Retinoblastoma Outcomes Based on the 8th Edition American Joint Committee on Cancer Pathological Classification in 1411 Patients.

PURPOSE: To evaluate the outcomes of retinoblastoma (RB) based on the 8th edition of the American Joint Committee on Cancer (AJCC) pathological classification in a global cohort of patients. DESIGN: Retrospective, multicentre, intercontinental collaborative study PARTICIPANTS: 1411 patients INTERVENTION(S): Primary enucleation with/without adjuvant chemotherapy/radiotherapy MAIN OUTCOMES(S): Orbital tumor recurrence, tumor-related metastasis, tumor-related death RESULTS: Based on the 8th edition AJCC pathological classification, 645 (46%) eyes belonged to pT1, 164 (11%) to pT2, 493 (35%) to pT3, and 109 (8%) to pT4 categories. At a mean follow-up of 38 months (median, 35 months; <1-149 months), orbital tumor recurrence was seen in 8 (1%), 5 (3%), 22 (4%) and 25 (23%) of pT1, pT2, pT3, and pT4 (p<0.001) categories, respectively; tumor-related metastasis was seen in 7 (1%), 5 (3%), 40 (8%), and 46 (43%) of pT1, pT2, pT3, and pT4 (p<0.001) categories, respectively; tumor-related death was seen in 12 (2%), 7 (4%), 64 (13%), and 64 (59%) of pT1, pT2, pT3, and pT4 (p<0.001) categories, respectively. Multivariate Cox proportional hazards analysis of outcomes revealed pT category and adjuvant therapy as independent predictors of outcomes. Categories pT3b (p=0.005), pT3c (p<0.001), pT3d (p<0.001), and pT4 (p<0.001) had a greater hazard for orbital recurrence; categories pT2a (p=0.015), pT3a (p<0.001), pT3b (p<0.001), pT3c (p<0.001), pT3d (p<0.001) and pT4 (p<0.001) had a greater hazard for tumor-related metastasis; and categories pT2a (p=0.068), pT2b (p=0.004), pT3a (p<0.001), pT3b (p<0.001), pT3c (p<0.001), pT3d (p<0.001) and pT4 (p<0.001) had a greater hazard for tumor-related death when compared to the pT1 category. Patients who did not receive adjuvant therapy had greater hazards of orbital tumor recurrence in categories pT3b (p=0.005), pT3c (p=0.003), and pT4 (p=0.002); greater hazards of tumor-related metastasis in categories pT3a (p=0.001), pT3b (p=0.01), pT3c (p=0.001), and pT4 (p=0.007); and tumor-related death in categories pT3a (p<0.001), pT3b (p=0.009), pT3c (p=0.018), and pT4 (p<0.001) when compared to those who received adjuvant therapy. CONCLUSION: The 8th edition AJCC pathological classification predicts outcomes in patients undergoing primary enucleation for RB, and adjuvant therapy is associated with a lower risk of orbital recurrence, tumor-related metastasis, and tumor-related death in the pT3 and pT4 categories.

Genetic diversity varies with species traits and latitude in predatory soil arthropods (Myriapoda: Chilopoda).

Aim: To investigate the drivers of intra-specific genetic diversity in centipedes, a group of ancient predatory soil arthropods. Location: Asia, Australasia and Europe. Time Period: Present. Major Taxa Studied: Centipedes (Class: Chilopoda). Methods: We assembled a database of 1245 mitochondrial cytochrome c oxidase subunit I sequences representing 128 centipede species from all five orders of Chilopoda. This sequence dataset was used to estimate genetic diversity for centipede species and compare its distribution with estimates from other arthropod groups. We studied the variation in centipede genetic diversity with species traits and biogeography using a beta regression framework, controlling for the effect of shared evolutionary history within a family. Results: A wide variation in genetic diversity across centipede species (0-0.1713) falls towards the higher end of values among arthropods. Overall, 27.57% of the variation in mitochondrial COI genetic diversity in centipedes was explained by a combination of predictors related to life history and biogeography. Genetic diversity decreased with body size and latitudinal position of sampled localities, was greater in species showing maternal care and increased with geographic distance among conspecifics. Main Conclusions: Centipedes fall towards the higher end of genetic diversity among arthropods, which may be related to their long evolutionary history and low dispersal ability. In centipedes, the negative association of body size with genetic diversity may be mediated by its influence on local abundance or the influence of ecological strategy on long-term population history. Species with maternal care had higher genetic diversity, which goes against expectations and needs further scrutiny. Hemispheric differences in genetic diversity can be due to historic climatic stability and lower seasonality in the southern hemisphere. Overall, we find that despite the differences in mean genetic diversity among animals, similar processes related to life-history strategy and biogeography are associated with the variation within them.

