Neuroimaging of Inflammation in Memory and Related Other Disorders (NIMROD) study protocol: a deep phenotyping cohort study of the role of brain inflammation in dementia, depression and other neurological illnesses

$\textit{Introduction}$ Inflammation of the central nervous system is increasingly regarded as having a role in cognitive disorders such as dementia and depression, but it is not clear how such neuroinflammation relates to other aspects of neuropathology (e.g., tau and amyloid pathology) as well as to structural and functional changes in the brain and symptoms (as assessed via MRI and clinical and neuropsychological assessment). This study will explore these pathophysiological mechanisms using positron emission tomography (PET) which allows $\textit{in vivo}$ imaging of inflammation, amyloid and tau deposition, together with neuropsychological profiling, magnetic resonance imaging (MRI) and peripheral biomarker analysis. \textit{Methods & analysis} Using PET imaging of the ligand [11C]PK11195 we will test for increased neuroinflammation $\textit{in vivo}$ in patients with Alzheimer’s disease, Lewy body dementia, frontotemporal dementia, progressive supranuclear palsy, late onset depression and mild cognitive impairment, when compared to healthy controls. We will assess whether areas of inflammatory change are associated with amyloid and tau deposition (assessed using $^{11}$C-labelled Pittsburgh Compound B ([$^{11}$C]PiB) and $^{18}$F-labelled AV-1451 respectively), as well as structural and functional connectivity changes found on MRI. Inflammatory biomarker analysis and immune-phenotyping of peripheral blood monocytes will determine the correlation between central (i.e., neural) and peripheral inflammation. Finally, we will examine whether neuroinflammatory changes seen on PET imaging are associated with global and domain specific cognitive impairments, or predict cognitive decline over 12 months. \textit{Ethics & dissemination} The study protocol was approved by the local ethics committee, East of England - Cambridge Central Research Ethics Committee (reference: 13/EE/0104). The study is also ARSAC approved as part of this process. Data will be disseminated by presentation at national and international conferences and by publication, predominantly in journals of neuroscience as well as clinical neurology and psychiatry. $\textit{Strengths}$ Multimodal deep phenotyping Comparisons between diseases as well as with controls Longitudinal neuropsychology data Comparison of central and peripheral inflammation $\textit{Weaknesses}$ Lack of longitudinal neuroimaging Not a prospective study, unable to assess causationThe study is funded by the UK National Institute of Health Research Cambridge Biomedical Research Unit in Dementia (Project 4 - RNAG/293). JBR is supported by the Wellcome Trust (103838). JPC is supported by the UK National Institute of Health Research Biomedical Research Centre at Cambridge. PVR is supported by the PSP Association

The Detectability of Earth's Biosignatures Across Time

Over the past two decades, enormous advances in the detection of exoplanets have taken place. Currently, we have discovered hundreds of earth-sized planets, several of them within the habitable zone of their star. In the coming years, the efforts will concentrate in the characterization of these planets and their atmospheres to try to detect the presence of biosignatures. However, even if we discovered a second Earth, it is very unlikely that it would present a stage of evolution similar to the present-day Earth. Our planet has been far from static since its formation about 4.5 Ga ago; on the contrary, during this time, it has undergone multiple changes in it's atmospheric composition, it's temperature structure, it's continental distribution, and even changes in the forms of life that inhabit it. All these changes have affected the global properties of Earth as seen from an astronomical distance. Thus, it is of interest not only to characterize the observables of the Earth as it is today, but also at different epochs. Here we review the detectability of the Earth's globally-averaged properties over time. This includes atmospheric composition and biosignatures, and surface properties that can be interpreted as sings of habitability (bioclues). The resulting picture is that truly unambiguous biosignatures are only detectable for about 1/4 of the Earth's history. The rest of the time we rely on detectable bioclues that can only establish an statistical likelihood for the presence of life on a given planet.Comment: To appear in "Handbook of Exoplanets", eds. Deeg, H.J. & Belmonte, J.A, Springer (2018). arXiv admin note: text overlap with arXiv:astro-ph/0609398 by other author

Phytochemicals as antibiotic alternatives to promote growth and enhance host health

