Georgetown University

Abstract Given assumptions about the characteristics of knowledge and the knowledge requirements of production, the firm is conceptualized as an institution for integrating knowledge. The primary contribution of the paper is in exploring the coordination mechanisms through which firms integrate the specialist knowledge of their members. In contrast to earlier literature, knowledge is viewed as residing within the individual, and the primary role of the organization is knowledge application rather than knowledge creation. The resulting theory has implications for the basis of organizational capability, the principles of organization design (in particular, the analysis of hierarchy and the distribution of decision‐making authority), and the determinants of the horizontal and vertical boundaries of the firm. More generally, the knowledge‐based approach sheds new light upon current organizational innovations and trends and has far‐reaching implications for management practice.

One method of evaluating the degree of neurologic impairment in MS has been the combination of grades (0 = normal to 5 or 6 = maximal impairment) within 8 Functional Systems (FS) and an overall Disability Status Scale (DSS) that had steps from 0 (normal) to 10 (death due to MS). A new Expanded Disability Status Scale (EDSS) is presented, with each of the former steps (1,2,3 . . . 9) now divided into two (1.0, 1.5, 2.0 . . . 9.5). The lower portion is obligatorily defined by Functional System grades. The FS are Pyramidal, Cerebellar, Brain Stem, Sensory, Bowel & Bladder, Visual, Cerebral, and Other; the Sensory and Bowel & Bladder Systems have been revised. Patterns of FS and relations of FS by type and grade to the DSS are demonstrated.

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles ("MISEV") guidelines for the field in 2014. We now update these "MISEV2014" guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

?The stakeholder theory has been advanced and justified in the management literature on the basis of its descriptive accuracy, instrumental power, and normative validity. These three aspects of the theory, although interrelated, are quite distinct; they involve different types of evidence and argument and have different implications. In this article, we examine these three aspects of the theory and critique and integrate important contributions to the literature related to each. We conclude that the three aspects of stakeholder theory are mutually supportive and that the normative base of the theory-which includes the modern theory of property rights-is fundamental. If the unity of the corporate body is real, then there is reality and not simply legal fiction in the proposition that the managers of the unit are fiduciaries for it and not merely for its individual members, that they are . . . trustees for an institution [with multiple constituents] rather than attorneys for the stockholders.

Probiotics are widely regarded as live microorganisms that, when administered in sufficient amounts, confer a health benefit, but guidance is needed on the most appropriate use of the term. This Consensus Statement outlines recommendations for the scope and definition of the term 'probiotic' as determined by an expert panel convened by the International Scientific Association for Probiotics and Prebiotics in October 2013. An expert panel was convened in October 2013 by the International Scientific Association for Probiotics and Prebiotics (ISAPP) to discuss the field of probiotics. It is now 13 years since the definition of probiotics and 12 years after guidelines were published for regulators, scientists and industry by the Food and Agriculture Organization of the United Nations and the WHO (FAO/WHO). The FAO/WHO definition of a probiotic—“live microorganisms which when administered in adequate amounts confer a health benefit on the host”—was reinforced as relevant and sufficiently accommodating for current and anticipated applications. However, inconsistencies between the FAO/WHO Expert Consultation Report and the FAO/WHO Guidelines were clarified to take into account advances in science and applications. A more precise use of the term 'probiotic' will be useful to guide clinicians and consumers in differentiating the diverse products on the market. This document represents the conclusions of the ISAPP consensus meeting on the appropriate use and scope of the term probiotic.

This study addressed the nature and functioning of relationships of interpersonal trust among managers and professionals in organizations, the factors influencing trust's development, and the implications of trust for behavior and performance. Theoretical foundations were drawn from the sociological literature on trust and the social-psychological literature on trust in close relationships. An initial test of the proposed theoretical framework was conducted in a field setting with 194 managers and professionals.

