Determination of optimal drug dose and light dose index to achieve minimally invasive focal ablation of localised prostate cancer using WST11-vascular-targeted photodynamic (VTP) therapy

Objective: To determine the optimal drug and light dose for prostate ablation using WST11 (TOOKAD® Soluble) for vascular-targeted photodynamic (VTP) therapy in men with low-risk prostate cancer. Patients and Methods: In all, 42 men with low-risk prostate cancer were enrolled in the study but two who underwent anaesthesia for the procedure did not receive the drug or light dose. Thus, 40 men received a single dose of 2, 4 or 6 mg/kg WST11 activated by 200 J/cm light at 753 nm. WST11 was given as a 10-min intravenous infusion. The light dose was delivered using cylindrical diffusing fibres within hollow plastic needles positioned in the prostate using transrectal ultrasonography (TRUS) guidance and a brachytherapy template. Magnetic resonance imaging (MRI) was used to assess treatment effect at 7 days, with assessment of urinary function (International Prostate Symptom Score [IPSS]), sexual function (International Index of Erectile Function [IIEF]) and adverse events at 7 days, 1, 3 and 6 months after VTP. TRUS-guided biopsies were taken at 6 months. Results: In all, 39 of the 40 treated men completed the follow-up. The Day-7 MRI showed maximal treatment effect (95% of the planned treatment volume) in men who had a WST11 dose of 4 mg/kg, light dose of 200 J/cm and light density index (LDI) of >1. In the 12 men treated with these parameters, the negative biopsy rate was 10/12 (83%) at 6 months, compared with 10/26 (45%) for the men who had either a different drug dose (10 men) or an LDI of <1 (16). Transient urinary symptoms were seen in most of the men, with no significant difference in IPSS score between baseline and 6 months after VTP. IIEF scores were not significantly different between baseline and 6 months after VTP. Conclusion: Treatment with 4 mg/kg TOOKAD Soluble activated by 753 nm light at a dose of 200 J/cm and an LDI of >1 resulted in treatment effect in 95% of the planned treatment volume and a negative biopsy rate at 6 months of 10/12 men (83%)

Radical prostatectomy after vascular-targeted photodynamic therapy (VTP) with TOOKAD® : feasibility, early and intermediate results

Purpose: Vascular targeted photodynamic therapy with TOOKAD® is a new therapeutic option for localized prostate cancer management. The objectives of this study were to assess the feasibility of radical prostatectomy after vascular targeted photodynamic therapy and describe functional and oncologic outcomes. Materials and Methods: We retrospectively included in study 45 patients who underwent salvage radical prostatectomy after vascular targeted photodynamic therapy for recurrent prostate cancer at a total of 14 surgical centers in Europe between October 2008 and March 2017. Of the 42 radical prostatectomies performed 16 were robot-assisted, 6 were laparoscopic and 20 were open surgery. Primary end points were morbidity and technical difficulties. Secondary end points were early and intermediate postoperative functional and oncologic outcomes. Results: Median operative time was 180 minutes (IQR 150-223). Median blood loss was 200 ml (IQR 155-363). According to the surgeons the surgery was easy in 29 patients (69%) and difficult in 13 (31%). Nerve sparing was feasible in 14 patients (33%). Five postoperative complications (12%) were found, including 2 Clavien I, 2 Clavien II and 1 Clavien IIIB complications. Of the cases 13 (31%) were pT3 and 21 (50%) were pT2c. Surgical margins were positive in 13 patients (31%). Prostate specific antigen was undetectable at 6 to 12 months in 37 patients (88%). Nine patients underwent complementary radiotherapy. Four patients had final prostate specific antigen greater than 0.2 ng/ml at a median followup of 23 months (IQR 12-36). At 1 year 27 patients (64%) were completely continent (no pads) and 10 (24%) had low incontinence (1 pad). Four patients (11%) recovered potency without treatment and 23 (64%) recovered potency with appropriate treatment. Conclusions: Salvage radical prostatectomy after vascular targeted photodynamic therapy treatment was feasible and safe without difficulty for most of the surgeons

Padeliporfin vascular-targeted photodynamic therapy versus active surveillance in men with low-risk prostate cancer (CLIN1001 PCM301): an open-label, phase 3, randomised controlled trial

