Proactive Maintenance Strategy Based on Resilience Empowerment for Complex Buildings

Resilience of the built environment, particularly in complex buildings, is strictly related to the effectiveness of systems and sub-systems that provide the expected features to manage risk scenarios in routine and non-routine conditions. In this perspective, maintenance is therefore a key factor to assure building resilience by keeping systems and equipment in the required operational state. Risk management can be empowered if system resilience and disruptive events are monitored in real-time, and, to this aim, proactive maintenance can nowadays monitor systems resilience with innovative digital tools

Nutrient intake and risk of open-angle glaucoma: the Rotterdam Study

Open-angle glaucoma (OAG) is the commonest cause of irreversible blindness worldwide. Apart from an increased intraocular pressure (IOP), oxidative stress and an impaired ocular blood flow are supposed to contribute to OAG. The aim of this study was to determine whether the dietary intake of nutrients that either have anti-oxidative properties (carotenoids, vitamins, and flavonoids) or influence the blood flow (omega fatty acids and magnesium) is associated with incident OAG. We investigated this in a prospective population-based cohort, the Rotterdam Study. A total of 3502 participants aged 55 years and older for whom dietary data at baseline and ophthalmic data at baseline and follow-up were available and who did not have OAG at baseline were included. The ophthalmic examinations comprised measurements of the IOP and perimetry; dietary intake of nutrients was assessed by validated questionnaires and adjusted for energy intake. Cox proportional hazard regression analysis was applied to calculate hazard ratios of associations between the baseline intake of nutrients and incident OAG, adjusted for age, gender, IOP, IOP-lowering treatment, and body mass index. During an average follow-up of 9.7 years, 91 participants (2.6%) developed OAG. The hazard ratio for retinol equivalents (highest versus lowest tertile) was 0.45 (95% confidence interval 0.23–0.90), for vitamin B1 0.50 (0.25–0.98), and for magnesium 2.25 (1.16–4.38). The effects were stronger after the exclusion of participants taking supplements. Hence, a low intake of retinol equivalents and vitamin B1 (in line with hypothesis) and a high intake of magnesium (less unambiguous to interpret) appear to be associated with an increased risk of OAG

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Volume III. DUNE far detector technical coordination

