Feasibility and Short-Term Outcomes in Liver-First Approach: A Spanish Snapshot Study (the RENACI Project).

(1) Background: The liver-first approach may be indicated for colorectal cancer patients with synchronous liver metastases to whom preoperative chemotherapy opens a potential window in which liver resection may be undertaken. This study aims to present the data of feasibility and short-term outcomes in the liver-first approach. (2) Methods: A prospective observational study was performed in Spanish hospitals that had a medium/high-volume of HPB surgeries from 1 June 2019 to 31 August 2020. (3) Results: In total, 40 hospitals participated, including a total of 2288 hepatectomies, 1350 for colorectal liver metastases, 150 of them (11.1%) using the liver-first approach, 63 (42.0%) in hospitals performing <50 hepatectomies/year. The proportion of patients as ASA III was significantly higher in centers performing ≥50 hepatectomies/year (difference: 18.9%; p = 0.0213). In 81.1% of the cases, the primary tumor was in the rectum or sigmoid colon. In total, 40% of the patients underwent major hepatectomies. The surgical approach was open surgery in 87 (58.0%) patients. Resection margins were R0 in 78.5% of the patients. In total, 40 (26.7%) patients had complications after the liver resection and 36 (27.3%) had complications after the primary resection. One-hundred and thirty-two (89.3%) patients completed the therapeutic regime. (4) Conclusions: There were no differences in the surgical outcomes between the centers performing <50 and ≥50 hepatectomies/year. Further analysis evaluating factors associated with clinical outcomes and determining the best candidates for this approach will be subsequently conducted.

Prevalencia de enfermedad psiquiátrica entre los suicidios consumados en la provincia de Badajoz en el periodo 2015-2017 / Prevalence of psychiatric pathology among completed suicides in the province of Badajoz in the period 2015-2017

Se realiza un estudio en 157 sujetos que durante el periodo establecido entre el 1 de julio de 2015 y el 31 de diciembre de 2017 cometieron un suicidio consumado en la provincia de Badajoz, para investigar qué porcentaje de los suicidios consumados tenían antecedentes de enfermedad mental. Los resultados indican que existe una menor relación de la esperable entre el acto suicida y la presencia de antecedentes personales psiquiátricos, ya que estos solo aparecen en dos quintas partes de la muestra. Si existen estos, el diagnóstico más frecuente es el de trastorno depresivo y el tratamiento con mayor frecuencia, antidepresivos. Estos datos contrastan con otros recogidos en la literatura que hablan de porcentajes mucho más altos de enfermedad psiquiátrica en sujetos que cometen suicidio. (AU)

A study is carried out in 157 subjects who during the period established between July 01, 2015 and December 31, 2017 committed a consummated suicide in the province of Badajoz to investigate what percentage of consummated suicides had a history of mental pathology. The results indicate that there is a lower-than-expected relationship between the suicidal act and the presence of a personal psychiatric history, as these only appear in two-fifths of the sample. If they do exist, the most frequent diagnosis is depressive disorder and the most frequent treatment is antidepressants. These data contrast with other data collected in the literature that report much higher percentages of psychiatric pathology in subjects who commit suicide. (AU)

Distinct phenotype of SARS-CoV-2 Omicron BA.1 in human primary cells but no increased host range in cell lines of putative mammalian reservoir species.

SARS-CoV-2's genetic plasticity has led to several variants of concern (VOCs). Here we studied replicative capacity for seven SARS-CoV-2 isolates (B.1, Alpha, Beta, Gamma, Delta, Zeta, and Omicron BA.1) in primary reconstituted airway epithelia (HAE) and lung-derived cell lines. Furthermore, to investigate the host range of Delta and Omicron compared to ancestral SARS-CoV-2, we assessed replication in 17 cell lines from 11 non-primate mammalian species, including bats, rodents, insectivores and carnivores. Only Omicron's phenotype differed in vitro, with rapid but short replication and efficient production of infectious virus in nasal HAEs, in contrast to other VOCs, but not in lung cell lines. No increased infection efficiency for other species was observed, but Delta and Omicron infection efficiency was increased in A549 cells. Notably replication in A549 and Calu3 cells was lower than in nasal HAE. Our results suggest better adaptation of VOCs towards humans, without an extended host range, and may be relevant to the search for the putative intermediate host and reservoirs prior to the pandemic.

