Geographic Variation Research Articles

Prevalence, Risk Factors, and Clinical Profiles of Hepatitis D Virus in Nigeria: A Systematic Review, 2009–2024

Background: The World Health Organization (WHO) recommends hepatitis D virus (HDV) screening among hepatitis B virus (HBV) infected individuals, with a focus on priority populations in resource-limited settings like Nigeria. HDV infection is a growing public health challenge, particularly among individuals with chronic hepatitis B virus (HBV) infection. HDV accelerates liver disease progression and significantly increases the risk of cirrhosis and hepatocellular carcinoma. Despite this, the epidemiology of HDV in Nigeria remains inadequately documented. This scoping review critically evaluates the prevalence, risk factors, and clinical outcomes of HDV co-infection among HBV patients in Nigeria. Method: We conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The review included observational cross-sectional studies published between 2009 and 2024. We focused on studies that used Immunoglobulin G (IgG) antibody testing or RNA-based diagnostics to assess HDV prevalence. We included PubMed, Google Scholar, and Dimensions databases due to their broad indexing and coverage of peer-reviewed articles and accessibility. We screened the studies for their relevance to HDV prevalence, risk factors, and clinical outcomes, while excluding those that only tested for IgM or HDV antigen. Eleven studies, with a combined sample size of 2308 participants, were included in the final analysis. We performed a narrative synthesis of the findings, considering geographic, gender, and age-based variations in HDV prevalence and clinical impact. Results: HDV prevalence among HBV-infected individuals in Nigeria ranged from 2.0% to 31.6%. The highest prevalence was reported in the Southwest (31.6%) among malaria patients, while lower rates were observed in the Southeast (2.8%). Prevalence was higher in males, particularly those aged 21–30 years in the Southwest and 31–40 years in other regions. RNA-based testing provided more accurate data on active viremia, with viremic HDV prevalence rates ranging from 3.2% to 16%. Triple infection with HIV/HBV/HDV was associated with significantly lower CD4+ cell counts and worse clinical outcomes, including elevated liver enzymes and rapid progression to liver cancer. Key risk factors for HDV co-infection included multiple sexual partners, sharing of needles, and unsafe medical practices. Co-infected patients demonstrated worse clinical outcomes, such as elevated liver enzymes, decompensated cirrhosis, and higher rates of hepatocellular carcinoma. Conclusions: Our review underscores the urgent need for routine HDV screening among HBV patients in Nigeria, especially given the severe clinical consequences of co-infection. The recent WHO guidelines recommending HDV screening align with our findings, which emphasize the importance of RNA-based HDV testing among HBV-positive patients to improve diagnostic accuracy. Public health efforts should prioritize tailored interventions based on geographic, age, and gender disparities in HDV prevalence. Triple infection with HIV/HBV/HDV requires integrated care models to address both immune suppressions as indicated by diminished CD4 cell count and liver disease progression, as these patients face worse outcomes. Targeted HDV screening in mostly affected demographics and geographies and improved Nigeria capacity for cheaper HDV RNA/PCR diagnostics can reduce liver-related morbidity and mortality caused by HBV, which can be worsened and accelerated by HDV coinfection.

Determinant of Rural and Urban Student Performance in Ghana

Despite the large number of remedial students entering tertiary institutions in Ghana, very little empirical research has examined the impact of geographical and socio-economic variables on student performance. This study uses microdata on 360 urban and rural remedial students to examine the differences in educational outcomes between those attending remedial schools in rural areas and those enrolled in urban remedial schools. The study further analyzes the determinants of educational outcomes, with a focus on the relevance of geographical location. The descriptive analysis shows that the academic outcomes of urban remedial students are generally better than those of rural students. In contrast, the results from the student’s t-test indicate a statistically significant difference in the performance of urban and rural remedial students. The determinants of these performances include age, gender, number of papers written, parental education, and, most importantly, the location of the remedial student. From a policy perspective, the findings of this paper support actions aimed at improving educational conditions in rural areas.