open966siAcknowledgments This document was prepared by the DUNE collaboration using the resources of the Fermi National Accelerator Laboratory (Fermilab), a U.S. Department of Energy, Office of Science, HEP User Facility. Fermilab is managed by Fermi Research Alliance, LLC (FRA), acting under Contract No. DE-AC02-07CH11359. The DUNE collaboration also acknowledges the international, national, and regional funding agencies supporting the institutions who have contributed to completing this Technical Design Report.The preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay-these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. The Deep Underground Neutrino Experiment (DUNE) is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- A nd dual-phase DUNE liquid argon TPC far detector modules. Volume III of this TDR describes how the activities required to design, construct, fabricate, install, and commission the DUNE far detector modules are organized and managed. This volume details the organizational structures that will carry out and/or oversee the planned far detector activities safely, successfully, on time, and on budget. It presents overviews of the facilities, supporting infrastructure, and detectors for context, and it outlines the project-related functions and methodologies used by the DUNE technical coordination organization, focusing on the areas of integration engineering, technical reviews, quality assurance and control, and safety oversight. Because of its more advanced stage of development, functional examples presented in this volume focus primarily on the single-phase (SP) detector module.openAbi B.; Acciarri R.; Acero M.A.; Adamov G.; Adams D.; Adinolfi M.; Ahmad Z.; Ahmed J.; Alion T.; Monsalve S.A.; Alt C.; Anderson J.; Andreopoulos C.; Andrews M.; Andrianala F.; Andringa S.; Ankowski A.; Antonova M.; Antusch S.; Aranda-Fernandez A.; Ariga A.; Arnold L.O.; Arroyave M.A.; Asaadi J.; Aurisano A.; Aushev V.; Autiero D.; Azfar F.; Back H.; Back J.J.; Backhouse C.; Baesso P.; Bagby L.; Bajou R.; Balasubramanian S.; Baldi P.; Bambah B.; Barao F.; Barenboim G.; Barker G.; Barkhouse W.; Barnes C.; Barr G.; Monarca J.B.; Barros N.; Barrow J.L.; Bashyal A.; Basque V.; Bay F.; Alba J.B.; Beacom J.F.; Bechetoille E.; Behera B.; Bellantoni L.; Bellettini G.; Bellini V.; Beltramello O.; Belver D.; Benekos N.; Neves F.B.; Berger J.; Berkman S.; Bernardini P.; Berner R.M.; Berns H.; Bertolucci S.; Betancourt M.; Bezawada Y.; Bhattacharjee M.; Bhuyan B.; Biagi S.; Bian J.; Biassoni M.; Biery K.; Bilki B.; Bishai M.; Bitadze A.; Blake A.; Siffert B.B.; Blaszczyk F.; Blazey G.; Blucher E.; Boissevain J.; Bolognesi S.; Bolton T.; Bonesini M.; Bongrand M.; Bonini F.; Booth A.; Booth C.; Bordoni S.; Borkum A.; Boschi T.; Bostan N.; Bour P.; Boyd S.; Boyden D.; Bracinik J.; Braga D.; Brailsford D.; Brandt A.; Bremer J.; Brew C.; Brianne E.; Brice S.J.; Brizzolari C.; Bromberg C.; Brooijmans G.; Brooke J.; Bross A.; Brunetti G.; Buchanan N.; Budd H.; Caiulo D.; Calafiura P.; Calcutt J.; Calin M.; Calvez S.; Calvo E.; Camilleri L.; Caminata A.; Campanelli M.; Caratelli D.; Carini G.; Carlus B.; Carniti P.; Terrazas I.C.; Carranza H.; Castillo A.; Castromonte C.; Cattadori C.; Cavalier F.; Cavanna F.; Centro S.; Cerati G.; Cervelli A.; Villanueva A.C.; Chalifour M.; Chang C.; Chardonnet E.; Chatterjee A.; Chattopadhyay S.; Chaves J.; Chen H.; Chen M.; Chen Y.; Cherdack D.; Chi C.; Childress S.; Chiriacescu A.; Cho K.; Choubey S.; Christensen A.; Christian D.; Christodoulou G.; Church E.; Clarke P.; Coan T.E.; Cocco A.G.; Coelho J.; Conley E.; Conrad J.; Convery M.; Corwin L.; Cotte P.; Cremaldi L.; Cremonesi L.; Crespo-Anadon J.I.; Cristaldo E.; Cross R.; Cuesta C.; Cui Y.; Cussans D.; Dabrowski M.; Motta H.D.; Peres L.D.S.; David Q.; Davies G.S.; Davini S.; Dawson J.; De K.; Almeida R.M.D.; Debbins P.; Bonis I.D.; Decowski M.; Gouvea A.D.; Holanda P.C.D.; Astiz I.L.D.I.; Deisting A.; Jong P.D.; Delbart A.; Delepine D.; Delgado M.; Dell'acqua A.; Lurgio P.D.; Neto J.R.D.M.; Demuth D.M.; Dennis S.; Densham C.; Deptuch G.; Roeck A.D.; Romeri V.D.; Vries J.D.; Dharmapalan R.; Dias M.; Diaz F.; Diaz J.; Domizio S.D.; Giulio L.D.; Ding P.; Noto L.D.; Distefano C.; Diurba