Numerical modelling for retrieval of the coating thickness variations from wavefront errors measurements.

Multilayers coating are needed for large optical components performances, but the thickness non-uniformities over the useful aperture can generate spatial and chromatic variations of the reflectance, the transmittance and the wavefront errors. Although these dependences can be measured, they are difficult to anticipate if the underlying thickness variations are unknown. We present a model to retrieve these variations from wavefront error measurements that enables the computation of any optical properties over the useful aperture at any wavelength, angle of incidence or polarization.

Rituximab is an effective treatment in patients with pemphigus vulgaris and demonstrates a steroid-sparing effect.

BACKGROUND: Corticosteroids (CS) with or without adjuvant immunosuppressant agents are standard treatment for pemphigus vulgaris (PV). The efficacy of adjuvant therapies in minimizing steroid-related adverse events (AEs) is unproven. OBJECTIVES: To utilize data collected in a French investigator-initiated, phase III, open-label, randomized controlled trial to demonstrate the efficacy and safety of rituximab and seek approval for its use in PV. METHODS: This was an independently conducted post hoc analysis of the moderate-to-severe PV subset enrolled in the Ritux 3 study. Patients were randomized to rituximab plus 0·5 or 1·0 mg kg-1 per day prednisone tapered over 3 or 6 months, or 1·0 or 1·5 mg kg-1 per day prednisone alone tapered over 12 or 18 months, respectively (according to disease severity). The primary end point was complete remission at month 24 without CS (CRoff) for ≥ 2 months, and 24-month efficacy and safety results were also reported. RESULTS: At month 24, 34 of 38 patients (90%) on rituximab plus prednisone achieved CRoff ≥ 2 months vs. 10 of 36 patients (28%) on prednisone alone. Median total cumulative prednisone dose was 5800 mg in the rituximab plus prednisone arm vs. 20 520 mg for prednisone alone. Eight of 36 patients (22%) who received prednisone alone withdrew from treatment owing to AEs; one rituximab-plus-prednisone patient withdrew due to pregnancy. Overall, 24 of 36 patients (67%) on prednisone alone experienced a grade 3/4 CS-related AE vs. 13 of 38 patients (34%) on rituximab plus prednisone. CONCLUSIONS: In patients with moderate-to-severe PV, rituximab plus short-term prednisone was more effective than prednisone alone. Patients treated with rituximab had less CS exposure and were less likely to experience severe or life-threatening CS-related AEs. What's already known about this topic? Pemphigus vulgaris (PV) is the most common type of pemphigus. Corticosteroids, a standard first-line treatment for PV, have significant side-effects. Although their effects are unproven, adjuvant corticosteroid-sparing agents are routinely used to minimize steroid exposure and corticosteroid-related side-effects. There is evidence that the anti-CD20 antibody rituximab is effective in the treatment of patients with severe recalcitrant pemphigus and in patients with newly diagnosed pemphigus. What does this study add? This study provides a more detailed analysis of patients with PV enrolled in an investigator-initiated trial. Rituximab plus prednisone had a steroid-sparing effect and more patients achieved complete remission off prednisone. Fewer patients experienced grade 3 or grade 4 steroid-related adverse events than those on prednisone alone. This collaboration between academia and industry, utilizing independent post hoc analyses, led to regulatory authority approvals of rituximab in moderate-to-severe PV.

Progress in the measurement and reduction of thermal noise in optical coatings for gravitational-wave detectors.

Coating thermal noise is a fundamental limit for precision experiments based on optical and quantum transducers. In this review, after a brief overview of the techniques for coating thermal noise measurements, we present the latest worldwide research activity on low-noise coatings, with a focus on the results obtained at the Laboratoire des Matériaux Avancés. We report new updated values for the Ta2O5, Ta2O5-TiO2, and SiO2 coatings of the Advanced LIGO, Advanced Virgo, and KAGRA detectors, and new results from sputtered Nb2O5, TiO2-Nb2O5, Ta2O5-ZrO2, MgF2, AlF3, and silicon nitride coatings. Amorphous silicon, crystalline coatings, high-temperature deposition, multi-material coatings, and composite layers are also briefly discussed, together with the latest developments in structural analyses and models.

