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Purpose: To evaluate anti-VEGF treatment patterns and the influence of patient demographic and clinical characteristics on up to 6-year vision outcomes in neovascular age-related macular degeneration. Design: Retrospective, multicenter, noninterventional registry study with up to 6 years of follow-up. Participants: A cohort of 254 655 eyes (226 767 patients) with first anti-VEGF injection and at least 2 years of follow-up; 160 423 eyes had visual acuity (VA) data. Methods: Anonymized patient data were collected in the United States through the IRIS® Registry (Intelligent Research in Sight). Main Outcome Measures: Changes in VA from baseline; frequency of and gaps between intravitreal anti-VEGF injections; treatment discontinuations; switching anti-VEGF agents; and influence of baseline clinical and demographic characteristics on VA. Results: After a mean VA increase of 3.0 ETDRS letters at year 1, annual decreases led to a net loss from baseline of 4.6 letters after 6 years. Patients with longer follow-ups had better baseline and follow-up VA. From a mean of 7.2 in year 1 and 5.6 in year 2, mean injections plateaued between 4.2 to 4.6 in years 3 through 6. Treatment was discontinued in 38.8% of eyes and switched in 32.3%. When adjusting for differences at baseline, every additional injection resulted in a 0.68 letter improvement from baseline to year 1; thus, multiple injections in a year have the potential to be clinically meaningful. Older age, male gender, Medicaid insurance, and not being treated by a retina specialist were associated with a higher likelihood of vision loss at year 1. Of the patients, 58.5% lost ≥ 10 letters VA at least once during follow-up, with 14.5% of patients experiencing sustained poor vision after a median of 3.4 years. Conclusions: After modest mean VA improvement with intravitreal anti-VEGF injections at year 1, patients netted a loss of VA by year 6. Injection frequency decreased over time, and this was paired with a relatively high rate of discontinuation. Modeling suggested that more frequent injections were associated with better VA. Difficulty with continuous adherence to frequent intravitreal injections may have contributed to undertreatment resulting in less-than-optimal vision outcomes. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Caenorhabditis elegans is a model system widely used in fundamental research. Even though, nematodes are easy to maintain in the laboratory, obtaining large populations of worms require a lot of work and is time consuming. Furthermore, because C. elegans are mainly hermaphrodite it is even more complicated to obtain large amounts of males which make high-throughput experiments using C. elegans males very challenging.In order to overcome these limitations, we developed affordable and rapid methods to:(1) grow large synchronous worm populations(2) easily obtain large amounts of malesWe developed a culture method on plates to grow big synchronized worm populations with the standard incubators used on all worm labs. We also established an easy filtration method allowing to obtain large male populations in an hour. After filtering, the worm population contains more than 90% of adult males and no adult hermaphrodites since all the contaminants are larva and embryos.The culture and the filtering methods we developed are easy to implement and require a very limited investment in equipment and consumables beside the standard one present in worm labs. In addition, this filtering method could be applied to nematode's species similar in size to C. elegans.

Introduction and Objectives: Ablation of multifocal premature ventricular complexes (PVCs) is challenging. Activation mapping can be performed for the predominant morphology, but may be useless for other less prevalent ones. We aimed to describe the efficacy of an automated pace-mapping software-based ablation strategy for ablating the site of origin of multiple PVC locations. Methods: Consecutive patients referred for ablation of multifocal PVCs were prospectively enrolled. Spontaneous PVC templates were recorded and a detailed pace-mapping map was generated to spot the site of origin of PVCs. Results: A total of 47 PVCs were targeted in 21 patients (five and 16 patients with three or two PVCs morphologies each, respectively). Detailed pace-mapping comprising 73.5±41.6 different pacing locations was performed (best matching 97.2% [IQR 95.9-98.3%] similar to the clinical PVC). Activation points were acquired if possible, although ablation was only based on pace-mapping in 13 (27.6%) foci. Complete acute procedural success was obtained in 14 (66.7%) patients, while one PVC morphology was deliberately not ablated in five patients (23.8%). After 12.3±9.4 months of follow-up, PVC burden decreased from 24.4±10.4% to 5.6±5.0% (p