Total en bloc vertebrectomy and immunochemotherapy for chondrosarcoma colliding with intraosseous lymphoma.

A 59-year-old woman diagnosed with a Grade I chondrosarcoma in T7 underwent total en bloc vertebrectomy. Analysis of the surgical piece established diagnosis of a Grade 1 chondrosarcoma confined to T7. Surprisingly, an infiltration with diffuse large B-cell lymphoma was found. Systemic disease was ruled out and diagnosis was established as intracompartmental Grade 1 chondrosarcoma colliding with intraosseous extranodal diffuse large B-cell lymphoma. Resection of chondrosarcoma was considered complete and treatment with four cycles of RCHOP was indicated. Two years after surgery, the patient remains at complete metabolic response. To date, this is the first reported case of chondrosarcoma colliding with lymphoma. Although Grade 1 chondrosarcoma is typically managed with local control through complete surgical resection, the mentioned finding of the lymphoma indicated the need for systemic treatment with immunochemotherapy.

Trace Organic Contaminant Removal from Municipal Wastewater by Styrenic ß-Cyclodextrin Polymers.

Trace organic contaminants (TrOCs) present major removal challenges for wastewater treatment. TrOCs, such as perfluoroalkyl and polyfluoroalkyl substances (PFAS), are associated with chronic toxicity at ng L-1 exposure levels and should be removed from wastewater to enable safe reuse and release of treated effluents. Established adsorbents, such as granular activated carbon (GAC), exhibit variable TrOC removal and fouling by wastewater constituents. These shortcomings motivate the development of selective novel adsorbents that also maintain robust performance in wastewater. Cross-linked ß-cyclodextrin (ß-CD) polymers are promising adsorbents with demonstrated TrOC removal efficacy. Here, we report a simplified and potentially scalable synthesis of a porous polymer composed of styrene-linked ß-CD and cationic ammonium groups. Batch adsorption experiments demonstrate that the polymer is a selective adsorbent exhibiting complete removal for six out of 13 contaminants with less adsorption inhibition than GAC in wastewater. The polymer also exhibits faster adsorption kinetics than GAC and ion exchange (IX) resin, higher adsorption affinity for PFAS than GAC, and is regenerable by solvent wash. Rapid small-scale column tests show that the polymer exhibits later breakthrough times compared to GAC and IX resin. These results demonstrate the potential for ß-CD polymers to remediate TrOCs from complex water matrices.

Malodour classification with low-cost flexible electronics.

Understanding body malodour in a measurable manner is essential for developing personal care products. Body malodour is the result of bodily secretion of a highly complex mixture of volatile organic compounds. Current body malodour measurement methods are manual, time consuming and costly, requiring an expert panel of assessors to assign a malodour score to each human test subject. This article proposes a technology-based solution to automate this task by developing a custom-designed malodour score classification system comprising an electronic nose sensor array, a sensor readout interface and a machine learning hardware fabricated on low-cost flexible substrates. The proposed flexible integrated smart system is to augment the expert panel by acting like a panel assessor but could ultimately replace the panel to reduce the test and measurement costs. We demonstrate that it can classify malodour scores as good as or even better than half of the assessors on the expert panel.

The management of neovascular age-related macular degeneration: A systematic literature review of patient-reported outcomes, patient mental health and caregiver burden.

PURPOSE: The aim of this systematic literature review was to describe patient-reported outcomes, mental health and caregiver burden in patients with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents in routine clinical practice. METHODS: Electronic searches were conducted in Embase and MEDLINE according to pre-defined criteria. RESULTS: Of 856 records identified, 63 met inclusion criteria. Depression or depressive symptoms were reported in up to 42% of patients with nAMD. Of 25/63 (40%) studies evaluating quality of life (QoL) and using various tools, eight studies reported composite National Eye Institute Visual Functioning Questionnaire scores following anti-VEGF treatment. Of these, seven reported a statistically significant improvement at the earliest time point measured (Month 3-12) and approximately 50% reported sustained QoL benefits at 12 months. In studies comparing the attributed or different regimens, the most important factor from the patient's perspective was the likelihood that a particular regimen would maintain vision. There was a preference towards treat and extend, which was associated with a perceived reduction in patient and caregiver burden, compared to fixed dosing. CONCLUSIONS: A coordinated holistic approach to patient care is key to optimizing patient well-being as well as visual outcomes. Further research regarding the patient-reported impact of nAMD management outside the trial setting (particularly international longitudinal studies) is warranted. Standardization of QoL studies would assist in establishing whether sustained QoL improvement, rather than prevention of QoL decline, should be a realistic expectation of treatment of nAMD in the longer term.

