Multiple and spectrally robust photonic magic angles in reconfigurable α-MoO3 trilayers.

The emergence of a topological transition of the polaritonic dispersion in twisted bilayers of anisotropic van der Waals materials at a given twist angle-the photonic magic angle-results in the diffractionless propagation of polaritons with deep-subwavelength resolution. This type of propagation, generally referred to as canalization, holds promise for the control of light at the nanoscale. However, the existence of a single photonic magic angle hinders such control since the canalization direction in twisted bilayers is unique and fixed for each incident frequency. Here we overcome this limitation by demonstrating multiple spectrally robust photonic magic angles in reconfigurable twisted α-phase molybdenum trioxide (α-MoO3) trilayers. We show that canalization of polaritons can be programmed at will along any desired in-plane direction in a single device with broad spectral ranges. These findings open the door for nanophotonics applications where on-demand control is crucial, such as thermal management, nanoimaging or entanglement of quantum emitters.

The World Organisation for Animal Health Observatory: a data-driven approach to address the needs of its Members.

This article reviews the Observatory of the World Organisation for Animal Health (WOAH, founded as OIE), including its objectives, direction and progress achieved so far. It explains the benefits offered by this data-driven programme in improving access to data and information analysis while ensuring confidentiality. In addition, the authors examine the challenges that the Observatory faces and its inextricable link to the Organisation's data management. The development of the Observatory is of the utmost importance, not only for its relevance to the development of WOAH International Standards and their implementation worldwide, but also because of its role as one of the drivers of WOAH's digital transformation plan. This transformation is essential, given the major role of information technologies in supporting regulation for animal health, animal welfare and veterinary public health.

Cet article consacré à l'Observatoire de l'Organisation mondiale de la santé animale (OMSA, fondée en tant qu'OIE) fait le point sur ses objectifs, ses orientations et les accomplissements réalisés à ce jour. Les auteurs expliquent les bénéfices et améliorations apportés par ce programme axé sur les données, en termes à la fois d'accès aux données, d'analyse de l'information et de confidentialité. Ils abordent aussi les défis auxquels l'Observatoire doit faire face et son lien indissociable avec la gestion des données de l'Organisation. Le développement de l'Observatoire revêt une importance fondamentale, non seulement en regard de sa pertinence pour l'élaboration et la mise en oeuvre des normes internationales de l'OMSA partout dans le monde, mais aussi parce qu'il est le moteur de la planification de la transformation numérique de l'OMSA. Cette transformation est cruciale, compte tenu du rôle majeur que jouent les technologies de l'information en appui de la réglementation de la santé animale, du bien-être animal et de la santé publique vétérinaire.

Los autores presentan el Observatorio de la Organización Mundial de Sanidad Animal (OMSA, fundada como OIE), deteniéndose en particular en sus objetivos, su orientación y el camino recorrido hasta ahora. También exponen las ventajas que ofrece este programa centrado en los datos para mejorar tanto el acceso a los datos como los análisis de información, asegurando al mismo tiempo la confidencialidad. Además, examinan las dificultades a que hace frente el Observatorio y el indisociable vínculo que este guarda con la gestión de datos de la Organización. El desarrollo del Observatorio reviste una importancia capital, no solo por su utilidad para la elaboración de las normas internacionales de la OMSA y su aplicación en todo el mundo, sino también porque constituye uno de los motores del plan de transformación digital de la OMSA. Se trata de un proceso de transformación esencial, dada la importante función que cumplen las tecnologías de la información a la hora de regular la sanidad y el bienestar animales y la salud pública veterinaria.

Bonebridge® bone conduction implant. Hearing outcomes and quality of life in patients with conductive/mixed hearing loss.

