"Aggregation Bias" DOES explain the PPP puzzle

This article summarizes our views on the role of an "aggregation bias" in explaining the PPP Puzzle, in response to the several papers recently written in reaction to our initial contribution. We discuss in particular the criticisms of Imbs, Mumtaz, Ravn and Rey (2002) presented in Chen and Engel (2005). We show that their contentions are based on: (i) analytical counter-examples which are not empirically relevant; (ii) simulation results minimizing the extent of "aggregation bias"; (iii) unfounded claims on the impact of measurement errors on our results; and (iv) problematic implementation of small-sample bias corrections. We conclude, as in our original paper, that "aggregation bias" goes a long way towards explaining the PPP puzzle

Continuous flow photochemical and thermal multi-step synthesis of bioactive 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones

An effective multi-step continuous flow approach towards N-diaminoalkylated 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones, including the local anesthetic compound AL-12, has been realized. Compared to the traditional decoupled batch processes, the combined photochemical–thermal–thermal flow setup rapidly provides the desired target compounds in superior yields and significantly shorter reaction times

Multi-objective optimisation for minimum quantity lubrication assisted milling process based on hybrid response surface methodology and multi-objective genetic algorithm

© 2019 by SAGE Publications Ltd.Parametric modelling and optimisation play an important role in choosing the best or optimal cutting conditions and parameters during machining to achieve the desirable results. However, analysis of optimisation of minimum quantity lubrication–assisted milling process has not been addressed in detail. Minimum quantity lubrication method is very effective for cost reduction and promotes green machining. Hence, this article focuses on minimum quantity lubrication–assisted milling machining parameters on AISI 1045 material surface roughness and power consumption. A novel low-cost power measurement system is developed to measure the power consumption. A predictive mathematical model is developed for surface roughness and power consumption. The effects of minimum quantity lubrication and machining parameters are examined to determine the optimum conditions with minimum surface roughness and minimum power consumption. Empirical models are developed to predict surface roughness and power of machine tool effectively and accurately using response surface methodology and multi-objective optimisation genetic algorithm. Comparison of results obtained from response surface methodology and multi-objective optimisation genetic algorithm depict that both measured and predicted values have a close agreement. This model could be helpful to select the best combination of end-milling machining parameters to save power consumption and time, consequently, increasing both productivity and profitability.Peer reviewedFinal Published versio

The emerging face of the HIV epidemic in the Middle East and North Africa.

PURPOSE OF REVIEW: A volume of quality HIV data has materialized recently in the Middle East and North Africa (MENA). This review provides a thematic narrative of the patterns of HIV infection transmission in this region in light of these data. RECENT FINDINGS: Tens of integrated bio-behavioral surveillance surveys among hard-to-reach key populations at higher risk have been conducted in MENA in the recent years. Many of the studies reported appreciable and growing HIV prevalence. A few studies found alarming prevalence of as much as 87.2% HIV prevalence among people who inject drugs in Tripoli, Libya. The discovery of these hitherto hidden epidemics was unsettling to some authorities after years in which the importance of a focus on HIV prevention among key populations was not recognized. SUMMARY: The new data from MENA indicate growing HIV epidemics among key populations across the region. There is heterogeneity, however, as to which key populations are affected and in what proportions in different countries. In a few countries, HIV appears to affect only one key population and often there is substantial geographical heterogeneity in HIV transmission. Data are indicative of a growing HIV disease burden in this part of the globe, in contrast with the declining epidemics in most other regions

Investigation of electric discharge machining parameters to minimize surface roughness

: Surface roughness during electrical discharge machining (EDM) was determined, in which material is removed by thermo-electric process due to the occurrence of successive discharge between workpiece and electrode. Box-Behnken design (BBD) involving four parameters discharge current (I), Pulse ON time (PON), Pulse OFF time (POFF) and Gap voltage, with three levels was employed to minimize the surface roughness. Other parameters such as Servo speed, Polarity and Die-electric pressure were kept constant throughout the machining. A copper electrode tool was used to machine the holes in AISI 1045 steel work piece. Mathematical models were developed using Response Surface Methodology (RSM), while Analysis of variance (ANOVA) was used to observe individual effect, interaction between parameters, and to check validity of models. Results revealed that pulse on time and discharge current were two main significant parameters that statistically affected surface roughness

Neisseria meningitidis Opc Invasin Binds to the Sulphated Tyrosines of Activated Vitronectin to Attach to and Invade Human Brain Endothelial Cells

