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With the rising use of facial recognition systems in a range of real-world scenarios and applications, attackers are also increasing their efforts, with a number of spoofing techniques emerging. As a result, developing a reliable spoof detection mechanism is critical. Active-based techniques have been shown to be good at finding spoofs, but they have a number of problems, such as being intrusive, expensive, hard to compute, not being able to be used in many situations, and usually needing extra hardware. This research presented an active-based robust spoof detection technique capable of detecting a wide range of media or 2D attacks while being less intrusive, less expensive, low in complexity, and more generalizable than other activebased techniques. It doesn't require any additional hardware, so it can easily be integrated into current systems. The distortion variations of video frames of the user's face collected at varying distances from the camera are analyzed to detect spoofing. Both the legitimate and spoof attack datasets were created using real-world facial photo and video data. The proposed approach achieved a spoof detection accuracy of 98.18% using both machine learning classifiers and a deep learning model, with an equal error rate and a half total error rate as low as 0.023 and 0.021, respectively. [ABSTRACT FROM AUTHOR]

The article presents the discussion on academic family medicine faces an impending leadership crisis. Topics include allopathic departments of family medicine in the US, and a number of osteopathic departments, large academic medical center departments; and prompting the ADFM's Leadership Development Committee to study and addressing the leadership vacuum in family medicine.

The construct and criterion‐related validity of 11 High‐Performance Competencies (H‐PC) are explored through data collected by three highly reliable methods: work shadowing, assessment centres, and Strategic Management Simulation Technology. A large international managerial sample indicates that some H‐PC are more highly developed than others. This suggests that managers may have a restricted capacity to co‐operatively address the multidimensional issues that loom large today. Strategic Management Simulation Technology is discussed as a way of developing a more balanced leadership capability profile and enhancing desirable real‐world outcomes. [ABSTRACT FROM AUTHOR]

This paper provides a synopsis of the origins and subsequent development of behavioral complexity theory (BCT). First, the foundational contributions of personal construct theory, conceptual systems theory, and the conceptual complexity theory are described. Second, the diversification of BCT via integrative complexity theory, Strategic Management Simulations, and Metacomplexity Simulations is outlined. Next, the discussion emphasizes the contemporary relevance and importance of BCT, suggests that more scalable assessment and development technologies should be created (especially of integration), and ends by calling for enhanced interaction within the BCT community. [ABSTRACT FROM AUTHOR]

Treatment of nonhuman primates and mice with a humanized antigen-binding fragment (Fab) antibody (UCBFab) inhibiting transforming growth factor β via daily inhalation for up to 13 weeks resulted in low systemic exposure but high local exposure in the lung. Target engagement was demonstrated by reduced levels of signal transducers, phosphoSMAD and plasminogen activator inhibitor-1 in the bronchoalveolar lavage fluid (BALF). Treatment was associated with a high frequency and titer of antidrug antibodies, indicating high local immunogenicity, and local pathology within the lung and draining lymph nodes. Microscopic changes were characterized by perivascular (PV) and peribronchiolar (PB) mononuclear inflammatory cell (MIC) infiltrates that were principally lymphocytic in nature and mixed inflammatory cell infiltrates and/or inflammation within the alveoli. Immunohistochemical investigation revealed a predominantly CD68-positive macrophage and CD3- and CD8>CD4-positive T-cell response in the alveoli, whereas within the airways, there was a variable mixture of CD3-positive T cells, CD20-positive B cells, and CD68-positive macrophages. Increased cellularity of the draining lymph nodes was also noted, indicating the presence of an immune response to the inhaled test article. Morphologic changes did not progress over time, and all changes partially recovered. Increased leukocytes (principally macrophages) in BALF cytology correlated with the changes seen by histopathology. [ABSTRACT FROM AUTHOR]

This paper explores the method of Pade approximation to solve a system of heat equation; The Pade method of solving PDEs is a well-established method because of its added advantage of naturally increasing the domain of convergence of truncated power series. The solution of the heat equation has been directly expressed as a rational power series of the independent variable known as the Pade approximant. Attempt is made to solve the heat equation and obtain solutions in terms of their exponential matrix. A test on the stability of the solutions via conventional numerical procedures through some form of John Neumann stability method confirmed the scheme to be L0 - stable and therefore produced solutions that are well behaved. [ABSTRACT FROM AUTHOR]