Abstract— A method has been developed for the simultaneous measurement of the rates of glucose consumption in the various structural and functional components of the brain in vivo. The method can be applied to most laboratory animals in the conscious state. It is based on the use of 2‐deoxy‐D‐[ 14 C]glucose ([ 14 C]DG) as a tracer for the exchange of glucose between plasma and brain and its phosphorylation by hexokinase in the tissues. [ 14 C]DG is used because the label in its product, [ 14 C]deoxyglucose‐6‐phosphate, is essentially trapped in the tissue over the time course of the measurement. A model has been designed based on the assumptions of a steady state for glucose consumption, a first order equilibration of the free [ 14 C]DG pool in the tissue with the plasma level, and relative rates of phosphorylation of [ 14 C]DG and glucose determined by their relative concentrations in the precursor pools and their respective kinetic constants for the hexokinase reaction. An operational equation based on this model has been derived in terms of determinable variables. A pulse of [ 14 C]DG is administered intravenously and the arterial plasma [ 14 C]DG and glucose concentrations monitored for a preset time between 30 and 45min. At the prescribed time, the head is removed and frozen in liquid N 2 ‐chilled Freon XII, and the brain sectioned for autoradiography. Local tissue concentrations of [ 14 C]DG are determined by quantitative autoradiography. Local cerebral glucose consumption is calculated by the equation on the basis of these measured values. The method has been applied to normal albino rats in the conscious state and under thiopental anesthesia. The results demonstrate that the local rates of glucose consumption in the brain fall into two distinct distributions, one for gray matter and the other for white matter. In the conscious rat the values in the gray matter vary widely from structure to structure (54‐197 μmol/100 g/min) with the highest values in structures related to auditory function, e.g. medial geniculate body, superior olive, inferior colliculus, and auditory cortex. The values in white matter are more uniform (i.e. 33–40 μmo1/100 g/min) at levels approximately one‐fourth to one‐half those of gray matter. Heterogeneous rates of glucose consumption are frequently seen within specific structures, often revealing a pattern of cytoarchitecture. Thiopental anesthesia markedly depresses the rates of glucose utilization throughout the brain, particularly in gray matter, and metabolic rate throughout gray matter becomes more uniform at a lower level.

