male mice had significant impairments in spatial learning and memory. In the dose-response study when taurine treatment continued throughout behavioral experiments, females had significant impairments. We also found sex differences in neurotransmitter levels with females having higher levels of glutamate, DOPAC and 5-HIAA. We conclude that both females and males are at risk from excess taurine consumption during final brain maturation.

T cells expressing the lupus susceptibility allele Pbx1d enhance autoimmunity and atherosclerosis in dyslipidemic mice.

Patients with systemic lupus erythematosus (SLE) present a high incidence of atherosclerosis, which contributes significantly to morbidity and mortality in this autoimmune disease. An impaired balance between regulatory (Treg) and follicular helper (Tfh) CD4+ T cells is shared by both diseases. However, whether there are common mechanisms of CD4+ T cell dysregulation between SLE and atherosclerosis remains unclear. Pre-B cell leukemia transcription factor 1 isoform d (Pbx1d) is a lupus susceptibility gene that regulates Tfh cell expansion and Treg cell homeostasis. Here, we investigated the role of T cells overexpressing Pbx1d in low-density lipoprotein receptor-deficient (Ldlr-/-) mice fed with a high-fat diet, an experimental model for atherosclerosis. Pbx1d-transgenic T cells exacerbated some phenotypes of atherosclerosis, which were associated with higher autoantibody production, increased Tfh cell frequency, and impaired Treg cell regulation, in Ldlr-/- mice as compared with control T cells. In addition, we showed that dyslipidemia and Pbx1d-transgenic expression independently impaired the differentiation and function of Treg cells in vitro, suggesting a gene/environment additive effect. Thus, our results suggest that the combination of Pbx1d expression in T cells and dyslipidemia exacerbates both atherosclerosis and autoimmunity, at least in part through a dysregulation of Treg cell homeostasis.

Gut microbiota dysbiosis and altered tryptophan catabolism contribute to autoimmunity in lupus-susceptible mice.

The autoimmune disease systemic lupus erythematosus (SLE) is characterized by the production of pathogenic autoantibodies. It has been postulated that gut microbial dysbiosis may be one of the mechanisms involved in SLE pathogenesis. Here, we demonstrate that the dysbiotic gut microbiota of triple congenic (TC) lupus-prone mice (B6.Sle1.Sle2.Sle3) stimulated the production of autoantibodies and activated immune cells when transferred into germfree congenic C57BL/6 (B6) mice. Fecal transfer to B6 mice induced autoimmune phenotypes only when the TC donor mice exhibited autoimmunity. Autoimmune pathogenesis was mitigated by horizontal transfer of the gut microbiota between co-housed lupus-prone TC mice and control congenic B6 mice. Metabolomic screening identified an altered distribution of tryptophan metabolites in the feces of TC mice including an increase in kynurenine, which was alleviated after antibiotic treatment. Low dietary tryptophan prevented autoimmune pathology in TC mice, whereas high dietary tryptophan exacerbated disease. Reducing dietary tryptophan altered gut microbial taxa in both lupus-prone TC mice and control B6 mice. Consequently, fecal transfer from TC mice fed a high tryptophan diet, but not a low tryptophan diet, induced autoimmune phenotypes in germfree B6 mice. The interplay of gut microbial dysbiosis, tryptophan metabolism and host genetic susceptibility in lupus-prone mice suggest that aberrant tryptophan metabolism may contribute to autoimmune activation in this disease.

Hirsch Index Value and Variability Related to General Surgery in a UK Deanery.

OBJECTIVES: The Hirsch Index (h-index) is often used to assess research impact, and on average a social science senior lecturer will have an h-index of 2.29, yet its validity within the context of UK General Surgery (GS) is unknown. The aim of this study was to calculate the h-indices of a cohort of GS consultants in a UK Deanery to assess its relative validity. DESIGN: Individual h-indices and total publication (TP) counts were obtained for GS consultants via the Scopus and Web of Science (WoS) Internet search engines. Assessment of construct validity and reliability of these 2 measures of the h-index was undertaken. SETTING: All hospitals in a single UK National Health Service Deanery were included (14 general hospitals). PARTICIPANTS: All 136 GS consultants from the Deanery were included. RESULTS: Median h-index (Scopus) was 5 (0-52) and TP 15 (0-369), and strong correlation was found between h-index and TP (ρ = 0.932, p < 0.001), with the intraclass correlation between Scopus and WoS h-index also significant (intraclass correlation coefficient = 0.973 [95% CI: 0.962-0.981], p < 0.001). Academic GS consultants had higher h-indices than nonacademic University Hospital and District General Hospital consultants (Scopus 12 vs 7 vs 4 [p < 0.001] and WoS 10.5 vs 7 vs 4 [p < 0.001]). h-Index was >2.29 in 57.4% of consultants. No subspecialty differences were apparent in median h-indices (p = 0.792) and TP (p = 0.903). CONCLUSIONS: h-Index is a valid GS research productivity metric with over half of consultants performing at levels equivalent to social science Senior Lecturers.