Articoli di riviste sul tema "1000-1099"

The story of how Domne Eafe acquired the land for her monastery at Thanet when her brothers were murdered by a councillor of her cousin, Ecgberht of Kent (664–73), is variously related in a number of Latin and Old English works. The full version (involving Domne Eafe's tame hind and the death of the councillor) is found in three Latin Lives. These are: a passio of the murdered princes attributed to Byrhtferth, which is the earliest recorded account of the foundation of Thanet, dated c. 1000, and written for the monks at Ramsey, who believed the relics translated to their monastery in 978 × 992 to be those of Domne Eafe's brothers; Goscelin's Vita S. Mildrethae, dated 1089 × 1099, and written for the monks at St Augustine's, Canterbury, who acquired the relics of Mildrith from Thanet in 1030; a passio of the murdered princes found in Oxford, Bodleian Library, Bodley 285, also from Ramsey, which was composed sometime between the mid-eleventh century and the early thirteenth.

Background. Soybeans accessions from the VIR collection were tested in Primorsky Territory, Russia. These accessions had not been studied earlier in that area.Materials and methods. The testing was carried out at the Far East Experiment Station of VIR and involved 570 soybean accessions of various geographic origin. The work was performed according to VIR’s methodological guidelines.Results. The selected accessions were evaluated for their flowering and ripening schedule, seed yield, various seed characteristics (primary color of seed coat, seed hilum color, etc.), 1000 seed weight, plant height, the lower pod setting height, etc. The maximum seed yield (18.0–21.9 g) was registered for 4 accessions: ‘Primorskaya 1099’(k-9700), ‘Primorskaya 1102’ (k-9707) (Russia, Primorsky Territory); ‘Epps’(k-9308) and ‘Pioneer 3981’(k-9651) (USA). Their growing season lasted 121– 130 days. The earliest accessions ‘1337’ and ‘738-4’ (Sweden) had growing seasons of 81–90 days and low seed yields. The weight of 1000 seeds varied from 71 g to 250 g. Only one accession had 1000 seed weight higher than 300 g. The correlation between seed yield and growing season duration was medium (r = 0.57), and between seed yield and 1000 seed weight it was small (r = 0.13). Stem length varied from 15–30 to 111–130 cm. Accessions with the highest seed yield had stem lengths of 51–90 cm. The lower pod setting height ranged from a minimal level (< 6.1 cm) to 18.1–20.0 cm. Among the 92 accessions with high seed productivity (> 14.0 g) only 5 produced their lower pods at a height above 12 cm. Full-scale characterization of the material was published in Catalogue of the VIR Global Collection, Issue 905, 2019.Conclusion. The accomplished study helped to describe earlier untested accessions, grown under the environmental conditions important for soybean production. The accessions with the best economic characteristics can be used in breeding practice.

Abstract We report multiepoch astrometric very long baseline interferometry observations of the chromospherically active binary HR 1099 (V711 Tau, HD 22468) at six epochs over 63 days using the Very Long Baseline Array at 22.2 GHz. We determined hourly radio positions at each epoch with a positional uncertainty significantly smaller than the component separation. The aggregate radio positions at all epochs define an ellipse in the comoving reference frame with an inclination i = 39 .° 5 − 3 .° 5 + 3 .° 6 and longitude of ascending node Ω = 212° ± 22°. The ellipse center is offset from the Third Gaia Celestial Reference Frame position by Δα = − 0.81 − 0.37 + 0.25 , Δδ = 0.45 − 0.25 + 0.23 mas. All radio centroids are well displaced from the binary center of mass at all epochs, ruling out emission from the interbinary region. We examined the motion of the radio centroids within each epoch by comparing hourly positions over several hours. The measured speeds were not statistically significant for five of the six epochs, with 2σ upper limits in the range 200–1000 km s−1. However, for one flaring epoch, there was a 3σ detection v ⊥ = 228 ± 85 km s−1. This speed is comparable to the mean speed of observed coronal mass ejections on the Sun.