BACKGROUND: Vascular-targeted photodynamic therapy, a novel tissue-preserving treatment for low-risk prostate cancer, has shown favourable safety and efficacy results in single-arm phase 1 and 2 studies. We compared this treatment with the standard of care, active surveillance, in men with low-risk prostate cancer in a phase 3 trial. METHODS: This randomised controlled trial was done in 47 European university centres and community hospitals. Men with low-risk, localised prostate cancer (Gleason pattern 3) who had received no previous treatment were randomly assigned (1:1) to vascular-targeted photodynamic therapy (4 mg/kg padeliporfin intravenously over 10 min and optical fibres inserted into the prostate to cover the desired treatment zone and subsequent activation by laser light 753 nm with a fixed power of 150 mW/cm for 22 min 15 s) or active surveillance. Randomisation was done by a web-based allocation system stratified by centre with balanced blocks of two or four patients. Best practice for active surveillance at the time of study design was followed (ie, biopsy at 12-month intervals and prostate-specific antigen measurement and digital rectal examination at 3-month intervals). The co-primary endpoints were treatment failure (histological progression of cancer from low to moderate or high risk or death during 24 months' follow-up) and absence of definite cancer (absence of any histology result definitely positive for cancer at month 24). Analysis was by intention to treat. Treatment was open-label, but investigators assessing primary efficacy outcomes were masked to treatment allocation. This trial is registered with ClinicalTrials.gov, number NCT01310894. FINDINGS: Between March 8, 2011, and April 30, 2013, we randomly assigned 206 patients to vascular-targeted photodynamic therapy and 207 patients to active surveillance. Median follow-up was 24 months (IQR 24-25). The proportion of participants who had disease progression at month 24 was 58 (28%) of 206 in the vascular-targeted photodynamic therapy group compared with 120 (58%) of 207 in the active surveillance group (adjusted hazard ratio 0·34, 95% CI 0·24-0·46; p<0·0001). 101 (49%) men in the vascular-targeted photodynamic therapy group had a negative prostate biopsy result at 24 months post treatment compared with 28 (14%) men in the active surveillance group (adjusted risk ratio 3·67, 95% CI 2·53-5·33; p<0·0001). Vascular-targeted photodynamic therapy was well tolerated. The most common grade 3-4 adverse events were prostatitis (three [2%] in the vascular-targeted photodynamic therapy group vs one [<1%] in the active surveillance group), acute urinary retention (three [2%] vs one [<1%]) and erectile dysfunction (two [1%] vs three [1%]). The most common serious adverse event in the vascular-targeted photodynamic therapy group was retention of urine (15 patients; severe in three); this event resolved within 2 months in all patients. The most common serious adverse event in the active surveillance group was myocardial infarction (three patients). INTERPRETATION: Padeliporfin vascular-targeted photodynamic therapy is a safe, effective treatment for low-risk, localised prostate cancer. This treatment might allow more men to consider a tissue-preserving approach and defer or avoid radical therapy. FUNDING: Steba Biotech

Energy Resolution Performance of the CMS Electromagnetic Calorimeter

The energy resolution performance of the CMS lead tungstate crystal electromagnetic calorimeter is presented. Measurements were made with an electron beam using a fully equipped supermodule of the calorimeter barrel. Results are given both for electrons incident on the centre of crystals and for electrons distributed uniformly over the calorimeter surface. The electron energy is reconstructed in matrices of 3 times 3 or 5 times 5 crystals centred on the crystal containing the maximum energy. Corrections for variations in the shower containment are applied in the case of uniform incidence. The resolution measured is consistent with the design goals

European consensus statement on diagnosis and treatment of adult ADHD: The European Network Adult ADHD.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that persists into adulthood in the majority of cases. The evidence on persistence poses several difficulties for adult psychiatry considering the lack of expertise for diagnostic assessment, limited treatment options and patient facilities across Europe. METHODS: The European Network Adult ADHD, founded in 2003, aims to increase awareness of this disorder and improve knowledge and patient care for adults with ADHD across Europe. This Consensus Statement is one of the actions taken by the European Network Adult ADHD in order to support the clinician with research evidence and clinical experience from 18 European countries in which ADHD in adults is recognised and treated. RESULTS: Besides information on the genetics and neurobiology of ADHD, three major questions are addressed in this statement: (1) What is the clinical picture of ADHD in adults? (2) How can ADHD in adults be properly diagnosed? (3) How should ADHD in adults be effectively treated? CONCLUSIONS: ADHD often presents as an impairing lifelong condition in adults, yet it is currently underdiagnosed and treated in many European countries, leading to ineffective treatment and higher costs of illness. Expertise in diagnostic assessment and treatment of ADHD in adults must increase in psychiatry. Instruments for screening and diagnosis of ADHD in adults are available and appropriate treatments exist, although more research is needed in this age group

Numerical Modeling of Fuel Rod Resistance Butt Welding

International audienceResistance butt welding (RBW) is the main process used by AREVA to weld end plugs to fuel rod cladding. The combination of current, electrical resistivity of the plug–cladding contact, and applied pressure is set so as to weld the parts without fusion of the materials. Because this is a solid state welding process, one of its main advantages is that the corrosion behavior of the welds is very good, because it is not affected by any potential contamination from the welding atmosphere or other components. The RBW welds are geometrically characterized by plastic deformation of the welded interface that depends on process parameters such as applied current and pressure, welding time, and initial geometry of the parts. Microstructural evolutions and extension of the heat-affected zones are also consequences of these parameters. In order to better understand the multiphysical phenomena involved during the very short welding time of this process, numerical modeling of RBW was developed. The model is also very useful for investigating new configurations and further optimizing weld quality with a reduced number of welding samples. The RBW numerical model was implemented within the finite element code FORGE, and electrical phenomena were coupled with thermal and mechanical ones. Mechanical properties of the tube and the plug were described as a function of strain, strain rate, and temperature. The temperature and pressure dependence of the electrical contact resistance were also determined and taken into account. Thanks to a good description of the thermal and mechanical history of the weld, numerical results, such as weld geometry, plastic strain, and heat-affected zones, were in good agreement with experimental ones. The model was primarily used to understand the effects of process parameters on geometry and temperature, but it was also used to optimize welding conditions

