The Reinforced Treat-and-Extend Protocol for Exudative Age-Related Macular Degeneration: Retrospective Assessment of 24-Month Real-World Outcomes in France.

INTRODUCTION: The aim of this work is to evaluate the real-world outcomes of the reinforced treat-and-extend (RTE) protocol for the treatment of exudative age-related macular degeneration with intravitreal injections of aflibercept or ranibizumab (anti-vascular endothelial growth factor therapies). METHODS: This was a retrospective review of patients from two tertiary ophthalmology centers in France initiating the RTE protocol between February 2018 and June 2021. The primary outcome was change in best-corrected visual acuity (BCVA) after 24 months. Secondary outcomes were change in central retinal thickness (CRT), recurrence, and management-related factors (injection interval, number of injections/consultations). Outcomes were additionally evaluated after protocol changes (strict versus modified RTE protocol groups). RESULTS: Sixty-eight patients (72 eyes) were included (68% females; mean age 82.2 ± 7.8 years). After 24 months, mean BCVA significantly improved (65.22 ± 14 vs. 71.96 ± 13 Early Treatment Diabetic Retinopathy Study letters; p < 0.001) and CRT significantly decreased (388.6 ± 104 vs. 278.8 ± 51 µM; p < 0.001) with 21% of eyes showing signs of exudation. Over the 24 months, a mean total of 14.9 ± 4.0 injections and 8.6 ± 1.4 consultations were performed. Mean 24-month injection interval was 7.9 ± 2.3 weeks. Initial and 24-month ophthalmic outcomes for eyes in the strict (47%) versus modified (53%) groups were not significantly different, but mean time interval to first recurrence of disease activity was significantly shorter for the modified group (7.3 ± 2.4 vs. 9.9 ± 2.5 weeks; p < 0.001). Patients in the strict RTE group received significantly less injections (13.9 ± 3.6 vs. 16.5 ± 3.9; p = 0.006) and mean 24-month injection interval was significantly longer (9.5 ± 2.7 vs. 6.5 ± 2.1 weeks; p < 0.001). Consultation number was similar (8.5 ± 1.9 vs. 8.8 ± 1.6; p = 0.93). Treatment with aflibercept versus ranibizumab did not influence ophthalmic or management outcomes. CONCLUSIONS: The RTE protocol, even when modified, reduced consultations but improved ophthalmic outcomes. The RTE protocol could reduce hospital visits and overall burden while also encouraging better patient compliance. Video Abstract available for this article. VIDEO ABSTRACT: Vincent Soler and François-Philippe Roubelat summarize the Reinforced Treat-and-Extend Protocol and main results (MP4 225022 KB).

Perspectives on children's autistic traits in UK-based British and Egyptian/Sudanese communities.

BACKGROUND: While most autism research is conducted in White Western samples, culture may affect perceptions and reporting of autistic traits. We explored how UK-based British and Egyptian/Sudanese communities perceive autism features. METHODS AND PROCEDURES: Nineteen participants self-identifying as British and 20 as Egyptian/Sudanese participated in focus group discussions on child development norms, and individual interviews on items of the Autism-spectrum Quotient: Children's version (AQ-Child; Auyeung et al., 2007), measuring autistic traits. Data were analysed using template analysis. OUTCOMES AND RESULTS: Three themes were developed: 1) Value judgements of behaviours; 2) Considerations on differences between children; 3) Problematic interpretations of AQ-Child items. These processes may affect how parents and community members report on children's autistic traits. Cross-cultural comparisons suggested subtle differences in interpretations and judgements, and British participants referred to age expectations and comparisons with other children more than Egyptian/Sudanese participants. However, within-group variability, sometimes attributed to socioeconomic status and generation, appeared larger than cross-cultural differences. CONCLUSIONS AND IMPLICATIONS: Our findings further the insights on influence of culture and within-community factors on reporting children's behaviour relevant to autism. These can inform the adaptation of screening tools in multi-cultural settings, to promote better autism recognition in communities where it may be underdiagnosed.

Computer security incident response teams: are they legally regulated? The Swiss example.