Optical coherence tomography angiography as predictor of visual outcomes in retinal vein occlusion treated with antiangiogenic therapy.

PURPOSE: Evaluate optical coherence tomography angiography (OCT-A) features in retinal vein occlusions (RVO) associated with visual outcomes after anti-VEGF. METHODS: Analytical observational study performed in eyes with macular edema secondary to RVO treated with anti-VEGF, with at least 6 months of follow-up. Bradley et al. classification of macular ischemia was used. Logistic regression analysis was used to investigate associations between final best-corrected visual acuity (BCVA) and OCT-A. RESULTS: A total of 62 eyes, 61 subjects, mean age of 70 ± 12,6 years were included. Median follow up time 21,2 months (IQR 24.8), 53,2% had central retinal vein occlusion (CRVO) and 46,8% branch retinal vein occlusion (BRVO). Median BCVA pre-treatment was 0,84 logMAR (IQR 0,83) and post-treatment 0,47 logMAR (IQR 0,52). BCVA improved at the end of follow-up (p = 0,01), as well as central retinal thickness (CRT) (p = 0,02). Regarding capillary densities (CD), there was a decrease for both plexus, Superficial CD (p = 0,01) and Deep CD (p = 0,01), being more involved the superficial plexus. The lower the capillary density in both plexus, the worse BCVA, Superficial CD (r - 0,27, p = 0,03) and Deep CD (r - 0,29, p = 0,02). Media FAZ pre-treatment was 0,30 mm2 (IQR 0,23), with enlargement to 0,37 mm2 (IQR 0,32) (p = 0,01) post-treatment. Preservation of External Limiting Membrane/ Ellipsoid Zone (ELM/EZ) was seen in 60% of subjects (n = 37). The majority had grade 3 macular ischemia. Variables that best explain visual results were, baseline visual acuity (p = 0,01), pre-treatment CRT (p = 0,02) and pretreatment foveal superficial CD (p = 0,02). CONCLUSIONS: Variables that best explain final vision after anti-VEGF were baseline visual acuity, CRT and foveal superficial CD.

Intravitreal aflibercept for the treatment of patients with neovascular age-related macular degeneration in routine clinical practice in Latin America: the AQUILA study.

BACKGROUND: AQUILA (NCT03470103) was a prospective, observational, 12-month cohort study evaluating treatment patterns, clinical effectiveness, and safety of intravitreal aflibercept (IVT-AFL) in patients from Latin America with neovascular age-related macular degeneration (nAMD). METHODS: Treatment-naïve and previously treated (switching to IVT-AFL) patients (aged ≥ 55 years) were enrolled from March 2018, with a primary completion date of September 2020, from Argentina, Colombia, Costa Rica, and Mexico. Patients received IVT-AFL in a routine clinical practice setting. RESULTS: Of 274 patients in the full analysis set, 201 were treatment-naïve and 73 had received previous treatment. The mean ± standard deviation number of IVT-AFL injections received by month 12 was 4.2 ± 1.9 (treatment-naïve) and 5.2 ± 2.7 (previously treated). The median duration from diagnosis to IVT-AFL treatment was 1.2 months (treatment-naïve) and 19.5 months (previously treated). Mean best-corrected visual acuity (BCVA) (Early Treatment Diabetic Retinopathy Study [ETDRS] letters) improved from baseline to month 12 by + 5.2 ± 18.3 (treatment-naïve; baseline: 48.2 ± 23.5) and + 3.1 ± 15.3 letters (previously treated; baseline: 47.7 ± 21.4). CONCLUSION: AQUILA is the first study to assess the use of IVT-AFL in routine clinical practice in Latin America. Mean BCVA and other visual acuity outcomes improved in both treatment groups, despite many patients not receiving the IVT-AFL label-recommended regimen of three initial monthly doses, or seven or more injections in 12 months. Patients who did receive the label-recommended number of injections had numerically greater improvements in visual acuity outcomes. Patients with nAMD treated regularly and more frequently with IVT-AFL, therefore, have the potential to achieve outcomes consistent with those observed in interventional studies. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03470103. Registered February 5, 2018, https://clinicaltrials.gov/ct2/show/NCT03470103.