PURPOSE: The aim of this study was to analyze the hearing outcomes and quality of life in a series of 52 patients affected by conductive or mixed hearing loss and treated with Bonebridge®. METHODS: 52 of 71 patients implanted with Bonebridge® between October 2012 and January 2022, were included in the study. We compared the air conduction thresholds at the frequencies 500, 1000, 2000, 3000, 4000 Hz, the SRT50% and the World Recognition Score at an intensity of 50 dB with and without the implant. The Abbreviated Profile of Hearing Aid Benefit (APHAB) was employed to assess the quality of life of patients. RESULTS: The liminal tone audiometry (free field) pure tone average for air conduction after 6 months with the implant was 35.12 dB, obtaining a mean gain of 31.83 dB. With Bonebridge®, the mean SRT was 34.17 dB, whereas before the surgery no patient achieved 50% of correct answers at a sound intensity of 50 dB. The world recognition score at 50 dB changed from 11% without the implant to 85% with it. We observed one case of implant failure and one case of implant exposure. The APHAB questionnaire showed an improvement after implantation in practically all the subscales. CONCLUSIONS: The hearing outcomes and the subjective benefits reported by patients obtained in our study are similar to those published in the literature. Bonebridge® represents an excellent method for the rehabilitation of patients with conductive and mixed hearing loss, showing a low rate of complications.

Effect of COVID-19 prevention as part of an urban renewal programme.

OBJECTIVES: To address existing inequalities, the Barcelona City Council launched a Neighbourhood Plan in 2016-2020. During the first wave of the COVID-19 pandemic, the Neighbourhood Plan interventions were intensified. This study aimed to assess the effect of the plan on the incidence of COVID-19 during the first wave of the pandemic in Barcelona. STUDY DESIGN: We used a quasi-experimental design with 16 intervention neighbourhoods and 17 neighbourhoods in the comparison group with similar socioeconomic characteristics. METHODS: We calculated the cumulative incidence rate (CIR) of COVID-19 per 100,000 inhabitants by sex, age groups, and neighbourhood of residence. Poisson regression models were fitted to estimate the crude relative risk and relative risk adjusted by socioeconomic status (cRR and aRR) and their 95% confidence intervals (CIs). RESULTS: The CIR of COVID-19 was lower in the intervention neighbourhoods (CIR: 841 per 100,000 inhabitants) than in the comparison group (CIR: 973 per 100,000 inhabitants). On multivariate analysis, the aRR was 0.77 (CI: 0.70-0.83) for men and 0.89 (CI: 0.83-0.96) for women. Among men older than 75 years (aRR = 0.73; CI: 0.62-0.86), statistically significant differences were found in the intervention neighbourhoods compared to the comparison group. This pattern was not observed in women older than 75 years (aRR = 1.13; CI: 0.99-1.30). CONCLUSION: This research finds positive short-term effect in the intervention neighbourhoods. We conclude that the COVID-19 control and prevention interventions are likely to explain the better performance in the neighbourhoods included in the Neighbourhood Plan.

Better caregiver mastery is associated with less anxiety in individuals with cognitive impairment.

BACKGROUND: When caregivers have a high level of caregiver mastery, their care recipients with cognitive impairment have less behavioral health problems. However, the relationship between caregiver mastery and anxiety among care recipients over time is unknown. Therefore, this study was conducted to examine that better caregiver mastery is associated with less anxiety in individuals with cognitive impairment over time. METHODS: A secondary data analysis was conducted using the Healthy Patterns Clinical Trial (NCT03682185) dataset and guided by Factors Associated with Behavioral and Psychological Symptoms of Dementia conceptual framework. This study included 154 dyads of individuals with cognitive impairment and their caregivers. Multiple linear regression analyses were performed on changes in anxiety. Model 1 included variables at the level of neurodegeneration (i.e., cognitive impairment and age). Model 2 added patient factors (i.e., sleep problems and depression) with the Model 1. Finally, Model 3 included caregiver factor (i.e., caregiver mastery) with the Model 2 to examine how changes in caregiver mastery influence changes in anxiety of care recipients. RESULTS: Model 3 was statistically significant; after controlling for variables at the level of neurodegeneration associated with cognitive impairment and patient factors, improvement of caregiver mastery over time (ß =-0.230, p = 0.015) was related to decreased anxiety over time (R2 = 0.1099). CONCLUSIONS: Caregivers with high caregiver mastery may have better knowledge on how to care for their loved ones and how to manage their neuropsychiatric symptoms. Therefore, improving the level of caregiver mastery by providing psychoeducational programs and resources that family caregivers need will help reduce the frequency of anxiety in individuals with cognitive impairment.