AUTORES: Daniel J Klionsky1745,1749*, Kotb Abdelmohsen840, Akihisa Abe1237, Md Joynal Abedin1762, Hagai Abeliovich425,
\nAbraham Acevedo Arozena789, Hiroaki Adachi1800, Christopher M Adams1669, Peter D Adams57, Khosrow Adeli1981,
\nPeter J Adhihetty1625, Sharon G Adler700, Galila Agam67, Rajesh Agarwal1587, Manish K Aghi1537, Maria Agnello1826,
\nPatrizia Agostinis664, Patricia V Aguilar1960, Julio Aguirre-Ghiso784,786, Edoardo M Airoldi89,422, Slimane Ait-Si-Ali1376,
\nTakahiko Akematsu2010, Emmanuel T Akporiaye1097, Mohamed Al-Rubeai1394, Guillermo M Albaiceta1294,
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\nNihal Altan-Bonnet848, Dario C Altieri1205, Silvia Alvarez1497, Lydia Alvarez-Erviti1395, Sandro Alves107,
\nGiuseppina Amadoro860, Atsuo Amano930, Consuelo Amantini1554, Santiago Ambrosio1458, Ivano Amelio756,
\nAmal O Amer918, Mohamed Amessou2089, Angelika Amon726, Zhenyi An1538, Frank A Anania291, Stig U Andersen6,
\nUsha P Andley2079, Catherine K Andreadi1690, Nathalie Andrieu-Abadie502, Alberto Anel2027, David K Ann58,
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\nAgnieszka Bagniewska-Zadworna2, Hua Bai90, Jie Bai667, Xue-Yuan Bai1133, Yannick Bailly884,
\nKithiganahalli Narayanaswamy Balaji473, Walter Balduini2002, Andrea Ballabio316, Rena Balzan1711, Rajkumar Banerjee239,
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\nLisa A Brennan322, Emery H Bresnick2022, Patrick Brest490, Dave Bridges1939, Marie-Agn es Bringer124, Marisa Brini1822,
\nGlauber C Brito1311, Bertha Brodin631, Paul S Brookes1872, Eric J Brown352, Karen Brown1690, Hal E Broxmeyer480,
\nAlain Bruhat486,1339, Patricia Chakur Brum1893, John H Brumell446, Nicola Brunetti-Pierri315,1171,
\nRobert J Bryson-Richardson781, Shilpa Buch1777, Alastair M Buchan1819, Hikmet Budak1022, Dmitry V Bulavin118,505,1789,
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\nMargit Burmeister1750, Peter B€utikofer1473, Laura Caberlotto1987, Ken Cadwell896, Monika Cahova112, Dongsheng Cai24,
\nJingjing Cai2099, Qian Cai1018, Sara Calatayud2007, Nadine Camougrand1343, Michelangelo Campanella1700,
\nGrant R Campbell1525, Matthew Campbell1249, Silvia Campello556,1876, Robin Candau1769, Isabella Caniggia1983,
\nLavinia Cantoni560, Lizhi Cao116, Allan B Caplan1656, Michele Caraglia1051, Claudio Cardinali1043, Sandra Morais Cardoso1579, Jennifer S Carew208, Laura A Carleton874, Cathleen R Carlin101, Silvia Carloni2002,
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\nSusana Castro-Obregon214, Gabriella Cavallini1841, Isabella Ceccherini568, Francesco Cecconi253,555,1884,
\nArthur I Cederbaum459, Valent ın Ce~na199,1281, Simone Cenci1323,2064, Claudia Cerella444, Davide Cervia1996,
\nSilvia Cetrullo1478, Hassan Chaachouay2028, Han-Jung Chae187, Andrei S Chagin634, Chee-Yin Chai626,628,
\nGopal Chakrabarti1502, Georgios Chamilos1601, Edmond YW Chan1142, Matthew TV Chan181, Dhyan Chandra1003,
\nPallavi Chandra548, Chih-Peng Chang818, Raymond Chuen-Chung Chang1653, Ta Yuan Chang345, John C Chatham1434,
\nSaurabh Chatterjee1910, Santosh Chauhan527, Yongsheng Che62, Michael E Cheetham1263, Rajkumar Cheluvappa1783,
\nChun-Jung Chen1153, Gang Chen598,1676, Guang-Chao Chen9, Guoqiang Chen1078, Hongzhuan Chen1077, Jeff W Chen1514,