Метою цієї роботи є формування ознакової колек-ції самозапилених ліній соняшнику, як за рівнем стійко-сті до гербіцидів групи сульфонілсечовин, так і за комп-лексом морфо-біологічних та морфо-метричних ознак,для подальшого використання в селекційних програмах.Методи. Оцінили стійкість 11 самозапилених ліній соняш-нику; Sures 1, Sures 2, Х-201 В, ОС 1001 В, ОС 1031 В,ОС 1091 В, ОС 1099 В, Од 1125 В, ОС 2017 В, ОС 1021 В, VLA-8 SU до трибенурон-метилу шляхом підрахунку кіль-кості стійких та нестійких рослин до гербіциду післяобробки гербіцидом Гранстар Про 75 в.г. на 14‑й день.Дослідження морфо-біологічних та морфо-метричнихознак соняшнику (HELIANTHUS L.) проводили за методи-кою Інституту рослинництва ім. В.Я. Юр’єва НААН. Рівеньолійності в насінні визначили експрес-методом із засто-суванням приладу ЯМР (ядерно магнітний резонатор)Newport Oxford Instruments, Buckinghamshire, England.Статистичну обробку даних провадили з використаннямінструментів програми «Excel». Зокрема, оцінку суттєвостівпливу фактору «генотип» на варіювання величин восьмиморфологічних ознак провадили в однофакторному дис-персійному комплексі з використанням параметричногокритерію Фішера (F). Для визначення меж граничнихвипадкових відхилень отриманих результатів викори-стали метод найменшої істотної різниці (НІР). Результати.Дослідження одинадцяти ліній соняшнику за морфо-біо-логічними та морфо-метричними ознаками відбувалосяпротягом 2019 та 2020 років. Усі досліджувані лінії пока-зали стійкість до трибенурон-метилу на високому рівні.Встановили наявність фенотипового різноманіття за біль-шістю морфо-біологічних ознак. Лінії також відрізнялисьодна від одної як інтенсивністю забарвлення окремих орга-нів, так і різноманітністю форм останніх. Незмінним для всіхзразків залишився оранжево-жовтий колір язичкових кві-ток. Результати досліджень ліній соняшнику за морфо-ме-тричними ознаками показали зумовленість варіюваннявеличин фактором «генотип». Лінії представляли собоюнизькорослі рослини, висота яких варіювалася залежновід року, у 2019 році вона не перевищувала 148,3 см,а у 2020 році – 119 см. Максимальній діаметр кошика буву лінії VLA 8 Su та мінімальний у ОС 1099 В. Зразок Sures1 виділився найбільшою площею листкової пластини(626,6 см2 у 2019 році та 513,4 см2 у 2020 році). Період«сходи-цвітіння» в середньому по лініям становив 65 дніву 2019 році та збільшився у 2020 році і становив 71 день.Умови року не вплинули суттєво на варіювання довжиниі ширини сім’янки. Максимальну масу 1000 насінин спо-стерігали у ліній Х-201 В та ОС 2017 В, що мала 38 г.Олійність колекційних зразків варіювала від 31,3 до 41,1%.Висновок. Проведені дослідження дозволили сформу-вати колекцію самозапилених ліній соняшнику стійких догербіцидів групи сульфонілсечовин та встановили високийрівень стійкості колекційних зразків до трибенурон‑метилу.

Optimization of planting dates under any climatic conditions is pre-requisite to improve the yield and quality of the major and minor crops. This study was conducted to evaluate the potential of various mungbean cultivars for morpho-physiological and yield traits under different planting dates. In this pot study twenty mungbean cultivars (MGP-17, DM-D4, C5/95-3-31, C6/95-3-8, 5-63-94, TM-1407, MGP-01, NM-11, MGP-41, 5-63-1, MGP-16, NM20-21, MUNG-88, NM-121-25, RAMZAN, NM-2016, NM-19-19, 1099, NM-51 and NM13-1) were planted on July 01 and August 01. Results revealed that various planting dates significantly affected all the attributes, however, genotypic variation was observed among the cultivars. Delayed planting reduced the stand establishment attributes as mean germination time (1.90%), germination index (3.10%), final germination percentage (7.34%), seedling growth including shoot length (14.88%), root length (23.31%), number of leaves (23.04%), leaf area (5.74%) and number of nodules (13.02%). Likely, gas exchange traits including photosynthetic rate (15.71%), transpiration rate (17.09%), sub-stomatal CO2 concentration (2.39%), stomatal conductance (30.56%), SPAD chlorophyll contents (7.42%) and water use efficiency (3.28%) were also reduced. Among morphological traits, various planting dates also reduced the number of pods per plant (5.04%), length of the pod (5.69%), number of grains per pod (28.68%) and 1000-grains weight (7.05%). Differential responses of all the mungbean cultivars were observed for all the pragmatic traits. Delayed planting significantly reduced the morpho-physiological and yield attributes of all mungbean cultivars. However, two mungbean cultivars (NM-121-25 and NM-2016) relatively performed better with minimum reductions in growth, yield and physiological attributes even in delayed planting while the DM-D4 and TM-1407 were found to be the most sensitive in delayed planting than other tested cultivars. Therefore, mungbean cultivars NM-121-25 and NM-2016 can be sown in late sown conditions to get higher yield. © 2021 Friends Science Publishers

Abstract Background The impact of discontinuing vs. continuing thiopurines at anti-TNF initiation in thiopurine experienced patients with inflammatory bowel disease (IBD) is unclear. Methods We used the nationwide Danish registers to establish a national cohort of patients with IBD who received thiopurines prior to initiating anti-TNF during 2003–2014. We compared patients who discontinued vs. continued thiopurine within 90 days of anti-TNF initiation. Our primary outcome was a composite of any clinical event: corticosteroids, hospitalisation, surgery, or death. We used Cox regression models to calculate adjusted hazard ratios (aHR) with 95% confidence intervals (CI). Analyses were adjusted for sex, diagnosis-age, IBD-subtype, disease duration, calendar year, pre-anti-TNF thiopurine duration, and past disease severity including hospitalisations the past year, surgery past 5 years, and corticosteroid use the past year. Results Of 6998 anti-TNF exposed, 1602 patients (Crohn’s disease, n = 1000, ulcerative colitis, n = 602) received thiopurines prior to anti-TNF. Of these, 489 (44%) received thiopurines for more than 180 days. At anti-TNF initiation, 503 patients discontinued thiopurines and were followed for a median 3.54 years and 1099 continued thiopurines with a median follow-up of 3.92 years. Discontinuing thiopurines at anti-TNF initiation statistically significantly increased the risk of the composite outcome (aHR 1.25; 95% CI 1.09 to 1.45). Analyses of the individual outcomes revealed a statistically significantly increased risk of later corticosteroid use in thiopurine discontinuers (aHR 1.31; 95% CI 1.11 to 1.56), but no increased risk of the remaining outcomes. IR; incidence rate, HR; hazard ratio, CI; confidence interval, IBD; inflammatory bowel disease. P-value is the test of interaction between the variable and the treatment groups. Conclusion In our nationwide cohort study of patients with IBD, we found that continuing thiopurines after anti-TNF initiation impacted the outcome favourably, especially regarding corticosteroid use. Further studies are warranted to investigate this central clinical question.