Since the 2008 financial crisis, business leaders have faced uncertainty regarding the impact of ethical leadership behaviors. Because small business leadership involves multiple facets of behavior and decision-making, small business leaders may have an insufficient understanding of the impact of ethical leadership behaviors on sustainability. The purpose of this study was to examine the relationship between ethical leadership and financial, social, and environmental sustainability in small businesses. The participants were 80 members of a Miami, Florida chamber of commerce. Correlation analysis and Bonferroni corrected calculation indicated significant relationships (p < .001) between ethical leadership behaviors and social and environmental sustainability. [ABSTRACT FROM AUTHOR]

It is generally accepted that the human abdominal wall comprises skin, subcutaneous tissues, muscles and their aponeuroses, and the parietal peritoneum. Understanding these layers and their mechanical properties provides valuable information to those designing procedural skills trainers, supporting surgical procedures (hernia repair), and engineering-based work (in silico simulation). However, there is little literature available on the mechanical properties of the abdominal wall in layers or as a composite in the context of designing a procedural skills trainer. This work characterizes the tensile properties of the human abdominal wall by layer and as a partial composite. Tissues were collected from fresh-never-frozen and fresh-frozen cadavers and tested in uniaxial tension at a rate of 5 mm/min until failure. Stress–strain curves were created for each sample, and the values for elastic moduli, ultimate tensile strength, and strain at failure were obtained. The experimental outcomes from this study demonstrated variations in tensile properties within and between tissues. The data also suggest that the tensile properties of composite abdominal walls are not additive. Ultimately, this body of work contributes to a deeper comprehension of these mechanical properties and will serve to enhance patient care, refine surgical interventions, and assist with more sophisticated engineering solutions. [ABSTRACT FROM AUTHOR]

In this paper, we study Navier – Stokes Equations in an infinite strip Ω = R×[-1,1 ]. We used the Uniformly Local Spaces as with focus on model situation where pressure has been omitted in the momentum equation. We obtain a priori estimates for the solutions and use the phase – portrait analysis to obtain bounds for them. We caution that the method used in this paper cannot be applied in general situation but is peculiar to only circumstances where the pressure term has been artificially removed. [ABSTRACT FROM AUTHOR]

This paper deals with the coupled system of Navier-Stokes equations and temperature (Thermohydraulics) in a strip in the class of spatially non-decaying (infinite-energy) solutions belonging to the properly chosen uniformly local Sobolev spaces. The global well-posedness and dissipativity of the Navier-Stokes equations in a strip in such spaces has been established in Zelik (2007). Similar protocol is observed using maximum principle to obtain bounds for the temperature solutions in Boussinesq approximation. [ABSTRACT FROM AUTHOR]

RNA folding is enabled by interactions between the nucleic acid and its ion atmosphere, the mobile sheath of aqueous ions that surrounds and stabilizes it. Understanding the ion atmosphere requires the interplay of experiment and theory. However, even an apparently simple experiment to probe the ion atmosphere, measuring the dependence of DNA duplex stability upon ion concentration and identity, suffers from substantial complexity, because the unfolded ensemble contains many conformational states that are difficult to treat accurately with theory. To minimize this limitation, we measured the unfolding equilibrium of a DNA hairpin using a single-molecule optical trapping assay, in which the unfolded state is constrained to a limited set of elongated conformations. The unfolding free energy increased linearly with the logarithm of monovalent cation concentration for several cations, such that smaller cations tended to favor the folded state. Mg2+ stabilized the hairpin much more effectively at low concentrations than did any of the monovalent cations. Poisson-Boltzmann theory captured trends in hairpin stability measured for the monovalent cation titrations with reasonable accuracy, but failed to do so for the Mg2+ titrations. This finding is consistent with previous work, suggesting that Poisson-Boltzmann and other mean-field theories fail for higher valency cations where ion-ion correlation effects may become significant. The high-resolution data herein, because of the straightforward nature of both the folded and the unfolded states, should serve as benchmarks for the development of more accurate electrostatic theories that will be needed for a more quantitative and predictive understanding of nucleic acid folding. [ABSTRACT FROM AUTHOR]

