Journal articles on the topic 'Emanuel Formation'

Представлен случай синдрома Эмануэль у новорожденной девочки с врожденным пороком сердца и высокой кишечной непроходимостью. Кариотип ребёнка: 47,XX,+der(22)t(11;22)(q11.2;q23). Приведен краткий обзор данных литературы о механизме возникновения перестройки, клинических проявлениях и генетическом консультировании при синдроме Эмануэль. We report on a case of Emanuel syndrome on a newborn girl with congenital heart defect and high bowel obstruction, karyotype: 47,XX,+der(22)t(11;22)(q11.2;q23)pat. The report contains brief review of information from literature about formation of such rearrangement, clinical implications, and genetic counseling for this syndrome.

ABSTRACT. A new convection parameterization scheme proposed by Emanuel (1991) is used to simulate the evolution of tropical cyclone. The numerical model used for this study is a 19 level axi-symmetric primitive equation, hydrostatic model in a z co-ordinate system. The vertical domain ranges from 0 to 18 km and the horizontal domain ranges upto 3114 km with a resolution of 20 km. in the central 400 km radius and with increasing radial distance thereafter. The evolution of an initially balanced vortex with an initial strength of 9 m/sec is studied. It is shown that Emanuel's convection scheme is successful in simulating the development of the initial vortex into a mature, intense cyclonic storm. At the mature stage, a minimum surface pressure of 930 hPa is attained with the associated low level maximum tangential wind speed of 70 m/sec. The simulated circulation features at the mature stage show the formation of an intense cyclone. Two different sensitivity experiments were performed. A set of experiments with the variation of sea surface temperature (SST) from 300.5° to 302° K in steps of 0.5° K have shown that the intensity of model cyclone increases with the increase of SST. Another set of experiments with variation of latitude has shown that the cyclonic storm is more intense at lower latitudes.

In this study, classroom discourse is chosen as the subject to be analysed in terms of the basic structures of conversation analysis (CA) which are turn-taking organisation, sequence organisation, repair and action formation, as developed principally by Harvey Sacks, Emanuel Schegloff and Gail Jefferson. As a form of educational talk, classroom interaction should be scrutinised not only in a conversational perspective, but also from an institutional view. Many controversies and debates regarding this particular discourse are present from the conversation analytic point of view, indicating that it is indeed an important subject that need extended studies on. This study analyses learner-learner interaction in task-oriented, learner-centred classrooms, instead of traditional classroom interaction, from the conversation analytic perspective. It helps expanding the research on this subject to a new focus, which is modern classroom interaction.

To the sound of trumpets and drums, the people gathered before the church of Our Lady of the Rosary in the square of the small town of Santa Cruz in southern Goiás. They were there for the “jogo dos cavaleiros” (the game of the cavalrymen). First of all, the troops processed from the commandant's house to the square, which was lined in the form of a cross. Enveloped in long mantles, the women of the commandant's family headed a second procession, including soldiers, musicians, and the Austrian visitor, Johann Emanuel Pohl, who accompanied the commander and the judge. The townspeople followed at the end. Receiving them in formation in the “spacious” square were the mounted cavalrymen dressed in Portuguese uniforms. With their swords, they saluted Pohl and the other men of high rank, who took their seats on the top of a stepped platform shaded by a thatched roof, while the soldiers sat below.

Self-assessment in the school environment can be defined as the students’ ability to make valuable judgements about their own academic performance, either by reference to the teacher’s educational goals, previous academic results, or the academic performance of other colleagues. The formation of such self-assessment skills is strongly influenced by a number of internal and external psycho-pedagogical factors, including chronological age, motivation for learning, level of cognitive development, perceived self-efficacy, the teacher's teaching style, the social status of the student's family, their group affiliation, etc. Starting from this point, the purpose of the present research was the analysis of the students’ degree of awareness of the role of perceived self-efficacy in the formation of objective didactic self-evaluation skills. The research sample consisted of 108 students, currently attending the Psycho-Pedagogy and Methodology Study Program courses at the University of Oradea and Emanuel University of Oradea, Romania. The research methodology was targeted at requesting these students to self-assess their performance in a subject of the afore-stated study program, respectively administering a scale for measuring personal self-efficacy. The results showed that most of the students tended to either evaluate themselves objectively or under-evaluate themselves, against the backdrop of a high level of perceived self-efficacy, respectively of superior academic performance. Keywords: academic performance, didactic self-evaluation skills, perceived self-efficacy, self-image, teaching career

Abstract In light of the questioning related to contemporary parental combinations, I maintain that whatever these combinations may be, in the majority of cases a good enough mixture of life and death sexual drives, of ethical ability and of vital narcissism, will exist in the parents’ psyche, even though proper genital sexuality has been either partially or completely excluded from procreation. This good enough mix lies at the foundation of a good enough child development for what concerns the unavoidable impact of the parental environment upon the child’s psyche’s formation. I will use the Oedipus’s “anamnesis”, describing the potential dynamics of any parents’ psyche through this myth. I will insist upon the ethical dimension, while, following Emanuel Levinas, I will define ethics as a responsibility for the other, an ability originating, in my view, in the feminine/ maternal of any human being and resulting first from the traces left in the infant and then the child’s psyche’s zone of infinity by the enigm-ethic messages coming from the adult world, which is in charge of him or her. Respecting this emotionally loaded asymmetric responsibility in the parent/child relationship, in any kind of parental constellation, facilitates a sense of singularity, of identity and of belonging in the child.

The upper Lower to Middle Devonian Bird Fiord Formation (late Emsian to late Eifelian) is a carbonate–siliciclastic succession, up to 900 m thick, that contains a diverse brachiopod-dominated fauna. Twenty-two species belonging to 21 genera have been recognized from the collection of more than 45 000 specimens, among which the atrypids form 52% of the biota, spiriferids ~13%, orthids ~8%, productids ~3%, rhynchonellids ~2%, terebratulids ~1%, and the strophomenids, pentamerids, and athyridids each <1%. Spinatrypina, Schizophoria, Elythyna, Desqumatia (Independentrypa), Cupularostrum, and Atrypa that collectively form more than 80% of the brachiopod biota. The following species are described here: Schizophoria (Schizophoria) sulcata, Ivdelinia grinnellensis, Cupularostrum repetitor, Hypothyridina cf. bifurcata, Atrypa sp., Emanuella bisinuata, Elythyna sverdrupi, Perryspirifer scheii, Costacranaena marlenae. Despite its endemic character, the brachiopod fauna from the Bird Fiord Formation of Arctic Canada can be assigned to the Old World Realm. Its strong affinity to Europe and western Canada supports the notion that, during the Devonian, faunal exchanges between Europe and North America took place via Arctic Canada.