There are heightened concerns globally on emerging drug-resistant superbugs and the lack of new antibiotics for treating human and animal diseases. For the agricultural industry, there is an urgent need to develop strategies to replace antibiotics for food-producing animals, especially poultry and livestock. The 2nd International Symposium on Alternatives to Antibiotics was held at the World Organization for Animal Health in Paris, France, December 12-15, 2016 to discuss recent scientific developments on strategic antibiotic-free management plans, to evaluate regional differences in policies regarding the reduction of antibiotics in animal agriculture and to develop antibiotic alternatives to combat the global increase in antibiotic resistance. More than 270 participants from academia, government research institutions, regulatory agencies, and private animal industries from >25 different countries came together to discuss recent research and promising novel technologies that could provide alternatives to antibiotics for use in animal health and production; assess challenges associated with their commercialization; and devise actionable strategies to facilitate the development of alternatives to antibiotic growth promoters (AGPs) without hampering animal production. The 3-day meeting consisted of four scientific sessions including vaccines, microbial products, phytochemicals, immune-related products, and innovative drugs, chemicals and enzymes, followed by the last session on regulation and funding. Each session was followed by an expert panel discussion that included industry representatives and session speakers. The session on phytochemicals included talks describing recent research achievements, with examples of successful agricultural use of various phytochemicals as antibiotic alternatives and their mode of action in major agricultural animals (poultry, swine and ruminants). Scientists from industry and academia and government research institutes shared their experience in developing and applying potential antibiotic-alternative phytochemicals commercially to reduce AGPs and to develop a sustainable animal production system in the absence of antibiotics.Fil: Lillehoj, Hyun. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Liu, Yanhong. University of California; Estados UnidosFil: Calsamiglia, Sergio. Universitat Autònoma de Barcelona; EspañaFil: Fernandez Miyakawa, Mariano Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; ArgentinaFil: Chi, Fang. Amlan International; Estados UnidosFil: Cravens, Ron L.. Amlan International; Estados UnidosFil: Oh, Sungtaek. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Gay, Cyril G.. United States Department of Agriculture. Agricultural Research Service; Argentin

Comparative study of paediatric prescription drug utilization between the spanish and immigrant population

<p>Abstract</p> <p>Background</p> <p>The immigrant population has increased greatly in Spain in recent years to the point where immigrants made up 12% of the infant population in 2008. There is little information available on the profile of this group with regard to prescription drug utilization in universal public health care systems such as that operating in Spain. This work studies the overall and specific differences in prescription drug utilization between the immigrant and Spanish population.</p> <p>Methods</p> <p>Use was made of the Aragonese Health Service databases for 2006. The studied population comprises 159,908 children aged 0-14 years, 13.6% of whom are foreign nationals. Different utilization variables were calculated for each group. Prescription-drug consumption is measured in Defined Daily Doses (DDD) and DDD/1000 persons/day/(DID).</p> <p>Results</p> <p>A total of 833,223 prescriptions were studied. Utilization is lower for immigrant children than in Spanish children for both DID (66.27 v. 113.67) and average annual expense (€21.55 v. €41.14). Immigrant children consume fewer prescription drugs than Spanish children in all of the therapy groups, with the most prescribed (in DID) being: respiratory system, anti-infectives for systemic use, nervous system, sensory organs. Significant differences were observed in relation to the type of drugs and the geographical background of immigrants.</p> <p>Conclusion</p> <p>Prescription drug utilization is much greater in Spanish children than in immigrant children, particularly with reference to bronchodilators (montelukast and terbutaline) and attention-disorder hyperactivity drugs such as methylphenidate. There are important differences regarding drug type and depending on immigrants' geographical backgrounds that suggest there are social, cultural and access factors underlying these disparities.</p

Optimizing both catalyst preparation and catalytic behaviour for the oxidative dehydrogenation of ethane of Ni-Sn-O catalysts