Severe cutaneous adverse reactions due to inappropriate medication use.

BACKGROUND: The proportion of severe cutaneous adverse reactions (SCARs) that could be avoided if medication use was consistent with good medical practice is unknown. OBJECTIVES: To estimate the proportion of SCARs related to inappropriate medication use. METHODS: We carried out a retrospective study of all validated SCARs collected in a French registry between 2003 and 2016. For each case, all plausible drugs suspected of inducing SCARs (i.e. not just the drug regarded as 'the most probable') were considered with regard to (i) prescription for an inappropriate indication, (ii) unintentional rechallenge despite a previous allergy to the drug or (iii) self-medication with prescription medicines. RESULTS: In total, 602 cases were included in the analyses. Antibiotics, anticonvulsants and allopurinol were the drugs most frequently involved, accounting for more than 50% of all cases. All suspected medications were considered to have been appropriately used for 417 of the 602 individuals included in the study population [69·3%, 95% confidence interval (CI) 65·6-73·0] and inappropriately used for 144 individuals (23·9%, 95% CI 20·5-27·3). These inappropriate uses were due mainly to prescriptions for an inappropriate indication (65·8%, 95% CI 58·4-73·2) or unintentional rechallenge (20·9%, 95% CI 14·6-27·2). Allopurinol and co-trimoxazole were the drugs most frequently involved in inappropriate indications. Antibiotics were the largest group involved in unintentional rechallenge. Nonsteroidal anti-inflammatory drugs, available on prescription, were most frequently involved in inappropriate self-medication. CONCLUSIONS: Our results underline the need for respecting the appropriate indication for drugs in order to reduce the incidence of SCARs. Reducing unintentional rechallenge also seems to be a necessary preventive measure.

Real-world treatment patterns and clinical outcomes in advanced cutaneous melanoma patients in France.

BACKGROUND: Since 2011, the management of advanced melanoma has radically changed with the availability of new therapies (immunotherapy and BRAF-targeted therapy) and with BRAF testing. OBJECTIVES: Following the introduction of these new therapies, the objectives of this AMEL study were to describe treatment patterns and evaluate overall survival (OS) among unresectable stage III/IV melanoma patients, in a real-life setting in France. METHODS: The AMEL study is a multicentre retrospective record review study. Thirty-three physicians working in 33 unique treatment centres participated in the study. Two hundred and sixty-four patients diagnosed between 1 January 2012 and 31 October 2012 with unresectable stage III/IV melanoma were included in the study. RESULTS: 94.7% of the patients received a first-line antitumour drug treatment, 62.5% a second-line treatment while 26.9% received a third-line treatment with no significant differences between patients with a BRAF mutation (50.4%) and BRAF wild type (47.0%). First-line treatment differs according to the BRAF status: 74.8% of patients with a BRAF mutation received a BRAF inhibitor while 79.3% of the BRAF wild-type patients were treated with conventional chemotherapy. In second line and over, the treatment patterns were more heterogeneous, depending on the BRAF mutation, the treatment received previously, the speed of progression of the disease and the availability of immunotherapy at the time the treatment was initiated. CONCLUSION: Regardless of the BRAF mutation status, the median OS of patients was 16 months (95% CI = 14-18). Compared to a similar study conducted in 2007 (MELODY), a gain of 4 months is observed. The gain seems to be higher for patients with a BRAF mutation (18 months) than for those without a BRAF mutation (14 months). The OS of patients who sequentially received both a BRAF inhibitor and ipilimumab (28 months) highlights the benefit of this treatment sequence.

Mirrors used in the LIGO interferometers for first detection of gravitational waves.

For the first time, direct detection of gravitational waves occurred in the Laser Interferometer Gravitational-wave Observatory (LIGO) interferometers. These advanced detectors require large fused silica mirrors with optical and mechanical properties and have never been reached until now. This paper details the main achievements of these ion beam sputtering coatings.

