Publications by authors named "Philip Lieberman"

30 Publications

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ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice.

Authors:
Jean Bousquet Josep M Anto Claus Bachert Tari Haahtela Torsten Zuberbier Wienczyslawa Czarlewski Anna Bedbrook Sinthia Bosnic-Anticevich G Walter Canonica Victoria Cardona Elisio Costa Alvaro A Cruz Marina Erhola Wytske J Fokkens Joao A Fonseca Maddalena Illario Juan-Carlos Ivancevich Marek Jutel Ludger Klimek Piotr Kuna Violeta Kvedariene Ltt Le Désirée E Larenas-Linnemann Daniel Laune Olga M Lourenço Erik Melén Joaquim Mullol Marek Niedoszytko Mikaëla Odemyr Yoshitaka Okamoto Nikos G Papadopoulos Vincenzo Patella Oliver Pfaar Nhân Pham-Thi Christine Rolland Boleslaw Samolinski Aziz Sheikh Mikhail Sofiev Charlotte Suppli Ulrik Ana Todo-Bom Peter-Valentin Tomazic Sanna Toppila-Salmi Ioanna Tsiligianni Arunas Valiulis Erkka Valovirta Maria-Teresa Ventura Samantha Walker Sian Williams Arzu Yorgancioglu Ioana Agache Cezmi A Akdis Rute Almeida Ignacio J Ansotegui Isabella Annesi-Maesano Sylvie Arnavielhe Xavier Basagaña Eric D Bateman Annabelle Bédard Martin Bedolla-Barajas Sven Becker Kazi S Bennoor Samuel Benveniste Karl C Bergmann Michael Bewick Slawomir Bialek Nils E Billo Carsten Bindslev-Jensen Leif Bjermer Hubert Blain Matteo Bonini Philippe Bonniaud Isabelle Bosse Jacques Bouchard Louis-Philippe Boulet Rodolphe Bourret Koen Boussery Fluvio Braido Vitalis Briedis Andrew Briggs Christopher E Brightling Jan Brozek Guy Brusselle Luisa Brussino Roland Buhl Roland Buonaiuto Moises A Calderon Paulo Camargos Thierry Camuzat Luis Caraballo Ana-Maria Carriazo Warner Carr Christine Cartier Thomas Casale Lorenzo Cecchi Alfonso M Cepeda Sarabia Niels H Chavannes Ekaterine Chkhartishvili Derek K Chu Cemal Cingi Jaime Correia de Sousa David J Costa Anne-Lise Courbis Adnan Custovic Biljana Cvetkosvki Gennaro D'Amato Jane da Silva Carina Dantas Dejan Dokic Yves Dauvilliers Giulia De Feo Govert De Vries Philippe Devillier Stefania Di Capua Gerard Dray Ruta Dubakiene Stephen R Durham Mark Dykewicz Motohiro Ebisawa Mina Gaga Yehia El-Gamal Enrico Heffler Regina Emuzyte John Farrell Jean-Luc Fauquert Alessandro Fiocchi Antje Fink-Wagner Jean-François Fontaine José M Fuentes Perez Bilun Gemicioğlu Amiran Gamkrelidze Judith Garcia-Aymerich Philippe Gevaert René Maximiliano Gomez Sandra González Diaz Maia Gotua Nick A Guldemond Maria-Antonieta Guzmán Jawad Hajjam Yunuen R Huerta Villalobos Marc Humbert Guido Iaccarino Despo Ierodiakonou Tomohisa Iinuma Ewa Jassem Guy Joos Ki-Suck Jung Igor Kaidashev Omer Kalayci Przemyslaw Kardas Thomas Keil Musa Khaitov Nikolai Khaltaev Jorg Kleine-Tebbe Rostislav Kouznetsov Marek L Kowalski Vicky Kritikos Inger Kull Stefania La Grutta Lisa Leonardini Henrik Ljungberg Philip Lieberman Brian Lipworth Karin C Lodrup Carlsen Catarina Lopes-Pereira Claudia C Loureiro Renaud Louis Alpana Mair Bassam Mahboub Michaël Makris Joao Malva Patrick Manning Gailen D Marshall Mohamed R Masjedi Jorge F Maspero Pedro Carreiro-Martins Mika Makela Eve Mathieu-Dupas Marcus Maurer Esteban De Manuel Keenoy Elisabete Melo-Gomes Eli O Meltzer Enrica Menditto Jacques Mercier Yann Micheli Neven Miculinic Florin Mihaltan Branislava Milenkovic Dimitirios I Mitsias Giuliana Moda Maria-Dolores Mogica-Martinez Yousser Mohammad Steve Montefort Ricardo Monti Mario Morais-Almeida Ralph Mösges Lars Münter Antonella Muraro Ruth Murray Robert Naclerio Luigi Napoli Leyla Namazova-Baranova Hugo Neffen Kristoff Nekam Angelo Neou Björn Nordlund Ettore Novellino Dieudonné Nyembue Robyn O'Hehir Ken Ohta Kimi Okubo Gabrielle L Onorato Valentina Orlando Solange Ouedraogo Julia Palamarchuk Isabella Pali-Schöll Peter Panzner Hae-Sim Park Gianni Passalacqua Jean-Louis Pépin Ema Paulino Ruby Pawankar Jim Phillips Robert Picard Hilary Pinnock Davor Plavec Todor A Popov Fabienne Portejoie David Price Emmanuel P Prokopakis Fotis Psarros Benoit Pugin Francesca Puggioni Pablo Quinones-Delgado Filip Raciborski Rojin Rajabian-Söderlund Frederico S Regateiro Sietze Reitsma Daniela Rivero-Yeverino Graham Roberts Nicolas Roche Erendira Rodriguez-Zagal Christine Rolland Regina E Roller-Wirnsberger Nelson Rosario Antonino Romano Menachem Rottem Dermot Ryan Johanna Salimäki Mario M Sanchez-Borges Joaquin Sastre Glenis K Scadding Sophie Scheire Peter Schmid-Grendelmeier Holger J Schünemann Faradiba Sarquis Serpa Mohamed Shamji Juan-Carlos Sisul Mikhail Sofiev Dirceu Solé David Somekh Talant Sooronbaev Milan Sova François Spertini Otto Spranger Cristiana Stellato Rafael Stelmach Michel Thibaudon Teresa To Mondher Toumi Omar Usmani Antonio A Valero Rudolph Valenta Marylin Valentin-Rostan Marilyn Urrutia Pereira Rianne van der Kleij Michiel Van Eerd Olivier Vandenplas Tuula Vasankari Antonio Vaz Carneiro Giorgio Vezzani Frédéric Viart Giovanni Viegi Dana Wallace Martin Wagenmann De Yun Wang Susan Waserman Magnus Wickman Dennis M Williams Gary Wong Piotr Wroczynski Panayiotis K Yiallouros Osman M Yusuf Heather J Zar Stéphane Zeng Mario E Zernotti Luo Zhang Nan Shan Zhong Mihaela Zidarn

Allergy 2021 01 23;76(1):168-190. Epub 2020 Oct 23.

