Synchronous inhibitory pathways create both efficiency and diversity in the retina.

Sensory receptive fields combine features that originate in different neural pathways. Retinal ganglion cell receptive fields compute intensity changes across space and time using a peripheral region known as the surround, a property that improves information transmission about natural scenes. The visual features that construct this fundamental property have not been quantitatively assigned to specific interneurons. Here, we describe a generalizable approach using simultaneous intracellular and multielectrode recording to directly measure and manipulate the sensory feature conveyed by a neural pathway to a downstream neuron. By directly controlling the gain of individual interneurons in the circuit, we show that rather than transmitting different temporal features, inhibitory horizontal cells and linear amacrine cells synchronously create the linear surround at different spatial scales and that these two components fully account for the surround. By analyzing a large population of ganglion cells, we observe substantial diversity in the relative contribution of amacrine and horizontal cell visual features while still allowing individual cells to increase information transmission under the statistics of natural scenes. Established theories of efficient coding have shown that optimal information transmission under natural scenes allows a diverse set of receptive fields. Our results give a mechanism for this theory, showing how distinct neural pathways synthesize a sensory computation and how this architecture both generates computational diversity and achieves the objective of high information transmission.

Effect of footplate neuromuscular electrical stimulation on functional and quality-of-life parameters in patients with peripheral artery disease: pilot, and subsequent randomized clinical trial.

BACKGROUND: Supervised exercise programmes for intermittent claudication have poor access and limited compliance. Neuromuscular electrical stimulation (NMES) may be an effective alternative. A proof-of-concept study and RCT were conducted. METHODS: In study 1, eligible patients underwent baseline assessment; treadmill testing for initial (ICD) and maximum (MCD) claudication distance; EuroQoL Five Dimensions five-level instrument (EQ-5D-5L™) and Intermittent Claudication Questionnaire (ICQ) assessment; and measurement of ultrasound haemodynamics of the superficial femoral artery. After familiarization with the NMES device, participants underwent a 30-min session of stimulation with concomitant recording of haemodynamic measures at 15 min, and after device cessation. Measurements were repeated after 6 weeks of daily use of NMES. In study 2, consecutive patients underwent baseline assessment before online randomization to a supervised exercise programme only, or adjunctive NMES treatment for 6 weeks, followed by repeat measurements. RESULTS: Study 1 (20 patients) showed a significant improvement in MCD (46 per cent; P < 0·001) and ICD (71 per cent; P < 0·001). The RCT (42 patients) showed a significant adjunctive benefit of NMES in ICD (46 per cent; P = 0·014). Improvements were seen in the ICQ (9 points; P = 0·009) and EQ-5D-5L™ (P = 0·007) in study 1, and there was a significant adjunctive benefit of NMES on the ICQ score in patients who did supervised exercise (11·2 points; P = 0·031). Blood volume flow and time-adjusted mean velocity increased significantly with the device on (P < 0·050). Overall, NMES compliance exceeded 95 per cent. CONCLUSION: Footplate NMES significantly improved walking distance in patients with intermittent claudication when used independently and also as an adjunct to supervised exercise. Registration number: trial 1, NCT02436200; trial 2, NCT02429310 (http://www.clinicaltrials.gov).