R.; Diwan M.; Djurcic Z.; Dokania N.; Dolinski M.; Domine L.; Douglas D.; Drielsma F.; Duchesneau D.; Duffy K.; Dunne P.; Durkin T.; Duyang H.; Dvornikov O.; Dwyer D.; Dyshkant A.; Eads M.; Edmunds D.; Eisch J.; Emery S.; Ereditato A.; Escobar C.; Sanchez L.E.; Evans J.J.; Ewart E.; Ezeribe A.C.; Fahey K.; Falcone A.; Farnese C.; Farzan Y.; Felix J.; Fernandez-Martinez E.; Menendez P.F.; Ferraro F.; Fields L.; Filkins A.; Filthaut F.; Fitzpatrick R.S.; Flanagan W.; Fleming B.; Flight R.; Fowler J.; Fox W.; Franc J.; Francis K.; Franco D.; Freeman J.; Freestone J.; Fried J.; Friedland A.; Fuess S.; Furic I.; Furmanski A.P.; Gago A.; Gallagher H.; Gallego-Ros A.; Gallice N.; Galymov V.; Gamberini E.; Gamble T.; Gandhi R.; Gandrajula R.; Gao S.; Garcia-Gamez D.; Garcia-Peris M.A.; Gardiner S.; Gastler D.; Ge G.; Gelli B.; Gendotti A.; Gent S.; Ghorbani-Moghaddam Z.; Gibin D.; Gil-Botella I.; Girerd C.; Giri A.; Gnani D.; Gogota O.; Gold M.; Gollapinni S.; Gollwitzer K.; Gomes R.A.; Bermeo L.G.; Fajardo L.S.G.; Gonnella F.; Gonzalez-Cuevas J.; Goodman M.C.; Goodwin O.; Goswami S.; Gotti C.; Goudzovski E.; Grace C.; Graham M.; Gramellini E.; Gran R.; Granados E.; Grant A.; Grant C.; Gratieri D.; Green P.; Green S.; Greenler L.; Greenwood M.; Greer J.; Griffith C.; Groh M.; Grudzinski J.; Grzelak K.; Gu W.; Guarino V.; Guenette R.; Guglielmi A.; Guo B.; Guthikonda K.; Gutierrez R.; Guzowski P.; Guzzo M.M.; Gwon S.; Habig A.; Hackenburg A.; Hadavand H.; Haenni R.; Hahn A.; Haigh J.; Haiston J.; Hamernik T.; Hamilton P.; Han J.; Harder K.; Harris D.A.; Hartnell J.; Hasegawa T.; Hatcher R.; Hazen E.; Heavey A.; Heeger K.M.; Hennessy K.; Henry S.; Morquecho M.H.; Herner K.; Hertel L.; Hesam A.S.; Hewes J.; Pichardo A.H.; Hill T.; Hillier S.J.; Himmel A.; Hoff J.; Hohl C.; Holin A.; Hoppe E.; Horton-Smith G.A.; Hostert M.; Hourlier A.; Howard B.; Howell R.; Huang J.; Huang J.; Hugon J.; Iles G.; Iliescu A.M.; Illingworth R.; Ioannisian A.; Itay R.; Izmaylov A.; James E.; Jargowsky B.; Jediny F.; Jesus-Valls C.; Ji X.; Jiang L.; Jimenez S.; Jipa A.; Joglekar A.; Johnson C.; Johnson R.; Jones B.; Jones S.; Jung C.; Junk T.; Jwa Y.; Kabirnezhad M.; Kaboth A.; Kadenko I.; Kamiya F.; Karagiorgi G.; Karcher A.; Karolak M.; Karyotakis Y.; Kasai S.; Kasetti S.P.; Kashur L.; Kazaryan N.; Kearns E.; Keener P.; Kelly K.J.; Kemp E.; Ketchum W.; Kettell S.; Khabibullin M.; Khotjantsev A.; Khvedelidze A.; Kim D.; King B.; Kirby B.; Kirby M.; Klein J.; Koehler K.; Koerner L.W.; Kohn S.; Koller P.P.; Kordosky M.; Kosc T.; Kose U.; Kostelecky V.; Kothekar K.; Krennrich F.; Kreslo I.; Kudenko Y.; Kudryavtsev V.; Kulagin S.; Kumar J.; Kumar R.; Kuruppu C.; Kus V.; Kutter T.; Lambert A.; Lande K.; Lane C.E.; Lang K.; Langford T.; Lasorak P.; Last D.; Lastoria C.; Laundrie A.; Lawrence A.; Lazanu I.; Lazur R.; Le T.; Learned J.; Lebrun P.; Miotto G.L.; Lehnert R.; De Oliveira M.L.; Leitner M.; Leyton M.; Li L.; Li S.; Li S.; Li T.; Li Y.; Liao H.; Lin C.; Lin S.; Lister A.; Littlejohn B.R.; Liu J.; Lockwitz S.; Loew T.; Lokajicek M.; Lomidze I.; Long K.; Loo K.; Lorca D.; Lord T.; Losecco J.; Louis W.C.; Luk K.; Luo X.; Lurkin N.; Lux T.; Luzio V.P.; MacFarland D.; MacHado A.; MacHado P.; MacIas C.; MacIer J.; Maddalena A.; Madigan P.; Magill S.; Mahn K.; Maio A.; Maloney J.A.; Mandrioli G.; Maneira J.C.; Manenti L.; Manly S.; Mann A.; Manolopoulos K.; Plata M.M.; Marchionni A.; Marciano W.; Marfatia D.; Mariani C.; Maricic J.; Marinho F.; Marino A.D.; Marshak M.; Marshall C.; Marshall J.; Marteau J.; Martin-Albo J.; Martinez N.; Caicedo D.A.M.; Martynenko S.; Mason K.; Mastbaum A.; Masud M.; Matsuno S.; Matthews J.; Mauger C.; Mauri N.; Mavrokoridis K.; Mazza R.; Mazzacane A.; Mazzucato E.; McCluskey E.; McConkey N.; McFarland K.S.; McGrew C.; McNab A.; Mefodiev A.; Mehta P.; Melas P.; Mellinato M.; Mena O.; Menary S.; Mendez H.; Menegolli A.; Meng G.; Messier M.; Metcalf W.; Mewes M.; Meyer H.; Miao T.; Michna G.; Miedema T.; Migenda J.; Milincic R.; Miller W.; Mills J.; Milne C.; Mineev O.; Miranda O.G.; Miryala S.; Mishra C.; Mishra S.; Mislivec A.; Mladenov D.; Mocioiu I.; Moffat K.; Moggi N.; Mohanta R.; Mohayai T.A.; Mokhov N.; Molina J.A.; Bueno L.M.; Montanari A.; Montanari C.; Montanari D.; Zetina