RECTO : REcommandation diminuant la Congestion par Transport Optimal

National audienceThe matching setting, a particular case of recommendation problem, focuses on applications where a so-called item can be attributed to at most one user, with the job market and the matrimonial market as chief examples. In such cases, recommending the items preferred by each user might contribute to a congestion issue as users aiming at the same item cannot be all satisfied. While some state of art approaches proceed by repairing the recommendationpolicy to account for the congestion issue, other approaches take inspiration from the optimal transport (OT) framework, and aim to map the user population onto the item population in order to minimize some global transportation cost. In OT-based recommendation state-of-art approaches,the collaborative matrix (reporting the user-item matches) is interpreted as if it were the result of an OT plan ; the underlying transport cost is inferred and used e.g. to propose new congestion-avoiding recommendation policies. In this paper, another OT-based recommendation strategy is defined, noting that the collaborative matrix reflecting the individual decisions can hardly be considered as the result of a (centralized) OT plan. Accordingly, the proposed algorithm first learns a recommendation score from the data and then defines a cost matrix, with the transportation cost decreasing depending on the matching relevance. The optimal transport plan is thereafter used for the recommendation. The experimental validation of the approach presents com-parative results on benchmark data on the matrimonial market, and proprietary real-world data on the job market, illustrating the trade-off between the recall and the congestion indicators. The discussion focuses on the integration of individual and collective criteria.La recommandation de biens rivaux (sur le marché du travail ou des rencontres) fait face au danger majeur de la congestion. Pour concevoir un système de recommandation évitant la congestion, une approche possible repose sur le transport optimal, cherchant un appariement global entre l'ensemble des utilisateurs et l'ensemble des items selon un coût de transport à définir. L'originalité de l'approche RECTO (REcommandation diminuant la Congestion parTransport Optimal) est de construire le coût de transport en fonction du score de recommandation, et de définir la politique de recommandation en fonction du plan de transport entre utilisateurs et items. Une validation expérimentale comparative, menée sur une base de données publiquerelative au marché matrimonial et une base de données propriétaire relative au marché du travail, illustre le compromis entre précision et congestion. La discussion porte sur l’intégration de critères individuels et collectifs

RECTO : REcommandation diminuant la Congestion par Transport Optimal

National audienceThe matching setting, a particular case of recommendation problem, focuses on applications where a so-called item can be attributed to at most one user, with the job market and the matrimonial market as chief examples. In such cases, recommending the items preferred by each user might contribute to a congestion issue as users aiming at the same item cannot be all satisfied. While some state of art approaches proceed by repairing the recommendationpolicy to account for the congestion issue, other approaches take inspiration from the optimal transport (OT) framework, and aim to map the user population onto the item population in order to minimize some global transportation cost. In OT-based recommendation state-of-art approaches,the collaborative matrix (reporting the user-item matches) is interpreted as if it were the result of an OT plan ; the underlying transport cost is inferred and used e.g. to propose new congestion-avoiding recommendation policies. In this paper, another OT-based recommendation strategy is defined, noting that the collaborative matrix reflecting the individual decisions can hardly be considered as the result of a (centralized) OT plan. Accordingly, the proposed algorithm first learns a recommendation score from the data and then defines a cost matrix, with the transportation cost decreasing depending on the matching relevance. The optimal transport plan is thereafter used for the recommendation. The experimental validation of the approach presents com-parative results on benchmark data on the matrimonial market, and proprietary real-world data on the job market, illustrating the trade-off between the recall and the congestion indicators. The discussion focuses on the integration of individual and collective criteria.La recommandation de biens rivaux (sur le marché du travail ou des rencontres) fait face au danger majeur de la congestion. Pour concevoir un système de recommandation évitant la congestion, une approche possible repose sur le transport optimal, cherchant un appariement global entre l'ensemble des utilisateurs et l'ensemble des items selon un coût de transport à définir. L'originalité de l'approche RECTO (REcommandation diminuant la Congestion parTransport Optimal) est de construire le coût de transport en fonction du score de recommandation, et de définir la politique de recommandation en fonction du plan de transport entre utilisateurs et items. Une validation expérimentale comparative, menée sur une base de données publiquerelative au marché matrimonial et une base de données propriétaire relative au marché du travail, illustre le compromis entre précision et congestion. La discussion porte sur l’intégration de critères individuels et collectifs