AbstractGymnolaemate bryozoans are common encrusters on bivalve shells from the early to middle Albian parts of the Glen Rose and Walnut formations of southcentral and northcentral Texas. Here, we report for the first time the presence of seven gymnolaemate bryozoans, all of which represent new species. They include the bioimmured ctenostome Simplicidium jontoddi n. sp., and the cheilostomes Rhammatopora glenrosa n. sp., Iyarispora ikaanakiteeh n. gen. n. sp., Iyarispora chiass n. gen. n. sp., Charixa bispinata n. sp., Charixa sexspinata n. sp., and Charixa emanuelae n. sp. The Glen Rose bryozoans slightly antedate the commencement of an explosive bryozoan radiation and the first appearance of neocheilostomes in the late Albian. Although the diversity of cheilostomes in the Glen Rose and Walnut formations is similar to that of cyclostomes, cheilostomes are more abundant and produced larger colonies. These formations therefore yield the oldest known bryozoan assemblage dominated in terms of biomass by cheilostomes. The genus concept of Charixa is discussed and amended.UUID: http://zoobank.org/d9e8f1a4-ae6a-4455-abb3-3b0a75a7d294

The internal morphology of ambocoeliid brachiopods from the Middle Devonian Hamilton Group of western New York indicates a need for several taxonomic revisions. “Ambocoelia” praeumbona is transferred to Emanuella. “Ambocoelia” spinosa and “A.” nana represent Crurispina n. gen. Specimens of species belonging to Crurispina have moderately well developed crural plates, and, accordingly, they are assigned to the subfamily Rhynchospiriferinae. Crural plates are small and obscure but clearly present in Ambocoelia umbonata, the type species of Ambocoelia. Thus, the diagnosis of the subfamily Ambocoeliinae is emended to include species with tiny crural plates.Ambocoeliid specimens from the Levanna Shale Member of the Skaneateles Formation, formerly referred to Echinocoelia, reveal several elaborate features in the pedicle valve, including an apical plate and a hollow tube supported by a median septum. These specimens represent a new genus and species, Mucroclipeus eliei. The homeomorphy found in the shape and size of these ambocoeliids may be the result of paedomorphosis. Additionally, their pattern of occurrence and minute size suggest that they attained their paedomorphic state through progenesis. The taxa Ambocoelia tuberculata n. sp., Crurispina n. gen., and Mucroclipeus eliei n. gen. and sp. are established.

Introduction Purified poloxamer188 (P188) (Mast Therapeutics) is a non-ionic, linear block copolymer composed of a central chain of hydrophobic polyoxypropylene and two flanking chains of hydrophylic polyoxyethylene (MW 8.5 kDa). This agent has hemorheologic properties which result in improved microvascular blood flow. P188 has been investigated in a number of indications and is currently under study in an international phase 3 clinical trial in sickle cell patients with vaso-occlusive crisis. Dextrans represent branched polysaccharides of 10-70 kDa that have been used as antithrombotic agents and plasma expanders. Sickle cell disease (SCD) represents a complex hemorheologic condition due to RBC aggregation and cell-fibrin/fibrinogen interactions. The erythrocyte sedimentation rate (ESR) is reflective of RBC and plasma interactions. This study was designed to compare the effect of P188 and dextrans on ESR’s in blood obtained from healthy subjects and patients with sickle cell disease who were seen at Loyola University Medical Center clinics. Material and Methods Whole EDTA blood collected from normal individuals (n=8) and sickle cell patients confirmed by electrophoresis (n=11) were supplemented with P188 or dextran 10K, 18K , 40K and 70K at various concentrations (or saline control). ESR was measured using standard laboratory technique. Results The ESR’s for sickle cell patients (26.4 ± 7.1 mm/hr) were significantly higher in comparison to the ESR’s for healthy subjects (14.6 ± 2.1 mm/hr). Supplementation of P188 decreased ESR’s in both populations. Normal blood ESR’s decreased to 9.1 ± 1.3 mm/hr (38%), whereas the sickle cell patient values decreased to 14.1 ± 4.6 mm/hr (47%). At comparable concentrations, none of the dextrans changed ESR’s in healthy subjects or patients with sickle cell disease. Discussion These results demonstrate that ESR in SCD patients are elevated compared to healthy subjects. P188 supplementation decreased (up to 50%) ESR’s in both the healthy subjects and sickle cell patients. This may be due to the inhibition of rouleaux formation resulting from P188 effects on RBC membranes or cell-protein interactions. None of the dextrans produced a similar decrease, suggesting that the observed lowering of ESR by P188 is unlikely to be due to a non-specific effect related to polymer molecular weight. Clinical Implications P188 is a potential therapeutic agent which may facilitate blood flow and reduce cell-fibrin/fibrinogen interactions in a variety of hemorrheologic disorders. The observed decrease in ESR both in normal and sickle cell blood samples by P188 may primarily be due to increased membrane hydration, fibrinogen dispersion and anti-adhesive effects of this agent. Disclosures: Emanuele: Mast Therapeutics: Employment. Fareed:Mast Therapeutics: Research Funding.

Abstract Renal Cell Carcinoma (RCC) is a type of kidney cancer which derives from renal tubular epithelial cells and is responsible for approximately 90-95% of cases in adults. Incidence and prevalence of RCC are rising, and 5-year survival of metastatic disease is close to 10%. The therapy of RCC mainly targets the angiogenic and immunosuppressive tumor microenvironment (TME), but it is rarely curative and drug resistance is almost inevitable. Lack of validated biomarkers and scarce knowledge of the biological processes occurring during RCC progression are main reasons of therapy failure. Using an immunocompetent murine model of RCC, we identified Interleukin-34 (IL34) as potential biomarker of RCC progression, whose expression is associated with advanced tumor stage and reduced survival in RCC patients. In cancer, IL34 was demonstrated to regulate cancer cell proliferation and monocytes survival and differentiation into macrophages. Regarding to RCC, IL34 role in the TME still remains elusive and has never been described. To elucidate the function of IL34 in RCC biology, we undertook different approaches: Gene Ontology enrichment analysis of IL34 co-expressed genes, using the KIRC-TCGA database, which revealed that such genes are involved in different immune system related processes; orthotopic implantation of IL34 over-expressing murine renal cancer cells (i.e. RENCA cell line) in BALB/c mice, where we observed, both in primary tumors and lung metastases, an accumulation of tumor associated macrophages (TAM) expressing M2-type macrophage markers (e.g. Cd206 and Cd163). Subsequently, to deeply investigate how IL34 can finely tune the tumor immune microenvironment of RCC, we also employed an experiment of Single Nuclei Sequencing using murine samples over-expressing IL34 (or control empty vector). Briefly, RENCA cancer cells were implanted in BALB/c mice using two different injection modalities: orthotopic implantation in the kidney, to generate primary tumors; 2) tail vein injection, for lung metastases formation. After tumor or metastases formation, samples were snap-frozen in liquid nitrogen and processed for cDNA library preparation for next generation sequencing. Our project aims to elucidate how IL34 can be implicated in the regulation of TME in RCC and, in particular, of the phenotype of the accumulated TAM. As TAM are known to promote cancer progression by enhancing tumor angiogenesis and immunosuppression, the study of IL34 role in the TME can reveal novel paradigms in RCC biology, and may be fundamental to improve the current therapy (e.g. using drugs targeting IL34 activity). Citation Format: Andrea Emanuelli, Wilfried Souleyreau, Tiffanie Chouleur, Marie-Alix Derieppe, Andreas Bikfalvi. Interleukin-34 regulates tumor immune microenvironment of renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3140.