University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
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http://dx.doi.org/10.1111/all.14422DOI Listing
January 2021

Next-generation ARIA care pathways for rhinitis and asthma: a model for multimorbid chronic diseases.

Authors:
J Jean Bousquet Holger J Schünemann Alkis Togias Marina Erhola Peter W Hellings Torsten Zuberbier Ioana Agache Ignacio J Ansotegui Josep M Anto Claus Bachert Sven Becker Martin Bedolla-Barajas Michael Bewick Sinthia Bosnic-Anticevich Isabelle Bosse Louis P Boulet Jean Marc Bourrez Guy Brusselle Niels Chavannes Elisio Costa Alvaro A Cruz Wienczyslawa Czarlewski Wytske J Fokkens Joao A Fonseca Mina Gaga Tari Haahtela Maddalena Illario Ludger Klimek Piotr Kuna Violeta Kvedariene L T T Le Desiree Larenas-Linnemann Daniel Laune Olga M Lourenço Enrica Menditto Joaquin Mullol Yashitaka Okamoto Nikos Papadopoulos Nhân Pham-Thi Robert Picard Hilary Pinnock Nicolas Roche Regina E Roller-Wirnsberger Christine Rolland Boleslaw Samolinski Aziz Sheikh Sanna Toppila-Salmi Ioanna Tsiligianni Arunas Valiulis Erkka Valovirta Tuula Vasankari Maria-Teresa Ventura Samantha Walker Sian Williams Cezmi A Akdis Isabella Annesi-Maesano Sylvie Arnavielhe Xavier Basagana Eric Bateman Anna Bedbrook K S Bennoor Samuel Benveniste Karl C Bergmann Slawomir Bialek Nils Billo Carsten Bindslev-Jensen Leif Bjermer Hubert Blain Mateo Bonini Philippe Bonniaud Jacques Bouchard Vitalis Briedis Christofer E Brightling Jan Brozek Roland Buhl Roland Buonaiuto Giorgo W Canonica Victoria Cardona Ana M Carriazo Warner Carr Christine Cartier Thomas Casale Lorenzo Cecchi Alfonso M Cepeda Sarabia Eka Chkhartishvili Derek K Chu Cemal Cingi Elaine Colgan Jaime Correia de Sousa Anne Lise Courbis Adnan Custovic Biljana Cvetkosvki Gennaro D'Amato Jane da Silva Carina Dantas Dejand Dokic Yves Dauvilliers Antoni Dedeu Giulia De Feo Philippe Devillier Stefania Di Capua Marc Dykewickz Ruta Dubakiene Motohiro Ebisawa Yaya El-Gamal Esben Eller Regina Emuzyte John Farrell Antjie Fink-Wagner Alessandro Fiocchi Jean F Fontaine Bilun Gemicioğlu Peter Schmid-Grendelmeir Amiran Gamkrelidze Judith Garcia-Aymerich Maximiliano Gomez Sandra González Diaz Maia Gotua Nick A Guldemond Maria-Antonieta Guzmán Jawad Hajjam John O'B Hourihane Marc Humbert Guido Iaccarino Despo Ierodiakonou Maddalena Illario Juan C Ivancevich Guy Joos Ki-Suck Jung Marek Jutel Igor Kaidashev Omer Kalayci Przemyslaw Kardas Thomas Keil Mussa Khaitov Nikolai Khaltaev Jorg Kleine-Tebbe Marek L Kowalski Vicky Kritikos Inger Kull Lisa Leonardini Philip Lieberman Brian Lipworth Karin C Lodrup Carlsen Claudia C Loureiro Renaud Louis Alpana Mair Gert Marien Bassam Mahboub Joao Malva Patrick Manning Esteban De Manuel Keenoy Gailen D Marshall Mohamed R Masjedi Jorge F Maspero Eve Mathieu-Dupas Poalo M Matricardi Eric Melén Elisabete Melo-Gomes Eli O Meltzer Enrica Menditto Jacques Mercier Neven Miculinic Florin Mihaltan Branislava Milenkovic Giuliana Moda Maria-Dolores Mogica-Martinez Yousser Mohammad Steve Montefort Ricardo Monti Mario Morais-Almeida Ralf Mösges Lars Münter Antonella Muraro Ruth Murray Robert Naclerio Luigi Napoli Leila Namazova-Baranova Hugo Neffen Kristoff Nekam Angelo Neou Enrico Novellino Dieudonné Nyembue Robin O'Hehir Ken Ohta Kimi Okubo Gabrielle Onorato Solange Ouedraogo Isabella Pali-Schöll Susanna Palkonen Peter Panzner Hae-Sim Park Jean-Louis Pépin Ana-Maria Pereira Oliver Pfaar Ema Paulino Jim Phillips Robert Picard Davor Plavec Ted A Popov Fabienne Portejoie David Price Emmanuel P Prokopakis Benoit Pugin Filip Raciborski Rojin Rajabian-Söderlund Sietze Reitsma Xavier Rodo Antonino Romano Nelson Rosario Menahenm Rottem Dermot Ryan Johanna Salimäki Mario M Sanchez-Borges Juan-Carlos Sisul Dirceu Solé David Somekh Talant Sooronbaev Milan Sova Otto Spranger Cristina Stellato Rafael Stelmach Charlotte Suppli Ulrik Michel Thibaudon Teresa To Ana Todo-Bom Peter V Tomazic Antonio A Valero Rudolph Valenta Marylin Valentin-Rostan Rianne van der Kleij Olivier Vandenplas Giorgio Vezzani Frédéric Viart Giovanni Viegi Dana Wallace Martin Wagenmann De Y Wang Susan Waserman Magnus Wickman Dennis M Williams Gary Wong Piotr Wroczynski Panayiotis K Yiallouros Arzu Yorgancioglu Osman M Yusuf Heahter J Zar Stéphane Zeng Mario Zernotti Luo Zhang Nan S Zhong Mihaela Zidarn

Clin Transl Allergy 2019 9;9:44. Epub 2019 Sep 9.