[EN] Bulk Ni-Sn-O catalysts have been synthesized, tested in the oxidative dehydrogenation of ethane and characterized by several physicochemical techniques. The catalysts have been prepared by evaporation of the corresponding salts using several additives in the synthesis gel, i.e. ammonium hydroxide, nitric acid, glyoxylic acid or oxalic acid, in the synthesis gel. The catalysts were finally calcined at 500 degrees C in air. Important changes in the catalytic behaviour have been observed depending on the additive. In fact, an important improvement in the catalytic performance is observed especially when some additives, such as glyoxylic or oxalic acid, are used. Thus the productivity to ethylene multiplies by 6 compared to the reference Ni-Sn-O catalyst if appropriate templates are used, and this is the result of an improvement in both the catalytic activity and the selectivity to ethylene. This improved performance has been explained in terms of the decrease of the crystallite size (and the increase in the surface area of catalyst) as well as the modification of the lattice parameter of nickel oxide.The authors would like to acknowledge the DGICYT in Spain (CTQ2015-68951-C3-1-R and CTQ2012-37925-C03-2) for financial support. We also thank the University of Valencia and SCSIE-UV for assistanceSolsona Espriu, BE.; López Nieto, JM.; Agouram, S.; Soriano Rodríguez, MD.; Dejoz, A.; Vázquez, MI.; Concepción Heydorn, P. (2016). Optimizing both catalyst preparation and catalytic behaviour for the oxidative dehydrogenation of ethane of Ni-Sn-O catalysts. Topics in Catalysis. 59(17-18):1564-1572. https://doi.org/10.1007/s11244-016-0674-zS156415725917-18Heracleous E, Lee AF, Wilson K, Lemonidou AA (2005) J Catal 231:159–171Heracleous E, Lemonidou AA (2006) J Catal 237:162–174Savova B, Loridant S, Filkova D, Millet JMM (2010) Appl Catal A 390:148–157Heracleous E, Lemonidou AA (2010) J Catal 270:67–75Solsona B, Nieto JML, Concepcion P, Dejoz A, Ivars F, Vazquez MI (2011) J Catal 280:28–39Skoufa Z, Heracleous E, Lemonidou AA (2012) Catal Today 192:169–176Zhu H, Ould-Chikh S, Anjum DH, Sun M, Biausque G, Basset JM, Caps V (2012) J Catal 285:292–303Skoufa Z, Heracleous E, Lemonidou AA (2012) Chem Eng Sci 84:48–56Zhu H, Rosenfeld DC, Anjum DH, Caps V, Basset JM (2015) ChemSusChem 8:1254–1263Heracleous E, Lemonidou AA (2015) J Catal 322:118–129Solsona B, Concepcion P, Demicol B, Hernandez S, Delgado JJ, Calvino JJ, Nieto JML (2012) J Catal 295:104–114Nieto JML, Solsona B, Grasselli RK, Concepción P (2014) Top Catal 57:1248–1255Popescu I, Skoufa Z, Heracleous E, Lemonidou AA, Marcu IC (2015) PCCP 17:8138–8147Zhang X, Gong Y, Yu G, Xie Y (2002) J Mol Catal A 180:293–298Popescu I, Skoufa Z, Heracleous E, Lemonidou A, Marcu I-C (2015) Phys Chem Chem Phys 17:8138–8147Nakamura KI, Miyake T, Konishi T, Suzuki T (2006) J Mol Catal A 260:144–151Solsona B, Dejoz AM, Vazquez MI, Ivars F, Nieto JML (2009) Top Catal 52:751–757Bortolozzi JP, Gutierrez LB, Ulla MA (2013) Appl Catal A 452:179–188Takeguchi T, Furukawa S, Inoue M (2001) J Catal 202:14–24Richardson JT, Turk B, Twigg MV (1996) Appl Catal 148:97–112Biju V, Khadar MA (2002) J Nanopart Res 4:247–253Van Veenendaal MA, Sawatzky GA (1993) Phys Rev Lett 70:2459–2462Vedrine JC, Hollinger G, Duc TM (1978) J Phys Chem 82:1515–1520Salagre P, Fierro JLG, Medina F, Sueiras JE (1996) J Mol Catal A 106:125–13

Lateral variability of ichnological content in muddy contourites: Weak bottom currents affecting organisms’ behavior

Although bioturbation is commonly recognized in contourites, only a few studies have analyzed the ichnological content of these deposits in detail. These studies have mainly focused on meso-scale bigradational sequence (a coarsening upward followed by a fining-upward sequence resulting from variations in current velocity). Here we present data from gravitational cores collected along the NW Iberian Margin showing systematic variation in ichnological content across proximal to distal depocenters within a large-scale elongated contourite drift. Data demonstrate that tracemakers’ behavior varies depending on the distance relative to the bottom current core. Trace fossils are already known to be a useful tool for studying of contouritic deposits and are even used as criterion for differentiating associated facies (e.g., turbidites, debrites), though not without controversy. We propose a mechanism by which the distance to the bottom current core exerts tangible influence on specific macro-benthic tracemaker communities in contourite deposits. This parameter itself reflects other bottom current features, such as hydrodynamic energy, grain size, nutrient transport, etc. Ichnological analysis can thus resolve cryptic features of contourite drift depositional settings.The contribution and research by JD was funded through the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 792314 (ICON-SE). The research of FJR-T was funded by project CGL2015-66835-P (Secretaría de Estado de Investigacion, Desarrollo e Innovacion, Spain), Research Group RNM-178 (Junta de Andalucía), and Scientific Excellence Unit UCE-2016- 05 (Universidad de Granada). AM’s research is funded by the I2C program of the Xunta de Galicia Postdoctoral programme (ED481B 2016/029-0). The research was conducted as part of “The Drifters Research Group” (RHUL) and “Ichnology and Palaeoenvironment Research Group” (UGR) programs

Immunohistochemical and transcriptional expression of Matrix Metalloproteinases in full-term human umbilical cord and Human Umbilical Vein Endothelial Cells