Intravitreal aflibercept for the treatment of patients with diabetic macular edema in routine clinical practice in Latin America: the AQUILA study.

BACKGROUND: AQUILA (NCT03470103) was a prospective, observational, 12-month cohort study to understand treatment patterns and to evaluate the clinical effectiveness and safety of intravitreal aflibercept (IVT-AFL) in patients from Latin America with diabetic macular edema (DME). METHODS: Treatment-naïve and previously treated (switching to IVT-AFL) patients (aged ≥ 18 years) were enrolled from March 2018, with a primary completion date of September 2020, from Argentina, Colombia, Costa Rica and Mexico. Patients received IVT-AFL in a routine clinical practice setting. RESULTS: Of 258 patients in the full analysis set, 181 were treatment-naïve and 77 had received previous treatment. The mean ± standard deviation number of IVT-AFL injections by Month 12 was 3.7 ± 1.8 (treatment-naïve) and 4.0 ± 2.2 (previously treated). The median duration from diagnosis to IVT-AFL treatment was 1.8 months (treatment-naïve) and 16.0 months (previously treated). Mean best-corrected visual acuity (Early Treatment Diabetic Retinopathy Study letters) improved from baseline to Month 12 by + 8.1 ± 17.7 (treatment-naïve; baseline: 54.5 ± 19.4) and + 4.6 ± 15.4 letters (previously treated; baseline: 52.9 ± 18.6). CONCLUSION: AQUILA is the first study to assess the use of IVT-AFL in routine clinical practice in Latin America. Despite few patients being treated with the label-recommended regimen of 5 initial monthly doses or receiving ≥ 8 injections in 12 months, functional and anatomic visual outcomes improved during 12 months of treatment with IVT-AFL. Patients receiving the label-recommended number of injections had numerically greater improvements in visual acuity outcomes. Patients with DME treated regularly and more frequently with IVT-AFL therefore have the potential to achieve outcomes consistent with those observed in interventional studies. Trial registration Clinicaltrials.gov, NCT03470103. Registered February 5, 2018, https://clinicaltrials.gov/ct2/show/NCT03470103.

Neoplastic degeneration of chronic sacrococcygeal pilonidal sinus: report of seven cases and literature review.

INTRODUCTION: Neoplastic degeneration is an uncommon but extremely serious complication of pilonidal sinus (PS) disease. We pretend to determine the factors that influence in the prognosis of the neoplastic disease assessing clinical features and histological findings. MATERIALS AND METHODS: We retrospectively studied the patients diagnosed of malignization of PS in our institution from 2000 to 2019. RESULTS: Seven male patients with a mean age at diagnosis of 64.8 years old were collected. Average time between the initial symptoms of PS disease and the tumor diagnosis was 33.7 years. The patients presenting an ulcerative pattern in the primary tumor showed in all the cases perineural invasion, local deep structures infiltration, and neoplastic dissemination to the regional lymph nodes. All these patients died in an average time of 7 months. On the other hand, patients with exophytic patterns in the primary tumor did not present local invasion or regional nodes affectation. All the cases survive with an average follow-up of 70.5 months. CONCLUSIONS: Ulcerated lesions clearly show a worse prognosis than tumors with exophytic morphology. Factors as perineural infiltration, local deep structures infiltration, or regional lymph node involvement dramatically decrease survival rates.

