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Slik, J. W. Ferry ; Franklin, Janet ; Arroyo-Rodríguez, Víctor ; Field, Richard ; Aguilar, Salomon ; Aguirre, Nikolay ; Ahumada, Jorge ; Aiba, Shin-Ichiro ; Alves, Luciana F. ; Anitha, Kamalakumari ; Avella, Andres ; Mora, Francisco ; Aymard, Gerardo A. ; Báez, Selene ; Balvanera, Patricia ; Bastian, Meredith L. ; Bastin, Jean-François ; Bellingham, Peter ; van den Berg, Eduardo ; da Conceição Bispo, Polyanna ; Boeckx, Pascal ; Böhning-Gaese, Katrin ; Bongers, Frans ; Boyle, Brad ; Brambach, Fabian ; Brearley, Francis Q. ; Brown, Sandra ; Chai, Shauna-Lee ; Chazdon, Robin L. ; Chen, Shengbin ; Chhang, Phourin ; Chuyong, George ; Ewangog, Corneille ; Coronado, Indiana ; Cristóbal-Azkarate, Jurgi ; Culmsee, Heike ; Damas, Kipiro ; Dattaraja, Handanakere Shivaramaiah ; Davidar, Priya ; DeWalt, Saara J. ; Din, Hazimah ; Drake, Donald R. ; Duque, Alvaro ; Durigan, Giselda ; Eichhorn, Karl ; Schmidt Eler, Eduardo ; Enoki, Tsutomu ; Ensslin, Andreas ; Fandohan, Adandé Belarmain ; Farwig, Nina ; Feeley, Kenneth J. ; Fischer, Markus ; Forshed, Olle ; Garcia, Queila Souza ; Garkoti, Satish Chandra ; Gillespie, Thomas William ; Gillet, Jean-Francois ; Gonmadje, Christelle ; Granzow-de la Cerda, Iñigo ; Griffith, Daniel M. ; Grogan, James ; Hakeem, Khalid Rehman ; Harris, David J. ; Harrison, Rhett D. ; Hector, Andy ; Hemp, Andreas ; Homeier, Jürgen ; Hussain, M. Shah ; Ibarra Manríquez, Guillermo ; Hanum, I. Faridah ; Imai, Nobuo ; Jansen, Patrick A. ; Joly, Carlos Alfredo ; Joseph, Shijo ; Kartawinata, Kuswata ; Kearsley, Elizabeth ; Kelly, Daniel L. ; Kessler, Michael ; Killeen, Timothy J. ; Kooyman, Robert ; Laumonier, Yves ; Laurance, Susan G. ; Laurance, William F. ; Lawes, Michael J. ; Letcher, Susan G. ; Lindsell, Jeremy ; Lovett, Jon ; Lozada, Jose ; Lu, Xinghui ; Lykke, Anne Mette ; Bin Mahmud, Khairil ; Mahayani, Ni Putu Diana ; Mansor, Asyraf ; Marshall, Andrew R. ; Martin, Emanuel H. ; Leal Matos, Darley Calderado ; Meave, Jorge A. ; Melo, Felipe P. L. ; Aguirre Mendoza, Zhofre ; Metali, Faizah ; Medjibe, Vincent P. ; Metzger, Jean Paul ; Metzker, Thiago ; Mohandass, Dharmalingam ; Munguía-Rosas, Miguel A. ; Muñoz, Rodrigo ; Nurtjahy, Eddy ; Lenza de Oliveira, Eddie ; Onrizal, Onrizal ; Parolin, Pia ; Parren, Marc ; Parthasarathy, Narayanaswamy ; Paudel, Ekananda ; Perez, Rolando ; Pérez-García, Eduardo A. ; Pommer, Ulf ; Poorter, Lourens ; Qi, Lan ; F. Piedade, Maria Teresa ; Rodrigues Pinto, José Roberto ; Dalberg Poulsen, Axel ; Poulsen, John R. ; Powers, Jennifer S. ; Prasad, Rama Chandra ; Puyravaud, Jean-Philippe ; Rangel, Orlando ; Reitsma, Jan ; S. B. Rocha, Diogo ; Rolim, Samir ; Rovero, Francesco ; Rozak, Andes ; Ruokolainen, Kalle ; Rutishauser, Ervan ; Rutten, Gemma ; Mohd. Said, Mohd. Nizam ; Saiter, Felipe Z. ; Saner, Philippe ; Santos, Braulio ; dos Santos, João Roberto ; Sarker, Swapan Kumar ; Schmitt, Christine B. ; Schöngart, Jochen ; Schulze, Mark ; Sheil, Douglas ; Sist, Plinio ; Souza, Alexandre F. ; Spironello, Wilson Roberto ; Sposito, Tereza ; Steinmetz, Robert ; Stevart, Tariq ; Suganuma, Marcio Seiji ; Sukri, Rahayu ; Sultana, Aisha ; Sukumar, Raman ; Sunderland, Terry ; Supriyadi, Agus ; Suresh, Hebbalalu S. ; Suzuki, Eizi ; Tabarelli, Marcelo ; Tang, Jianwei ; Tanner, Edmund V. J. ; Targhetta, Natalia ; Theilade, Ida ; Thomas, Duncan ; Timberlake, Jonathan ; de Morisson Valeriano, Márcio ; Valkenburg, Johan van ; Do, Tran Van ; Sam, Hoang Van ; Vandermeer, John H. ; Verbeeck, Hans ; Vetaas, Ole Reidar ; Adekunle, Victor ; Vieira, Simone A. ; Webb, Campbell O. ; Webb, Edward L. ; Whitfeld, Timothy ; Wich, Serge ; Williams, John ; Wiser, Susan ; Wittmann, Florian ; Yang, Xiaobo ; Adou Yao, C. Yves ; Yap, Sandra L. ; Zahawie, Rakan A. ; Zakaria, Rahmad ; Zang, Runguo