260University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.

Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy.

Main Body: As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Santé as a Good Practice in the field of digitally-enabled, integrated, person-centred care.

Conclusion: In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.
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http://dx.doi.org/10.1186/s13601-019-0279-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734297PMC
September 2019

The antiquity and evolution of the neural bases of rhythmic activity.

Authors:
Philip Lieberman

Ann N Y Acad Sci 2019 10 1;1453(1):114-124. Epub 2019 Aug 1.

Department of Cognitive, Linguistic, and Psychological Sciences, Brown University, Providence, Rhode Island.

The evolution of the anatomy and neural circuits that regulate the rhythm of speech can be traced back to the Devonian age, 400 million years ago. Epigenetic processes 100 million years later modified these circuits. Natural selection on similar genetic processes occurred during the evolution of archaic hominins and humans. The lungs and larynx-anatomy that produces the rhythmic fundamental frequency patterns of speech-have a deep evolutionary history. Neural circuits linking the cortex, basal ganglia, and other subcortical structures plan, sequence, and execute motor as well as cognitive acts. These neural circuits generate the rhythm of speech, singing, and chanting. The human form of the transcription factor FOXP2 increased synaptic connectivity and plasticity in basal ganglia circuits, enhancing motor control and cognitive and linguistic capabilities in humans as well as Neanderthals. The archeological record also suggests that Neanderthals passed spoken language. Homologous circuits existed in amphibians. In songbirds, the avian form of FOXP2 acted on similar neural circuits allowing birds to learn and produce new songs. Current studies point to natural selection on genetic events enhancing these and other neural circuits to yield fully human rhythmic speech, and motor, cognitive, and linguistic capabilities, rather than the saltation proposed by Noam Chomsky.
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http://dx.doi.org/10.1111/nyas.14199DOI Listing
October 2019

Guiding Principles for the Recognition, Diagnosis, and Management of Infants with Anaphylaxis: An Expert Panel Consensus.

J Allergy Clin Immunol Pract 2019 04 5;7(4):1148-1156.e5. Epub 2019 Feb 5.

Division of Allergy and Immunology, University of Tennessee Health Science Center, Memphis, Tenn.

Infant anaphylaxis is an emerging risk, with food allergy the most common cause. Although the presentation of anaphylaxis involves the same systems as in older children and adults, there are real-world challenges to identifying symptoms of an allergic emergency in nonverbal children, as well as implementing optimal treatment. Recognition of anaphylaxis in infants can be challenging because allergic symptoms and certain normal infant behaviors may overlap. Intramuscular epinephrine is the treatment of choice for infants, as it is for older children and adults, and an epinephrine autoinjector approved by the Food and Drug Administration is now available for infants weighing between 7.5 and 15 kg. A panel of experts sought to develop guiding principles for the recognition, diagnosis, and management of anaphylaxis in infants, and provide a framework for the development of new guidelines and future research. Accordingly, anaphylaxis emergency action planning for infants was addressed by the panel. In considering formation of future infant anaphylaxis guidelines, health care providers should be aware of the needs to improve the recognition, diagnosis, and management of infants with anaphylaxis. Future research should identify and validate clinical criteria for the diagnosis of anaphylaxis in infants, as well as risk factors for the most severe reactions.
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http://dx.doi.org/10.1016/j.jaip.2018.10.052DOI Listing
April 2019

Contribution of language studies to the understanding of cognitive impairment and its progression over time in Parkinson's disease.

Neurosci Biobehav Rev 2017 Sep 3;80:657-672. Epub 2017 Aug 3.

Department of Clinical Neurosciences, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Canada.

Parkinson's disease is a frequent neurodegenerative disease that is mostly known for its motor symptoms. However, cognitive impairment is now recognised as an important part of the disease. Studies of cognitive impairment in Parkinson's disease reveal considerable heterogeneity in terms of which cognitive domains are impaired, and of how cognitive impairment progresses over time. In parallel, a growing body of research reports language difficulties in Parkinson's disease, more specifically in the domains of sentence processing and lexical-semantic processing. In this review, the performance of patients with Parkinson's disease in these domains of language will be reviewed with a focus on the links that they have with the rest of cognition and on how they could contribute to the earlier and more precise characterization and prediction of cognitive impairment in Parkinson's disease. More specifically, the potential for modulation of complexity and sensitivity of language tasks to mild deficits and difficulties that are predictive of further decline will be emphasized. Other motivations for studying language difficulties in this disease will also be discussed.
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http://dx.doi.org/10.1016/j.neubiorev.2017.07.014DOI Listing
September 2017

Comment on "Monkey vocal tracts are speech-ready".

Authors:
Philip Lieberman

Sci Adv 2017 07 7;3(7):e1700442. Epub 2017 Jul 7.

Department of Cognitive and Linguistic Sciences, Brown University, Providence, RI 02912, USA.

Monkey vocal tracts are capable of producing monkey speech, not the full range of articulate human speech. The evolution of human speech entailed both anatomy and brains. Fitch, de Boer, Mathur, and Ghazanfar in claim that "monkey vocal tracts are speech-ready," and conclude that "…the evolution of human speech capabilities required neural change rather than modifications of vocal anatomy." Neither premise is consistent either with the data presented and the conclusions reached by de Boer and Fitch themselves in their own published papers on the role of anatomy in the evolution of human speech or with the body of independent studies published since the 1950s.
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http://dx.doi.org/10.1126/sciadv.1700442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5501499PMC
July 2017

The evolution of language and thought.