L.M.M.; Moon J.; Mooney M.; Moor A.; Moreno D.; Morgan B.; Morris C.; Mossey C.; Motuk E.; Moura C.A.; Mousseau J.; Mu W.; Mualem L.; Mueller J.; Muether M.; Mufson S.; Muheim F.; Muir A.; Mulhearn M.; Muramatsu H.; Murphy S.; Musser J.; Nachtman J.; Nagu S.; Nalbandyan M.; Nandakumar R.; Naples D.; Narita S.; Navas-Nicolas D.; Nayak N.; Nebot-Guinot M.; Necib L.; Negishi K.; Nelson J.K.; Nesbit J.; Nessi M.; Newbold D.; Newcomer M.; Newhart D.; Nichol R.; Niner E.; Nishimura K.; Norman A.; Northrop R.; Novella P.; Nowak J.A.; Oberling M.; Campo A.O.D.; Olivier A.; Onel Y.; Onishchuk Y.; Ott J.; Pagani L.; Pakvasa S.; Palamara O.; Palestini S.; Paley J.M.; Pallavicini M.; Palomares C.; Pantic E.; Paolone V.; Papadimitriou V.; Papaleo R.; Papanestis A.; Paramesvaran S.; Parke S.; Parsa Z.; Parvu M.; Pascoli S.; Pasqualini L.; Pasternak J.; Pater J.; Patrick C.; Patrizii L.; Patterson R.B.; Patton S.; Patzak T.; Paudel A.; Paulos B.; Paulucci L.; Pavlovic Z.; Pawloski G.; Payne D.; Pec V.; Peeters S.J.; Penichot Y.; Pennacchio E.; Penzo A.; Peres O.L.; Perry J.; Pershey D.; Pessina G.; Petrillo G.; Petta C.; Petti R.; Piastra F.; Pickering L.; Pietropaolo F.; Pillow J.; Plunkett R.; Poling R.; Pons X.; Poonthottathil N.; Pordes S.; Potekhin M.; Potenza R.; Potukuchi B.V.; Pozimski J.; Pozzato M.; Prakash S.; Prakash T.; Prince S.; Prior G.; Pugnere D.; Qi K.; Qian X.; Raaf J.; Raboanary R.; Radeka V.; Rademacker J.; Radics B.; Rafique A.; Raguzin E.; Rai M.; Rajaoalisoa M.; Rakhno I.; Rakotondramanana H.; Rakotondravohitra L.; Ramachers Y.; Rameika R.; Delgado M.R.; Ramson B.; Rappoldi A.; Raselli G.; Ratoff P.; Ravat S.; Razafinime H.; Real J.; Rebel B.; Redondo D.; Reggiani-Guzzo M.; Rehak T.; Reichenbacher J.; Reitzner S.D.; Renshaw A.; Rescia S.; Resnati F.; Reynolds A.; Riccobene G.; Rice L.C.; Rielage K.; Rigaut Y.; Rivera D.; Rochester L.; Roda M.; Rodrigues P.; Alonso M.R.; Rondon J.R.; Roeth A.; Rogers H.; Rosauro-Alcaraz S.; Rossella M.; Rout J.; Roy S.; Rubbia A.; Rubbia C.; Russell B.; Russell J.; Ruterbories D.; Saakyan R.; Sacerdoti S.; Safford T.; Sahu N.; Sala P.; Samios N.; Sanchez M.; Sanders D.A.; Sankey D.; Santana S.; Santos-Maldonado M.; Saoulidou N.; Sapienza P.; Sarasty C.; Sarcevic I.; Savage G.; Savinov V.; Scaramelli A.; Scarff A.; Scarpelli A.; Schaffer T.; Schellman H.; Schlabach P.; Schmitz D.; Scholberg K.; Schukraft A.; Segreto E.; Sensenig J.; Seong I.; Sergi A.; Sergiampietri F.; Sgalaberna D.; Shaevitz M.; Shafaq S.; Shamma M.; Sharma H.R.; Sharma R.; Shaw T.; Shepherd-Themistocleous C.; Shin S.; Shooltz D.; Shrock R.; Simard L.; Simos N.; Sinclair J.; Sinev G.; Singh J.; Singh V.; Sipos R.; Sippach F.; Sirri G.; Sitraka A.; Siyeon K.; Smargianaki D.; Smith A.; Smith A.; Smith E.; Smith P.; Smolik J.; Smy M.; Snopok P.; Nunes M.S.; Sobel H.; Soderberg M.; Salinas C.J.S.; Soldner-Rembold S.; Solomey N.; Solovov V.; Sondheim W.E.; Sorel M.; Soto-Oton J.; Sousa A.; Soustruznik K.; Spagliardi F.; Spanu M.; Spitz J.; Spooner N.J.; Spurgeon K.; Staley R.; Stancari M.; Stanco L.; Steiner H.; Stewart J.; Stillwell B.; Stock J.; Stocker F.; Stokes T.; Strait M.; Strauss T.; Striganov S.; Stuart A.; Summers D.; Surdo A.; Susic V.; Suter L.; Sutera C.; Svoboda R.; Szczerbinska B.; Szelc A.; Talaga R.; Tanaka H.; Oregui B.T.; Tapper A.; Tariq S.; Tatar E.; Tayloe R.; Teklu A.; Tenti M.; Terao K.; Ternes C.A.; Terranova F.; Testera G.; Thea A.; Thompson J.L.; Thorn C.; Timm S.; Tonazzo A.; Torti M.; Tortola M.; Tortorici F.; Totani D.; Toups M.; Touramanis C.; Trevor J.; Trzaska W.H.; Tsai Y.T.; Tsamalaidze Z.; Tsang K.; Tsverava N.; Tufanli S.; Tull C.; Tyley E.; Tzanov M.; Uchida M.A.; Urheim J.; Usher T.; Vagins M.; Vahle P.; Valdiviesso G.; Valencia E.; Vallari Z.; Valle J.W.; Vallecorsa S.; Berg R.V.; De Water R.G.V.; Forero D.V.; Varanini F.; Vargas D.; Varner G.; Vasel J.; Vasseur G.; Vaziri K.; Ventura S.; Verdugo A.; Vergani S.; Vermeulen M.A.; Verzocchi M.; De Souza H.V.; Vignoli C.; Vilela C.; Viren B.; Vrba T.; Wachala T.; Waldron A.V.; Wallbank M.; Wang H.; Wang J.; Wang Y.; Wang Y.; Warburton K.; Warner D.; Wascko M.; Waters D.; Watson A.; Weatherly P.; Weber A.; Weber M.; Wei H.; Weinstein A.; Wenman D.; Wetstein M.; While