Knowledge about the biogeographic affinities of the world’s tropical forests helps to better understand regional differences in forest structure, diversity, composition, and dynamics. Such understanding will enable anticipation of region-specific responses to global environmental change. Modern phylogenies, in combination with broad coverage of species inventory data, now allow for global biogeographic analyses that take species evolutionary distance into account. Here we present a classification of the world’s tropical forests based on their phylogenetic similarity. We identify five principal floristic regions and their floristic relationships: (i) Indo-Pacific, (ii) Subtropical, (iii) African, (iv) American, and (v) Dry forests. Our results do not support the traditional neo- versus paleotropical forest division but instead separate the combined American and African forests from their Indo-Pacific counterparts. We also find indications for the existence of a global dry forest region, with representatives in America, Africa, Madagascar, and India. Additionally, a northern-hemisphere Subtropical forest region was identified with representatives in Asia and America, providing support for a link between Asian and American northern-hemisphere forests.
Caudillo-Plath, Lucía ; Rörup, Birte ; Heinritzi, Martin ; Marie, Guillaume ; Simon, Mario ; Wagner, Andrea C. ; Müller, Tatjana ; Granzin, Manuel ; Amorim, António ; Ataei, Farnoush ; Baalbaki, Rima ; Bertozzi, Barbara ; Brasseur, Zoé ; Chiu, Randall ; Chu, Biwu ; Dada, Lubna ; Duplissy, Jonathan ; Finkenzeller, Henning ; Gonzalez Carracedo, Loïc ; He, Xu-Cheng ; Hofbauer, Victoria ; Kong, Weimeng ; Lamkaddam, Houssni ; Lee, Chuan P. ; Lopez, Brandon ; Mahfouz, Naser G. A. ; Makhmutov, Vladimir ; Manninen, Hanna E. ; Marten, Ruby ; Massabò, Dario ; Mauldin, Roy L. ; Mentler, Bernhard ; Molteni, Ugo ; Onnela, Antti ; Pfeifer, Joschka ; Philippov, Maxim ; Piedehierro, Ana A. ; Schervish, Meredith ; Scholz, Wiebke ; Schulze, Benjamin ; Shen, Jiali ; Stolzenburg, Dominik ; Stožkov, Ju. I. ; Surdu, Mihnea ; Tauber, Christian ; Tham, Yee Jun ; Tian, Ping ; Tomé, António ; Vogt, Steffen ; Wang, Mingyi ; Wang, Dongyu S. ; Weber, Stefan K. ; Welti, André ; Yonghong, Wang ; Yusheng, Wu ; Zauner-Wieczorek, Marcel ; Baltensperger, Urs ; El Haddad, Imad ; Flagan, Richard C. ; Hansel, Armin ; Höhler, Kristina ; Kirkby, Jasper ; Kulmala, Markku ; Lehtipalo, Katrianne ; Möhler, Ottmar ; Saathoff, Harald ; Volkamer, Rainer ; Winkler, Paul M. ; Donahue, Neil M. ; Kürten, Christoph Andreas ; Curtius, Joachim
Biogenic organic precursors play an important role in atmospheric new particle formation (NPF). One of the major precursor species is α-pinene, which upon oxidation can form a suite of products covering a wide range of volatilities. Highly oxygenated organic molecules (HOMs) comprise a fraction of the oxidation products formed. While it is known that HOMs contribute to secondary organic aerosol (SOA) formation, including NPF, they have not been well studied in newly formed particles due to their very low mass concentrations. Here we present gas- and particle-phase chemical composition data from experimental studies of α-pinene oxidation, including in the presence of isoprene, at temperatures (−50 and −30 ∘C) and relative humidities (20 % and 60 %) relevant in the upper free troposphere. The measurements took place at the CERN Cosmics Leaving Outdoor Droplets (CLOUD) chamber. The particle chemical composition was analyzed by a thermal desorption differential mobility analyzer (TD-DMA) coupled to a nitrate chemical ionization–atmospheric pressure interface–time-of-flight (CI-APi-TOF) mass spectrometer. CI-APi-TOF was used for particle- and gas-phase measurements, applying the same ionization and detection scheme. Our measurements revealed the presence of C8−10 monomers and C18−20 dimers as the major compounds in the particles (diameter up to ∼ 100 nm). Particularly, for the system with isoprene added, C5 (C5H10O5−7) and C15 compounds (C15H24O5−10) were detected. This observation is consistent with the previously observed formation of such compounds in the gas phase. However, although the C5 and C15 compounds do not easily nucleate, our measurements indicate that they can still contribute to the particle growth at free tropospheric conditions. For the experiments reported here, most likely isoprene oxidation products enhance the growth of particles larger than 15 nm. Additionally, we report on the nucleation rates measured at 1.7 nm (J1.7 nm) and compared with previous studies, we found lower J1.7 nm values, very likely due to the higher α-pinene and ozone mixing ratios used in the present study.