Authors:
Philip Lieberman

J Anthropol Sci 2016 Jun 8;94:127-46. Epub 2015 Mar 8.

Brown University, Cognitive, Linguistic and Psychological Sciences, Providence RI 02912, USA,

Language primarily evolved as a vocal medium that transmits the attributes of human culture and the necessities of daily communication. Human language has a long, complex evolutionary history. Language also serves as an instrument of thought since it has become evident that in the course of this process neural circuits that initially evolved to regulate motor control, motor responses to external events, and ultimately talking were recycled to serve tasks such as working memory, cognitive flexibility linguistic tasks such as comprehending distinctions in meaning conveyed by syntax. This precludes the human brain possessing an organ devoted exclusively to language, such as the Faculty of Language proposed by Chomsky (1972, 2012). In essence like Fodor's (1983) modular model, a restatement of archaic phrenological theories (Spurzheim, 1815). The subcortical basal ganglia can be traced back to early anurans. Although our knowledge of the neural circuits of the human brain is at a very early stage and incomplete, the findings of independent studies over the past 40 years, discussed here, have identified circuits linking the basal ganglia with various areas of prefrontal cortex, posterior cortical regions and other subcortical structures. These circuits are active in linguistic tasks such as lexical access, comprehending distinctions in meaning conferred by syntax and the range of higher cognitive tasks involving executive control and play a critical role in conferring cognitive flexibility. The cingulate cortex which appeared in Therapsids, transitional mammal-like reptiles who lived in age of the dinosaurs, most likely enhanced mother-infant interaction, contributing to success in the Darwinian (1859) "Struggle for Existence" - the survival of progeny. They continue to fill that role in present-day mammals as well as being involved in controlling laryngeal phonation during speech and directing attention (Newman & MacLean, 1983; Cummings, 1993". The cerebellum and hippocampus, archaic structures, play role in cognition. Natural selection acting on genetic and epigenetic events in the last 500,000 years enhanced human cognitive and linguistic capabilities. It is clear that human language did not suddenly come into being 70,000 to 100,000 years as Noam Chomsky (Bolhuis et al., 2014) and others claim. The archeological record and analyses of fossil and genetic evidence shows that Neanderthals, who diverged from the human line at least 500,000 years ago possessed some form of language. Nor did the human population suddenly acquire the capability to relate two seemingly unrelated concepts by means of associative learning 100,000 years ago, re-coined "Merge" by Chomsky and his adherents, Merge supposedly is the key to syntax but associative learning, one of the cognitive processes by which children learn languages and the myriad complexities of their cultures, is a capability present in dogs and virtually all animals.
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http://dx.doi.org/10.4436/JASS.94029DOI Listing
June 2016

Language did not spring forth 100,000 years ago.

Authors:
Philip Lieberman

PLoS Biol 2015 Feb 13;13(2):e1002064. Epub 2015 Feb 13.

Cognitive, Linguistic and Psychological Sciences, Brown University, Providence, Rhode Island, United States of America.

In response to an Essay by Johan Bolhuis and co-authors, Phillip Lieberman contends that rather than arising from a key recent innovation ("merge"), language arose by gradual evolution of ancient capabilities.
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http://dx.doi.org/10.1371/journal.pbio.1002064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4332681PMC
February 2015

Anaphylaxis in America: A national physician survey.

J Allergy Clin Immunol 2015 Mar 7;135(3):830-3. Epub 2015 Jan 7.

Department of Pediatrics, Division of Allergy and Immunology, Johns Hopkins University School of Medicine, Baltimore, Md. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2014.10.049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4859205PMC
March 2015

Why we can talk, debate, and change our minds: neural circuits, basal ganglia operations, and transcriptional factors.

Authors:
Philip Lieberman

Behav Brain Sci 2014 Dec;37(6):561-2; discussion 577-604

Department of Cognitive,Linguistic and Psychological Sciences,Brown University,Providence,RI

Ackermann et al. disregard attested knowledge concerning aphasia, Parkinson disease, cortical-to-striatal circuits, basal ganglia, laryngeal phonation, and other matters. Their dual-pathway model cannot account for "what is special about the human brain." Their human cortical-to-laryngeal neural circuit does not exist. Basal ganglia operations, enhanced by mutations on FOXP2, confer human motor-control, linguistic, and cognitive capabilities.
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http://dx.doi.org/10.1017/S0140525X13004093DOI Listing
December 2014

Neuroscience. Synapses, language, and being human.

Authors:
Philip Lieberman

Science 2013 Nov;342(6161):944-5

Cognitive and Linguistic Sciences, Brown University, 190 Thayer Street, Providence, RI 02912, USA.

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http://dx.doi.org/10.1126/science.1247515DOI Listing
November 2013

Anaphylaxis in America: the prevalence and characteristics of anaphylaxis in the United States.

J Allergy Clin Immunol 2014 Feb 18;133(2):461-7. Epub 2013 Oct 18.

Department of Pediatrics and Child Health, Section of Allergy and Clinical Immunology, University of Manitoba, Winnipeg, Manitoba, Canada.

Background: Although anaphylaxis is recognized as an important life-threatening condition, data are limited regarding its prevalence and characteristics in the general population.

Objective: We sought to estimate the lifetime prevalence and overall characteristics of anaphylaxis.

Methods: Two nationwide, cross-sectional random-digit-dial surveys were conducted. The public survey included unselected adults, whereas the patient survey captured information from household members reporting a prior reaction to medications, foods, insect stings, or latex and idiopathic reactions in the previous 10 years. In both surveys standardized questionnaires queried anaphylaxis symptoms, treatments, knowledge, and behaviors.

Results: The public survey included 1,000 adults, of whom 7.7% (95% CI, 5.7% to 9.7%) reported a prior anaphylactic reaction. Using increasingly stringent criteria, we estimate that 5.1% (95% CI, 3.4% to 6.8%) and 1.6% (95% CI, 0.8% to 2.4%) had probable and very likely anaphylaxis, respectively. The patient survey included 1,059 respondents, of whom 344 reported a history of anaphylaxis. The most common triggers reported were medications (34%), foods (31%), and insect stings (20%). Forty-two percent sought treatment within 15 minutes of onset, 34% went to the hospital, 27% self-treated with antihistamines, 10% called 911, 11% self-administered epinephrine, and 6.4% received no treatment. Although most respondents with anaphylaxis reported 2 or more prior episodes (19% reporting ≥5 episodes), 52% had never received a self-injectable epinephrine prescription, and 60% did not currently have epinephrine available.