\nJian-Kang Chen370,371, Min Chen249, Mingzhou Chen2104, Peiwen Chen1823, Qi Chen1674, Quan Chen172,
\nShang-Der Chen138, Si Chen325, Steve S-L Chen10, Wei Chen2125, Wei-Jung Chen829, Wen Qiang Chen979, Wenli Chen1113,
\nXiangmei Chen1133, Yau-Hung Chen1157, Ye-Guang Chen1250, Yin Chen1447, Yingyu Chen953,955, Yongshun Chen2135,
\nYu-Jen Chen712, Yue-Qin Chen1145, Yujie Chen1208, Zhen Chen339, Zhong Chen2123, Alan Cheng1702,
\nChristopher HK Cheng184, Hua Cheng1728, Heesun Cheong814, Sara Cherry1836, Jason Chesney1703,
\nChun Hei Antonio Cheung817, Eric Chevet1359, Hsiang Cheng Chi140, Sung-Gil Chi656, Fulvio Chiacchiera308,
\nHui-Ling Chiang958, Roberto Chiarelli1826, Mario Chiariello235,567,577, Marcello Chieppa835, Lih-Shen Chin290,
\nMario Chiong1285, Gigi NC Chiu878, Dong-Hyung Cho676, Ssang-Goo Cho650, William C Cho982, Yong-Yeon Cho105,
\nYoung-Seok Cho1064, Augustine MK Choi2095, Eui-Ju Choi656, Eun-Kyoung Choi387,400,685, Jayoung Choi1563,
\nMary E Choi2093, Seung-Il Choi2116, Tsui-Fen Chou412, Salem Chouaib395, Divaker Choubey1574, Vinay Choubey1936,
\nKuan-Chih Chow822, Kamal Chowdhury730, Charleen T Chu1856, Tsung-Hsien Chuang827, Taehoon Chun657,
\nHyewon Chung652, Taijoon Chung978, Yuen-Li Chung1194, Yong-Joon Chwae18, Valentina Cianfanelli254,
\nRoberto Ciarcia1775, Iwona A Ciechomska886, Maria Rosa Ciriolo1876, Mara Cirone1042, Sofie Claerhout1694,
\nMichael J Clague1698, Joan Cl aria1457, Peter GH Clarke1687, Robert Clarke361, Emilio Clementi1045,1398, C edric Cleyrat1781,
\nMiriam Cnop1366, Eliana M Coccia574, Tiziana Cocco1459, Patrice Codogno1375, J€orn Coers271, Ezra EW Cohen1533,
\nDavid Colecchia235,567,577, Luisa Coletto25, N uria S Coll123, Emma Colucci-Guyon516, Sergio Comincini1829,
\nMaria Condello578, Katherine L Cook2073, Graham H Coombs1929, Cynthia D Cooper2076, J Mark Cooper1395,
\nIsabelle Coppens601, Maria Tiziana Corasaniti1387, Marco Corazzari485,1884, Ramon Corbalan1566,
\nElisabeth Corcelle-Termeau251, Mario D Cordero1899, Cristina Corral-Ramos1289, Olga Corti507,1109, Andrea Cossarizza1767,
\nPaola Costelli1993, Safia Costes1518, Susan L Cotman721, Ana Coto-Montes946, Sandra Cottet566,1688, Eduardo Couve1301,
\nLori R Covey1015, L Ashley Cowart762, Jeffery S Cox1536, Fraser P Coxon1427, Carolyn B Coyne1846, Mark S Cragg1919,
\nRolf J Craven1679, Tiziana Crepaldi1995, Jose L Crespo1300, Alfredo Criollo1285, Valeria Crippa558, Maria Teresa Cruz1576,
\nAna Maria Cuervo26, Jose M Cuezva1277, Taixing Cui1907, Pedro R Cutillas987, Mark J Czaja27, Maria F Czyzyk-Krzeska1572,
\nRuben K Dagda2068, Uta Dahmen1404, Chunsun Dai800, Wenjie Dai1187, Yun Dai2059, Kevin N Dalby1940,
\nLuisa Dalla Valle1822, Guillaume Dalmasso1340, Marcello D’Amelio557, Markus Damme188, Arlette Darfeuille-Michaud1340,
\nCatherine Dargemont950, Victor M Darley-Usmar1433, Srinivasan Dasarathy205, Biplab Dasgupta202, Srikanta Dash1254,
\nCrispin R Dass242, Hazel Marie Davey8, Lester M Davids1560, David D avila227, Roger J Davis1731, Ted M Dawson604,
\nValina L Dawson606, Paula Daza1898, Jackie de Belleroche470, Paul de Figueiredo1180,1182,
\nRegina Celia Bressan Queiroz de Figueiredo135, Jos e de la Fuente1023, Luisa De Martino1775,
\nAntonella De Matteis1171, Guido RY De Meyer1443, Angelo De Milito631, Mauro De Santi2002,