Caudillo-Plath, Lucı́a ; Rörup, Birte ; Heinritzi, Martin ; Marie, Guillaume ; Simon, Mario ; Wagner, Andrea C. ; Müller, Tatjana ; Granzin, Manuel ; Amorim, Antonio ; Ataei, Farnoush ; Baalbaki, Rima ; Bertozzi, Barbara ; Brasseur, Zoé ; Chiu, Randall ; Chu, Biwu ; Dada, Lubna ; Duplissy, Jonathan ; Finkenzeller, Henning ; Gonzalez Carracedo, Loïc ; He, Xu-Cheng ; Hofbauer, Victoria ; Kong, Weimeng ; Lamkaddam, Houssni ; Lee, Chuan P ; Lopez, Brandon ; Mahfouz, Naser G. A. ; Makhmutov, Vladimir ; Manninen, Hanna E. ; Marten, Ruby ; Massabò, Dario ; Mauldin, Roy L. ; Mentler, Bernhard ; Molteni, Ugo ; Onnela, Antti ; Pfeifer, Joschka ; Philippov, Maxim ; Piedehierro, Ana A. ; Schervish, Meredith ; Scholz, Wiebke ; Schulze, Benjamin ; Shen, Jiali ; Stolzenburg, Dominik ; Stožkov, Ju. I. ; Surdu, Mihnea ; Tauber, Christian ; Tham, Yee Jun ; Tian, Ping ; Tomé, António ; Vogt, Steffen ; Wang, Mingyi ; Wang, Dongyu S. ; Weber, Stefan K. ; Welti, André ; Yonghong, Wang ; Yusheng, Wu ; Zauner-Wieczorek, Marcel ; Baltensperger, Urs ; El Haddad, Imad ; Flagan, Richard C. ; Hansel, Armin ; Höhler, Kristina ; Kirkby, Jasper ; Kulmala, Markku ; Lehtipalo, Katrianne ; Möhler, Ottmar ; Saathoff, Harald ; Volkamer, Rainer ; Winkler, Paul M. ; Donahue, Neil M. ; Kürten, Christoph Andreas ; Curtius, Joachim
Biogenic organic precursors play an important role in atmospheric new particle formation (NPF). One of the major precursor species is α-pinene, which upon oxidation can form a suite of products covering a wide range of volatilities. Highly oxygenated organic molecules (HOMs) comprise a fraction of the oxidation products formed. While it is known that HOMs contribute to secondary organic aerosol (SOA) formation, including NPF, they have not been well studied in newly formed particles due to their very low mass concentrations. Here we present gas- and particle-phase chemical composition data from experimental studies of α-pinene oxidation, including in the presence of isoprene, at temperatures (−50 and −30 ∘C) and relative humidities (20 % and 60 %) relevant in the upper free troposphere. The measurements took place at the CERN Cosmics Leaving Outdoor Droplets (CLOUD) chamber. The particle chemical composition was analyzed by a thermal desorption differential mobility analyzer (TD-DMA) coupled to a nitrate chemical ionization–atmospheric pressure interface–time-of-flight (CI-APi-TOF) mass spectrometer. CI-APi-TOF was used for particle- and gas-phase measurements, applying the same ionization and detection scheme. Our measurements revealed the presence of C8−10 monomers and C18−20 dimers as the major compounds in the particles (diameter up to ∼ 100 nm). Particularly, for the system with isoprene added, C5 (C5H10O5−7) and C15 compounds (C15H24O5−10) were detected. This observation is consistent with the previously observed formation of such compounds in the gas phase. However, although the C5 and C15 compounds do not easily nucleate, our measurements indicate that they can still contribute to the particle growth at free tropospheric conditions. For the experiments reported here, most likely isoprene oxidation products enhance the growth of particles larger than 15 nm. Additionally, we report on the nucleation rates measured at 1.7 nm (J1.7 nm) and compared with previous studies, we found lower J1.7 nm values, very likely due to the higher α-pinene and ozone mixing ratios used in the present study.