Computer Security Incident Response Teams (CSIRTs) or Computer Emergency Response Teams (CERTs) are an integral part of incident handling capabilities and are increasingly demanded by organizations such as critical infrastructures. They can hold many different skills and are of great interest to organizations in terms of cyber security and, more concretely, cyber incident management. This contribution seeks to analyze the extent to which their activity is regulated under Swiss law, considering that private CSIRTs are not regulated in the same way as governmental and national CSIRTs such as the Computer Emergency Response Team of the Swiss government and official national CERT of Switzerland (GovCERT).

Evaluation of the Effects of Vitrectomy with Primary Epiretinal Membrane Peel on Optical Quality Using Double-Pass Aberrometry.

INTRODUCTION: We performed a prospective, single-center, cohort study in order to evaluate the effects of vitrectomy with epiretinal membrane (ERM) peel on optical quality in patients with primary ERM. METHODS: Thirty patients treated for primary ERM by vitrectomy with ERM peel were included from our tertiary university hospital ophthalmology department. The main study outcome was a variation in optical quality parameters measured using the HD Analyzer™ between preoperative and 2-month postoperative evaluations in operated eyes. Optical quality parameters comprised point spread function (PSF) width at 10% and 50%, objective scatter index (OSI), and modulation transfer function (MTF) cutoff. Contralateral non-operated eyes were used as an internal control for measurement reproducibility. RESULTS: Mean PSF width at 10% (42.22 vs. 27.37 arc/min; p = 0.0002) and mean OSI (3.32 vs. 2.32; p = 0.0003) were significantly improved between pre- versus postoperative evaluations. Mean PSF width at 50% and mean MTF cutoff showed no changes. Subgroup analysis according to crystalline lens status gave similar results, demonstrating that improvements in mean PSF width at 10% and OSI were not lens-related. Non-operated eyes showed no changes in any of the parameters analyzed. CONCLUSION: Reduced light scattering measured by OSI indicates improved optical quality following vitrectomy with ERM peel among patients with primary ERM. OSI measurement could thus be a new parameter of interest in the preoperative assessment of primary ERM and other pre-vitrectomy assessments.

Marsquake Locations and 1-D Seismic Models for Mars From InSight Data.

We present inversions for the structure of Mars using the first Martian seismic record collected by the InSight lander. We identified and used arrival times of direct, multiples, and depth phases of body waves, for 17 marsquakes to constrain the quake locations and the one-dimensional average interior structure of Mars. We found the marsquake hypocenters to be shallower than 40 km depth, most of them being located in the Cerberus Fossae graben system, which could be a source of marsquakes. Our results show a significant velocity jump between the upper and the lower part of the crust, interpreted as the transition between intrusive and extrusive rocks. The lower crust makes up a significant fraction of the crust, with seismic velocities compatible with those of mafic to ultramafic rocks. Additional constraints on the crustal thickness from previous seismic analyses, combined with modeling relying on gravity and topography measurements, yield constraints on the present-day thermochemical state of Mars and on its long-term history. Our most constrained inversion results indicate a present-day surface heat flux of 22 ± 1 mW/m2, a relatively hot mantle (potential temperature: 1740 ± 90 K) and a thick lithosphere (540 ± 120 km), associated with a lithospheric thermal gradient of 1.9 ± 0.3 K/km. These results are compatible with recent seismic studies using a reduced data set and different inversion approaches, confirming that Mars' potential mantle temperature was initially relatively cold (1780 ± 50 K) compared to that of its present-day state, and that its crust contains 10-12 times more heat-producing elements than the primitive mantle.

Clinical and Cost-Effectiveness of PSYCHOnlineTHERAPY: Study Protocol of a Multicenter Blended Outpatient Psychotherapy Cluster Randomized Controlled Trial for Patients With Depressive and Anxiety Disorders.