Objective: To evaluate high-frequency (10-kHz) spinal cord stimulation (SCS) treatment in refractory painful diabetic neuropathy. Patients and Methods: A prospective, multicenter randomized controlled trial was conducted between Aug 28, 2017 and March 16, 2021, comparing conventional medical management (CMM) with 10-kHz SCS+CMM. The participants had hemoglobin A1c level of less than or equal to 10% and pain greater than or equal to 5 of 10 cm on visual analog scale, with painful diabetic neuropathy symptoms 12 months or more refractory to gabapentinoids and at least 1 other analgesic class. Assessments included measures of pain, neurologic function, and health-related quality of life (HRQoL) over 12 months with optional crossover at 6 months. Results: The participants were randomized 1:1 to CMM (n=103) or 10-kHz SCS+CMM (n=113). At 6 months, 77 of 95 (81%) CMM group participants opted for crossover, whereas none of the 10-kHz SCS group participants did so. At 12 months, the mean pain relief from baseline among participants implanted with 10-kHz SCS was 74.3% (95% CI, 70.1-78.5), and 121 of 142 (85%) participants were treatment responders (≥50% pain relief). Treatment with 10-kHz SCS improved HRQoL, including a mean improvement in the EuroQol 5-dimensional questionnaire index score of 0.136 (95% CI, 0.104-0.169). The participants also reported significantly less pain interference with sleep, mood, and daily activities. At 12 months, 131 of 142 (92%) participants were “satisfied” or “very satisfied” with the 10-kHz SCS treatment. Conclusion: The 10-kHz SCS treatment resulted in substantial pain relief and improvement in overall HRQoL 2.5- to 4.5-fold higher than the minimal clinically important difference. The outcomes were durable over 12 months and support 10-kHz SCS treatment in patients with refractory painful diabetic neuropathy. Trial registration: clincaltrials.gov Identifier: NCT03228420

Background: Timely use of an automated external defibrillator (AED) improves outcomes in sudden cardiopulmonary arrest (SCA). Our project aims were to: 1) identify the barriers to optimal AED use in the Québec City area elementary schools; 2) create targeted educational material regarding AEDs; and 3) measure the impact of the teaching module. Methods: Using a quality improvement in health-care framework, a survey exploring the barriers to AED use was sent to 139 elementary schools. We then developed a video teaching module on using AEDs to address these barriers. A convenience sample of 92 elementary school professionals participated in a mock scenario. Metrics related to AED use were assessed at baseline and after completing the post-teaching module. The primary outcome was the time to first shock and secondary outcomes consisted of evaluating the completion of each step required for safe and effective AED use. Results: The barrier analysis survey received a response rate of 52.5%. Most schools reported having an AED (95%), but 48.6% indicated that no formal training was offered. After the teaching module, the appropriate use of the AED in an SCA simulation improved from 53% to 92% (P < 0.001). The average time elapsed before first shock was 66 (95% confidence interval [CI], 63-70) seconds at baseline compared with 47 (95% CI, 45-49) seconds post-teaching module (P < 0.001). Conclusions: Lack of training, the main barrier to optimal use of AEDs in elementary schools, can be addressed through a brief video teaching module, thus improving the ability to deliver timely and effective defibrillation. Résumé: Contexte: L’utilisation rapide d’un défibrillateur externe automatisé (DEA) améliore les résultats en cas d’arrêt cardiorespiratoire soudain (ACS). Les objectifs de notre projet étaient les suivants : 1) déterminer les obstacles à l’utilisation optimale d’un DEA dans les écoles primaires de la région de Québec; 2) créer du matériel éducatif ciblé à propos des DEA; et 3) mesurer l’impact du module d’enseignement. Méthodologie: Dans le cadre d’un projet d’amélioration de la qualité des soins de santé, un sondage explorant les obstacles à l’utilisation des DEA a été envoyé à 139 écoles primaires. Nous avons ensuite mis au point un module d’enseignement vidéo sur l’utilisation des DEA afin de surmonter ces obstacles. Un échantillon de commodité comprenant 92 professionnels des écoles primaires a participé à un scénario fictif. Les paramètres liés à l’utilisation des DEA ont été évalués au départ et après le visionnement du module d’enseignement vidéo. Le principal critère d’évaluation était le temps écoulé entre l’ACS et l’administration du premier choc et les critères secondaires consistaient à évaluer la réalisation de chaque étape requise pour une utilisation sûre et efficace d’un DEA. Résultats: Le sondage d’analyse des obstacles a généré un taux de réponse de 52,5 %. La plupart des écoles ont signalé avoir un DEA (95 %), mais 48,6 % ont indiqué qu’aucune formation n’était offerte. Après le visionnement du module d’enseignement, l’utilisation appropriée du DEA dans le cadre d’une simulation d’ACS est passée de 53 à 92 % (P