OBJETIVO: La cancerificación es una complicación infrecuente pero grave de la enfermedad por sinus pilonidal. Intentaremos determinar los factores que influyen en el pronóstico de la enfermedad neoplásica basándonos en hallazgos clínicos e histopatológicos. MATERIAL Y MÉTODOS: retrospectivamente se revisan pacientes diagnosticados de malignización de sinus pilonidal en nuestra institución del 2000 a 2019. RESULTADOS: fueron recopilados los casos de siete varones con una media de edad al diagnóstico de 64.8 años. El promedio entre el inicio de los síntomas de sinus pilonidal y el diagnóstico del tumor fue de 33.7 años. Los pacientes con un patrón ulcerativo en el tumor primario presentaron todos invasión perineural, infiltración de estructuras profundas y diseminación a linfáticos regionales. Todos estos pacientes fallecieron en una media de 7 meses. Por el contrario, los pacientes que mostraban un patrón exofítico, no presentaron invasión local o afectación de los linfáticos regionales. Todos estos casos sobrevivieron, con una media de seguimiento de 70.5 meses. CONCLUSIONES: tumores primarios ulcerativos claramente presentan un peor pronóstico que los casos de morfología exofítica. Factores como la infiltración perineural, la invasión local de estructuras profundas o la afectación de los ganglios linfáticos regionales van ligados a una disminución dramática en la supervivencia.

Announcement Signals and Automatic Braking Using Virtual Balises in Railway Transport Systems.

In rail transport, various automatic protection systems are available to ensure the safe operation of trains and to facilitate automation and optimization tasks. For this purpose, a set of physical balises is used, which are placed at fixed points along the railway track. Based on the information provided by these balises, different information is displayed to the driver, and control actions are generated. The use of physical balises located at fixed points does not allow for automatic protection actions on sections of track where they are not installed. This is a major drawback as in many cases, temporary automatic protection actions are necessary on sections of the railway line without balises due to various circumstances (work on the track, accidents, etc.). To solve this problem, this paper presents a solution called announcement signals and automatic braking using virtual balises (ASAB-VB). This proposal allows the incorporation of virtual balises at points on the track where it is necessary to temporarily perform automatic protection actions. For this purpose, the ASAB-VB system allows obtaining the train position in real-time and storing a digital map of the track that will be made by each train. This digital map includes geographic information about the balises (both physical and virtual ones) located on the track. At the same time, the train position is obtained by merging the information provided by a GNSS, an odometer, and an inertial system (gyro and accelerometers).

Recommendations for OCT Angiography Reporting in Retinal Vascular Disease: A Delphi Approach by International Experts.

PURPOSE: To develop a consensus nomenclature for reporting OCT angiography (OCTA) findings in retinal vascular disease (e.g., diabetic retinopathy, retinal vein occlusion) by international experts. DESIGN: Delphi-based survey. SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: Twenty-five retinal vascular disease and OCTA imaging experts. METHODS, INTERVENTION, OR TESTING: A Delphi method of consensus development was used, comprising 2 rounds of online questionnaires, followed by a face-to-face meeting conducted virtually. Twenty-five experts in retinal vascular disease and retinal OCTA imaging were selected to constitute the OCTA Nomenclature in Delphi Study Group for retinal vascular disease. The 4 main areas of consensus were: definition of the parameters of "wide-field (WF)" OCTA, measurement of decreased vascular flow on conventional and WF-OCTA, nomenclature of OCTA findings, and OCTA in retinal vascular disease management and staging. The study end point was defined by the degree of consensus for each question: "strong consensus" was defined as ≥85% agreement, "consensus" as 80% to 84%, and "near consensus" as 70% to 79%. MAIN OUTCOME MEASURES: Consensus and near consensus on OCTA nomenclature in retinal vascular disease. RESULTS: A consensus was reached that a meaningful change in percentage of flow on WF-OCTA imaging should be an increase or decrease ≥30% of the absolute imaged area of flow signal and that a "large area" of WF-OCTA reduced flow signal should also be defined as ≥30% of the absolute imaged area. The presence of new vessels and intraretinal microvascular abnormalities, the foveal avascular zone parameters, the presence and amount of "no-flow areas," and the assessment of vessel density in various retinal layers should be added for the staging and classification of diabetic retinopathy. Decreased flow ≥30% of the absolute imaged area should define an ischemic central retinal vein occlusion. Several other items did not meet consensus requirements or were rejected in the final discussion round. CONCLUSIONS: This study provides international consensus recommendations for reporting OCTA findings in retinal vascular disease, which may help to improve the interpretability and description in clinic and clinical trials. Further validation in these settings is warranted and ongoing. Efforts are continuing to address unresolved questions.