Riboswitches are motifs in the untranslated regions (UTRs) of RNA transcripts that sense metabolite levels and modulate the expression of the corresponding genes for metabolite import, export, synthesis, or degradation. All riboswitches contain an aptamer: an RNA structure that, upon binding ligand, folds to expose or sequester regulatory elements in the adjacent sequence through alternative nucleotide pairing. The coupling between ligand binding and aptamer folding is central to the regulatory mechanisms of thiamine pyrophosphate (TPP) riboswitches and has not been fully characterized. Here, we show that TPP aptamer folding can be decomposed into ligand-independent and -dependent steps that correspond to the formation of secondary and tertiary structures, respectively. We reconstructed the full energy landscape for folding of the wild-type (WT) aptamer and measured perturbations of this landscape arising from mutations or ligand binding. We show that TPP binding proceeds in two steps, from a weakly to a strongly bound state. Our data imply a hierarchical folding sequence, and provide a framework for understanding molecular mechanism throughout the TPP riboswitch family. [ABSTRACT FROM AUTHOR]

The article presents a discussion on the Gospel of Luke and the Acts of the Apostle in the New Testament of the Bible which dealt on concepts and issues with regard to bible-based learning or scholarship. A brief history of the ideology that has brought a universally accepted paradigm for study based on Luke's Gospel, is presented which traces back to the huge outpouring of historical-critical post-War German and English-speaking scholarship. Several critical assumptions are considered as basis in support to the post-War New Testament thought including one on the acceptance of the relatively late composition for Luke and Acts which has created a negative value-judgment in terms of historical liability.

Partisan theories of political economy expect that bondholders will panic with the election of a left-wing presidential candidate. The latter seems to be what happened in Brazil in the 2002 presidential elections. However, quantitative analysis of perceptions of sovereign credit risk in Argentine, Brazilian, Mexican, and Venezuelan presidential elections from 1994 until 2007 shows no real evidence of a link between partisanship and perceptions of risk, even if the left-right divide is further broken down into left, center-left, centerright, right. Instead, international and domestic economic fundamentals have a stronger influence on risk evaluations. Qualitative analysis of the individual presidential elections shows the importance of policy uncertainty in explaining why certain electoral periods seemed more critical than others and how bondholders select between multiple equilibria. This research helps shift political analysis away from partisanship and more in the direction of policies and articulation. [ABSTRACT FROM AUTHOR]

At points of crisis of political representations and economic insecurity, populists are more likely to emerge. That was true of earlier forms of populism in Latin America and it seems to be so now. There are some important differences though and these are shown by exploring Chavismo as an “extreme” case study of populism. Chavez has pushed a model of citizenship which is antithetical to neoliberal models in that it encourages politically engaged citizens, increases worker rights through an increasingly interventionist state, and encourages anti-imperialist solidarity and actions. By understanding how populist orientations of Chavez created possibilities and constraints on that citizenship, social scientists can better understand what populism is and is not. [ABSTRACT FROM AUTHOR]

Nucleic acid hairpins provide a powerful model system for understanding macromolecular folding, with free-energy landscapes that can be readily manipulated by changing the hairpin sequence. The full shapes of energy landscapes for the reversible folding of DNA hairpins under controlled loads exerted by an optical force clamp were obtained by deconvolution from high-resolution, single-molecule trajectories. The locations and heights of the energy barriers for hairpin folding could be tuned by adjusting the number and location of G:C base pairs, and the presence and position of folding intermediates were controlled by introducing single-nucleotide mismatches. [ABSTRACT FROM AUTHOR]

Obesity is associated with significant morbidity and mortality, which can be attributed to increased risk of a number of medical conditions including, type 11 diabetes mellitus, hypertension and coronary heart disease. The most common cause of premature mortality in the obese population, less well known, are associations between obesity and several cancers including breast, endometrial, prostate and bowel cancer. Obesity predisposes to osteoarthritis, particularly, in the large weight-bearing joints and to respiratory problems including obstructive sleep apnoea. Thus, obesity poses an immense and increasing public health burden.

Examines the convergence strategy of the Caribbean Community (CARICOM) for building sub-regional linkages in the current process of hemispheric integration in the Caribbean Area. Developments in regional integration in the Hemisphere; Extent to which convergence has been feasible through attempts to link CARICOM to other regions; Need for a new diplomacy based on a new configuration of smallness and development criteria for CARICOM states to consolidate a convergence strategy.

