Characterizing Diffusion from Microdialysis Catheters in the Human Brain: A Magnetic Resonance Imaging Study With Gadobutrol.

Cerebral microdialysis (CMD) catheters allow continuous monitoring of patients' cerebral metabolism in severe traumatic brain injury (TBI). The catheters consist of a terminal semi-permeable membrane that is inserted into the brain's interstitium to allow perfusion fluid to equalize with the surrounding cerebral extracellular environment before being recovered through a central non-porous channel. However, it is unclear how far recovered fluid and suspended metabolites have diffused from within the brain, and therefore what volume or region of brain tissue the analyses of metabolism represent. We assessed diffusion of the small magnetic resonance (MR)-detectible molecule gadobutrol from microdialysis catheters in six subjects (complete data five subjects, incomplete data one subject) who had sustained a severe TBI. Diffusion pattern and distance in cerebral white matter were assessed using T1 (time for MR spin-lattice relaxation) maps at 1 mm isotropic resolution in a 3 Tesla MR scanner. Gadobutrol at 10 mmol/L diffused from cerebral microdialysis catheters in a uniform spheroidal (ellipsoid of revolution) pattern around the catheters' semipermeable membranes, and across gray matter-white matter boundaries. Evidence of gadobutrol diffusion was found up to a mean of 13.4 ± 0.5 mm (mean ± standard deviation [SD]) from catheters, but with a steep concentration drop off so that ≤50% of maximum concentration was achieved at ∼4 mm, and ≤10% of maximum was found beyond ∼7 mm from the catheters. There was little variation between subjects. The relaxivity of gadobutrol in human cerebral white matter was estimated to be 1.61 ± 0.38 L.mmol-1sec-1 (mean ± SD); assuming gadobutrol remained extracellular thereby occupying 20% of total tissue volume (interstitium), and concentration equilibrium with perfusion fluid was achieved immediately adjacent to catheters after 24 h of perfusion. No statistically significant change was found in the concentration of the extracellular metabolites glucose, lactate, pyruvate, nor the lactate/pyruvate ratio during gadobutrol perfusion when compared with period of baseline microdialysis perfusion. Cerebral microdialysis allows continuous monitoring of regional cerebral metabolism-the volume of which is now clearer from this study. It also has the potential to deliver small molecule therapies to focal pathologies of the human brain. This study provides a platform for future development of new catheters optimally designed to treat such conditions.

In-vitro gadolinium retro-microdialysis in agarose gel-a human brain phantom study.

Rationale and objectives: Cerebral microdialysis is a technique that enables monitoring of the neurochemistry of patients with significant acquired brain injury, such as traumatic brain injury (TBI) and subarachnoid haemorrhage (SAH). Cerebral microdialysis can also be used to characterise the neuro-pharmacokinetics of small-molecule study substrates using retrodialysis/retromicrodialysis. However, challenges remain: (i) lack of a simple, stable, and inexpensive brain tissue model for the study of drug neuropharmacology; and (ii) it is unclear how far small study-molecules administered via retrodialysis diffuse within the human brain. Materials and methods: Here, we studied the radial diffusion distance of small-molecule gadolinium-DTPA from microdialysis catheters in a newly developed, simple, stable, inexpensive brain tissue model as a precursor for in-vivo studies. Brain tissue models consisting of 0.65% weight/volume agarose gel in two kinds of buffers were created. The distribution of a paramagnetic contrast agent gadolinium-DTPA (Gd-DTPA) perfusion from microdialysis catheters using magnetic resonance imaging (MRI) was characterized as a surrogate for other small-molecule study substrates. Results: We found the mean radial diffusion distance of Gd-DTPA to be 18.5 mm after 24 h (p < 0.0001). Conclusion: Our brain tissue model provides avenues for further tests and research into infusion studies using cerebral microdialysis, and consequently effective focal drug delivery for patients with TBI and other brain disorders.

Development and validation of GLVS (Generic Laparoscopic Video Scoring System), a tool for assessment of laparoscopic skills in gynaecology using videotaped procedures: Are edited videos representative of their full-length version?