Conclusions: The prevalence of anaphylaxis in the general population is at least 1.6% and probably higher. Patients do not appear adequately equipped to deal with future episodes, indicating the need for public health initiatives to improve anaphylaxis recognition and treatment.
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http://dx.doi.org/10.1016/j.jaci.2013.08.016DOI Listing
February 2014

Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal.

Int Arch Allergy Immunol 2012 27;157(3):215-25. Epub 2011 Oct 27.

Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.

Activation of tissue mast cells (MCs) and their abnormal growth and accumulation in various organs are typically found in primary MC disorders also referred to as mastocytosis. However, increasing numbers of patients are now being informed that their clinical findings are due to MC activation (MCA) that is neither associated with mastocytosis nor with a defined allergic or inflammatory reaction. In other patients with MCA, MCs appear to be clonal cells, but criteria for diagnosing mastocytosis are not met. A working conference was organized in 2010 with the aim to define criteria for diagnosing MCA and related disorders, and to propose a global unifying classification of all MC disorders and pathologic MC reactions. This classification includes three types of 'MCA syndromes' (MCASs), namely primary MCAS, secondary MCAS and idiopathic MCAS. MCA is now defined by robust and generally applicable criteria, including (1) typical clinical symptoms, (2) a substantial transient increase in serum total tryptase level or an increase in other MC-derived mediators, such as histamine or prostaglandin D(2), or their urinary metabolites, and (3) a response of clinical symptoms to agents that attenuate the production or activities of MC mediators. These criteria should assist in the identification and diagnosis of patients with MCAS, and in avoiding misdiagnoses or overinterpretation of clinical symptoms in daily practice. Moreover, the MCAS concept should stimulate research in order to identify and exploit new molecular mechanisms and therapeutic targets.
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http://dx.doi.org/10.1159/000328760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3224511PMC
May 2012

The 10-second rule and other myths about epinephrine and autoinjectors.

Authors:
Philip Lieberman

Ann Allergy Asthma Immunol 2011 Sep;107(3):189-90

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http://dx.doi.org/10.1016/j.anai.2011.07.007DOI Listing
September 2011

Ophthalmodynamometry for ICP prediction and pilot test on Mt. Everest.

BMC Neurol 2010 Nov 1;10:106. Epub 2010 Nov 1.

Dept of Neurology, Rhode Island Hospital, Warren Alpert Medical School, Brown University Providence, RI 02903, USA.

Background: A recent development in non-invasive techniques to predict intracranial pressure (ICP) termed venous ophthalmodynamometry (vODM) has made measurements in absolute units possible. However, there has been little progress to show utility in the clinic or field. One important application would be to predict changes in actual ICP during adaptive responses to physiologic stress such as hypoxia. A causal relationship between raised intracranial pressure and acute mountain sickness (AMS) is suspected. Several MRI studies report that modest physiologic increases in cerebral volume, from swelling, normally accompany subacute ascent to simulated high altitudes.

Objectives: 1) Validate and calibrate an advanced, portable vODM instrument on intensive patients with raised intracranial pressure and 2) make pilot, non-invasive ICP estimations of normal subjects at increasing altitudes.

Methods: The vODM was calibrated against actual ICP in 12 neurosurgical patients, most affected with acute hydrocephalus and monitored using ventriculostomy/pressure transducers. The operator was blinded to the transducer read-out. A clinical field test was then conducted on a variable data set of 42 volunteer trekkers and climbers scaling Mt. Everest, Nepal. Mean ICPs were estimated at several altitudes on the ascent both across and within subjects.

Results: Portable vODM measurements increased directly and linearly with ICP resulting in good predictability (r = 0.85). We also found that estimated ICP increases normally with altitude (10 ± 3 mm Hg; sea level to 20 ± 2 mm Hg; 6553 m) and that AMS symptoms did not correlate with raised ICP.

Conclusion: vODM technology has potential to reliably estimate absolute ICP and is portable. Physiologic increases in ICP and mild-mod AMS are separate responses to high altitude, possibly reflecting swelling and vasoactive instability, respectively.
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http://dx.doi.org/10.1186/1471-2377-10-106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2987855PMC
November 2010

Histamine, antihistamines, and the central nervous system.

Authors:
Philip Lieberman

Allergy Asthma Proc 2009 Sep-Oct;30(5):482-6

Departments of Medicine and Pediatrics, University of Tennessee, Memphis, Tennessee, USA.

Histamine is a central nervous system (CNS) neurotransmitter. It acts in the brain via three receptors, H(1), H(2), and H(3). It is a mediator of "wakefulness" and its activity is necessary to maintain wakefulness, alertness, and reaction time. These activities can be impaired by H(1)-antagonists (reverse agonists) capable of penetrating the blood-brain barrier. By blocking the homeostatic effects of histamine in the CNS, drowsiness and functional impairment with or without drowsiness can occur. Several tests have been designed to assess the effects of antihistamines on the CNS. These include subjective measurements of drowsiness and more objective measurements of impairment. Second-generation antihistamines have been designed to minimize blood-brain barrier penetration by reducing lipophilicity and increasing the affinity for P-aminnoglycoprotein.
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http://dx.doi.org/10.2500/aap.2009.30.3264DOI Listing
December 2009

Intranasal antihistamines for allergic rhinitis: mechanism of action.

Authors:
Philip Lieberman

Allergy Asthma Proc 2009 Jul-Aug;30(4):345-8

Division of Allergy and Immunology, University of Tennessee, 7205 Wolf River Boulevard, Suite 200, Germantown, TN 38138, USA.