Objective: The prevalence of pre-diabetes is increasing globally with more than 470 million people projected to develop pre-diabetes by 2030. In Africa, the average prevalence of pre-diabetes was estimated at 7.3% in 2015 and affected individual will develop type 2 diabetes mellitus within few decades. The aim of the study was to determine the prevalence of pre-diabetes and associated risk factors among residents of Iganga municipality. A cross-sectional study was conducted among males and females aged 13–60 years. District health office provided updated household list from which sampling of the villages was performed based on probability proportionate to population. Consented participants were prepared for the study, allowing fasting for 8 to 10 h before blood collection the next morning. Individuals with impaired fasting glucose, were subjected to OGTT. Results: 130 participants were enrolled, of which 98 were women. The mean age of the participants was 35 years. The prevalence of pre-diabetes was 3.8%. The proportion of impaired glucose tolerance was higher in current smokers (p = 0.01), obese participants (p = 0.002) and hypertensive participants (p < 0.001). Prevalence of pre-diabetes is high in this community and is associated with current smoking, hypertension and high BMI. [ABSTRACT FROM AUTHOR]

Investigates the deaths caused by primary angiosarcoma of the liver (ASL) from the period 1963 to 1973 in Great Britain. Submission of histological material to a panel of histopathologist; Occupational and residential histories for the cases agreed of ASL; Findings of a single case associated with exposure to vinyl chloride.

Background: Between 10% and 15% of hypothyroid patients experience persistent symptoms despite achieving biochemical euthyroidism. Unexplained persistent symptoms can be a sign of somatization. This is associated with distress and high health care resource use and can be classified as somatic symptom disorder (SSD). Prevalence rates for SSD differ depending on classification criteria and how they are ascertained, varying between 4% and 25%. As this has not been studied in hypothyroid patients before, the aim of this study was to document somatization in people with hypothyroidism and to explore associations with other patient characteristics and outcomes. Methods: Online, multinational cross-sectional survey of individuals with self-reported, treated hypothyroidism, which included the validated Patient Health Questionnaire-15 (PHQ-15) for assessment of somatization. Chi-squared tests with the Bonferroni correction were used to explore outcomes for respondents with a PHQ-15 score ≥10 (probable somatic symptom disorder [pSSD]) versus a PHQ-15 score <10 (absence of SSD). Results: A total of 3915 responses were received, 3516 of which contained the valid PHQ-15 data (89.8%). The median score was 11.3 (range 0–30 [confidence interval 10.9–11.3]). The prevalence of pSSD was 58.6%. Associations were found between pSSD and young age (p < 0.001), women (p < 0.001), not working (p < 0.001), having below average household income (p < 0.001), being treated with levothyroxine (LT4) (rather than combination of LT4 and L-triiodothyronine [LT3], LT3 alone, or desiccated thyroid extract) (p < 0.001), expression of the view that the thyroid medication taken did not control the symptoms of hypothyroidism well (p < 0.001), and with number of comorbidities (p < 0.001). pSSD was associated with respondent attribution of most PHQ-15 symptoms to the hypothyroidism or its treatment (p < 0.001), dissatisfaction with care and treatment of hypothyroidism (p < 0.001), a negative impact of hypothyroidism on daily living (p < 0.001), and with anxiety and low mood/depression (p < 0.001). Conclusions: This study demonstrates a high prevalence of pSSD among people with hypothyroidism and associations between pSSD and negative patient outcomes, including a tendency to attribute persistent symptoms to hypothyroidism or its treatment. SSD may be an important determinant of dissatisfaction with treatment and care among some hypothyroid patients. [ABSTRACT FROM AUTHOR]

This paper is aimed at estimating Radio Frequency (RF) radiation absorbed by humans around Base Transceiver Stations (BTS) within Kaduna metropolis. RF radiation absorbed by humans from forty two (42) selected (BTS) tagged M1 to M42 of the four major network providers (MTN, 9mobile, Airtel and Globacom) within Kaduna metropolis, Kaduna State, Nigeria within radial distance intervals of 20 m to 100 m from the foot of each BTS were estimated. The Average Power Density (PDAve) and Specific Absorption Rate of data obtained from these BTS were computed, and the results indicated that the average amount of SAR for the selected forty two (42) base transceiver BTS facilities were within the range of 16.9 - 331.7 × 10-9 W/kg and 0.648-10.659 × 10-6 W/m² respectively. These values are lower than the recommended limit by International Commission on Non Ionization Radiation Protection (ICNIRP) which is 0.08 W/kg for the human body. This study has shown that RF radiation absorbed by people either residing or transiting the study area has negligible effect on their health. [ABSTRACT FROM AUTHOR]