Background: Anonymized videotaped endoscopic procedures can be used for the assessment of surgical competence, but a reliable non-procedure-specific scoring system is needed for gynaecology. Objectives: To design and evaluate the validity of the Generic Laparoscopic Video Scoring System (GLVS), a novel tool in the assessment of various gynaecological laparoscopic procedures. Materials and Methods: Seventeen anonymized unedited video recordings of various gynaecological laparoscopic procedures and the 4-minute-long edited versions of the same videos were independently scored by two experts, twice, using GLVS. Main outcome measures: Internal consistency reliability, test-retest, and inter-rater reliability of GLVS. We also compared the scored achieved by edited videos with those of the full-length version of the same videos. Results: The mean score achieved by 4-minute-long edited videos was similar to that of the unedited version (p= 0.13 - 0.19). There was excellent correlation between the pooled scores for edited and unedited versions (intra-class correlation coefficient = 0.86). GLVS had excellent internal consistency reliability (Cronbach's alpha 0.92-0.97). Test-retest and inter-rater reliability were generally better for edited 4-minute-long videos compared to their full-length version. Test-retest reliability for edited videos was excellent for scorer 1 and good for scorer 2 with intra-class correlation coefficient (ICC) of 0.88 and 0.62 respectively. Inter-rater reliability was good for edited videos (ICC=0.64) but poor for full-length versions (ICC= -0.24). Conclusion: GLVS allows for objective surgical skills assessment using anonymized shortened self-edited videos of basic gynaecological laparoscopic procedures. Shortened video clips of procedures seem to be representative of their full-length version for the assessment of surgical skills. What's new?: We devised and undertook a validation study for a novel tool to assess surgical skills using surgical video clips. We believe this addition clearly delineates the unique contributions of our study.

High-physiological and supra-physiological 1,2-13C2 glucose focal supplementation to the traumatised human brain.

How to optimise glucose metabolism in the traumatised human brain remains unclear, including whether injured brain can metabolise additional glucose when supplied. We studied the effect of microdialysis-delivered 1,2-13C2 glucose at 4 and 8 mmol/L on brain extracellular chemistry using bedside ISCUSflex, and the fate of the 13C label in the 8 mmol/L group using high-resolution NMR of recovered microdialysates, in 20 patients. Compared with unsupplemented perfusion, 4 mmol/L glucose increased extracellular concentrations of pyruvate (17%, p = 0.04) and lactate (19%, p = 0.01), with a small increase in lactate/pyruvate ratio (5%, p = 0.007). Perfusion with 8 mmol/L glucose did not significantly influence extracellular chemistry measured with ISCUSflex, compared to unsupplemented perfusion. These extracellular chemistry changes appeared influenced by the underlying metabolic states of patients' traumatised brains, and the presence of relative neuroglycopaenia. Despite abundant 13C glucose supplementation, NMR revealed only 16.7% 13C enrichment of recovered extracellular lactate; the majority being glycolytic in origin. Furthermore, no 13C enrichment of TCA cycle-derived extracellular glutamine was detected. These findings indicate that a large proportion of extracellular lactate does not originate from local glucose metabolism, and taken together with our earlier studies, suggest that extracellular lactate is an important transitional step in the brain's production of glutamine.

Characterizing cerebral metabolite profiles in anorexia and bulimia nervosa and their associations with habitual behavior.

Anorexia nervosa (AN) and bulimia nervosa (BN) are associated with altered brain structure and function, as well as increased habitual behavior. This neurobehavioral profile may implicate neurochemical changes in the pathogenesis of these illnesses. Altered glutamate, myo-inositol and N-acetyl aspartate (NAA) concentrations are reported in restrictive AN, yet whether these extend to binge-eating disorders, or relate to habitual traits in affected individuals, remains unknown. We therefore used single-voxel proton magnetic resonance spectroscopy to measure glutamate, myo-inositol, and NAA in the right inferior lateral prefrontal cortex and the right occipital cortex of 85 women [n = 22 AN (binge-eating/purging subtype; AN-BP), n = 33 BN, n = 30 controls]. To index habitual behavior, participants performed an instrumental learning task and completed the Creature of Habit Scale. Women with AN-BP, but not BN, had reduced myo-inositol and NAA concentrations relative to controls in both regions. Although patient groups had intact instrumental learning task performance, both groups reported increased routine behaviors compared to controls, and automaticity was related to reduced prefrontal glutamate and NAA participants with AN-BP. Our findings extend previous reports of reduced myo-inositol and NAA levels in restrictive AN to AN-BP, which may reflect disrupted axonal-glial signaling. Although we found inconsistent support for increased habitual behavior in AN-BP and BN, we identified preliminary associations between prefrontal metabolites and automaticity in AN-BP. These results provide further evidence of unique neurobiological profiles across binge-eating disorders.

