Airlangga University

Rhinosinusitis is a significant and increasing health problem which results in a large financial burden on society. This evidence based position paper describes what is known about rhinosinusitis and nasal polyps, offers evidence based recommendations on diagnosis and treatment, and considers how we can make progress with research in this area. Rhinitis and sinusitis usually coexist and are concurrent in most individuals; thus, the correct terminology is now rhinosinusitis. Rhinosinusitis (including nasal polyps) is defined as inflammation of the nose and the paranasal sinuses characterised by two or more symptoms, one of which should be either nasal blockage/obstruction/congestion or nasal discharge (anterior/posterior nasal drip), +/- facial pain/pressure, +/- reduction or loss of smell; and either endoscopic signs of polyps and/or mucopurulent discharge primarily from middle meatus and/or; oedema/mucosal obstruction primarily in middle meatus, and/or CT changes showing mucosal changes within the ostiomeatal complex and/or sinuses. The paper gives different definitions for epidemiology, first line and second line treatment and for research. Furthermore the paper describes the anatomy and (patho)physiology, epidemiology and predisposing factors, inflammatory mechanisms, evidence based diagnosis, medical and surgical treatment in acute and chronic rhinosinusitis and nasal polyposis in adults and children. Evidence based schemes for diagnosis and treatment are given for the first and second line clinicians. Moreover attention is given to complications and socio-economic cost of chronic rhinosinusitis and nasal polyps. Last but not least the relation to the lower airways is discussed.

<h3>Importance</h3> Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data. <h3>Objective</h3> To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning. <h3>Evidence Review</h3> We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence. <h3>Findings</h3> In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572 000 deaths and 15.2 million DALYs), and stomach cancer (542 000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819 000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601 000 deaths and 17.4 million DALYs), TBL cancer (596 000 deaths and 12.6 million DALYs), and colorectal cancer (414 000 deaths and 8.3 million DALYs). <h3>Conclusions and Relevance</h3> The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care.

IMPORTANCE: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden. OBJECTIVE: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019. EVIDENCE REVIEW: The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs). FINDINGS: In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles. CONCLUSIONS AND RELEVANCE: The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.

Importance: Detailed information about the association of COVID-19 with outcomes in pregnant individuals compared with not-infected pregnant individuals is much needed. Objective: To evaluate the risks associated with COVID-19 in pregnancy on maternal and neonatal outcomes compared with not-infected, concomitant pregnant individuals. Design, Setting, and Participants: In this cohort study that took place from March to October 2020, involving 43 institutions in 18 countries, 2 unmatched, consecutive, not-infected women were concomitantly enrolled immediately after each infected woman was identified, at any stage of pregnancy or delivery, and at the same level of care to minimize bias. Women and neonates were followed up until hospital discharge. Exposures: COVID-19 in pregnancy determined by laboratory confirmation of COVID-19 and/or radiological pulmonary findings or 2 or more predefined COVID-19 symptoms. Main Outcomes and Measures: The primary outcome measures were indices of (maternal and severe neonatal/perinatal) morbidity and mortality; the individual components of these indices were secondary outcomes. Models for these outcomes were adjusted for country, month entering study, maternal age, and history of morbidity. Results: A total of 706 pregnant women with COVID-19 diagnosis and 1424 pregnant women without COVID-19 diagnosis were enrolled, all with broadly similar demographic characteristics (mean [SD] age, 30.2 [6.1] years). Overweight early in pregnancy occurred in 323 women (48.6%) with COVID-19 diagnosis and 554 women (40.2%) without. Women with COVID-19 diagnosis were at higher risk for preeclampsia/eclampsia (relative risk [RR], 1.76; 95% CI, 1.27-2.43), severe infections (RR, 3.38; 95% CI, 1.63-7.01), intensive care unit admission (RR, 5.04; 95% CI, 3.13-8.10), maternal mortality (RR, 22.3; 95% CI, 2.88-172), preterm birth (RR, 1.59; 95% CI, 1.30-1.94), medically indicated preterm birth (RR, 1.97; 95% CI, 1.56-2.51), severe neonatal morbidity index (RR, 2.66; 95% CI, 1.69-4.18), and severe perinatal morbidity and mortality index (RR, 2.14; 95% CI, 1.66-2.75). Fever and shortness of breath for any duration was associated with increased risk of severe maternal complications (RR, 2.56; 95% CI, 1.92-3.40) and neonatal complications (RR, 4.97; 95% CI, 2.11-11.69). Asymptomatic women with COVID-19 diagnosis remained at higher risk only for maternal morbidity (RR, 1.24; 95% CI, 1.00-1.54) and preeclampsia (RR, 1.63; 95% CI, 1.01-2.63). Among women who tested positive (98.1% by real-time polymerase chain reaction), 54 (13%) of their neonates tested positive. Cesarean delivery (RR, 2.15; 95% CI, 1.18-3.91) but not breastfeeding (RR, 1.10; 95% CI, 0.66-1.85) was associated with increased risk for neonatal test positivity. Conclusions and Relevance: In this multinational cohort study, COVID-19 in pregnancy was associated with consistent and substantial increases in severe maternal morbidity and mortality and neonatal complications when pregnant women with and without COVID-19 diagnosis were compared. The findings should alert pregnant individuals and clinicians to implement strictly all the recommended COVID-19 preventive measures.