Introduction: Internet- and mobile-based interventions (IMIs) and their integration into routine psychotherapy (i.e., blended therapy) can offer a means of complementing psychotherapy in a flexible and resource optimized way. Objective: The present study will evaluate the non-inferiority, cost-effectiveness, and safety of two versions of integrated blended psychotherapy for depression and anxiety compared to standard cognitive behavioral therapy (CBT). Methods: A three-armed multicenter cluster-randomized controlled non-inferiority trial will be conducted comparing two implementations of blended psychotherapy (PSYCHOnlineTHERAPYfix/flex) compared to CBT. Seventy-five outpatient psychotherapists with a CBT-license will be randomized in a 1:1:1 ratio. Each of them is asked to include 12 patients on average with depressive or anxiety disorders resulting in a total sample size of N = 900. All patients receive up to a maximum of 16 psychotherapy sessions, either as routine CBT or alternating with Online self-help sessions (fix: 8/8; flex: 0-16). Assessments will be conducted at patient study inclusion (pre-treatment) and 6, 12, 18, and 24 weeks and 12 months post-inclusion. The primary outcome is depression and anxiety severity at 18 weeks post-inclusion (post-treatment) using the Patient Health Questionnaire Anxiety and Depression Scale. Secondary outcomes are depression and anxiety remission, treatment response, health-related quality of life, patient satisfaction, working alliance, psychotherapy adherence, and patient safety. Additionally, several potential moderators and mediators including patient characteristics and attitudes toward the interventions will be examined, complemented by ecological day-to-day digital behavior variables via passive smartphone sensing as part of an integrated smart-sensing sub-study. Data-analysis will be performed on an intention-to-treat basis with additional per-protocol analyses. In addition, cost-effectiveness and cost-utility analyses will be conducted from a societal and a public health care perspective. Additionally, qualitative interviews on acceptance, feasibility, and optimization potential will be conducted and analyzed. Discussion: PSYCHOnlineTHERAPY will provide evidence on blended psychotherapy in one of the largest ever conducted psychotherapy trials. If shown to be non-inferior and cost-effective, PSYCHOnlineTHERAPY has the potential to innovate psychotherapy in the near future by extending the ways of conducting psychotherapy. The rigorous health care services approach will facilitate a timely implementation of blended psychotherapy into standard care. Trial Registration: The trial is registered in the German Clinical Trials Register (DRKS00023973; date of registration: December 28th 2020).

Analysis of tetrahydroxylated benzo[a]pyrene isomers in hair as biomarkers of exposure to benzo[a]pyrene.

A first gas chromatography-tandem mass spectrometry (GC-MS/MS) method was designed for analysis of four tetrahydroxylated benzo[a]pyrene metabolites (benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydrotetrol, benzo[a]pyrene-r-7,t-8,t-9,t-10-tetrahydrotetrol, benzo[a]pyrene-r-7,t-8,c-9,c-10-tetrahydrotetrol, and benzo[a]pyrene-r-7,t-8,c-9,t-10-tetrahydrotetrol) in hair. Hair powder extract was submitted to liquid-solid extraction, followed by C18 solid-phase purification. The analytes were derivatized with use of N-methyl-N-(trimethylsilyl)trifluoroacetamide and then analyzed by GC-MS/MS in negative chemical ionization mode. The calibration curve was linear from the limit of quantification (LOQ) to 20 pg/mg in hair. The coefficient of determination of the calibration curve was more than 0.975 for all the analytes investigated. The LOQs ranged from 0.075 to 0.2 pg/mg in hair. The method was afterward applied to the analysis of hair of 16 rats randomly allocated to experimental groups receiving 16 polycyclic aromatic hydrocarbons solubilized in oil at 0 or 0.8 mg/kg body weight by oral administration three times per week for 90 days. The analysis of monohydroxylated and dihydroxylated benzo[a]pyrenes was conducted in parallel by GC-MS/MS on the same samples. All tetrahydroxylated benzo[a]pyrene isomers were detected in hair samples collected from rats exposed to polycyclic aromatic hydrocarbons. Benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydrotetrol, the most abundant isomer in hair of treated rats, was also the principal isomer released in DNA adduct hydrolysis in humans. Moreover, the benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydrotetrol concentrations in hair were significantly greater than those of 2-hydroxybenzo[a]pyrene, 1-hydroxybenzo[a]pyrene, 7-hydroxybenzo[a]pyrene, and 4-hydroxybenzo[a]pyrene and similar to those of 9-hydroxybenzo[a]pyrene and 3-hydroxybenzo[a]pyrene. The method was also sufficiently sensitive to monitor environmental levels of exposure because two hair specimens in the eight analyzed from smokers were above the LOQ for benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydrotetrol and benzo[a]pyrene-r-7,t-8,c-9,t-10-tetrahydrotetrol. This study therefore demonstrated that tetrahydroxylated benzo[a]pyrenes in hair might be a useful biomarker for the assessment of both the general population and occupationally exposed workers.