Focally administered succinate improves cerebral metabolism in traumatic brain injury patients with mitochondrial dysfunction.

Following traumatic brain injury (TBI), raised cerebral lactate/pyruvate ratio (LPR) reflects impaired energy metabolism. Raised LPR correlates with poor outcome and mortality following TBI. We prospectively recruited patients with TBI requiring neurocritical care and multimodal monitoring, and utilised a tiered management protocol targeting LPR. We identified patients with persistent raised LPR despite adequate cerebral glucose and oxygen provision, which we clinically classified as cerebral 'mitochondrial dysfunction' (MD). In patients with TBI and MD, we administered disodium 2,3-13C2 succinate (12 mmol/L) by retrodialysis into the monitored region of the brain. We recovered 13C-labelled metabolites by microdialysis and utilised nuclear magnetic resonance spectroscopy (NMR) for identification and quantification.Of 33 patients with complete monitoring, 73% had MD at some point during monitoring. In 5 patients with multimodality-defined MD, succinate administration resulted in reduced LPR(-12%) and raised brain glucose(+17%). NMR of microdialysates demonstrated that the exogenous 13C-labelled succinate was metabolised intracellularly via the tricarboxylic acid cycle. By targeting LPR using a tiered clinical algorithm incorporating intracranial pressure, brain tissue oxygenation and microdialysis parameters, we identified MD in TBI patients requiring neurointensive care. In these, focal succinate administration improved energy metabolism, evidenced by reduction in LPR. Succinate merits further investigation for TBI therapy.

Novel homozygous variant in BMP1 associated with a rare osteogenesis imperfecta phenotype.

Osteogenesis imperfecta (OI) is characterized by bone fragility and increased fracture susceptibility. BMP1 variants have been reported in the rare OI type XIII, specifically referred to herein as BMP1-associated autosomal recessive (AR) OI. We report the clinical presentation and diagnostic evaluation of a patient found to have a novel homozygous variant in BMP1. We also provide an overview of reported BMP1 variants to date, with discussion focusing on the use of bisphosphonate therapy in these patients. A 7-year-old male with speech and motor delay sustained five bilateral tibial fractures with minimal trauma since age 2.5 years. At age 6, he developed severe back pain after a fall. Diffuse spinal osteopenia and multiple vertebral compression fractures (VCF) at T9, L1, L3, and L5 were identified. Total hip BMD was generous (adjusted Z-score* = 1.76), and femoral neck BMD was high (adjusted Z-score* = 2.67). VCFs precluded assessment of lumbar spine BMD. Genetic analysis identified a homozygous missense variant in exon 4 of BMP1 (c.C505T; p.Arg169Cys). Unlike most forms of OI, patients with BMP1-associated AR OI may have normal or paradoxically increased BMD, making BMD and fracture risk correlation difficult. While bisphosphonates (BP) may help reduce recurrent fractures and provide symptomatic relief, the broad phenotypic spectrum and underlying bone pathology, often in the setting of increased BMD, complicate management. HR-pQCT assessment of bone microarchitecture and quality may aid in the decision of BP therapy and subsequent monitoring. Evidence is limited with respect to the effectiveness of BP in this rare form of OI. *Z-score was adjusted for height Z-score.

GABA and glutamate deficits from frontotemporal lobar degeneration are associated with disinhibition.

