17 research outputs found
Study Protocol PROMETHEUS:Prospective Multicenter Study to Evaluate the Correlation Between Safety Margin and Local Recurrence After Thermal Ablation Using Image Co-registration in Patients with Hepatocellular Carcinoma
Purpose: The primary objective is to determine the minimal ablation margin required to achieve a local recurrence rate of 18 years with Barcelona Clinic Liver Cancer stage 0/A hepatocellular carcinoma (or B with a maximum of two lesions < 5 cm each) are eligible. Patients will undergo dual-phase contrast-enhanced computed tomography directly before and after ablation. Ablation margins will be quantitatively assessed using co-registration software, blinding assessors (i.e. two experienced radiologists) for outcome. Presence and location of recurrence are evaluated independently on follow-up scans by two other experienced radiologists, blinded for the quantitative margin analysis. A sample size of 189 tumors (~ 145 patients) is required to show with 80% power that the risk of local recurrence is confidently below 10%. A two-sided binomial z-test will be used to test the null hypothesis that the local recurrence rate is ≥ 10% for patients with a minimal ablation margin ≥ 2 mm. Logistic regression will be used to find the relationship between minimal ablation margins and local recurrence. Kaplan–Meier estimates are used to assess local and overall recurrence, disease-free and overall survival. Discussion: It is expected that this study will result in a clear understanding of the correlation between ablation margins and local recurrence. Using co-registration software in future patients undergoing ablation for hepatocellular carcinoma may improve intraprocedural evaluation of technical success. Trial registration The Netherlands Trial Register (NL9713), https://www.trialregister.nl/trial/9713
Increased Intestinal Permeability Correlates with Sigmoid Mucosa alpha-Synuclein Staining and Endotoxin Exposure Markers in Early Parkinson's Disease
Parkinson's disease (PD) is the second most common neurodegenerative disorder of aging. The pathological hallmark of PD is neuronal inclusions termed Lewy bodies whose main component is alpha-synuclein protein. The finding of these Lewy bodies in the intestinal enteric nerves led to the hypothesis that the intestine might be an early site of PD disease in response to an environmental toxin or pathogen. One potential mechanism for environmental toxin(s) and proinflammatory luminal products to gain access to mucosal neuronal tissue and promote oxidative stress is compromised intestinal barrier integrity. However, the role of intestinal permeability in PD has never been tested. We hypothesized that PD subjects might exhibit increased intestinal permeability to proinflammatory bacterial products in the intestine. To test our hypothesis we evaluated intestinal permeability in subjects newly diagnosed with PD and compared their values to healthy subjects. In addition, we obtained intestinal biopsies from both groups and used immunohistochemistry to assess bacterial translocation, nitrotyrosine (oxidative stress), and alpha-synuclein. We also evaluated serum markers of endotoxin exposure including LPS binding protein (LBP). Our data show that our PD subjects exhibit significantly greater intestinal permeability (gut leakiness) than controls. In addition, this intestinal hyperpermeability significantly correlated with increased intestinal mucosa staining for E. coli bacteria, nitrotyrosine, and alpha-synuclein as well as serum LBP levels in PD subjects. These data represent not only the first demonstration of abnormal intestinal permeability in PD subjects but also the first correlation of increased intestinal permeability in PD with intestinal alpha-synuclein (the hallmark of PD), as well as staining for gram negative bacteria and tissue oxidative stress. Our study may thus shed new light on PD pathogenesis as well as provide a new method for earlier diagnosis of PD and suggests potential therapeutic targets in PD subjects.Clinicaltrials.gov NCT01155492
Phytoplankton evolution during the creation of a biofloc system for shrimp culture