Klebsiella pneumoniae is now recognized as an urgent threat to human health because of the emergence of multidrug-resistant strains associated with hospital outbreaks and hypervirulent strains associated with severe community-acquired infections. K. pneumoniae is ubiquitous in the environment and can colonize and infect both plants and animals. However, little is known about the population structure of K. pneumoniae, so it is difficult to recognize or understand the emergence of clinically important clones within this highly genetically diverse species. Here we present a detailed genomic framework for K. pneumoniae based on whole-genome sequencing of more than 300 human and animal isolates spanning four continents. Our data provide genome-wide support for the splitting of K. pneumoniae into three distinct species, KpI (K. pneumoniae), KpII (K. quasipneumoniae), and KpIII (K. variicola). Further, for K. pneumoniae (KpI), the entity most frequently associated with human infection, we show the existence of >150 deeply branching lineages including numerous multidrug-resistant or hypervirulent clones. We show K. pneumoniae has a large accessory genome approaching 30,000 protein-coding genes, including a number of virulence functions that are significantly associated with invasive community-acquired disease in humans. In our dataset, antimicrobial resistance genes were common among human carriage isolates and hospital-acquired infections, which generally lacked the genes associated with invasive disease. The convergence of virulence and resistance genes potentially could lead to the emergence of untreatable invasive K. pneumoniae infections; our data provide the whole-genome framework against which to track the emergence of such threats.

Abstract Four new iridoid glucosides 1 – 4 , named blumeosides A–D, were isolated from the methanolic stem‐bark extract of Fagraea blumei G. D ON . (Loganiaceae). They were accompanied by the benzyl‐alcohol derivative di‐ O ‐methylcrenatin ( 5 ) and the flavone C ‐glucoside swertisin ( 6 ). The structures of 1 – 4 were established by spectroscopic methods, including FAB‐MS, and 1 H‐ and 13 C‐NMR, and by alkaline hydrolysis. Blumeosides A ( 1 ) and C ( 3 ) are 10‐ O ‐(2,5‐dihydroxytercphthalo) adoxosidic acid and 10‐ O ‐(2‐hydroxyterephthalo)adoxosidic acid, respectively. In blumeosides B ( 4 ) and D ( 2 ), both carboxylic groups of the terephthalic‐acid moiety are esterified by adoxosidic‐acid units, Blumeosides A–D ( 1 – 4 ) inhibited bleaching of crocin induced by alkoxyl radicals. Blumeosides A ( 1 ) and D ( 2 ) also demonstrated scavenging properties towards the 2,2‐diphenyl‐1‐picryl‐hvdrazvl (CDPPH) radical in TLC autographic and spectrophotometric assays.

This research focuses on the discussion regarding antecedent variable of transformational leadership with its effect to work performance of the middle-level leaders at the organization of Pelabuhan Indonesia III Inc. The samples used in this study are 30 respondents as 75% of the population. The technique used to collect the data from the respondents is questionnaires to minimize any interpretation differences between respondents and the researcher. Further, analysis model used is structural equation model (SEM) with the basis of theory and concept, from the package of Partial Least Square (PLS) program so that the results are accurate. This study found that transformational leadership has direct significant effect on job satisfaction and organizational commitment. However transformational leadership cannot give significant impact to work performance when it is intervened by the organizational commitment as well as it cannot give direct impact on work performance.

