Pastoral Neolithic Settlement at Luxmanda, Tanzania

The later Holocene spread of pastoralism throughout eastern Africa profoundly changed socio-economic and natural landscapes. During the Pastoral Neolithic (ca. 5000–1200 B.P.), herders spread through southern Kenya and northern Tanzania—areas previously occupied only by hunter-gatherers—eventually developing the specialized forms of pastoralism that remain vital in this region today. Research on ancient pastoralism has been primarily restricted to rockshelters and special purpose sites. This paper presents results of surveys and excavations at Luxmanda, an open-air habitation site located farther south in Tanzania, and occupied many centuries earlier, than previously expected based upon prior models for the spread of herding. Technological and subsistence patterns demonstrate ties to northerly sites, suggesting that Luxmanda formed part of a network of early herders. The site is thus unlikely to stand alone, and further surveys are recommended to better understand the spread of herding into the region, and ultimately to southern Africa

Mechanisms of enhanced heterogeneous nucleation during solidification in binary Al-Mg alloys

This is the post-print version of the Article. The official published version can be accessed from the link below - Copyright @ 2012 ElsevierThe mechanisms involved in the grain refinement of Al–Mg alloys through varying the Mg content and applying intensive melt shearing were investigated. It was found that the oxide formed in Al–Mg alloys under normal melting conditions is MgAl2O4, which displays an equiaxed and faceted morphology with {1 1 1} planes exposed as its natural surfaces. Depending on the Mg content, MgAl2O4 particles exist either as oxide films in dilute Al–Mg alloys (Mg 1 wt.%). Such MgAl2O4 particles can act as potent sites for nucleation of α-Al grains, which is evidenced by the well-defined cube-on-cube orientation relationship between MgAl2O4 and α-Al. Enhanced heterogeneous nucleation in Al–Mg alloys can be attributed to the high potency of MgAl2O4 particles with a lattice misfit of 1.4% and the increased number density of MgAl2O4 particles due to either natural dispersion by the increased Mg content or forced dispersion through intensive melt shearing. It was also found that intensive melt shearing leads to significant grain refinement of dilute Al–Mg alloys by effective dispersion of the MgAl2O4 particles entrapped in oxide films, but it has marginal effect on the grain refinement of concentrated Al–Mg alloys, where MgAl2O4 particles have been naturally dispersed into individual particles by the increased Mg content.This study is funded from the EPSRC Grant EP/H026177/1

Discovery of a small molecule agonist of phosphatidylinositol 3-kinase p110α that reactivates latent HIV-1

Combination antiretroviral therapy (cART) can effectively suppress HIV-1 replication, but the latent viral reservoir in resting memory CD4+ T cells is impervious to cART and represents a major barrier to curing HIV-1 infection. Reactivation of latent HIV-1 represents a possible strategy for elimination of this reservoir. In this study we describe the discovery of 1,2,9,10-tetramethoxy-7H-dibenzo[de,g]quinolin-7-one (57704) which reactivates latent HIV-1 in several cell-line models of latency (J89GFP, U1 and ACH-2). 57704 also increased HIV-1 expression in 3 of 4 CD8+-depleted blood mononuclear cell preparations isolated from HIV-1-infected individuals on suppressive cART. In contrast, vorinostat increased HIV-1 expression in only 1 of the 4 donors tested. Importantly, 57704 does not induce global T cell activation. Mechanistic studies revealed that 57704 reactivates latent HIV-1 via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. 57704 was found to be an agonist of PI3K with specificity to the p110a isoform, but not the p110β, δ or γ isoforms. Taken together, our work suggests that 57704 could serve as a scaffold for the development of more potent activators of latent HIV-1. Furthermore, it highlights the involvement of the PI3K/Akt pathway in the maintenance of HIV-1 latency. © 2014 Doyon et al

A systematic review of the evidence for single stage and two stage revision of infected knee replacement

BACKGROUND: Periprosthetic infection about the knee is a devastating complication that may affect between 1% and 5% of knee replacement. With over 79 000 knee replacements being implanted each year in the UK, periprosthetic infection (PJI) is set to become an important burden of disease and cost to the healthcare economy. One of the important controversies in treatment of PJI is whether a single stage revision operation is superior to a two-stage procedure. This study sought to systematically evaluate the published evidence to determine which technique had lowest reinfection rates. METHODS: A systematic review of the literature was undertaken using the MEDLINE and EMBASE databases with the aim to identify existing studies that present the outcomes of each surgical technique. Reinfection rate was the primary outcome measure. Studies of specific subsets of patients such as resistant organisms were excluded. RESULTS: 63 studies were identified that met the inclusion criteria. The majority of which (58) were reports of two-stage revision. Reinfection rated varied between 0% and 41% in two-stage studies, and 0% and 11% in single stage studies. No clinical trials were identified and the majority of studies were observational studies. CONCLUSIONS: Evidence for both one-stage and two-stage revision is largely of low quality. The evidence basis for two-stage revision is significantly larger, and further work into direct comparison between the two techniques should be undertaken as a priority