Quantitative Analysis of Human Activities and Climatic Change in Grassland Ecosystems in the Qinghai–Tibet Plateau

Net primary production (NPP) serves as a critical proxy for monitoring changes in the global capacity for vegetation carbon sequestration. The assessment of the factors (i.e., human activities and climate changes) influencing NPP is of great value for the study of terrestrial systems. To investigate the influence of factors on grassland NPP, the ecologically vulnerable Qinghai–Tibet Plateau region was considered an appropriate study area for the period from 2000 to 2020. We innovated the use of the RICI index to quantitatively represent human activities and analyzed the effects of RICI and climatic factors on grassland NPP using the geographical detector. In addition, the future NPP was predicted through the integration of two modeling approaches: The Patch-Generating Land Use Simulation (PLUS) model and the Carnegie–Ames–Stanford Approach (CASA) model. The assessment revealed that the expanded grassland contributed 7.55 × 104 Gg C (Gg = 109 g) to the total NPP, whereas the deterioration of grassland resulted in a decline of 1.06 × 105 Gg C. The climatic factor was identified as the dominant factor in grassland restoration, representing 70.85% of the total NPP, as well as the dominant factor in grassland degradation, representing 92.54% of the total NPP. By subdividing the climate change and human activity factors into sub-factors and detecting them with a geographical detector, the results show that climate change and anthropogenic factors have significant ability to explain geographic variation in NPP to a considerable extent, and the effect on NPP is greater when the factors interact. The q-values of the Relative Impact Contribution Index (RICI) and the RICI of the land use change NPP are consistently greater than 0.6, with the RICI of the human management practices NPP and the evapotranspiration remaining at approximately 0.5. The analysis of the interaction between climate and human activity factors reveals an average impact of greater than 0.8. By 2030, the NPP of the natural development scenario, economic development scenario (ED), and ecological protection scenario (EP) show a decreasing trend due to climate change, the dominant factor, causing them to decrease. Human activities play a role in the improvement. The EP indicates a positive expansion in the growth rate of forests, water, and wetlands, while the ED reveals rapid urbanization. It is notable that this is accompanied by a temporary suspension of urban greening.

Geo-climatic factors co-drive the phenotypic diversity of wild hemp (Cannabis sativa L.) in the Potohar Plateau and Lesser Himalayas

Hemp (Cannabis sativa L.) is an annual, and dioecious herb belonging to the Cannabaceae family. This plant is native to Central and Southeast Asia. The wild races of this species are commonly growing in Khyber Pakhtunkhwa and Punjab provinces, as well as in Islamabad, Pakistan. This study provides crucial insights into how environmental variables influence the wild hemp populations, which can be utilized in for conservation and breeding. The present study was aimed at evaluating the effects of key environmental factors such as altitude, geographical location, precipitation, relative humidity, maximum, minimum, and average temperature on 16 morpho-agronomic traits of a wild population of hemp growing in the Potohar Plateau and Lesser Himalayas. Our findings indicated that high relative humidity (> 64%), low average temperature (< 15 °C), intermediate average temperature (19–22 °C), and high average temperature (> 22 °C) played significant roles in determining the distribution pattern of the wild hemp. Correlation analysis demonstrated that average annual temperature contributed a higher percentage of variation in phenotypic diversity than geographic variables. Additionally, cluster analysis indicated three groups for the selected 35 populations. Clustering and Principal Component Analysis (PCA) of the morpho-agronomic traits indicated that group 1 from the Lesser Himalayas showed high relative humidity (> 64%) and low average temperature (< 15 °C). Conversely, Group 2 populations from the Potohar Plateau demonstrated intermediate average temperature (19–22 °C). There is an existence of Group 3 in the Potohar Plateau with a high average temperature (> 22 °C) compared to Group 1 and Group 2. Our examination highlights the complex interplay between ecological factors, and morphological attributes in native landraces of Cannabis sativa, giving significant insight into knowledge for preservation and breeding initiatives. A study of genetic diversity could complement morpho-agronomic traits in future research to learn more about how genetic variation affects environmental adaptation.