Oxybutynin as a treatment for generalized hyperhidrosis: a randomized, placebo-controlled trial.

BACKGROUND: Hyperhidrosis is a disorder that can impair quality of life. Localized treatments may be cumbersome and ineffective, and no systemic treatments have proven to be significantly beneficial. OBJECTIVES: To evaluate the effectiveness and tolerance of low-dose oxybutynin for hyperhidrosis. METHODS: We conducted a prospective, randomized, placebo-controlled trial. From June 2013 to January 2014, 62 patients with localized or generalized hyperhidrosis were enrolled. Oxybutynin was started at a dose of 2·5 mg per day and increased gradually to 7·5 mg per day. The primary outcome was defined as improvement of at least one point on the Hyperhidrosis Disease Severity Scale (HDSS). Dermatology Life Quality Index (DLQI) and tolerance were also reported. RESULTS: Most patients (83%) in our study had generalized hyperhidrosis. Oxybutynin was superior to placebo in improving the HDSS: 60% of patients treated with oxybutynin, compared with 27% of patients treated with placebo, improved at least one point on the HDSS (P = 0·009). The mean improvement in quality of life measured by DLQI was significantly better in the oxybutynin arm (6·9) than in the placebo arm (2·3). The most frequent side-effect was dry mouth, which was observed in 43% of the patients in the oxybutynin arm, compared with 11% in the placebo arm. CONCLUSIONS: Treatment with low-dose oxybutynin is effective in reducing symptoms of hyperhidrosis in generalized or localized forms. Side-effects were frequent but minor and mainly involved dry mouth.

Sun exposure profile in the French population. Results of the EDIFICE Melanoma survey.

BACKGROUND: The incidence of melanoma is increasing worldwide, causing significant economic burden at community and individual levels. Ultraviolet radiation, from natural sunlight or artificial sources, is the main environmental, modifiable risk factor for melanoma. OBJECTIVES: The present analysis assesses the profile of sun exposure in the French population as well as the level of awareness about ultraviolet risk and protection. METHODS: The survey was conducted via telephone interviews in September and October 2011. In total, 1502 respondents were questioned about their own sun exposure with the question "do you ever, even occasionally, spend time in the sun, during leisure-time, vacation or your professional occupation?" They were also asked about sun protection measures used: protective clothing, a hat or sunscreen. RESULTS: More than three respondents out of four (78%) declared exposing themselves to the sun, with an average of 113 days per year. Of these, 38% did not use appropriate sun protection measures. We identified the following characteristics of individuals declaring high sun exposure: chiefly men under the age of 40, higher socio-professional levels, and adults with no children. Individuals who make a poor use of protective measures are mostly men and of low educational levels. Individuals declaring low sun exposure were chiefly: women, individuals over the age of 60, and those with no professional activity. The high sun protection population comprises mostly: women, higher socio-professional levels, with no specific age-group profile. CONCLUSIONS: Analysis of the EDIFICE Melanoma survey provides information about the attitudes of the French population towards sun exposure. The most frequent contexts of sun exposure and the associated socio-demographic characteristics of the population with at-risk attitudes regarding sun exposure are identified. This deeper insight into the profile of at-risk populations will allow interventions to be more accurately targeted, thus potentially improving public health benefits.

EDIFICE Melanoma survey: knowledge and attitudes on melanoma prevention and diagnosis.

