Analysis of multiply spliced transcripts in lymphoid tissue reservoirs of rhesus macaques infected with RT-SHIV during HAART.

Highly active antiretroviral therapy (HAART) can reduce levels of human immunodeficiency virus type 1 (HIV-1) to undetectable levels in infected individuals, but the virus is not eradicated. The mechanisms of viral persistence during HAART are poorly defined, but some reservoirs have been identified, such as latently infected resting memory CD4⁺ T cells. During latency, in addition to blocks at the initiation and elongation steps of viral transcription, there is a block in the export of viral RNA (vRNA), leading to the accumulation of multiply-spliced transcripts in the nucleus. Two of the genes encoded by the multiply-spliced transcripts are Tat and Rev, which are essential early in the viral replication cycle and might indicate the state of infection in a given population of cells. Here, the levels of multiply-spliced transcripts were compared to the levels of gag-containing RNA in tissue samples from RT-SHIV-infected rhesus macaques treated with HAART. Splice site sequence variation was identified during development of a TaqMan PCR assay. Multiply-spliced transcripts were detected in gastrointestinal and lymphatic tissues, but not the thymus. Levels of multiply-spliced transcripts were lower than levels of gag RNA, and both correlated with plasma virus loads. The ratio of multiply-spliced to gag RNA was greatest in the gastrointestinal samples from macaques with plasma virus loads <50 vRNA copies per mL at necropsy. Levels of gag RNA and multiply-spliced mRNA in tissues from RT-SHIV-infected macaques correlate with plasma virus load

Motor Competence in Early Childhood Is Positively Associated with Bone Strength in Late Adolescence

The onset of walking in early childhood results in exposure of the lower limb to substantial forces from weight bearing activity that ultimately contribute to adult bone strength. Relationships between gross motor score (GMS), at 18 months and bone outcomes measured at age 17 years were examined in 2327 participants in the Avon Longitudinal Study of Parents and Children (ALSPAC). Higher GMS indicated greater motor competence in weight‐bearing activities. Total hip bone mineral density (BMD) and hip cross‐sectional moment of inertia (CSMI) were assessed from dual‐energy X‐ray absorptiometry (DXA). Bone measures including cortical bone mineral content (BMC), periosteal circumference (PC), cortical thickness (CT), cortical bone area (CBA), cortical BMD (BMD(C)) and cross‐sectional moment of inertia (CSMI) were assessed by peripheral quantitative computed tomography (pQCT) at 50% distal‐proximal length. Before adjustment, GMS was associated with hip BMD, CSMI, and tibia BMC, PC, CT, CBA and CSMI (all p < 0.001) but not BMD(C) (p > 0.25). Strongest associations (standardized regression coefficients with 95% CI) were between GMS and hip BMD (0.086; 95% CI, 0.067 to 0.105) and tibia BMC (0.105; 95% CI, 0.089 to 0.121). With the exception of hip BMD, larger regression coefficients were observed in males (gender interactions all p < 0.05). Adjustment for lean mass resulted in substantial attenuation of regression coefficients, suggesting associations between impaired motor competence and subsequent bone development are partly mediated by alterations in body composition. In conclusion, impaired motor competence in childhood is associated with lower adolescent bone strength, and may represent a risk factor for subsequent osteoporosis. © 2015 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR)

Meeting Report: Application of Genotyping Methods to Assess Risks from Cryptosporidium in Watersheds

A workshop titled "Application of Genotyping Methods to Assess Pathogen Risks from Cryptosporidium in Drinking Water Catchments" was held at the International Water Association biennial conference, Marrakech, Morocco, 23 September 2004. The workshop presented and discussed the findings of an interlaboratory trial that compared methods for genotyping Cryptosporidium oocysts isolated from feces. The primary goal of the trial and workshop was to assess the utility of current Cryptosporidium genotyping methods for determining the public health significance of oocysts isolated from feces in potable-water-supply watersheds. An expert panel of 16 watershed managers, public health practitioners, and molecular parasitologists was assembled for the workshop. A subordinate goal of the workshop was to educate watershed management and public health practitioners. An open invitation was extended to all conference delegates to attend the workshop, which drew approximately 50 interested delegates. In this report we summarize the peer consensus emerging from the workshop. Recommendations on the use of current methods by watershed managers and public health practitioners were proposed. Importantly, all the methods that were reported in the trial were mutually supporting and found to be valuable and worthy of further utility and development. Where there were choices as to which method to apply, the small-subunit ribosomal RNA gene was considered to be the optimum genetic locus to target. The single-strand conformational polymorphism method was considered potentially the most valuable for discriminating to the subtype level and where a large number of samples were to be analyzed. A research agenda for protozoan geneticists was proposed to improve the utility of methods into the future. Standardization of methods and nomenclature was promoted