M.R.; White A.; Whitehead L.H.; Whittington D.; Wilking M.J.; Wilkinson C.; Williams Z.; Wilson F.; Wilson R.J.; Wolcott J.; Wongjirad T.; Wood K.; Wood L.; Worcester E.; Worcester M.; Wret C.; Wu W.; Wu W.; Xiao Y.; Yang G.; Yang T.; Yershov N.; Yonehara K.; Young T.; Yu B.; Yu J.; Zalesak J.; Zambelli L.; Zamorano B.; Zani A.; Zazueta L.; Zeller G.; Zennamo J.; Zeug K.; Zhang C.; Zhao M.; Zhivun E.; Zhu G.; Zimmerman E.D.; Zito M.; Zucchelli S.; Zuklin J.; Zutshi V.; Zwaska R.Abi B.; Acciarri R.; Acero M.A.; Adamov G.; Adams D.; Adinolfi M.; Ahmad Z.; Ahmed J.; Alion T.; Monsalve S.A.; Alt C.; Anderson J.; Andreopoulos C.; Andrews M.; Andrianala F.; Andringa S.; Ankowski A.; Antonova M.; Antusch S.; Aranda-Fernandez A.; Ariga A.; Arnold L.O.; Arroyave M.A.; Asaadi J.; Aurisano A.; Aushev V.; Autiero D.; Azfar F.; Back H.; Back J.J.; Backhouse C.; Baesso P.; Bagby L.; Bajou R.; Balasubramanian S.; Baldi P.; Bambah B.; Barao F.; Barenboim G.; Barker G.; Barkhouse W.; Barnes C.; Barr G.; Monarca J.B.; Barros N.; Barrow J.L.; Bashyal A.; Basque V.; Bay F.; Alba J.B.; Beacom J.F.; Bechetoille E.; Behera B.; Bellantoni L.; Bellettini G.; Bellini V.; Beltramello O.; Belver D.; Benekos N.; Neves F.B.; Berger J.; Berkman S.; Bernardini P.; Berner R.M.; Berns H.; Bertolucci S.; Betancourt M.; Bezawada Y.; Bhattacharjee M.; Bhuyan B.; Biagi S.; Bian J.; Biassoni M.; Biery K.; Bilki B.; Bishai M.; Bitadze A.; Blake A.; Siffert B.B.; Blaszczyk F.; Blazey G.; Blucher E.; Boissevain J.; Bolognesi S.; Bolton T.; Bonesini M.; Bongrand M.; Bonini F.; Booth A.; Booth C.; Bordoni S.; Borkum A.; Boschi T.; Bostan N.; Bour P.; Boyd S.; Boyden D.; Bracinik J.; Braga D.; Brailsford D.; Brandt A.; Bremer J.; Brew C.; Brianne E.; Brice S.J.; Brizzolari C.; Bromberg C.; Brooijmans G.; Brooke J.; Bross A.; Brunetti G.; Buchanan N.; Budd H.; Caiulo D.; Calafiura P.; Calcutt J.; Calin M.; Calvez S.; Calvo E.; Camilleri L.; Caminata A.; Campanelli M.; Caratelli D.; Carini G.; Carlus B.; Carniti P.; Terrazas I.C.; Carranza H.; Castillo A.; Castromonte C.; Cattadori C.; Cavalier F.; Cavanna F.; Centro S.; Cerati G.; Cervelli A.; Villanueva A.C.; Chalifour M.; Chang C.; Chardonnet E.; Chatterjee A.; Chattopadhyay S.; Chaves J.; Chen H.; Chen M.; Chen Y.; Cherdack D.; Chi C.; Childress S.; Chiriacescu A.; Cho K.; Choubey S.; Christensen A.; Christian D.; Christodoulou G.; Church E.; Clarke P.; Coan T.E.; Cocco A.G.; Coelho J.; Conley E.; Conrad J.; Convery M.; Corwin L.; Cotte P.; Cremaldi L.; Cremonesi L.; Crespo-Anadon J.I.; Cristaldo E.; Cross R.; Cuesta C.; Cui Y.; Cussans D.; Dabrowski M.; Motta H.D.; Peres L.D.S.; David Q.; Davies G.S.; Davini S.; Dawson J.; De K.; Almeida R.M.D.; Debbins P.; Bonis I.D.; Decowski M.; Gouvea A.D.; Holanda P.C.D.; Astiz I.L.D.I.; Deisting A.; Jong P.D.; Delbart A.; Delepine D.; Delgado M.; Dell'acqua A.; Lurgio P.D.; Neto J.R.D.M.; Demuth D.M.; Dennis S.; Densham C.; Deptuch G.; Roeck A.D.; Romeri V.D.; Vries J.D.; Dharmapalan R.; Dias M.; Diaz F.; Diaz J.; Domizio S.D.; Giulio L.D.; Ding P.; Noto L.D.; Distefano C.; Diurba R.; Diwan M.; Djurcic Z.; Dokania N.; Dolinski M.; Domine L.; Douglas D.; Drielsma F.; Duchesneau D.; Duffy K.; Dunne P.; Durkin T.; Duyang H.; Dvornikov O.; Dwyer D.; Dyshkant A.; Eads M.; Edmunds D.; Eisch J.; Emery S.; Ereditato A.; Escobar C.; Sanchez L.E.; Evans J.J.; Ewart E.; Ezeribe A.C.; Fahey K.; Falcone A.; Farnese C.; Farzan Y.; Felix J.; Fernandez-Martinez E.; Menendez P.F.; Ferraro F.; Fields L.; Filkins A.; Filthaut F.; Fitzpatrick R.S.; Flanagan W.; Fleming B.; Flight R.; Fowler J.; Fox W.; Franc J.; Francis K.; Franco D.; Freeman J.; Freestone J.; Fried J.; Friedland A.; Fuess S.; Furic I.; Furmanski A.P.; Gago A.; Gallagher H.; Gallego-Ros A.; Gallice N.; Galymov V.; Gamberini E.; Gamble T.; Gandhi R.; Gandrajula R.; Gao S.; Garcia-Gamez D.; Garcia-Peris M.A.; Gardiner S.; Gastler D.; Ge G.; Gelli B.; Gendotti A.; Gent S.; Ghorbani-Moghaddam Z.; Gibin D.; Gil-Botella I.; Girerd C.; Giri A.; Gnani D.; Gogota O.; Gold M.; Gollapinni S.; Gollwitzer K.; Gomes R.A.; Bermeo L.G.; Fajardo L.S.G.; Gonnella F.; Gonzalez-Cuevas J.; Goodman M.C.; Goodwin O.; Goswami S.; Gotti C.; Goudzovski E.; Grace C.; Graham M.; Gramellini E.; Gran