[Ten-year survival after off-pump coronary artery bypass grafting compared with traditional bypass grafting]. / Cirugía de revascularización miocárdica: comparación de supervivencia a 10 años de la cirugía coronaria con y sin circulación extracorpórea mediante Propensity Score Matching.

BACKGROUND: Long-term outcomes of Off-Pump Coronary Artery Bypass Grafting (OPCAB) as an alternative to the traditional Coronary Artery Bypass Grafting (CABG) technique with cardiopulmonary bypass (CPB) are not well defined. AIM: To compare 10-year survival of isolated OPCAB versus CABG with CPB. MATERIAL AND METHODS: Analysis of information obtained from databases, clinical records and surgical protocols of patients treated with isolated CABG between January 2006 and November 2008 at a Regional Hospital. Of 658 isolated CABG, 192 (29.2%) were OPCAB and 466 (79.9%) CPB. Propensity Score Matching (PSM) was performed to compare both groups. After PSM, two groups of 192 cases were obtained. Mortality data was obtained from the Chilean public identification service. Ten-year survival was calculated and compared with Kaplan-Meier and log-rank methods. RESULTS: Follow-up data was obtained in all cases. No statistically significant differences were found when comparing 10-year survival between OPCAB versus CPB (78.6% and 80.2% respectively, p 0.720). There was also no statistical difference in cardiovascular death free survival (90.1% with CPB versus 89.1% OPCAB, p 0.737). Survival was comparable when analyzing subgroups with diabetes mellitus, left ventricular dysfunction or chronic kidney disease, among others. CONCLUSIONS: In our series, OPBAB has a comparable 10-year survival with CABG with CPB.

Search for Dark-Matter-Induced Oscillations of Fundamental Constants Using Molecular Spectroscopy.

A possible implication of an ultralight dark matter field interacting with the standard model degrees of freedom is oscillations of fundamental constants. Here, we establish direct experimental bounds on the coupling of an oscillating ultralight dark matter field to the up, down, and strange quarks and to the gluons, for oscillation frequencies between 10 and 10^{8} Hz. We employ spectroscopic experiments that take advantage of the dependence of molecular transition frequencies on the nuclear masses. Our results apply to previously unexplored frequency bands and improve on existing bounds at frequencies >5 MHz. We also improve on the bounds for coupling to the electromagnetic field and the electron field, in particular spectral windows. We identify a sector of ultralight dark matter and standard model coupling space where the bounds from equivalence principle tests may be challenged by next-generation experiments of the present kind.

The Role of National Paid Family and Medical Leave Policies in Promoting Health Equity for Older Adults and Their Caregivers.

More than 48 million unpaid family/friend caregivers in the United States provide care to older adults. This unpaid workforce provides essential support for family members or friends who have a serious, long-term illness or disability. However, family caregivers are often under supported, which contributes to negative health, economic, and psychological consequences. Despite the significant contributions of family caregivers, there are limited policy supports aimed at alleviating the hardships of care on this growing community. National paid family and medical leave policy in particular holds substantial potential to alleviate the compounding burdens faced by family caregivers and address systemic inequities that contribute to disproportionately poorer caregiving outcomes among historically marginalized older adults and their caregivers. The purpose of the current article is to provide an overview of the economic burdens and caregiving-related health disparities experienced by Black/African American and Hispanic/Latinx family caregivers and discuss the impact of paid leave policies on the overall health and well-being of older adults. We propose a "Call to Action" for gerontological nurses to work in partnership with transdisciplinary colleagues, stakeholders, and advocates to ensure all family care-givers have access to paid leave. [Journal of Gerontological Nursing, 48(3), 5-10.].

[Suturing basic procedural skills training for medical students during COVID-19 pandemic]. / Entrenamiento procedimental básico (EPROBA) en suturas para estudiantes de medicina durante pandemia por SARS-CoV-2 (COVID-19).