Al-Shahi Salman, Rustam ; Frantzias, Joseph ; Lee, Robert J. ; Lyden, Patrick D. ; Battey, Thomas W. K. ; Ayres, Alison M. ; Goldstein, Joshua Norkin ; Mayer, Stephan A. ; Steiner, Thorsten ; Wang, Xia ; Arima, Hisatomi ; Hasegawa, Hitoshi ; Oishi, Makoto ; Godoy, Daniel Agustín ; Masotti, Luca ; Dowlatshahi, Dar ; Rodríguez-Luna, David ; Molina, Carlos ; Jang, Dong-Kyu ; Davalos, Antonio ; Castillo, José ; Yao, Xiaoying ; Claassen, Jan ; Volbers, Bastian ; Kazui, Seiji ; Okada, Yasushi ; Fujimoto, Shigeru ; Toyoda, Kazunori ; Li, Qi ; Khoury, Jane ; Delgado, Pilar ; Álvarez-Sabín, José ; Hernández-Guillamon, Mar ; Prats-Sánchez, Luis ; Cai, Chunyan ; Kate, Mahesh ; McCourt, Rebecca ; Venkatasubramanian, Chitra ; Diringer, Michael N. ; Ikeda, Yukio ; Worthmann, Hans ; Ziai, Wendy C. ; D’Esterre, Christopher D. ; Aviv, Richard I. ; Raab, Peter ; Murai, Yasuo ; Zazulia, Allyson R. ; Butcher, Kenneth ; Seyedsaadat, Seyed Mohammad ; Grotta, James C. ; Martí-Fàbregas, Joan ; Montaner, Joan ; Broderick, Joseph ; Yamamoto, Haruko ; Staykov, Dimitre ; Connolly, Edward Sander ; Selim, Magdy ; Leira, Rogelio ; Moon, Byung Hoo ; Demchuk, Andrew M. ; Di Napoli, Mario ; Fujii, Yukihiko ; Anderson, Craig S. ; Rosand, Jonathan
Background: Intracerebral haemorrhage growth is associated with poor clinical outcome and is a therapeutic target for improving outcome. We aimed to determine the absolute risk and predictors of intracerebral haemorrhage growth, develop and validate prediction models, and evaluate the added value of CT angiography.
Methods: In a systematic review of OVID MEDLINE—with additional hand-searching of relevant studies' bibliographies— from Jan 1, 1970, to Dec 31, 2015, we identified observational cohorts and randomised trials with repeat scanning protocols that included at least ten patients with acute intracerebral haemorrhage. We sought individual patient-level data from corresponding authors for patients aged 18 years or older with data available from brain imaging initially done 0·5–24 h and repeated fewer than 6 days after symptom onset, who had baseline intracerebral haemorrhage volume of less than 150 mL, and did not undergo acute treatment that might reduce intracerebral haemorrhage volume. We estimated the absolute risk and predictors of the primary outcome of intracerebral haemorrhage growth (defined as >6 mL increase in intracerebral haemorrhage volume on repeat imaging) using multivariable logistic regression models in development and validation cohorts in four subgroups of patients, using a hierarchical approach: patients not taking anticoagulant therapy at intracerebral haemorrhage onset (who constituted the largest subgroup), patients taking anticoagulant therapy at intracerebral haemorrhage onset, patients from cohorts that included at least some patients taking anticoagulant therapy at intracerebral haemorrhage onset, and patients for whom both information about anticoagulant therapy at intracerebral haemorrhage onset and spot sign on acute CT angiography were known.