ANTECEDENTES: Los programas de ejercicio supervisado (supervised exercise programmes, SEP) para la claudicación intermitente (intermittent claudication, IC) tienen un acceso y un cumplimiento deficientes. La estimulación eléctrica neuromuscular (neuromuscular electrical stimulation, NMES) puede ser una alternativa clínicamente efectiva. Se realizó un estudio de prueba de concepto y un ensayo controlado aleatorizado. MÉTODOS: Estudio 1: Veinte pacientes elegibles se sometieron a una evaluación inicial que incluía una prueba en la cinta de correr para la distancia inicial de claudicación (initial claudication distance, ICD) y la distancia máxima de claudicación (maximum claudication distance, MCD), EuroQoL-5D (EQ-5D), valoración mediante el cuestionario de claudicación intermitente (intermittent claudication questionnaire, ICQ), y hemodinámica por ecografía de la arteria femoral superficial. Después de familiarizarse con el dispositivo NMES, los participantes se sometieron a una sesión de estimulación de 30 minutos con el registro concomitante de medidas hemodinámicas a los 15 minutos y después del cese del dispositivo. Se realizaron mediciones repetidas después de 6 semanas de uso diario de NMES. Estudio 2: Se reclutaron 42 pacientes que tras una evaluación inicial y posterior aleatorización al azar en línea, se asignaron al Grupo A, utilizando SEP solamente; o al el Grupo B, con tratamiento NMES complementario durante 6 semanas seguido de medidas repetidas. RESULTADOS: El estudio 1 mostró una mejoría significativa de la MCD (46%, P < 0,0001) y de la ICD (71%, P < 0.004). El ensayo clínico mostró un beneficio coadyuvante significativo de NMES en la ICD (46%, P = 0,014). Se observaron mejorías en la puntuación del ICQ (9 puntos, P < 0,01) y del EQ-5D (P < 0,05) en el estudio 1, con un beneficio coadyuvante significativo de NMES en la puntuación del ICQ (11 puntos, P < 0,05). El flujo de volumen de sangre (CC/min) y TAMV (cm/s) aumentaron significativamente con el dispositivo en funcionamiento (P < 0,05). El cumplimiento global de la NMES superó el 95%. CONCLUSIÓN: La plataforma de NMES para el pie mejora significativamente las distancias de caminar en la claudicación intermitente cuando se usa de forma independiente y también proporciona un beneficio complementario al ejercicio supervisado en la distancia caminada sin dolor. La mejora del flujo sanguíneo puede ser un mecanismo para explicar estos resultados.

A mobile telehealth program for behavioral treatment of urinary incontinence in women veterans: Development and pilot evaluation of MyHealtheBladder.

AIM: To develop and pilot test an interactive mobile telehealth program (mHealth) for behavioral treatment of women veterans with urinary incontinence (UI). METHODS: We developed an evidence-based 8-week behavioral mHealth program, MyHealtheBladder, with input from women veterans, behavioral medicine and health education experts, and clinical providers treating UI in the VA system. The program was story-based and included pelvic floor muscle exercises, bladder control strategies, fluid management, risk factor reduction, and self-monitoring. Participants were women veterans seeking outpatient treatment for UI occurring at least twice weekly. The primary efficacy estimate was the change in UI frequency, volume and impact on the quality of life as measured by the validated International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF; range: 0-21, 2.5 points for minimal clinically important difference [MCID]). RESULTS: We enrolled 29 women veterans (ages 29-77 years; mean = 54.4 ± 10.4), including 15 (52%) African-American women, 13 (45%) women with high school education, and 16 (55%) with a college degree. Twenty of 29 women (69%) completed all 8 weeks of the intervention with a 97% adherence rate to the daily sessions among completers. We found reductions in ICIQ-SF scores from a mean 12.6 ± 3.9 at baseline to 10.4 ± 4.11 at 5 weeks, to 8.7 ± 4.0 at the end of the 8-week intervention. CONCLUSIONS: Women veterans using an 8-week behavioral mHealth program for the treatment of UI had symptom improvements that exceeded the MCID for the ICIQ-SF. Our next step involves comparing the effectiveness of MyHealtheBladder to usual care in a larger clinical trial.

Observational study of the medical management of patients with peripheral artery disease.