[EN] Microalgae play a key role in the dynamics of biofloc technology aquaculture systems. Some phytoplankton groups, such as diatoms, are desired for their high nutritional value and contribution to water quality. Other groups, such as cyanobacteria, are undesired because of their low nutritional value and capacity of producing toxins. So, monitoring the phytoplankton community structure and succession is key for managing biofloc systems. However, research on phytoplankton in these systems is scarce and mostly done by microscopy. The primary objective of this research was to estimate phytoplankton community structure in shrimp biofloc system water samples, using high-performance liquid chromatography methods and CHEMTAX software. The major groups present in our system were diatoms, euglenophytes, cyanobacteria and chlorophytes, while dinoflagellates were only remarkable at the initial period. We observed a clear dominance of diatoms all along the 5 months that comprised a complete biofloc system culture. The characteristic succession of autotrophic processes by heterotrophs of the biofloc systems, was observed by the reduction of net primary production. Light intensity played a key role in determining the phytoplankton composition and abundance. Algal pigment analyses using high-performance liquid chromatography and subsequent CHEMTAX analysis in water samples was useful for estimating the phytoplankton community structure in the biofloc systems. However, we found some limitations when the biofloc system was in heterotrophic mode. Under these conditions, some dinoflagellates and cyanobacteria behaved as heterotrophs and lost or decreased their biomarkers pigments. So, further research is needed to increase knowledge on the accuracy of high-performance liquid chromatography /CHEMTAX under these conditions.Financial support for this research was provided by Conselleria d’Educació, Investigació, Cultura i Esport of the Generalitat Valenciana, through the program VALi+D, fle number ACIF/2014/244. We would like to express our deepest thanks to Professor Luis Henrique da Silva Poersch of FURG (Universidade Federal do Rio Grande) and Ivan Vidal (Langostinos el Real) for his support. Finally, the authors wish to thank Le Gouessant and Michaël Metz for providing the commercial feed.Llario-Sempere, F.; Rodilla, M.; Escrivá-Perales, J.; Falco, S.; Sebastiá-Frasquet, M. (2018). Phytoplankton evolution during the creation of a biofloc system for shrimp culture. International Journal of Environmental Science and Technology. 1-12. https://doi.org/10.1007/s13762-018-1655-5S112Ahmed A, Kurian S, Gauns M, Chndrasekhararao AV, Mulla A, Naik B, Naik H, Naqvi SWA (2016) Spatial variability in phytoplankton community structure along the eastern Arabian Sea during the onset of south-west monsoon. Cont Shelf Res 119:30–39. https://doi.org/10.1016/j.csr.2016.03.005Avnimelech Y (1999) Carbon/nitrogen ratio as a control element in aquaculture systems. Aquaculture 176:227–235. https://doi.org/10.1016/S0044-8486(99)00085-XAvnimelech Y (2007) Feeding with microbial flocs by tilapia in minimal discharge bio-flocs technology ponds. Aquaculture 264:140–147. https://doi.org/10.1016/j.aquaculture.2006.11.025Avnimelech Y (2009) Biofloc technology. A practical guide book. The World Aquaculture Society, Baton RougeAzim ME, Little DC (2008) The biofloc technology (BFT) in indoor tanks: water quality, biofloc composition, and growth and welfare of Nile tilapia (Oreochromis niloticus). Aquaculture 283:29–35. https://doi.org/10.1016/j.aquaculture.2008.06.036Ballester ELC, Abreu PC, Cavalli RO, Emerenciano M, de Abreu L, Wasielesky WJ (2010) Effect of practical diets with different protein levels on the performance of Farfantepenaeus paulensis juveniles nursed in a zero exchange suspended microbial flocs intensive system. Aquac Nutr 16:163–172. https://doi.org/10.1111/j.1365-2095.2009.00648.xBaloi M, Arantes R, Schveitzer R, Magnotti C, Vinatea L (2013) Performance of Pacific white shrimp Litopenaeus vannamei raised in biofloc systems with varying levels of light exposure. Aquac Eng 52:39–44. https://doi.org/10.1016/j.aquaeng.2012.07.003Baumgarten MGZ, Wallner-Kersanach M, Niencheski LFH (2010) Manual de análises em oceanografia química. Furg, Rio GrandeBecerra-Dórame MJ, Martínez-Córdova LR, Martínez-Porchas M, Lopez-Elías JA (2011) Evaluation of autotrophic and heterotrophic microcosm- based systems on the production response of Litopenaeus vannamei intensively nursed without Artemia and with zero water exchange. Isr J Aquac Bamidgeh 63:7Brito LO, dos Santos IGS, de Abreu JL, de Araújo MT, Severi