Although antihistamines have been in common use for treatment of allergic diseases including rhinitis for >60 years and topical therapy of the respiratory tract has been common for centuries, it is only in the past few years that topical intranasal antihistamine therapy has been widely used for treatment of allergic rhinitis. Much research has been done over the past several years showing broad anti-inflammatory effects of these medications, involving many different pathways. Effects have been shown on mediators including histamine, leukotrienes, platelet-activating factor, and substance P, as well as on cytokines, adhesion molecules, and chemokines involved in chemotaxis. It is significant that these effects have been seen at clinically relevant concentrations of the topical drugs, as opposed to the situation with oral antihistamines where anti-inflammatory effects are generally found only at concentrations much higher than that achieved with routine dosing. Clinically, it appears that this delivery of high local concentrations allows for other pharmacologic activity to be expressed. These anti-inflammatory actions may be part of the reason why these drugs also are effective in relieving many symptoms of nonallergic rhinitis, where histamine has much less of a role and where oral antihistamines have traditionally been of minimal help.
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http://dx.doi.org/10.2500/aap.2009.30.3263DOI Listing
May 2010

FOXP2 and Human Cognition.

Authors:
Philip Lieberman

Cell 2009 May;137(5):800-2

Cognitive and Linguistic Sciences, Brown University, Providence, RI 02912, USA.

Using a mouse model, Enard et al. (2009) show that the human form of the FOXP2 gene increases synaptic plasticity and dendrite connectivity in the basal ganglia. These results partly explain the enhanced capability of cortico-basal ganglia circuits in the human brain that regulate critical aspects of language, cognition, and motor control.
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http://dx.doi.org/10.1016/j.cell.2009.05.013DOI Listing
May 2009

Weather/temperature-sensitive vasomotor rhinitis may be refractory to intranasal corticosteroid treatment.

Allergy Asthma Proc 2009 Mar-Apr;30(2):120-7

Biogenics Research Institute, San Antonio, Texas 78229, USA.

Vasomotor rhinitis (VMR) is a common but poorly understood disorder of which there are two major subgroups: VMR(w/t), triggered by weather/temperature and VMR(ir), triggered by airborne irritants. No specific biological pathways or specific treatments for VMR(w/t) or VMR(ir) have been identified. However, intranasal corticosteroids (INSs) are effective in treating many forms of nonallergic rhinitis that include these conditions. A recently introduced INS with established efficacy in allergic rhinitis and enhanced affinity, fluticasone furoate, may possess the potency and safety profile required to treat chronic VMR(w/t). Two replicate studies (FFR30006 and FFR30007) were conducted in six countries to evaluate the efficacy and safety of fluticasone furoate nasal spray in subjects with VMR(w/t). After a 7- to 14-day screening period, subjects (n = 699) with symptomatic VMR(w/t) received fluticasone furoate, 110 mug q.d. or placebo for 4 weeks in these two randomized, double-blind, parallel-group studies. Subjects rated their nasal symptoms (congestion, rhinorrhea, and postnasal drip) twice daily on a 4-point categorical scale and evaluated their overall response to treatment at study end. Fluticasone furoate did not significantly improve daily reflective total nasal symptom scores, the primary end point, versus placebo (p = 0.259) and there was no improvement in any other measure of efficacy. The active treatment was well tolerated. Fluticasone furoate was not effective in treating subjects with a newly defined condition, weather-sensitive VMR. These unexpected results suggest that VMR(w/t) is a distinct subgroup of VMR that is refractory to treatment with INSs. Additional study of other treatments for VMR(w/t) (including INSs) is warranted.
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http://dx.doi.org/10.2500/aap.2009.30.3206DOI Listing
July 2009

Seafood allergy and radiocontrast media: are physicians propagating a myth?

Am J Med 2008 Feb;121(2):158.e1-4

Section of Allergy and Clinical Immunology, Division of Immunobiology, Department of Internal Medicine, Saint Louis University School of Medicine, St Louis, MO 63104, USA.

Background: Recent surveys have indicated that the misconception that seafood allergy confers a disproportionately increased risk of adverse reactions to radiocontrast media remains pervasive among physicians and patients. One possible explanation for the persistence of this notion is that physicians responsible for radiocontrast administration are inadvertently contributing to its propagation.

Methods: An anonymous survey was sent to 231 faculty radiologist and interventional cardiologists at 6 Midwest academic medical centers. Two questions dealt directly with seafood allergy related to radiocontrast media administration, and 6 questions served as distracters.

Results: Sixty-nine percent of responders indicated that they inquire about a history of seafood allergy before radiocontrast media administration. Some 37.2% of responders replied that they would withhold radiocontrast media or recommend premedication on the basis of a history of seafood allergy.

Conclusion: Even among faculty physicians at university medical centers, the notion of seafood allergy as a significant risk factor for adverse radiocontrast media reactions remains pervasive. Even if no action is taken on the basis of the answer, it seems probable that the act of inquiring about seafood allergy before radiocontrast media administration could lead patients and trainees to presume an inherent risk in patients who are seafood allergic, thus propagating the notion. Physician education with respect to seafood allergy and radiocontrast media administration is vital to halting the persistence of this misconception.
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http://dx.doi.org/10.1016/j.amjmed.2007.08.025DOI Listing
February 2008

An autosomal dominant genetically heterogeneous variant of rolandic epilepsy and speech disorder.

Epilepsia 2008 Jun 31;49(6):1086-90. Epub 2008 Jan 31.

Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.

We report a three generation pedigree with 11 of 22 affected with a variant form of rolandic epilepsy, speech impairment, oromotor apraxia, and cognitive deficit. The core features comprised nocturnal rolandic seizures, interictal centrotemporal spike waves with early age of onset and late age of offset. The transmission of the phenotype was consistent with autosomal dominant inheritance, with variable expressivity but no evidence of anticipation. We found evidence that the seizure and speech traits may be dissociated. No abnormalities were found by cytogenetic analysis. Linkage analysis excluded loci at 11p, 15q, 16p12, and Xq22 for related phenotypes, suggesting genetic heterogeneity.
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http://dx.doi.org/10.1111/j.1528-1167.2007.01517.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2435390PMC
June 2008

SAFE: a multidisciplinary approach to anaphylaxis education in the emergency department.

Ann Allergy Asthma Immunol 2007 Jun;98(6):519-23

Division of Allergy and Immunology, Department of Internal Medicine and Pediatrics, University of Tennessee College of Medicine, Memphis, Tennessee, USA.