Behavioural disinhibition is a common feature of the syndromes associated with frontotemporal lobar degeneration (FTLD). It is associated with high morbidity and lacks proven symptomatic treatments. A potential therapeutic strategy is to correct the neurotransmitter deficits associated with FTLD, thereby improving behaviour. Reductions in the neurotransmitters glutamate and GABA correlate with impulsive behaviour in several neuropsychiatric diseases and there is post-mortem evidence of their deficit in FTLD. Here, we tested the hypothesis that prefrontal glutamate and GABA levels are reduced by FTLD in vivo, and that their deficit is associated with impaired response inhibition. Thirty-three participants with a syndrome associated with FTLD (15 patients with behavioural variant frontotemporal dementia and 18 with progressive supranuclear palsy, including both Richardson's syndrome and progressive supranuclear palsy-frontal subtypes) and 20 healthy control subjects were included. Participants undertook ultra-high field (7 T) magnetic resonance spectroscopy and a stop-signal task of response inhibition. We measured glutamate and GABA levels using semi-LASER magnetic resonance spectroscopy in the right inferior frontal gyrus, because of its strong association with response inhibition, and in the primary visual cortex, as a control region. The stop-signal reaction time was calculated using an ex-Gaussian Bayesian model. Participants with frontotemporal dementia and progressive supranuclear palsy had impaired response inhibition, with longer stop-signal reaction times compared with controls. GABA concentration was reduced in patients versus controls in the right inferior frontal gyrus, but not the occipital lobe. There was no group-wise difference in partial volume corrected glutamate concentration between patients and controls. Both GABA and glutamate concentrations in the inferior frontal gyrus correlated inversely with stop-signal reaction time, indicating greater impulsivity in proportion to the loss of each neurotransmitter. We conclude that the glutamatergic and GABAergic deficits in the frontal lobe are potential targets for symptomatic drug treatment of frontotemporal dementia and progressive supranuclear palsy.

Multi-centre, multi-vendor reproducibility of 7T QSM and R2* in the human brain: Results from the UK7T study.

INTRODUCTION: We present the reliability of ultra-high field T2* MRI at 7T, as part of the UK7T Network's "Travelling Heads" study. T2*-weighted MRI images can be processed to produce quantitative susceptibility maps (QSM) and R2* maps. These reflect iron and myelin concentrations, which are altered in many pathophysiological processes. The relaxation parameters of human brain tissue are such that R2* mapping and QSM show particularly strong gains in contrast-to-noise ratio at ultra-high field (7T) vs clinical field strengths (1.5-3T). We aimed to determine the inter-subject and inter-site reproducibility of QSM and R2* mapping at 7T, in readiness for future multi-site clinical studies. METHODS: Ten healthy volunteers were scanned with harmonised single- and multi-echo T2*-weighted gradient echo pulse sequences. Participants were scanned five times at each "home" site and once at each of four other sites. The five sites had 1× Philips, 2× Siemens Magnetom, and 2× Siemens Terra scanners. QSM and R2* maps were computed with the Multi-Scale Dipole Inversion (MSDI) algorithm (https://github.com/fil-physics/Publication-Code). Results were assessed in relevant subcortical and cortical regions of interest (ROIs) defined manually or by the MNI152 standard space. RESULTS AND DISCUSSION: Mean susceptibility (χ) and R2* values agreed broadly with literature values in all ROIs. The inter-site within-subject standard deviation was 0.001-0.005 ppm (χ) and 0.0005-0.001 ms-1 (R2*). For χ this is 2.1-4.8 fold better than 3T reports, and 1.1-3.4 fold better for R2*. The median ICC from within- and cross-site R2* data was 0.98 and 0.91, respectively. Multi-echo QSM had greater variability vs single-echo QSM especially in areas with large B0 inhomogeneity such as the inferior frontal cortex. Across sites, R2* values were more consistent than QSM in subcortical structures due to differences in B0-shimming. On a between-subject level, our measured χ and R2* cross-site variance is comparable to within-site variance in the literature, suggesting that it is reasonable to pool data across sites using our harmonised protocol. CONCLUSION: The harmonized UK7T protocol and pipeline delivers on average a 3-fold improvement in the coefficient of reproducibility for QSM and R2* at 7T compared to previous reports of multi-site reproducibility at 3T. These protocols are ready for use in multi-site clinical studies at 7T.

Phosphorus spectroscopy in acute TBI demonstrates metabolic changes that relate to outcome in the presence of normal structural MRI.

