The challenge of liberalising airline competition in a less developed country: The case of Nepal

A new wave of liberalisation of airline markets is taking place in less devel oped nations, although the initial motivation in most cases is to supplement the capacity of the government’s own airline. Liberalisation tends to begin with free market entry and a strong interest in privatisation whilst other regulatory controls are maintained. This position is untenable and policy makers in the less developed countries are having to learn quickly without the benefit of the detailed analyses that preceded liberalisation in the developed countries. This set of circumstances is illustrated with an examination of the situation in Nepal where, until recently, the Government's own airline enjoyed a monopoly. Though the entry of private sector airlines in Nepal has added capacity and improved services, challenges remain to be addressed. This paper explores these problems and focuses on the lessons that policy makers in the less developed countries can draw from experiences elsewhere

Temporal Progression of Aortic Valve Pathogenesis in a Mouse Model of Osteogenesis Imperfecta.

Organization of extracellular matrix (ECM) components, including collagens, proteoglycans, and elastin, is essential for maintaining the structure and function of heart valves throughout life. Mutations in ECM genes cause connective tissue disorders, including Osteogenesis Imperfecta (OI), and progressive debilitating heart valve dysfunction is common in these patients. Despite this, effective treatment options are limited to end-stage interventions. Mice with a homozygous frameshift mutation in col1a2 serve as a murine model of OI (oim/oim), and therefore, they were used in this study to examine the pathobiology of aortic valve (AoV) disease in this patient population at structural, functional, and molecular levels. Temporal echocardiography of oim/oim mice revealed AoV dysfunction by the late stages of disease in 12-month-old mice. However, structural and proteomic changes were apparent much earlier, at 3 months of age, and were associated with disturbances in ECM homeostasis primarily related to collagen and proteoglycan abnormalities and disorganization. Together, findings from this study provide insights into the underpinnings of late onset AoV dysfunction in connective tissue disease patients that can be used for the development of mechanistic-based therapies administered early to halt progression, thereby avoiding late-stage surgical intervention

Elastogenesis Correlates With Pigment Production in Murine Aortic Valve Leaflets

Objective: Aortic valve (AV) leaflets rely on a precise extracellular matrix (ECM) microarchitecture for appropriate biomechanical performance. The ECM structure is maintained by valvular interstitial cells (VICs), which reside within the leaflets. The presence of pigment produced by a melanocytic population of VICs in mice with dark coats has been generally regarded as a nuisance, as it interferes with histological analysis of the AV leaflets. However, our previous studies have shown that the presence of pigment correlates with increased mechanical stiffness within the leaflets as measured by nanoindentation analyses. In the current study, we seek to better characterize the phenotype of understudied melanocytic VICs, explore the role of these VICs in ECM patterning, and assess the presence of these VICs in human aortic valve tissues. Approach and Results: Immunofluorescence and immunohistochemistry revealed that melanocytes within murine AV leaflets express phenotypic markers of either neuronal or glial cells. These VIC subpopulations exhibited regional patterns that corresponded to the distribution of elastin and glycosaminoglycan ECM proteins, respectively. VICs with neuronal and glial phenotypes were also found in human AV leaflets and showed ECM associations similar to those observed in murine leaflets. A subset of VICs within human AV leaflets also expressed dopachrome tautomerase, a common melanocyte marker. A spontaneous mouse mutant with no aortic valve pigmentation lacked elastic fibers and had reduced elastin gene expression within AV leaflets. A hyperpigmented transgenic mouse exhibited increased AV leaflet elastic fibers and elastin gene expression. Conclusions: Melanocytic VIC subpopulations appear critical for appropriate elastogenesis in mouse AVs, providing new insight into the regulation of AV ECM homeostasis. The identification of a similar VIC population in human AVs suggests conservation across species

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Association of DC-SIGN Promoter Polymorphism with Increased Risk for Parenteral, but Not Mucosal, Acquisition of Human Immunodeficiency Virus Type 1 Infection