Unstable market conditions caused by innovation and increasing intensity and diversity of competition have resulted in organizational capabilities rather than served markets becoming the primary basis upon which firms establish their long-term strategies. If the strategically most important resource of the firm is knowledge, and if knowledge resides in specialized form among individual organizational members, then the essence of organizational capability is the integration of individuals' specialized knowledge. This paper develops a knowledge-based theory of organizational capability and draws upon research into competitive dynamics, the resource-based view of the firm, organizational capabilities, and organizational learning. Central to the theory is analysis of the mechanisms through which knowledge is integrated within firms in order to create capability. The theory is used to explore firms' potential for establishing competitive advantage in dynamic market settings, including the role of firm networks under conditions of unstable linkages between knowledge inputs and product outputs. The analysis points to the difficulties in creating the “dynamic” and “flexible-response capabilities” which have been deemed critical to success in hypercompetitive markets.

The purpose of this work was to modernize recommendations for evaluation, staging, and response assessment of patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). A workshop was held at the 11th International Conference on Malignant Lymphoma in Lugano, Switzerland, in June 2011, that included leading hematologists, oncologists, radiation oncologists, pathologists, radiologists, and nuclear medicine physicians, representing major international lymphoma clinical trials groups and cancer centers. Clinical and imaging subcommittees presented their conclusions at a subsequent workshop at the 12th International Conference on Malignant Lymphoma, leading to revised criteria for staging and of the International Working Group Guidelines of 2007 for response. As a result, fluorodeoxyglucose (FDG) positron emission tomography (PET)–computed tomography (CT) was formally incorporated into standard staging for FDG-avid lymphomas. A modification of the Ann Arbor descriptive terminology will be used for anatomic distribution of disease extent, but the suffixes A or B for symptoms will only be included for HL. A bone marrow biopsy is no longer indicated for the routine staging of HL and most diffuse large B-cell lymphomas. However, regardless of stage, general practice is to treat patients based on limited (stages I and II, nonbulky) or advanced (stage III or IV) disease, with stage II bulky disease considered as limited or advanced disease based on histology and a number of prognostic factors. PET-CT will be used to assess response in FDG-avid histologies using the 5-point scale. The product of the perpendicular diameters of a single node can be used to identify progressive disease. Routine surveillance scans are discouraged. These recommendations should improve evaluation of patients with lymphoma and enhance the ability to compare outcomes of clinical trials.

BACKGROUND: Among patients with aortic stenosis who are at intermediate or high risk for death with surgery, major outcomes are similar with transcatheter aortic-valve replacement (TAVR) and surgical aortic-valve replacement. There is insufficient evidence regarding the comparison of the two procedures in patients who are at low risk. METHODS: We randomly assigned patients with severe aortic stenosis and low surgical risk to undergo either TAVR with transfemoral placement of a balloon-expandable valve or surgery. The primary end point was a composite of death, stroke, or rehospitalization at 1 year. Both noninferiority testing (with a prespecified margin of 6 percentage points) and superiority testing were performed in the as-treated population. RESULTS: At 71 centers, 1000 patients underwent randomization. The mean age of the patients was 73 years, and the mean Society of Thoracic Surgeons risk score was 1.9% (with scores ranging from 0 to 100% and higher scores indicating a greater risk of death within 30 days after the procedure). The Kaplan-Meier estimate of the rate of the primary composite end point at 1 year was significantly lower in the TAVR group than in the surgery group (8.5% vs. 15.1%; absolute difference, -6.6 percentage points; 95% confidence interval [CI], -10.8 to -2.5; P<0.001 for noninferiority; hazard ratio, 0.54; 95% CI, 0.37 to 0.79; P = 0.001 for superiority). At 30 days, TAVR resulted in a lower rate of stroke than surgery (P = 0.02) and in lower rates of death or stroke (P = 0.01) and new-onset atrial fibrillation (P<0.001). TAVR also resulted in a shorter index hospitalization than surgery (P<0.001) and in a lower risk of a poor treatment outcome (death or a low Kansas City Cardiomyopathy Questionnaire score) at 30 days (P<0.001). There were no significant between-group differences in major vascular complications, new permanent pacemaker insertions, or moderate or severe paravalvular regurgitation. CONCLUSIONS: Among patients with severe aortic stenosis who were at low surgical risk, the rate of the composite of death, stroke, or rehospitalization at 1 year was significantly lower with TAVR than with surgery. (Funded by Edwards Lifesciences; PARTNER 3 ClinicalTrials.gov number, NCT02675114.).