Background: Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death. Allergists and emergency department (ED) physicians recognize the need for multidisciplinary efforts to increase public awareness of anaphylaxis, improve patient education, and enhance emergency and long-term management for the millions of Americans at risk for anaphylactic reactions.

Objectives: To provide an overview of the scientific literature documenting inconsistencies and limitations in the management of anaphylaxis in the ED, to highlight the need to enhance ED discharge instructions and patient education materials, and to introduce the SAFE system, an aid to improve the ongoing management and avoidance of factors that contribute to anaphylaxis.

Methods: An expert panel of allergists and ED physicians was convened by the American College of Allergy, Asthma and Immunology and the American College of Emergency Physicians to develop recommendations for educational materials on anaphylaxis for ED personnel and patients.

Results: The panel developed the acronym SAFE, a mnemonic device to remind physicians of the 4 basic action steps suggested for the care of a patient with anaphylaxis: (1) Seek support, (2) Allergen identification and avoidance, (3) Follow-up for specialty care, and (4) Epinephrine for emergencies.

Conclusion: The SAFE system is designed as a tool to raise awareness of anaphylaxis and its treatments among individuals at risk and the ED personnel charged with their care. Future studies need to examine the impact of the SAFE system in decreasing the morbidity and mortality rates associated with anaphylaxis and other severe allergic reactions.
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http://dx.doi.org/10.1016/s1081-1206(10)60729-6DOI Listing
June 2007

Regional differences in EpiPen prescriptions in the United States: the potential role of vitamin D.

J Allergy Clin Immunol 2007 Jul 7;120(1):131-6. Epub 2007 Jun 7.

Center for D-receptor Activation Research, Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

Background: The epidemiology of anaphylaxis is uncertain, especially its geographic distribution.

Objective: To address this deficit, we examined regional rates of EpiPen prescriptions in the United States.

Methods: EpiPen prescriptions in 2004 were obtained for all 50 states and Washington, DC, from NDCHealth, Pharmaceutical Audit Suite (Alpharetta, Ga). Data included the number of total filled prescriptions, including refills, and the actual number of EpiPens prescribed. Several data sets were used to obtain state-specific populations, as well as multiple demographic, health, and weather characteristics. State population was used to calculate the average number of prescriptions written per person.

Results: Overall, there were 1,511,534 EpiPen prescriptions filled during 2004. These prescriptions accounted for 2,495,188 EpiPens. On average, there were 5.71 EpiPens prescribed per 1000 persons. Massachusetts had the highest number of prescriptions per 1000 persons (11.8), whereas Hawaii had the lowest (2.7). In addition to state-to-state variation, there was an obvious regional difference: New England (Connecticut, Rhode Island, Massachusetts, Vermont, New Hampshire, Maine) had the highest values, with 8 to 12 EpiPen prescriptions per 1000 persons, whereas the southern states (between and including California and Mississippi) had only 3 prescriptions per 1000 persons. The New England finding persisted even when controlling for all available factors (eg, population demographic characteristics, number of health care providers, prescriptions for other medications).

Conclusion: A strong north-south gradient was observed for the prescription of EpiPens in the United States, with the highest rates found in New England.

Clinical Implications: The regional differences in EpiPen prescribing may provide important etiologic clues (vitamin D status) and merit further investigation.
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http://dx.doi.org/10.1016/j.jaci.2007.03.049DOI Listing
July 2007

The roles of sequencing and verbal working memory in sentence comprehension deficits in Parkinson's disease.

Brain Lang 2006 Jun 5;97(3):243-57. Epub 2005 Dec 5.

Department of Cognitive and Linguistic Sciences, Brown University, Providence, RI, USA.

Studies of sentence comprehension deficits in Parkinson's disease (PD) patients suggest that language processing involves circuits connecting subcortical and cortical regions. Anatomically segregated neural circuits appear to support different cognitive and motor functions. To investigate which functions are implicated in PD comprehension deficits, we tested comprehension, verbal working memory span, and cognitive set-switching in a non-linguistic task in 41 PD patients; we also obtained speech measurements reflecting motor sequencing processes that may be involved in articulatory rehearsal within working memory. Comprehension of sentences with center-embedded or final relative clauses was impaired when they could not be understood from lexical semantic content alone. Overall comprehension error rates correlated strongly with impaired set-switching and significantly with reduced working memory span and speech motor sequencing deficits. Correlations with comprehension of different sentence structures indicate that these impairments do not represent a single deficit; rather, PD comprehension deficits appear to arise from several independent mechanisms. Deficits in cognitive set-switching or underlying inhibitory processes may compromise the ability to process relative clauses. Deficits in verbal working memory appear to impair comprehension of long-distance dependencies. Speech sequencing correlated with neither set-switching nor verbal working memory span, consistent with their being supported by independent, segregated cortico-subcortical circuits.
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http://dx.doi.org/10.1016/j.bandl.2005.10.011DOI Listing
June 2006

Mount Everest: a space analogue for speech monitoring of cognitive deficits and stress.

Aviat Space Environ Med 2005 Jun;76(6 Suppl):B198-207

Department of Cognitive and Linguistic Sciences, Brown University, Providence, RI 02912, USA.

In deep-space missions, the basal ganglia and hippocampus, subcortical structures of the brain that play critical roles in motor activity, cognition, and memory, will be vulnerable to damage from cosmic rays. These metabolically active structures are also sensitive to damage arising from the low oxygen content of air at extreme altitudes. We have, therefore, used Mount Everest as an analogue for deep space, where astronauts will be subject to danger and stress as well as neural damage. We can ethically obtain data because our climber-subjects already intend to climb Mt. Everest. We record speech and test cognitive and linguistic performance before, during, and after exposure to hypoxic conditions. From these data we have derived and validated computer-implemented acoustic voice measures that track slight as well as profound cognitive impairment. Vowel duration and speech motor sequencing errors increase as climbers ascend, reflecting degraded basal ganglia activity. These metrics detect deficits in language comprehension and the ability to change plans in changing circumstances. Preliminary analyses also reveal memory deficits reflecting hippocampal damage. Our speech metrics are unobtrusive and do not reveal the content of a verbal message; they could be derived automatically, allowing space crews to detect subtle motor and cognitive deficits and invoke countermeasures before performance is profoundly impaired. In future work we will be validating the voice metrics of stress in collaboration with the Dinges NSBRI laboratory study of task-induced stress. Our procedures can also be applied in general aviation and in the treatment of Parkinson's disease, Alzheimer's dementia, and other neurological disorders.
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June 2005

On the nature and evolution of the neural bases of human language.