Sympatric populations of crop and wild carrots (Daucus carota ssp.) have distinct viromes, with shared core species more prevalent in farm-grown populations

Viral exchanges between crops and wild plants are important considerations in virus ecology and epidemiology but remain poorly understood. To investigate such exchanges, we compared the viromes of wild and farmed carrots (Daucus carota ssp.) growing near each other in France. Farm populations included cultivated varieties and off-type carrots (resembling wild ones) growing among them. This crop - wild relative pathosystem offers notable opportunities for virus exchange due to the hosts’ genetic closeness and geographic proximity. High-throughput sequencing found that viral taxonomic richness was greatest in wild carrots. However, hierarchical clustering and bipartite network analyses revealed that wild and farm carrot viromes differed in their seed-borne and vector-borne components. While ~50% of viral taxa were shared among carrot population types, others were uniquely associated with either wild or farm carrots. Individual-plant RT-PCR testing of 16 aphid-borne agents from the shared core virome found their prevalence was generally greatest in farm populations, with some geographic variability in virus pressure. The viromes of off-type and cultivated carrots were most similar, suggesting that proximity and/or management practices influence virome properties. For some aphid-borne viruses, similar isolates were found in wild and cultivated carrots, suggesting exchanges between them or with a shared source. However, isolates of other aphid-borne viruses clustered by carrot type, indicating barriers to viral fluxes, that might involve differential susceptibility of populations, vector preferences, or unidentified factors. To improve virus management, we need better understanding of how specific facilitators and barriers of viral exchange can be manipulated to reduce negative viral impacts.

Insights into Helicobacter pylori macrolide resistance: a comprehensive systematic review and meta-analysis.

Helicobacter pylori infection is a primary global health concern. However, the widespread use of antibiotics, particularly macrolides such as clarithromycin, has increased resistance among H. pylori strains. This study aimed to investigate the prevalence of macrolide resistance in H. pylori in different world regions. This systematic literature search was performed using the appropriate search syntax after searching PubMed, Embase, Web of Science, and Scopus databases between May 2015 and December 2023. Statistical analysis was performed using Pooled and random effects model in R and the metafor package. A total of 7,768 articles were retrieved. After a thorough evaluation, 155 studies (by 178 reports) were finally eligible for inclusion in this systematic review and meta-analysis. According to the results, the majority of studies (178 reports from 43 countries) assessed clarithromycin susceptibility, with a pooled prevalence of 33.3% and high heterogeneity between studies (I 2 = 98.57%, p < 0.001). The rate of erythromycin resistance was moderate (22.8%, 10 reports), while azithromycin resistance was 34.4% (4 reports). Subgroup analysis revealed significant differences in the prevalence of resistance based on geographic location, continent, and year of publication. Clarithromycin resistance increased from 29.1% (2015-2019) to 36.5% (2020-2023). This study highlights the critical challenges of macrolide resistance in treating H. pylori infection. The high prevalence and geographic variation underscore the need for tailored treatment strategies based on regional resistance patterns. Furthermore, continuously monitoring resistance trends and investigating contributing factors are essential to optimize treatment. https://www.crd.york.ac.uk/prospero; CRD42024557749.

Children with disabilities: Left behind or forgotten? Empirical evidence from Botswana using multidimensional poverty measures

The 2030 Agenda for Sustainable Development recognises the importance of multidimensional poverty and disability. Although there is compelling evidence suggesting that people with disabilities have a higher probability of being poor, studies that compare children with disabilities with those without disabilities remain scarce and limited to developed countries. Using the 2015/16 Botswana multi-topic household survey, we examined the link between childhood disability and multidimensional child poverty in Botswana. The study employs the conceptual framing of the capability and human rights-based approaches. Results reveal significant disparities in poverty levels between children with and those without disabilities across demographic, economic and geographical variables, with children with disabilities experiencing higher poverty levels than the rest of the children population. We conclude that children with disabilities in Botswana are left out and argue that deliberate efforts should be put in place to implement existing and develop new inclusive policies that ensure equal opportunities for children with disabilities in order not to be left behind. The paper provides policy implications for childhood disability and multidimensional child poverty research in Botswana.