BACKGROUND: Melanoma incidence is increasing worldwide thus justifying information campaigns aimed at reducing ultraviolet exposure levels and promoting early diagnosis. OBJECTIVES: We set out to assess awareness, knowledge and attitudes of the French population with regard to melanoma prevention and early diagnosis, following more than 15 years of nationwide information campaigns. METHODS: The French nationwide observational survey, EDIFICE Melanoma, was conducted after the summer (September to October 2011) through structured telephone interviews of a representative sample of 1502 individuals aged ≥18 years, using the quota method. All French regions were represented. RESULTS: Respondents had heard of sun-induced skin damage: 92% knew that sun increases melanoma risk. Knowledge of sun-protection measures was also good: 97% correctly cited at least one method of photoprotection (clothing 80%, sunscreens 69%) and 97% declared that sun exposure should be reduced between 12 pm and 4 pm in France. Knowledge of melanoma was encouraging: 70% of respondents could define the disease accurately and 60% knew the ABCDE rule for early diagnosis. However, self-tanning and sunbed use were considered by 25% and 13% of respondents, respectively, to provide protection from skin cancer. Although 43% of respondents (58% of high-risk respondents) declared they had consulted a doctor at least once for a suspect skin lesion, their actual behaviour was less encouraging: 30% declared never or almost never protecting their skin; 25% declared regularly checking their skin for atypical nevi; 12% declared checking the entire skin surface. Declared behaviour was better in fair-skin responders and those with a history of sunburn or skin cancer. CONCLUSIONS: Awareness of melanoma, early-diagnosis procedures and preventive behaviour has improved in the general French population since 1990. However, despite the good level of information, numerous misconceptions persist. Improved information campaigns in the future may help reduce the ever-increasing incidence of melanoma in France.

Comparison of sun protection modalities in parents and children.

BACKGROUND: Routine sun protection is recommended to prevent skin cancer. The aims of the present analysis were to assess and compare modalities of sun protection in parents and their children. METHODS: EDIFICE Melanoma is a French nationwide observational survey. It was conducted through phone interviews among a representative sample of 1502 individuals aged ≥18 years, using the method of quotas. The survey took place shortly after the summer, from 28 September to 20 October 2011. RESULTS: Of the 1502 subjects interviewed, 1067 reported sun exposure (SE) at least 10 days per year, 748 were parents and 319 had no children. Sun protection measures seemed adequate in both the 'parents' and 'non-parents' groups: 74% used clothing and 43% used sunscreen, which was reapplied regularly in 57% of cases. Sun protection measures used by SE parents for SE children were superior, both qualitatively and quantitatively, to those used for themselves, i.e., 50% of parents reported using clothing, sunglasses and hats for their children vs. 23% for themselves. In 87% of cases, parents reported regular re-application of sunscreen for their children vs. 44% for themselves. The sunscreen SPF (Sun Protection Factor) was significantly lower for parents than for their children. CONCLUSIONS: Sun protection awareness appears to be globally satisfactory in the French population, with no difference between adults who are parents and those who are not. From both qualitative and quantitative standpoints, French parents use sun protective measures more efficiently for their children than for themselves.

Evolution of sun-protection measures for children.

BACKGROUND: The prevention of melanoma can be significantly improved by targeting information directly towards the subpopulation of children and, as a means to achieve it, towards young parents. OBJECTIVES: The objective of this analysis was to determine the evolution over time of the sun-protection measures adopted by parents for their young children. METHODS: The Edifice Melanoma survey was based on telephone interviews of a representative sample of 1502 subjects aged ≥18 years. This particular analysis focuses on 864 adults whose children are exposed to the sun for more than 10 days a year. We compared the characteristics and attitudes of two sub-groups of parents with regard to sun protection of young children: current-day behaviour of parents with children <15 years and behaviour in the past of parents whose children are now ≥15 years. RESULTS: Present-day parents are more likely than those of previous generations to systematically or often use hats (96% vs. 90%, P < 0.01), protective clothes (92% vs. 84%, P < 0.01), sunscreen (89% vs. 80%, P < 0.01) and sunglasses (63% vs. 44%, P < 0.01) for their children. Systematic application of sunscreen is also more frequent today than several years ago as reported by 81% of present-day parents vs. 74% of those in the past (P < 0.05). Cream is reapplied every 2 h by 41% of present-day parents, compared to 33%, in the past (P < 0.05). CONCLUSIONS: The attitude of parents towards sun protection for their children has improved over the past decade.

Personal vs. intrinsic melanoma risk awareness: results of the EDIFICE Melanoma survey.