Abstract The release of extracellular vesicles (EVs) is a phenomenon shared by all cell types as a means of communication. Characterization and classification of EVs is challenging and still a matter of debate. However, a general consensus on EVs nomenclatura has been made, on the basis of their size, formation and release mechanisms. EVs has been classified into exosomes, secreted via exocytosis from the late endosome multivesicular bodies, whereas microvesicles (MVs) bud from the plasma membrane and apoptotic bodies are released by cells undergoing apoptosis. Initially regarded as cellular debris, EVs have gained considerable interest in basic sciences and medical research, both as biomarkers and mediators of biological functions. Indeed, EVs carry regulatory molecules including lipid, proteins and different RNA species through the extracellular spaces and deliver these cargos to target cells to modify cellular activity, thereby contributing to both physiological and pathological responses. Because EVs bear markers derived from their parent cells and can be detected in most body fluids, characterization of EVs of different cellular origin is an underestimated source of biological information on cellular activation during disease evolution, and will probably serve as valuable diagnostic and prognostic biomarker in the future. However, the current methods used for the EVs isolation and analysis have several limitations and lack standardization, leading to uncertainties regarding the subtypes of EVs studied and how to interpret the data. After a rapid overview of the current knowledge on the mechanisms of formation, subcellular origin and composition of the different types of EVs, this presentation will focus on microvesicles (MVs). We will first address how their structure/function diversity determines their multifaceted biological functions in coagulation, inflammation, angiogenesis and endothelial dysfunction (ref 1, 2, 3). Secondly, we will summarize the current debate on the different methodologies available for their analysis and quantification in body fluids. A specific attention will be devoted to standardization of sample processing and MVs analysis, and also to recommendations from scientific societies for EVs translational applications as emerging biomarkers measurable in liquid biopsies (ref 4, 5, 6). Finally, focusing on cardiovascular diseases and cancer as emerging field where MVs detection have promising impact to improve patient management, we will illustrate how combination of increasing fundamental knowledge, technological progress and standardization will push MVs towards reliable biomarkers ready for the clinics. 1- Ridger VC, Boulanger CM, Angelillo-Scherrer A, Badimon L, Blanc-Brude O, Bochaton-Piallat ML, Boilard E, Buzas EI, Caporali A, Dignat-George F, Evans PC, Lacroix R, Lutgens E, Ketelhuth DFJ, Nieuwland R, Toti F, Tunon J, Weber C, Hoefer IE. Microvesicles in vascular homeostasis and diseases. Position Paper of the European Society of Cardiology (ESC) Working Group on Atherosclerosis and Vascular Biology. Thromb Haemost. 2017;28;117(7):1296-1316. 2- Todorova D, Simoncini S, Lacroix R, Sabatier F, Dignat-George F. Extracellular Vesicles in Angiogenesis. Circ Res. 2017;12;120(10):1658-1673. 3- Lacroix R, Dubois C, Leroyer AS, Sabatier F, Dignat-George F. Revisited role of microparticles in arterial and venous thrombosis. J Thromb Haemost. 2013;11 Suppl 1:24-35. 4- Coumans FAW, Brisson AR, Buzas EI, Dignat-George F, Drees EEE, El-Andaloussi S, Emanueli C, Gasecka A, Hendrix A, Hill AF, Lacroix R, Lee Y, van Leeuwen TG, Mackman N, Mäger I, Nolan JP, van der Pol E, Pegtel DM, Sahoo S, Siljander PRM, Sturk G, de Wever O, Nieuwland R. Methodological Guidelines to Study Extracellular Vesicles. Circ Res. 2017;12;120(10):1632-1648. 5-Lacroix R, Judicone C, Mooberry M, Boucekine M, Key NS, Dignat-George F; The ISTH SSC Workshop. Standardization of pre-analytical variables in plasma microparticle determination: results of the International Society on Thrombosis and Haemostasis SSC Collaborative workshop. J Thromb Haemost. 2013 Apr 2. 6- Cointe S, Judicone C, Robert S, Mooberry MJ, Poncelet P, Wauben M, Nieuwland R, Key NS, Dignat-George F, Lacroix R. Standardization of microparticle enumeration across different flow cytometry platforms: results of a multicenter collaborative workshop. J Thromb Haemost. 2017;15(1):187-193. Disclosures No relevant conflicts of interest to declare.