Abstract Gene expression profiling of plasma cells (GEP-PC) has provided major insights into myeloma pathobiology. However the data about GEP-PC in preneoplastic gammopathy (MGUS) or asymptomatic myeloma (AM) are limited, and gene expression patterns that might predict outcome in these patients have not been defined. We analyzed GEP (using U133Plus Affymetrix microarrays), of plasma cells isolated by immuno-magnetic bead selection with CD138 microbeads, from the bone marrow of patients with MGUS (n=16) and asymptomatic myeloma (AM; n=18) enrolled in a prospective South West Oncology Group (SWOG) observational study. Data from normal plasma cells (PCs) and from 105 myeloma PCs were included as controls. Myeloma PCs were randomly selected to include at least 15 patients from each of the 7 subgroups previously identified based on GEP of myeloma tumor cells (Zhan and Shaughnessy, ASH 2004). After the suppression of immunoglobulin (Ig) genes, there were 1297 genes that significantly differed in expression between MGUS-PCs and MM-PCs, and 1099 genes that differed between MGUS-PCs and normal PCs with a 1% false discovery rate. Hierarchical cluster analysis of all samples was performed using 1000 plasma cell signature genes that were most differentially expressed between normal and myeloma PCs. These data demonstrated that both MGUS and AM samples were distributed between normal and MM samples. A prediction analysis of microarrays (PAM) model (PNAS99:6567, 2002) utilizing 134 genes was then developed to determine if the signature from these genes in MGUS/AM was more similar to normal or to myeloma plasma cells. In this analysis, 11/16 (69%) of the MGUS samples were more similar to normal PC, compared to 6/18 (33%) of the AM samples (p=0.04). At present, there are no reliable phenotypic markers to distinguish between normal and malignant PCs within the bulk CD138+ population. Gene expression spikes for cyclin D1 and MAF/MAF-B were seen in both MGUS and AM cohorts, including in some patients with normal PC signature. These data provide the largest comparison to date, of GEP of PCs in preneoplastic versus malignant gammopathies and suggest that GEP may be a useful tool to prospectively identify subsets of patients within the MGUS/AM population with dominant normal PC or MM PC signatures, and potentially differing prognosis. Further analysis of differentially expressed genes between MGUS/MM PCs identified in this dataset may allow insights into the genomic changes in tumor cells underlying the malignant progression of myeloma.

Background Telehealth has been shown to improve access to health care and to reduce costs to the patient and health care system, especially for patients living in rural settings. However, unique challenges arise when implementing telehealth in remote communities. Objective The study aimed to explore the current use, challenges, and opportunities of the Yukon Telehealth System. The lessons learned from this study were used to determine important factors to consider when attempting to advance and expand telehealth programs in remote communities. Methods A mixed methods approach was used to evaluate the Yukon Telehealth System and to determine possible future advances. Quantitative data were obtained through usage logs. Web-based questionnaires were administered to nurses in each of the 14 Yukon community health centers outside of Whitehorse and patients who had used telehealth. Qualitative data included focus groups and semistructured interviews with 36 telehealth stakeholders. Results Since 2008, there has been a consistent number of telehealth sessions of about 1000 per year, with clinical care as the main use (69.06% [759/1099] of all sessions in 2015). From the questionnaire (11 community nurses and 10 patients) and the interview data, there was a consensus among the clinicians and patients that the system provided timely access and cost savings from reduced travel. However, they believed that it was underutilized, and the equipment was outdated. The following 4 factors were identified, which should be considered when trying to advance and expand a telehealth program: (1) patient and clinician buy-in: past telehealth experiences (eg, negative clinician experiences with outdated technology) should be considered when advancing the system. Expansion of services in orthopedics, dermatology, and psychiatry were found to be particularly feasible and beneficial in Yukon; (2) workflow: the use and scheduling of telehealth should be streamlined and automated as much as possible to reduce dependencies on the single Yukon telehealth coordinator; (3) access to telehealth technology: clinicians and patients should have easy access to up-to-date telehealth technology. The use of consumer products, such as mobile technology, should be leveraged as appropriate; and (4) infrastructure: the required human resources and technology need to be established when expanding and advancing telehealth. Conclusions While clinicians and patients had generally positive perceptions of the Yukon Telehealth System, there was consensus that it was underutilized. Many opportunities exist to expand the types of telehealth services and the number of telehealth sessions, including the expansion of services in several new specialty areas, updating telehealth equipment to streamline workflows and increase convenience and uptake, and integrating novel technologies. The identified barriers and recommendations from this evaluation can be applied to the development and expansion of telehealth in other remote communities to realize telehealth’s potential for providing efficient, safe, convenient, and cost-effective care delivery.

