Conceptualizing and measuring distance in international business research:Recurring questions and best practice guidelines

Distance is a central concept in international business research, yet there is debate about the construct as well as its operationalization. In this editorial, we address three of the most important recurring questions posed by authors, editors, and reviewers by examining the theory, methods, and data of distance research. We discuss (1) how to theorize on distance, and (2) what method and (3) what data to use when constructing a distance index. We develop practical recommendations grounded in theory, illustrating and supporting them by calculating cross-country distance indices for all available country pairs and two of the most used distance indices: cultural and institutional. We show that, whereas a specific method to calculate distance may matter to some extent, the choice for a specific cultural or institutional framework to measure cultural or institutional distance has a major impact on country-pair distances. Overall, this editorial highlights the importance of matching data and method to the theoretical argument.</p

Understanding the Emergence of HIV-2 Group F, a Novel, Pathogenic HIV-2 Indigenous to Sierra Leone

Background: AIDS is caused by infection with pathogenic strains of HIV-1 or 2. HIV-2 is broken into 9 groups, A-I. Groups A and B are epidemic in West Africa while the remaining groups are individual cases and are not known to be pathogenic. HIV-2F is an exception being both pathogenic and found in 2 persons, suggesting transmissibility. HIV's origins have been widely studied, however, questions remain. The simian ancestry of HIV is well established yet exactly how SIV adapted to HIV in humans is still unknown. Several theories have been put forth to explain HIV emergence from SIV including the serial passage theory of HIV emergence. Here we conduct an HIV survey in northern Sierra Leone (SL) to assess the public health threat of HIV-2F and also model the serial passage theory of emergence both in vivo and in vitro to elucidate mechanisms of adaptation. Materials and methods: For the human HIV study in northern SL, we enrolled persons presenting for a voluntarily HIV test following education and outreach activities and those referred for an HIV test. This is a targeted, higher risk population than the general population. Commercial HIV-1/2 rapid tests were used in the field. Proviral DNA was amplified with PCR methods and sequenced with Sanger methods. Parallel pigtailed (PTM) and rhesus macaque in vivo and in vitro models were used to test the serial passage theory of HIV emergence. Virus was detected with an HIV-2F specific qPCR and commercial SIV p27 Antigen ELISA. Illumina methods were used to deep sequence day 3 samples with peak virus loads. A SNP analysis was conducted to investigate virus variation over serial passage. Results: To date we have found the prevalence of HIV in the targeted sample population to be 6.36%. HIV-2 rates in the targeted sample were 0.50%, HIV-1 was 4.81% and apparent co-infections were seen in 1.06% of those tested. Two HIV-1 samples have been sequenced and typed to CRF02_AG. Attempts to PCR amplify proviral DNA from HIV-2 antibody positives were negative, possibly due to low virus load. In vitro, over serial passage, peak virus load decreased to undetectable, the opposite of what was expected. In fact, the in vitro serial passage results exactly contradict what was observed in a parallel in vivo serial passage experiment. In vivo we saw an increase in PVL over serial passage in the PTMs and viral escape in passages 2 and 3. SNP analysis showed mutations over serial passage allowing the virus to adapt to a new host in vivo. Conclusion: In this study we asked two main research questions. First, is HIV-2F a public health threat? This question remains unanswered due to our inability to sequence the HIV-2 samples collected in this study. However, the samples remain preserved for applying different techniques. We described HIV burden in a self-selected, at risk population in northern Sierra Leone providing the first HIV-2 data in 20 years. We also provided the first HIV-1 sequence data from Sierra Leoneans living in Sierra Leone, all previous data are from SL immigrants to Europe or the USA. The second question was, can the serial passage hypothesis of HIV emergence be modeled to elucidate the role of serial passage in HIV cross-species transmission, adaptation and diversity? We successfully showed that this can be done through the in vivo serial passage experiment in pigtailed macaques. Together the data from the field studies along with the in vivo and in vitro models presented in this thesis provide a better understanding of mechanisms of HIV emergence as well as much needed information about HIV distribution and genetic diversity in northern Sierra Leone

344 Understanding drivers of post-Ebola syndrome (PES) in pediatric survivors of Ebolavirus disease: characterization and the way forward.