Effects of Microwave Heating on Sensory Characteristics of Kiwifruit Puree

The effect of microwave processing on the characteristics of kiwifruit puree was evaluated by applying various gentle treatments. Different combinations of microwave power/processing time were applied, with power among 200-1,000 W and time among 60-340 s, and various sensory and instrumental measurements were performed with the aim of establishing correlations and determining which instrumental parameters were the most appropriate to control the quality of kiwi puree. The water and soluble solids of the product, 83 and 14/100 g sample, respectively, did not change due to treatments. For sensory assessment, an expert panel was previously trained to describe the product. Fourteen descriptors were defined, but only the descriptors 'typical kiwifruit colour', 'tone', 'lightness', 'visual consistency' and 'typical taste' were significant to distinguish between kiwifruit puree samples. The instrumental analysis of samples consisted in measuring consistency, viscosity, colour and physicochemical characteristics of the treated and fresh puree. Applying intense treatments (600 W-340 s, 900 W-300 s and 1,000 W-200 s) through high power or long treatment periods or a combination of these factors, mainly affects the consistency (flow distance decreased from 5. 9 to 3. 4 mm/g sample), viscosity (increased from 1. 6 to 2. 5 Pa/s), colour (maximun ¿E was 6 U) and taste of the product. As a result, samples were thicker and with an atypical flavour and kiwifruit colour due to increased clarity (L* increased from 38 to 43) and slight changes in the yellow-green hue (h* decreased from 95 to 94). For the instrumental determinations of colour and visual perception of consistency, the most suitable parameters for quality control are the colour coordinates L*, a*, h*, whiteness index and flow distance measured with a Bostwick consistometer. © 2011 Springer Science+Business Media, LLC.The authors thank the Ministerio de Educacion y Ciencia for the financial support given throughout the Project AGL 2010-22176. The authors are indebted to the Generalitat Valenciana (Valencia, Spain) for the Grant awarded to the author Maria Benlloch. The translation of this paper was funded by the Universidad Politecnica de Valencia, Spain.Benlloch Tinoco, M.; Varela Tomasco, PA.; Salvador Alcaraz, A.; Martínez Navarrete, N. (2012). Effects of Microwave Heating on Sensory Characteristics of Kiwifruit Puree. Food and Bioprocess Technology. 5(8):3021-3031. https://doi.org/10.1007/s11947-011-0652-1S3021303158Albert, A., Varela, P., Salvador, A., & Fiszman, S. M. (2009). 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Low Dose Organochlorine Pesticides and Polychlorinated Biphenyls Predict Obesity, Dyslipidemia, and Insulin Resistance among People Free of Diabetes

There is emerging evidence that background exposure to persistent organic pollutants (POPs) are important in the development of conditions predisposing to diabetes as well as of type 2 diabetes itself. We recently reported that low dose POPs predicted incident type 2 diabetes in a nested case-control study. The current study examined if low dose POPs predicted future adiposity, dyslipidemia, and insulin resistance among controls without diabetes in that study.The 90 controls were diabetes-free during 20 years follow-up. They were a stratified random sample, enriched with overweight and obese persons. POPs measured in 1987-88 (year 2) sera included 8 organochlorine (OC) pesticides, 22 polychlorinated biphenyls (PCBs), and 1 polybrominated biphenyl (PBB). Body mass index (BMI), triglycerides, HDL-cholesterol, LDL-cholesterol, and homeostasis model assessment value for insulin resistance (HOMA-IR) were study outcomes at 2005-06 (year 20). The evolution of study outcomes during 18 years by categories of serum concentrations of POPs at year 2 was evaluated by adjusting for the baseline values of outcomes plus potential confounders. Parallel to prediction of type 2 diabetes, many statistically significant associations of POPs with dysmetabolic conditions appeared at low dose, forming inverted U-shaped dose-response relations. Among OC pesticides, p,p'-DDE most consistently predicted higher BMI, triglycerides, and HOMA-IR and lower HDL-cholesterol at year 20 after adjusting for baseline values. Oxychlordane, trans-nonachlor, and hexachlorobenzene also significantly predicted higher triglycerides. Persistent PCBs with ≥7 chlorides predicted higher BMI, triglycerides, and HOMA-IR and lower HDL-cholesterol at year 20 with similar dose-response curves.Simultaneous exposure to various POPs in the general population may contribute to development of obesity, dyslipidemia, and insulin resistance, common precursors of type 2 diabetes and cardiovascular diseases. Although obesity is a primary cause of these metabolic abnormalities, POPs exposure may contribute to excess adiposity and other features of dysmetabolism