Authors:
Philip Lieberman

Am J Phys Anthropol 2002 ;Suppl 35:36-62

Department of Cognitive and Linguistic Sciences, Brown University, Providence, Rhode Island 02912-1978, USA.

The traditional theory equating the brain bases of language with Broca's and Wernicke's neocortical areas is wrong. Neural circuits linking activity in anatomically segregated populations of neurons in subcortical structures and the neocortex throughout the human brain regulate complex behaviors such as walking, talking, and comprehending the meaning of sentences. When we hear or read a word, neural structures involved in the perception or real-world associations of the word are activated as well as posterior cortical regions adjacent to Wernicke's area. Many areas of the neocortex and subcortical structures support the cortical-striatal-cortical circuits that confer complex syntactic ability, speech production, and a large vocabulary. However, many of these structures also form part of the neural circuits regulating other aspects of behavior. For example, the basal ganglia, which regulate motor control, are also crucial elements in the circuits that confer human linguistic ability and abstract reasoning. The cerebellum, traditionally associated with motor control, is active in motor learning. The basal ganglia are also key elements in reward-based learning. Data from studies of Broca's aphasia, Parkinson's disease, hypoxia, focal brain damage, and a genetically transmitted brain anomaly (the putative "language gene," family KE), and from comparative studies of the brains and behavior of other species, demonstrate that the basal ganglia sequence the discrete elements that constitute a complete motor act, syntactic process, or thought process. Imaging studies of intact human subjects and electrophysiologic and tracer studies of the brains and behavior of other species confirm these findings. As Dobzansky put it, "Nothing in biology makes sense except in the light of evolution" (cited in Mayr, 1982). That applies with as much force to the human brain and the neural bases of language as it does to the human foot or jaw. The converse follows: the mark of evolution on the brains of human beings and other species provides insight into the evolution of the brain bases of human language. The neural substrate that regulated motor control in the common ancestor of apes and humans most likely was modified to enhance cognitive and linguistic ability. Speech communication played a central role in this process. However, the process that ultimately resulted in the human brain may have started when our earliest hominid ancestors began to walk.
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http://dx.doi.org/10.1002/ajpa.10171DOI Listing
April 2003

Speech motor control and acute mountain sickness.

Aviat Space Environ Med 2002 Aug;73(8):766-72

Thermal and Mountain Medicine Division, U.S. Army Research Institute of Environmental Medicine, Natick, MA 01760, USA.

Background: An objective method that accurately quantifies the severity of Acute Mountain Sickness (AMS) symptoms is needed to enable more reliable evaluation of altitude acclimatization and testing of potentially beneficial interventions.

Hypothesis: Changes in human articulation, as quantified by timed variations in acoustic waveforms of specific spoken words (voice onset time; VOT), are correlated with the severity of AMS.

Methods: Fifteen volunteers were exposed to a simulated altitude of 4300 m (446 mm Hg) in a hypobaric chamber for 48 h. Speech motor control was determined from digitally recorded and analyzed timing patterns of 30 different monosyllabic words characterized as voiced and unvoiced, and as labial, alveolar, or velar. The Environmental Symptoms Questionnaire (ESQ) was used to assess AMS.

Results: Significant AMS symptoms occurred after 4 h, peaked at 16 h, and returned toward baseline after 48 h. Labial VOTs were shorter after 4 and 39 h of exposure; velar VOTs were altered only after 4 h; and there were no changes in alveolar VOTs. The duration of vowel sounds was increased after 4 h of exposure and returned to normal thereafter. Only 1 of 15 subjects did not increase vowel time after 4 h of exposure. The 39-h labial (p = 0.009) and velar (p = 0.037) voiced-unvoiced timed separations consonants and the symptoms of AMS were significantly correlated.

Conclusions: Two objective measures of speech production were affected by exposure to 4300 m altitude and correlated with AMS severity. Alterations in speech production may represent an objective measure of AMS and central vulnerability to hypoxia.
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August 2002

Histamine and antihistamines in anaphylaxis.

Clin Allergy Immunol 2002 ;17:287-317

University of Tennessee College of Medicine, Memphis, Tennessee, USA.

Anaphylaxis and anaphylactoid reactions are potentially fatal. These disorders are sometimes iatrogenic, and increase with increased exposure to drugs, synthetic substances, and medical procedures. Non-IgE-mediated anaphylactoid reactions are common in medical settings and are clinically indistinguishable from anaphylaxis. These reactions may be unrecognized if a rigid classic definition of anaphylaxis is used. Histamine is a primary mediator of anaphylaxis and signs and symptoms of anaphylaxis can be reproduced by histamine infusion. Histamine triggers a cascade of inflammatory mediators and modulates its own release. H1-antihistamines are adjunctive treatment therapy for acute anaphylaxis and anaphylactoid reactions, in which many mediators of inflammation are involved. Compared with epinephrine, the first-response medication of choice, antihistamines have a slow onset of action, and they cannot block events that occur subsequent to histamine binding to its receptors. Antihistamines are an important component of regimens for the prevention of anaphylaxis and anaphylactoid reactions in patients at risk, and may eventually have more widespread application in the perioperative setting. In some instances, such as with exercise-induced anaphylaxis and reactions to latex in sensitized individuals, prophylaxis regimens are not always effective. H2-antagonists are not detrimental in the therapy of anaphylaxis and many studies show a favorable outcome when combining H1- and H2-antagonist therapy for prophylaxis. They should be added to therapy at the discretion of the treating physician. Because of decreased antimuscarinic and central nervous system side effects, the newer antihistamines can be given in high doses, allowing more complete blockade of histamine receptors. These agents should lead to a reevaluation of the usefulness of antihistamines in both the treatment of acute anaphylaxis and in prophylactic regimens. The unavailability of parenterally administered second-generation H1-antagonists limits their usefulness in acute anaphylaxis and perioperative prophylaxis.
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July 2002