Birth Cohort Effects in Breast Cancer Incidence: Global Patterns and Trends.

Breast cancer is the most common neoplasm in the world among women. The age-specific incidences and onset ages vary widely between Asian and Western countries/regions. Invasive breast cancer cases among women from 1997 to 2011 were abstracted from the International Agency for Research on Cancer and the Taiwan Cancer Registry. Age-period-cohort analysis was performed to examine the trends. The cohort effect was prominent in South Korea, Taiwan, Japan, and Thailand, possibly related to the timing of westernization. The risk of breast cancer initially rose with the birth cohorts in Hong Kong and India (both former British colonies), peaked, and then declined in recent birth cohorts. Unlike other Asian countries/regions, virtually no birth cohort effect was identified in the Philippines (a Spanish colony in 1565 and the first Asian country to adopt Western cultural aspects). Moreover, an at-most negligible birth cohort effect was identified for all ethnic groups (including Asian immigrants) in the United States. This global study identified birth cohort effects in most Asian countries/regions but virtually no impact in Western countries/regions. The timing of westernization was associated with the birth cohort effect.

Mental health, welfare or justice: An introductory global overview of differences between countries in the scale and approach to secure placements of children and young people.

BACKGROUND: Estimates suggest that over a million children per year are deprived of their liberty across the world. Little is known about the types, ethos or distribution of secure beds in which they are detained. AIM: This study aims to provide quantitative data with background information, to explore similarities and differences across jurisdictions, and to inform critical inquiry into key concepts and practices. METHODS: Data was obtained using an opportunistic sample of affluent countries, derived from an emerging academic/practice network of senior professionals. Depending on jurisdiction, data was already in the public domain or specifically requested. Data requests were related to the nature and size of health, welfare and criminal justice elements of secure beds and recent occupancy. Key professionals working in child secure settings, within jurisdictions, provided commentary on local approaches. RESULTS: Data was incomplete but allowed for comparisons between 10 jurisdictions. The proportions of the populations of children and young people detained varied by jurisdiction as did their distribution across variations of secure settings. Not all jurisdictions had all three kinds of secure settings. Definitions of secure beds varied depending on the use of relational, procedural or physical security. CONCLUSION: Findings are tentative but suggestion solely considering numerical descriptions of children's detention is misleading; our study highlights ways in which comparative studies may be improved. Within reported jurisdictions, the framework of health, welfare and justice was meaningful but this may not hold true with a wider international application of this method. Open interrogation of this data would be enhanced by the inclusion of children's perspectives.

Association between the Mediterranean Diet Score and Healthy Life Expectancy: A Global Comparative Study.

OBJECTIVES: Extending healthy life expectancy (HALE), defined as the average number of years that a person can expect to live in "full health" by taking into account years lived in less than full health due to disease and/or injury, is a common topic worldwide. This study aims to clarify the relationships between the Mediterranean diet score (MDS) and life expectancy (LE) and HALE globally using publicly available international data. SETTING: Analyses were conducted on 130 countries with populations of 1 million or more for which all data were available. Individual countries were scored from 0 to 9 to indicate adherence to the Mediterranean diet according to the MDS scoring method. The supply of vegetables, legumes, fruits and nuts, cereals, fish, and olive oil per 1,000 kcal per country was calculated based on the Food and Agriculture Organization Corporate Statistical Database, with a score of 1 for above the median and 0 for below. The same method was used to calculate scores of presumed detrimental components (meat and dairy), with consumption below the median given a value of 1, and consumption above the median given a value of 0. For ethanol, a score of 1 was given for 10g to 50 g of consumption. We investigated the cross-sectional associations between the MDS and LE and HALE at birth in 2009, and the longitudinal associations between the MDS in 2009 and LE and HALE between 2009 and 2019, controlling for covariates at baseline using linear mixed models. RESULTS: In the cross-sectional analysis, the MDS was significantly positively associated with LE (ß=0.906 [95% confidence interval, 0.065-1.747], p=0.037) and HALE (ß=0.875 [0.207-1.544], p=0.011) after controlling for all covariates. The longitudinal analysis also revealed significantly positive associations between the MDS and LE (0.621 [0.063-1.178], p=0.030) and HALE (0.694 [0.227-1.161], p=0.004) after controlling for all covariates. CONCLUSION: The present study, based on an analysis using 10 years of international data, showed that countries with a higher MDS showed a positive association with HALE.