Findings: Of 4191 studies identified, 77 were eligible for inclusion. Overall, 36 (47%) cohorts provided data on 5435 eligible patients. 5076 of these patients were not taking anticoagulant therapy at symptom onset (median age 67 years, IQR 56–76), of whom 1009 (20%) had intracerebral haemorrhage growth. Multivariable models of patients with data on antiplatelet therapy use, data on anticoagulant therapy use, and assessment of CT angiography spot sign at symptom onset showed that time from symptom onset to baseline imaging (odds ratio 0·50, 95% CI 0·36–0·70; p<0·0001), intracerebral haemorrhage volume on baseline imaging (7·18, 4·46–11·60; p<0·0001), antiplatelet use (1·68, 1·06–2·66; p=0·026), and anticoagulant use (3·48, 1·96–6·16; p<0·0001) were independent predictors of intracerebral haemorrhage growth (C-index 0·78, 95% CI 0·75–0·82). Addition of CT angiography spot sign (odds ratio 4·46, 95% CI 2·95–6·75; p<0·0001) to the model increased the C-index by 0·05 (95% CI 0·03–0·07).
Interpretation: In this large patient-level meta-analysis, models using four or five predictors had acceptable to good discrimination. These models could inform the location and frequency of observations on patients in clinical practice, explain treatment effects in prior randomised trials, and guide the design of future trials.
Funding: UK Medical Research Council and British Heart Foundation.
Harris, John W. ; Odyniec, Grazyna Janina ; Pugh, Howel G. ; Schroeder, Lee S. ; Tincknell, Mark L. ; Rauch, Wolfgang ; Stock, Reinhard ; Bock, Rudolf ; Brockmann, Robert ; Sandoval, Andres ; Ströbele, Herbert ; Renfordt, Rainer Arno Ernst ; Schall, Dietmar ; Bangert, Dieter ; Sullivan, John P. ; Wolf, Kevin L. ; Dacal, Ángel ; Guerra, C. ; Ortiz, Maria Esther
Vigne, Paula ; Simões, Bruno F. T. ; B. de Menezes, Gabriela ; Fortes, Pedro P. ; Dias, Rafaela V. ; Laurito, Luana D. ; Loureiro, Carla P. ; Moreira-de-Oliveira, Maria Eduarda ; Albertella, Lucy ; Lee, Rico S. C. ; Stangier, Ulrich ; Fontenelle, Leonardo F.
Background: A growing number of studies are questioning the validity of current DSM diagnoses, either as "discrete" or distinct mental disorders and/or as phenotypically homogeneous syndromes. In this study, we investigated how symptom domains in patients with a main diagnosis of obsessive-compulsive disorder (OCD), panic disorder (PD) and social anxiety disorder (SAD) coaggregate. We predicted that symptom domains would be unrelated to DSM diagnostic categories and less likely to cluster with each other as severity increases.
Methods: One-hundred eight treatment seeking patients with a main diagnosis of OCD, SAD or PD were assessed with the Dimensional Obsessive-Compulsive Scale (DOCS), the Social Phobia Inventory (SPIN), the Panic and Agoraphobia Scale (PAS), the Anxiety Sensitivity Index-Revised (ASI-R), and the Beck Depression and Anxiety Inventories (BDI and BAI, respectively). Subscores generated by each scale (herein termed "symptom domains") were used to categorize individuals into mild, moderate and severe subgroups through K-means clusterization and subsequently analysed by means of multiple correspondence analysis.
Results: Broadly, we observed that symptom domains of OCD, SAD or PD tend to cluster on the basis of their severities rather than their DSM diagnostic labels. In particular, symptom domains and disorders were grouped into (1) a single mild "neurotic" syndrome characterized by multiple, closely related and co-occurring mild symptom domains; (2) two moderate (complicated and uncomplicated) "neurotic" syndromes (the former associated with panic disorder); and (3) severe but dispersed "neurotic" symptom domains.
Conlusion: Our findings suggest that symptoms domains of treatment seeking patients with OCD and anxiety disorders tend to be better conceptualized in terms of severity rather than rigid diagnostic boundaries.