An analysis into the rise of private healthcare in England by geographical location and time period

Abstract Background Private healthcare is a rapidly growing industry in the UK, particularly for surgical procedures. Across the pandemic period, waiting lists for elective surgical and consultant-led care increased from 4.4 to 7.5 million patients. This study aimed to analyse the trends and geographical variations in privately funded and NHS-funded orthopaedic private procedures across England compared to NHS waiting times. Methods We conducted a longitudinal study using quarterly national data between 2019 and 2023 in England. Descriptive analysis of quarterly orthopaedic surgical volumes per 10,000 people, and quarterly orthopaedic surgery wait times stratified by geographical location and time period was conducted. Results Between 2019 and 2023 there were a total of 1,469,450 procedures across the private sector, comprising 1,030,095 NHS-commissioned private orthopaedic procedures and 439,355 private orthopaedic procedures. The South of England performed a higher total number of private procedures per year compared to the North (63 vs 57/10,000 people); whilst there was almost double the number of privately funded procedures (23 vs 12/10,000), the difference was less amongst NHS-funded procedures (45 vs 40/10,000 respectively). There was a large variation in the number of NHS-funded procedures per 10,000 between regions. The North has consistently shorter waiting times than the South. Conclusions Our findings indicate considerable geographical variation in the use of private healthcare between regions, suggesting a two-tier healthcare system. The founding principles of the NHS, healthcare free at the point of use based on clinical need irrespective of ability to pay, continue to be eroded. Policy makers and politicians urgently need to find solutions to ensure all members of society can access the same high quality health care. Key messages • Private healthcare utilization in the UK for orthopaedic procedures, has increased significantly, contributing to an emerging two-tier healthcare system. • There are large geographical disparities in access to healthcare services, with he South of England performing more private proceeds with longer NHS waiting times compared to the North.

6.X.1. Disentangling Long-COVID: prevalence, risk factors and impact

Abstract Background Prolonged symptoms after the acute SARS-COV2 infection significantly alter daily functioning and work ability for substantial number of people. Application of different long COVID definitions result in variable prevalence estimations, while aetiology of long COVID as well as its impact is insufficiently understood. Our workshop is set to discuss the public health impact of long COVID in the general population, to identify risk factors of developing long COVID, and stimulate dialog to advance adequate health care and public health actions aimed to reduce the impact of this condition. Objectives and Key Questions The overall objective is to discuss the public health impact as well as geographic variations across Europe in long COVID prevalence, major risk factors for long COVID and impact on work capacity, accounting for different population-based and hospital study settings. Specifically, the workshop will address the following key questions: 1) what are the challenges in estimating prevalence of long COVID? 2) what are the risk factors of long COVID and some of the most vulnerable population groups? 3) what is a distribution of long COVID in Europe? 4) what is the impact of long COVID on work ability? Brief Overview The workshop will include 3 presentations (in combined total duration of 12 min) on challenges for research and practice attributable to variability in defining long COVID, prevalence of long COVID across several European countries, risks factors of long COVID and impact on work ability. Active discussion of 13 min will conclude the session. Key messages • Standardized definitions, such as WHO-PCC definition with severity thresholds would facilitate surveillance of long COVID and advance knowledge on the risk factors related to this condition. • Understanding better the risk factors and impact of long COVID will inform more adequate screening and therapeutic strategies, and possibly anticipate effects of potential new infectious threats.

Geographic variation in kidney failure and transplantation in Aotearoa New Zealand: A population-based data linkage study.