BACKGROUND: The availability of multiple, essentially complete genome sequences of prokaryotes and eukaryotes spurred both the demand and the opportunity for the construction of an evolutionary classification of genes from these genomes. Such a classification system based on orthologous relationships between genes appears to be a natural framework for comparative genomics and should facilitate both functional annotation of genomes and large-scale evolutionary studies. RESULTS: We describe here a major update of the previously developed system for delineation of Clusters of Orthologous Groups of proteins (COGs) from the sequenced genomes of prokaryotes and unicellular eukaryotes and the construction of clusters of predicted orthologs for 7 eukaryotic genomes, which we named KOGs after eukaryotic orthologous groups. The COG collection currently consists of 138,458 proteins, which form 4873 COGs and comprise 75% of the 185,505 (predicted) proteins encoded in 66 genomes of unicellular organisms. The eukaryotic orthologous groups (KOGs) include proteins from 7 eukaryotic genomes: three animals (the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster and Homo sapiens), one plant, Arabidopsis thaliana, two fungi (Saccharomyces cerevisiae and Schizosaccharomyces pombe), and the intracellular microsporidian parasite Encephalitozoon cuniculi. The current KOG set consists of 4852 clusters of orthologs, which include 59,838 proteins, or approximately 54% of the analyzed eukaryotic 110,655 gene products. Compared to the coverage of the prokaryotic genomes with COGs, a considerably smaller fraction of eukaryotic genes could be included into the KOGs; addition of new eukaryotic genomes is expected to result in substantial increase in the coverage of eukaryotic genomes with KOGs. Examination of the phyletic patterns of KOGs reveals a conserved core represented in all analyzed species and consisting of approximately 20% of the KOG set. This conserved portion of the KOG set is much greater than the ubiquitous portion of the COG set (approximately 1% of the COGs). In part, this difference is probably due to the small number of included eukaryotic genomes, but it could also reflect the relative compactness of eukaryotes as a clade and the greater evolutionary stability of eukaryotic genomes. CONCLUSION: The updated collection of orthologous protein sets for prokaryotes and eukaryotes is expected to be a useful platform for functional annotation of newly sequenced genomes, including those of complex eukaryotes, and genome-wide evolutionary studies.

PURPOSE: Standardized response criteria are needed to interpret and compare clinical trials and for approval of new therapeutic agents by regulatory agencies. METHODS: The International Working Group response criteria (Cheson et al, J Clin Oncol 17:1244, 1999) were widely adopted, but required reassessment because of identified limitations and the increased use of [18F]fluorodeoxyglucose-positron emission tomography (PET), immunohistochemistry (IHC), and flow cytometry. The International Harmonization Project was convened to provide updated recommendations. RESULTS: New guidelines are presented incorporating PET, IHC, and flow cytometry for definitions of response in non-Hodgkin's and Hodgkin's lymphoma. Standardized definitions of end points are provided. CONCLUSION: We hope that these guidelines will be adopted widely by study groups, pharmaceutical and biotechnology companies, and regulatory agencies to facilitate the development of new and more effective therapies to improve the outcome of patients with lymphoma.

The initial study describing the development of the Multidimensional Scale of Perceived Social Support (MSPSS) indicated that it was a psychometrically sound instrument (Zimet, Dahlem, Zimet, & Farley, 1988). The current study attempted to extend the initial findings by demonstrating the internal reliability, factorial validity, and subscale validity of the MSPSS using three different subject groups: (a) 265 pregnant women, (b) 74 adolescents living in Europe with their families, and (c) 55 pediatric residents. The MSPSS was found to have good internal reliability across subject groups. In addition, strong factorial validity was demonstrated, confirming the three-subscale structure of the MSPSS: Family, Friends, and Significant Other. Finally, strong support was also found for the validity of the Family and Significant Other subscales.

OBJECTIVE: Brain-computer interfaces (BCI) enable direct communication with a computer, using neural activity as the control signal. This neural signal is generally chosen from a variety of well-studied electroencephalogram (EEG) signals. For a given BCI paradigm, feature extractors and classifiers are tailored to the distinct characteristics of its expected EEG control signal, limiting its application to that specific signal. Convolutional neural networks (CNNs), which have been used in computer vision and speech recognition to perform automatic feature extraction and classification, have successfully been applied to EEG-based BCIs; however, they have mainly been applied to single BCI paradigms and thus it remains unclear how these architectures generalize to other paradigms. Here, we ask if we can design a single CNN architecture to accurately classify EEG signals from different BCI paradigms, while simultaneously being as compact as possible. APPROACH: In this work we introduce EEGNet, a compact convolutional neural network for EEG-based BCIs. We introduce the use of depthwise and separable convolutions to construct an EEG-specific model which encapsulates well-known EEG feature extraction concepts for BCI. We compare EEGNet, both for within-subject and cross-subject classification, to current state-of-the-art approaches across four BCI paradigms: P300 visual-evoked potentials, error-related negativity responses (ERN), movement-related cortical potentials (MRCP), and sensory motor rhythms (SMR). MAIN RESULTS: We show that EEGNet generalizes across paradigms better than, and achieves comparably high performance to, the reference algorithms when only limited training data is available across all tested paradigms. In addition, we demonstrate three different approaches to visualize the contents of a trained EEGNet model to enable interpretation of the learned features. SIGNIFICANCE: Our results suggest that EEGNet is robust enough to learn a wide variety of interpretable features over a range of BCI tasks. Our models can be found at: https://github.com/vlawhern/arl-eegmodels.