O presente trabalho examina a produção de temas de recursos repetitivos no âmbito do Superior Tribunal de Justiça, com vistas à realização de uma análise panorâmica do perfil de afetação e julgamento dos temas submetidos ao rito qualificado. A pesquisa empírica adotou como universo de investigação o total de 1099 propostas de afetação, apreciadas segundo variáveis que permitem construir as reflexões essenciais necessárias à percepção da evolução macroscópica desse modelo de precedentes. Na sequência, em sede de eficácia de paradigmas decisórios, o estudo investiga 10 temas submetidos ao sistema de recursos repetitivos que foram alvo de superveniente revisão, a fim de analisá-los sob a ótica das técnicas de superação a que foram submetidos.

The effect of oral glutathione (GSH) supplementation was studied in obese subjects with and without type 2 diabetes (T2DM) on measures of glucose homeostasis and markers of oxidative stress. Twenty subjects (10 patients with T2DM and 10 obese subjects) were recruited for the study, and randomized in a double-blinded placebo-controlled manner to consume either 1000 mg GSH per day or placebo for 3 weeks. Before and after the 3 weeks insulin sensitivity was measured with the hyperinsulinemic-euglycemic clamp and a muscle biopsy was obtained to measure GSH and skeletal muscle mitochondrial hydrogen peroxide (H2O2) emission rate. Whole body insulin sensitivity increased significantly in the GSH group. Skeletal muscle GSH was numerically increased (∼19%) in the GSH group; no change was seen in GSH to glutathione disulfide ratio. Skeletal muscle mitochondrial H2O2 emission rate did not change in response to the intervention and neither did the urinary excretion of the RNA oxidation product 8-oxo-7,8-dihydroguanosine or the DNA oxidation product 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), although 8-oxodG decreased as a main effect of time. Oral GSH supplementation improves insulin sensitivity in obese subjects with and without T2DM, although it does not alter markers of oxidative stress. The study has been registered in clinicaltrials.gov (NCT02948673). Novelty: Reduced glutathione supplementation increases insulin sensitivity in obese subjects with and without T2DM. H2O2 emission rate from skeletal muscle mitochondria was not affected by GSH supplementation.

Abstract This research aimed to test and study presence sensitive roadway lighting in a housing area in Finland, and to evaluate drivers’ experiences and attitudes of it. The lighting adapted both to motor vehicles using the road and to the measured traffic density along it. The case study was conducted on a collector road in Salo, a town in southern Finland. New, controllable LED lighting with PIR (passive infrared) presence sensors was built along the road, and test scenarios were designed, programmed, and tested. Drivers’ experiences and attitudes of the lighting were collected in a three-phase evaluation with questionnaires from the community of about 1000 households using the road as part of their daily mobility. The results indicate that as an experience, presence sensitive lighting in a road environment was at least as positive as traditional, uncontrolled lighting. The experiences of presence sensitive lighting did not differ from the experiences of uncontrolled lighting regarding pleasantness, uniformity, glare, and road visibility. Most of the drivers (86 %) did not notice any dynamic change in lighting. When informed about the tested lighting strategies, most of the participants (72 %) would prefer either one of the intelligent lighting modes to be the permanent lighting solution. The results encourage the use of intelligent lighting in striving towards more sustainable lighting solutions while maintaining user comfort and safety.

Phthalocyanines are the second most important class of colorant, and copper phthalocyanine is the single largest-volume colorant sold. Traditional uses of phthalocyanine colorants are as blue and green pigments for automotive paints and printing inks and as blue/cyan dyes for textiles and paper. Phthalocyanines have also found extensive use in many of the modern high technologies, e.g. as cyan dyes for ink jet printing, in electrophotography as charge generation materials for laser printers and as colorants for cyan toners. In the visible region, phthalocyanines are limited to blue, cyan and green colours. However, their absorption may be extended into the near infrared and by suitable chemical engineering it is possible to fingerprint the 700-1000 nm region. The properties and effects of these infrared-absorbing phthalocyanines are diverse and cover many important hi-tech applications, including photodynamic therapy, optical data storage, reverse saturable absorbers and solar screens.

Intermediates of the cobalt tetrasulfophthalocyanine ( CoTSPc )-catalyzed thiol autoxidation were studied by UV-vis spectroscopy. All thiolates react with CoTSPc resulting in the formation of 1:1 complexes. Three major factors control both the stability and aggregation of the complexes: thiolate basicity, metal-to-ligand charge transfer (MLCT) and π stacking. Basic thiolates partially reduce C oII TSPc , whereas CoTSPc complexes with low-basicity aliphatic thiolates ( p K a < 4) do not exhibit Co (II) reduction, based on the absence of the characteristic Co (I) charge transfer band at 450 nm. CoTSPc complexes with aliphatic and bulky aromatic thiolates appear to be aggregated in aqueous solutions and are characterized by a broad band at 650 nm. Non-bulky aromatic thiolates of low basicity ( p K a < 6) form unique stable monomeric Co II TSPc complexes. This unique spectral feature can be attributed to π stacking between the phthalocyanine ring and thiolate. Comparison of binding constants shows that the partial reduction of Co (II) significantly contributes to the thiolate binding. A combination of aromatic π stacking and MLCT appears to be responsible for the observed 1000-fold stronger binding of non-basic aromatic thiolates as compared with aliphatic ligands of similar basicity. Kinetic studies confirm the importance of the thiolate binding type for catalysis.