BACKGROUND: The adoption of sanitary measures due to the SARS-CoV-2 pandemic hampered teaching and learning methods in medicine. AIM: To communicate the results of a wound suture training workshop, based on the Basic Procedural Skills Training methodology and adapted to the pandemic context. MATERIAL AND METHODS: One hundred fourteen students were randomized in small groups due to sanitary measures and trained with a modification of the Basic Procedural Skills Training methodology. An informed consent was obtained from every student. The suturing skills were evaluated before and after the intervention with "The Objective Structured Assessment Of Technical Skills" (OSATS) instrument. The perception of the workshop and the implementation of the COVID-19 prevention measures were also evaluated. RESULTS: The students showed a statistically significant improvement after the intervention. In the OSATS verification list, the average score increased from 4.5 to 8.6 (p < 0.01). In the OSATS global scale, the average score increased from 13.0 to 25.3 (p < 0.01). The perception of the workshop and the prevention measures were well evaluated. CONCLUSIONS: Despite all the limitations of the pandemic context, we achieved a significant improvement after the intervention and a very good perception by the students.

[Risk factors associated with 10-year survival after coronary artery bypass grafting]. / Enfermedad coronaria: factores de riesgo y supervivencia a 10 años en la cirugía coronaria.

BACKGROUND: Coronary artery bypass grafting (CABG) is the treatment of choice for a broad spectrum of patients with coronary disease. AIM: To describe global survival and factors associated with lower long-term survival in patients operated with isolated CABG. MATERIAL AND METHODS: Analysis of a cohort of patients who underwent CABG between January 2006 and December 2008 at a public hospital. The database and operation records of 1.003 cardiac surgeries were reviewed. Of these, an isolated CABG was performed in 658 patients aged 62 ± 9 years including 516 male (78%). Survival data were obtained from the Chilean Civil Registry Office and a complete ten-year follow up was accomplished. Survival was analyzed with Kaplan-Meier method with log-rank test and Cox regression. RESULTS: Operative mortality occurred in 13 patients (2%). Survival at 1, 3, 5 and 10 years was 97, 94, 91 and 76%, respectively. One, 3, 5 and 10-year free of cardiovascular death survival was 98, 97, 95 y 89%, respectively. Factors associated with long-term survival were chronic kidney disease in hemodialysis (Hazard ratio (HR) 7.9; 95% confidence intervals (CI) 4.6-13.6), chronic obstructive pulmonary disease (HR 2.3; 95% CI 1.4-3.7), chronic arterial occlusive disease (HR 2.2; 95% CI 1.4-3.4) and diabetes mellitus (HR 1.9; 95% CI 1.4-2.6). According to EuroSCORE, 10-year survival was 86, 75 and 62% (p < 0.01) in low, medium and high-risk patients, respectively. CONCLUSIONS: These patients had a 10-year survival comparable to large international series. Groups associated with lower 10-year survival were identified.

Electrocardiographic findings in true acute left main coronary total occlusion a subanalisys from ATOLMA registry.

INTRODUCTION: Acute total occlusion of the left main coronary artery (ATOLMA) usually leads to a catastrophic presentation. Prediction of ATOLMA by electrocardiogram (ECG) may contribute to early detection and reperfusion. Limited data have been reported previously. This study aims to identify the admission 12­leads ECG features that can predict the presence of ATOLMA and in-Hospital mortality in these patients. METHODS: The admission ECGs findings in 24 patients from the previously reported ATOLMA multicenter registry were compared to the ECGs findings in 15 patients with an acute subtotal occlusion of the left main (ASOLMA) and to 15 patients with anterior ST-elevation myocardial infarction of the proximal left anterior descending (LADp-STEMI). RESULTS: Some ECG features at presentation can predict an ATOLMA: QRS left axis deviation (-61.17 ± 9 degrees); ST-segment elevation in aVL (1.9 ± 0.65 mm); absence of ST-segment elevation in V1 (0.0 ± 0.6 mm); bifascicular block (58%); fragmented QRS (62.5%); prolongation of QTc interval (465 ± 19 ms) and of QRS interval (136 ± 12 mm). The multivariate analysis found that the independent predictors to distinguish ATOLMA from ASOLMA were aVL ST-segment deviation (OR 5.6(95% CI 1.5-21), p = 0.01) and absence of V1 ST-segment elevation (OR 27(95% CI 1.4-52), p = 0.01); and from LADp-STEMI was QRS width (OR 1.1(95% CI 1.02-1.2), p = 0.02). Fragmented QRS was the only independent predictor of in-hospital mortality in ATOLMA (OR 0.125(95% CI 0.01-0.81), p = 0.03). CONCLUSIONS: aVL ST-segment elevation, the absence of V1 ST-segment elevation, left axis deviation, the presence of bifascicular block, and prolongation of QRS and QTc interval are predictors of ATOLMA. Fragmented QRS predicts in-hospital mortality in ATOLMA.