This study aimed to describe the epidemiology of kidney replacement therapy (KRT) in Aotearoa New Zealand and assess the impact of residential location on access to kidney transplantation. AcceSS and Equity in Transplantation (ASSET), a health-linked data platform, was used to identify people commencing KRT in New Zealand from 2006 to 2019 and analyse regional epidemiology. Health services were classified as 'transplanting', 'intermediate' or 'remote' depending on their degree of separation from a transplant centre. Multiple logistic regression modelling was used to assess the predictors of deceased donor waitlisting or living donor transplantation within 6 months after starting KRT. Web-based mapping software was used to develop interactive geospatial maps. The cohort was 7704 people newly starting KRT. Living in an intermediate [odds ratio (OR): 0.73 (95% confidence interval (CI): 0.61-0.88)] or remote [OR: 0.38 (95% CI: 0.27-0.54)) region and Māori (OR: 0.35 (95% CI: 0.28-0.44)], Pacific [OR: 0.32 (95% CI: 0.24-0.42)) and Asian (OR: 0.66 (95% CI: 0.50-0.87)] ethnicity were associated with a decreased likelihood of timely waitlisting or transplantation. Regional maps can be explored here. There is marked geospatial and ethnic variation in the epidemiology of kidney failure and access to kidney transplantation across New Zealand. Geospatial mapping of kidney failure epidemiology and transplantation outcomes can provide opportunities to direct resources towards populations at greatest need.

Geographical variation in prostate cancer testing explained by socio-economic position in Stockholm

Abstract Background Prostate cancer screening using prostate-specific antigen (PSA) testing is controversial but remains prevalent in many countries. Despite its prevalence there is little information in Sweden or globally on the spatial heterogeneity in PSA testing. This study aims to describe the spatio-temporal variation in PSA testing in the Stockholm region specifically at the municipality and small area level. Additionally, it aims to quantify the extent to which socio-economic position (SEP) indicators such as education, income, and country of birth explain the observed variation in PSA testing. Methods A retrospective population-based register study was conducted, encompassing men aged 40 years and older residing in the Stockholm region from 2007 to 2016. Utilizing spatial smoothing techniques, we calculated the age-standardised proportion of men undergoing PSA testing prior to any prostate cancer diagnosis within each area for every calendar year. Furthermore, we used Bayesian logistic regression models with spatial random effects to estimate the individual-level association between PSA testing and socio-economic position. The proportion of variance in PSA testing explained by various measures of SEP was also estimated at both the municipality and small area levels. Results Significant geographical disparities in PSA testing were observed across small areas within Stockholm. The proportion of variance explained in PSA testing at the small area level was highest for income (32.6%), followed by education (9.7%) and country of birth (7.4%). Incorporating all SEP measures led to a higher proportion of explained variance at the small area level (41.6%) compared to the municipality level (24.8%). Conclusions PSA testing was significantly associated with various socio-economic indicators and some of the spatial variation could be explained by SEP. It would be useful to ascertain whether similar patterns are observed in other regions or countries. Key messages • The findings suggested widespread and consistent opportunistic prostate cancer screening practices within the Stockholm region, raising concerns regarding potential overdiagnosis and overtreatment. • The socio-economic differences in prostate cancer screening could partially explain the differences in cancer incidence and mortality.

Modeling spatiotemporal dynamics of Amblyomma americanum questing activity in the central Great Plains.

Ticks represent important vectors of a number of bacterial and viral disease agents, owing to their hematophagous nature and their questing behavior (the process in which they seek new hosts). Questing activity is notably seasonal with spatiotemporal dynamics that needs to be understood in detail as part of mediating and mitigating tick-borne disease risk. Models of the geography of tick questing activity developed to date, however, have ignored the temporal dimensions of that behavior; more fundamentally, they have often not considered the sampling underlying available occurrence data. Here, we have addressed these shortfalls for Amblyomma americanum, the most commonly encountered tick in the central Great Plains, via (1) detailed, longitudinal sampling to characterize the spatiotemporal dimensions of tick questing activity; (2) randomization tests to establish in which environmental dimensions a species is manifesting selective use; and (3) modeling methods that include both presence data and absence data, taking fullest advantage of the information available in the data resource. The outcome was a detailed picture of geographic and temporal variation in suitability for the species through the two-year course of this study. Such models that take full advantage of available information will be crucial in understanding the risk of tick-borne disease into the future.

Efficiency of coronavirus testing from a spatial perspective: the Israeli case

ABSTRACT A prominent characteristic of. COVID-19 is the long incubation period, the lack of symptoms during that period, and significant geographic variation in prevalence and testing. This article investigates the relationship between testing and infection based on an Israeli sample of 193 municipalities and a report from 11 May 2020. Results support an exponential rise in the fraction of positive. COVID-19 outcomes with the fraction of tests. Finally, under conditions of equal socioeconomic ranking, population density and income inequality, the projected efficiency of tests rises with population density and the Gini index and drops with socioeconomic ranking.

Temporal trends, regional and socio-economic disparities of colorectal cancer burden in Cyprus

Abstract Background Colorectal cancer (CRC) is one of the main causes of mortality and morbidity worldwide and it is the third most common cancer in Cyprus. Previous studies have documented variations in CRC burden over time, across regions and area-based socio-economic deprivation. The aim of this study was to analyse the burden of CRC over time, across regions and area-based socio-economic deprivation in Cyprus for the time period 2000 to 2015. Methods A small area ecological study was performed, with census tracts as units of spatial analysis. The incidence and death date, sex and age of CRC were obtained from the population-based cancer registry of Cyprus. Indirect standardization was used to calculate the sex and age Standardize Incidence Ratios (SIRs) and Standardized Mortality Ratios (SMRs) of CRC while the smoothed estimates of SIRs and SMRs were derived from the Spatiotemporal Bayesian Poisson log-linear model. To investigate temporal trends in the association between area-based socioeconomic deprivation and CRC burden, we have used the national socio-economic index. Results The burden of CRC was rising over time. The CRC cumulative incidence increase from 243.7 in the time period 2000-2007 to 347.3 per 100,000 persons in the time period 2008-2015.There was also a more pronounced geographical variation in SIR and SMR in the time period 2008-2015. Four areas out of 369 had smoothed SIR&amp;gt;1.15 while twenty-six areas had smoothed SMR&amp;gt;1.15, with most of those areas located at the east coast of the island and around the capital city. There was a temporal trend in the socio-economic inequalities of CRC burden. The areas in the third and fourth quartile of the socio-economic index had 23% and 45% lower rates of CRC incidence, and 33% and 47% lower rates of CRC mortality in the period 2008-2015. Conclusions These findings could shape national prevention policies, such as the national screening program of CRC starting in 2025 and protection strategies for CRC mortality. Key messages • Colorectal cancer screening should be geographically targeted for efficient resource allocation. • Public health interventions to improve colorectal-specific mortality risk should be geographically targeted.

Diabetes mellitus EU comorbidity index: using data from EHIS 2019 and GBD disability weights

Abstract Background Individuals with diabetes mellitus (DM) exhibit several of comorbidity burdens, with lower perceived quality of life also being a factor. Literature on the impact of DM is available, including studies on the index devised by (A. Andreella et al., 2023) for the assessment of comorbidities of health conditions. This study aims to adapt and validate this index for use as a standardized DM comorbidity index within the EU. Methods A cross-sectional study was carried out using microdata from the European Health Interview Survey (EHIS) 2019. The study included adults aged 25 years or older who reported having DM (n = 20,042) from 27 EU member states. Comorbidity index was calculated to assess the comorbidity of having 9 non-communicable diseases using disability weights obtained from the Global Burden of Disease 2019 and self-perceived general health using multiplicative approach. Beta regression analysis was used to evaluate the association between comorbidity index and several demographic, socioeconomic and lifestyle variables. Comorbidity index was calculated for each nomenclature of territorial units for statistics (NUTS 2). Results The comorbidity index ranged from 0.049 to 0.993. The results indicated that having a higher education and residing in urban areas were less likely to have a high comorbidity index. Being unemployed or in other employment statuses demonstrated a significant, positive association with the index. Income exhibited a gradual, positive association with each quintile, while consuming fruits and vegetables less than once a week was found to be associated with an increased index. The highest comorbidity index was observed in Calabria (Italy), followed by Lubuskie (Poland), and the lowest was observed in Antwerp (Belgium), followed by Övre Norrland (Sweden). Conclusions By identifying comorbidity burden, targeted interventions and regional-specific strategies can be implemented to improve the quality of life for individuals with DM. Key messages • Quantifying the burden of comorbidities allows understanding of health status of DM patients. • Comorbidity index shows geographic variation in the EU which contributes to tailored policy interventions.

