Mapping and understanding organizational change:Ireland 1922-2010

Capturing, mapping, and understanding organizational change within bureaucracies is inherently problematic, and the paucity of empirical research in this area reflects the traditional reluctance of scholars to pursue this endeavor. In this article, drawing on the Irish case of organizational change, potential avenues for overcoming such challenges are presented. Drawing on the resources of a time-series database that captures and codes the life cycle of all Irish public organizations since independence, the article explores the evolution of the Irish administrative system since the independence of the state in 1922. These findings provide some pointers toward overcoming the challenges associated with studying change in Whitehall-type bureaucracies. © Taylor & Francis Group, LLC.

The Interlaboratory Robustness Of Next-Generation Sequencing (IRON) Study Phase II: Deep-Sequencing Analyses Of Hematological Malignancies Performed In 8,867 Cases By An International Network Involving 27 Laboratories

Introduction: Amplicon deep-sequencing using second-generation sequencing technology is an innovative molecular diagnostic technique and enables a highly-sensitive detection of mutations. As an international consortium we had investigated previously the robustness, precision, and reproducibility of 454 amplicon next-generation sequencing (NGS) across 10 laboratories from 8 countries (Leukemia, 2011;25:1840-8).

Aims: In Phase II of the study, we established distinct working groups for various hematological malignancies, i.e. acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), and multiple myeloma. Currently, 27 laboratories from 13 countries are part of this research consortium. In total, 74 gene targets were selected by the working groups and amplicons were developed for a NGS deep-sequencing assay (454 Life Sciences, Branford, CT). A data analysis pipeline was developed to standardize mutation interpretation both for accessing raw data (Roche Amplicon Variant Analyzer, 454 Life Sciences) and variant interpretation (Sequence Pilot, JSI Medical Systems, Kippenheim, Germany).

Results: We will report on the design, standardization, quality control aspects, landscape of mutations, as well as the prognostic and predictive utility of this assay in a cohort of 8,867 cases. Overall, 1,146 primer sequences were designed and tested. In detail, for example in AML, 924 cases had been screened for CEBPA mutations. RUNX1 mutations were analyzed in 1,888 cases applying the deep-sequencing read counts to study the stability of such mutations at relapse and their utility as a biomarker to detect residual disease. Analyses of DNMT3A (n=1,041) were focused to perform landscape investigations and to address the prognostic relevance. Additionally, this working group is focusing on TET2, ASXL1, and TP53 analyses. A novel prognostic model is being developed allowing stratification of AML into prognostic subgroups based on molecular markers only. In ALL, 1,124 pediatric and adult cases have been screened, including 763 assays for TP53 mutations both at diagnosis and relapse of ALL. Pediatric and adult leukemia expert labs developed additional content to study the mutation incidence of other B and T lineage markers such as IKZF1, JAK2, IL7R, PAX5, EP300, LEF1, CRLF2, PHF6, WT1, JAK1, PTEN, AKT1, IL7R, NOTCH1, CREBBP, or FBXW7. Further, the molecular landscape of CLL is changing rapidly. As such, a separate working group focused on analyses including NOTCH1, SF3B1, MYD88, XPO1, FBXW7 and BIRC3. Currently, 922 cases were screened to investigate the range of mutational burden of NOTCH1 mutations for their prognostic relevance. In MDS, RUNX1 mutation analyses were performed in 977 cases. The prognostic relevance of TP53 mutations in MDS was assessed in additional 327 cases, including isolated deletions of chromosome 5q. Next, content was developed targeting genes of the cellular splicing component, e.g. SF3B1, SRSF2, U2AF1, and ZRSR2. In BCR-ABL1-negative MPN, nine genes of interest (JAK2, MPL, TET2, CBL, KRAS, EZH2, IDH1, IDH2, ASXL1) have been analyzed in a cohort of 155 primary myelofibrosis cases searching for novel somatic mutations and addressing their relevance for disease progression and leukemia transformation. Moreover, an assay was developed and applied to CMML cases allowing the simultaneous analysis of 25 leukemia-associated target genes in a single sequencing run using just 20 ng of starting DNA. Finally, nine laboratories are studying CML, applying ultra-deep sequencing of the BCR-ABL1 tyrosine kinase domain. Analyses were performed on 615 cases investigating the dynamics of expansion of mutated clones under various tyrosine kinase inhibitor therapies.