Role of Intratympanic Dexamethasone for Intractable Posterior Canal Benign Paroxysmal Positional Vertigo.

BACKGROUND: Benign paroxysmal positional vertigo is a frequent diagnosed disorder, most of the patients are successfully treated with reposition maneuvers. In between 3-12.5% of these patients remain symptomatic. Recent studies support the use of intratympanic corticosteroid for intractable vertigo with promising results. MATERIAL AND METHODS: Patients diagnosed with benign paroxysmal positional vertigo between June 2017 and December 2019 in a tertiary university hospital and in two private hospitals were included in the study and analyzed prospectively. They were treated and followed with repositioning maneuvers and intratympanic dexamethasone injections if the criteria was met. RESULTS: 4 out 72 patients included in the study developed criteria for intractable vertigo after at least 6 repositioning maneuvers. The posterior semicircular canal was affected in all cases, 3 out of 4 patients experienced symptom resolution, after two, four and five intratympanic dexamethasone injections respectively. CONCLUSIONS: The use of intratympanic steroids to treat patients with refractory benign paroxysmal positional vertigo showed encouraging results. We believe a multicenter randomized clinical trial should be performed to assess the efficacy of intratympanic steroids in the treatment of this pathology.

Primary Angioplasty in a Catastrophic Presentation: Acute Left Main Coronary Total Occlusion-The ATOLMA Registry.

OBJECTIVES: To determine the outcome predictors of in-hospital mortality in acute total occlusion of the left main coronary artery (ATOLMA) patients referred to emergent angioplasty and to describe the clinical presentation and the long-term outcome of these patients. BACKGROUND: ATOLMA is an uncommon angiographic finding that usually leads to a catastrophic presentation. Limited and inconsistent data have been previously reported regarding true ATOLMA, yet comprehensive knowledge remains scarce. METHODS: This is a multicenter retrospective cohort that includes patients presenting with myocardial infarction due to a confirmed ATOLMA who underwent emergency percutaneous coronary intervention (PCI). RESULTS: In the period of the study, 7930 emergent PCI were performed in the five participating centers, and 46 of them had a true ATOLMA (0.58%). At admission, cardiogenic shock was present in 89% of patients, and cardiopulmonary resuscitation was required in 67.4%. All the patients had right dominance. Angiographic success was achieved in 80.4% of the procedures, 13 patients (28.2%) died during the catheterization, and the in-hospital mortality rate was 58.6% (27/46). At one-year and at the final follow-up, 18 patients (39%) were alive, including four cases successfully transplanted. Multivariate analysis showed that postprocedural TIMI flow was the only independent predictor of in-hospital mortality (OR 0.23, (95% CI 0.1-0.36), p < 0.001). CONCLUSIONS: Our study confirms that the clinical presentation of ATOLMA is catastrophic, presenting a high in-hospital mortality rate; nevertheless, primary angioplasty in this setting is feasible. Postprocedural TIMI flow resulted as the only independent predictor of in-hospital mortality. In-hospital survivors presented an encouraging outcome. ATOLMA and left dominance could be incompatible with life.

Experimental characterization of a biosensor based on a tapered optical fiber for kisspeptin detection.

This paper presents the development of a biosensor based on optical fiber, using a polyclonal antibody kisspeptin receptor as a biological recognition element that is connected to puberty onset and may also help to suppress metastasis in melanoma breast cancer. The fiber surface was chemically prepared to immobilize the antibody. The structural homogeneity of the biosensor, at each stage of the self-assembly, was characterized by Fourier transform infrared spectroscopy and by measurements of the transmission at the output of the biosensor. The morphological homogeneity analysis was performed by optical microscopy and scanning electron microscopy. The biosensor developed was checked to detect kisspeptin in brain tissues by spectral transmission using a superluminescent diode. The data were analyzed using principal component analysis. The interaction of the kisspeptin with its counterpart by means of the evolution of the transmission spectrum as a function of time was observed.

Scalar Dark Matter in the Radio-Frequency Band: Atomic-Spectroscopy Search Results.