BACKGROUND: Previous research has suggested that patients with peripheral artery disease (PAD) are not offered adequate risk factor modification, despite their high cardiovascular risk. The aim of this study was to assess the cardiovascular profiles of patients with PAD and quantify the survival benefits of target-based risk factor modification. METHODS: The Vascular and Endovascular Research Network (VERN) prospectively collected cardiovascular profiles of patients with PAD from ten UK vascular centres (April to June 2018) to assess practice against UK and European goal-directed best medical therapy guidelines. Risk and benefits of risk factor control were estimated using the SMART-REACH model, a validated cardiovascular prediction tool for patients with PAD. RESULTS: Some 440 patients (mean(s.d.) age 70(11) years, 24·8 per cent women) were included in the study. Mean(s.d.) cholesterol (4·3(1·2) mmol/l) and LDL-cholesterol (2·7(1·1) mmol/l) levels were above recommended targets; 319 patients (72·5 per cent) were hypertensive and 343 (78·0 per cent) were active smokers. Only 11·1 per cent of patients were prescribed high-dose statin therapy and 39·1 per cent an antithrombotic agent. The median calculated risk of a major cardiovascular event over 10 years was 53 (i.q.r. 44-62) per cent. Controlling all modifiable cardiovascular risk factors based on UK and European guidance targets (LDL-cholesterol less than 2 mmol/l, systolic BP under 140 mmHg, smoking cessation, antiplatelet therapy) would lead to an absolute risk reduction of the median 10-year cardiovascular risk by 29 (20-38) per cent with 6·3 (4·0-9·3) cardiovascular disease-free years gained. CONCLUSION: The medical management of patients with PAD in this secondary care cohort was suboptimal. Controlling modifiable risk factors to guideline-based targets would confer significant patient benefit.

Electron Ghost Imaging.

In this Letter we report a demonstration of electron ghost imaging. A digital micromirror device directly modulates the photocathode drive laser to control the transverse distribution of a relativistic electron beam incident on a sample. Correlating the structured illumination pattern to the total sample transmission then retrieves the target image, avoiding the need for a pixelated detector. In our example, we use a compressed sensing framework to improve the reconstruction quality and reduce the number of shots compared to raster scanning a small beam across the target. Compressed electron ghost imaging can reduce both acquisition time and sample damage in experiments for which spatially resolved detectors are unavailable (e.g., spectroscopy) or in which the experimental architecture precludes full frame direct imaging.

Age bias in survey sampling and implications for estimating HIV prevalence in men who have sex with men: insights from mathematical modelling.

Respondent-driven sampling (RDS) is widely used to estimate HIV prevalence in men who have sex with men (MSM). Mathematical models that are calibrated to these data may be compromised if they fail to account for selection biases in RDS surveys. To quantify the potential extent of this bias, an agent-based model of HIV in South Africa was calibrated to HIV prevalence and sexual behaviour data from South African studies of MSM, first reweighting the modelled MSM population to match the younger age profile of the RDS surveys (age-adjusted analysis) and then without reweighting (unadjusted analysis). The model estimated a median HIV prevalence in South African MSM in 2015 of 34.6% (inter-quartile range (IQR): 31.4-37.2%) in the age-adjusted analysis, compared with 26.1% (IQR: 24.1-28.4%) in the unadjusted analysis. The median lifetime risk of acquiring HIV in exclusively homosexual men was 88% (IQR: 82-92%) in the age-adjusted analysis, compared with 76% (IQR: 64-85%) in the unadjusted analysis. These results suggest that RDS studies may under-estimate the exceptionally high HIV prevalence rates in South African MSM because of over-sampling of younger MSM. Mathematical models that are calibrated to these data need to control for likely over-sampling of younger MSM.

Truncal varicose vein diameter and patient-reported outcome measures.

BACKGROUND: Varicose veins and chronic venous disease are common, and some funding bodies ration treatment based on a minimum diameter of the incompetent truncal vein. This study assessed the effect of maximum vein diameter on clinical status and patient symptoms. METHODS: A prospective observational cohort study of patients presenting with symptomatic varicose veins to a tertiary referral public hospital vascular clinic between January 2011 and July 2012. Patients underwent standardized assessment with venous duplex ultrasonography, and completed questionnaires assessing quality of life (QoL) and symptoms (Aberdeen Varicose Vein Questionnaire, EuroQol Five Domain QoL assessment and EuroQol visual analogue scale). Clinical scores (Venous Clinical Severity Score (VCSS) and Clinical Etiologic Anatomic Pathophysiologic (CEAP) class) were also calculated. Regression analysis was used to investigate the relationship between QoL, symptoms and vein diameter. RESULTS: Some 330 patients were assessed before surgery. The median maximum vein diameter was 7·0 (i.q.r. 5·3-9·2) mm overall, 7·9 (6·0-9·8) mm for great saphenous vein and 6·0 (5·2-8·9) mm for small saphenous vein. In linear regression analysis, vein diameter was shown to have a significant association with VCSS (P = 0·041). For every 1-mm increase in vein diameter, there was a 2·75-fold increase in risk of being in CEAP class C4 compared with C2. No other QoL or symptom measures were related to vein diameter. CONCLUSION: Incompetent truncal vein diameter was associated with increasing VCSS, but not a variety of other varicose vein disease-specific and generic patient-reported outcome measures.