A systematic review and meta-analysis of health-related quality of life (HRQoL) outcomes in randomised controlled trials for pulmonary arterial hypertension (PAH)

Abstract Introduction ESC guidelines recognise the under use of disease-specific health-related quality of life (HRQoL) instruments. These include CAMPHOR, PAH-SYMPACT, Emphasis-10 and Living with Pulmonary Hypertension (LPH). Patients highly value HRQoL as a treatment outcome in PAH. This is the first meta-analysis to evaluate HRQoL instruments and outcomes in RCTs in pulmonary arterial hypertension (PAH). Purpose To evaluate which PAH-RCT interventions improve HRQoL outcomes and compare the suitability of HRQoL instruments used. Method We searched MEDLINE (Jan 1970 to Dec 2023) and Cochrane Library from Jan 1990 to Dec 2023 (EMBASE, CT.gov, ICTRP, CINAHL) for RCTs in PAH. Abstracts and unpublished studies were excluded and PRISMA reporting structure followed. Trials meeting final selection criteria included HRQoL instruments sufficiently powered to detect a minimal clinically important difference (MCID). Effective sample sizes were calculated in GPower3.1 from a two independent means model for 80% power, 5% significance, one-tailed test. Meta-analysis was performed in SPSSv28.1. Full search criteria are registered on PROSPERO (ID: CRD42024484021). Results After removal of duplicates, 896 records were screened, 43 studies included a HRQoL endpoint. 8 studies were included in the meta-analysis after exclusion for insufficient data (n=10) or power (n=25). 3 of these did not meet the MCID (&amp;gt;33m) for six-minute walk distance (6MWD) and evaluated separately to discriminate accuracy of HRQoL instrument. Instruments available for comparison were Short Form-36(SF-36), EuroQol (EQ-5D-5L) and Living with Pulmonary Hypertension (LPH). Studies not reaching MCID for 6MWD also showed no change in HRQoL (figure 1). Ambrisentan and exercise training demonstrate a significant improvement (p&amp;lt;0.05) in SF-36 physical(P) component (figure 2). This component was anchored to determine 6MWD MCID; other HRQoL values responded variably. Utility weighting to account for geographical variation was not reported with EQ-5D-5L and SF-36 in multicentre studies however AIR 2002 (Iloprost) was significant for both EQ-5D-5L instruments. The total component score of the disease-specific LPH was more sensitive to functional improvements and overall change in HRQoL compared to EQ-5D-5L (p&amp;lt;0.05). Conclusion Fewer than 10% of all RCTs in PAH have adequately considered a HRQoL outcome measure. 8 RCTs were powered to assess HRQoL. Iloprost, ambrisentan, riociguat and exercise training interventions demonstrate significant improvement in HRQoL. LPH was the only PAH-instrument powered to detect change. LPH was more sensitive to HRQoL than generic instruments and is multidimensional. Geographical indexing should be considered for generic instruments such as EQ-5D-5L and SF-36 in multicentre trials. As a highly valued outcome for patients, future studies should prioritise HRQoL as an endpoint.Figure 1Figure 2

Unveiling Geographical Variation and Chemotypes of Cupressus torulosa Needle Essential Oil: A Novel Approach Using t‐SNE and HCA