This study explored the correlates of climate anxiety in a diverse range of national contexts. We analysed cross-sectional data gathered in 32 countries (N = 12,246). Our results show that climate anxiety is positively related to rate of exposure to information about climate change impacts, the amount of attention people pay to climate change information, and perceived descriptive norms about emotional responding to climate change. Climate anxiety was also positively linked to pro-environmental behaviours and negatively linked to mental wellbeing. Notably, climate anxiety had a significant inverse association with mental wellbeing in 31 out of 32 countries. In contrast, it had a significant association with pro-environmental behaviour in 24 countries, and with environmental activism in 12 countries. Our findings highlight contextual boundaries to engagement in environmental action as an antidote to climate anxiety, and the broad international significance of considering negative climate-related emotions as a plausible threat to wellbeing.

COVID-19, a new strain of coronavirus (CoV), was identified in Wuhan, China, in 2019. No specific therapies are available and investigations regarding COVID-19 treatment are lacking. Liu et al. (2020) successfully crystallised the COVID-19 main protease (Mpro), which is a potential drug target. The present study aimed to assess bioactive compounds found in medicinal plants as potential COVID-19 Mpro inhibitors, using a molecular docking study. Molecular docking was performed using Autodock 4.2, with the Lamarckian Genetic Algorithm, to analyse the probability of docking. COVID-19 Mpro was docked with several compounds, and docking was analysed by Autodock 4.2, Pymol version 1.7.4.5 Edu, and Biovia Discovery Studio 4.5. Nelfinavir and lopinavir were used as standards for comparison. The binding energies obtained from the docking of 6LU7 with native ligand, nelfinavir, lopinavir, kaempferol, quercetin, luteolin-7-glucoside, demethoxycurcumin, naringenin, apigenin-7-glucoside, oleuropein, curcumin, catechin, epicatechin-gallate, zingerol, gingerol, and allicin were -8.37, -10.72, -9.41, -8.58, -8.47, -8.17, -7.99, -7.89, -7.83, -7.31, -7.05, -7.24, -6.67, -5.40, -5.38, and -4.03 kcal/mol, respectively. Therefore, nelfinavir and lopinavir may represent potential treatment options, and kaempferol, quercetin, luteolin-7-glucoside, demethoxycurcumin, naringenin, apigenin-7-glucoside, oleuropein, curcumin, catechin, and epicatechin-gallate appeared to have the best potential to act as COVID-19 Mpro inhibitors. However, further research is necessary to investigate their potential medicinal use.

Purpose The purpose of this paper is to determine the direct influence of the mechanism of good corporate governance (GCG) and corporate social responsibility (CSR) on financial performance as well as through earnings management as a mediating variable. Design/methodology/approach The data used in this research are secondary data involving 102 companies listed on the Indonesian Stock Exchange for the period 2014. The data used in this study were analyzed using partial least square and carried out with the help of software WarpPLS 5.0. Findings The results show that the mechanism of GCG and CSR has a positive effect on financial performance as well as the CSR on financial performance. Originality/value The results also show partial mediation of earnings management on impact of GCG mechanisms on financial performance and full mediation of earnings management on impact of CSR on financial performance.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.