There is considerable debate about the fundamental mechanisms that underlie and restrict acquisition of human immunodeficiency virus type 1 (HIV-1) infection. In light of recent studies demonstrating the ability of C type lectins to facilitate infection with HIV-1, we explored the potential relationship between polymorphisms in the DC-SIGN promoter and risk for acquisition of HIV-1 according to route of infection. Using samples obtained from 1,611 European-American participants at risk for parenteral (n = 713) or mucosal (n = 898) infection, we identified single-nucleotide polymorphisms in the DC-SIGN promoter using single-strand conformation polymorphism. Individuals at risk for parenterally acquired infection who had −336C were more susceptible to infection than were persons with −336T (odds ratio = 1.87, P = 0.001). This association was not observed in those at risk for mucosally acquired infection. A potential role for DC-SIGN specific to systemic acquisition and dissemination of infection is suggested

Skin Cancer Knowledge, Beliefs, Self-Efficacy, and Preventative Behaviors among North Mississippi Landscapers

There are slightly over one million workers in the landscape service industry in the US. These workers have potential for high levels of solar ultraviolet radiation exposure, increasing their risk of skin cancer. A cross-sectional sample of 109 landscapers completed a self-administered questionnaire based on Health Belief Model (HBM). The participants correctly answered 67.1% of the knowledge questions, 69.7% believed they were more likely than the average person to get skin cancer, and 87.2% perceived skin cancer as a severe disease. Participants believed that the use of wide-brimmed hats, long sleeved shirts/long pants, and sunscreen was beneficial but reported low usage of these and other sun protective strategies. The primary barriers to using sun protection were “I forget to wear it” and “it is too hot to wear.” Of the HBM variables, perceived benefits outweighing perceived barrier (, ) and self-efficacy (, ) were correlated with sun protection behaviors. The reasons for absence of the relationship between perceived skin cancer threat and sun protection behaviors could be lack of skin cancer knowledge and low rate of personal skin cancer history

Elastogenesis Correlates With Pigment Production in Murine Aortic Valve Leaflets

Objective: Aortic valve (AV) leaflets rely on a precise extracellular matrix (ECM) microarchitecture for appropriate biomechanical performance. The ECM structure is maintained by valvular interstitial cells (VICs), which reside within the leaflets. The presence of pigment produced by a melanocytic population of VICs in mice with dark coats has been generally regarded as a nuisance, as it interferes with histological analysis of the AV leaflets. However, our previous studies have shown that the presence of pigment correlates with increased mechanical stiffness within the leaflets as measured by nanoindentation analyses. In the current study, we seek to better characterize the phenotype of understudied melanocytic VICs, explore the role of these VICs in ECM patterning, and assess the presence of these VICs in human aortic valve tissues.Approach and Results: Immunofluorescence and immunohistochemistry revealed that melanocytes within murine AV leaflets express phenotypic markers of either neuronal or glial cells. These VIC subpopulations exhibited regional patterns that corresponded to the distribution of elastin and glycosaminoglycan ECM proteins, respectively. VICs with neuronal and glial phenotypes were also found in human AV leaflets and showed ECM associations similar to those observed in murine leaflets. A subset of VICs within human AV leaflets also expressed dopachrome tautomerase, a common melanocyte marker. A spontaneous mouse mutant with no aortic valve pigmentation lacked elastic fibers and had reduced elastin gene expression within AV leaflets. A hyperpigmented transgenic mouse exhibited increased AV leaflet elastic fibers and elastin gene expression.Conclusions: Melanocytic VIC subpopulations appear critical for appropriate elastogenesis in mouse AVs, providing new insight into the regulation of AV ECM homeostasis. The identification of a similar VIC population in human AVs suggests conservation across species

Risk and Clinical Risk Factors associated With Late Lower Cranial Neuropathy in Long-Term oropharyngeal Squamous Cell Carcinoma Survivors