W, Gàlvez AO (2016) Effect of the addition of diatoms (Navicula spp.) and rotifers (Brachionus plicatilis) on water quality and growth of the Litopenaeus vannamei postlarvae reared in a biofloc system. Aquac Res 47:3990–3997. https://doi.org/10.1111/are.12849Campa-Córdova AI, Núñez-Vázquez EJ, Luna-González A, Romero-Geraldo MJ, Ascencio F (2009) Superoxide dismutase activity in juvenile Litopenaeus vannamei and Nodipecten subnodosus exposed to the toxic dinoflagellate Prorocentrum lima. Comp Biochem Physiol C Toxicol Pharmacol 149:317–322. https://doi.org/10.1016/j.cbpc.2008.08.006Casé M, Leça EE, Leitão SN, SantAnna EE, Schwamborn R, de Moraes Junior AT (2008) Plankton community as an indicator of water quality in tropical shrimp culture ponds. Mar Pollut Bull 56:1343–1352. https://doi.org/10.1016/j.marpolbul.2008.02.008Chen YC (2001) Immobilized microalga Scenedesmus quadricauda (Chlorophyta, Chlorococcales) for long-term storage and for application for water quality control in fish culture. Aquaculture 195:71–80. https://doi.org/10.1016/S0044-8486(00)00540-8Correia ES, Wilkenfeld JS, Morris TC, Wei L, Prangnell DI, Samocha TM (2014) Intensive nursery production of the Pacific white shrimp Litopenaeus vannamei using two commercial feeds with high and low protein content in a biofloc-dominated system. Aquac Eng 59:48–54. https://doi.org/10.1016/j.aquaeng.2014.02.002Duarte CM, Marrasé C, Vaqué D, Estrada M (1990) Counting error and the quantitative analysis of phytoplankton communities. J Plankton Res 12:295–304. https://doi.org/10.1093/plankt/12.2.295Ebeling J, Timmons M, Bisogni J (2006) Engineering analysis of the stoichiometry of photoautotrophic, autotrophic, and heterotrophic removal of ammonia–nitrogen in aquaculture systems. Aquaculture 257:346–358. https://doi.org/10.1016/j.aquaculture.2006.03.019El-Dahhar AA, Salama M, Elebiary EH (2015) Effect of energy to protein ratio in biofloc technology on water quality, survival and growth of mullet (Mugil cephalus). J Arab Aquac Soc 10:15–32. https://doi.org/10.12816/0026633Emerenciano MGC, Martínez-Córdova LR, Martínez-Porchas M, Miranda-Baeza A (2017) Biofloc technology (BFT): a tool for water quality management. In: Tutu H (ed) water quality. InTech, Rijeka. https://doi.org/10.5772/66416Figueroa F, Niell F, Figueiras F, Villarino M (1998) Diel migration of phytoplankton and spectral light field in the Ria de Vigo (NW Spain). Mar Biol 130:491–499Gaona CAP, Poersch LH, Krummenauer D, Foes GK, Wasielesky WJ (2011) The effect of solids removal on water quality, growth and survival of Litopenaeus vannamei in a biofloc technology culture system. Int J Recirc Aquac. https://doi.org/10.21061/ijra.v12i1.1354Garrido JL, Airs RL, Rodríguez F, Van Heukelem L, Zapata M (2011) New HPLC separation techniques. In: Roy S, Llewellyn CA, Egeland ES, Johnsen G (eds) Phytoplankton pigments: characterization, chemotaxonomy, and applications in oceanography. University Press, Cambridge, pp 165–194Ge H, Li J, Chang Z, Chen P, Shen M, Zhao F (2016) Effect of microalgae with semicontinuous harvesting on water quality and zootechnical performance of white shrimp reared in the zero water exchange system. Aquac Eng 72–73:70–76. https://doi.org/10.1016/j.aquaeng.2016.04.006Godoy LC, Odebrecht C, Ballester E, Martins TG, Wasielesky WJ (2012) Effect of diatom supplementation during the nursery rearing of Litopenaeus vannamei (Boone, 1931) in a heterotrophic culture system. Aquac Int 20:559–569. https://doi.org/10.1007/s10499-011-9485-1Grasshoff K (1976) Methods of seawater analysis. Verlag Chemie: Weinstei, New YorkGreen BW, Schrader KK, Perschbacher PW (2014) Effect of stocking biomass on solids, phytoplankton communities, common off-flavors, and production parameters in a channel catfish biofloc technology production system. Aquac Res 45:1442–1458. https://doi.org/10.1111/are.12096Gris B, Sforza E, Morosinotto T, Bertucco A, La Rocca N (2017) Influence of light and temperature on growth and high-value molecules productivity from Cyanobacterium aponinum. J Appl Phycol 29:1781–1790. https://doi.org/10.1007/s10811-017-1133-3Higgins HW, Wright SW, Schlüter L (2011) Quantitative interpretation of chemotaxonomic pigment data. In: Roy S, Llewellyn CA, Egeland ES, Johnsen G (eds) Phytoplankton pigments: characterization, chemotaxonomy, and applications in oceanography. Cambridge University Press, Cambridge, pp 