Background: Early detection, diagnosis, and treatment of children with CHD has been the focus of research attention. Hainan is the southernmost underdeveloped province in China, where the technology of screening, diagnosis, and treatment for children with CHD has not been fully developed. Objectives: This study aimed to introduce and promote an appropriate technology system for screening, diagnosis, and evaluation of neonatal CHD. Methods: Two indicators, namely cardiac auscultation plus pulse oximetry (POX), were used by screening staff to screen live newborns within six to 72 hours after birth at all screening institutions in Hainan province from January 1, 2019, to December 31, 2021. Diagnosis procedure for the screened-positive newborns was performed in 31 certified medical institutions, and evaluation procedure for the newborns confirmed with CHD was performed in six certified medical institutions. Data about screening, diagnosis, evaluation, and treatment were obtained, uploaded, and managed online through a neonatal CHD screening information management net. Results: A total of 321447 live births were included in the CHD screening project, and an overall screening rate of 97.59% (321447/329387) was determined. According to our results, 8032 cases were screened-positive. A total of 1099 cases of CHD were confirmed, suggesting a CHD prevalence of 3.419 per 1000 live births. Atrial septal defect (ASD) was the most common CHD lesion, with a prevalence of 1.313 per 1000 live births. The sensitivity of cardiac auscultation, POX, and two indicators’ combination (i.e., cardiac auscultation plus POX) for CHD detection were 69.15%, 33.49%, and 91.90%, respectively; and the specificity of them were 98.36%, 99.43%, and 97.81%, respectively. The ratio of both positive in two indicators among the children with major (serious and critical) CHD at the initial screening was significantly higher than that of single positive in any indicator (χ2 = 59.455, P < 0.001). All children with CHD were evaluated, out of who 154 children with major CHD were treated promptly. Only 15 cases of children with major CHD died, and the standardized mortality of children aged 0 - 1 years with CHD was 4.67/100,000. Conclusions: It was concluded that the combination of two indicators (i.e., cardiac auscultation plus POX) for CHD screening was reliable as well as non-invasive, simple, and easy to operate so that it was conducive for promotion. It was also found that introducing and promoting an appropriate technology for screening, diagnosis, and evaluation of neonatal CHD were extremely significant since they may have contributed to the timely diagnosing and treating children with CHD, especially those with major CHD.

Background: Early detection, diagnosis, and treatment of children with CHD has been the focus of research attention. Hainan is the southernmost underdeveloped province in China, where the technology of screening, diagnosis, and treatment for children with CHD has not been fully developed. Objectives: This study aimed to introduce and promote an appropriate technology system for screening, diagnosis, and evaluation of neonatal CHD. Methods: Two indicators, namely cardiac auscultation plus pulse oximetry (POX), were used by screening staff to screen live newborns within six to 72 hours after birth at all screening institutions in Hainan province from January 1, 2019, to December 31, 2021. Diagnosis procedure for the screened-positive newborns was performed in 31 certified medical institutions, and evaluation procedure for the newborns confirmed with CHD was performed in six certified medical institutions. Data about screening, diagnosis, evaluation, and treatment were obtained, uploaded, and managed online through a neonatal CHD screening information management net. Results: A total of 321447 live births were included in the CHD screening project, and an overall screening rate of 97.59% (321447/329387) was determined. According to our results, 8032 cases were screened-positive. A total of 1099 cases of CHD were confirmed, suggesting a CHD prevalence of 3.419 per 1000 live births. Atrial septal defect (ASD) was the most common CHD lesion, with a prevalence of 1.313 per 1000 live births. The sensitivity of cardiac auscultation, POX, and two indicators’ combination (i.e., cardiac auscultation plus POX) for CHD detection were 69.15%, 33.49%, and 91.90%, respectively; and the specificity of them were 98.36%, 99.43%, and 97.81%, respectively. The ratio of both positive in two indicators among the children with major (serious and critical) CHD at the initial screening was significantly higher than that of single positive in any indicator (χ2 = 59.455, P < 0.001). All children with CHD were evaluated, out of who 154 children with major CHD were treated promptly. Only 15 cases of children with major CHD died, and the standardized mortality of children aged 0 - 1 years with CHD was 4.67/100,000. Conclusions: It was concluded that the combination of two indicators (i.e., cardiac auscultation plus POX) for CHD screening was reliable as well as non-invasive, simple, and easy to operate so that it was conducive for promotion. It was also found that introducing and promoting an appropriate technology for screening, diagnosis, and evaluation of neonatal CHD were extremely significant since they may have contributed to the timely diagnosing and treating children with CHD, especially those with major CHD.