Toxigenic strains of Clostridium difficile have been reported to produce both toxins A and B nearly always, and nontoxigenic strains have been reported to produce neither of these toxins. Recent studies indicate that it is not always true. We established a PCR assay to differentiate toxin A-negative, toxin B-positive (toxin A-, toxin B+) strains from both toxin-positive (toxin A+, toxin B+) strains and both toxin-negative (toxin A-, toxin B-) strains as an alternative to cell culture assay and enzyme-linked immunosorbent assay (ELISA). By using the PCR primer set NK11 and NK9 derived from the repeating sequences of the toxin A gene, a shorter segment (ca. 700 bp) was amplified from toxin A-, toxin B+ strains compared to the size of the segment amplified from toxin A+, toxin B+ strains (ca. 1,200 bp), and no product was amplified from toxin A-, toxin B-strains. We examined a total of 421 C. difficile isolates by PCR. Of these, 48 strains showed a shorter segment by the PCR, were negative by ELISAs for the detection of toxin A, and were positive by cell culture assay. Although the cytotoxin produced by the toxin A-, toxin B+ strains was neutralized by anti-toxin B serum, the appearance of the cytotoxic effects on Vero cell monolayers was distinguishable from that of toxin A+, toxin B+ strains. By immunoblotting, the 44 toxin A-, toxin B+ strains were typed to serogroup F and the remaining four strains were serogroup X. Pulsed-field gel electrophoresis separated the 48 strains into 19 types. The PCR assay for the detection of the repeating sequences combined with PCR amplification of the nonrepeating sequences of either the toxin A or the toxin B gene is indicated to be useful for differentiating toxin A-, toxin B+ strains from toxin A+, toxin B+ and toxin A-, toxin B- strains and will contribute to elucidation of the precise role of toxin A-, toxin B+ strains in intestinal diseases.

Abstract In recent years, cultural intelligence (CQ, or the ability that an expatriate has to adapt across cultures), cultural effectiveness (the ability to interact and communicate with host nationals), and cultural adjustment are regarded as three of the most important factors for expatriate performance. However, the interrelationships between these variables have largely been ignored. Moreover, the role of previous international experiences on the above interrelationships has also not been determined. This study focuses on how CQ and expatriates' experience affects cultural adjustment, cultural effectiveness, and expatriates' performance. The results reveal that the positive effect of CQ needs to be mediated by cultural adjustment and cultural effectiveness before affecting expatriate performance. Furthermore, expatriates' prior international working and travel experiences moderate the effects of CQ on cultural adjustment and cultural effectiveness. Keywords: adjustmentcultural intelligence (CQ)effectivenessinternational experienceperformance

The study's objective was to assess the features and content of the COVID-19 mobile applications accessible in the Apple AppStore. A content analysis, comparison, and functionality evaluation of a few COVID-19 related mobile applications was performed. The search for COVID -19 related apps in the iOS AppStore took place between February 1 and March 31, 2022. The mobile applications received a maximum of 7 points (basic feature assessment) and 8 points overall (functionality assessment). The requirements were fully met by receiving one point. Frequencies from descriptive statistics were used to allude to the applications' features according to the app's basic purpose. A total of 234 applications were recognized using the keywords to exploreCOVID-19 related mobile applications in Apple AppStore. However, 58 mobile applications (24.8%) relevant to COVID-19 were evaluated. According to the findings of an evaluation of basic aspects of mobile applications, 89.7% require an internet connection, 70.7% have a size of less than 50 MB, 96.6% require no funding, 58.6% include educational content, and 60.3% offer advice from the applications. In terms of score, 41.4% scored three or below, whereas 58.6% scored four or above. Functionality assessment wise, 79.3% included information regarding COVID-19, 12.1% included COVID-19 contact tracing, 17.2% had vaccination status, a health authority maintained 50%, 31.0% included COVID-19 statistics, and 25.8% were able to report ART/PCR test. In terms of score, 91.4% scored three points or less, and 8.6% scored four points or more. This study has discovered several applications that could effectively prevent COVID-19 pandemic spread. Based on the findings, mobile applications that would be recommended are the ones supported by the government health administration of the respective country. App development companies’ applications show that competent healthcare personnel was not involved in developing the applications. Online consultation with healthcare professionals might help the public who do not have access to the nearest hospital.

