Diamondoid diacids ('O4' species) in oil sands process-affected water.

RATIONALE: As a by-product of oil sands extraction, large volumes of oil sands process water (OSPW) are generated, which are contaminated with a large range of water-soluble organic compounds. The acids are thought to be derived from hydrocarbons via natural biodegradation pathways such as α- and β-oxidation of alkyl substituents, which could produce mono- and diacids, for example. However, while several monoacids ('O2' species) have been identified, the presence of diacids (i.e. 'O4' species) has only been deduced from results obtained via Fourier transform infrared (FTIR) spectroscopy, Fourier transform ion cyclotron resonance high-resolution mass spectrometry (FTICR-HRMS) and nuclear magnetic resonance ((1)H-NMR) spectroscopy and the structures have never been confirmed. METHODS: An extract of an OSPW from a Canadian tailings pond was analysed and the retention times and the electron ionization mass spectra of some analytes were compared with those of bis-methyl esters of authentic diacids by gas chromatography × gas chromatography/time-of-flight mass spectrometry (GCxGC/TOFMS) in nominal and accurate mass configurations. RESULTS: Two diamondoid diacids (3-carboxymethyladamantane-1-carboxylic acid and adamantane-1,3-dicarboxylic acid) were firmly identified as their bis-methyl esters by retention time and mass spectral matching and several other structural isomers were more tentatively assigned. Diacids have substantially increased polarity over the hydrocarbon and monoacid species from which they probably derive: as late members of biodegradation processes they may be useful indicators of weathering and ageing, not only of OSPW, but potentially of crude oil residues more generally. CONCLUSIONS: Structures of O4 species in OSPW have been identified. This confirms pathways of microbial biodegradation, which were only postulated previously, and may be a further indication that remediation of OSPW toxicity can occur by natural microbial action. The presence and abundance of these diacids might therefore be useful as a measure of biodegradation and weathering

Diversity not quantity in caregiver speech: using computational modeling to isolate the effects of the quantity and the diversity of the input on vocabulary growth

Children who hear large amounts of diverse speech learn language more quickly than children who do not. However, high correlations between the amount and the diversity of the input in speech samples makes it difficult to isolate the influence of each. We overcame this problem by controlling the input to a computational model so that amount of exposure to linguistic input (quantity) and the quality of that input (lexical diversity) were independently manipulated. Sublexical, lexical, and multi-word knowledge were charted across development (Study 1), showing that while input quantity may be important early in learning, lexical diversity is ultimately more crucial, a prediction confirmed against children’s data (Study 2). The model trained on a lexically diverse input also performed better on nonword repetition and sentence recall tests (Study 3) and was quicker to learn new words over time (Study 4). A language input that is rich in lexical diversity outperforms equivalent richness in quantity for learned sublexical and lexical knowledge, for well-established language tests, and for acquiring words that have never been encountered before

Cytomegalovirus Infection May Contribute to the Reduced Immune Function, Growth, Development, and Health of HIV-Exposed, Uninfected African Children.

With increasing access to antiretroviral therapy (ART) in Africa, most children born to HIV-infected mothers are not themselves HIV-infected. These HIV-exposed, uninfected (HEU) children are at increased risk of mortality and have immune, growth, development, and health deficits compared to HIV-unexposed children. HEU children are known to be at higher risk than HIV-unexposed children of acquiring cytomegalovirus (CMV) infection in early life. This risk is largely unaffected by ART and is increased by breastfeeding, which itself is critically important for child health and survival. Early CMV infection, namely in utero or during early infancy, may contribute to reduced growth, altered or impaired immune functions, and sensory and cognitive deficits. We review the evidence that CMV may be responsible for the health impairments of HEU children. There are currently no ideal safe and effective interventions to reduce postnatal CMV infection. If a clinical trial showed proof of the principle that decreasing early CMV infection improved health and development of HEU children, this could provide the impetus needed for the development of better interventions to improve the health of this vulnerable population

Association Between Sedentary Time and Quality of Life From the Osteoarthritis Initiative: Who Might Benefit Most From Treatment?

Objective To investigate the relationship between sedentary behavior and quality-adjusted life years (QALYs) among participants in the Osteoarthritis Initiative. Design Longitudinal, observational design. Setting Osteoarthritis Initiative cohort. Participants Individuals (N=1794) from a prospective, multicenter longitudinal cohort were classified into quantile groups based on average daily sedentary time (most sedentary, quartile 1 [Q1] ≥11.6h; 10.7h≤ Q2 Interventions Not applicable. Main Outcome Measures Individual QALYs were estimated over 2 years from the area under the curve of health-related utility scores derived from the Medical Outcomes Study 12-Item Short-Form Health Survey versus time. The relationship between baseline sedentary behavior and median 2-year QALYs was estimated using quantile regression adjusted for socioeconomic factors and body mass index. Results Lower QALYs over 2 years were more frequently found among the most sedentary (Q1, median 1.59), and QALYs increased as time spent in baseline sedentary behavior decreased (median QALYs for Q2, 1.64; Q3, 1.65; Q4, 1.65). The relationship of sedentary time and median QALY change was only significant for the most sedentary Q1 group, where an additional hour of sedentary behavior significantly reduced QALYs by −.072 (95% confidence interval, −.121 to −.020). Conclusions Our findings suggest that individuals with the most extreme sedentary profiles may be vulnerable to additional losses of quality of life if they become more sedentary. Targeting these individuals to decrease sedentary behavior has the potential to be cost-effective

Physical Activity Minimum Threshold Predicting Improved Function in Adults With Lower‐Extremity Symptoms