Metabolic dysfunction is a key pathophysiological process in the acute phase of traumatic brain injury (TBI). Although changes in brain glucose metabolism and extracellular lactate/pyruvate ratio are well known, it was hitherto unknown whether these translate to downstream changes in ATP metabolism and intracellular pH. We have performed the first clinical voxel-based in vivo phosphorus magnetic resonance spectroscopy (31P MRS) in 13 acute-phase major TBI patients versus 10 healthy controls (HCs), at 3T, focusing on eight central 2.5 × 2.5 × 2.5 cm3 voxels per subject. PCr/γATP ratio (a measure of energy status) in TBI patients was significantly higher (median = 1.09) than that of HCs (median = 0.93) (p < 0.0001), due to changes in both PCr and ATP. There was no significant difference in PCr/γATP between TBI patients with favourable and unfavourable outcome. Cerebral intracellular pH of TBI patients was significantly higher (median = 7.04) than that of HCs (median = 7.00) (p = 0.04). Alkalosis was limited to patients with unfavourable outcome (median = 7.07) (p < 0.0001). These changes persisted after excluding voxels with > 5% radiologically visible injury. This is the first clinical demonstration of brain alkalosis and elevated PCr/γATP ratio acutely after major TBI. 31P MRS has potential for non-invasively assessing brain injury in the absence of structural injury, predicting outcome and monitoring therapy response.

Measuring the impacts of aquatic animal diseases: the role of economic analysis.

Aquaculture is an important industry both economically and socially. The majority of this industry is focused on the production of aquatic animals, which may be substantially adversely affected by disease. Economic analyses may be used to inform decision-makers on the aquatic animal disease control choices that are economically optimal. Examples of such analyses are presented in this paper, ranging from basic cost estimates of disease impact to complex, spatial- temporal, bio-economic models. Regardless of the complexity of the analysis, there is a consistent need to collect and analyse good quality data measuring both the production and health of aquatic animals. This would require a variety of individuals and groups, including farmers, scientists and the government, to collaboratively contribute to this end. Given the necessary data, more sophisticated models may be better used to inform decision-making from the farm to the national level. Finally, economic analyses should not be limited to simple aggregated cost and benefit results but rather should include the social and gender impacts of financial decisions, as well as the potential externalities both within and among the various impacted sectors in order to optimise investment at both the farm and national levels.

Le secteur de l'aquaculture joue un rôle important aux plans tant économique que social. La majorité des filières du secteur sont axées sur la production d'animaux aquatiques, espèces susceptibles à des maladies à l'impact souvent considérable. Les décideurs ont la possibilité de recourir à des analyses économiques afin de sélectionner les stratégies de lutte contre les maladies des animaux aquatiques optimales au plan économique. L'auteur présente quelques exemples de ce type d'analyses, qui vont de l'estimation basique des coûts liés à l'impact d'une maladie à des modèles analytiques complexes, spatiotemporels et bioéconomiques. Indépendamment de la complexité de l'analyse, il est à chaque fois indispensable de collecter et d'analyser des données de bonne qualité concernant la production et la santé des animaux aquatiques. La réussite d'une telle entreprise nécessite la contribution d'un large éventail d'acteurs individuels et collectifs travaillant en collaboration, dont les éleveurs, les chercheurs et les instances gouvernementales. Dès lors que l'on dispose des données nécessaires, des modèles plus sophistiqués pourront être utilisés afin d'étayer les prises de décision depuis les élevages jusqu'au niveau national. Enfin, les analyses économiques ne devraient pas se limiter à de simples résultats agrégés des coûts et des bénéfices mais devraient prendre en compte les impacts sociaux des décisions financières et leurs répercussions sexospécifiques, ainsi que les effets externes potentiels sur et parmi les divers secteurs affectés, dans le but d'optimiser les investissements réalisés aussi bien au niveau des élevages qu'à l'échelle nationale.

La acuicultura es una actividad industrial importante, a la vez económica y socialmente. El grueso del sector está dedicado a la producción de animales acuáticos, en los que pueden hacer estragos las enfermedades. Los análisis económicos pueden ser utilizados por las instancias decisorias para decidir con conocimiento de causa acerca de las líneas de actuación económicamente idóneas para combatir las enfermedades de dichos animales. El autor presenta ejemplos de este tipo de análisis, que van desde estimaciones básicas del costo de las consecuencias de una enfermedad hasta complejos modelos bioeconómicos que integran la dimensión espaciotemporal. Ahora bien, sea cual sea el nivel de complejidad del análisis, siempre es necesario reunir y analizar datos de buena calidad que midan tanto la producción como el estado de salud de los animales acuáticos. Para hacer posible tal objetivo sería menester que diversas personas y colectividades, entre ellas productores, científicos y administraciones públicas, trabajaran de consuno con este fin. Habida cuenta de los datos necesarios, es posible dar un mejor uso a modelos más sofisticados para fundamentar los procesos decisorios a todos los niveles, desde la explotación hasta el ámbito nacional. Los resultados de los análisis económicos, por último, lejos de ofrecer meras sumas de costos y beneficios, deberían también dar cuenta de los efectos sociales o ligados al género de las decisiones de índole económica, así como de eventuales influencias externas que se dejen sentir en los diversos sectores afectados, o que se ejerzan de uno a otro de esos sectores, con el fin de optimizar las inversiones tanto en cada explotación como a escala nacional.