A systematic review of calcium channel antagonists in bipolar disorder and some considerations for their future development.

l-type calcium channel (LTCC) antagonists have been used in bipolar disorder for over 30 years, without becoming an established therapeutic approach. Interest in this class of drugs has been rekindled by the discovery that LTCC genes are part of the genetic aetiology of bipolar disorder and related phenotypes. We have therefore conducted a systematic review of LTCC antagonists in the treatment and prophylaxis of bipolar disorder. We identified 23 eligible studies, with six randomised, double-blind, controlled clinical trials, all of which investigated verapamil in acute mania, and finding no evidence that it is effective. Data for other LTCC antagonists (diltiazem, nimodipine, nifedipine, methyoxyverapamil and isradipine) and for other phases of the illness are limited to observational studies, and therefore no robust conclusions can be drawn. Given the increasingly strong evidence for calcium signalling dysfunction in bipolar disorder, the therapeutic candidacy of this class of drugs has become stronger, and hence we also discuss issues relevant to their future development and evaluation. In particular, we consider how genetic, molecular and pharmacological data can be used to improve the selectivity, efficacy and tolerability of LTCC antagonists. We suggest that a renewed focus on LTCCs as targets, and the development of 'brain-selective' LTCC ligands, could be one fruitful approach to innovative pharmacotherapy for bipolar disorder and related phenotypes.

Randomised Controlled Trial: Potential Benefit of a Footplate Neuromuscular Electrical Stimulation Device in Patients with Chronic Venous Disease.

OBJECTIVES: Chronic venous disease (CVD) is common, affecting a quarter of the population. Current conservative methods of treatment aim to prevent progression of disease by reducing ambulatory venous pressure. Neuromuscular electrical stimulation (NMES) refers to the use of electrical impulses to elicit muscle contraction. This pilot randomised controlled trial investigates the effect of a footplate NMES device (REVITIVE) on venous flow parameters, limb oedema, and quality of life outcome measures in patients with CVD. METHODS: Twenty-two patients with Clinical Etiological Anatomical and Pathophysiological (CEAP) clinical class C2-C4 venous disease were randomised to receive a sham or test device. The recommended duration of use was for 30 minutes daily for 6 weeks. Venous flow parameters (duplex ultrasound), limb volume (optoelectric volumeter), and quality of life outcome measures were measured at baseline and after 6 weeks. RESULTS: The mean age of participants was 62 years, body mass index 28.6, with a 15:7 female preponderance. There was a significant difference in the percentage change in femoral vein flow parameters (from baseline) between the test and sham group while using the device (Week 0 time-averaged mean velocity 102.4% vs. -9.1%, p < .0001; volume flow 107.9% vs. -3.7%, p < .0001; peak velocity 377.7% vs. -6.7%, p < .0001). Limb volume was observed to increase significantly in the sham group (2.0% at Week 0 and 1.2% at Week 6; p < .01). This was prevented in the test group (+0.8% at Week 0 and 1.0% at Week 6; p = .06). There was a significant difference in the Aberdeen Varicose Vein Questionnaire between the two groups over the 6 weeks. CONCLUSIONS: This trial demonstrated a significant difference in venous flow parameters and prevention of orthostatic limb oedema with NMES. There was a positive effect on quality of life. Larger studies are required to determine the clinical significance of this in patients with venous disease.

A Review of the Evidence to Support Neuromuscular Electrical Stimulation in the Prevention and Management of Venous Disease.