Abstract Background:The introduction of anti-HER2 therapies, trastuzumab and pertuzumab (HP) to the treatment of metastatic HER2-positive breast cancer has had a transformational impact on the outcomes for this disease. Nevertheless, disease progression is ultimately observed in most patients within 3 years carrying the potential for morbidity and potentially more toxic therapies. To identify selective strategies to prevent disease progression, we sought to elucidate mechanisms of resistance to anti-HER2 therapies by analyzing a large cohort of genomically and clinically annotated HER2+ breast cancers. Methods: Patients with advanced HER2+ breast cancer who underwent prospective clinical tumor sequencing utilizing MSK-IMPACT assay between April 2014 and February 2021 were included in the analysis. Clinical HER2 positivity was defined as per ASCO/CAP guidelines. Cox proportional hazard models were used to determine the association between genomic alterations and progression-free survival (PFS) on 1st line HP and taxane-based therapy (THP). Only patients with a sequenced pre-treatment tumor sample were included in the survival analysis. Recurrent mutations identified were modeled in HER2+ breast cancer cell lines using short hairpin RNAs and CRISPR/Cas9, and the sensitivity of these isogenic pairs to HER2-targeted therapies was evaluated via metabolic and colony formation assays of cell proliferation. Results: We identified 733 ERBB2-amplified primary (n=385) and metastatic (n=348) that underwent sequencing. Concurrent PIK3CA mutations were identified in 30% of the tumors. Pathogenic activating alterations involving the MAPK pathway were observed in 12.8% of tumors with the most frequent alterations being NF1 loss, ERBB2 and RAS activating mutations. MAPK alterations were significantly enriched in the metastatic tumors (16.6%) compared to the treatment-naïve primaries (9.8%, p=0.020). The outcome analysis included 145 patients with advanced clinically HER2+ breast cancer whose tumors were sequenced prior to starting 1st line THP. Twenty percent (29/145) of tumors did not show genomic ERBB2 amplification as detected by NGS and had a significantly worse outcome (median PFS of 9.4 months [95% CI 5.5-19] and 23 months [95% CI 17-30], respectively; p=0.015). PIK3CA mutations were also associated with a shorter PFS (mutant: 13 months [95%CI: 7.7-18] vs wild type: 23 months [95%CI 17-16], p=0.0013). We further found reduced PFS in MAPK altered tumors (median PFS 9.9 months; 95% CI: 5.5-17) compared to the rest of the population (median PFS 21 months; 95% CI: 17-30; p=0.01). On multivariable analysis adjusted for estrogen receptor status, and presence of PIK3CA/AKT1/PTEN mutations and genomic ERBB2 amplification, MAPK pathway alterations were independently associated with worse outcome (HR: 2.25; 95% CI: 1.29, 3.93; multivariate p = 0.0043). To establish a causal role for MAPK alterations in reducing efficacy of anti-HER2 therapy, we depleted NF1 expression or expressed mutant KRAS or BRAF in a panel of HER2+ breast cancer cell lines. Consistently, MAPK-altered cell lines exhibited resistance to FDA approved HER2 inhibitors in vitro and in vivo. Conclusions: This clinicogenomic analysis of mechanisms of resistance to anti-HER2 therapy demonstrated that PIK3CA activating mutations and lack of genomic ERBB2 amplification as detected by tumor sequencing are associated with shortened PFS on HP-based therapy. Our analysis uniquely identified MAPK pathway alterations as additional potential drivers of resistance to anti-HER2 therapy. Inhibition of the PI3K or MAPK pathway in such tumors may represent a new therapeutic strategy to extend H/P benefit. Citation Format: Emanuela Ferraro, Alison Smith, Anton Safonov, Paulino Tallon De Lara, Cristina Bernado', Enrique J. Arenas Lahuerta, Joaquín Arribas, David Solit, Jorge S. Reis-Filho, Neal Rosen, Larry Norton, Shanu Modi, Mark E. Robson, Chau T. Dang, Giuseppe Curigliano, Sarat Chandarlapaty, Pedram Razavi. Genomic analysis of 733 HER2+ breast cancers identifies recurrent pathways alterations associated with anti-HER2 resistance and new therapeutic vulnerabilities [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr GS3-03.

Abstract Background: Despite major technological and conceptual advancements, treatment decisions in HER2+ metastatic breast cancer (mBC) remain largely based on clinical evidence, with no established predictive biomarkers to direct treatment for individual patients. The tumour suppressor Neurofibromatosis 1 (NF1) has been implicated in endocrine resistance but its role remains incompletely characterized in mBC. NF1 is best known as a GTPase-activating protein (GAP) that attenuates RAS signalling. However, the GAP function is likely not limited to RAS, and NF1 has been involved in other GTP-dependent processes including cytoskeletal dynamics. Data mining and analysis of public mutational registries revealed NF1 mutations as particularly enriched in HER2+ mBC compared to other molecular subtypes. Methods: To investigate the biological consequences of NF1 loss, we generated NF1 KO HER2+ mBC cell lines (BT474 and SKBR3) by CRISPR-Cas9 and both 2D and 3D proliferations assays were used for drug sensitivity profiling; live-cell imaging, high-resolution confocal microscopy and an ad-hoc computational algorithm were employed to study cell fate and microtubule conformational changes. Patient data were obtained from the Northwestern University through a prospective observational study in mBC patients. Results: Screening of several compounds approved for HER2+ mBC showed that response was generally equal or reduced in NF1 KO vs WT cells. However, response to trastuzumab-emtansine (T-DM1) was significantly increased in NF1 KO cells (IC50 ~0,3 vs 1,6 μg/mL in NF1WT). This sensitization was not observed with other antibody drug conjugates (ADCs) like DS-8201 and was reproducible with maytansine alone, suggesting a pharmacologically relevant NF1 activity on microtubules. Using the FUCCI(Ca) reporter, which tracks cell cycle progression at single-cell level, we saw a more prominent G2/M phase arrest and cell death upon T-DM1 treatment in NF1 KO compared to WT cells. Notably, NF1 KO cells exhibited a higher frequency of aberrant mitotic figures (chromosome alignment defects and multipolar spindle formation) and stronger β-galactosidase activity, an established marker of senescence. Collectively, these results suggest that NF1 KO cells become particularly subject to T-DM1-triggered mitotic catastrophe. Dephosphorylation of GTP-bound tubulin is required for appropriate microtubular dynamics; so-called “GTP islands” within the inner microtubule region are prone to rapid repolymerization and are normally kept at low levels. We hypothesize that expanded GTP-tubulin islands generated by the loss of NF1 GAP activity is a major cause of microtubular instability in NF1 KO cells. Preliminary evidence in support of this model was obtained by quantification of GTP-tubulin with a specific antibody. Finally, we assessed the predictive role of NF1 as a biomarker for T-DM1 response in a cohort of 300 mBC patients with mutational data in circulating tumour DNA (Guardant 360); we identified 13 heavily pretreated patients (&gt;4 prior lines) who received T-DM1, of which 3 had loss-of-function NF1 mutations and 10 were NF1 WT. Median progression-free survival was higher in NF1-mutated than WT patients (334 vs 80 days); given the small sample size, these results cannot yet be considered significant (p=0.14). Conclusions: These results provide preliminary mechanistic and clinical evidence supporting the use of NF1 loss to guide treatment in HER2+ mBC. As novel HER2-specific agents are being rapidly added to the therapeutic arsenal, we propose biology-driven criteria to identify patients that may benefit specifically from T-DM1. In addition, NF1 dependence for correct microtubular dynamics may be exploited by other inhibitors of microtubular polymerization in use as ADC payloads, further extending the potential usefulness of NF1 determination. Citation Format: Bruno A Duso, Elena Gavilán Dorronzoro, Giulia Tini, Maria R de Filippo, Emanuele Bonetti, Maria R Ippolito, Chiara Soriani, Paolo D'Amico, Simona Rodighiero, Giuseppe Curigliano, Stefano Santaguida, Massimo Cristofanilli, Pier Giuseppe Pelicci, Luca Mazzarella. NF1 mutations render HER2+ breast cancer highly sensitive to T-DM1 by altering microtubule dynamics [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-13-04.