BACKGROUND: The efficiency of skin cancer prevention programmes is strongly correlated with the information dispensed, and with the level of risk awareness, of the overall population on one hand, and on the other, of specific sub-populations, according to their risk profiles. OBJECTIVES: The primary objective of this analysis was to establish a correlation between individual perceptions of the risk of developing a melanoma, and the recognized intrinsic risk factors for a given individual. Secondary objectives were to assess factors that are potentially associated with acceptable, high or low perception of melanoma risk. METHODS: The EDIFICE Melanoma survey was conducted in 2011 via telephone interviews of a representative sample of 1502 individuals aged 18 and older in the French population. RESULTS: Although most respondents (73%) had a true estimation of their intrinsic risk for melanoma, those who did not (underestimation, 17%; overestimation, 10%) had an attitude towards environmental risk factors (sun exposure, sun protection, sunbed use) that did not compensate for this misplaced perception. CONCLUSIONS: Skin cancer prevention messages need to be reinforced, new methods of evaluating understanding of the messages need to be implemented, and both need to be included into personal risk assessment.

Prevalence of sunbed use, and characteristics and knowledge of sunbed users: results from the French population-based Edifice Melanoma survey.

BACKGROUND: In addition to natural sunlight, indoor tanning has emerged as a common source of ultraviolet (UV) radiation associated with an increased risk of melanoma. It is classified as a class I human carcinogen by the World Health Organization. OBJECTIVES: This analysis presents data on the prevalence of sunbed use in France, on factors associated with sunbed use, and on risk factors, attitude and awareness of risk among sunbed users and non-users. METHODS: Edifice Melanoma, a nationwide observational survey, was conducted in France via telephone interviews among a representative sample of 1502 subjects aged ≥18 years, using the quota method. Sunbed users were defined as individuals who reported having used a sunbed at least once in their lifetime. Logistical regressions were conducted in order to identify which factors differentiate the population of sunbed users from that of non-users. RESULTS: One in ten respondents was a sunbed user and three out of four declared having used tanning facilities for over one year. In multivariate analysis, factors significantly associated with the sunbed-user group were female gender (OR = 3.897 [2.573-5.903], P < 0.001), a higher socio-professional category (OR = 2.227 [1.542-3.217]; P < 0.001), fair hair (OR = 1.583 [1.025-2.447], P = 0.039), fair skin (OR = 1.879 [1.086-3.253]; P = 0.024), freckles (OR = 1.570 [1.071-2.302]; P = 0.021) and a history of smoking (OR = 2.383 [1.633-3.476]; P < 0.001). In a second multivariate model, the fact of having a large number of melanoma risk factors was strongly associated with sunbed use (P = 0.001). Sunbed users were more likely to be informed of the role of sun exposure in reducing the skin's regenerative capacity (OR = 2.181 [1.319-3.607]; P = 0.002) but were nevertheless more likely to consider that a tan makes a person look more attractive (OR = 2.309 [1.312-4.064]; P = 0.004) and protects the skin (OR = 2.490 [1.532-4.046]; P < 0.001); they were also more frequently exposed to natural sunlight (OR = 2.214 [1.196-4.102]; P = 0.011). CONCLUSIONS: Compared to non-users, sunbed users cumulate risk factors for melanoma. Knowledge, attitudes and intentions of individuals are critical targets for public education programmes. However, awareness campaigns focusing on sunbed use, and more generally on skin cancer, should also take social and cultural norms into account.

Melanoma risk-takers: fathers and sons.