IMPORTANCE: Lower cranial neuropathy (LCNP) is a rare, but permanent, late effect of radiotherapy and other cancer therapies. Lower cranial neuropathy is associated with excess cancer-related symptoms and worse swallowing-related quality of life. Few studies have investigated risk and clinical factors associated with late LCNP among patients with long-term survival of oropharyngeal squamous cell carcinoma (OPSCC survivors). OBJECTIVE: to estimate the cumulative incidence of and identify clinical factors associated with late LCNP among long-term OPSCC survivors. DESIGN, SETTING, AND PARTICIPANTS: This single-institution cohort study included disease-free adult OPSCC survivors who completed curative treatment from January 1, 2000, to December 31, 2013. Exclusion criteria consisted of baseline LCNP, recurrent head and neck cancer, treatment at other institutions, death, and a second primary, persistent, or recurrent malignant neoplasm of the head and neck less than 3 months after treatment. Median survival of OPSCC among the 2021 eligible patients was 6.8 (range, 0.3-18.4) years. Data were analyzed from October 12, 2019, to November 13, 2020. MAIN OUTCOMES AND MEASURES: Late LCNP events were defined by neuropathy of the glossopharyngeal, vagus, and/or hypoglossal cranial nerves at least 3 months after cancer therapy. Cumulative incidence of LCNP was estimated using the Kaplan-Meier method, and multivariable Cox proportional hazards models were fit. RESULTS: Among the 2021 OPSCC survivors included in the analysis of this cohort study (1740 [86.1%] male; median age, 56 [range, 28-86] years), 88 (4.4%) were diagnosed with late LCNP, with median time to LCNP of 5.4 (range, 0.3-14.1) years after treatment. Cumulative incidence of LCNP was 0.024 (95% CI, 0.017-0.032) at 5 years, 0.061 (95% CI, 0.048-0.078) at 10 years, and 0.098 (95% CI, 0.075-0.128) at 15 years of follow-up. Multivariable Cox proportional hazards regression identified T4 vs T1 classification (hazard ratio [HR], 3.82; 95% CI, 1.85-7.86) and accelerated vs standard radiotherapy fractionation (HR, 2.15; 95% CI, 1.34-3.45) as independently associated with late LCNP status, after adjustment. Among the subgroup of 1986 patients with nonsurgical treatment, induction chemotherapy regimens including combined docetaxel, cisplatin, and fluorouracil (TPF) (HR, 2.51; 95% CI, 1.35-4.67) and TPF with cetuximab (HR, 5.80; 95% CI, 1.74-19.35) along with T classification and accelerated radiotherapy fractionation were associated with late LCNP status after adjustment. CONCLUSIONS AND RELEVANCE: This single-institution cohort study found that, although rare in the population overall, cumulative risk of late LCNP progressed to 10% during the survivors\u27 lifetime. As expected, clinical factors associated with LCNP primarily reflected greater tumor burden and treatment intensity. Further efforts are necessary to investigate risk-reduction strategies as well as surveillance and management strategies for this disabling late effect of cancer treatment

NASA Hybrid Wing Aircraft Aeroacoustic Test Documentation Report

This report summarizes results of the Hybrid Wing Body (HWB) N2A-EXTE model aeroacoustic test. The N2A-EXTE model was tested in the NASA Langley 14- by 22-Foot Subsonic Tunnel (14x22 Tunnel) from September 12, 2012 until January 28, 2013 and was designated as test T598. This document contains the following main sections: Section 1 - Introduction, Section 2 - Main Personnel, Section 3 - Test Equipment, Section 4 - Data Acquisition Systems, Section 5 - Instrumentation and Calibration, Section 6 - Test Matrix, Section 7 - Data Processing, and Section 8 - Summary. Due to the amount of material to be documented, this HWB test documentation report does not cover analysis of acquired data, which is to be presented separately by the principal investigators. Also, no attempt was made to include preliminary risk reduction tests (such as Broadband Engine Noise Simulator and Compact Jet Engine Simulator characterization tests, shielding measurement technique studies, and speaker calibration method studies), which were performed in support of this HWB test. Separate reports containing these preliminary tests are referenced where applicable