Type 1 diabetes affects the brain functional connectivity underlying working memory processing.

Visuospatial working memory (VSWM) deficits have been demonstrated to occur during the development of type-1-diabetes (T1D). Despite confirming the early appearance of distinct task-related brain activation patterns in T1D patients compared to healthy controls, the effect of VSWM load on functional brain connectivity during task performance is still unknown. Using electroencephalographic methods, the present study evaluated this topic in clinically well-controlled T1D young patients and healthy individuals, while they performed a VSWM task with different memory load levels during two main VSWM processing phases: encoding and maintenance. The results showed a significantly lower number of correct responses and longer reaction times in T1D while performing the task. Besides, higher and progressively increasing functional connectivity indices were found for T1D patients in response to cumulative degrees of VSWM load, from the beginning of the VSWM encoding phase, without notably affecting the VSWM maintenance phase. In contrast, healthy controls managed to solve the task, showing lower functional brain connectivity during the initial VSWM processing steps with more gradual task-related adjustments. Present results suggest that T1D patients anticipate high VSWM load demands by early recruiting supplementary processing resources as the probable expression of a more inefficient, though paradoxically better adjusted to task demands cognitive strategy.

Central serous chorioretinopathy imaging biomarkers.

PURPOSE: To identify the factors predicting the visual and anatomical outcomes in eyes with central serous chorioretinopathy (CSCR) through 12 months. METHODS: Patients with diagnosis of CSCR, either acute or chronic, were included in this multicentric, retrospective study. Demographic factors; systemic risk factors; central macular thickness (CMT), subfoveal choroidal thickness (SFCT), linear extent of ellipsoid zone (EZ) and interdigitation zone damage on optical coherence tomography; details of leak on fluorescein angiography and indocyanine green angiography were included as predictors of anatomical and visual outcomes. Regression analysis was performed to correlate the changes in best corrected visual acuity (BCVA) and resolution of disease activity. RESULTS: A total of 231 eyes of 201 patients with a mean age (49.7±11.8 years) were analysed. A total of 97 and 134 eyes were classified as acute and chronic CSCR. BCVA (0.35±0.31 to 0.24±0.34; p<0.001), baseline optical coherence tomography (OCT) parameters including CMT (p<0.001), subretinal fluid (SRF) height (p<0.001) and SFCT (p=0.05) showed a significant change through 12 months. Multivariate regression analysis showed change in CMT (p≤0.01) and SRF height at baseline (p=0.05) as factors predictive of good visual outcome. Logistic regression analysis revealed changes in both CMT (p=0.009) and SFCT (p=0.01) through 12 months to correlate with the resolution of disease. CONCLUSION: OCT parameters such as changes in both CMT and SFCT along with subfoveal EZ damage can be predictive of disease resolution whereas changes in CMT and baseline SRF height correlate well with changes in BCVA through 12 months.

Improved collection of hematopoietic stem cells and progenitors from Fanconi anemia patients for gene therapy purposes.

Difficulties in the collection of hematopoietic stem and progenitor cells (HSPCs) from Fanconi anemia (FA) patients have limited the gene therapy in this disease. We have investigated (ClinicalTrials.gov, NCT02931071) the safety and efficacy of filgrastim and plerixafor for mobilization of HSPCs and collection by leukapheresis in FA patients. Nine of eleven enrolled patients mobilized beyond the threshold level of 5 CD34+ cells/µL required to initiate apheresis. A median of 21.8 CD34+ cells/µL was reached at the peak of mobilization. Significantly, the oldest patients (15 and 16 years old) were the only ones who did not reach that threshold. A median of 4.27 million CD34+ cells/kg was collected in 2 or 3 aphereses. These numbers were markedly decreased to 1.1 million CD34+ cells/kg after immunoselection, probably because of weak expression of the CD34 antigen. However, these numbers were sufficient to facilitate the engraftment of corrected HSPCs in non-conditioned patients. No procedure-associated serious adverse events were observed. Mobilization of CD34+ cells correlated with younger age, higher leukocyte counts and hemoglobin values, lower mean corpuscular volume, and higher proportion of CD34+ cells in bone marrow (BM). All these values offer crucial information for the enrollment of FA patients for gene therapy protocols.