Objective To identify an evidence‐based minimum physical activity threshold to predict improved or sustained high function for adults with lower‐extremity joint symptoms. Methods Prospective multisite data from 1,629 adults, age ≥49 years with symptomatic lower‐extremity joint pain/aching/stiffness, participating in the Osteoarthritis Initiative accelerometer monitoring substudy were clinically assessed 2 years apart. Improved/high function in 2‐year gait speed and patient‐reported outcomes (PROs) were based on improving or remaining in the best (i.e., maintaining high) function quintile compared to baseline status. Optimal thresholds predicting improved/high function were investigated using classification trees for the legacy federal guideline metric requiring 150 minutes/week of moderate‐vigorous (MV) activity in bouts lasting 10 minutes or more (MV‐bout) and other metrics (total MV, sedentary, light intensity activity, nonsedentary minutes/week). Results Optimal thresholds based on total MV minutes/week predicted improved/high function outcomes more strongly than the legacy or other investigated metrics. Meeting the 45 total MV minutes/week threshold had increased relative risk (RR) for improved/high function (gait speed RR 1.8, 95% confidence interval [95% CI] 1.6, 2.1 and PRO physical function RR 1.4, 95% CI 1.3, 1.6) compared to less active adults. Thresholds were consistent across sex, body mass index, knee osteoarthritis status, and age. Conclusion These results supported a physical activity minimum threshold of 45 total MV minutes/week to promote improved or sustained high function for adults with lower‐extremity joint symptoms. This evidence‐based threshold is less rigorous than federal guidelines (≥150 MV‐bout minutes/week) and provides an intermediate goal towards the federal guideline for adults with lower‐extremity symptoms

Experimental hut and bioassay evaluation of the residual activity of a polymer-enhanced suspension concentrate (SC-PE) formulation of deltamethrin for IRS use in the control of Anopheles arabiensis.

BACKGROUND: The Stockholm Convention on Persistent Organic Pollutants (POPs) came into effect in 2004; the use of DDT for malaria control has been allowed to continue under exemption since then due to a perceived absence of equally effective and efficient alternatives. Alternative classes of insecticide for indoor residual spraying (IRS) have a relatively short residual duration of action (2-6 months according to WHO). In areas of year-round transmission multiple spray cycles are required, resulting in significantly higher costs for malaria control programs and user fatigue. This study evaluated performance of a new formulation of deltamethrin (pyrethroid) with polymer (SC-PE) to prolong the effective residual action to >6 months. METHODS: Deltamethrin SC-PE was evaluated alongside an existing water dispersible granule (WG) formulation and DDT water dispersible powder (WP) in laboratory and hut bioassays on mud, concrete, palm thatch and plywood substrates. An experimental hut trial was conducted in Lower Moshi Rice Irrigation Zone, Tanzania from 2008-2009 against wild, free-flying, pyrethroid susceptible An. arabiensis. Performance was measured in terms of insecticide-induced mortality, and blood-feeding inhibition. Bioassays were carried out monthly on sprayed substrates to assess residual activity. RESULTS: Bioassays in simple huts (designed for bioassay testing only) and experimental huts (designed for testing free flying mosquitoes) showed evidence that SC-PE improved longevity on mud and concrete over the WG formulation. Both deltamethrin SC-PE and WG outperformed DDT in bioassays on all substrates tested in the laboratory and simple huts. In experimental hut trials SC-PE, WG and DDT produced high levels of An. arabiensis mortality and the treatments were equivalent over nine months' duration. Marked seasonal changes in mortality were recorded for DDT and deltamethrin treatments, and may have been partly influenced by outdoor temperature affecting indoor resting duration of mosquitoes on sprayed surfaces, although no clear correlation was demonstrated. CONCLUSIONS: There is a limited range of alternative insecticides for IRS, and deltamethrin SC-PE is likely to have an important role as part of a rotation strategy with one or more different insecticide classes rotated annually, particularly in areas that currently have low levels of pyrethroid resistance or low LLIN coverage and year-round malaria transmission

Inefficient Cytotoxic T Lymphocyte–Mediated Killing of HIV-1–Infected Cells In Vivo

Understanding the role of cytotoxic T lymphocytes (CTLs) in controlling HIV-1 infection is vital for vaccine design. However, it is difficult to assess the importance of CTLs in natural infection. Different human leukocyte antigen (HLA) class I alleles are associated with different rates of progression to AIDS, indicating that CTLs play a protective role. Yet virus clearance rates following antiretroviral therapy are not impaired in individuals with advanced HIV disease, suggesting that weakening of the CTL response is not the major underlying cause of disease progression and that CTLs do not have an important protective role. Here we reconcile these apparently conflicting studies. We estimate the selection pressure exerted by CTL responses that drive the emergence of immune escape variants, thereby directly quantifying the efficiency of HIV-1–specific CTLs in vivo. We estimate that only 2% of productively infected CD4þ cell death is attributable to CTLs recognising a single epitope. We suggest that CTLs kill a large number of infected cells (about 107) per day but are not responsible for the majority of infected cell death

Effects of HIV infection and ART on phenotype and function of circulating monocytes, natural killer, and innate lymphoid cells.

HIV infection causes upregulation of markers of inflammation, immune activation and apoptosis of host adaptive, and innate immune cells particularly monocytes, natural killer (NK) and innate lymphoid cells (ILCs). Although antiretroviral therapy (ART) restores CD4 T-cell counts, the persistent aberrant activation of monocytes, NK and ILCs observed likely contributes to the incomplete recovery of T-cell effector functions. A better understanding of the effects of HIV infection and ART on the phenotype and function of circulating monocytes, NK, and ILCs is required to guide development of novel therapeutic interventions to optimize immune recovery