The WHO Nomenclature Committee for Factors of the HLA System has met several times since the publication of the last major report in 2010.1 It met most recently in September 2023, to discuss additions to the serological defined HLA antigens. This report documents the additions and revisions to the nomenclature of HLA specificities following the principles established in previous reports.1-19 Links to these reports and details of HLA Nomenclature can be found on the website: hla.alleles.org The HLA-OLI pseudogene has been reported and officially named HLA-R. A full list of all recognised HLA genes is given in Table 1.20 Although at present it is only a recommendation that full-length sequences of the coding region of novel alleles be submitted, it was widely felt that in the future this should become a requirement for submission. Such requirement would remove many of the currently encountered ambiguities in the assignment of names to alleles for which partial sequences have been submitted and should not be burdensome as sequencing techniques have improved substantially since the submission conditions were first devised. In cases where novel mutations or polymorphisms are detected in non-coding regions of the gene, it will be a requirement that full-length sequences be submitted of both the novel allele and its most closely related allele. It should be noted with some caution that cells from which only partial sequences have been obtained may later be shown to have different or novel alleles when further sequencing is performed. This is of particular importance in cases where partial sequences of what appears to be the same allele have been obtained from several different cells. In such cases, all cells studied have been listed in this report. The list of those genes in the HLA region considered by the WHO Nomenclature Committee for Factors of the HLA System is given in Table 1. Current practice is that official designations will be promptly assigned to newly described alleles in periods between Nomenclature Committee meetings, provided that the submitted data and its accompanying description meet the criteria outlined above. A list of the newly reported alleles is published every three months in nomenclature updates in the journals HLA, Human Immunology and the International Journal of Immunogenetics. The listing of references to new sequences does not imply priority of publication. The use of numbers or names for alleles, genes or specificities which pre-empt assignment of official designations by the Nomenclature Committee is strongly discouraged. A total of 43,758 HLA alleles have been named as of December 2025. A complete listing of the numbers of alleles assigned for each HLA genes is given in Table 2. In September 2023, the WHO Nomenclature Committee for Factors of the HLA System met at the Stanford Blood Center located at Stanford University following the 18th International HLA and Immunogenetics Workshop held in Noordwijkerhout, the Netherlands in May 2022. The committee met to evaluate a proposal for the definition of additional and novel antigens defined in silico21. The in silico definition of HLA antigens was achieved by the systematic examination and cataloguing the amino acid (AA) replacements at specific residues determining epitopes (DEP) in all common HLA alleles at the classical HLA class I and class II loci [Common and Well Documented (CWD2.0) for alleles of HLA-DRB3, -DRB4, -DRB5, -DQA1 and -DPA1 and Common, Intermediate and Well Documented (CIWD3.0) for alleles of HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1].21-23 The committee voted to accept the proposed serologic nomenclature update provided that a validation study was conducted. The manuscript aiming to confirm these computationally predicted antigens defined by DEP residues for the 11 HLA loci was designed to assess and compare the antibody reactivity of patients' sera in solid phase assays with Single Antigen Bead (SAB) preparations from various HLA proteins24. The differences in correlation confirmed the distinctions between proposed associated antigens and identified a few additional antigens.21, 25 A full listing of all the serological specificities for HLA-A, -B, -C, -DR, -DQ, and -DP and cellular defined specificities for HLA-Dw and HLA-DPw are given in Table 3. The concept of an HLA Associated Antigen was introduced in 1991, with the understanding that serological types would be more closely associated with the allele sequence defining them. Thirteen associated antigens were named at this time: A203, A210, A2403, B703, B3901, B3902, B4005, B5102, B5103, B7801, DR103, DR1403, and DR1404.12 In 1996 the B2708 associated antigen was named and it was decided to shorten the B7801 antigen name to B78.15 Following the definition of novel associated antigens documented below, it has been necessary to update the names of four of these: A203, A210, B703, and DR103, have been updated to A0203, A0210, B0703, and DR0103. A full listing of all the Associated Antigens for HLA-A, -B, -C, −and -DR are given in Table 4. This report includes nomenclature for the serological specificities encoded by both the HLA-DQA1 and HLA-DQB1 genes. As such it is now possible to define a nomenclature for the paired combination of both subunits of HLA-DQ molecules. Table 5 lists those proteins encoded in cis by common DQ haplotype blocks. The specificities resulting from trans-encoded heterodimers should be presented in the same format. The newly assigned HLA antigens and associated antigens will be implemented in April 2026 and will be made available through the IPD-IMGT/HLA Database (www.ebi.ac.uk/ipd/imgt/hla) with the April 2026 release of the database.26-28 The IPD-IMGT/HLA Database continues to act as the official repository for HLA sequences named by the WHO Nomenclature Committee for Factors of the HLA System.26-28 The database contains sequences for all HLA alleles officially recognised by the WHO Nomenclature Committee for Factors of the HLA System and provides users with online tools and facilities for their retrieval and analysis. These include allele reports, alignment tools, and detailed descriptions of the source cells. The online IPD-IMGT/HLA Database submission tool allows both new and confirmatory sequences to be submitted directly to the WHO Nomenclature Committee. New releases of the database are made every three months, in January, April, July and October, with the latest version (release 3.63.0 January 2026) containing 43,758 HLA alleles. The database may be accessed via the worldwide web at www.ebi.ac.uk/ipd/imgt/hla. The IPD-IMGT/HLA Database is currently supported by the following organisations: NMDP, TxMiller Foundation, CareDx, DKMS, Gift of Life, Werfen, Scisco Genetics, the European Federation for Immunogenetics (EFI), GenDx, Pirche, ThermoFisher, the American Society for Histocompatibility and Immunogenetics (ASHI), LabCorp, Histogenetics, the Asia-Pacific Histocompatibility and Immunogenetics Association (APHIA), BAG Diagnostics, Protrans, Inno-train, and Anthony Nolan. The Committee would like to thank Dominic Barker, Michael Cooper, Sebastian Hopper and Surayia Akter for their work with the IPD-IMGT/HLA Database. Also thanked is Andy Yates and the staff at the European Bioinformatics Institute for their continued support of the IPD-IMGT/HLA Database. We would also like to thank the many organisations that provide financial support for the IPD-IMGT/HLA Database and Benjamin Hester of the ‘NMDP Foundation’ for his work in soliciting and coordinating the funding of this project. We are grateful to Stanford Blood Center for covering the cost for providing open access for this article. SGE Marsh, University College London, London, UK (Chairman) WF Bodmer, Oncology Department, Oxford University, Oxford, UK MN Carrington, Basic Science Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, MD, USA and Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA & Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA HA Erlich, Benioff UCSF Children's Hospital Oakland Research Institute, Oakland, USA M Fernández-Viña, Stanford Blood Center, Palo Alto, USA & Department of Pathology, Stanford University School of Medicine, Stanford, USA S Heidt, Erasmus Medical Center, Rotterdam, & Leiden University Medical Center, Leiden, The Netherlands R Holdsworth, University of Melbourne, Melbourne, Australia WR Mayr, University of Vienna, Vienna, Austria M Maiers, Center for International Blood and Marrow Transplant Research, (CIBMTR), NMDP, Minneapolis, USA P Parham, Stanford University School of Medicine, Stanford, USA EW Petersdorf, Fred Hutchinson Cancer Center, Seattle, USA J Robinson, Anthony Nolan Research Institute, & University College London, London, UK J Trowsdale, Cambridge University, Cambridge, UK RE Bontrop, Biomedical Primate Research Centre, Rijswijk, The Netherlands K Osoegawa, Stanford Blood Center, Palo Alto, USA New sequences should be communicated to the WHO Nomenclature Committee for Factors of the HLA System via the sequence submission tool of the IPD-IMGT/HLA Database to receive official names, www.ebi.ac.uk/ipd/imgt/hla. The data that support the findings of this study are available from the corresponding author upon reasonable request.