BACKGROUND: For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and locations, while reflecting on the remaining post-COVID-19 challenges to achieving our collective global health ambitions. METHODS: The GBD 2023 combined analysis estimated years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 375 diseases and injuries, and risk-attributable burden associated with 88 modifiable risk factors. Of the more than 310 000 total data sources used for all GBD 2023 (about 30% of which were new to this estimation round), more than 120 000 sources were used for estimation of disease and injury burden and 59 000 for risk factor estimation, and included vital registration systems, surveys, disease registries, and published scientific literature. Data were analysed using previously established modelling approaches, such as disease modelling meta-regression version 2.1 (DisMod-MR 2.1) and comparative risk assessment methods. Diseases and injuries were categorised into four levels on the basis of the established GBD cause hierarchy, as were risk factors using the GBD risk hierarchy. Estimates stratified by age, sex, location, and year from 1990 to 2023 were focused on disease-specific time trends over the 2010-23 period and presented as counts (to three significant figures) and age-standardised rates per 100 000 person-years (to one decimal place). For each measure, 95% uncertainty intervals [UIs] were calculated with the 2·5th and 97·5th percentile ordered values from a 250-draw distribution. FINDINGS: Total numbers of global DALYs grew 6·1% (95% UI 4·0-8·1), from 2·64 billion (2·46-2·86) in 2010 to 2·80 billion (2·57-3·08) in 2023, but age-standardised DALY rates, which account for population growth and ageing, decreased by 12·6% (11·0-14·1), revealing large long-term health improvements. Non-communicable diseases (NCDs) contributed 1·45 billion (1·31-1·61) global DALYs in 2010, increasing to 1·80 billion (1·63-2·03) in 2023, alongside a concurrent 4·1% (1·9-6·3) reduction in age-standardised rates. Based on DALY counts, the leading level 3 NCDs in 2023 were ischaemic heart disease (193 million [176-209] DALYs), stroke (157 million [141-172]), and diabetes (90·2 million [75·2-107]), with the largest increases in age-standardised rates since 2010 occurring for anxiety disorders (62·8% [34·0-107·5]), depressive disorders (26·3% [11·6-42·9]), and diabetes (14·9% [7·5-25·6]). Remarkable health gains were made for communicable, maternal, neonatal, and nutritional (CMNN) diseases, with DALYs falling from 874 million (837-917) in 2010 to 681 million (642-736) in 2023, and a 25·8% (22·6-28·7) reduction in age-standardised DALY rates. During the COVID-19 pandemic, DALYs due to CMNN diseases rose but returned to pre-pandemic levels by 2023. From 2010 to 2023, decreases in age-standardised rates for CMNN diseases were led by rate decreases of 49·1% (32·7-61·0) for diarrhoeal diseases, 42·9% (38·0-48·0) for HIV/AIDS, and 42·2% (23·6-56·6) for tuberculosis. Neonatal disorders and lower respiratory infections remained the leading level 3 CMNN causes globally in 2023, although both showed notable rate decreases from 2010, declining by 16·5% (10·6-22·0) and 24·8% (7·4-36·7), respectively. Injury-related age-standardised DALY rates decreased by 15·6% (10·7-19·8) over the same period. Differences in burden due to NCDs, CMNN diseases, and injuries persisted across age, sex, time, and location. Based on our risk analysis, nearly 50% (1·27 billion [1·18-1·38]) of the roughly 2·80 billion total global DALYs in 2023 were attributable to the 88 risk factors analysed in GBD. Globally, the five level 3 risk factors contributing the highest proportion of risk-attributable DALYs were high systolic blood pressure (SBP), particulate matter pollution, high fasting plasma glucose (FPG), smoking, and low birthweight and short gestation-with high SBP accounting for 8·4% (6·9-10·0) of total DALYs. Of the three overarching level 1 GBD risk factor categories-behavioural, metabolic, and environmental and occupational-risk-attributable DALYs rose between 2010 and 2023 only for metabolic risks, increasing by 30·7% (24·8-37·3); however, age-standardised DALY rates attributable to metabolic risks decreased by 6·7% (2·0-11·0) over the same period. For all but three of the 25 leading level 3 risk factors, age-standardised rates dropped between 2010 and 2023-eg, declining by 54·4% (38·7-65·3) for unsafe sanitation, 50·5% (33·3-63·1) for unsafe water source, and 45·2% (25·6-72·0) for no access to handwashing facility, and by 44·9% (37·3-53·5) for child growth failure. The three leading level 3 risk factors for which age-standardised attributable DALY rates rose were high BMI (10·5% [0·1 to 20·9]), drug use (8·4% [2·6 to 15·3]), and high FPG (6·2% [-2·7 to 15·6]; non-significant). INTERPRETATION: Our findings underscore the complex and dynamic nature of global health challenges. Since 2010, there have been large decreases in burden due to CMNN diseases and many environmental and behavioural risk factors, juxtaposed with sizeable increases in DALYs attributable to metabolic risk factors and NCDs in growing and ageing populations. This long-observed consequence of the global epidemiological transition was only temporarily interrupted by the COVID-19 pandemic. The substantially decreasing CMNN disease burden, despite the 2008 global financial crisis and pandemic-related disruptions, is one of the greatest collective public health successes known. However, these achievements are at risk of being reversed due to major cuts to development assistance for health globally, the effects of which will hit low-income countries with high burden the hardest. Without sustained investment in evidence-based interventions and policies, progress could stall or reverse, leading to widespread human costs and geopolitical instability. Moreover, the rising NCD burden necessitates intensified efforts to mitigate exposure to leading risk factors-eg, air pollution, smoking, and metabolic risks, such as high SBP, BMI, and FPG-including policies that promote food security, healthier diets, physical activity, and equitable and expanded access to potential treatments, such as GLP-1 receptor agonists. Decisive, coordinated action is needed to address long-standing yet growing health challenges, including depressive and anxiety disorders. Yet this can be only part of the solution. Our response to the NCD syndemic-the complex interaction of multiple health risks, social determinants, and systemic challenges-will define the future landscape of global health. To ensure human wellbeing, economic stability, and social equity, global action to sustain and advance health gains must prioritise reducing disparities by addressing socioeconomic and demographic determinants, ensuring equitable health-care access, tackling malnutrition, strengthening health systems, and improving vaccination coverage. We live in times of great opportunity. FUNDING: Gates Foundation and Bloomberg Philanthropies.