The ventricle of the salmonid heart consists of an outer compact layer of circumferentially arranged cardiomyocytes encasing a spongy myocardium that spans the lumen of the ventricle with a fine arrangement of muscular trabeculae. While many studies have detailed the anatomical structure of fish hearts, few have considered how these two cardiac muscle architectures are attached to form a functional working unit. The present study considers how the spindle-like cardiomyocytes, unlike the more rectangular structure of adult mammalian cardiomyocytes, form perpendicular connections between the two muscle layers that withstand the mechanical forces generated during cardiac systole and permit a simultaneous, coordinated contraction of both ventricular components. Therefore, hearts of rainbow trout ( Oncorhynchus mykiss) and sockeye salmon ( Oncorhynchus nerka) were investigated in detail using scanning electron microscopy (SEM) and various light microscopic techniques. In contrast to earlier suggestions, we found no evidence for a distinct connective tissue layer between the two muscle architectures that might ‘glue’ together the compact and the spongy myocardium. Instead, the contact layer between the compact and the spongy myocardium was characterized by a significantly higher amount of desmosome-like (D) and fascia adhaerens-like (FA) adhering junctions compared with either region alone. In addition, we observed that the trabeculae form muscular sheets of fairly uniform thickness and variable width rather than thick cylinders of variable diameter. This sheet-like trabecular anatomy would minimize diffusion distance while maximizing the area of contact between the trabecular muscle and the venous blood as well as the muscle tension generated by a single trabecular sheet. [ABSTRACT FROM AUTHOR]

Delirium is an acute change in attention and cognition occurring in ~ 65% of severe SARS-CoV-2 cases. It is also common following surgery and an indicator of brain vulnerability and risk for the development of dementia. In this work we analyzed the underlying role of metabolism in delirium-susceptibility in the postoperative setting using metabolomic profiling of cerebrospinal fluid and blood taken from the same patients prior to planned orthopaedic surgery. Distance correlation analysis and Random Forest (RF) feature selection were used to determine changes in metabolic networks. We found significant concentration differences in several amino acids, acylcarnitines and polyamines linking delirium-prone patients to known factors in Alzheimer's disease such as monoamine oxidase B (MAOB) protein. Subsequent computational structural comparison between MAOB and angiotensin converting enzyme 2 as well as protein–protein docking analysis showed that there potentially is strong binding of SARS-CoV-2 spike protein to MAOB. The possibility that SARS-CoV-2 influences MAOB activity leading to the observed neurological and platelet-based complications of SARS-CoV-2 infection requires further investigation. [ABSTRACT FROM AUTHOR]

Several independent research studies have shown that consumption of green tea reduces the development of cancer in many animal models. Epidemiological observations, though inconclusive, are suggesting that green tea consumption may also reduce the risk of some cancers in humans. These anti-carcinogenic effects of green tea have been attributed to its constituent polyphenols. Angiogenesis is a crucial step in the growth and metastasis of cancers. We have investigated the effect of the major polyphenolic constituent of green tea, epigallocatechin-3-gallate (EGCG), on the tube formation of human umbilical vein endothelial cells (HUVEC) on matrigel. Tube formation was inhibited by treatment both prior to plating and after plating endothelial cells on matrigel. EGCG treatment also was found to reduce the migration of endothelial cells in matrigel plug model. The role of matrix metalloproteinases (MMP) has been shown to play an important role during angiogenesis. Zymography was performed to determine if EGCG had any effect on MMPs. Zymographs of EGCG-treated culture supernatants modulated the gelatinolytic activities of secreted proteinases indicating that EGCG may be exerting its inhibitory effect by regulating proteinases. These findings suggest that EGCG acts as an angiogenesis inhibitor by modulating protease activity during endothelial morphogenesis. [Copyright &y& Elsevier]