R.; Granados E.; Grant A.; Grant C.; Gratieri D.; Green P.; Green S.; Greenler L.; Greenwood M.; Greer J.; Griffith C.; Groh M.; Grudzinski J.; Grzelak K.; Gu W.; Guarino V.; Guenette R.; Guglielmi A.; Guo B.; Guthikonda K.; Gutierrez R.; Guzowski P.; Guzzo M.M.; Gwon S.; Habig A.; Hackenburg A.; Hadavand H.; Haenni R.; Hahn A.; Haigh J.; Haiston J.; Hamernik T.; Hamilton P.; Han J.; Harder K.; Harris D.A.; Hartnell J.; Hasegawa T.; Hatcher R.; Hazen E.; Heavey A.; Heeger K.M.; Hennessy K.; Henry S.; Morquecho M.H.; Herner K.; Hertel L.; Hesam A.S.; Hewes J.; Pichardo A.H.; Hill T.; Hillier S.J.; Himmel A.; Hoff J.; Hohl C.; Holin A.; Hoppe E.; Horton-Smith G.A.; Hostert M.; Hourlier A.; Howard B.; Howell R.; Huang J.; Huang J.; Hugon J.; Iles G.; Iliescu A.M.; Illingworth R.; Ioannisian A.; Itay R.; Izmaylov A.; James E.; Jargowsky B.; Jediny F.; Jesus-Valls C.; Ji X.; Jiang L.; Jimenez S.; Jipa A.; Joglekar A.; Johnson C.; Johnson R.; Jones B.; Jones S.; Jung C.; Junk T.; Jwa Y.; Kabirnezhad M.; Kaboth A.; Kadenko I.; Kamiya F.; Karagiorgi G.; Karcher A.; Karolak M.; Karyotakis Y.; Kasai S.; Kasetti S.P.; Kashur L.; Kazaryan N.; Kearns E.; Keener P.; Kelly K.J.; Kemp E.; Ketchum W.; Kettell S.; Khabibullin M.; Khotjantsev A.; Khvedelidze A.; Kim D.; King B.; Kirby B.; Kirby M.; Klein J.; Koehler K.; Koerner L.W.; Kohn S.; Koller P.P.; Kordosky M.; Kosc T.; Kose U.; Kostelecky V.; Kothekar K.; Krennrich F.; Kreslo I.; Kudenko Y.; Kudryavtsev V.; Kulagin S.; Kumar J.; Kumar R.; Kuruppu C.; Kus V.; Kutter T.; Lambert A.; Lande K.; Lane C.E.; Lang K.; Langford T.; Lasorak P.; Last D.; Lastoria C.; Laundrie A.; Lawrence A.; Lazanu I.; Lazur R.; Le T.; Learned J.; Lebrun P.; Miotto G.L.; Lehnert R.; De Oliveira M.L.; Leitner M.; Leyton M.; Li L.; Li S.; Li S.; Li T.; Li Y.; Liao H.; Lin C.; Lin S.; Lister A.; Littlejohn B.R.; Liu J.; Lockwitz S.; Loew T.; Lokajicek M.; Lomidze I.; Long K.; Loo K.; Lorca D.; Lord T.; Losecco J.; Louis W.C.; Luk K.; Luo X.; Lurkin N.; Lux T.; Luzio V.P.; MacFarland D.; MacHado A.; MacHado P.; MacIas C.; MacIer J.; Maddalena A.; Madigan P.; Magill S.; Mahn K.; Maio A.; Maloney J.A.; Mandrioli G.; Maneira J.C.; Manenti L.; Manly S.; Mann A.; Manolopoulos K.; Plata M.M.; Marchionni A.; Marciano W.; Marfatia D.; Mariani C.; Maricic J.; Marinho F.; Marino A.D.; Marshak M.; Marshall C.; Marshall J.; Marteau J.; Martin-Albo J.; Martinez N.; Caicedo D.A.M.; Martynenko S.; Mason K.; Mastbaum A.; Masud M.; Matsuno S.; Matthews J.; Mauger C.; Mauri N.; Mavrokoridis K.; Mazza R.; Mazzacane A.; Mazzucato E.; McCluskey E.; McConkey N.; McFarland K.S.; McGrew C.; McNab A.; Mefodiev A.; Mehta P.; Melas P.; Mellinato M.; Mena O.; Menary S.; Mendez H.; Menegolli A.; Meng G.; Messier M.; Metcalf W.; Mewes M.; Meyer H.; Miao T.; Michna G.; Miedema T.; Migenda J.; Milincic R.; Miller W.; Mills J.; Milne C.; Mineev O.; Miranda O.G.; Miryala S.; Mishra C.; Mishra S.; Mislivec A.; Mladenov D.; Mocioiu I.; Moffat K.; Moggi N.; Mohanta R.; Mohayai T.A.; Mokhov N.; Molina J.A.; Bueno L.M.; Montanari A.; Montanari C.; Montanari D.; Zetina L.M.M.; Moon J.; Mooney M.; Moor A.; Moreno D.; Morgan B.; Morris C.; Mossey C.; Motuk E.; Moura C.A.; Mousseau J.; Mu W.; Mualem L.; Mueller J.; Muether M.; Mufson S.; Muheim F.; Muir A.; Mulhearn M.; Muramatsu H.; Murphy S.; Musser J.; Nachtman J.; Nagu S.; Nalbandyan M.; Nandakumar R.; Naples D.; Narita S.; Navas-Nicolas D.; Nayak N.; Nebot-Guinot M.; Necib L.; Negishi K.; Nelson J.K.; Nesbit J.; Nessi M.; Newbold D.; Newcomer M.; Newhart D.; Nichol R.; Niner E.; Nishimura K.; Norman A.; Northrop R.; Novella P.; Nowak J.A.; Oberling M.; Campo A.O.D.; Olivier A.; Onel Y.; Onishchuk Y.; Ott J.; Pagani L.; Pakvasa S.; Palamara O.; Palestini S.; Paley J.M.; Pallavicini M.; Palomares C.; Pantic E.; Paolone V.; Papadimitriou V.; Papaleo R.; Papanestis A.; Paramesvaran S.; Parke S.; Parsa Z.; Parvu M.; Pascoli S.; Pasqualini L.; Pasternak J.; Pater J.; Patrick C.; Patrizii L.; Patterson R.B.; Patton S.; Patzak T.; Paudel A.; Paulos B.; Paulucci L.; Pavlovic Z.; Pawloski G.; Payne D.; Pec V.; Peeters S.J.; Penichot Y.; Pennacchio E.; Penzo A.; Peres O.L.; Perry J.; Pershey D.; Pessina G.; Petrillo G.; Petta C.; Petti R.; Piastra F.; Pickering