Background: Carotid-femoral PWV (cfPWV), a well-studied measure of central arterial stiffness is associated with cardiovascular disease and mortality. Brachial-ankle PWV (baPWV) is commonly used in Asian countries as a measure of peripheral arterial stiffness. Few studies have evaluated the population distributions of cfPWV and baPWV and the degree to which they may measure the same arterial characteristics. Objectives: Characterize cfPWV and baPWV in a population of older adults by age, gender and race. Methods: We analyzed 2,403 adults (1473 females; mean age 75 years) from the population-based Atherosclerosis Risk in Communities (ARIC) study who had data on cfPWV and baPWV, after excluding 763 individuals due to arrhythmias, 165 with BMI >40 kg/m2, and 300 with missing covariates of interest. Technicians used Omron VP-1000 plus system (Colin Co., Komaki, Japan) and followed a standardized protocol, to measure cfPWV and baPWV twice, and the results were averaged. The cumulative distributions of cfPWV and the right baPWV by age dichotomized at median, sex and race (African American (AA) and non-AA) were evaluated with the Kolmogorov-Smirnov test and the relationship between cfPWV and baPWV assessed by the Pearson correlation coefficient. Results: The mean (SD) cfPWV and baPWV was 1159 (303) and 1736 (319) cm/sec. The empirical distribution function of both these measures was higher (p<0.001) among those 75 years and older than those younger than 75 years i.e., mean (SD) of cfPWV was 1229 (321) vs.1099 (274) cm/sec, respectively, and mean (SD) of baPWV was 1814 (328) vs. 1670 (295) cm/sec, respectively. The distribution function of cfPWV was higher among AAs (p<0.001) but the distribution of baPWV was not different by race (p=0.76). The mean (SD) in cm/sec for AA participants compared to non-AA participants for cfPWV was 1232 (335) vs. 1138 (290), and baPWV was 1725 (324) vs. 1740 (317). The distributions of cfPWV and baPWV did not differ by gender, p=0.21 and p=0.23, respectively. The mean (SD) cfPWV and baPWV among males was 1174 (305) and 1728 (318), and among to females was 1150 (302) and 1742 (320) cm/sec. Correlation analysis showed that cfPWV and baPWV were positively correlated, r=0.45, (p<0.001). Conclusion: The distributions of cfPWV and baPWV were similar by gender but were different by age and by race. Despite having comparable measure of peripheral vascular stiffness, African Americans showed a higher degree of central vascular stiffness compared to non-African Americans. Our findings indicate that cfPWV and baPWV are correlated measures of arterial stiffness but likely reflect different aspects of segment-specific vascular impairment and cardiovascular risk.