OBJECTIVES: The incidence of skin cancers, melanoma in particular, is increasing rapidly. Consequently, specific recommendations for sun-protection measures now exist. This survey set out to assess the compliance of the general population with these guidelines. METHODS: The French nationwide observational survey, EDIFICE Melanoma, was conducted (28 September to 20 October 2011) through phone interviews of a representative sample of 1502 subjects aged ≥ 18 years, using the quota method. Sun-protection was defined as frequent or systematic use of clothes or sunscreen. The group of individuals who declared exposure to the sun (N = 1172) was subdivided: risk-takers (N = 442), and those who used sun protection (N = 730). RESULTS: Risk-takers were significantly more often male (62% vs. 44%, P < 0.01), had a lower level of education (40% vs. 26%, P < 0.01), lower incomes (2587 euros vs. 2948 euros/month) and were more often smokers (42% vs. 31%, P < 0.01). In contrast, age, marital status and use of sunbeds were not significantly different between the two groups. Interestingly, risk-takers had less risk factors for melanoma. However, they were less well-informed about high-risk exposure and optimal use of sunscreen. Sun-protection measures for their children were less stringent than those of the group who used sun protection: systematic/frequent use of sunglasses (42% vs. 59%, P < 0.01), systematic use of sunscreen (77% vs. 86%, P < 0.01), and frequent renewal (69% vs. 82%, P < 0.01), high sun protection factors (SPF) (46% vs. 56%, P < 0.01), use of clothing (84% vs. 92%, P < 0.01) and hats (88% vs. 94%, P < 0.01). CONCLUSIONS: Risk-takers are characterized by a lesser understanding of sun-protection measures and behaviours. Their children benefit less from protective measures than those of people who use sun protection themselves. Improved understanding may well improve behaviours; one can therefore legitimately predict a considerable impact on parents' attitude to their own protection and that of their children.

Cutaneous melanoma in patients treated with tumour necrosis factor inhibitors: a retrospective series of 15 patients.

BACKGROUND: Several case reports suggested that tumour necrosis factor-α (TNF) inhibitors might increase the incidence and/or alter the natural course of melanoma towards a more aggressive behaviour. OBJECTIVE: Our objective was to point if history of melanoma in patients exposed to TNF inhibitors could present with a particular pattern at diagnosis or during follow-up. METHODS: We performed a retrospective multicentre study settled in the West part of France to collect and analyse all cases of patients with melanoma who received anti-TNF therapy. RESULTS: Fifteen cases were included. First, 10 patients (mean age: 55.6 years; sex ratio: 1) had a melanoma diagnosed after TNF inhibitors initiation. The mean duration between initiation of treatment and melanoma was 48.7 months. Two patients died of metastatic disease. Second, four patients had a past history of melanoma before anti-TNF therapy (mean duration of treatment: 10.8 months). None experienced a progression of melanoma disease. Last, one woman had a past history of melanoma before and then developed a second melanoma when exposed to biotherapy. CONCLUSION: Our case series does not reveal a distinct profile of melanoma in the patients exposed to TNF inhibitors. Additional prospective trials including larger number of patient are needed to demonstrate the possible link between biological therapy with TNF inhibitors and development of melanoma.

[Management of patients with metastatic cutaneous melanoma: French national guidelines. French National Cancer Institute]. / Prise en charge thérapeutique des patients atteints d'un mélanome cutané métastatique : recommandations nationales françaises. L'Institut national du cancer.

BACKGROUND: Recent years have seen the emergence of new molecules for the treatment of patients with metastatic cutaneous melanoma, with significant benefits in terms of survival and the opening of new therapeutic perspectives. In addition, many techniques are currently being developed for locoregional treatment of metastatic sites. Management of metastatic melanoma is thus fast-changing and is marked by innovative therapeutic approaches. However, the availability of these new treatments has prompted debate among healthcare professionals concerning their use and their place in therapeutic strategy. AIMS: Since 2008, the French National Cancer Institute (INCa) has been leading a project to define and diffuse national clinical practice guidelines. It has performed a review of these treatment methods, which it aims to circulate, and it is seeking to develop recommendations in order to allow nationwide implementation of innovative approaches while promoting good use thereof. METHODS: The clinical practice guidelines development process is based on systematic literature review and critical appraisal by experts within a multidisciplinary working group, with feedback from specialists in cancer care delivery. The recommendations are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines are reviewed by independent practitioners in cancer care delivery. RESULTS: This article presents the national recommendations for first- and second-line systemic treatment and for locoregional treatment of metastatic sites in patients presenting metastatic cutaneous melanoma.