INTRODUCTION: The prevention and management of venous disease is a therapeutic challenge. Movement of blood through the venous system is augmented by the action of muscles on the deep veins, and can be achieved through the application of electrical current. The efficacy of currently available clinical devices for this purpose is unknown, and is investigated here. METHODS: A literature search of the EMBASE and Medline databases was performed, and studies were included if they were full text articles, written in english, pertaining to venous disease and neuromuscular electrical stimulation (NMES). RESULTS: NMES devices increase venous haemodynamic parameters such as peak velocity and volume flow. Studies report them to be non-inferior to intermittent pneumatic compression. They are effective in the prevention of venous thromboembolism, though inferior to low molecular weight heparin. NMES can reduce symptoms of chronic venous disease. DISCUSSION: NMES is an important tool in the prevention and management of venous disease, and avoids the significant risks associated with heparin administration. Data explored here is heterogenous in device, protocol, and reported end-points, therefore should be interpreted with care. Long term effects of treatment with NMES have not been explored.

Factors impacting on patient perception of procedural success and satisfaction following treatment for varicose veins.

BACKGROUND: Patient-reported outcome measures (PROMs) have been collected from patients undergoing varicose vein treatments in the National Health Service since 2009. The aim of this retrospective cohort study was to examine PROMs for varicose vein interventions, characterizing factors that might predict patient-reported perception of procedural success and satisfaction. METHODS: Centrally compiled PROMs data for varicose vein procedures carried out from 2009 to 2011 were obtained from the Hospital Episode Statistics data warehouse for England. As data were not distributed normally, non-parametric statistical tests were employed. RESULTS: Data for 35 039 patient episodes (62·8 per cent women) were available for analysis. Some 23·4 per cent of patients reported a degree of anxiety or depression before treatment; a formal diagnosis of depression was present in 7·8 per cent. Quality of life, measured by generic EQ-5D-3L™ index and the Aberdeen Varicose Vein Questionnaire (AVVQ) improved after intervention by 11·7 per cent (0·77 to 0·86) and 40·1 per cent (18·95 to 11·36) respectively. No significant improvement was found in EQ-5D™ visual analogue scale scores. There was a significant improvement in self-perceived anxiety or depression after the intervention (P < 0·001, McNemar-Bowker test). Both preoperative and postoperative depression or anxiety had a statistically significant relationship with self-reported success and satisfaction (both P < 0·001, χ(2) test). CONCLUSION: This analysis of PROMs is evidence that treatment of varicose veins improves quality of life, and anxiety or depression. Preoperative and postoperative anxiety or depression scores impact on patient-perceived success and satisfaction rates.

Neurology of the cryopyrin-associated periodic fever syndrome.

BACKGROUND AND PURPOSE: The cryopyrin-associated periodic fever syndrome (CAPS) is an autosomal dominant autoinflammatory disorder caused by mutations in the NLRP3 gene and is typified by recurrent episodes of systemic inflammation resulting in fever, urticarial rash and arthralgia. In addition to these systemic aspects, CAPS has multiple neurological manifestations. The largest case series to date is presented focusing on the neurological features of this disorder. METHODS: The case histories of a cohort of 38 UK patients with genetically proven CAPS who were treated with interleukin 1ß (IL-1ß) inhibition as part of a national treatment programme and underwent detailed neurological assessment were reviewed. RESULTS: Across the entire disease course neurological manifestations were present in 95% of patients; 84% had some form of headache; 66% sensorineural hearing loss; 60% myalgia; 34% papilloedema and 26% optic atrophy. Patients with the T348M mutation tended to have a more severe neurological phenotype with an earlier age of onset. Four patients had cerebrospinal fluid examination, three of whom had evidence of aseptic meningitis. There was a marked response to IL-1ß inhibition, which has revolutionized management of these patients (29/32 patients with headache responding). CONCLUSION: Neurological symptoms are extremely common in CAPS and these results highlight the importance of increasing awareness amongst neurologists, particularly as highly effective therapies are available.

Imaging Molecular Motion: Femtosecond X-Ray Scattering of an Electrocyclic Chemical Reaction.