Supernova neutrino burst detection with the Deep Underground Neutrino Experiment

The Deep Underground Neutrino Experiment (DUNE), a 40-kton underground liquid argon time projection chamber experiment, will be sensitive to the electron-neutrino flavor component of the burst of neutrinos expected from the next Galactic core-collapse supernova. Such an observation will bring unique insight into the astrophysics of core collapse as well as into the properties of neutrinos. The general capabilities of DUNE for neutrino detection in the relevant few- to few-tens-of-MeV neutrino energy range will be described. As an example, DUNE's ability to constrain the νe spectral parameters of the neutrino burst will be considered

'Statins in retinal disease'

Statins are known for their blood cholesterol-lowering effect and are widely used in patients with cardiovascular and metabolic diseases. Research over the past three decades shows that statins have diverse effects on different pathophysiological pathways involved in angiogenesis, inflammation, apoptosis, and anti-oxidation, leading to new therapeutic options. Recently, statins have attracted considerable attention for their immunomodulatory effect. Since immune reactivity has been implicated in a number of retinal diseases, such as uveitis, age-related macular degeneration (AMD) and diabetic retinopathy, there is now a growing body of evidence supporting the beneficial effects of statins in these retinopathies. This review evaluates the relationship between statins and the pathophysiological basis of these diseases, focusing on their potential role in treatment. A PubMed database search and literature review was conducted. Among AMD patients, there is inconsistent evidence regarding protection against development of early AMD or delaying disease progression; though they have been found to reduce the risk of developing choroidal neovascular membranes (CNV). In patients with retinal vein occlusion, there was no evidence to support a therapeutic benefit or a protective role with statins. In patients with diabetic retinopathy, statins demonstrate a reduction in disease progression and improved resolution of diabetic macular oedema (DMO). Among patients with uveitis, statins have a protective effect by reducing the likelihood of uveitis development

Alzheimer's Therapeutics Targeting Amyloid Beta 1-42 Oligomers II: Sigma-2/PGRMC1 Receptors Mediate Abeta 42 Oligomer Binding and Synaptotoxicity