This keynote lecture is a product of many years of hard work but today this is delivered in honor of Professor and Founding President of ORLIAC, Professor Emeritus Jan Veldman. Thank you for the opportunity to host ORLIAC in Manila way back in March 2018. For those who attended this, I gave a special lecture during the celebration of World Hearing Day on March 3, 2018, when ORLIAC was held in Manila and this gives an update on how we managed in the past four and a half years, with a COVID-19 pandemic in the past two and half years. The Philippines is an archipelago of more than 7,100 islands during high tide and up to 7,600 when it is low tide. It is situated in the Southeast Asian region. It is one of the countries with the highest population density, with a total population of 110 million spread over 300,000 square kilometers. The crude birthrate is at 19.9 per 1000 – in stark contrast with surrounding Southeast Asian nations now with a decreasing population such as Thailand, Vietnam, and Malaysia among others There have been three World Health Assembly (WHA) resolutions that emphasized the prevention of deafness and hearing loss. WHA 38.19 in 1985 then ten years later WHA 48.9 in 1995 and the last WHA 70.13 in 2017. These resolutions from the World Health Assembly emphasized that prevention of deafness and hearing loss should be incorporated in primary health care. As a result of the 2017 WHA 70.13 resolution, a World Hearing Report1was formulated and released last year in 2021 (Figure 1). The WHO Call to Action in 2000 recommended that Universal Newborn Hearing Screening (NHS) be implemented in all countries where rehabilitation services are established.2 In 1998, we did the first cochlear implantation in my country3 and established as well the graduate program of Masters in Clinical Audiology at the UP College of Medicine where I now work as Dean. This graduate program is one of only two in the country and is government-subsidized such that slots are limited and entry is quite competitive. It is jointly offered with the College of Allied Medical Professions.4 We consider this program to be a key element in producing the necessary healthcare workforce needed for the implementation of programs to defeat deafness in my country. The world hearing report published last year by the World Health Organization (WHO) highlighted the increasing number of people living with hearing loss and in need of services. There is of course the disproportionate burden of hearing loss in low-to middle-income countries like the Philippines.6Our publications from 2003, from a study looking at results of newborn hearing screening in the neonatal intensive unit in the hospital7,8 then to the community, thus providing the evidence for the eventual policy on UNHS that we proposed to the Department of Health (DOH) and to congress for legislation.We initially embarked on basic epidemiological studies using otoacoustic emissions testing in the hospital then in the community. We noted the age of referral at our hospital for children with hearing impairment to be at around 34 months.9 Our focus then was just providing otological clinical services so we decided to work for the establishment of the Philippine National Ear Institute (PNEI) – a research institute formed by Republic Act 9245 and part of the National Institutes of Health of the University of the Philippines – Manila.10 The PNEI laid down the researches needed for the stable foundation of a national health program focused on newborn hearing. From 2003 to 2008, we conducted several studies to establish the prevalence of bilateral permanent hearing loss in newborns both in the hospital and community settings as a prelude to the enactment of the law, and in order to defend having a program on newborn hearing, we conducted a cost-analysis of hospital-based universal newborn hearing screening.11 Notably in 2007, a population-based study showed the prevalence of bilateral profound Congenital Hearing Loss at 1.4 per 1000 births.12 This translates to more than 3,000 babies annually or 8 babies per day who may be profoundly deaf in my country.13 If there were proper intervention for a child with hearing impairment, the cost of treating hearing translates to a lifetime savings of about 80,000 dollars or about PhP 4.3M for the patient’s family. The government and the family would have spent about PhP 4.3 M to raise, educate, and support a deaf-mute child to adulthood. This was presented to the Senate of the Philippines and highlighted during the Inaugural Congress of the ASEAN Academy of Neuro-Oto-Audiology (AANOA). This was supported by Senator Loren Legarda, PNEI Director Dr. Generoso Abes, AANOA founding member Dr. Helmi Balfas, IFOS Regional Secretary Chong Sun Kim, PSOHNS President Gil Vicente, AANOA President Dato Lokman Saim, and Hearing International Secretary Dr. Norberto Martinez (Figure 2). Mandating NHS in the country also entailed involving stakeholders, including otolaryngologists from the different regions who committed to convince their local officials and local hospital administrators the need for instituting these newborn hearing screening programs. After we had the local data at hand, the PSOHNS created a task force on NHS and crafted a position statement on the need for UNHS. As then Vice President, we drafted the position paper that will be presented to Congress while at the same time seeking support from the Department of Health under DOH Secretary Francisco Duque who agreed that Philhealth should be able to support this program when enacted into law. A Technical Working Group was formed, gathering all stakeholders and service providers. Multiple meetings were held, groundwork for launch, and implementation of newborn hearing screening program were instituted with ten Collaboration for Newborn Hearing Screening Advocacy (CONHScA) annual symposia with otolaryngology, audiology, and other hearing screening advocates all over the country.14 (Figure 3). On August 12, 2009, President Gloria Macapagal-Arroyo signed RA 9709, an act that established universalnewborn hearing screening program for the prevention, early diagnosis, and intervention of hearing loss.15 On the modality to be used, reporting, accreditation and training, monitoring and evaluation, and most especially costing of the services and financing for sustainability were also done. We advocated for legislation on UNHS, and once ratified, developed a national program with the Department of Health as lead agency and continued with policy implementation as part of a national technical working group under the DOH. This led to the creation of national Newborn Hearing Screening Reference Center (NHSRC) that was inaugurated in 2013 at the National Institutes of Health with Professor Cor Cremers of Radboud University Nijmegen as special guest. We also started to increase the awareness on the importance of NHS even on national television (Figure 4). Aside from the cost-effectiveness study of hospital-based newborn hearing screening program, we also looked at the budget impact of a community-based UNHSP in the Philippines from both the public payer and the societal perspectives. This study of Rivera et al. published in 201716 showed that cost effectiveness is sensitive to treatment rate, prevalence, follow-up rate, number of rehabilitation sessions, and coverage of the program. It was not sensitive to cost per rehabilitation session, cost of diagnosis with OAE and ABR, education costs, refer rates, recurrent costs, cost of machines, and sensitivity rates. From the societal perspective, the UNHSP was found to be cost-saving for the full range of parameters tested for cost of screening, amplification, education, rehabilitation, and fixed program costs. Ensuring treatment of at least 31 percent and follow-up rate of 24% for a community-based newborn hearing would likely be important benchmarks. The technical arm of the lead agency for this program, the Department of Health, is the Newborn Hearing Screening Reference Center that gives assistance in defining and recommending NHS testing and follow-up protocols which include hearing screening methods, devices used, location, manner, and timing of newborn hearing screening testing. The current protocol uses the 2007 JCIH recommendation of 1-3-6 rule, with screening at 1 month, confirmation of hearing loss at 3 months, and appropriate intervention at 6 months of age.17 With respect to the preferred method of screening, the recent study by Neumann K et al. showed OAE as most prevalent in the country.18 Ten years ago in 2010, an initial web registry for reporting of the