Two amino acids (lysine at position 627 or asparagine at position 701) in the polymerase subunit PB2 protein are considered critical for the adaptation of avian influenza A viruses to mammals. However, the recently emerged pandemic H1N1 viruses lack these amino acids. Here, we report that a basic amino acid at position 591 of PB2 can compensate for the lack of lysine at position 627 and confers efficient viral replication to pandemic H1N1 viruses in mammals. Moreover, a basic amino acid at position 591 of PB2 substantially increased the lethality of an avian H5N1 virus in mice. We also present the X-ray crystallographic structure of the C-terminus of a pandemic H1N1 virus PB2 protein. Arginine at position 591 fills the cleft found in H5N1 PB2 proteins in this area, resulting in differences in surface shape and charge for H1N1 PB2 proteins. These differences may affect the protein's interaction with viral and/or cellular factors, and hence its ability to support virus replication in mammals.

Purpose The purpose of this paper is to explore whether green innovation strategy has a positive effect on green innovation. Furthermore, this study investigates whether both green organizational identity and environmental organizational legitimacy mediate the relationship between green innovation strategy and green innovation. Design/methodology/approach This study is designed as a quantitative research using questionnaires to collect data and employing a variance-based or partial least squares structural equation modeling to test the hypotheses. Findings The empirical results show that green innovation strategy positively affects green innovation. This study also demonstrates that green innovation strategy positively affects green innovation indirectly via green organizational identity and environmental organizational legitimacy in manufacturing companies in Indonesia as a developing country. This study suggests that firms should develop green innovation strategy and it must be reflected as green organizational identity to get environmental organizational legitimacy, and then firms will achieve a better green innovation performance. Research limitations/implications This study has the following limitations. First, a structural equation modeling is used as an approach to test the hypotheses and this may raise the issue of causality. Second, although examining the antecedents of green innovation, this study does not investigate its consequences. Third, the sample size used in this study is relatively small and limited to companies in the Surabaya Industrial Estate Rungkut, Indonesia. Finally, this study employs a cross-sectional survey and the data obtained are based on the Likert scales that may raise the issue of perception bias of the sampled managers. Practical implications The results of this study suggest that managers need to verify the roles of green organizational identity and environmental organizational legitimacy in their companies. In the era of environmentally conscious society, managers need to start with developing a green innovation strategy. However, managers also need to understand that having a strategy is not sufficient enough to directly enhance green innovation performance. Managers need to seek approaches on how to cultivate a strong green organizational identity and use the identity to get environmental organizational legitimacy from the stakeholders. Social implications This research model and results provide the empirical evidence of the importance of green innovation and its antecedents, namely, a green innovation strategy, green organizational identity and environmental organizational legitimacy. When manufacturing companies in Indonesia implement this model of managing environmental issues, the society will get more benefits in terms of the reduction of environmental degradation, the availability of more green products and programs, the improvements in resource efficiencies and economic development and the enhancement of the quality of life. Originality/value A research framework exploring the mediating roles of green organizational identity and environmental organizational legitimacy on green innovation strategy–green innovation relationship is developed to provide the empirical evidence for the organizational identity theory and the organizational legitimacy theory. This study also provides practical implications for managers who are facing the environmental awareness business environment. If they want to achieve a better green innovation performance, managers should enhance their awareness in managing the antecedents of green innovation performance, namely, green innovation strategy, green organizational identity and environmental organizational legitimacy.

