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897 result(s) for "Spencer, Jennifer"
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MNEs and corruption: the impact of national institutions and subsidiary strategy
We argue that the pressure MNE subsidiaries face to engage in corrupt practices in their host country varies positively with the institutionalization of corrupt practices in both host and home country environments. We further argue that the relationship between an MNE's home country environment and the pressure it faces in the host country is moderated by its localization strategy. Results suggest a positive relationship between the host country corruption environment and the pressure subsidiaries face to engage in bribery locally. Mixed results emerged concerning MNEs from home countries participating in the OECD Convention for Combating Bribery. Results concerning the impact of the home country corruption environment are best viewed in light of significant moderating effects. When MNEs did not have local partners, firms from less corrupt home countries reported less pressure to engage in corrupt practices locally; however, the presence of local partners eliminated this relationship. Results will help managers understand the pressures their firm is likely to face when operating in corrupt host country environments, and also offer guidance concerning how the firm might reduce its exposure to those local institutional pressures.
Mosquito saliva alone has profound effects on the human immune system
Mosquito saliva is a very complex concoction of >100 proteins, many of which have unknown functions. The effects of mosquito saliva proteins injected into our skin during blood feeding have been studied mainly in mouse models of injection or biting, with many of these systems producing results that may not be relevant to human disease. Here, we describe the numerous effects that mosquito bites have on human immune cells in mice engrafted with human hematopoietic stem cells. We used flow cytometry and multiplex cytokine bead array assays, with detailed statistical analyses, to detect small but significant variations in immune cell functions after 4 mosquitoes fed on humanized mice footpads. After preliminary analyses, at different early times after biting, we focused on assessing innate immune and subsequent cellular responses at 6 hours, 24 hours and 7 days after mosquito bites. We detected both Th1 and Th2 human immune responses, and delayed effects on cytokine levels in the blood, and immune cell compositions in the skin and bone marrow, up to 7 days post-bites. These are the first measurements of this kind, with human immune responses in whole animals, bitten by living mosquitoes, versus previous studies using incomplete mouse models and salivary gland extracts or needle injected saliva. The results have major implications for the study of hematophagous insect saliva, its effects on the human immune system, with or without pathogen transmission, and the possibility of determining which of these proteins to target for vaccination, in attempts to block transmission of numerous tropical diseases.
Dengue viruses infect human megakaryocytes, with probable clinical consequences
One of the most important clinical signs of dengue virus infection is the reduction of white blood cells and platelets in human peripheral blood (leukopenia and thrombocytopenia, respectively), which may significantly impair the clearance of dengue virus by the immune system. The cause of thrombocytopenia and leukopenia during dengue infection is still unknown, but may be related to severe suppression of bone marrow populations including hematopoietic stem cells and megakaryocytes, the progenitors of white blood cells and platelets respectively. Here, we explored the possibility that bone marrow suppression, including ablation of megakaryocyte populations, is caused by dengue virus infection of megakaryocytes. We used three different models to measure dengue virus infection and replication: in vitro, in a human megakaryocyte cell line with viral receptors, ex vivo, in primary human megakaryocytes, and in vivo, in humanized mice. All three systems support dengue virus infection and replication, including virus strains from serotypes 1, 2, and 3, and clinical signs, in vivo; all assays showed viral RNA and/or infectious viruses 7-14 days post-infection. Although we saw no significant decrease in cell viability in vitro, there was significant depletion of mature megakaryocytes in vivo. We conclude that megakaryocytes can produce dengue viruses in the bone marrow niche, and a reduction of cell numbers may affect bone marrow homeostasis.