257–313Hooker S, Firestone E, Claustre H, Ras J (2001) The first SeaWiFS HPLC analysis round-robin experiment (SeaHARRE-1). https://ntrs.nasa.gov/search.jsp?R=20010072242 . Accessed 19 July 2017Horabun T (1997) Relationships between water quality and phytoplankton in the Bangpakong river. http://agris.fao.org/agris-search/search.do?recordID=TH2000001898 . Accessed 19 July 2017Ismael AA (2003) Succession of heterotrophic and mixotrophic dinoflagellates as well as autotrophic microplankton in the harbour of Alexandria, Egypt. J Plankton Res 25:193–202. https://doi.org/10.1093/plankt/25.2.193Jeffrey SW, Sielicki M, Haxo FT (1975) Chloroplast pigment patterns in dinoflagellates. J Phycol 11:374–384. https://doi.org/10.1111/j.1529-8817.1975.tb02799.xJeong HJ, Yoo YD, Kim JS, Seong KA, Kang NS, Kim TH (2010) Growth, feeding and ecological roles of the mixotrophic and heterotrophic dinoflagellates in marine planktonic food webs. Ocean Sci J 45:65–91. https://doi.org/10.1007/s12601-010-0007-2Jory DE, Cabrera TR, Dugger DM, Fegan D, Lee PG, Lawrence L, Jackson C, Mcintosh R, Castañeda J, International B, Park H, Hwy N, Pierce F (2001) A global review of shrimp feed management: status and perspectives. Aquaculture 318:104–152Ju ZY, Forster I, Conquest L, Dominy W, Kuo WC, Horgen FD (2008) Determination of microbial community structures of shrimp floc cultures by biomarkers and analysis of floc amino acid profiles. Aquac Res 39:118–133. https://doi.org/10.1111/j.1365-2109.2007.01856.xKingston MB (1999) Effect of light on vertical migration and photosynthesis of Euglena proxima (euglenophyta). J Phycol 35:245–253. https://doi.org/10.1046/j.1529-8817.1999.3520245.xLatasa M, Scharek R, Vidal M, Vila-Reixach G (2010) Preferences of phytoplankton groups for waters of different trophic status in the northwestern Mediterranean Sea. Mar Ecol Prog Ser 40:27–42. https://doi.org/10.3354/meps08559Li Y, Swift E, Buskey EJ (1996) Photoinhibition of mechanically stimulable bioluminescence in the heterotrophic dinoflagellate Protoperidinium depressum (pyrrophyta). J Phycol 32:974–982. https://doi.org/10.1111/j.0022-3646.1996.00974.xLi A, Stoecker D, Adolf J (1999) Feeding, pigmentation, photosynthesis and growth of the mixotrophic dinoflagellate Gyrodinium galatheanum. Aquat Microb Ecol 19:163–176. https://doi.org/10.3354/ame019163Lin YC, Chen JC (2001) Acute toxicity of ammonia on Litopenaeus vannamei (Boone) juveniles at different salinity levels. J Exp Mar Biol Ecol 259:109–119. https://doi.org/10.1016/S0022-0981(01)00227-1Lin YC, Chen JC (2003) Acute toxicity of nitrite on Litopenaeus vannamei (Boone) juveniles at different salinity levels. Aquaculture 224:93–201. https://doi.org/10.1016/S0044-8486(03)00220-5Lohscheider JN, Strittmatter M, Küpper H, Adamska I, Heaney S, Cunningham C (2011) Vertical distribution of epibenthic freshwater cyanobacterial Synechococcus spp. Strains depends on their ability for photoprotection. PLoS ONE. https://doi.org/10.1371/journal.pone.0020134Lukwambe B, Qiuqian L, Wu J, Zhang D, Wang K, Zheng Z (2015) The effects of commercial microbial agents (probiotics) on phytoplankton community structure in intensive white shrimp (Litopenaeus vannamei) aquaculture ponds. Aquac Int 23:1443–1455. https://doi.org/10.1007/s10499-015-9895-6Mackey MD, Mackey DJ, Higgins HW, Wright SW (1996) CHEMTAX—a program for estimating class abundances from chemical markers: application to HPLC measurements of phytoplankton. Mar Ecol Prog Ser 144:265–283Maicá PF, de Borba MR, Wasielesky WJ (2012) Effect of low salinity on microbial floc composition and performance of Litopenaeus vannamei (Boone) juveniles reared in a zero-water-exchange super-intensive system. Aquac Res 43:361–370. https://doi.org/10.1111/j.1365-2109.2011.02838.xManan H, Moh JHZ, Kasan NA, Suratman S, Ikhwanuddin M (2016) Identification of biofloc microscopic composition as the natural bioremediation in zero water exchange of Pacific white shrimp, Penaeus vannamei, culture in closed hatchery system. Appl Water Sci. https://doi.org/10.1007/s13201-016-0421-4Marinho YF, Brito LO, Campos S, Severi W, Andrade HA, Galvez AO (2016) Effect of the addition of Chaetoceros calcitrans, Navicula sp. and Phaeodactylum tricornutum (diatoms) on phytoplankton composition and growth of Litopenaeus vannamei (Boone) postlarvae reared in a biofloc system. Aquac Res 48:4155–4164. https://doi.org/10.1111/are.13235Martins