Among the prominent candidates for dark matter are bosonic fields with small scalar couplings to the standard-model particles. Several techniques are employed to search for such couplings, and the current best constraints are derived from tests of gravity or atomic probes. In experiments employing atoms, observables would arise from expected dark-matter-induced oscillations in the fundamental constants of nature. These studies are primarily sensitive to underlying particle masses below 10^{-14} eV. We present a method to search for fast oscillations of fundamental constants using atomic spectroscopy in cesium vapor. We demonstrate sensitivity to scalar interactions of dark matter associated with a particle mass in the range 8×10^{-11} to 4×10^{-7} eV. In this range our experiment yields constraints on such interactions, which within the framework of an astronomical-size dark matter structure are comparable with, or better than, those provided by experiments probing deviations from the law of gravity.

Arabinoxylan from Argentinian whole wheat flour promote the growth of Lactobacillus reuteri and Bifidobacterium breve.

Arabinoxylans are part of dietary fibre and have received attention given their emergent prebiotic character. Four arabinoxylans extracts were obtained from Argentinian soft and hard wheat. In vitro assays were performed to describe the extent to which the extracts from whole wheat flour support selective growth of Bifidobacterium breve and probiotic Lactobacillus reuteri ATCC23272 in a defined media. The prebiotic effect was evaluated by three quantitative scores: relative growth, prebiotic activity score and prebiotic index. For prebiotic index equation the growth of Bacteroides and Clostridium strains was compared to that of bifidobacteria and lactic acid bacteria. All the arabinoxylans extracts supported the growth of Lactobacillus and Bifidobacterium, reaching higher prebiotic activity score values than inulin (0·37 and 0·36 for Lactobacillus and Bifidobacterium respectively). AX2 from soft wheat and AX4 from hard showed similar prebiotic index value to commercial inulin (2·64, 2·52 and 2·22 respectively), and AX3 extract presented higher prebiotic index value (4·09) than the positive control and other prebiotic index reported for arabinoxylans. These extracts could be used as prebiotic, synbiotic compositions or novel food prototypes to treat dysbiosis associated with many diseases. SIGNIFICANCE AND IMPACT OF THE STUDY: The present work demonstrates that AX extracts from Argentinian soft and hard wheat promote efficiently the growth of probiotic strain L. reuteri ATCC23272 and B. breve 286, validated with three different parameters that consider the growth of representative strains of Bacteria genera found in the gut. The evaluation of AX extracts as a food supplement in a murine model could confirm their ability to modulate the microbiome. Novel food prototypes including AX and probiotics could relieve local symptoms and may act as psychobiotics with a beneficial effect on microbiome-brain axis.

Pharmacokinetic variations of nimesulide in mongrel dogs according to age.

The purpose of this research was to investigate the possible variations to the pharmacokinetics of nimesulide by the effect of age using an animal model. An experimental, analytical, prospective and longitudinal study in five dogs, from birth to 730 days of age was carried out. Nimesulide blood levels were measured in different months; concentrations were determined by HPLC-UV. Pharmacokinetic parameters were calculated by using the WinNonlin software. There were statistically significant differences (p <0.05) in most of the pharmacokinetic parameters between study of 6 months against the other three studies in different ages. Changes in the pharmacokinetic parameters of nimesulide as a result of age, are determined by the growing and maturation of the animals. Resulting data suggest that nimesulide can be used safely as a long-term analgesic in dogs, but, the dosing regimens in humans should be different when administered at early age.

Best practices and inclusion of team science principles in appointment promotion and tenure documents in research intensive schools of nursing.

BACKGROUND: Nurse scientists are highly sought after and find satisfaction in serving as members of interdisciplinary research teams. These teams also tend to be highly productive. However, nurse scientists in academia also have to reach certain productivity milestones to be promoted and receive tenure that may be incongruent with team science principles. PURPOSE: This study therefore sought to examine whether APT documents in research intensive nursing schools incorporate team science principles. METHODS: Qualitatively analyzed the appointment, promotion and tenure documents of 18 U.S. based research intensive schools of nursing with over $2 million in NIH funding in fiscal year 2014. FINDINGS: The study found that only 8 of 18 documents included any reference to team science principles and even these mentions were largely negligible. There were few best practices to recommend across documents. By not recognizing team science within these documents, nursing risks marginalization within the larger scientific community by limiting mentorship and learning opportunities for early career nurse scientists. DISCUSSION: Schools of nursing should revisit their promotion and tenure criteria and include a greater commitment to encouragement of team science.