Although technological and processing advancements occurred in the past forty years, industrial firms are still struggling to provide solutions to corrosion protection as well as reduction of toxic wastes. Specifically, large-scale industrialization of electroplating techniques will continue to be limited by strict environmental regulations. Moreover, price volatility of the highly demanding electroplated materials like gold, palladium, copper and nickel will heavily impact the market in the next years. In that respect, alloy plating offers better answers in terms of economic growth and environmental sustainability due to fine tuning composition, morphology and crystallinity [1]. The main categories of alloy compounds are presented and the most important properties for the manufacturing process discussed. Particular attention is devoted to advances in industrial quality control and viable solutions for the reduction of precious metal content in electroplated accessories as well as replacement of cyanide and nickel baths with non-toxic compounds, also considering the commercial needs of wear resistance and aesthetic characteristics of gloss. The electrodeposition of Cu-Sn alloys (bronze) has earned considerable interest thanks to the chemical-physical properties of this alloy, which make it a valid substitute for nickel in fashion industry. Generally, most of the bronze coatings are electroplated starting from baths containing cyanides, and the metal precursors are selected as cyanide compounds. Free cyanide is a well-known problem in the galvanic production cycle both in terms of toxicity for the workers as well as for the environment, and in terms of costs associated with its disposal. The aim of this study is to develop an electroplating bath totally cyanide-free, therefore formulated in an innovative way and which, in addition to being free from this dangerous species, has an eco-friendly support electrolyte. To achieve this goal, methanesulfonic acid (MSA) was chosen as electrolyte, which is biodegradable as part of the natural sulfur cycle. We've studied different formulations in terms of metal precursors, organic additives and their concentrations [2-3]. The same cyanide issue is present also in for the electrodeposition of silver, for this reason the influence of polyethyleneimine (PEI) as additive for cyanide-free silver bath, in combination with 5,5-dimethylhydantoin (DMH) as complexing agent, was studied [4]. Chronoamperometry was used to investigate the electrodeposition mechanism, which is found to be a three-dimensional diffusion-controlled nucleation and growth mechanism, according to the Scharifker–Mostany’s model. Smoother, brighter and blue colored silver deposits are obtained in the presence of PEI in a Hull’s cell test, at low density current. Eventually, the influence of nitrate anion is also investigated. The presence of nitrate increases the range of current density allowing for an effective Ag deposition. We also investigated the use of modulated currents to increase the throwing power of electroplating, obtaining a more uniform deposition and reducing the amount of metals but maintaining the required characteristics. Pulsed current justifies its practical application mainly through its ability to influence the mechanisms of electrocrystallisation, which in turn control the mechanical and physical properties of the deposited metal. By simply adjusting the amplitude and length of the pulses, it is possible to control not only the composition and thickness, in atomic order, of the deposits, but to improve their characteristics such as grain size, porosity and homogeneity [5]. The authors acknowledge Regione Toscana POR CreO FESR 2014-2020 – azione 1.1.5 sub-azione a1 – Bando 1 “Progetti Strategici di ricerca e sviluppo” which made possible the projects “A.C.A.L. 4.0” (CUP 3553.04032020.158000165_1385), “A.M.P.E.R.E.” (CUP 3553.04032020.158000223_1538) and “GoodGalv” (3647.04032020.157000060). References [1] Giurlani, W.; Zangari, G.; Gambinossi, F.; Passaponti, M.; Salvietti, E.; Di Benedetto, F.; Caporali, S.; Innocenti, M. Electroplating for Decorative Applications: Recent Trends in Research and Development. Coatings 2018, 8, 260, doi:10.3390/coatings8080260. [2] Fabbri, L.; Sun, Y.; Piciollo, E.; Salvietti, E.; Zangari, G.; Passaponti, M.; Innocenti, M. Electrodeposition of White Bronzes on the Way to CZTS Absorber Films. J. Electrochem. Soc. 2020 , 167, 022513, doi: 10.1149/1945-7111/ab6c59. [3] Fabbri, L.; Giurlani, W.; Mencherini, G.; De Luca, A.; Passaponti, M.; Piciollo, E.; Fontanesi, C.; Caneschi, A.; Innocenti, M. Optimisation of Thiourea Concentration in a Decorative Copper Plating Acid Bath Based on Methanesulfonic Electrolyte. Coatings 2022, 12, 376, doi:10.3390/coatings12030376. [4] Pizzetti, F.; Salvietti, E.; Giurlani, W.; Emanuele, R.; Fontanesi, C.; Innocenti, M. Cyanide-free silver electrodeposition with polyethyleneimine and 5,5-dimethylhydantoin as organic additives for an environmentally friendly formulation. J. Electroanal. Chem. 2022, 911, 116196, doi:10.1016/j.jelechem.2022.116196. [5] Popov, K.I.; Nikolić, N.D. General Theory of Disperse Metal Electrodeposits Formation. In; Djokić, S.S., Ed.; Modern Aspects of Electrochemistry; Springer US: Boston, MA, 2012; Vol. 54, pp. 1–62 ISBN 978-1-4614-2379-9.

Abstract: In this paper, the relationship between Tropical Cyclone (TC) Genesis Potential Index (GPI) and the number of TC (NTC) associated with ENSO over the Vietnam East Sea (VES) was investigated. Observed TC data of the Regional Specialized Meteorological Center (RSMC) Tokyo Typhoon Center and ERA Interim reanalysis data for the period 1985-2015 were used. The results show a good agreement between GPI and NTC over the VES with the correlation coefficient is 0.84. There were more TCs formed over the VES during La Nina years and less TCs during El Nino years. There were positive anomalies of GPI, environmental factors (relative humidity, sea surface temperature, absolute vorticity, potential intensity)over the region where the highest densityof TCs genesis locatedduring La Nina years while there were negative anomalies found during El Nino years. Relative humidity has the largest contribution to the positive difference GPI between La Nina years and El Nino years, the less contribution comes from the potential intensity, absolute vorticity, and wind shear. Keywords: GPI, Tropical Cyclone Genesis, ENSO, Vietnam East Sea. References: [1] K.A. Emanuel, D.S. Nolan, Tropical cyclone activity and global climate, Reprints, 26th Conference on hurricane and Tropical Meteorology, American meteorological Society: Miami, (2004) 240–241.[2] D.S. Nolan, E.D. Rappin, K.A. Emanuel., Tropical cyclogenesis sensitivity to environmental parameters in radiative-convective equilibrium, Quarterly Journal of the Royal Meteorological Society. 133 (2007) 2085–2107.[3] S.J. Camargo, K.A. Emanuel, A.H. Sobel, Use of the Genesis Potential Index to Diagnose ENSO effected on Tropical Cyclone Genesis, American Meteorological Society.20 (2007) 4819-4834[4] C.L. Bruyere, G.J. Holland, E. Towler, Investigating the Used of a Genesis Potential Index for Tropical Cyclones in the North Atlatic Basin, American Meteorological Society..25 (2012) 8611-8626[5] Song Yuan, Wang Lei, Lei Xiaoyan and Wang Xidong, Tropical cyclone genesis potential index over western north Pacific simulated by CMIP5 models, (2015).[6] Lei Wang, Diagnostic of the ENSO modulation of Tropical cyclogenesis over the southern South China Sea using a genesis potential index, Acta Oceanol. Sin., Vol. 31, No. 5 (2012) 54-68.[7] Xin Kieu-Thi, Hang Vu-Thanh, Truong Nguyen-Minh, Duc Le, Linh Nguyen-Manh, Izuru Takayabu, Hidetaka Sasaki, Akio Kito, Rainfall and tropical cyclone activity over Vietnam simulated and projected by the Non-Hydrostatic Regional Climate Model – NHRCM, Journal of the Meteorological Society of Japan. 94A (2016) 135-150.[8] https://www.jma.go.jp/jma/jma-eng/jma-center/ rsmc-hp-pub-eg/trackarchives.html[9] Trần Quang Đức, Xu thế biến động của một số đặc trưng ENSO, Tạp chí Khoa học Đại học Quốc gia Hà Nội, Khoa học Tự nhiên và Công nghệ. 1S (2011) 29-36.[10] https://origin.cpc.ncep.noaa.gov/products/analysis_monitoring/ensostuff/ONI_v5.php[11] E. Palmen, Formation and development of tropical cyclones, Proceedings of tropical cyclone Symposium, Brisbane, Australian Bur. Meteorol., Melbourne, (1956) 213-231[12] M. DeMaria, The effect of vertical wind shear on tropical cyclone intensity change, Jounal of Atmospheric Sicences. 53 (1996) 2076-2087.[13] S.J. Camargo, Diagnosis of the MJO modulation of Tropical cyclogenesis using an empirical index. American Meteorological Society. 66 (2009) 3061-3074.[14] S.J. Camargo, A.H. Sobel, Anthony G. Barnston, K.A. Emanuel, Tropical cyclone genesis potential index in climate models, Tellus A: Dynamic Meteorology and Ocenaography. 59:4 (2007) 428-443. doi: 10.1111/j.1600-0870.2007. 00238.

