The distributional consequences of a tax reform on a VAT for Pakistan

To what extent do rich or poor lose or gain from different tax reform packages ? The authors compare the consequences of different options by analyzing actual patterns of consumption and production. Pakistan, which relies on a narrow tax base has difficulty ensuring that the tax system keeps pace with the growth in national income and activity, without frequent discretionary changes. These changes increase the distortions caused by cascading, with adverse effects on both exports and poor households. The authors'method of estimating the consequences of tax reform shows, for example, that a value added tax would make Pakistan's tax system more buoyant and reduce the production distortions.Environmental Economics&Policies,Public Sector Economics&Finance,Economic Theory&Research,Banks&Banking Reform,Municipal Financial Management

Physical Activity and Telomere Biology: Exploring the Link with Aging-Related Disease Prevention

Physical activity is associated with reduced risk of several age-related diseases as well as with increased longevity in both rodents and humans. Though these associations are well established, evidence of the molecular and cellular factors associated with reduced disease risk and increased longevity resulting from physical activity is sparse. A long-standing hypothesis of aging is the telomere hypothesis: as a cell divides, telomeres shorten resulting eventually in replicative senescence and an aged phenotype. Several reports have recently associated telomeres and telomere-related proteins to diseases associated with physical inactivity and aging including cardiovascular disease, insulin resistance, and hypertension. Interestingly several reports have also shown that longer telomeres are associated with higher physical activity levels, indicating a potential mechanistic link between physical activity, reduced age-related disease risk, and longevity. The primary purpose of this review is to discuss the potential importance of physical activity in telomere biology in the context of inactivity- and age-related diseases. A secondary purpose is to explore potential mechanisms and important avenues for future research in the field of telomeres and diseases associated with physical inactivity and aging

Therapy outcome measure for inducible laryngeal obstruction and chronic cough: development and testing of reliability and validity

A Therapy Outcome Measure (TOM) is a practical tool for measuring outcomes of care, providing a quick and simple measure which can be used over time in a routine clinical setting. The TOM allows therapists to reflect on the dimensions of impairment, activity, participation, and well-being on an 11-point ordinal scale. Currently there are no therapy outcome measures for Inducible Laryngeal Obstruction (ILO) and Chronic Cough (CC). The purpose of this study was to develop two TOMs, one for ILO (TOM ILO) and one for CC (TOM CC), and to test the reliability and validity of each. Respiratory professionals working with patients with ILO and CC from eight UK locations received training in the use of TOM ILO and TOM CC. Face validity, inter-rater reliability and test-retest reliability were tested and analysed. TOM ILO and TOM CC both have strong face validity. The TOM ILO had strong intra-rater reliability and inter-rater reliability. The TOM CC had poor intra-rater but strong inter-rater reliability. TOM ILO and TOM CC have readily been adapted by those who received training. TOM ILO and TOM CC can now be used as a validated outcome measure

Chronic Exercise Modifies Age-Related Telomere Dynamics in a Tissue-Specific Fashion

We evaluated the impact of long-term exercise on telomere dynamics in wild-derived short telomere mice (CAST/Ei) over 1 year. We observed significant telomere shortening in liver and cardiac tissues in sedentary 1-year-old mice compared with young (8 weeks) baseline mice that were attenuated in exercised 1-year-old animals. In contrast, skeletal muscle exhibited significant telomere shortening in exercise mice compared with sedentary and young mice. Telomerase enzyme activity was increased in skeletal muscle of exercise compared with sedentary animals but was similar in cardiac and liver tissues. We observed significant age-related decreases in expression of telomere-related genes that were attenuated by exercise in cardiac and skeletal muscle but not liver. Protein content of TRF1 was significantly increased in plantaris muscle with age. In summary, long-term exercise altered telomere dynamics, slowing age-related decreases in telomere length in cardiac and liver tissue but contributing to shortening in exercised skeletal muscle

Exercise, APOE, and Working Memory: MEG and Behavioral Evidence for Benefit of Exercise in Epsilon4 Carriers

Performance on the Sternberg working memory task, and MEG cortical response on a variation of the Sternberg task were examined in middle-aged carriers and non-carriers of the APOE ε4 allele. Physical activity was also assessed to examine whether exercise level modifies the relationship between APOE genotype and neurocognitive function. Regression revealed that high physical activity was associated with faster RT in the six- and eight-letter conditions of the Sternberg in ε4 carriers, but not in the non-carriers after controlling for age, gender, and education (N = 54). Furthermore, the MEG analysis revealed that sedentary ε4 carriers exhibited lower right temporal lobe activation on matching probe trials relative to high-active ε4 carriers, while physical activity did not distinguish non-carriers (N = 23). The M170 peak was identified as a potential marker for pre-clinical decline as ε4 carriers exhibited longer M170 latency, and highly physically active participants exhibited greater M170 amplitude to matching probe trials

The use of predictive fall models for older adults receiving aged care, using routinely collected electronic health record data : a systematic review