Efficacy, Immunogenicity, and Safety of a 9-Valent Human Papillomavirus Vaccine: Subgroup Analysis of Participants From Asian Countries.

Background: A 9-valent human papillomavirus-6/11/16/18/31/33/45/52/58 (9vHPV) vaccine extends coverage to 5 next most common oncogenic types (31/33/45/52/58) in cervical cancer versus quadrivalent HPV (qHPV) vaccine. We describe efficacy, immunogenicity, and safety in Asian participants (India, Hong Kong, South Korea, Japan, Taiwan, and Thailand) from 2 international studies: a randomized, double-blinded, qHPV vaccine-controlled efficacy study (young women aged 16-26 years; NCT00543543; Study 001); and an immunogenicity study (girls and boys aged 9-15 years; NCT00943722; Study 002). Methods: Participants (N = 2519) were vaccinated at day 1 and months 2 and 6. Gynecological samples (Study 001 only) and serum were collected for HPV DNA and antibody assessments, respectively. Injection-site and systemic adverse events (AEs) were monitored. Data were analyzed by country and vaccination group. Results: 9vHPV vaccine prevented HPV-31/33/45/52/58-related persistent infection with 90.4%-100% efficacy across included countries. At month 7, ≥97.9% of participants seroconverted for each HPV type. Injection-site AEs occurred in 77.7%-83.1% and 81.9%-87.5% of qHPV and 9vHPV vaccine recipients in Study 001, respectively, and 62.4%-85.7% of girls/boys in Study 002; most were mild to moderate. Conclusions: The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Asian participants. Data support 9vHPV vaccination programs in Asia. Clinical Trials Registration: NCT00543543; NCT00943722.

Combined immunotherapy encompassing intratumoral poly-ICLC, dendritic-cell vaccination and radiotherapy in advanced cancer patients.

Background: Combination immunotherapy has the potential to achieve additive or synergistic effects. Combined local injections of dsRNA analogues (mimicking viral RNA) and repeated vaccinations with tumor-lysate loaded dendritic cells shows efficacy against colon cancer mouse models. In the context of immunotherapy, radiotherapy can exert beneficial abscopal effects. Patients and methods: In this two-cohort pilot phase I study, 15 advanced cancer patients received two 4-week cycles of four intradermal daily doses of monocyte-derived dendritic cells preloaded with autologous tumor lysate and matured for 24 h with poly-ICLC (Hiltonol), TNF-α and IFN-α. On days +8 and +10 of each cycle, patients received intratumoral image-guided 0.25 mg injections of the dsRNA-analogue Hiltonol. Cyclophosphamide 600 mg/m2 was administered 1 week before. Six patients received stereotactic ablative radiotherapy (SABR) on selected tumor lesions, including those injected with Hiltonol. Expression of 25 immune-relevant genes was sequentially monitored by RT-PCR on circulating peripheral blood mononuclear cell (PBMCs) and serum concentrations of a cytokine panel were sequentially determined before and during treatment. Pre- and post-treatment PBMC from patients achieving durable stable disease (SD) were studied by IFNγ ELISPOT-assays responding to tumor-lysate loaded DC and by TCRß sequencing. Results: Combined treatment was, safe and well tolerated. One heavily pretreated castration-resistant prostate cancer patient experienced a remarkable mixed abscopal response to SABR+ immunotherapy. No objective responses were observed, while nine patients presented SD (five of them in the six-patient radiotherapy cohort). Intratumoral Hiltonol increased IFN-ß and IFN-α mRNA in circulating PBMC. DC vaccination increased serum IL-12 and IL-1ß concentrations, especially in patients presenting SD. IFNγ-ELISPOT reactivity to tumor lysates was observed in two patients experiencing durable SD. Conclusions: This radio-immunotherapy combination strategy, aimed at resembling viral infection in tumor tissue in combination with a dendritic-cell vaccine and SABR, is safe and shows immune-associated activity and signs of preliminary clinical efficacy.