Background/Issues: The AHA/ASA commends the formation of multidisciplinary quality improvement teams in order to achieve high level organization and efficiency in the treatment of acute stroke. Emanuel Medical Center’s process in obtaining weight information was determined by two provider estimations. Historical review of charts revealed over and under dosing of IV tPA. This quality enhancement project was designed to develop a process to capture actual weights prior to the initiation of IV tPA. Purpose: Have 100% acute ischemic stroke patients weighed prior to tPA administration. Method: Utilizing Plan-Do-Study-Act (PDSA) quality improvement methodology, a multidisciplinary team consisting of Neurologist, Stroke Coordinator RN, ED Supervisor, and Stroke NP was created to establish a standard method in obtaining weights in the ED. The team identified a shortage of scales, lack of designated location, and absence of weighing patients in the ED workflow as main barriers. Review of current literature and institutional policies led to a proposal for new scales, designated location, development of standardized process for timing of weighing patients, and entering information in chart. Additional interventions involved extensive education of staff through active and passive learning methods with development of an educational module for ED staff. One month post implementation and cycle analysis of PDSA, ED supervisor discovered new stretcher scales required being plugged in for operation. The new clinical practice algorithm includes the following steps: arrival by EMS and taking patient directly to CT; placement on CT table; patient transfer onto stretcher scale post scan; plugging-in scale; obtaining weight; and entering into chart. Results: Compliance was 0% (0/3) in the first month of implementation and 100% in the two consecutive months (6/6), and (1/1). All cases reviewed by the Stroke Coordinator and ED supervisor (inter-rater reliability of Cohen’s kappa 0.71). Feedback is given on all cases within 48 hours to the stroke leadership team. ED supervisor provides staff feed-back and analyzes outliers. Conclusion: Developing a standard process for capturing actual weights in the ED prior to initiating tPA is feasible utilizing PDSA methodology.