A novel accelerometer-based method to describe day-to-day exposure to potentially osteogenic vertical impacts in older adults: findings from a multi-cohort study

Summary: This observational study assessed vertical impacts experienced in older adults as part of their day-to-day physical activity using accelerometry and questionnaire data. Population-based older adults experienced very limited high-impact activity. The accelerometry method utilised appeared to be valid based on comparisons between different cohorts and with self-reported activity. Introduction: We aimed to validate a novel method for evaluating day-to-day higher impact weight-bearing physical activity (PA) in older adults, thought to be important in protecting against osteoporosis, by comparing results between four cohorts varying in age and activity levels, and with self-reported PA levels. Methods: Participants were from three population-based cohorts, MRC National Survey of Health and Development (NSHD), Hertfordshire Cohort Study (HCS) and Cohort for Skeletal Health in Bristol and Avon (COSHIBA), and the Master Athlete Cohort (MAC). Y-axis peaks (reflecting the vertical when an individual is upright) from a triaxial accelerometer (sampling frequency 50 Hz, range 0–16 g) worn at the waist for 7 days were classified as low (0.5–1.0 g), medium (1.0–1.5 g) or higher (≥1.5 g) impacts. Results: There were a median of 90, 41 and 39 higher impacts/week in NSHD (age 69.5), COSHIBA (age 76.8) and HCS (age 78.5) participants, respectively (total n = 1512). In contrast, MAC participants (age 68.5) had a median of 14,322 higher impacts/week. In the three population cohorts combined, based on comparison of beta coefficients, moderate-high-impact activities as assessed by PA questionnaire were suggestive of stronger association with higher impacts from accelerometers (0.25 [0.17, 0.34]), compared with medium (0.18 [0.09, 0.27]) and low impacts (0.13 [0.07,0.19]) (beta coefficient, with 95 % CI). Likewise in MAC, reported moderate-high-impact activities showed a stronger association with higher impacts (0.26 [0.14, 0.37]), compared with medium (0.14 [0.05, 0.22]) and low impacts (0.03 [−0.02, 0.08]). Conclusions: Our new accelerometer method appears to provide valid measures of higher vertical impacts in older adults. Results obtained from the three population-based cohorts indicate that older adults generally experience very limited higher impact weight-bearing PA

Habitual levels of higher, but not medium or low, impact physical activity are positively related to lower limb bone strength in older women:findings from a population based study using accelerometers to classify impact magnitude

Summary: This study assessed the effect of accelerometry-measured higher impacts resulting from habitual weight-bearing activity on lower limb bone strength in older women. Despite higher impacts being experienced rarely in this population-based cohort, positive associations were observed between higher vertical impacts and lower limb bone size and strength.  Introduction: We investigated whether the benefit of habitual weight-bearing physical activity (PA) for lower limb bone strength in older women is explained by exposure to higher impacts, as previously suggested by observations in younger individuals.  Methods: Four hundred and eight women from the Cohort for Skeletal Health in Bristol and Avon (COSHIBA), mean 76.8 years, wore tri-axial accelerometers at the waist for a mean of 5.4 days. Y-axis peaks were categorised, using previously identified cutoffs, as low (0.5–1.0 g), medium (1.0–1.5 g), and higher (≥1.5 g) impacts. Mid and distal peripheral quantitative computed tomography scans of the tibia and radius were performed, as were hip and lumbar spine Dual X-ray Absorptiometry (DXA) scans. Regressions between (log transformed) number of low, medium and high impacts, and bone outcomes were adjusted for artefact error grade, age, height, fat and lean mass and impacts in other bands.  Results: Eight thousand eight hundred and nine (4047, 16,882) low impacts were observed during the measurement week, 345 (99, 764) medium impacts and 42 (17, 106) higher impacts (median with 25th and 75th quartiles). Higher vertical impacts were positively associated with lower limb bone strength as reflected by cross-sectional moment of inertia (CSMI) of the tibia [0.042 (0.012, 0.072) p = 0.01] and hip [0.067 (0.001, 0.133) p = 0.045] (beta coefficients show standard deviations change per doubling in impacts, with 95 % confidence interval). Higher impacts were positively associated with tibial periosteal circumference (PC) [0.015 (0.003, 0.027) p = 0.02], but unrelated to hip BMD. Equivalent positive associations were not seen for low or medium impacts. Conclusions: Despite their rarity, habitual levels of higher impacts were positively associated with lower limb bone size and strength, whereas equivalent relationships were not seen for low or medium impacts