Alcohol use and mental health symptoms in female firefighter recruits.

BACKGROUND: Limited research suggests that female firefighters report problem drinking at higher rates than the general population. AIMS: To identify longitudinal drinking patterns in female firefighters, make comparisons to male firefighters and examine problem drinking in relation to post-traumatic stress disorder (PTSD) and depression. METHODS: Study participants included 33 female and 289 male firefighter recruits, who were assessed over their first 3 years of fire service. RESULTS: Female firefighters consumed increasing numbers of drinks per week, with a median of 0.90 drinks per week at baseline, and 1.27 drinks in year 3. Female firefighters reported binge drinking at high rates, with nearly half binging at least once per year across all time points (44-74%). The percentage that reported binge drinking three or more times per month doubled over the course of the study (from 9% to 18%). Overall, males reported higher rates of binge drinking and a greater number of drinks per week; however, binge drinking rates among females increased over time and became comparable to rates of binge drinking among males. A greater percentage of female than male firefighters met the criteria for problem drinking by year 1. Problem drinking was associated with screening positive for PTSD at year 1 and depression at year 2, but not with occupational injury. CONCLUSIONS: Over time, female firefighters reported increasing amounts of drinking, more frequent binge drinking and more negative consequences from drinking. These findings along with existing literature indicate female firefighters change their drinking in the direction of their male counterparts.

Development and validation of models to predict personal ventilation rate for air pollution research.

Air pollution intake represents the amount of pollution inhaled into the body and may be calculated by multiplying an individual's ventilation rate with the concentration of pollutant present in their breathing zone. Ventilation rate is difficult to measure directly, and methods for estimating ventilation rate (and intake) are lacking. Therefore, the goal of this work was to examine how well linear models using heart rate and other basic physiologic data can predict personal ventilation rate. We measured personal ventilation and heart rate among a panel of subjects (n = 36) while they conducted a series of specified routine tasks of varying exertion levels. From these data, 136 candidate models were identified using a series of variable transformation and selection algorithms. A second "free­living" validation study (n = 26) served as an independent validation dataset for these candidate models. The top­performing model, which included heart rate (Hr), resting heart rate (Hrest), age, sex, and hip circumference and interactions between sex with Hr, Hrest, age, and hip predicted ventilation rate (Ve) to within 11% and 33% for moderate (Ve = 45 L/min) and low (Ve = 15 L/min) intensity activities, respectively, based on the validation study. Many of the promising candidate models performed substantially worse under independent validation. Our results indicate that while measures of air pollution exposure and intake are highly correlated within tasks for a given individual, this correlation decreases substantially across tasks (i.e., as individuals go about a series of typical daily activities). This discordance between exposure and intake may influence exposure­response estimates in epidemiological studies. New air pollution studies should consider the trade­offs between the predictive ability of intake models and the error potentially introduced by not accounting for ventilation rate.

Route of hysterectomy: a retrospective, cohort study in English NHS Hospitals from 2011 to 2017.