OBJECTIVES/GOALS: Ebolavirus disease survivors report persistent, debilitating health concerns dubbed Post-Ebola Syndrome (PES). Attention to PES in young survivors is lacking, we describe PES in pediatric EVD survivors in Eastern Sierra Leone. Additionally, we introduce our proposal investigating differential presentations of PES in pediatric survivors. METHODS/STUDY POPULATION: EVD survivors were enrolled a median of 2.5 years after resolution of disease. Survivors were eligible if listed in a national register maintained by the Sierra Leone Association of Ebola Survivors. Household contacts (HCs) were identified by survivors. Participants were assigned into three comparison groups: pediatric (7-11), adolescent (12-17) and young adult (18-25). A self-reported symptom questionnaire, and a physical exam were conducted. Variables were clustered within organ system and compared across groups. RESULTS/ANTICIPATED RESULTS: Pediatric survivors had lower levels of long-term sequelae compared to adolescents and young adults. Symptoms and abnormal physical exam signs increase with age. Musculoskeletal, psychiatric, ophthalmologic, and GI signs and symptoms were significantly different between groups. Pediatric survivors had significantly more persistent sequelae than age-matched HCs with no history of EVD; particularly within the cardiac/GI (p=.006) and psychiatric/neurological (p=.025) clusters. PES is heterogeneous with respect to age, calling for a deeper understanding of age-based differences. Even the youngest group of survivors experienced significantly more sequelae than HCs, highlighting the elevated symptom burden in these children over their peers. DISCUSSION/SIGNIFICANCE: Understanding mechanistic drivers will ultimately improve targeted treatments for PES. We will characterize symptom groups defining PES in children, determine the relationship between accelerated aging and PES in this population, and test how immune profiles associated with accelerated aging relate to the development of PES in children

Ophthalmic manifestations and vision impairment in Lassa fever survivors.

The purpose of this study was to describe the ocular findings, structural ocular complications, and vision impairment in a cohort of Lassa fever survivors in Kenema, Sierra Leone. A retrospective, uncontrolled, cross-sectional study of 31 Lassa fever survivors (62 eyes) who underwent an ophthalmic evaluation in January 2018 at the Kenema Government Hospital in Kenema, Sierra Leone was performed. Data collection included demographic information, ocular/systemic symptoms, visual acuity (VA), and ophthalmic examination findings. Main outcome measures included anterior and posterior segment ophthalmic manifestations and level of VA impairment in Lassa fever survivors. Anterior segment findings included cataract (18%) and pterygium (2%), while posterior segment manifestations consisted of glaucoma (6%), preretinal hemorrhage (2%), and lattice degeneration (2%). Findings suggestive of prior sequelae of uveitis included chorioretinal scarring (5%), retinal fibrosis (3%), and vitreous opacity (2%). Visual acuity was normal/mildly impaired in 53 eyes (85%), moderately impaired in 6 eyes (10%), and 3 eyes (5%) were considered blind by the World Health Organization (WHO) criteria. Median VA was worse in Lassa fever survivors with ophthalmic disease findings (p<0.0001) for both anterior segment (p<0.0001) and posterior segment disease (p<0.013). Untreated cataract was a significant cause of visual acuity impairment (p<0.0001). Lassa fever survivors in this cohort were found to have cataract and posterior segment findings that potentially represent sequelae of uveitis associated with visual impairment. Future studies are warranted to improve our understanding of the spectrum of ocular disease in this emerging infectious disease of public health consequence

The prevalence of Post-Ebola Syndrome hearing loss, Sierra Leone

Abstract Background Globally, hearing loss is the second leading cause of disability, affecting approximately 18.7% of the world’s population. However, the burden of hearing loss is unequally distributed, with the majority of affected individuals located in Asia or Sub-Saharan Africa. Following the 2014 West African Ebola Outbreak, disease survivors began to describe hearing loss as part of the constellation of symptoms known as Post-Ebola Syndrome. The goal of this study was to more fully characterize hearing loss among Ebola Virus Disease (EVD) survivors. Methodology and principal findings EVD survivors and their household contacts were recruited (n = 1,12) from Eastern Sierra Leone. Each individual completed a symptom questionnaire, physical exam, and a two-step audiometry process measuring both air and bone conduction thresholds. In comparison to contacts, EVD survivors were more likely to have complaints or abnormal findings affecting every organ system. A significantly greater percentage of EVD survivors were found to have hearing loss in comparison to contacts (23% vs. 9%, p < 0.001). Additionally, survivors were more likely to have bilateral hearing loss of a mixed etiology. Logistic regression revealed that the presence of any symptoms of middle or inner ear (p < 0.001), eye (p = 0.005), psychiatric (p = 0.019), and nervous system (p = 0.037) increased the odds of developing hearing loss. Conclusions and significance This study is the first to use an objective and standardized measurement to report hearing loss among EVD survivors in a clinically meaningful manner. In this study it was found that greater than 1/5th of EVD survivors develop hearing loss. The association between hearing impairment and symptoms affecting the eye and nervous system may indicate a similar mechanism of pathogenesis, which should be investigated further. Due to the quality of life and socioeconomic detriments associated with untreated hearing loss, a greater emphasis must be placed on understanding and mitigating hearing loss following survival to aid in economic recovery following infectious disease epidemics