ABSTRACTThis study aimed to assess the geographical variation in the content and chemical composition of Cupressus torulosa needles essential oil across different locations in the Himalayan region of India. The methodology involved the collection of needles from 14 distinct locations, followed by hydro‐distillation using a Clevenger‐type apparatus. Qualitative analysis was conducted using gas chromatography–mass spectrometry (GC–MS), while gas chromatography with flame ionisation detector (GC‐FID) was employed for quantitative analysis. The GC–MS analysis identified a total of 57 compounds, with oxygenated monoterpenes and monoterpene hydrocarbons being the dominant chemical constituents, ranging from 22.5% to 63.01% and from 10.39% to 63.95%, respectively. Terpinen‐4‐ol emerged as the major compound, with concentrations ranging from 101.2 ± 45.7 μg/mg to 393.8 ± 12.5 μg/mg across different locations, with the highest concentration observed in the Dehradun location. The application of t‐distributed stochastic neighbour embedding (t‐SNE) analysis and hierarchical cluster analysis (HCA) revealed the presence of five distinct chemotypes within the essential oil, characterised by different combinations of chemical constituents. These chemotypes were identified as terpinen‐4‐ol/limonene, terpinen‐4‐ol/sabinene, terpinen‐4‐ol, terpinen‐4‐ol/umbellulone, and terpinen‐4‐ol/totarol chemotypes. This research serves as a foundational framework for future investigations aimed at harnessing the unique properties of different chemotypes for specific purposes, potentially facilitating the successful commercialization and utilisation of C. torulosa needles essential oil.

Marketization of Shadow Education in Switzerland: How “Edupreneurs” Promote Preparation Programmes for a Selective School Transition

Private supplementary tutoring (PST) is a flourishing market for edupreneurs whose services relate closely to mainstream education. While international research elaborates on geographical variations in PST and edupreneurs’ marketing strategies, the PST market in Switzerland has been largely understudied. This paper contributes to fill this research gap by presenting a thematic analysis of the websites of edupreneurs offering preparation programmes for the highly selective central entrance examination (CEE) to the academically focused public school track of Gymnasium in Zurich. Conceptually, we draw on “problematization” and “commodificiation” as key terms elaborated by “geographies of marketization”. With this performative conceptualisation of the education market, we examine the marketing strategies of the edupreneurs offering CEE preparation courses. We offer two contributions to the existing research. First, the analysis elaborates that private CEE preparation courses are advertised as a market solution that compensates for an omission caused by public education. Second, we show how edupreneurs use rational and emotional arguments to convince families of the need of booking CEE preparation courses for their children. In the discussion, we engage with the findings of our local case study and argue that selective educational transitions have much wider relevance for policy and society elsewhere.

Phylogenetic Insights into H7Nx Influenza Viruses: Uncovering Reassortment Patterns and Geographic Variability

Influenza A viruses (IAVs), which belong to the Orthomyxoviridae family, are RNA viruses characterized by a segmented genome that allows them to evolve and adapt rapidly. These viruses are mainly transmitted by wild waterfowl. In this study, we investigated the evolutionary processes of H7Nx (H7N1, H7N2, H7N3, H7N4, H7N5, H7N6, H7N7, H7N8, H7N9) viruses, which pose a significant pandemic risk due to the known cases of human infection and their potential for rapid genetic evolution and reassortment. The complete genome sequences of H7Nx influenza viruses (n = 3239) were compared between each other to investigate their phylogenetic relationships and reassortment patterns. For the selected viruses, phylogenetic trees were constructed for eight genome segments (PB2, PB1, PA, HA, NP, NA, M, NS) to assess the genetic diversity and geographic distribution of these viruses. Distinct phylogenetic clades with remarkable geographic patterns were found for the different segments. While the viruses were consistently grouped by subtype based on the NA segment sequences, the phylogeny of the other segment sequences, with the exception of the NS segment, showed distinct grouping patterns based on geographic origin rather than formal subtype assignment. Reassortment events leading to complex phylogenetic relationships were frequently observed. In addition, multiple cases of previously undescribed reassortments between subtypes were detected, emphasizing the fluidity of H7Nx virus populations. These results indicate a high degree of genetic diversity and reassortment within H7Nx influenza viruses. In other words, H7Nx viruses exist as constantly changing combinations of gene pools rather than stable genetic lineages.

Advance Layoff Notice Provision and the WARN Act

We find that the incidence of advance layoff notice more than doubled in the years following the passage of the federal Worker Adjustment and Retraining Notification (WARN) Act. Geographic variation confirms that the act was likely responsible for this increase. We also find that state-level mini-WARN Acts that increased notification coverage had no discernible effect on the incidence of advance notice in these states. But the mini-WARN Act in New York that increased the required length of notice resulted in a commensurate increase in advance notice for affected workers.