El-Helou, Sabine M. ; Biegner, Anika-Kerstin ; Bode, Sebastian ; Ehl, Stephan ; Heeg, Maximilian ; Maccari, Maria E. ; Ritterbusch, Henrike ; Speckmann, Carsten ; Rusch, Stephan ; Scheible, Raphael ; Warnatz, Klaus ; Atschekzei, Faranaz ; Beider, Renata ; Ernst, Diana ; Gerschmann, Stev ; Jablonka, Alexandra ; Mielke, Gudrun ; Schmidt, Reinhold E. ; Schürmann, Gesine ; Sogkas, Georgios ; Baumann, Ulrich ; Klemann, Christian ; Viemann, Dorothee ; Bernuth, Horst von ; Krüger, Renate ; Hanitsch, Leif Gunnar ; Scheibenbogen, Carmen ; Wittke, Kirsten ; Albert, Michael H. ; Eichinger, Anna ; Hauck, Fabian ; Klein, Christoph ; Rack-Hoch, Anita ; Sollinger, Franz ; Avila, Anne ; Borte, Michael ; Borte, Stephan ; Fasshauer, Maria ; Hauenherm, Anja ; Kellner, Nils ; Müller, Anna H. ; Ülzen, Anett ; Bader, Peter ; Bakhtiar, Shahrzad ; Lee, Jae-Yun ; Heß, Ursula ; Schubert, Ralf ; Wölke, Sandra ; Zielen, Stefan ; Ghosh, Sujal ; Laws, Hans-Jürgen ; Neubert, Jennifer ; Oommen, Prasad Thomas ; Hönig, Manfred ; Schulz, Ansgar ; Steinmann, Sandra ; Schwarz, Klaus ; Dückers, Gregor ; Lamers, Beate ; Langemeyer, Vanessa ; Niehues, Tim ; Shai, Sonu ; Graf, Dagmar ; Müglich, Carmen ; Schmalzing, Marc ; Schwaneck, Eva C. ; Tony, Hans-Peter ; Dirks, Johannes ; Haase, Gabriele ; Liese, Johannes G. ; Morbach, Henner ; Föll, Dirk ; Hellige, Antje ; Wittkowski, Helmut ; Masjosthusmann, Katja ; Mohr, Michael ; Geberzahn, Linda ; Hedrich, Christian Michael ; Müller, Christiane ; Rösen-Wolff, Angela ; Roesler, Joachim ; Zimmermann, Antje ; Behrends, Uta ; Rieber, Nikolaus ; Schauer, Uwe ; Handgretinger, Rupert ; Holzer, Ursula ; Henes, Jörg Christoph ; Kanz, Lothar ; Boesecke, Christoph ; Rockstroh, Jürgen ; Schwarze-Zander, Carolynne ; Wasmuth, Jan-Christian ; Dilloo, Dagmar ; Hülsmann, Brigitte ; Schönberger, Stefan ; Schreiber, Stefan ; Zeuner, Rainald ; Ankermann, Tobias ; Bismarck, Philipp von ; Huppertz, Hans-Iko ; Kaiser-Labusch, Petra ; Greil, Johann ; Jakoby, Donate ; Kulozik, Andreas ; Metzler, Markus ; Naumann-Bartsch, Nora ; Sobik, Bettina ; Graf, Norbert ; Heine, Sabine ; Kobbe, Robin ; Lehmberg, Kai ; Müller, Ingo ; Herrmann, Friedrich ; Horneff, Gerd ; Klein, Ariane ; Peitz, Joachim ; Schmidt, Nadine ; Bielack, Stefan S. ; Groß-Wieltsch, Ute ; Classen, Carl Friedrich ; Klasen, Jessica ; Deutz, Peter ; Kamitz, Dirk ; Lassay, Lisa ; Tenbrock, Klaus ; Wagner, Norbert ; Bernbeck, Benedikt ; Brummel, Bastian ; Lara-Villacanas, Eusebia ; Münstermann, Esther ; Schneider, Dominik T. ; Tietsch, Nadine ; Westkemper, Marco ; Weiß, Michael ; Kramm, Christof M. ; Kühnle, Ingrid ; Kullman, Silke ; Girschick, Hermann ; Specker, Christof ; Vinnemeier-Laubenthal, Elisabeth ; Haenicke, Henriette ; Schulz, Claudia ; Schweigerer, Lothar ; Müller, Thomas G. ; Stiefel, Martina ; Belohradsky, Bernd H. ; Soetedjo, Veronika ; Kindle, Gerhard ; Grimbacher, Bodo
Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs.
Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel.
Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy.
Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment.