HIV prevalence and lifetime risk of dying of AIDS

The paper examines the relationship between the lifetime risk of dying from AIDS and HIV prevalence, using a female stable population model in which the epidemic has stabilized. In addition to prevalence, lifetime risk is determined by various other factors, notably the level of mortality from causes other than AIDS, age at infection, and survival time between infection and death. Typically, the lifetime risk of dying from AIDS is between three and five times the HIV prevalence. Regression equations are developed for estimating lifetime risk from the prevalence and other parameters. The methods are applied to data for Kenya, and it is shown that the 1995 prevalence estimate of 7.5 per cent for the population aged 15 and over would be equivalent to a lifetime risk of about 30 per cent

Chemical Weathering Processes Leading to Soil Development in Arctic Glacial Forefields

Few Arctic forefields have been studied previously for their role in soil formation and in the carbon cycle. Yet, despite their prevailing polar climate, their soils may develop quickly and be extensive. Rock water residence times are prolonged in glacial tills that contain a rock flour component with high surface area and reactive that amasses in the forefields of glaciers as they retreat. Rapid sulfide oxidation and carbonate dissolution could be a potential CO2 source to the atmosphere, while silicate-weathering and soil organic carbon accumulation a CO2 sink. The extent of these sink-source reactions, and the soil forming processes that affect these, were tested over a century of Arctic forefield soil formation. In young, subglacial till-based moraine soils, the rapid depletion of accessory sulfide and carbonates minerals in the initial, and up to about 60-years of exposure, reflected widespread sulfide oxidation and carbonate dissolution. Defining young forefield soils as a potential transient CO2 source to the atmosphere, since potential CO2 sinks, namely calcium silicate mineral weathering and soil organic carbon accumulation were retarded, and limited to the older moraine soils. The slow onset of biological evolution in Arctic forefields and proton consumption by carbonates, present in the forefield lithologies, are suggested as the principal reasons for the limited silicate weathering and in turn soil formation. The results from this thesis may have new implications for the carbon cycle. Given glacial–interglacial cycles that have waxed and waned throughout Earth history, and carbonate and sulfide minerals are common in most lithologies made up of low to medium grade metamorphic and metasedimentary rocks. However, higher resolution temporal (diurnal to seasonal) and spatial field studies are needed in-order to more confidentially up-scale these findings beyond a glacier catchment scale

Quantifying the Role of Adverse Events in the Mortality Difference between First and Second-Generation Antipsychotics in Older Adults: Systematic Review and Meta-Synthesis

Background: Observational studies have reported higher mortality among older adults treated with first-generation antipsychotics (FGAs) versus second-generation antipsychotics (SGAs). A few studies examined risk for medical events, including stroke, ventricular arrhythmia, venous thromboembolism, myocardial infarction, pneumonia, and hip fracture. Objectives: 1) Review robust epidemiologic evidence comparing mortality and medical event risk between FGAs and SGAs in older adults; 2) Quantify how much these medical events explain the observed mortality difference between FGAs and SGAs. Data sources Pubmed and Science Citation Index. Study eligibility criteria, participants, and interventions Studies of antipsychotic users that: 1) evaluated mortality or medical events specified above; 2) restricted to populations with a mean age of 65 years or older 3) compared FGAs to SGAs, or both to a non-user group; (4) employed a “new user” design; (5) adjusted for confounders assessed prior to antipsychotic initiation; (6) and did not require survival after antipsychotic initiation. A separate search was performed for mortality estimates associated with the specified medical events. Study appraisal and synthesis methods For each medical event, we used a non-parametric model to estimate lower and upper bounds for the proportion of the mortality difference—comparing FGAs to SGAs—mediated by their difference in risk for the medical event. Results: We provide a brief, updated summary of the included studies and the biological plausibility of these mechanisms. Of the 1122 unique citations retrieved, we reviewed 20 observational cohort studies that reported 28 associations. We identified hip fracture, stroke, myocardial infarction, and ventricular arrhythmias as potential intermediaries on the causal pathway from antipsychotic type to death. However, these events did not appear to explain the entire mortality difference. Conclusions: The current literature suggests that hip fracture, stroke, myocardial infarction, and ventricular arrhythmias partially explain the mortality difference between SGAs and FGAs

Enantioselective synthesis of non-proteinogenic 2-arylallyl-α-amino acids via Pd/In catalytic cascades

An efficient synthesis of both R- and S-enantiomers of 2-arylallyl-α-amino acids via a diastereoselective Pd/In mediated catalytic allylation of chiral N-sulfinyl-α-imino esters is described. The potential for further enhancement of molecular complexity and creating contiguous chiral centres by interfacing these processes with catalytic cyclisation–anion capture methodology is demonstrated

The kinetics and mechanism of the organo-iridium catalysed racemisation of amines