Modified vaccinia Ankara expressing EEHV1A glycoprotein B elicits humoral and cell-mediated immune responses in mice
Elephant endotheliotropic herpesvirus (EEHV) can cause lethal hemorrhagic disease (EEHV-HD) in Asian elephants and is the largest cause of death in captive juvenile Asian elephants in North America and Europe. EEHV-HD also has been documented in captive and wild elephants in their natural range countries. A safe and effective vaccine to prevent lethal EEHV infection would significantly improve conservation efforts for this endangered species. Recent studies from our laboratory suggest that EEHV morbidity and mortality are often associated with primary infection. Therefore, we aim to generate a vaccine, particularly for EEHV1 naïve animals, with the goal of preventing lethal EEHV-HD. To address this goal, we generated a Modified Vaccinia Ankara (MVA) recombinant virus expressing a truncated form of glycoprotein B (gBΔfur731) from EEHV1A, the strain associated with the majority of lethal EEHV cases. Vaccination of CD-1 mice with this recombinant virus induced robust antibody and polyfunctional T cell responses significantly above mice inoculated with wild-type MVA. Although the vaccine-induced T cell response was mainly observed in CD8 + T cell populations, the CD4 + T cell response was also polyfunctional. No adverse responses to vaccination were observed. Overall, our data demonstrates that MVA-gBΔfur731 stimulates robust humoral and cell-mediated responses, supporting its potential translation for use in elephants.
Assessment of US Preventive Services Task Force Guideline–Concordant Cervical Cancer Screening Rates and Reasons for Underscreening by Age, Race and Ethnicity, Sexual Orientation, Rurality, and Insurance, 2005 to 2019
Cervical cancer screening rates are suboptimal in the US. Population-based assessment of reasons for not receiving screening is needed, particularly among women from historically underserved demographic groups. To estimate changes in US Preventive Service Task Force guideline-concordant cervical cancer screening over time and assess the reasons women do not receive up-to-date screening by sociodemographic factors. This pooled population-based cross-sectional study used data from the US National Health Interview Survey from 2005 and 2019. A total of 20 557 women (weighted, 113.1 million women) aged 21 to 65 years without previous hysterectomy were included. Analyses were conducted from March 30 to August 19, 2021. Sociodemographic factors, including age, race and ethnicity, sexual orientation, rurality of residence, and health insurance type. Primary outcomes were US Preventive Services Task Force guideline-concordant cervical cancer screening rates and self-reported primary reasons for not receiving up-to-date screening. For 2005, up-to-date screening was defined as screening every 3 years for women aged 21 to 65 years. For 2019, up-to-date screening was defined as screening every 3 years with a Papanicolaou test alone for women aged 21 to 29 years and screening every 3 years with a Papanicolaou test alone or every 5 years with high-risk human papillomavirus testing or cotesting for women aged 30 to 65 years. Population estimation included sampling weights. Among 20 557 women (weighted, 113.1 million women) included in the study, most were aged 30 to 65 years (16 219 women; weighted, 86.3 million women [76.3%]) and had private insurance (13 571 women; weighted, 75.8 million women [67.0%]). With regard to race and ethnicity, 997 women (weighted, 6.9 million women [6.1%]) were Asian, 3821 women (weighted, 19.5 million women [17.2%]) were Hispanic, 2862 women (weighted, 14.8 million women [13.1%]) were non-Hispanic Black, 12 423 women (weighted, 69.0 million women [61.0%]) were non-Hispanic White, and 453 women (weighted, 3.0 million women [2.7%]) were of other races and/or ethnicities (including Alaska Native and American Indian [weighted, 955 000 women (0.8%)] and other single and multiple races or ethnicities [weighted, 2.0 million women (1.8%)]). In 2019, women aged 21 to 29 years had a significantly higher rate of overdue screening (29.1%) vs women aged 30 to 65 years (21.1%; P < .001). In both age groups, the proportion of women without up-to-date screening increased significantly from 2005 to 2019 (from 14.4% to 23.0%; P < .001). Significantly higher rates of overdue screening were found among those of Asian vs non-Hispanic White race and ethnicity (31.4% vs 20.1%; P = .01), those identifying as LGBQ+ (gender identity was not assessed because of a small sample) vs heterosexual (32.0% vs 22.2%; P < .001), those living in rural vs urban areas (26.2% vs 22.6%; P = .04), and those without insurance vs those with private insurance (41.7% vs 18.1%; P < .001). The most common reason for not receiving timely screening across all groups was lack of knowledge, ranging from 47.2% of women identifying as LGBQ+ to 64.4% of women with Hispanic ethnicity. Previous receipt of a human papillomavirus vaccine was not a primary reason for not having up-to-date screening (<1% of responses). From 2005 to 2019, among women aged 30 to 65 years, lack of access decreased significantly as a primary reason for not receiving screening (from 21.8% to 9.7%), whereas lack of knowledge (from 45.2% to 54.8%) and not receiving recommendations from health care professionals (from 5.9% to 12.0%) increased significantly. This cross-sectional study found that cervical cancer screening that was concordant with US Preventive Services Task Force guidelines decreased in the US between 2005 and 2019, with lack of knowledge reported as the biggest barrier to receiving timely screening. Campaigns addressing patient knowledge and provider communication may help to improve screening rates, and cultural adaptation of interventions is needed to reduce existing disparities.