OBJECTIVE: To assess variation in the route of hysterectomy over 7 years and to assess regional variation in practice. DESIGN: Retrospective cohort study. SETTING: English NHS Hospitals 2011-2017. POPULATION: 230 876 patients having a hysterectomy for six diagnostic categories (endometrial cancer, endometriosis and pain, menstrual disorders, fibroids, benign adnexal masses, and 'other') identified from Hospital Episode Statistics. METHODS: The proportion of hysterectomies carried out by each route was calculated for each year overall and for each primary diagnosis by year. Comparisons between 2011 and 2017 were via chi-square test. Rank correlation coefficients were calculated to assess trends over the study period. Analysis of regional variation in practice was restricted to 2017. A multivariable logistic regression was performed to obtain crude and adjusted odds of having a minimal access hysterectomy. MAIN OUTCOME MEASURES: The proportion of abdominal, vaginal, laparoscopic, and failed laparoscopic procedures for each primary diagnosis by study year. Odds of a minimal access hysterectomy in 2017. RESULTS: The proportion of hysterectomies performed laparoscopically increased from 20.2% in 2011 to 47.2% in 2017, as did the proportion of failed laparoscopic procedures; 1.7% in 2011 to 2.8% in 2017. The proportion of abdominal hysterectomies decreased from 70.4% in 2011 to 46.5% in 2017. There was a smaller decrease in vaginal procedures from 7.8% in 2011 to 3.5% in 2017. Regional variation in the route of hysterectomy was demonstrated in 2017, which persisted when adjusted for confounding factors. CONCLUSIONS: The proportion of laparoscopic procedures has increased, and it was the commonest route of hysterectomy for this cohort in 2017. There were significant regional differences in route of hysterectomy in 2017. TWEETABLE ABSTRACT: Increasing laparoscopic hysterectomy and decreasing abdominal hysterectomy rates from 2011 to 2017 with regional variation in practice.

The effect of succinate on brain NADH/NAD+ redox state and high energy phosphate metabolism in acute traumatic brain injury.

A key pathophysiological process and therapeutic target in the critical early post-injury period of traumatic brain injury (TBI) is cell mitochondrial dysfunction; characterised by elevation of brain lactate/pyruvate (L/P) ratio in the absence of hypoxia. We previously showed that succinate can improve brain extracellular chemistry in acute TBI, but it was not clear if this translates to a change in downstream energy metabolism. We studied the effect of microdialysis-delivered succinate on brain energy state (phosphocreatine/ATP ratio (PCr/ATP)) with 31P MRS at 3T, and tissue NADH/NAD+ redox state using microdialysis (L/P ratio) in eight patients with acute major TBI (mean 7 days). Succinate perfusion was associated with increased extracellular pyruvate (+26%, p < 0.0001) and decreased L/P ratio (-13%, p < 0.0001) in patients overall (baseline-vs-supplementation over time), but no clear-cut change in 31P MRS PCr/ATP existed in our cohort (p > 0.4, supplemented-voxel-vs-contralateral voxel). However, the percentage decrease in L/P ratio for each patient following succinate perfusion correlated significantly with their percentage increase in PCr/ATP ratio (Spearman's rank correlation, r = -0.86, p = 0.024). Our findings support the interpretation that L/P ratio is linked to brain energy state, and that succinate may support brain energy metabolism in select TBI patients suffering from mitochondrial dysfunction.

A Comparison of Oxidative Lactate Metabolism in Traumatically Injured Brain and Control Brain.

Metabolic abnormalities occur after traumatic brain injury (TBI). Glucose is conventionally regarded as the major energy substrate, although lactate can also be an energy source. We compared 3-13C lactate metabolism in TBI with "normal" control brain and muscle, measuring 13C-glutamine enrichment to assess tricarboxylic acid (TCA) cycle metabolism. Microdialysis catheters in brains of nine patients with severe TBI, five non-TBI brain surgical patients, and five resting muscle (non-TBI) patients were perfused (24 h in brain, 8 h in muscle) with 8 mmol/L sodium 3-13C lactate. Microdialysate analysis employed ISCUS and nuclear magnetic resonance. In TBI, with 3-13C lactate perfusion, microdialysate glucose concentration increased nonsignificantly (mean +11.9%, p = 0.463), with significant increases (p = 0.028) for lactate (+174%), pyruvate (+35.8%), and lactate/pyruvate ratio (+101.8%). Microdialysate 13C-glutamine fractional enrichments (median, interquartile range) were: for C4 5.1 (0-11.1) % in TBI and 5.7 (4.6-6.8) % in control brain, for C3 0 (0-5.0) % in TBI and 0 (0-0) % in control brain, and for C2 2.9 (0-5.7) % in TBI and 1.8 (0-3.4) % in control brain. 13C-enrichments were not statistically different between TBI and control brain, showing both metabolize 3-13C lactate via TCA cycle, in contrast to muscle. Several patients with TBI exhibited 13C-glutamine enrichment above the non-TBI control range, suggesting lactate oxidative metabolism as a TBI "emergency option."

Corrigendum: Assessing Metabolism and Injury in Acute Human Traumatic Brain Injury with Magnetic Resonance Spectroscopy: Current and Future Applications.