TG, Odebrecht C, Jensen LV, D’Oca MG, Wasielesky WJ (2016) The contribution of diatoms to bioflocs lipid content and the performance of juvenile Litopenaeus vannamei (Boone, 1931) in a BFT culture system. Aquac Res 47:1315–1326. https://doi.org/10.1111/are.12592Murphy J, Riley JP (1962) A modified single solution method for the determination of phosphate in natural waters. Anal Chim Acta 27:31–36. https://doi.org/10.1016/S0003-2670(00)88444-5Natrah FMI, Bossier P, Sorgeloos P, Yusoff FM, Defoirdt T (2014) Significance of microalgal-bacterial interactions for aquaculture. Rev Aquac 6:48–61. https://doi.org/10.1111/raq.12024Niemi G, Wardrop D, Brooks R, Anderson S, Brady V, Paerl H, Rakocinski C, Brouwer M, Levinson B, McDonald M (2004) Rationale for a new generation of indicators for coastal waters. Environ Health Perspect 112:979–986. https://doi.org/10.1289/ehp.6903Paerl H, Tucker C (1995) Ecology of blue-green algae in aquaculture ponds. J World Aquac 26:109–131. https://doi.org/10.1111/j.1749-7345.1995.tb00235.xPérez-Linares J, Ochoa JL, GagoMartínez A (2008) Effect of PSP toxins in white leg shrimp Litopenaeus vannamei Boone, 1931. J Food Sci 73:T69–T73. https://doi.org/10.1111/j.1750-3841.2008.00710.xPérez-Morales A, Band-Schmidt CJ, Martínez-Díaz SF (2017) Mortality on zoea stage of the Pacific white shrimp Litopenaeus vannamei caused by Cochlodinium polykrikoides (Dinophyceae) and Chattonella spp. (Raphidophyceae). Mar Biol 164:57. https://doi.org/10.1007/s00227-017-3083-3Ray AJ, Dillon KS, Lotz JM (2011) Water quality dynamics and shrimp (Litopenaeus vannamei) production in intensive, mesohaline culture systems with two levels of biofloc management. Aquac Eng 45:127–136. https://doi.org/10.1016/j.aquaeng.2011.09.001Schlüter L, Lauridsen T, Krogh G (2006) Identification and quantification of phytoplankton groups in lakes using new pigment ratios–a comparison between pigment analysis by HPLC and microscopy. Freshwater 51:1474–1485. https://doi.org/10.1111/j.1365-2427.2006.01582.x/fullSchlüter L, Behl S, Striebel M, Stibor H (2016) Comparing microscopic counts and pigment analyses in 46 phytoplankton communities from lakes of different trophic state. Freshw Biol 61:1627–1639. https://doi.org/10.1111/fwb.12803Schrader KK, Green BW, Perschbacher PW (2011) Development of phytoplankton communities and common off-flavors in a biofloc technology system used for the culture of channel catfish (Ictalurus punctatus). Aquac Eng 45:118–126. https://doi.org/10.1016/j.aquaeng.2011.08.004Sebastiá M, Rodilla M (2013) Nutrient and phytoplankton analysis of a Mediterranean Coastal area. Environ Manage 51:225–240. https://doi.org/10.1007/s00267-012-9986-3Sebastiá M, Rodilla M, Sanchis J, Altur V (2012) Influence of nutrient inputs from a wetland dominated by agriculture on the phytoplankton community in a shallow harbour at the Spanish Mediterranean coast. Agric Ecosyst Environ 152:10–20. https://doi.org/10.1016/j.agee.2012.02.006Seoane S, Garmendia M, Revilla M, Borja Á, Franco J, Orive E, Valencia V (2011) Phytoplankton pigments and epifluorescence microscopy as tools for ecological status assessment in coastal and estuarine waters, within the Water Framework. Mar Pollut 62:1484–1497. https://doi.org/10.1016/j.marpolbul.2011.04.010Sinden A, Sinang SC (2016) Cyanobacteria in aquaculture systems: linking the occurrence, abundance and toxicity with rising temperatures. Int J Environ Sci Technol 13:2855–2862. https://doi.org/10.1007/s13762-016-1112-2Sospedra J, Niencheski LFH, Falco S, Andrade CF, Attisano KK, Rodilla M (2017) Identifying the main sources of silicate in coastal waters of the Southern Gulf of Valencia (Western Mediterranean Sea). Oceanologia. https://doi.org/10.1016/j.oceano.2017.07.004Strickland J (1960) Measuring the production of marine phytoplankton. Bull Fish Res Bd Canada 122:172Ter Braak CJF (1994) Canonical community ordination. Part I: basic theory and linear methods. Écoscience 1:127–140. https://doi.org/10.1080/11956860.1994.11682237Ter Braak C, Smilauer P (2002) CANOCO reference manual and CanoDraw for Windows user’s guide: software for canonical community ordination (version 4.5). http://library.wur.nl/WebQuery/wurpubs/wever/341885 . Accessed 19 July 2017Utermohl M (1985) Zur Vervollkommnung der quantitative Phytoplankton-Methodik. Limnologie 9:1–38Van Wyk P, Scarpa J (1999) Water quality