Matrix metalloproteinases (MMPs) are extracellular zinc-dependent endopeptidases involved in the degradation and remodelling of extracellular matrix in physiological and pathological processes. MMPs also have a role on cell proliferation, migration, differentiation, angiogenesis and apoptosis. Umbilical cord is a special organ subjected to many changes during pre-natal life and whose cells can maintain a certain degree of plasticity also in post-natal period; for example recently they have been used as a source of stem cells. In this work we investigated the expression of MMPs in human umbilical cord and Human Umbilical Vein Endothelial Cells (HUVEC) though immunohistochemistry, RT-PCR and gelatin zymography. MMP-2 protein is expressed in the amniotic epithelium of human umbilical cord and in few sub-epithelial fibroblasts, while MMP-3 and MMP-10 only in the umbilical epithelium. MMP-8, MMP-9 and MMP-13 immunoreactivity is localised in the epithelium and in Wharton\u2019s jelly mesenchymal cells. Immunocytochemistry also revealed protein expression for MMP-2, 3, 8, 9 and 10 in cultured HUVEC. In agreement with immunohistochemical data, RT-PCR analysis performed on samples of whole umbilical cord confirmed the transcriptional expression for the genes encoding all the six matrix metalloproteinases investigated, while in HUVEC only the expression of MMP-2, 3, 9, 10 and 13 mRNAs was detected. Gelatin zymograpgy showed a clear MMP-2 and MMP-9 enzymatic activity in the conditioned medium of HUVEC at different culture passages, suggesting that HUVEC secrete gelatinases, that afterwards undergo extracellular activation, and this ability is not affected by passage number

The mental health, quality of life and life satisfaction of internally displaced persons living in Nakuru County, Kenya

Background Internally displaced persons (IDPs) are among the most vulnerable people in the world today. Previous research highlights that conflict-induced forced displacement can cause problems with mental health and wellbeing. This study aimed to contribute to this body of knowledge by investigating the mental health, quality of life, and life satisfaction among IDPs living in Nakuru, Kenya. Methods A questionnaire that included the General Health Questionnaire-12, Satisfaction with Life Scale, and a modified version of the WHO Quality of Life-BREF tool was used for data collection. The questionnaire also included an open-ended question inviting qualitative responses about their experience as an IDP. The questionnaire was distributed through a three-stage sampling approach across four refugee camps from four regions of the Nakuru County in Kenya. Results One hundred IDPs participated in this study. All participants scored substantially higher than the applied GHQ-12 threshold for caseness (mean GHQ-12 score = 28.7, SD = 3.6). Quality of life and life satisfaction scores were also very poor (M = 10.24, SD = 1.9; M = 6.82, SD = 1.5 respectively). The qualitative results reflected these findings with statements reflecting suicidal thoughts, unhappiness with the government, lack of support, and fear for themselves and their children. Significantly higher GHQ-12 scores were found among older IDPs (rho = .202, sig = .046), widowers compared to married IDPs (mean difference = −2.41, SE = .885, sig = .027), while lower scores were found among IDPs who reported having friends as a source of support (U = 834, sig = .045), while quality of life scores were higher among IDPs who reported receiving governmental support (U = 248, sig = .018). Conclusion The findings revealed poor levels of mental health, quality of life and life satisfaction. Older, widowed IDPs and those who did not perceive support from friends or the government were found to be at the highest risk of poor health and wellbeing

The membrane-spanning 4-domains, subfamily A (MS4A) gene cluster contains a common variant associated with Alzheimer's disease

Background\ud In order to identify novel loci associated with Alzheimer's disease (AD), we conducted a genome-wide association study (GWAS) in the Spanish population.\ud \ud Methods\ud We genotyped 1,128 individuals using the Affymetrix Nsp I 250K chip. A sample of 327 sporadic AD patients and 801 controls with unknown cognitive status from the Spanish general population were included in our initial study. To increase the power of the study, we combined our results with those of four other public GWAS datasets by applying identical quality control filters and the same imputation methods, which were then analyzed with a global meta-GWAS. A replication sample with 2,200 sporadic AD patients and 2,301 controls was genotyped to confirm our GWAS findings.\ud \ud Results\ud Meta-analysis of our data and independent replication datasets allowed us to confirm a novel genome-wide significant association of AD with the membrane-spanning 4-domains subfamily A (MS4A) gene cluster (rs1562990, P = 4.40E-11, odds ratio = 0.88, 95% confidence interval 0.85 to 0.91, n = 10,181 cases and 14,341 controls).\ud \ud Conclusions\ud Our results underscore the importance of international efforts combining GWAS datasets to isolate genetic loci for complex diseases