Conclusion: Molecular characterization of hematological malignancies today requires high diagnostic sensitivity and specificity. As part of the IRON-II study, a network of laboratories analyzed a variety of disease entities applying amplicon-based NGS assays. Importantly, the consortium not only standardized assay design for disease-specific panels, but also achieved consensus on a common data analysis pipeline for mutation interpretation. Distinct working groups have been forged to address scientific tasks and in total 8,867 cases had been analyzed thus far.

The Economics of Total War and Reconstruction, 1914-1922

This chapter features a discussion of the economy and mobilization for the First World War. The authors analyse the implications and cost of total war, concluding with an examination of its contradictory legacies. In studying the war’s impact on Germany in particular, the chapter provides an in-depth look at the consequences of war on Europe’s strongest pre-war economy, without the complications of separating out the issues of a developing country, which can mimic those faced in wartime. The economic challenges that warring parties faced during the war included mobilization, warfare, labour shortage, impaired domestic economic activity, restricted international trade, a systematic redistribution of resources towards the war economy, food rationing, the predictable emergence of black markets, and a drop in living standards. The authors also discuss strategies to meet the significant financial demands associated with the war, and its tumultuous economic and political aftermath.

A European Culture War in the Twentieth Century? Antic-Catholicism and Anti-Bolshevism between Moscow, Berlin, and the Vatican 1922 to 1933

The term “culture war” has become a generic expression for secular-catholic conflicts across nineteenth-century Europe. Yet, if measured by acts of violence, anticlericalism peaked in the years between 1927 and 1939, when thousands of Catholic priests and believers were imprisoned or executed and hundreds of churches razed in Mexico, Spain and Russia. This essay argues that not only in these three countries, but indeed across Europe a culture war raged in the interwar period. It takes, as a case study, the interaction of communist and Catholic actors located in the Vatican, the Soviet Union, and Germany in the period between the beginning of the Pontificate of Pius XI in 1922 and Hitler’s appointment as chancellor of Germany in 1933. Using correspondence and reports from the Vatican archives, this essay shows how Papal officials and communist leaders each sought to mobilize the German populace to achieve their own diplomatic ends. German Catholics and communists gladly responded to the call to arms that sounded from Rome and Moscow in 1930, but they did so also to further their own domestic goals. The case study shows how national contexts inflected the transnational dynamics of radical anti-Catholicism in interwar Europe. In the end, agitation against “godlessness” did not lead to the return of a “Christian State” desired by many conservative Christians. Instead, the culture war further destabilized the republic and added a religious dimension to a landscape well suited to National Socialist efforts to reach a Christian population otherwise mistrustful of its völkisch and anticlerical elements.

Commemorating Women in Irish History, 1912-1922

This is a pilot project to create a website identifying places in Ireland that relate to the history of women, 1912-1922. I have also submitted a grant application to the Heritage Lottery Fund to extend this project to a longer chronological period. This is a collaborative project with Professor Bernadette Whelan in the University of Limerick.

Avoiding Negligence and Profusion: The failure of the Joint-Stock form in the Anglo-Indian Tea Trade, 1840-1870

In the 19th century, firms operating in the Anglo-Indian tea trade were organised using a variety ownership forms including the partnership, joint-stock and a combination of the two known as the Managing agency. Faced with both an increasing need for fixed capital and high agency costs caused by the distance between owners and managers, the firms adapted and increasingly adopted the hybrid managing agency model to overcome these problems. Using new data from Calcutta and Bengal Commercial Registers and detailed case studies of the Assam Company and Gillanders, Arbuthnot and Co, this paper demonstrates that British entrepreneurs did not see the choice of ownership as a dichotomy or firm boundaries as fixed, but instead innovatively drew on the strengths of different forms of ownership to compete and grow successfully.

Christian Gottlob Neefe and the Early Reception of Le nozze di Figaro and Don Giovanni

A brief account of Christian Gottlob Neefe's engagement with Mozart's Le nozze di Figaro and Don Giovanni as exemplified in his correspondence.