Elevations of α-fetoprotein in patients undergoing chemotherapy for pure testicular seminoma: a retrospective cohort study
Background α-Fetoprotein (AFP) is conventionally absent in testicular classical seminoma (TCS). However, moderate AFP elevations can occur in TCS patients, as observed at this and other centres, which can be challenging to diagnostic and management practices. Methods This retrospective cohort study considered AFP concentration in the context of germ-cell tumour diagnosis and characterisation at baseline (BL), disease status during chemotherapy, and long-term surveillance. The study considered patients with histologically diagnosed stage 1 TCS requiring chemotherapy over six years. For those with AFP above the reference interval at BL, histological imaging, case notes, and biochemical data were reviewed from BL to surveillance completion. Outcomes included AFP changes, diagnoses, therapy, disease progression, and death. Results Of the 175 patients included, eight (4.6%) had elevated AFP at BL. Of these, two showed statistically but not clinically significant AFP changes during therapy, while six had moderate, stable AFP elevations with no changes in diagnosis during follow-up. During therapy, one patient developed metastases, and one died of causes likely unrelated to their TCS. Conclusions Mild elevations of AFP in TCS may lead to diagnostic uncertainty or inappropriate management and investigation. However, AFP changes, alongside imaging, did not affect diagnosis, therapy, or follow-up at this centre for any of the patients examined. A subgroup of TCS patients has stable, moderate AFP elevations unrelated to tumour aetiology.
Sialokinin in mosquito saliva shifts human immune responses towards intracellular pathogens
Mosquito saliva is a mix of numerous proteins that are injected into the skin while the mosquito searches for a blood meal. While mosquito saliva is known to be immunogenic, the salivary components driving these immune responses, as well as the types of immune responses that occur, are not well characterized. We investigated the effects of one potential immunomodulatory mosquito saliva protein, sialokinin, on the human immune response. We used flow cytometry to compare human immune cell populations between humanized mice bitten by sialokinin knockout mosquitoes or injected with sialokinin, and compared them to those bitten by wild-type mosquitoes, unbitten, or saline-injected control mice. Humanized mice received 4 mosquito bites or a single injection, were euthanized after 7 days, and skin, spleen, bone marrow, and blood were harvested for immune cell profiling. Our results show that bites from sialokinin knockout mosquitoes induced monocyte and macrophage populations in the skin, blood, bone marrow, and spleens, and primarily affected CD11c- cell populations. Other increased immune cells included plasmacytoid dendritic cells in the blood, natural killer cells in the skin and blood, and CD4+ T cells in all samples analyzed. Conversely, we observed that mice bitten with sialokinin knockout mosquitoes had decreased NKT cell populations in the skin, and fewer B cells in the blood, spleen, and bone marrow. Taken together, we demonstrated that sialokinin knockout saliva induces elements of a T H 1 cellular immune response, suggesting that the sialokinin peptide is inducing a T H 2 cellular immune response during wild-type mosquito biting. These findings are an important step towards understanding how mosquito saliva modulates the human immune system and which components of saliva may be critical for arboviral infection. By identifying immunomodulatory salivary proteins, such as sialokinin, we can develop vaccines against mosquito saliva components and direct efforts towards blocking arboviral infections.