Background: Anti-hypertensives that modify the renin angiotensin system may reduce Alzheimer's disease (AD) pathology and reduce the rate of disease progression.Objective: To conduct a phase II, two arm, double-blind, placebo-controlled, randomized trial of losartan to test the efficacy of Reducing pathology in Alzheimer's Disease through Angiotensin TaRgeting (RADAR).Methods: Men and women aged at least 55 years with mild-to-moderate AD will be randomly allocated 100 mg encapsulated generic losartan or placebo once daily for 12 months after successful completion of a 2-week open-label phase and 2-week placebo washout to establish drug tolerability. 228 participants will provide at least 182 subjects with final assessments to provide 84% power to detect a 25% difference in atrophy rate (therapeutic benefit) change over 12 months at an alpha level of 0.05. We will use intention-to-treat analysis, estimating between-group differences in outcomes derived from appropriate (linear or logistic) multivariable regression models adjusting for minimization variables.Results: The primary outcome will be rate of whole brain atrophy as a surrogate measure of disease progression. Secondary outcomes will include changes to 1) white matter hyperintensity volume and cerebral blood flow; 2) performance on a standard series of assessments of memory, cognitive function, activities of daily living, and quality of life. Major assessments (for all outcomes) and relevant safety monitoring of blood pressure and bloods will be at baseline and 12 months. Additional cognitive assessment will also be conducted at 6 months along with safety blood pressure and blood monitoring. Monitoring of blood pressure, bloods, and self-reported side effects will occur during the open-label phase and during the majority of the post-randomization dispensing visits.Conclusion: This study will identify whether losartan is efficacious in the treatment of AD and whether definitive Phase III trials are warranted. [ABSTRACT FROM AUTHOR]

Lysosomes are acidic cytoplasmic organelles that are present in all nucleated mammalian cells and are involved in a variety of cellular processes including repair of the plasma membrane, defense against pathogens, cholesterol homeostasis, bone remodeling, metabolism, apoptosis and cell signaling. Defects in lysosomal enzyme activity have been associated with a variety of neurological diseases including Parkinson’s Disease, Lysosomal Storage Diseases, Alzheimer's disease and Huntington's disease. Fluorogenic lysosomal staining probes were synthesized for labeling lysosomes and other acidic organelles in a live-cell format and were shown to be capable of monitoring lysosomal metabolic activity. The new targeted substrates were prepared from fluorescent dyes having a low pKa value for optimum fluorescence at the lower physiological pH found in lysosomes. They were modified to contain targeting groups to direct their accumulation in lysosomes as well as enzyme-cleavable functions for monitoring specific enzyme activities using a live-cell staining format. Application to the staining of cells derived from blood and skin samples of patients with Metachromatic Leukodystrophy, Krabbe and Gaucher Diseases as well as healthy human fibroblast and leukocyte control cells exhibited localization to the lysosome when compared with known lysosomal stain LysoTracker® Red DND-99 as well as with anti-LAMP1 Antibody staining. When cell metabolism was inhibited with chloroquine, staining with an esterase substrate was reduced, demonstrating that the substrates can be used to measure cell metabolism. When applied to diseased cells, the intensity of staining was reflective of lysosomal enzyme levels found in diseased cells. Substrates specific to the enzyme deficiencies in Gaucher or Krabbe disease patient cell lines exhibited reduced staining compared to that in non-diseased cells. The new lysosome-targeted fluorogenic substrates should be useful for research, diagnostics and monitoring the effect of secondary therapeutic agents on lysosomal enzyme activity in drug development for the lysosomal storage disorders and allied diseases. [ABSTRACT FROM AUTHOR]