requirements and management. In: Institution Harbor Branch Oceanographic (ed) Farming marine shrimp in recirculating freshwater systems. Florida Department of Agriculture and Consumer Services, Florida, pp 128–138Vinatea L, Gálvez AO, Browdy CL, Stokes A, Venero J, Haveman J, Lewis BL, Lawson A, Shuler A, Leffler JW (2010) Photosynthesis, water respiration and growth performance of Litopenaeus vannamei in a super-intensive raceway culture with zero water exchange: interaction of water quality variables. Aquac Eng 42:17–24. https://doi.org/10.1016/j.aquaeng.2009.09.001Wright S, Jeffrey S, Mantoura R (1991) Improved HPLC method for the analysis of chlorophylls and carotenoids from marine phytoplankton. Mar Ecol Prog Ser 77:186–196Yu H, Jia S, Dai Y (2009) Growth characteristics of the cyanobacterium Nostoc flagelliforme in photoautotrophic, mixotrophic and heterotrophic cultivation. J Appl Phycol 21:127–133. https://doi.org/10.1007/s10811-008-9341-5Yusoff FM, Zubaidah MS, Matias HB, Kwan TS (2002) Phytoplankton succession in intensive marine shrimp culture ponds treated with a commercial bacterial product. Aquac Res 33:269–278. https://doi.org/10.1046/j.1355-557x.2002.00671.
Identification and Validation of Novel Cerebrospinal Fluid Biomarkers for Staging Early Alzheimer's Disease
Ideally, disease modifying therapies for Alzheimer disease (AD) will be applied during the 'preclinical' stage (pathology present with cognition intact) before severe neuronal damage occurs, or upon recognizing very mild cognitive impairment. Developing and judiciously administering such therapies will require biomarker panels to identify early AD pathology, classify disease stage, monitor pathological progression, and predict cognitive decline. To discover such biomarkers, we measured AD-associated changes in the cerebrospinal fluid (CSF) proteome.CSF samples from individuals with mild AD (Clinical Dementia Rating [CDR] 1) (n = 24) and cognitively normal controls (CDR 0) (n = 24) were subjected to two-dimensional difference-in-gel electrophoresis. Within 119 differentially-abundant gel features, mass spectrometry (LC-MS/MS) identified 47 proteins. For validation, eleven proteins were re-evaluated by enzyme-linked immunosorbent assays (ELISA). Six of these assays (NrCAM, YKL-40, chromogranin A, carnosinase I, transthyretin, cystatin C) distinguished CDR 1 and CDR 0 groups and were subsequently applied (with tau, p-tau181 and Aβ42 ELISAs) to a larger independent cohort (n = 292) that included individuals with very mild dementia (CDR 0.5). Receiver-operating characteristic curve analyses using stepwise logistic regression yielded optimal biomarker combinations to distinguish CDR 0 from CDR>0 (tau, YKL-40, NrCAM) and CDR 1 from CDR<1 (tau, chromogranin A, carnosinase I) with areas under the curve of 0.90 (0.85-0.94 95% confidence interval [CI]) and 0.88 (0.81-0.94 CI), respectively.Four novel CSF biomarkers for AD (NrCAM, YKL-40, chromogranin A, carnosinase I) can improve the diagnostic accuracy of Aβ42 and tau. Together, these six markers describe six clinicopathological stages from cognitive normalcy to mild dementia, including stages defined by increased risk of cognitive decline. Such a panel might improve clinical trial efficiency by guiding subject enrollment and monitoring disease progression. Further studies will be required to validate this panel and evaluate its potential for distinguishing AD from other dementing conditions
The early effects of afforestation on biodiversity of grasslands in Ireland
Abstract The target rate of afforestation in Ireland over the next 30 years is 20,000 ha per year, which would result in an increase of the forest cover from the current 10% to 17%. In order to promote sustainable forest management practices, it is essential to know the composition and conservation value of habitats where afforestation is planned and the effects of subsequent planting upon biodiversity. The objectives of this study were to investigate changes in vegetation composition and diversity of grasslands 5 years after afforestation with Sitka spruce (Picea sitchensis) and determine the primary ecological and management factors responsible for these changes. Species cover, environmental and management data were collected from 16 afforested and unplanted improved and wet grassland site pairs in Ireland. Our results indicate that 5 years after