[This corrects the article on p. 426 in vol. 8, PMID: 28955291.].

Economics for assisting policy-makers to take decisions about new and endemic diseases.

Animal health policy-makers are frequently faced with making decisions concerning the control and exclusion of diseases in livestock and wildlife populations. Economics is one of the tools they have to aid their decision-making. It can enable them to make objective decisions based on the expected costs and benefits of their policy. In addition, economics can help them determine both the distribution impact and the indirect impact of their decisions. However, economics is only one of many tools available to policy-makers, who also need to consider non-economic outcomes in their decision-making process. While there are sophisticated epidemic and economic (epinomic) models that are available to help evaluate complex problems, these models typically require extensive data and well-trained analysts to run and interpret their results. In addition, effective communication between analysts and policy-makers is important to ensure that results are clearly conveyed to the policy-makers. This may be facilitated by early and continued discussions between these two potentially disparate groups. If successfully performed and communicated, economic analyses may present valuable information to policy-makers, enabling them to not only better understand the economic implications of their policy, but also to communicate the policy to relevant stakeholders, further ensuring their likelihood of participating in the planned policy and hence increasing its likelihood of success.

Les responsables des politiques de santé animale sont souvent confrontés à la nécessité de prendre des décisions au sujet de la lutte à mener contre les maladies animales affectant les populations domestiques et sauvages ou de leur éradication. L'économie est l'un des outils d'aide à la décision à leur disposition. L'économie peut les aider à prendre des décisions objectives basées sur les coûts et les avantages attendus des politiques envisagées. Elle peut aussi les aider à déterminer l'impact de leurs décisions en termes de portée et d'effets indirects. Néanmoins, l'économie n'est qu'un des nombreux outils disponibles et les décideurs doivent également intégrer les résultats non économiques lors de leur processus décisionnel. Un certain nombre de modèles épidémiques et économiques (« épinomiques ¼) sophistiqués permettent d'évaluer des problèmes complexes ; ils nécessitent cependant un volume considérable de données ainsi que des analystes qualifiés pour les mettre en oeuvre et en interpréter les résultats. En outre, une communication efficace doit être mise en place entre les analystes et les décideurs afin de s'assurer que les résultats obtenus sont rapportés à ces derniers dans un langage clair. Ceci peut être facilité par des échanges précoces et permanents entre ces deux groupes potentiellement hétérogènes. Des analyses économiques bien réalisées et faisant l'objet d'une bonne communication fournissent aux décideurs des informations de qualité grâce auxquelles ils peuvent appréhender plus clairement les conséquences économiques de leurs politiques, mais aussi expliquer ces politiques aux principales parties prenantes, ce qui accroît la probabilité de les faire adhérer aux mesures planifiées et améliore d'autant les chances de succès.

Los planificadores de políticas zoosanitarias se ven con frecuencia en la tesitura de adoptar decisiones acerca del control y la exclusión de enfermedades en poblaciones de ganado o de animales salvajes. La economía es una de las herramientas en las que pueden apoyarse para ello, pues les ayuda a tomar decisiones objetivas basándose en los costos y beneficios previstos de determinada política. Además, la economía puede serles útil para determinar tanto el impacto distributivo como el impacto indirecto de sus decisiones. Sin embargo, la economía es solo una de las muchas herramientas de que disponen los planificadores, que en su proceso decisorio también deben tener en cuenta efectos de carácter no económico. Si bien para ayudarles a aprehender problemas complejos existen sofisticados modelos epidemiológicos y económicos (epinómicos), estos suelen requerir un gran número de datos, así como el concurso de analistas cualificados para aplicar los modelos e interpretar sus resultados. Asimismo, para que los resultados obtenidos por los analistas lleguen con claridad a los planificadores es importante que existan cauces eficaces de comunicación entre los primeros y los segundos, lo que puede verse facilitado si estos dos grupos, en potencia tan dispares, dialogan desde buen comienzo y de forma continua. Si se llevan a cabo y se comunican correctamente, los análisis económicos pueden ofrecer información útil a los planificadores, que les sirva no solo para aprehender mejor las consecuencias económicas de sus políticas, sino también para explicar determinada política a todos los interlocutores del sector, con lo cual estos serán más proclives a participar en dicha política y esta tendrá más probabilidades de éxito.