Cluster Analysis of Urban Acoustic Environments on Barcelona Sensor Network Data.

As cities grow in size and number of inhabitants, continuous monitoring of the environmental impact of sound sources becomes essential for the assessment of the urban acoustic environments. This requires the use of management systems that should be fed with large amounts of data captured by acoustic sensors, mostly remote nodes that belong to a wireless acoustic sensor network. These systems help city managers to conduct data-driven analysis and propose action plans in different areas of the city, for instance, to reduce citizens' exposure to noise. In this paper, unsupervised learning techniques are applied to discover different behavior patterns, both time and space, of sound pressure levels captured by acoustic sensors and to cluster them allowing the identification of various urban acoustic environments. In this approach, the categorization of urban acoustic environments is based on a clustering algorithm using yearly acoustic indexes, such as Lday, Levening, Lnight and standard deviation of Lden. Data collected over three years by a network of acoustic sensors deployed in the city of Barcelona, Spain, are used to train several clustering methods. Comparison between methods concludes that the k-means algorithm has the best performance for these data. After an analysis of several solutions, an optimal clustering of four groups of nodes is chosen. Geographical analysis of the clusters shows insights about the relation between nodes and areas of the city, detecting clusters that are close to urban roads, residential areas and leisure areas mostly. Moreover, temporal analysis of the clusters gives information about their stability. Using one-year size of the sliding window, changes in the membership of nodes in the clusters regarding tendency of the acoustic environments are discovered. In contrast, using one-month windowing, changes due to seasonality and special events, such as COVID-19 lockdown, are recognized. Finally, the sensor clusters obtained by the algorithm are compared with the areas defined in the strategic noise map, previously created by the Barcelona city council. The developed k-means model identified most of the locations found on the overcoming map and also discovered a new area.

Defining Nonadherence and Nonpersistence to Anti-Vascular Endothelial Growth Factor Therapies in Neovascular Age-Related Macular Degeneration.

Importance: Poor adherence or persistence to treatment can be a barrier to optimizing clinical practice (real-world) outcomes to intravitreal injection therapy in patients with neovascular age-related macular degeneration (nAMD). Currently, there is a lack of consensus on the definition and classification of adherence specific to this context. Objective: To describe the development and validation of terminology on patient nonadherence and nonpersistence to anti-vascular endothelial growth factor therapy. Design, Setting, and Participants: Following a systematic review of currently used terminology in the literature, a subcommittee panel of retinal experts developed a set of definitions and classification for validation. Definitions were restricted to use in patients with nAMD requiring intravitreal anti-vascular endothelial growth factor therapy. Validation by the full nAMD Barometer Leadership Coalition was established using a modified Delphi approach, with predetermined mean scores of 7.5 or more signifying consensus. Subsequent endorsement of the definitions was provided from a second set of retinal experts, with more than 50% members agreeing or strongly agreeing with all definitions. Main Outcomes and Measures: Development of consensus definitions for the terms adherence and persistence and a classification system for the factors associated with treatment nonadherence or nonpersistence in patients with nAMD. Results: Nonadherence was defined as missing 2 or more treatment or monitoring visits over a period of 12 months, with a visit considered missed if it exceeded more than 2 weeks from the recommended date. Nonpersistence was defined by nonattendance or an appointment not scheduled within the last 6 months. The additional terms planned discontinuation and transfer of care were also established. Reasons for treatment nonadherence and nonpersistence were classified into 6 dimensions: (1) patient associated, (2) condition associated, (3) therapy associated, (4) health system and health care team associated, (5) social/economic, and (6) other, with subcategories specific to treatment for nAMD. Conclusions and Relevance: This classification system provides a framework for assessing treatment nonadherence and nonpersistence over time and across different health settings in the treatment of nAMD with current intravitreal anti-vascular endothelial growth factor treatments. This may have additional importance, given the potential association of the coronavirus pandemic on adherence to treatment in patients with nAMD.