The dimeric iodo-iridium complex [IrCp*I2 ]2 (Cp*=pentamethylcyclopentadiene) is an efficient catalyst for the racemisation of secondary and tertiary amines at ambient and higher temperatures with a low catalyst loading. The racemisation occurs with pseudo-first-order kinetics and the orresponding four rate constants were obtained by monitoring the time dependence of the concentrations of the (R) and (S) enantiomers starting with either pure (R) or (S) and show a first-order dependence on catalyst concentration. Low temperature 1H NMR data is consistent with the formation of a 1:1 complex with the amine coordinated to the iridium and with both iodide anions still bound to the metal-ion, but at the higher temperatures used for kinetic studies binding is weak and so no saturation zero-order kinetics are observed. A cross-over experiment with isotopically labelled amines demonstrates the intermediate formation of an imine which can dissociate from the iridium complex. Replacing the iodides in the catalyst by other ligands or having an amide substituent in Cp* results in a much less effective catalysts for the racemisation of amines. The rate constants for a deuterated amine yield a significant primary kinetic isotope effect kH/kD = 3.24 ndicating that hydride transfer is involved in the rate-limiting step

Influence of augmentation of biochar during anaerobic co-digestion of Chlorella vulgaris and cellulose

The anaerobic co-digestion (AcoD) of microalgae is a prospective option for generating biomethane from renewable sources. This study investigates the effects of inoculum-to-substrate ratio (ISR), C/N ratio and biochar (BC) load on the AcoD of Chlorella vulgaris and cellulose. An initial augmentation of BC at ISR 0.5–0.9 and C/N ratio 10–30 offered a pH buffering effect and resulted in biomethane yields of 233–241 mL CH4/g VS, corresponding to 1.8–4.6 times the controls. BC addition ameliorated significantly AcoD, supporting the digestate stability at less favourable conditions. The effect of the process variables was further studied with a 23 factorial design and response optimisation. Under the design conditions, the variables had less influence over methane production. Higher ISRs and C/N ratios favoured AcoD, whereas increasing amounts of BC reduced biomethane yield but enhanced production rate. The factorial design highlighted the importance of BC-load on AcoD, establishing an optimum of 0.58 % (w/v)

The Kinetics and Mechanism of the Organo-Iridium-Catalysed Enantioselective Reduction of Imines

The iridium complex of pentamethylcyclopentadiene and (S,S)-1,2-diphenyl-N′-tosylethane- 1,2-diamine is an effective catalyst for the asymmetric transfer hydrogenation of imine substrates under acidic conditions. Using the Ir catalyst and a 5:2 ratio of formic acid: triethylamine as the hydride source for the asymmetric transfer hydrogenation of 1-methyl-3,4- dihydroisoquinoline and its 6,7-dimethoxy substituted derivative, in either acetonitrile or dichloromethane, shows unusual enantiomeric excess (ee) profiles for the product amines. The reactions initially give predominantly the (R) enantiomer of the chiral amine products with >90% ee but which then decreases significantly during the reaction. The decrease in ee is not due to racemisation of the product amine, but because the rate of formation of the (R)- enantiomer follows first-order kinetics whereas that for the (S)-enantiomer is zero-order. This difference in reaction order explains the change in selectivity as the reaction proceeds - the rate formation of the (R)-enantiomer decreases exponentially with time while that for the (S)- enantiomer remains constant. A reaction scheme is proposed which requires rate-limiting hydride transfer from the iridium hydride to the iminium ion for the first-order rate of formation of the (R)-enantiomer amine and rate-limiting dissociation of the product for the zero-order rate of formation of the (S)-enantiomer

Automated Self-Optimisation of Multi-Step Reaction and Separation Processes Using Machine Learning

There has been an increasing interest in the use of automated self-optimising continuous flow platforms for the development and manufacture in synthesis in recent years. Such processes include multiple reactive and work-up steps, which need to be efficiently optimised. Here, we report the combination of multi-objective optimisation based on machine learning methods (TSEMO algorithm) with self-optimising platforms for the optimisation of multi-step continuous reaction processes. This is demonstrated for a pharmaceutically relevant Sonogashira reaction. We demonstrate how optimum reaction conditions are re-evaluated with the changing downstream work-up specifications in the active learning process. Furthermore, a Claisen-Schmidt condensation reaction with subsequent liquid-liquid separation was optimised with respect to three-objectives. This approach provides the ability to simultaneously optimise multi-step processes with respect to multiple objectives, and thus has the potential to make substantial savings in time and resources

NADH Shuttling Couples Cytosolic Reductive Carboxylation of Glutamine with Glycolysis in Cells with Mitochondrial Dysfunction.

The bioenergetics and molecular determinants of the metabolic response to mitochondrial dysfunction are incompletely understood, in part due to a lack of appropriate isogenic cellular models of primary mitochondrial defects. Here, we capitalize on a recently developed cell model with defined levels of m.8993T>G mutation heteroplasmy, mTUNE, to investigate the metabolic underpinnings of mitochondrial dysfunction. We found that impaired utilization of reduced nicotinamide adenine dinucleotide (NADH) by the mitochondrial respiratory chain leads to cytosolic reductive carboxylation of glutamine as a new mechanism for cytosol-confined NADH recycling supported by malate dehydrogenase 1 (MDH1). We also observed that increased glycolysis in cells with mitochondrial dysfunction is associated with increased cell migration in an MDH1-dependent fashion. Our results describe a novel link between glycolysis and mitochondrial dysfunction mediated by reductive carboxylation of glutamine

Stereoselective synthesis of chiral β2,3-disubstituted-β-amino acid derivatives using Pd/In transmetallation cascade processes

A new, highly efficient synthesis of chiral β2,3-disubstituted-β-amino acid derivatives has been developed, based on an allylation procedure employing allene and a catalytic Pd/In bimetallic process