IntroductionNew Orleans is one of a number of infamous swamp cities—cities built in swamps, near them or on land “reclaimed” from them, such as London, Paris, Venice, Boston, Chicago, Washington, Petersburg, and Perth. New Orleans seemed to be winning the battle against the swamps until Hurricane Katrina of 2005, or at least participating in an uneasy truce between its unviable location and the forces of the weather to the point that the former was forgotten until the latter intruded as a stark reminder of its history and geography. Around the name “Katrina” a whole series of events and images congregate, including those of photographer Robert Polidori in his monumental book, After the Flood. Katrina, and the exacerbating factors of global warming and drained wetlands, and their impacts, especially on the city of New Orleans (both its infrastructure and residents), point to the cultural construction and production of the disaster. This suite of occurrences is a salutary instance of the difficulties of trying to maintain a hard and fast divide between nature and culture (Hirst and Woolley 23; Giblett, Body 16–17) and the need to think and live them together (Giblett, People and Places). A hurricane is in some sense a natural event, but in the age of global warming it is also a cultural occurrence; a flood produced by a river breaking its banks is a natural event, but a flood caused by breeched levees and drained wetlands is a cultural occurrence; people dying is a natural event, but people dying by drowning in a large and iconic American city created by drainage of wetlands is a cultural disaster of urban planning and relief logistics; and a city set in a swamp is natural and cultural, with the cultural usually antithetical to the natural. “Katrina” is a salutary instance of the cultural and natural operating together in and as “one single catastrophe” of history, as Benjamin (392) put it, and of geography I would add in the will to fill, drain, or reclaim wetlands. Rather than a series of catastrophes proceeding one after the other through history, Benjamin's (392) “Angel of History” sees one single catastrophe of history. This single catastrophe, however, occurs not only in time, in history, but also in space, in a place, in geography. The “Angel of Geography” sees one single catastrophe of geography of wetlands dredged, filled, and reclaimed, cities set in them and cities being re-reclaimed by them in storms and floods. In the case of “Katrina,” the catastrophe of history and geography is tied up with the creation, destruction, and recreation of New Orleans in its swampy location on the Mississippi delta.New OrleansNew Orleans is not only “the nation’s quintessential river city” as Kelman (199) puts it, but also one of a number of infamous swamp cities. In his post-Katrina preface to his study of New Orleans as what he calls “an unnatural metropolis,” Colten notes:While other cities have occupied wetlands, few have the combination of poorly-drained and flood-susceptible territory of New Orleans. Portions of Washington, D.C. occupied wetlands, but there was ample solid ground above the reach of the Potomac [River’s] worst floods. Chicago’s founders platted their city on a wetland site, but the sluggish Chicago River did not drain the massive territory of the Mississippi. (5)“Occupied” is arguably a euphemism for dredging, draining, filling, and reclaiming wetlands. Occupation also conjures up visions of an occupying army, which may be appropriate in the case of New Orleans as the Army Corps of Engineers have spearheaded much of the militarisation by dredging and draining wetlands in New Orleans and elsewhere in the U.S.The location for the city was not propitious. Wilson describes how “the city itself was constructed on an uneven patch of relatively high ground in the midst of a vast swamp” (86). New Orleans for Kelman “is surrounded by a wet world composed of terrain that is not quite land” (22) with the Mississippi River delta on one side and Lake Pontchartrain and the “backswamps” on the other, though the latter were later drained. The Mississippi River for Kelman is “the continent’s most famed and largest watercourse” (199). Perhaps it is also the continent’s most tamed and leveed watercourse. Earlier Kelman related how a prominent local commentator in 1847 “personified the Mississippi as a nurturing mother” because the river “hugged New Orleans to its ‘broad bosom’” (79). Supposedly this mother was the benign, malign, and patriarchal Mother Nature of the leveed river and not the recalcitrant, matrifocal Great Goddess of the swamps that threatened to break the levees and flood the city (see Giblett, Postmodern Wetlands; People and Places, especially Chapter 1). The Mississippi as the mother of all American rivers gave birth to the city of New Orleans at her “mouth,” or more precisely at the other end of her anatomy with the wetland delta as womb. Because of its location at the “mouth” of the Mississippi River, New Orleans for Flint was “historically the most important port in the United States” (230). Yet by the late 1860s the river was seen by New Orleanians, Kelman argues, only as “an alimentary canal, filled with raw waste and decaying animal carcasses” (124). The “mouth” of the river had ceased to be womb and had become anus; the delta had ceased to be womb and had become bowel. The living body of the earth was dying. The river, Kelman concludes, was “not sublime” and had become “an interstate highway” (146). The Angel of Geography sees the single catastrophe of wetlands enacted in the ways in which the earth is figured in a politics of spaces and places. Ascribing the qualities of one place to another to valorise one place and denigrate another and to figure one pejoratively or euphemistically (as in this case) is “placist” (Giblett, Landscapes 8 and 36). Deconstructing and decolonising placism and its use of such figures can lead to a more eco-friendly figuration of spaces and places. New Orleans is one place to do so.What Colten calls “the swampy mire behind New Orleans” was drained in the first 40 years of the twentieth century (46). Colten concludes that, “by the 1930s, drainage and landfilling efforts had successfully reclaimed wetland between the city and the lake, and in the post-war years similar campaigns dewatered marshlands for tract housing eastward and westward from the city” (140–1). For Wilson “much of New Orleans’s history can be seen as a continuing battle with the swamp” (86). New Orleans was a frontline in the modern war against wetlands, the kind of war that Fascists such as Mussolini liked to fight because they were so easy to win (see Giblett, Postmodern Wetlands 115). Many campaigns were fought against wetlands using the modern weapons of monstrous dredgers. The city had struck what Kelman calls “a Faustian bargain with the levees-only policy” (168). In other words, it had sold its soul to the devil of modern industrial technology in exchange for temporary power. New Orleans tried to dominate wetlands with the ironic result that not only “efforts to drain the city dominate early New Orleans history into the present day” as Wilson (86) puts it, but also that these efforts occasionally failed with devastating results. The city became dominated by the waters it had sought to dominate in an irony of history and geography not lost on the student of wetlands. Katrina was the means that reversed the domination of wetlands by the city. Flint argues that “Katrina’s wake-up call made it unconscionable to keep building on fragile coastlines […] and in floodplains” (232–3). And in swamps, I would add. Colten “traces the public’s abandonment of the belief that the city is no place for a swamp” (163). The city is also no place for the artificial swamp of the aftermath of Katrina depicted by Polidori. As the history of New Orleans attests, the swamp is no place for a city in the first place when it is being built, and the city is no place for a swamp in the second place when it is being ravaged by a hurricane and storm surges. City is antithetical and inimical to swamp. They are mutually exclusive. New Orleans for Wilson is “a city on a swamp” (90 my emphasis). In the 1927 flood (Wilson 111), for Kelman “one of the worst flood years in history” (157), and in the 2005 hurricane, the worst flood year so far in its history, New Orleans was transformed into a city of a swamp. The 1927 flood was at the time, and as Kelman puts it, “the worst ‘natural’ disaster in U.S. history” (161), only to be surpassed by the 2005 flood in New Orleans and the 2012 floods in north-eastern U.S. in the wake of Superstorm Sandy in which the drained marshlands of New York and New Jersey returned with a vengeance. In all these cases the swamp outside the city, or before the city, came into the city, became now. The swamp in the past returned in the present; the absent swamp asserted its presence. The historical barriers between city and swamp were removed. KatrinaKatrina for Kelman (xviii) was not a natural disaster. Katrina produced “water […] out of place” (Kelman x). In other words, and in Mary Douglas’s terms for whom dirt is matter out of place (Douglas 2), this water was dirt. It was not merely that the water was dirty in colour or composition but that the water was in the wrong place, in the buildings and streets, and not behind levees, as Polidori graphically illustrates in his photographs. Bodies were also out of place with “corpses floating in dirty water” (Kelman x) (though Polidori does not photograph these, unlike Dean Sewell in Aceh in the aftermath of the Asian tsunami in what I call an Orientalist pornography of death (Giblett, Landscapes 158)). Dead bodies became dirt: visible, smelly, water-logged. Colten argues that “human actions […] make an extreme event into a disaster […]. The extreme event that became a disaster was not just the result of Katrina but the product of three centuries of urbanization in a precarious site” (xix). Yet Katrina was not only the product of three centuries of urbanisation of New Orleans’ precarious and precious watershed, but also the product of three centuries of American urbanisation of the precarious and precious airshed through pollution with greenhouse gases.The watery geographical location of New Orleans, its history of drainage and levee-building, the fossil-fuel dependence of modern industrial capitalist economies, poor relief efforts and the storm combined to produce the perfect disaster of Katrina. Land, water, and air were mixed in an artificial quaking zone of elements not in their normal places, a feral quaking zone of the elements of air, earth and water that had been in the native quaking zone of swamps now ran amok in a watery wasteland (see Giblett, Landscapes especially Chapter 1). Water was on the land and in the air. In the beginning God, when created the heavens and the earth, darkness and chaos moved over the face of the waters, and the earth was without form and void in the geographical location of a native quaking zone. In the ending, when humans are recreating the heavens and the earth, darkness and chaos move over the face of the waters, and the earth is without form and void in the the geographical location and catastrophe of a feral quaking zone. Humans were thrown into this maelstrom where they quaked in fear and survived or died. Humans are now recreating the city of New Orleans in the aftermath of “Katrina.” In the beginning of the history of the city, humans created the city; from the disastrous destruction of some cities, humans are recreating the city.It is difficult to make sense of “Katrina.” Smith relates that, “as well as killing some 1500 people, the bill for the devastation wrought by Hurricane Katrina on New Orleans […] was US$200 billion, making it the most costly disaster in American history,” more than “9/11” (303; see also Flint 230). A whole series of events and images congregate around the name “Katrina,” including those of photographer Robert Polidori in his book of photographs, After the Flood, with its overtones of divine punishment for human sin as with the biblical flood (Coogan et al. Genesis, Chapters 6–7). The flood returns the earth to the beginning when God created heaven and earth, when “the earth was without form and darkness moved […] upon the face of the waters” (Coogan et al. Genesis Chapter 1, Verse 2)—God's first, and arguably best, work (Giblett, Postmodern Wetlands 142–143; Canadian Wetlands “Preface”). The single catastrophe of history and geography begins here and now in the act of creation on the first day and in dividing land from water as God also did on the second day (Coogan et al. Genesis Chapter 1, Verse 7)—God’s second, and arguably second best, work. New Orleans began in the chaos of land and water. This chaos recurs in later disasters, such as “Katrina,” which merely repeat the creation and catastrophe of the beginning in the eternal recurrence of the same. New Orleans developed by dividing land from water and is periodically flooded by the division ceasing to be returning the city to its, and the, beginning but this time inflected as a human-made “swamp,” a feral quaking zone (Giblett, Landscapes Chapter 1). Catastrophe and creativity are locked together from the beginning. The creation of the world as wetland and the separation of land and water was a catastrophic action on God's part. Its repetition in the draining or filling of wetlands is a catastrophic event for the heavens and earth, and humans, as is the unseparation of land and water in floods. What Muecke calls the rhetoric of “natural disaster” (259, 263) looms large in accounts of “Katrina.” In an escalating scale of hyperbole, “Katrina” for Brinkley was a “natural disaster” (5, 60, 77), “the worst natural disaster in modern U.S. history” (62), “the biggest natural disaster in recent American history” (273), and “the worst natural disaster in modern American history” (331). Yet a hurricane in and by itself is not a disaster. It is a natural event. Perhaps all that could simply be said is that “Katrina was one of the most powerful storms ever recorded in U.S. history” (Brinkley 73). Yet to be recorded in U.S. history “Katrina” had to be more than just a storm. It had also to be more than merely what Muecke calls an “oceanic disaster” (259) out to sea. It had to have made land-fall, and it had to have had human impact. It was not merely an event in the history of weather patterns in the U.S. For Brinkley “the hurricane disaster was followed by the flood disaster, which was followed by human disasters” (249). These three disasters for Brinkley add up to “the overall disaster, the sinking of New Orleans, [which] was a man-made disaster, resulting from poorly designed and managed levees and floodwalls” (426). The result was that for Brinkley “the man-made misery was worse than the storm” (597). The flood and the misery amount to what Brinkley calls “the Great Deluge [which] was a disaster that the country brought on itself” (619). The storm could also be seen as a disaster that the country brought on itself through the use of fossil fuels. The overall disaster comprising the hurricane the flood, the sinking city and its drowning or displaced inhabitants was preceded and made possible by the disasters of dredging wetlands and of global warming. Brinkley cites the work of Kerry Emanuel and concludes that “global warming makes bad hurricanes worse” (74). Draining wetlands also makes bad hurricanes worse as “miles of coastal wetlands could reduce hurricane storm surges by over three or four feet” (Brinkley 10). Miles of coastal wetlands, however, had been destroyed. Brinkley relates that “nearly one million acres of buffering wetlands in southern Louisiana disappeared between 1990 and 2005” (9). They “disappeared” as the result, not of some sort of sleight of hand or mega-conjuring trick, nor of erosion from sea-intrusion (though that contributed), but of deliberate human practice. Brinkley relates how “too many Americans saw these swamps and coastal wetlands as wastelands” (9). Wastelands needed to be redeemed into enclave estates of condos and strip developments. In a historical irony that is not lost on students of wetlands and their history, destroying wetlands can create the wasteland of flooded cities and a single catastrophe of history and geography, such as New Orleans in the aftermath of Hurricane Katrina.In searching for a trope to explain these events Brinkley turns to the tried and true figure of the monster, usually feminised, and “Katrina” is no exception. For him, “Hurricane Katrina had been a palpable monster, an alien beast” (Brinkley xiv), “a monstrous hurricane” (72), “a monster hurricane” (115), and “the monster storm” (Brinkley 453 and Flint 230). A monster, according to The Concise Oxford Dictionary (Allen 768), is: (a) “an imaginary creature, usually large and frightening, composed of incongruous elements; or (b) a large or ugly or misshapen animal or thing.” Katrina was not imaginary, though it or she was and has been imagined in a number of ways, including as a monster. “She” was certainly large and frightening. “She” was composed of the elements of air and water. These may be incongruous elements in the normal course of events but not for a hurricane. “She” certainly caused ugliness and misshapenness to those caught in her wake of havoc, but aerial photographs show her to be a perfectly shaped hurricane, albeit with a deep and destructive throat imaginable as an orally sadistic monster. ConclusionNew Orleans, as Kelman writes in his post-Katrina preface, “has a horrible disaster history” (xii) in the sense that it has a history of horrible disasters. It also has a horrible history of the single disaster of its swampy location. Rather than “a chain of events that appears before us,” “the Angel of History” for Benjamin “sees one single catastrophe which keeps piling wreckage upon wreckage” (392). Rather than a series of disasters of the founding, drainage, disease, death, floods, hurricanes, etc. that mark the history of New Orleans, the Angel of History sees a single, catastrophic history, not just of New Orleans but preceding and post-dating it. This catastrophic history and geography began in the beginning when God created the heavens and the earth, darkness and chaos moved over the face of the waters, the earth was without form and void, and when God divided the land from the water, and is ending in industrial capitalism and its technologies, weather, climate, cities, floods, rivers, and wetlands intertwining and inter-relating together as entities and agents. Rather than a series of acts and sites of creativity and destruction that appear before us, the Angel of Geography sees one single process and place which keeps (re)creating order out of chaos and chaos out of order. This geography and history began at the beginning when God created the heavens and the earth, and the wetland, and divided land from water, and continues when and as humans drain(ed) wetlands, create(d) cities, destroy(ed) cites, rebuilt/d cities and rehabilitate(d) wetlands. “Katrina” is a salutary instance of the cultural and natural operating together in the one single catastrophe and creativity of divine and human history and geography.ReferencesAllen, Robert. The Concise Oxford Dictionary. 8th ed. Oxford: Clarendon Press, 1990.Benjamin, Walter. “On the Concept of History.” Selected Writings Volume 4: 1938–1940. Eds. Howard Eiland and Michael W. Jennings. Cambridge, MA: The Belknap Press of Harvard UP, 2003. 389–400.Brinkley, Douglas. 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