OAE results was formulated up to 2014 it was used in 9 centers which allowed gathering of preliminary data on the NHS program. From the data, there was a registry card that needed manual data encoding and in order to sustain operations, a 1 USD fee was levied per registration and was reimbursable thru Philhealth that paid around 4 USD per hearing screening test done. Personnel training, device, and facility certification standards were implemented for centers that chose to perform newborn hearing screening testing. Tiered categorization of centers was also done with screening centers as Category A, screening and diagnostic centers as category B, screening, diagnostic, and essential intervention with hearing aid amplification as category C, and the highest category D for centers with genetic testing and counselling, cochlear implantation surgery and speech rehabilitation services. Recent data showed there were 1072 category A, 18 category B and C, and 9 category D centers distributed all over the country (Figure 5). While some services were initially hampered by the COVID-19 pandemic, NHSRC defined safety protocols that needed to be followed. In an updated advisory, first released in April 2020, and is still in effect to date, NHSRC emphasizes that the centers should follow hospital/institution’s procedural protocol regarding disinfection and attire. Hearing tests in infants are non-invasive and non-aerosol producing procedures. The advisory also included recommendations in terms of timing, preparation, and testing procedures. One significant development that was accelerated during the pandemic was the online adaptation of the NHS personnel certifying course that was reported in recent publications by Rozul et al.19,20 To date, there have been about 3403 trained personnel in 1099 centers with significant increase noted in 2019 compared to previous years. This was not however reflected in the report of Neumann probably due to the time when data for this publication was collected prior to 2019. From the registry alone, the percent screened in the Philippines has been reported to be at least 7-13 percent of live births from the years 2019-2021. The report from Philhealth of 800 claims for NHS from 2018-2019 is still under verification. In 2020, based on manual submission, out of 1099 facilities, 26 percent submitted reports. In 2019, 95% already submitted reports so the pandemic impacted significantly on reporting of results by excel file and paper reports (Figures 6 and 7). The program is still beset with challenges like poor compliance with data submission, loss to follow-up, poor connectivity, sustainable funding of the program from both local and national government, lack of human resources, and a need of much awareness among stakeholders regarding the importance of newborn hearing screening. In a country where 60 percent die without seeing a doctor, there is much work to do. The cost of screening equipment is a major barrier so we conceptualized a biomedical device development project working with engineers in the university to create an AABR screening device which is now on phase two with a TLR 5 early phase rating scale and will now include recruitment of more subjects and refinements for improvements. Harnessing technology and making this more affordable remain as strategies for developing a sustainable hearing screening program and is the subject of HELE, which aims to increase the rates of newborn hearing screening with novel technologies and telehealth. “Hele” stands for lullaby a mother sings to a child. We thought this as very apt for emphasizing the importance of hearing from birth for optimal development. This received a substantial phase 1 grant in 2016 and a phase 2 was launched this year for the premarket development which now stand at technology readiness level 5. It has already spawned many products like the computer-based e-learning training modules, capacity building with provision of basic OAE equipment, and many research publications. It is hoped that a pre-production HELE device can already be produced soon with validated efficacy and reproducibility of all the AABR responses in a clinical setting. With the collaboration of University of California Berkeley and UC Davis, a formidable team has been created. The electronic national newborn hearing screening registry was launched during WORLD HEARING DAY in 2022 and the usability testing results have been published by Ricalde et al.21 In the recent manual of operations and procedures, success indicators were outlined. This is aligned with the WHO standards for monitoring and evaluation, and determining success of programs. Beyond NHS, what else have we learned? Our studies on the genetic causes of the more common causes of hearing impairment such as otitis media showed a unique mutation A2ML1 that affected protease inhibitors allowing better mucosal defense of the middle ear mucosa. Our findings showed microbiome shifts and when we looked at gingivitis, this was what we found. The genetic counseling we embarked on for this indigenous community taught us clinicians many lessons. Speaking to them in their native language was important and house to house invitations were more effective. What about genetic basis of congenital hearing loss? We have found that SLC26A4 mutations were more common than GJB2. There were novel mutations seen in our cohort suggesting the need for studies looking at genetic predisposition. We saw commonalities with Indonesia in terms of the prevalence of GJB2 mutations. From our studies on A2ML1 mutations predisposing to otitis media, we are monitoring this with ongoing study on Hispanic populations. Meanwhile, a seed fund for a national cochlear implant program was approved by Congress and 20 children underwent surgery (Figure 8), while two centers, one in Visayas (Corazon Locsin Montelibano Memorial Regional Hospital in Bacolod) and another in Mindanao (Southern Philippines Medical Center in Davao) were capacitated. Virtual multidisciplinary meetings to discuss the cases were held and provided a model for optimizing use of resources and outcomes. The initial data from the 20 implanted children are very encouraging. There are goals of expanding this program to more beneficiaries by having a Z package for Cochlear implantation, funding from DOH medical assistance fund for indigent patients, and development of services for other implantable hearing devices at the Philippine General Hospital. Moreover, research on hearing need more support given that our studies on genetics of hearing loss among Filipinos yielded very important data on novel genes, uniqueness of our genetic pool as well as mutations predisposing to increased prevalence of otitis media among our marginalized and indigenous population.22-26 As a low- to middle-income country, these researches will need to be continued and may provide valuable lessons for similarly challenged countries in the works as we highlighted in 2017 during the United Nations World Hearing Assembly Advocacy Event on hearing health (Figure 9). The recent National Academy of Science and Technology health policy forum where Professor Xing Kuan Bu was featured as keynote lecturer gave important data on experiences on hearing health program development in China and in the world (Figure 10). Clearly the sustainable development goals especially 3,4,8 and 10 covered by hearing health ensures equity and should be aspirational goals for national development. This is congruent with the vision of PNEI: “No Filipino shall be deprived of a functioning sense of hearing and balance.” Lastly, as the theme of this congress is East Meets West, the Philippines had a strong history of shipbuilding in an era when the galleon trade was very active and 148 of 200 ships that plied that route were ships built in the Philippines with our hardwood. Tracing therefore the history of the countries in ASEAN in particular with the Dutch, French, British, and Spanish influences, we need to dig deeper and look at genetic markers for both health and disease so that while we develop our friendship and scientific connections, history will prove that we have always been connected in so many ways and further exploration can be done in many dimensions. Charlotte M. Chiong, MD, PhDResearch Professor 12Project Leader of HeLeDean, UP College of Medicine (2018-present) _____________________________Paper presented in the Otology Rhinology Laryngology International Academic Conference, September 26, 2022, Auditorium Antonianum, Rome, Italy. Paper prepared in fulfillment of the Alfredo T. Ramirez Professorial Chair for 2022.