Amyloid beta (Abeta) 1–42 oligomers accumulate in brains of patients with Mild Cognitive Impairment (MCI) and disrupt synaptic plasticity processes that underlie memory formation. Synaptic binding of Abeta oligomers to several putative receptor proteins is reported to inhibit long-term potentiation, affect membrane trafficking and induce reversible spine loss in neurons, leading to impaired cognitive performance and ultimately to anterograde amnesia in the early stages of Alzheimer's disease (AD). We have identified a receptor not previously associated with AD that mediates the binding of Abeta oligomers to neurons, and describe novel therapeutic antagonists of this receptor capable of blocking Abeta toxic effects on synapses in vitro and cognitive deficits in vivo. Knockdown of sigma-2/PGRMC1 (progesterone receptor membrane component 1) protein expression in vitro using siRNA results in a highly correlated reduction in binding of exogenous Abeta oligomers to neurons of more than 90%. Expression of sigma-2/PGRMC1 is upregulated in vitro by treatment with Abeta oligomers, and is dysregulated in Alzheimer's disease patients' brain compared to age-matched, normal individuals. Specific, high affinity small molecule receptor antagonists and antibodies raised against specific regions on this receptor can displace synthetic Abeta oligomer binding to synaptic puncta in vitro and displace endogenous human AD patient oligomers from brain tissue sections in a dose-dependent manner. These receptor antagonists prevent and reverse the effects of Abeta oligomers on membrane trafficking and synapse loss in vitro and cognitive deficits in AD mouse models. These findings suggest sigma-2/PGRMC1 receptors mediate saturable oligomer binding to synaptic puncta on neurons and that brain penetrant, small molecules can displace endogenous and synthetic oligomers and improve cognitive deficits in AD models. We propose that sigma-2/PGRMC1 is a key mediator of the pathological effects of Abeta oligomers in AD and is a tractable target for small molecule disease-modifying therapeutics

Hepatitis C Virus Infection Epidemiology among People Who Inject Drugs in Europe: A Systematic Review of Data for Scaling Up Treatment and Prevention

Background: People who inject drugs (PWID) are a key population affected by hepatitis C virus (HCV). Treatment options are improving and may enhance prevention; however access for PWID may be poor. The availability in the literature of information on seven main topic areas (incidence, chronicity, genotypes, HIV co-infection, diagnosis and treatment uptake, and burden of disease) to guide HCV treatment and prevention scale-up for PWID in the 27 countries of the European Union is systematically reviewed. Methods and Findings: We searched MEDLINE, EMBASE and Cochrane Library for publications between 1 January 2000 and 31 December 2012, with a search strategy of general keywords regarding viral hepatitis, substance abuse and geographic scope, as well as topic-specific keywords. Additional articles were found through structured email consultations with a large European expert network. Data availability was highly variable and important limitations existed in comparability and representativeness. Nine of 27 countries had data on HCV incidence among PWID, which was often high (2.7-66/100 person-years, median 13, Interquartile range (IQR) 8.7–28). Most common HCV genotypes were G1 and G3; however, G4 may be increasing, while the proportion of traditionally ‘difficult to treat’ genotypes (G1+G4) showed large variation (median 53, IQR 43–62). Twelve countries reported on HCV chronicity (median 72, IQR 64–81) and 22 on HIV prevalence in HCV-infected PWID (median 3.9%, IQR 0.2–28). Undiagnosed infection, assessed in five countries, was high (median 49%, IQR 38–64), while of those diagnosed, the proportion entering treatment was low (median 9.5%, IQR 3.5–15). Burden of disease, where assessed, was high and will rise in the next decade. Conclusion: Key data on HCV epidemiology, care and disease burden among PWID in Europe are sparse but suggest many undiagnosed infections and poor treatment uptake. Stronger efforts are needed to improve data availability to guide an increase in HCV treatment among PWID

Experiment Simulation Configurations Approximating DUNE TDR

The Deep Underground Neutrino Experiment (DUNE) is a next-generation long-baseline neutrino oscillation experiment consisting of a high-power, broadband neutrino beam, a highly capable near detector located on site at Fermilab, in Batavia, Illinois, and a massive liquid argon time projection chamber (LArTPC) far detector located at the 4850L of Sanford Underground Research Facility in Lead, South Dakota. The long-baseline physics sensitivity calculations presented in the DUNE Physics TDR, and in a related physics paper, rely upon simulation of the neutrino beam line, simulation of neutrino interactions in the near and far detectors, fully automated event reconstruction and neutrino classification, and detailed implementation of systematic uncertainties. The purpose of this posting is to provide a simplified summary of the simulations that went into this analysis to the community, in order to facilitate phenomenological studies of long-baseline oscillation at DUNE. Simulated neutrino flux files and a GLoBES configuration describing the far detector reconstruction and selection performance are included as ancillary files to this posting. A simple analysis using these configurations in GLoBES produces sensitivity that is similar, but not identical, to the official DUNE sensitivity. DUNE welcomes those interested in performing phenomenological work as members of the collaboration, but also recognizes the benefit of making these configurations readily available to the wider community

Deep Underground Neutrino Experiment (DUNE), Far Detector Technical Design Report, Volume I: Introduction to DUNE

The preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay -- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. The Deep Underground Neutrino Experiment (DUNE) is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- and dual-phase DUNE liquid argon TPC far detector modules. This TDR is intended to justify the technical choices for the far detector that flow down from the high-level physics goals through requirements at all levels of the Project. Volume I contains an executive summary that introduces the DUNE science program, the far detector and the strategy for its modular designs, and the organization and management of the Project. The remainder of Volume I provides more detail on the science program that drives the choice of detector technologies and on the technologies themselves. It also introduces the designs for the DUNE near detector and the DUNE computing model, for which DUNE is planning design reports. Volume II of this TDR describes DUNE's physics program in detail. Volume III describes the technical coordination required for the far detector design, construction, installation, and integration, and its organizational structure. Volume IV describes the single-phase far detector technology. A planned Volume V will describe the dual-phase technology