Structural rearrangements within single molecules occur on ultrafast time scales. Many aspects of molecular dynamics, such as the energy flow through excited states, have been studied using spectroscopic techniques, yet the goal to watch molecules evolve their geometrical structure in real time remains challenging. By mapping nuclear motions using femtosecond x-ray pulses, we have created real-space representations of the evolving dynamics during a well-known chemical reaction and show a series of time-sorted structural snapshots produced by ultrafast time-resolved hard x-ray scattering. A computational analysis optimally matches the series of scattering patterns produced by the x rays to a multitude of potential reaction paths. In so doing, we have made a critical step toward the goal of viewing chemical reactions on femtosecond time scales, opening a new direction in studies of ultrafast chemical reactions in the gas phase.

Impact of risk scoring on decision-making in symptomatic moderate carotid atherosclerosis.

BACKGROUND: Benefit from carotid endarterectomy (CEA) in symptomatic moderate (50-69 per cent) carotid stenosis remains marginal. The Fourth National Clinical Guideline for Stroke recommends use of the risk score from the European Carotid Surgery Trial (ECST) to aid decision-making in symptomatic carotid disease. It is not known whether clinicians are, in fact, influenced by it. METHODS: Using the ECST risk prediction model, three scenarios of patients with a low (less than 10 per cent), moderate (20-25 per cent) and high (40-45 per cent) 5-year risk of stroke were devised and validated. Invitations to complete an online survey were sent by e-mail to vascular surgeons and stroke physicians, with responses gathered. The questionnaire was then repeated with the addition of the ECST risk score. RESULTS: Two hundred and one completed surveys were analysed (21·5 per cent response rate): 107 by stroke physicians and 94 by vascular surgeons. The high-risk scenario after the introduction of the ECST risk score showed an increased use of CEA (66·7 versus 80·1 per cent; P = 0·009). The low-risk scenario after risk score analysis demonstrated a swing towards best medical therapy (23·4 versus 57·2 per cent; P < 0·001). CEA was preferred in the moderate-risk scenario and this was not altered significantly by introduction of the risk score (71·6 versus 75·6 per cent; P = 0·609). Vascular surgeons exhibited a preference towards CEA compared with stroke physicians in both low- and moderate-risk scenarios (P < 0·001 and P = 0·003 respectively). CONCLUSION: The addition of a risk score appeared to influence clinicians in their decision-making towards CEA in high-risk patients and towards best medical therapy in low-risk patients.

Interpreting the retinal neural code for natural scenes: From computations to neurons.

Understanding the circuit mechanisms of the visual code for natural scenes is a central goal of sensory neuroscience. We show that a three-layer network model predicts retinal natural scene responses with an accuracy nearing experimental limits. The model's internal structure is interpretable, as interneurons recorded separately and not modeled directly are highly correlated with model interneurons. Models fitted only to natural scenes reproduce a diverse set of phenomena related to motion encoding, adaptation, and predictive coding, establishing their ethological relevance to natural visual computation. A new approach decomposes the computations of model ganglion cells into the contributions of model interneurons, allowing automatic generation of new hypotheses for how interneurons with different spatiotemporal responses are combined to generate retinal computations, including predictive phenomena currently lacking an explanation. Our results demonstrate a unified and general approach to study the circuit mechanisms of ethological retinal computations under natural visual scenes.

Valomaciclovir versus valacyclovir for the treatment of acute herpes zoster in immunocompetent adults: a randomized, double-blind, active-controlled trial.

Herpes zoster is a common infectious disease that can result in significant acute and chronic morbidity. The safety and efficacy of once-daily oral valomaciclovir (EPB-348) was evaluated for non-inferiority to 3-times daily valacyclovir, an approved therapy. In this study, 373 immunocompetent adults with onset of a herpes zoster rash within the preceding 72 hr were randomly assigned to receive one of four treatments for 7 days: (1) EPB-348 1,000 mg once-daily; (2) EPB-348 2,000 mg once-daily; (3) EPB-348 3,000 mg once-daily; or (4) valacyclovir 1,000 mg 3-times daily. A 20% margin was the reference for non-inferiority assessment. For the primary efficacy measure of time to complete crusting of the zoster rash by Day 28, non-inferiority criteria were met for once-daily EPB-348 2,000 mg and once-daily EPB-348 3,000 mg compared to 3-times daily valacyclovir. Additionally, EPB-348 3,000 mg significantly shortened the time to complete rash crusting by Day 28 compared to valacyclovir. For secondary efficacy measures, non-inferiority was achieved for the EPB-348 1,000 and 2,000 mg groups compared to the valacyclovir group for time to rash resolution by Day 28. No EPB-348 group was non-inferior to valacyclovir for time to cessation of new lesion formation or time to cessation of pain by Day 120, though no significant differences occurred between treatment groups. Nausea, headache, and vomiting were the most common adverse events. Based on these results, additional studies are warranted to define further EPB-348's potential as an effective and safe therapy for acute herpes zoster.