tree planting, there were significant changes in richness, composition, and abundance of species. Competitive and vigorous grasses were more abundant in planted than in unplanted sites, as were generalist species found in both open and wooded habitats, while small-stature shade-sensitive species were less abundant. Vascular plant species richness and Shannon’s diversity index were higher in unplanted wet grassland, than in the planted sites. Bryophyte species richness was higher in planted improved grassland than in unplanted sites. The differences were primarily the result of the exclusion of grazing, ground preparation, changes in nutrient management and drainage for afforestation. Drainage ditches provided a temporary habitat for less competitive species, but the overall effect of drainage was to reduce the diversity of species dependent on wet conditions. Variance partitioning showed differences in the relative influences of environmental and management variables on biodiversity in the two habitats, probably due to the greater pre-afforestation grazing pressure and fertilisation levels in improved grasslands. The differences in biodiversity between planted and unplanted grasslands indicate that afforestation represents a threat to semi-natural habitats where distinctive and highly localised plant communities could potentially occur
Older versus younger adults with gastric cancer receiving perioperative treatment: Results from the CRITICS trial
Aim: To evaluate treatment-related toxicity, treatment compliance, surgical complications and event-free survival (EFS) in older (≥70 years) versus younger (<70 years) adults who underwent perioperative treatment for gastric cancer. Methods: In the CRITICS trial, 788 patients with resectable gastric cancer were randomised before start of any treatment and received preoperative chemotherapy (3 cycles of epirubicin, cisplatin or oxaliplatin and capecitabine), followed by surgery, followed by either postoperative chemotherapy or chemoradiotherapy (45Gy + cisplatin + capecitabine). Results: 172 (22%) patients were older adults. During preoperative chemotherapy, 131 (77%) older adults versus 380 (62%) younger adults experienced severe toxicity (p < 0.001); older adults received significantly lower relative dose intensities (RDIs) for all chemotherapeutic drugs. Equal proportions of older versus younger adults underwent curative surgery: 137 (80%) versus 499 (81%), with comparable postoperative complications and postoperative mortality. Postoperative therapy after curative surgery started in 87 (64%) older adults versus 391 (78%) younger adults (p < 0.001). Incidence of severe toxicity during postoperative chemotherapy was 22 (54%) in older adults versus 113 (59%) in younger adults (p = 0.541); older adults received significantly lower RDIs for all chemotherapeutic drugs. Severe toxicity rates for postoperative chemoradiotherapy were 22 (48%) older adults versus 89 (45%) for younger adults (p = 0.703), with comparable chemotherapy RDIs and radiotherapy dose. Two-year EFS was 53% for older adults versus 51% for younger adults. Conclusion: Perioperative treatment compliance, especially in the postoperative phase, was poorer in older adults compared with younger adults. As comparable proportions of patients underwent curative surgery, future studies should focus on neo-adjuvant treatment. Trial registration: ClinicalTrials.gov identifier: NCT00407186. EudraCT number: 2006–00413032
Effect of Hospital Volume With Respect to Performing Gastric Cancer Resection on Recurrence and Survival: Results From the CRITICS Trial
OBJECTIVE: We examined the association between surgical hospital volume and both overall survival (OS) and disease-free survival (DFS) using data obtained from the international CRITICS (ChemoRadiotherapy after Induction chemotherapy In Cancer of the Stomach) trial. SUMMARY BACKGROUND DATA: In the CRITICS trial, patients with resectable gastric cancer were randomized to receive preoperative chemotherapy followed by adequate gastrectomy and either chemotherapy or chemoradiotherapy. METHODS: Patients in the CRITICS trial who underwent a gastrectomy with curative intent in a Dutch hospital were included in the analysis. The annual number of gastric cancer surgeries performed at the participating hospitals was obtained from the Netherlands Cancer Registry; the hospitals were then classified