The utilization of metal-based conventional coagulants/flocculants to remove suspended solids from drinking water and wastewater is currently leading to new concerns. Alarming issues related to the prolonged effects on human health and further pollution to aquatic environments from the generated nonbiodegradable sludge are becoming trending topics. The utilization of biocoagulants/bioflocculants does not produce chemical residue in the effluent and creates nonharmful, biodegradable sludge. The conventional coagulation-flocculation processes in drinking water and wastewater treatment, including the health and environmental issues related to the utilization of metal-based coagulants/flocculants during the processes, are discussed in this paper. As a counterpoint, the development of biocoagulants/bioflocculants for drinking water and wastewater treatment is intensively reviewed. The characterization, origin, potential sources, and application of this green technology are critically reviewed. This review paper also provides a thorough discussion on the challenges and opportunities regarding the further utilization and application of biocoagulants/bioflocculants in water and wastewater treatment, including the importance of the selection of raw materials, the simplification of extraction processes, the application to different water and wastewater characteristics, the scaling up of this technology to a real industrial scale, and also the potential for sludge recovery by utilizing biocoagulants/bioflocculants in water/wastewater treatment.

The need for a good understanding of the relationship between financial inclusion and economic growth has become a significant concern in national development. Both sectors play an essential role in formulating income distribution policies and reducing poverty, evidence from Eastern Indonesia. This paper, therefore, empirically analyzes the contribution of the financial inclusion to economic growth, poverty alleviation and income inequality in Eastern Indonesia. The Toda-Yamamoto VAR bivariate causality model and the dynamic Panel Vector Autoregression (PVAR) were the two approaches used in this research. The effect and relationship of financial inclusion on economic growth, poverty, inequality and other factors were analyzed using PVAR, and Toda-Yamamoto VAR bivariate causality model, respectively. The results of the bivariate causality model indicate a high relationship level between financial inclusion, economic growth, poverty, and income distribution in Eastern Indonesia. The socio-economic growth has a positive impact on the level of financial inclusion, with a negative impact on poverty. Meanwhile, financial inclusion has a positive effect on inequality, which leads to widespread income inequality in Eastern Indonesia.

Stunting reflects chronic undernutrition during the most critical periods of growth and development in early life. Stunting can be caused by many factors such as child characteristic and socioeconomic factors. The aim of this study was to determine factors associated to stunting among children under five. This research was an analitycal observational study using case control design in Puskesmas Tanah Kali Kedinding, Surabaya. The samples were 34 subject for each group which were selected by simple random sampling technique. Data were analyzed by Chi Square and Fisher Exact test. The result showed that low birth length (OR=4,091; CI=1,162-14,397), children who did not get exclusive breastfeeding (OR=4,643; CI=1,328-16,233), low family income (OR=3,250; CI=1,150-9,187), low mother’s education (OR=3,378; CI=1,246-9,157), and lack of mother’s nutrition knowledge (OR=3,877; CI=1,410- 10,658) had significant relationship with stunting among children under five. There was a relationship between birth length, exclusive breastfeeding, family income, mother’s education and mother’s nutrition knowledge with stunting among children under five. The need for an integrated and multisectoral programs to increase family income, maternal education, maternal nutrition knowledge, and exclusive breastfeeding for reducing the incidence of stunting.Keywords: children, socioeconomic, stunting