The burden of depression in patients with symptomatic varicose veins.

OBJECTIVE: To evaluate the burden and impact of depression in patients with symptomatic varicose veins. METHODS: Patients with varicose veins referred to the vascular surgeons for further management, were invited to complete a validated questionnaire relating to quality of life, using the Aberdeen Varicose Veins Questionnaire (AVVQ), EuroQol-5D questionnaire (EQ-5D) and the EuroQol-Visual Analogue Score (EQ-VAS); and depressive symptoms, using the Centre of Epidemiological Studies Depression Scale (CES-D). Social, demographic, clinical (CEAP classification, venous clinical severity score (VCSS)) and venous disability score (VDS) data was also collected. RESULTS: One hundred patients, mean age 52.7 years (63 females; 37 males) were recruited. Twenty-nine per cent of patients with varicose veins had depression scores suggestive of depression; no patient had previously been diagnosed or was on treatment. Depression scores were not influenced by age (p = 0.30) or gender (p = 0.60); and there was no correlation between depression scores and VCSS (p = 0.07, r2 = 0.034), or between VDS groups 1, 2 or 3 (p = 0.75). There was a weak correlation between depression scores and AVVQ (p = 0.0009, r2 = 0.12) and depression scores and EQ-5D (p < 0.0001, r2 = 0.32) and EQ-VAS (p < 0.0001, r2 = 0.25). CONCLUSION: Depression is prevalent in patients with symptomatic varicose veins, where it is commonly undiagnosed and untreated. A more holistic approach to patients with venous disease is therefore advocated.

Management of uncomplicated varicose veins - a case vignette for a clinical decision proposal.

Venous disorder is common in the general population. Uncomplicated varicose veins represent a significant proportion of the disease burden, and can impact considerably on quality of life, producing a wide spectrum of symptoms. Little is known about the natural course of the disease at this stage and the treatment strategy employed is often not based on robust scientific evidence. The aim of this article is to elucidate the options to manage uncomplicated varicose veins. There are likely to be significant geographic differences in the treatment strategy employed, and it is hoped that we will arouse discussion among physicians regarding the management of this very common medical condition. The reader will be asked for their preferred treatment choice for a given clinical case vignette.

A machine learning photon detection algorithm for coherent x-ray ultrafast fluctuation analysis.

X-ray free electron laser experiments have brought unique capabilities and opened new directions in research, such as creating new states of matter or directly measuring atomic motion. One such area is the ability to use finely spaced sets of coherent x-ray pulses to be compared after scattering from a dynamic system at different times. This enables the study of fluctuations in many-body quantum systems at the level of the ultrafast pulse durations, but this method has been limited to a select number of examples and required complex and advanced analytical tools. By applying a new methodology to this problem, we have made qualitative advances in three separate areas that will likely also find application to new fields. As compared to the "droplet-type" models, which typically are used to estimate the photon distributions on pixelated detectors to obtain the coherent x-ray speckle patterns, our algorithm achieves an order of magnitude speedup on CPU hardware and two orders of magnitude improvement on GPU hardware. We also find that it retains accuracy in low-contrast conditions, which is the typical regime for many experiments in structural dynamics. Finally, it can predict photon distributions in high average-intensity applications, a regime which up until now has not been accessible. Our artificial intelligence-assisted algorithm will enable a wider adoption of x-ray coherence spectroscopies, by both automating previously challenging analyses and enabling new experiments that were not otherwise feasible without the developments described in this work.