Deep-Inelastic Inclusive ep Scattering at Low x and a Determination of alpha_s

A precise measurement of the inclusive deep-inelastic e^+p scattering cross section is reported in the kinematic range 1.5<= Q^2 <=150 GeV^2 and 3*10^(-5)<= x <=0.2. The data were recorded with the H1 detector at HERA in 1996 and 1997, and correspond to an integrated luminosity of 20 pb^(-1). The double differential cross section, from which the proton structure function F_2(x,Q^2) and the longitudinal structure function F_L(x,Q^2) are extracted, is measured with typically 1% statistical and 3% systematic uncertainties. The measured partial derivative (dF_2(x,Q^2)/dln Q^2)_x is observed to rise continuously towards small x for fixed Q^2. The cross section data are combined with published H1 measurements at high Q^2 for a next-to-leading order DGLAP QCD analysis.The H1 data determine the gluon momentum distribution in the range 3*10^(-4)<= x <=0.1 to within an experimental accuracy of about 3% for Q^2 =20 GeV^2. A fit of the H1 measurements and the mu p data of the BCDMS collaboration allows the strong coupling constant alpha_s and the gluon distribution to be simultaneously determined. A value of alpha _s(M_Z^2)=0.1150+-0.0017 (exp) +0.0009-0.0005 (model) is obtained in NLO, with an additional theoretical uncertainty of about +-0.005, mainly due to the uncertainty of the renormalisation scale.Comment: 68 pages, 24 figures and 18 table

Efficacy of a brief multifactorial adherence-based intervention on reducing the blood pressure of patients with poor adherence: protocol for a randomized clinical trial

<p>Abstract</p> <p>Background</p> <p>Lowering of blood pressure by antihypertensive drugs reduces the risks of cardiovascular events, stroke, and total mortality. However, poor adherence to antihypertensive medications reduces their effectiveness and increases the risk of adverse events. In terms of relative risk reduction, an improvement in medication adherence could be as effective as the development of a new drug.</p> <p>Methods/Design</p> <p>The proposed randomized controlled trial will include patients with a low adherence to medication and uncontrolled blood pressure. The intervention group will receive a multifactorial intervention during the first, third, and ninth months, to improve adherence. This intervention will include motivational interviews, pill reminders, family support, blood pressure self-recording, and simplification of the dosing regimen.</p> <p>Measurement</p> <p>The primary outcome is systolic blood pressure. The secondary outcomes are diastolic blood pressure, proportion of patients with adequately controlled blood pressure, and total cost.</p> <p>Discussion</p> <p>The trial will evaluate the impact of a multifactorial adherence intervention in routine clinical practice. Ethical approval was given by the Ethical Committee on Human Research of Balearic islands, Spain (approval number IB 969/08 PI).</p> <p>Trial registration</p> <p>Current controlled trials ISRCTN21229328</p

New Insights into the Control of HIV-1 Transcription: When Tat Meets the 7SK snRNP and Super Elongation Complex (SEC)

Recent studies aimed at elucidating the mechanism controlling HIV-1 transcription have led to the identification and characterization of two multi-subunit complexes that both contain P-TEFb, a human transcription elongation factor and co-factor for activation of HIV-1 gene expression by the viral Tat protein. The first complex, termed the 7SK snRNP, acts as a reservoir where active P-TEFb can be withdrawn by Tat to stimulate HIV-1 transcription. The second complex, termed the super elongation complex (SEC), represents the form of P-TEFb delivered by Tat to the paused RNA polymerase II at the viral long terminal repeat during Tat transactivation. Besides P-TEFb, SEC also contains other elongation factors/co-activators, and they cooperatively stimulate HIV-1 transcription. Recent data also indicate SEC as a target for the mixed lineage leukemia (MLL) protein to promote the expression of MLL target genes and leukemogenesis. Given their roles in HIV-1/AIDS and cancer, further characterization of 7SK snRNP and SEC will help develop strategies to suppress aberrant transcriptional elongation caused by uncontrolled P-TEFb activation. As both complexes are also important for normal cellular gene expression, studying their structures and functions will elucidate the mechanisms that control metazoan transcriptional elongation in general