This study combined high resolution mass spectrometry (HRMS), advanced chemometrics and pathway enrichment analysis to analyse the blood metabolome of patients attending the memory clinic: cases of mild cognitive impairment (MCI; n = 16), cases of MCI who upon subsequent follow-up developed Alzheimer’s disease (MCI_AD; n = 19), and healthy age-matched controls (Ctrl; n = 37). Plasma was extracted in acetonitrile and applied to an Acquity UPLC HILIC (1.7μm x 2.1 x 100 mm) column coupled to a Xevo G2 QTof mass spectrometer using a previously optimised method. Data comprising 6751 spectral features were used to build an OPLS-DA statistical model capable of accurately distinguishing Ctrl, MCI and MCI_AD. The model accurately distinguished (R2 = 99.1%; Q2 = 97%) those MCI patients who later went on to develop AD. S-plots were used to shortlist ions of interest which were responsible for explaining the maximum amount of variation between patient groups. Metabolite database searching and pathway enrichment analysis indicated disturbances in 22 biochemical pathways, and excitingly it discovered two interlinked areas of metabolism (polyamine metabolism and L-Arginine metabolism) were differentially disrupted in this well-defined clinical cohort. The optimised untargeted HRMS methods described herein not only demonstrate that it is possible to distinguish these pathologies in human blood but also that MCI patients ‘at risk’ from AD could be predicted up to 2 years earlier than conventional clinical diagnosis. Blood-based metabolite profiling of plasma from memory clinic patients is a novel and feasible approach in improving MCI and AD diagnosis and, refining clinical trials through better patient stratification. [ABSTRACT FROM AUTHOR]

We developed molecular tension probes (TPs) that report traction forces of adherent cells with high spatial resolution, can in principle be linked to virtually any surface, and obviate monitoring deformations of elastic substrates. TPs consist of DNA hairpins conjugated to fluorophore-quencher pairs that unfold and fluoresce when subjected to specific forces. We applied TPs to reveal that cellular traction forces are heterogeneous within focal adhesions and localized at their distal edges. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this study was to evaluate the prevalence of self-diagnosis of malaria and other febrile illnesses in Bo, Sierra Leone. Methods: All households in two neighboring sections of Bo were invited to participate in a cross-sectional survey. Results: A total of 882 households (an 85% participation rate) that were home to 5410 individuals participated in the study. Of the 910 individuals reported to have had what the household considered to be malaria in the past month, only 41% were diagnosed by a healthcare professional or a laboratory test. Of the 1402 individuals reported to have had any type of febrile illness within the past six months, only 34% had sought a clinical or laboratory diagnosis. Self-diagnosis of influenza, yellow fever, typhoid, and pneumonia was also common. Conclusion: Self-diagnosis and presumptive treatment with antimalarial drugs and other antibiotic medications that are readily available without a prescription may compromise health outcomes for febrile adults and children. [ABSTRACT FROM AUTHOR]

Abstract: The apolipoprotein (APOE) ɛ4 allele is a genetic risk factor for the development of Alzheimer''s disease (AD). It has also been associated with vascular dementia (VaD) in some but not all studies. Previous studies have examined the role of APOE in predicting performance on cognitive tests in both demented and non-demented populations. In cognitively intact individuals, statistically significant group differences between APOE ɛ4 carriers and non-carriers have been demonstrated for several cognitive domains. In AD studies of the impact of APOE ɛ4 on cognition have been conflicting while no previous study has assessed cognition and impact of APOE ɛ4 in VaD. In this study we investigated the impact of APOE ɛ4 on performance in neuropsychological tests including information processing speed in patients with mild-moderate AD and VaD. We incorporated both computerized and pen and paper tests to ensure a sensitive method of assessing cognition. 109 patients participated in the study (VaD=41, AD=68). Neurocognitive performance of 44 ɛ4 present AD patients was compared to 24 ɛ4absent patients and performance of 23 ɛ4 present VaD patients was compared to 18 ɛ4 absent patients. There was evidence that APOE ɛ4 conferred a risk of poorer cognitive functioning in both patient groups. In the AD group presence of ɛ4 conferred a negative impact on some measures of speed of information processing and immediate recall while in the VaD group ɛ4 present patients had evidence of poorer accuracy on tasks such as choice reaction time and spatial working memory. In AD and VaD groups ɛ4 present patients showed impairment in selective attention. These findings provide further support of the negative impact of the ɛ4 allele in cognition. [Copyright &y& Elsevier]