Instructional experts and practitioners in sports, dance and rehabilitation need to assess and provide feedback on motor practice. To visualise, analyse and annotate motor practice, we have developed the user-friendly application MotionPerfection. Using just a single camera video recordings and a computer, MotionPerfection enables users to compare a focal user with a model reference, to assess and annotate the performance. We illustrate the software structure and functionality from video acquisition to feedback annotation. Researchers, instructors, clinicians and practitioners can use MotionPerfection to simplify, automate and standardise the analysis and feedback of motor routines in remote and face-to-face settings, in the laboratory and in the field, without the need of specialised equipment.

The push-pull technology (PPT) is considered as an alternative integrated pest management strategy for the control of fall armyworm and stemborer, among smallholder maize farmers in sub-Sahara African to conventional pesticides. However, the extent of PPT use in Rwanda where the technology was introduced in 2017 remains largely unexplored. This paper employed a fractional logit model to assess the factors influencing the intensity of adoption of PPT among smallholder maize farmers in Gatsibo and Nyagatare districts of Rwanda using survey data obtained from 194 PPT adopter households selected using a cluster sampling technique. While only 5 percent of smallholder farmers in Rwanda have adopted PPT as an integrated pest management strategy, on the average, these farmers cultivated 26 percent of their maize plots to the technology. Our results show that the perceived benefits of PPT, its perceived effectiveness in pest control, group membership, livestock ownership, and gender of the farmer had significant effects on the intensity of adoption of the PPT in Rwanda. These findings give compelling evidence to recommend that development initiatives should give emphasis on creating awareness on the perceived benefits of PPT adoption using group approaches that are gender disaggregated.

The internal mammary lymph node (IMN) chain, along with the axillary lymph node (ALN) chain, is the first echelon nodal drainage site in breast cancer (BC). ALN with/without IMN nodal involvement is known to have a prognostic value for loco-regional and distant recurrences in BC patients. Yet, IMN sampling is not routine in clinical practice, although its invasion by tumor cells may lead to an abrupt shift in the management of BC patients. We report a case of a patient presenting with early invasive ductal carcinoma (IDC) BC treated with modified radical mastectomy and axillary sentinel lymph node biopsy (SLNB) without evidence of pathologic involvement. Several months later, during free-flap breast reconstruction using IM vessels, an accidental IMN was harvested and sent for histopathological analysis, which confirmed IMN metastasis. This unexpected finding totally modified the patient's ultimate management. We also conducted a systematic review of the literature on the implications of IMN sampling during recipient site preparation in free-flap breast reconstruction (FFBR) on the prognosis and treatment of patients in the modern “personalized-medicine” era.