as low-volume (1-20 surgeries/year) or high-volume (≥21 surgeries/year) and matched with the CRITICS trial data. Univariate and multivariate analyses were then performed to evaluate the hazard ratio (HR) between hospital volume and both OS and DFS. RESULTS: From 2007 through 2015, 788 patients were included in the CRITICS trial. Among these 788 patients, 494 were eligible for our study; the median follow-up was 5.0 years. Five-year OS was 59.2% and 46.1% in the high-volume and low-volume hospitals, respectively. Multivariate analysis revealed that undergoing surgery in a high-volume hospital was associated with higher OS [HR = 0.69, 95% confidence interval (CI) = 0.50-0.94, P = 0.020] and DFS (HR = 0.73, 95% CI: 0.54-0.99, P = 0.040). CONCLUSIONS: In the CRITICS trial, hospitals with a high annual volume of gastric cancer surgery were associated with higher overall and DFS. These findings emphasize the value of centralizing gastric cancer surgeries in the Western world
Study Protocol PROMETHEUS: Prospective Multicenter Study to Evaluate the Correlation Between Safety Margin and Local Recurrence After Thermal Ablation Using Image Co-registration in Patients with Hepatocellular Carcinoma
Purpose: The primary objective is to determine the minimal ablation margin required to achieve a local recurrence rate of 18 years with Barcelona Clinic Liver Cancer stage 0/A hepatocellular carcinoma (or B with a maximum of two lesions < 5 cm each) are eligible. Patients will undergo dual-phase contrast-enhanced computed tomography directly before and after ablation. Ablation margins will be quantitatively assessed using co-registration software, blinding assessors (i.e. two experienced radiologists) for outcome. Presence and location of recurrence are evaluated independently on follow-up scans by two other experienced radiologists, blinded for the quantitative margin analysis. A sample size of 189 tumors (~ 145 patients) is required to show with 80% power that the risk of local recurrence is confidently below 10%. A two-sided binomial z-test will be used to test the null hypothesis that the local recurrence rate is ≥ 10% for patients with a minimal ablation margin ≥ 2 mm. Logistic regression will be used to find the relationship between minimal ablation margins and local recurrence. Kaplan–Meier estimates are used to assess local and overall recurrence, disease-free and overall survival. Discussion: It is expected that this study will result in a clear understanding of the correlation between ablation margins and local recurrence. Using co-registration software in future patients undergoing ablation for hepatocellular carcinoma may improve intraprocedural evaluation of technical success. Trial registration The Netherlands Trial Register (NL9713), https://www.trialregister.nl/trial/9713
Seasonal and regional controls of phytoplankton production along a climate gradient in south-west greenland during ice-cover and ice-free conditions
Across a small geographic area (< 180 km), the region of South West Greenland covers a
natural climate gradient. Variation in temperature and precipitation result in marked
differences in limnology at three discrete locations: ice sheet margin, inland and the coast.
Replicate lakes from each location were sampled for physical (temperature, light), chemical
(dissolved oxygen, pH, conductivity, nutrients) and biological (chlorophyll a (Chl a),
photosynthetic pigments) variables on three occasions within a 12 month period: July - August 2010, April - May 2011 and June - July 2011 spanning ice cover. Variation in ice
phenology was linked to the climate gradient; however phytoplankton production and
community composition did not differ regionally. Large-scale seasonal fluctuations in
temperature and nutrient availability were the strongest predictors of phytoplankton
production, with a shift from nitrate to phosphorus controlled production between ice cover
and ice free conditions. Underlying seasonal drivers, variables predicting production were
unique to each location: ice sheet margin (soluble reactive phosphorus), inland (temperature)
and coast (silicate) and reflect local differences in nutrient availability. Results from the
current study have important consequences when controls over phytoplankton production in Arctic lakes are inferred from a limited number of sites, but up-scaled to represent pan-Arctic trends