Perception towards vaccine effectiveness in controlling COVID-19 spread in rural and urban communities: A global survey.

Introduction: Several studies exhibited varying reports of perception toward vaccine effectiveness, vaccine hesitancy, and acceptance of COVID-19 vaccines. As this fluctuated with evidence generation, this study explored the perception toward vaccine effectiveness in rural and urban communities among various countries. Methods: A cross-sectional study was conducted online from April to August 2021 using convenience sampling among people from different countries approved by the Asia Metropolitan University Medical Research and Ethics. We adapted the questionnaire from the World Health Organization's (WHO) survey tool and guidance on COVID-19. The logistic regression models were performed to show perception toward vaccine effectiveness. Results: A total of 5,673 participants responded to the online survey. Overall, 64% of participants agreed that the vaccine effectively controlled viral spread, and 23% agreed that there was no need for vaccination if others were vaccinated. Males had 14% higher odds of believing that there was no need for vaccination. Less social media users had 39% higher odds of developing the belief that there is no need for vaccination than all other people vaccinated. Conclusion: People's perceptions toward vaccine acceptance have fluctuated with the information flow in various social media and the severity of COVID-19 cases. Therefore, it is important that the current scenario of peoples' perception toward vaccine acceptance and determinants affecting the acceptance are explored to promote the vaccination approach against COVID-19 prevention and transmission effectively.

Self-perceived loneliness and depression during the Covid-19 pandemic: a two-wave replication study.

The global Covid-19 pandemic has forced countries to impose strict lockdown restrictions and mandatory stay-at-home orders with varying impacts on individual's health. Combining a data-driven machine learning paradigm and a statistical approach, our previous paper documented a U-shaped pattern in levels of self-perceived loneliness in both the UK and Greek populations during the first lockdown (17 April to 17 July 2020). The current paper aimed to test the robustness of these results by focusing on data from the first and second lockdown waves in the UK. We tested a) the impact of the chosen model on the identification of the most time-sensitive variable in the period spent in lockdown. Two new machine learning models - namely, support vector regressor (SVR) and multiple linear regressor (MLR) were adopted to identify the most time-sensitive variable in the UK dataset from Wave 1 (n = 435). In the second part of the study, we tested b) whether the pattern of self-perceived loneliness found in the first UK national lockdown was generalisable to the second wave of the UK lockdown (17 October 2020 to 31 January 2021). To do so, data from Wave 2 of the UK lockdown (n = 263) was used to conduct a graphical inspection of the week-by-week distribution of self-perceived loneliness scores. In both SVR and MLR models, depressive symptoms resulted to be the most time-sensitive variable during the lockdown period. Statistical analysis of depressive symptoms by week of lockdown resulted in a U-shaped pattern between weeks 3 and 7 of Wave 1 of the UK national lockdown. Furthermore, although the sample size by week in Wave 2 was too small to have a meaningful statistical insight, a graphical U-shaped distribution between weeks 3 and 9 of lockdown was observed. Consistent with past studies, these preliminary results suggest that self-perceived loneliness and depressive symptoms may be two of the most relevant symptoms to address when imposing lockdown restrictions.

Benchmarking the Quality Practices of Global Pharmaceutical Manufacturing to Advance Supply Chain Resilience.