One of the major drawbacks of the thermoplastic Fused Filament Fabrication process (FFF) is the poor mechanical properties of the parts produced. This is mostly related to the macroporosities resulting from a limited coalescence between filaments. Coalescence is ruled by the viscosity and surface tension of a polymer. Thus, an accurate characterization of these two properties is required to model and optimize coalescence during filament deposition and cooling. In this work, a surface tension characterization procedure over a large temperature range (25–380 °C) is presented and applied to PolyEtherKetoneKetone (PEKK) material. Additionally, the Newtonian viscosity is characterized with rheometry. The coalescence is then simulated by coupling an existing semi-analytical model with a previously presented 2D heat transfer finite element simulation model. The results show the importance of the temperature dependent implementation of surface tension. Additionally, a parametric study provides an industrial understanding of the FFF process.

Summary: Loss of membrane potential of sperm mitochondria has been regarded as the first step preceding mitophagy degradation after their entry into the C. elegans oocyte at fertilization. This is in line with the classical view of mitophagy of defective or abnormal mitochondria and could serve as a recognition signal for their specific and quick autophagy degradation. Here, using TMRE (tetramethylrhodamine ethyl ester) and live imaging we show that this is not the case. Instead, sperm inherited mitochondria show a stable labeling with TMRE before and at the time of autophagosomes formation. Interestingly, this labeling remains in late-stage-embryos of autophagy-defective-mutants suggesting that the loss of membrane potential occurs upon the entry of the mitochondria into the autophagy pathway. These stabilized and still polarized sperm mitochondria remain distinct but associated with the maternal-derived mitochondrial network suggesting a mechanism that prevents their fusion and represents an efficient additional protective system against fertilization-induced heteroplasmy.

Culture-based microdilution and disk diffusion tests are two commonly used reference methods for determining the susceptibility of causative bacteria to antibiotics. However, these methods are slow and laborious. Automated antimicrobial susceptibility test (AST) instruments are extensively used in clinical microbiology labs, replacing manual methods to perform gold standard microdilution or disk diffusion methods. These automated instruments require the use of isolated bacteria grown in pure culture against a fixed antimicrobial panel, and the susceptibility tests are based on measuring bacterial growth or turbidity changes over a range of pre-determined antimicrobial conditions. As a result, these automated technologies remain inherently inflexible to frequent adjustment of minimum inhibitory concentrations published by the Clinical and Laboratory Standards Institute and are limited by the detection methods that consumables were designed for. Here, we present a stripwell that is compatible with the 96-well format of most lab automation systems to provide a streamlined workflow to inoculate microorganisms for a customized or routine AST. The main goal of this method of stripwell preparation with various antibiotic conditions is to enable the utility of lab automation for phenotypic antibiotic response assays to address the reproducibility issues due to manual operation.• A standardized and scalable solution from inoculation to antimicrobial incubation• Microplates in stripwell format offer the advantage of greater flexibility in clinical microbiology and diagnostics• Customized antimicrobials and dilution ranges tailored to unique specifications for research and development

The ability to assess and eliminate the matrix effect in bioanalytical methods is critical for reproducibility, but sample preparation procedures necessary to address the matrix effect for microbiological methods could be significantly different if viable pathogens are required for downstream microbiological response analysis. A pure bacterial culture remains essential for virulence, antibiotic susceptibility, and phenotypic response studies in order to facilitate the understanding and treatment of caused diseases. Bacterial culture involves the collection, inoculation, incubation, growth, and detection of viable organisms while avoiding contamination throughout the entire process. The goal of this method is to concentrate viable pathogens directly from clinical specimens such as whole blood and urine while removing most interfering matrix components through pelleting in an enriched media, which is designed to facilitate the growth of clinically relevant microorganisms. Nonselective culture media with no inhibitors is used to permit the growth of most of the microorganisms present in the clinical samples studied. Most of the species implicated in clinical infections are mesophilic bacterial species, so the pelleting procedure is conducted at medium temperatures of 37°C to facilitate optimal growth. • Viable bacterial pelleting for phenotypic response analysis. • Concentration of bacteria by centrifugation and matrix component removal for direct-from-specimen molecular analysis. • Viable pathogen recovery directly from whole blood and urine.