The host vasculature is believed to constitute the principal route of dissemination of Neisseria meningitidis (Nm) throughout the body, resulting in septicaemia and meningitis in susceptible humans. In vitro, the Nm outer membrane protein Opc can enhance cellular entry and exit, utilising serum factors to anchor to endothelial integrins; but the mechanisms of binding to serum factors are poorly characterised. This study demonstrates that Nm Opc expressed in acapsulate as well as capsulate bacteria can increase human brain endothelial cell line (HBMEC) adhesion and entry by first binding to serum vitronectin and, to a lesser extent, fibronectin. This study also demonstrates that Opc binds preferentially to the activated form of human vitronectin, but not to native vitronectin unless the latter is treated to relax its closed conformation. The direct binding of vitronectin occurs at its Connecting Region (CR) requiring sulphated tyrosines Y56 and Y59. Accordingly, Opc/vitronectin interaction could be inhibited with a conformation-dependent monoclonal antibody 8E6 that targets the sulphotyrosines, and with synthetic sulphated (but not phosphorylated or unmodified) peptides spanning the vitronectin residues 43–68. Most importantly, the 26-mer sulphated peptide bearing the cell-binding domain 45RGD47 was sufficient for efficient meningococcal invasion of HBMECs. To our knowledge, this is the first study describing the binding of a bacterial adhesin to sulphated tyrosines of the host receptor. Our data also show that a single region of Opc is likely to interact with the sulphated regions of both vitronectin and of heparin. As such, in the absence of heparin, Opc-expressing Nm interact directly at the CR but when precoated with heparin, they bind via heparin to the heparin-binding domain of the activated vitronectin, although with a lower affinity than at the CR. Such redundancy suggests the importance of Opc/vitronectin interaction in meningococcal pathogenesis and may enable the bacterium to harness the benefits of the physiological processes in which the host effector molecule participates

IFN-γ amplifies NFκB-dependent Neisseria meningitidis invasion of epithelial cells via specific upregulation of CEA-related cell adhesion molecule 1

Temporal relationship between viral and bacterial infections has been observed, and may arise via the action of virus-induced inflammatory cytokines. These, by upregulating epithelial receptors targeted by bacteria, may encourage greater bacterial infiltration. In this study, human epithelial cells exposed to interferon-gamma but not tumour necrosis factor-alpha or interleukin 1-beta supported increased meningococcal adhesion and invasion. The increase was related to Opa but not Opc or pili adhesin expression. De novo synthesis of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), a major Opa receptor, occurred in epithelial cells exposed to the cytokine, or when infected with Opa-expressing bacteria. Cell line-dependent differences in invasion that were observed could be correlated with CEACAM expression levels. There was also evidence for Opa/pili synergism leading to high levels of monolayer infiltration by capsulate bacteria. The use of nuclear factor-kappa B (NFκB) inhibitors, diferuloylmethane (curcumin) and SN50, abrogated bacterial infiltration of both untreated and interferon-gamma-treated cells. The studies demonstrate the importance of CEACAMs as mediators of increased cellular invasion under conditions of inflammation and bring to light the potential role of NFκB pathway in Opa-mediated invasion by meningococci. The data imply that cell-surface remodelling by virally induced cytokines could be one factor that increases host susceptibility to bacterial infection

Images in Clinical Urology: Complex open pyeloplasty in a pelvic kidney

A pelvic kidney occurs in between 1 in 2200 and 1 in 3000 people,1 due to failure of ascent during development. It is commonly asymptomatic and usually functions normally. Pelvic ureteral junction obstruction can either be congenital or acquired, and is characterized by intrinsic stenosis or extrinsic compression of the ureter at the junction with the pelvicalyceal renal system. This can cause symptomatic or asymptomatic hydronephrosis. We describe the complex case and management of a patient with a massive pelvic ureteral junction obstruction in a pelvic kidney

Improving the standards-based management: recognition initiative to provide high-quality, equitable maternal health services in Malawi. An implementation research protocol: Table 1

Background: The Government of Malawi is seeking evidence to improve implementation of its flagship quality of care improvement initiative — the Standards Based Management-Recognition for Reproductive Health (SBM-R(RH)). Objective: This implementation study will assess the quality of maternal healthcare in facilities where the SBM-R(RH) initiative has been employed, identify factors that support or undermine effectiveness of the initiative and develop strategies to further enhance its operation. Methods: Data will be collected in 4 interlinked modules using quantitative and qualitative research methods. Module 1 will develop the programme theory underlying the SBM-R(RH) initiative, using document review and in-depth interviews with policymakers and programme managers. Module 2 will quantitatively assess the quality and equity of maternal healthcare provided in facilities where the SBM-R(RH) initiative has been implemented, using the Malawi Integrated Performance Standards for Reproductive Health. Module 3 will conduct an organisational ethnography to explore the structures and processes through which SBM-R(RH) is currently operationalised. Barriers and facilitators will be identified. Module 4 will involve coordinated co-production of knowledge by researchers, policymakers and the public, to identify and test strategies to improve implementation of the initiative. Potential impact: The research outcomes will provide empirical evidence of strategies that will enhance the facilitators and address the barriers to effective implementation of the initiative. It will also contribute to the theoretical advances in the emerging science of implementation research