Until recently, the central nervous system (CNS) has been thought to be an immune privileged organ. However, it is now understood that neuroinflammation is linked with the development of several CNS diseases including late-onset Alzheimer’s disease (LOAD). The development of inflammation is a complex process involving a wide array of molecular interactions which in the CNS remains to be further characterized. The development of neuroinflammation may represent an important link between the early stages of LOAD and its pathological outcome. It is proposed that risks for LOAD, which include genetic, biological and environmental factors can each contribute to impairment of normal CNS regulation and function. The links between risk factors and the development of neuroinflammation are numerous and involve many complex interactions which contribute to vascular compromise, oxidative stress and ultimately neuroinflammation. Once this cascade of events is initiated, the process of neuroinflammation can become overactivated resulting in further cellular damage and loss of neuronal function. Additionally, neuroinflammation has been associated with the formation of amyloid plaques and neurofibrillary tangles, the pathological hallmarks of LOAD. Increased levels of inflammatory markers have been correlated with an advanced cognitive impairment. Based on this knowledge, new therapies aimed at limiting onset of neuroinflammation could arrest or even reverse the development of the disease. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Information about several papers discusses at a conference on molecule biophysics is presented. The conference covers an emerging discipline in which the behaviors of individual macromolecules are measured with a variety of biophysical techniques including optical trapping, atomic force microscopy, fluorescense microscopy and magnetic tweezers. single-molecule techniques have been used to study transcription by prokaryotic RNA polymerase with which transcription is initiated in bacteria.

In the article the authors reflect on the development of a national strategy for dementia care in Northern Ireland (NI). In September 2008, the Department of Health, Social Services and Public Safety (DHSSPS) appointed a group to develop a Dementia Strategy for NI. The article also examines relevant reports and policies that will influence the Strategy.

We report a case of Pisa syndrome (PS) due to the acetylcholinesterase inhibitor donepezil which may have been precipitated by pharmacokinetic interactions with commonly used medications. PS is defined as a reversible lateral bending of the trunk with a tendency to lean to one side. This is a rare but very distressing complication with this commonly used medication which was not initially recognised, leading to increasing disability for the patient and significant carer stress. Cessation of donepezil and modulation of potential interacting medications resulted in complete resolution. [ABSTRACT FROM AUTHOR]

Background: Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue currently approved for type 2 diabetes and obesity. Preclinical evidence in transgenic models of Alzheimer's disease suggests that liraglutide exerts neuroprotective effects by reducing amyloid oligomers, normalising synaptic plasticity and cerebral glucose uptake, and increasing the proliferation of neuronal progenitor cells. The primary objective of the study is to evaluate the change in cerebral glucose metabolic rate after 12 months of treatment with liraglutide in participants with Alzheimer's disease compared to those who are receiving placebo.Methods/design: ELAD is a 12-month, multi-centre, randomised, double-blind, placebo-controlled, phase IIb trial of liraglutide in participants with mild Alzheimer's dementia. A total of 206 participants will be randomised to receive either liraglutide or placebo as a daily injection for a year. The primary outcome will be the change in cerebral glucose metabolic rate in the cortical regions (hippocampus, medial temporal lobe, and posterior cingulate) from baseline to follow-up in the treatment group compared with the placebo group. The key secondary outcomes are the change from baseline to 12 months in z scores for clinical and cognitive measures (Alzheimer's Disease Assessment Scale-Cognitive Subscale and Executive domain scores of the Neuropsychological Test Battery, Clinical Dementia Rating Sum of Boxes, and Alzheimer's Disease Cooperative Study-Activities of Daily Living) and the incidence and severity of treatment-emergent adverse events or clinically important changes in safety assessments. Other secondary outcomes are 12-month change in magnetic resonance imaging volume, diffusion tensor imaging parameters, reduction in microglial activation in a subgroup of participants, reduction in tau formation and change in amyloid levels in a subgroup of participants measured by tau and amyloid imaging, and changes in composite scores using support machine vector analysis in the treatment group compared with the placebo group.Discussion: Alzheimer's disease is a leading cause of morbidity worldwide. As available treatments are only symptomatic, the search for disease-modifying therapies is a priority. If the ELAD trial is successful, liraglutide and GLP-1 analogues will represent an important class of compounds to be further evaluated in clinical trials for Alzheimer's treatment.Trial Registration: ClinicalTrials.gov, NCT01843075 . Registration 30 April 2013. [ABSTRACT FROM AUTHOR]

The article presents obituaries for several notable people in medicine including general practitioner Roointon Faridoon Boomla, pathologist Thomas Hargreaves, and paediatrician Geoffrey Peter McMullin.