The emergence and rapid spread of resistant bacteria has become a serious public health concern worldwide. Delayed antimicrobial therapy significantly increases mortality in high-risk infections with a particularly strong association with septic shock. Therefore, antimicrobial agents are often injudiciously used without any evidence-based microbiological confirmation. Antimicrobial consumption is strongly linked to the emergence and dissemination of antimicrobial-resistant bacteria strains in several epidemiological studies. According to CDC's recent publication, an estimated 30% of outpatient oral antimicrobial prescriptions may have been inappropriate. A compact and rapid pathogen identification (ID) and antimicrobial susceptibility testing (AST) can assist to address both the unnecessary use and overuse of antimicrobials, and therefore effectively reduce antimicrobial resistance. The overall goal of these AST protocols is to deliver a molecular diagnostic platform that is capable of profiling the antimicrobial susceptibility of causative pathogens in hours, not days. The presented AST utilizes an electrochemical sensor to quantify the microbial changes of 16S rRNA after exposure to various antimicrobial conditions either from clinical isolates or directly from unprocessed clinical specimens such as urine and blood. These protocols can be performed by our robotic lab automation systems or manual benchtop assays with associated reagent kits, AST stripwells and sensor chips. • A rapid, quantifiable antimicrobial efficacy profiling comparable to traditional AST reporting. • Customized antimicrobials and dilution ranges tailored to unique specifications for research and development. • Direct antimicrobial susceptibility of viable pathogen from whole blood, urine, or subculture.

Rothmund-Thomson Syndrome (RTS) is a rare autosomal recessive disease that manifests several clinical features of accelerated aging. These findings include atrophic skin and pigment changes, alopecia, osteopenia, cataracts, and an increased incidence of cancer for patients. Mutations in RECQL4 gene are responsible for cases of RTS. RECQL4 belongs to the RECQ DNA helicase family which has been shown to participate in many aspects of DNA metabolism. To be able to study the cellular defects related to the pathology, we derived an induced pluripotent cell line from RTS patient fibroblasts, with the ability to re-differentiate into the three embryonic germ layers.

Bloom syndrome is characterized by severe pre- and postnatal growth deficiency, immune abnormalities, sensitivity to sunlight, insulin resistance, and a high risk for many cancers that occur at an early age. The diagnosis is established on characteristic clinical features and/or presence of biallelic pathogenic variants in the BLM gene. An increased frequency of sister-chromatid exchanges is also observed and can be useful to diagnose BS patients with weak or no clinical features. For the first time, we derived an induced pluripotent cell line from a Bloom syndrome patient retaining the specific sister-chromatid exchange feature as a unique tool to model the pathology.

In this work, we studied the aptitude to sintering green bodies using γ-Al2O3 transition alumina as raw powder. We focused on the influence of the heating rate on densification and microstructural evolution. Phase transformations from transition alumina γ → δ → θ → α-Al2O3 were studied by in situ X-rays diffraction from the ambient to 1200 °C. XRD patterns revealed coexistence of various phase transformations during the heating cycle. DTA and dilatometry results showed that low heating rate leads to a significant reduction of the temperature of the α-Al2O3 alumina formation. Around 1190, 1217 and 1240 °C were found when using 5, 10 and 20 °C/min of heating rate, respectively. The activation energy for θ-Al2O3 → α-Al2O3 transformation calculated by Kissinger and JMA equations using dilatometry method were 464.29 and 488.79 kJ/mol, respectively and by DTA method were 450.72 and 475.49 kJ/mol, respectively. In addition, the sintering of the green bodies with low heating rate promotes the rearrangement of the grains during θ-Al2O3 → α-Al2O3 transformation, enhancing the relative density to 95% and preventing the development of a vermicular structure.

Werner syndrome (WS) is a rare human autosomal recessive disorder characterized by early onset of aging-associated diseases, chromosomal instability, and cancer predisposition, without therapeutic treatment solution. Major clinical symptoms of WS include common age-associated diseases, such as insulin-resistant diabetes mellitus, and atherosclerosis. WRN, the gene responsible for the disease, encodes a RECQL-type DNA helicase with a role in telomere metabolism. We derived a stable iPSC line from 53 years old patient's PBMC, with a normal karyotype, but exhibiting a short telomere length, as a major aspect of the cellular phenotype involved in the pathology.