The authors of this ambitious book address a fundamental political question: why are leaders who produce peace and prosperity turned out of office while those who preside over corruption, war, and misery endure? Considering this political puzzle, they also answer the related economic question of why some countries experience successful economic development and others do not. The authors construct a provocative theory on the selection of leaders and present specific formal models from which their central claims can be deduced. They show how political leaders allocate resources and how institutions for selecting leaders create incentives for leaders to pursue good and bad public policy. They also extend the model to explain the consequences of war on political survival. Throughout the book, they provide illustrations from history, ranging from ancient Sparta to Vichy France, and test the model against statistics gathered from cross-national data. The authors explain the political intuition underlying their theory in nontechnical language, reserving formal proofs for chapter appendixes. They conclude by presenting policy prescriptions based on what has been demonstrated theoretically and empirically.

Purpose To increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events in patients treated with immune checkpoint inhibitor (ICPi) therapy. Methods A multidisciplinary, multi-organizational panel of experts in medical oncology, dermatology, gastroenterology, rheumatology, pulmonology, endocrinology, urology, neurology, hematology, emergency medicine, nursing, trialist, and advocacy was convened to develop the clinical practice guideline. Guideline development involved a systematic review of the literature and an informal consensus process. The systematic review focused on guidelines, systematic reviews and meta-analyses, randomized controlled trials, and case series published from 2000 through 2017. Results The systematic review identified 204 eligible publications. Much of the evidence consisted of systematic reviews of observational data, consensus guidelines, case series, and case reports. Due to the paucity of high-quality evidence on management of immune-related adverse events, recommendations are based on expert consensus. Recommendations Recommendations for specific organ system-based toxicity diagnosis and management are presented. While management varies according to organ system affected, in general, ICPi therapy should be continued with close monitoring for grade 1 toxicities, with the exception of some neurologic, hematologic, and cardiac toxicities. ICPi therapy may be suspended for most grade 2 toxicities, with consideration of resuming when symptoms revert to grade 1 or less. Corticosteroids may be administered. Grade 3 toxicities generally warrant suspension of ICPis and the initiation of high-dose corticosteroids (prednisone 1 to 2 mg/kg/d or methylprednisolone 1 to 2 mg/kg/d). Corticosteroids should be tapered over the course of at least 4 to 6 weeks. Some refractory cases may require infliximab or other immunosuppressive therapy. In general, permanent discontinuation of ICPis is recommended with grade 4 toxicities, with the exception of endocrinopathies that have been controlled by hormone replacement. Additional information is available at www.asco.org/supportive-care-guidelines and www.asco.org/guidelineswiki .

Abstract Inorganic metal–oxygen cluster anions form a class of compounds that is unique in its topological and electronic versatility and is important in several disciplines. Names such as Berzelius , Werner , and Pauling appear in the early literature of the field. These clusters (so‐called isopoly‐ and heteropolyanions) contain highly symmetrical core assemblies of MO x units (M = V, Mo, W) and often adopt quasi‐spherical structures based on Archimedean and Platonic solids of considerable topological interest. Understanding the driving force for the formation of high‐nuclearity clusters is still a formidable challenge. Polyoxoanions are important models for elucidating the biological and catalytic action of metal–chalcogenide clusters, since metal–metal interactions in the oxo clusters range from very weak (virtually none) to strong (metal–metal bonding) and can be controlled by choice of metal (3d, 4d, 5d), electron population (degree of reduction), and extent of protonation. Mixed‐valence vanadates, in particular, show novel capacities for unpaired electrons, and the magnetic properties of these complexes may be tuned in a stepwise manner. Many vanadates also act as cryptands and clathrate hosts not only for neutral molecules and cations but also for anions, whereby a remarkable “induced self‐assembly process” often occurs. Polyoxometalates have found applications in analytical and clinical chemistry, catalysis (including photocatalysis), biochemistry (electron transport inhibition), medicine (antitumoral, antiviral, and even anti‐HIV activity), and solid‐state devices. These fields are the focus of much current research. Metal–oxygen clusters are also present in the geosphere and possibly in the biosphere. The mixed–valence vanadates contribute to an understanding of the extremely versatile geochemistry of the metal. The significant differences between the chemistry of the polyoxoanions and that of the thioanions of the same elements is of relevance to heterogeneous catalysis, bioinorganic chemistry, and veterinary medicine.

Genetic changes underlying clear cell renal cell carcinoma (ccRCC) include alterations in genes controlling cellular oxygen sensing (for example, VHL) and the maintenance of chromatin states (for example, PBRM1). We surveyed more than 400 tumours using different genomic platforms and identified 19 significantly mutated genes. The PI(3)K/AKT pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodelling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving downregulation of genes involved in the TCA cycle, decreased AMPK and PTEN protein levels, upregulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of miR-21 (also known as MIR21) and GRB10. Remodelling cellular metabolism thus constitutes a recurrent pattern in ccRCC that correlates with tumour stage and severity and offers new views on the opportunities for disease treatment. The Cancer Genome Atlas Research Network reports an integrative analysis of more than 400 samples of clear cell renal cell carcinoma based on genomic, DNA methylation, RNA and proteomic characterisation; frequent mutations were identified in the PI(3)K/AKT pathway, suggesting this pathway might be a potential therapeutic target, among the findings is also a demonstration of metabolic remodelling which correlates with tumour stage and severity. The Cancer Genome Atlas consortium reports an integrative analysis of more than 400 samples of clear cell renal carcinoma on the basis of genomic, DNA methylation, RNA and proteomic characterization. The data reveal frequent mutations in the PI(3)K/AKT pathway, suggesting that this pathway might be a potential therapeutic target, in addition to an array of epigenetic alterations that are linked to specific mutations in chromatin-associated proteins. One notable finding is the presence of a metabolic shift in aggressive cancers, correlating with tumour stage and severity.