Feasibility Study of Short Takeoff and Landing Urban Air Mobility Vehicles Using Geometric Programming

Electric Short Takeoff and Landing (eSTOL) vehicles are proposed as a path towards implementing an Urban Air Mobility (UAM) network that reduces critical vehicle certification risks and offers advantages in vehicle performance compared to the widely proposed Electric Vertical Takeoff and Landing (eVTOL) aircraft. An overview is given of the system constraints and key enabling technologies that must be incorporated into the design of the vehicle. The tradeoffs between vehicle performance and runway length are investigated using geometric programming, a robust optimization framework. Runway lengths as short as 100-300 ft are shown to be feasible, depending on the level of technology and the desired cruise speed. The tradeoffs between runway length and the potential to build new infrastructure in urban centers are investigated using Boston as a representative case study. The placement of some runways up to 600ft is shown to be possible in the urban center, with a significant increase in the number of potential locations for runways shorter than 300ft. Key challenges and risks to implementation are discussed

Home bitter home? Gender, living arrangements, and the exclusion from homeownership among older Europeans

Abstract Homeownership is the most important asset among the elderly in Europe, but very little is known about gender and living arrangement differences in this domain. This paper aims at exploring patterns of exclusion from homeownership among middle-aged and older Europeans from a gender perspective, and with a special focus on their household composition. The analysis is based on the fourth wave of the “Survey of Health, Aging and Retirement in Europe” and includes a sub-sample of about 56,000 individuals aged 50 or over, living in 16 European countries. We estimated a set of multinomial logit models to examine the probability of being either tenant or rent-free occupiers versus homeowners. Our findings show that women are generally more likely to be excluded from homeownership than men. Nevertheless, a closer look suggests that the gender gap in homeownership is essentially generated by compositional differences between men and women, with the most relevant factor being household type. Older women are almost as twice as likely as men to live alone, which is associated—other things being equal—with a particular low likelihood to be homeowners virtually in every European country

Electrochemistry of nanozeolite-immobilized cytochrome c in aqueous and nonaqueous solutions

peer-reviewedThe electrochemical properties of cytochrome c (cyt c) immobilized on multilayer nanozeolite-modified electrodes have been examined in aqueous and nonaqueous solutions. Layers of Linde type-L zeolites were assembled on indium tin oxide (ITO) glass electrodes followed by the adsorption of cyt c, primarily via electrostatic interactions, onto modified ITO electrodes. The heme protein displayed a quasi-reversible response in aqueous solution with a redox potential of +324 mV (vs NHE), and the surface coverage (Gamma*) increased linearly for the first four layers and then gave a nearly constant value of 200 pmol cm(-2). On immersion of the modified electrodes in 95% (v/v) nonaqueous solutions, the redox potential decreased significantly, a decrease that originated from changes in both the enthalpy and entropy of reduction. On reimmersion of the modified electrode in buffer, the faradic response immediately returned to its original value. These results demonstrate that nanozeolites are potential stable supports for redox proteins and enzymes.ACCEPTEDpeer-reviewe

The effect of the national minimum wage on the UK small business sector : a geographical analysis

A national minimum wage (NMW) was introduced into the United Kingdom in 1999 as part of New Labour's active labour-market approach. The level has been uprated on several occasions since then. Most research suggests that the NMW has benefited low-paid workers while having little adverse impact on employment levels. This paper explores the regional impact of the NMW on the small business sector, using data from the Federation of Small Businesses' biennial survey, the largest business survey in the United Kingdom. Overall, just over 21% of businesses with employees uprated employees and just under 10% of employees have benefited from pay uprates. The impact has varied across industries, with the greatest effects in the hotels and catering sector. In general, affected businesses have anticipated that they would be able to absorb the costs, although in some cases at the expense of a slight decline in profitability. The impact of the NMW also varies across the regions, having the least impact in London and the South East and the greatest impact in the 'north'. In the northern regions, businesses are less able to absorb the increased costs and more likely to respond by increasing prices. This has potential implications for the competitiveness of small and medium-sized enterprises in these regions, which is more likely to be based around price and cost advantages than their counterparts in the south. The Low Pay Commission therefore should give greater attention to the geographical impacts of the NMW in its evaluation and when proposing future increases in the rate