The effect of carbon additives on electrode formulation of bulk antimony was investigated in potassium-ion batteries. Several types of carbon including conventional carbon black, graphite and double-walled carbon nanotubes (DWCNT), employed as conductive agents, were found to play a non-negligible role on the electrochemical performance of antimony. While DWCNT alone show no reversible K+ storage compared to the other carbons, the Sb/DWCNT electrode exhibits better capacity retention and rate capability than Sb formulated with usual carbon additives or even with graphite. This can be ascribed to the specific structure of DWCNT acting not only as conductive additive but also as a mechanical reinforcement for the whole electrode, which has to withstand the large volume change of antimony during potassiation/depotassiation cycles. Keywords: Potassium-ion batteries, Negative electrodes, Composites, Antimony, Carbon nanotubes

Kabuki syndrome (KS) is a rare congenital disorder (1/32000 births) characterized by distinctive facial features, intellectual disability, short stature, and dermatoglyphic and skeletal abnormalities. In the last decade, mutations in KMT2D and KDM6A were identified as a major cause of kabuki syndrome. Although genetic abnormalities have been highlighted in KS, brain abnormalities have been little explored. Here, we have investigated brain abnormalities in 6 patients with KS (4 males; Mage = 10.96 years, SD = 2.97 years) with KMT2D mutation in comparison with 26 healthy controls (17 males; Mage = 10.31 years, SD = 2.96 years). We have used MRI to explore anatomical and functional brain abnormalities in patients with KS. Anatomical abnormalities in grey matter volume were assessed by cortical and subcortical analyses. Functional abnormalities were assessed by comparing rest cerebral blood flow measured with arterial spin labeling-MRI. When compared to healthy controls, KS patients had anatomical alterations characterized by grey matter decrease localized in the bilateral precentral gyrus and middle frontal gyrus. In addition, KS patients also presented functional alterations characterized by cerebral blood flow decrease in the left precentral gyrus and middle frontal gyrus. Moreover, subcortical analyses revealed significantly decreased grey matter volume in the bilateral hippocampus and dentate gyrus in patients with KS. Our results strongly indicate anatomical and functional brain abnormalities in KS. They suggest a possible neural basis of the cognitive symptoms observed in KS, such as fine motor impairment, and indicate the need to further explore the consequences of such brain abnormalities in this disorder. Finally, our results encourage further imaging-genetics studies investigating the link between genetics, anatomical and functional brain alterations in KS. Keywords: Kabuki syndrome, Congenital disorder, Voxel-based morphometry, Arterial spin labeling, Hippocampus, Brodmann area 6 and 9

Congenital anomalies of the inferior vena cava (IVC) are rare and very often diagnosed in asymptomatic patients during computed tomography performed for other purposes. These anomalies can have significant clinical implications, for example if electrophysiology procedures are needed. Diagnostic and ablation procedures are difficult since catheter manipulation and positioning are more complex. We present here a case of successful atrioventricular nodal reentrant tachycardia ablation in a patient with unexpected IVC agenesis, using an azygos route. Resumo: As anomalias congénitas da veia cava inferior são raras e são, muitas vezes, diagnosticadas em pacientes assintomáticos como achados de tomografia computorizada realizada com outros objetivos. Estas anomalias podem ter implicações clínicas importantes, nomeadamente quando estão programados estudos eletrofisiológicos. Os procedimentos de diagnóstico e de ablação são difíceis, uma vez que o manuseamento e posicionamento do cateter é mais complexo. Apresentamos o caso bem-sucedido de uma ablação de taquicardia por reentrada nodal auriculoventricular num doente com agenesia da veia cava inferior, utilizando uma via trans-ázigos. Keywords: Supraventricular tachycardia, Ablation, Inferior vena cava agenesis, Palavras-chave: Taquicardia supraventricular, Ablação, Agenesia de veia cava inferior