Over the past several decades, pharmaceutical manufacturing has become increasingly global and supply chains have become longer, more complex, and fragmented. While pharmaceutical products available to patients and customers typically conform with appropriate standards, supply chains are often affected by disruptive events and shocks that impact public health. One approach to assuring the availability of quality pharmaceutical products is to encourage drug manufacturers to invest in quality management maturity (QMM) and promote continual improvement. The interests of patients are served by risk-based drug shortage prevention and mitigation activities that help to proactively manage supply chain complexities and ensure availability of drugs. This paper demonstrates that adherence to certain quality practices enables improved manufacturing performance. Prior research has identified quality practices that are correlated with manufacturing performance. To better understand how these quality practices can be characterized, measured, and analyzed, this research project conducted a voluntary global study of pharmaceutical manufacturing establishments. Over 200 global pharmaceutical manufacturing establishments participated in this Quality Benchmarking Study (QBS) and provided data on manufacturing performance and self-assessments of adherence to quality practices. The analysis of these data found that the implementation level for selected quality management practices correlates positively with certain Key Performance Indicators (KPIs). More specifically, we found a significant positive correlation between (i) Delivery Performance and (ii) Application of QMM principles associated with Technical Production.

I'm alone but not lonely. U-shaped pattern of self-perceived loneliness during the COVID-19 pandemic in the UK and Greece.

OBJECTIVES: In the past months, many countries have adopted varying degrees of lockdown restrictions to control the spread of the COVID-19 virus. According to the existing literature, some consequences of lockdown restrictions on people's lives are beginning to emerge yet the evolution of such consequences in relation to the time spent in lockdown is understudied. To inform policies involving lockdown restrictions, this study adopted a data-driven Machine Learning approach to uncover the short-term time-related effects of lockdown on people's physical and mental health. STUDY DESIGN: An online questionnaire was launched on 17 April 2020, distributed through convenience sampling and was self-completed by 2,276 people from 66 different countries. METHODS: Focusing on the UK sample (N = 325), 12 aggregated variables representing the participant's living environment, physical and mental health were used to train a RandomForest model to estimate the week of survey completion. RESULTS: Using an index of importance, Self-Perceived Loneliness was identified as the most influential variable for estimating the time spent in lockdown. A significant U-shaped curve emerged for loneliness levels, with lower scores reported by participants who took part in the study during the 6th lockdown week (p = 0.009). The same pattern was replicated in the Greek sample (N = 137) for week 4 (p = 0.012) and 6 (p = 0.009) of lockdown. CONCLUSIONS: From the trained Machine Learning model and the subsequent statistical analysis, Self-Perceived Loneliness varied across time in lockdown in the UK and Greek populations, with lower symptoms reported during the 4th and 6th lockdown weeks. This supports the dissociation between social support and loneliness, and suggests that social support strategies could be effective even in times of social isolation.

Terminology and quantification of environmental heterogeneity in species-richness research.

Spatial environmental heterogeneity (EH) is an important driver of species diversity, and its influence on species richness has been analysed for numerous taxa, in diverse ecological settings, and over a large range of spatial scales. The variety and ambiguity of concepts and terminology, however, have hampered comparisons among studies. Based on a systematic literature survey of 192 studies including 1148 data points, we provide an overview of terms and measures related to EH, and the mechanisms that relate EH to species richness of plants and animals in terrestrial systems. We identify 165 different measures used to quantify EH, referred to by more than 350 measure names. We classify these measures according to their calculation method and subject area, finding that most studies have analysed heterogeneity in land cover, topography, and vegetation, whereas comparatively few studies have focused on climatic or soil EH. Overall, elevation range emerged as the most frequent measure in our dataset. We find that there is no consensus in the literature about terms (such as 'habitat diversity' or 'habitat complexity'), their meanings and associated quantification methods. More than 100 different terms have been used to denote EH, with largely imprecise delimitations. We reveal trends in use of terms and quantification with respect to spatial scales, study taxa, and locations. Finally, we discuss mechanisms involved in EH-richness relationships, differentiating between effects on species coexistence, persistence, and diversification. This review aims at guiding researchers in their selection of heterogeneity measures. At the same time, it shows the need for precise terminology and avoidance of ambiguous synonyms to enhance understanding and foster among-study comparisons and synthesis.