Background: Falls in older adults remain a pressing health concern. With advancements in data analytics and increasing uptake of electronic health records, developing comprehensive predictive models for fall risk is now possible. We aimed to systematically identify studies involving the development and implementation of predictive falls models which used routinely collected electronic health record data in home-based, community and residential aged care settings. Methods: A systematic search of entries in Cochrane Library, CINAHL, MEDLINE, Scopus, and Web of Science was conducted in July 2020 using search terms relevant to aged care, prediction, and falls. Selection criteria included English-language studies, published in peer-reviewed journals, had an outcome of falls, and involved fall risk modelling using routinely collected electronic health record data. Screening, data extraction and quality appraisal using the Critical Appraisal Skills Program for Clinical Prediction Rule Studies were conducted. Study content was synthesised and reported narratively. Results: From 7,329 unique entries, four relevant studies were identified. All predictive models were built using different statistical techniques. Predictors across seven categories were used: demographics, assessments of care, fall history, medication use, health conditions, physical abilities, and environmental factors. Only one of the four studies had been validated externally. Three studies reported on the performance of the models. Conclusions: Adopting predictive modelling in aged care services for adverse events, such as falls, is in its infancy. The increased availability of electronic health record data and the potential of predictive modelling to document fall risk and inform appropriate interventions is making use of such models achievable. Having a dynamic prediction model that reflects the changing status of an aged care client is key to this moving forward for fall prevention interventions

Predominant Infection of CD150+ Lymphocytes and Dendritic Cells during Measles Virus Infection of Macaques

Measles virus (MV) is hypothesized to enter the host by infecting epithelial cells of the respiratory tract, followed by viremia mediated by infected monocytes. However, neither of these cell types express signaling lymphocyte activation molecule (CD150), which has been identified as the receptor for wild-type MV. We have infected rhesus and cynomolgus macaques with a recombinant MV strain expressing enhanced green fluorescent protein (EGFP); thus bringing together the optimal animal model for measles and a virus that can be detected with unprecedented sensitivity. Blood samples and broncho-alveolar lavages were collected every 3 d, and necropsies were performed upon euthanasia 9 or 15 d after infection. EGFP production by MV-infected cells was visualized macroscopically, in both living and sacrificed animals, and microscopically by confocal microscopy and FACS analysis. At the peak of viremia, EGFP fluorescence was detected in skin, respiratory and digestive tract, but most intensely in all lymphoid tissues. B- and T-lymphocytes expressing CD150 were the major target cells for MV infection. Highest percentages (up to 30%) of infected lymphocytes were detected in lymphoid tissues, and the virus preferentially targeted cells with a memory phenotype. Unexpectedly, circulating monocytes did not sustain productive MV infection. In peripheral tissues, large numbers of MV-infected CD11c+ MHC class-II+ myeloid dendritic cells were detected in conjunction with infected T-lymphocytes, suggesting transmission of MV between these cell types. Fluorescent imaging of MV infection in non-human primates demonstrated a crucial role for lymphocytes and dendritic cells in the pathogenesis of measles and measles-associated immunosuppression

Early Target Cells of Measles Virus after Aerosol Infection of Non-Human Primates

Measles virus (MV) is highly infectious, and has long been thought to enter the host by infecting epithelial cells of the respiratory tract. However, epithelial cells do not express signaling lymphocyte activation molecule (CD150), which is the high-affinity cellular receptor for wild-type MV strains. We have generated a new recombinant MV strain expressing enhanced green fluorescent protein (EGFP), based on a wild-type genotype B3 virus isolate from Khartoum, Sudan (KS). Cynomolgus macaques were infected with a high dose of rMVKSEGFP by aerosol inhalation to ensure that the virus could reach the full range of potential target cells throughout the entire respiratory tract. Animals were euthanized 2, 3, 4 or 5 days post-infection (d.p.i., n = 3 per time point) and infected (EGFP+) cells were identified at all four time points, albeit at low levels 2 and 3 d.p.i. At these earliest time points, MV-infected cells were exclusively detected in the lungs by fluorescence microscopy, histopathology and/or virus isolation from broncho-alveolar lavage cells. On 2 d.p.i., EGFP+ cells were phenotypically typed as large mononuclear cells present in the alveolar lumen or lining the alveolar epithelium. One to two days later, larger clusters of MV-infected cells were detected in bronchus-associated lymphoid tissue (BALT) and in the tracheo-bronchial lymph nodes. From 4 d.p.i. onward, MV-infected cells were detected in peripheral blood and various lymphoid tissues. In spite of the possibility for the aerosolized virus to infect cells and lymphoid tissues of the upper respiratory tract, MV-infected cells were not detected in either the tonsils or the adenoids until after onset of viremia. These data strongly suggest that in our model MV entered the host at the alveolar level by infecting macrophages or dendritic cells, which traffic the virus to BALT or regional lymph nodes, resulting in local amplification and subsequent systemic dissemination by viremia

HIV-1 Inhibits Phagocytosis and Inflammatory Cytokine Responses of Human Monocyte-Derived Macrophages to P. falciparum Infected Erythrocytes

HIV-1 infection increases the risk and severity of malaria by poorly defined mechanisms. We investigated the effect of HIV-1Ba-L infection of monocyte-derived macrophages (MDM) on phagocytosis of opsonised P. falciparum infected erythrocytes (IE) and subsequent proinflammatory cytokine secretion. Compared to mock-infected MDM, HIV-1 infection significantly inhibited phagocytosis of IE (median (IQR) (10 (0–28) versus (34 (27–108); IE internalised/100 MDM; p = 0.001) and decreased secretion of IL-6 (1,116 (352–3,387) versus 1,552 (889–6,331); pg/mL; p = 0.0078) and IL-1β (16 (7–21) versus 33 (27–65); pg/mL; p = 0.0078). Thus inadequate phagocytosis and cytokine production may contribute to impaired control of malaria in HIV-1 infected individuals