Elevations of alpha-fetoprotein in patients undergoing chemotherapy for pure testicular seminoma: a retrospective cohort study
[alpha]-Fetoprotein (AFP) is conventionally absent in testicular classical seminoma (TCS). However, moderate AFP elevations can occur in TCS patients, as observed at this and other centres, which can be challenging to diagnostic and management practices. This retrospective cohort study considered AFP concentration in the context of germ-cell tumour diagnosis and characterisation at baseline (BL), disease status during chemotherapy, and long-term surveillance. The study considered patients with histologically diagnosed stage 1 TCS requiring chemotherapy over six years. For those with AFP above the reference interval at BL, histological imaging, case notes, and biochemical data were reviewed from BL to surveillance completion. Outcomes included AFP changes, diagnoses, therapy, disease progression, and death. Of the 175 patients included, eight (4.6%) had elevated AFP at BL. Of these, two showed statistically but not clinically significant AFP changes during therapy, while six had moderate, stable AFP elevations with no changes in diagnosis during follow-up. During therapy, one patient developed metastases, and one died of causes likely unrelated to their TCS. Mild elevations of AFP in TCS may lead to diagnostic uncertainty or inappropriate management and investigation. However, AFP changes, alongside imaging, did not affect diagnosis, therapy, or follow-up at this centre for any of the patients examined. A subgroup of TCS patients has stable, moderate AFP elevations unrelated to tumour aetiology.
What constitutes ‘poor’ adherence to medical advice for chronic diseases? Insights from a qualitative study among hypertension and diabetes patients in urban informal settlements, Mumbai Metropolitan Region
The problem of poor adherence to medical advice in the case of non-communicable diseases, the reasons thereof, and how these are exacerbated in low- and middle-income countries (LMICs) is well-recognized. However, there is less conceptual clarity on what 'poor' adherence encompasses in these settings. Conventional classifications treat poor adherence as a singular category, often disregarding its multifaceted nature. This study aimed to explore the nuances of what constitutes 'poor' adherence to medical advice for chronic diseases in vulnerable LMIC settings. This was done by examining the different ways in which hypertension and diabetes patients living in urban informal settlements in the Mumbai Metropolitan Region attempted to adhere to medical advice. This is a qualitative study using a grounded analysis approach. The study was part of larger research conducted to understand care-seeking for hypertension and diabetes in urban informal settlements. Purposive sampling was used to identify participants. Data was collected from September to November 2022 through in-depth interviews with 26 hypertension and diabetes patients. Emerging patterns of adherence were inductively coded and categorized using grounded analysis. The study highlights multiple ways in which patients attempted to adhere to medical advice. By tracing patient journeys and experiences in adherence, the study categorizes 'poor' adherence to medical advice as adherence to medication, lifestyle changes and follow-ups with various sub-categories within each. Most patients reported more than one way in which they tried to adhere to medical advice. Patients adhered well to some aspects of their medical advice and not to others, highlighting the complexities in understanding this concept. By understanding the nuances and complexities of 'poor' adherence in urban informal settlements, the study builds an empirically grounded typology on adherence. Such a typology is useful for research and practice on improving adherence to medical advice in vulnerable LMIC settings.
Bringing the Institutional Context Back In: A Cross-National Comparison of Alliance Partner Selection and Knowledge Acquisition
We suggest that firms' national institutional environments alter the logic of alliance partner selection and associated knowledge acquisition. We posit that cross-national variations in corporatist institutional structures (which reflect differences in underlying cooperative norms) influence the relative importance that firms place on a prospective partner's social value (evidenced from the partner's connectedness with members of its industry) and technological value (reflected in the technological complementarity and novelty of the partner's knowledge). We expect that as prospective partners' technological value increases, the probability of alliance formation increases the most for firms residing in less corporatist countries. Likewise, as prospective partners' social value increases, the probability of alliance formation increases the most for firms in more corporatist countries. We further argue that norms regarding knowledge acquisition within an alliance vary across countries, with deliberate learning approaches serving as the norm in less—not more—corporatist settings. We expect that such differences will lead to more immediate interpartner knowledge acquisition in less corporatist environments. Analysis of a longitudinal cross-national data set of alliances in the emergent fuel cell technology industry supports our arguments. Our findings highlight the significance of particular national institutions in specific organizational domains and the complementarity between institutional theory and other strategic resource-based perspectives in the context of interorganizational alliances.