Journal articles on the topic 'Feast of Weeks'

At Yale University, the Beinecke Rare Book and Manuscript Library's James Marshall and Marie-Louise Osborn Collection has recently acquired a fascinating manuscript of late sixteenth-century Roman Catholic devotional verse in English (Osborn Shelves a30). Following the liturgical year from Trinity Sunday to the feast of Saint Catherine on November 25th, these fifty-eight poems celebrate the solemnities, feasts, and memorials of the Roman liturgical calendar throughout the approximately twenty-six weeks comprising the major portion of ‘ordinary time’. Presumably, this collection would have had a companion volume, now lost, covering the period from Advent to Pentecost which includes the principal solemnities and great seasons of the liturgical year.

Liturgy possesses a socio-critical potential which greatly surpasses political activism. It bypasses the systems of a "complex society", such as socialisation, communication and economics, through its factual logic which stands independent of faith. This political fo-rce is already developed by the feast on Sinai, to which Israel is lead out of Egypt (Ex 5:1-3). There, Israel receives the Torah, in order that its life as the people or community of Yahweh may be successful in the Promised Land. The community is to renew itself on occasion of the three pilgrimage festivals. For this purpose, Deuteronomy developed two basic types of popular liturgy within the scope of its theology of the people of God. The first is constituted by the passion commemoration of the passover (Dt 16:1-8). It aims at the social liberation of everyone in Israel, in commemorating their being lead out of Egyptian slavery. The second type is presented in the Feast of Weeks and the Feast of Tabernacles (16:9-12, 13-15). They initiate a fraternal society devoid of poverty, and already realise this in a realistic-symbolic way, through the communal meal of rejoicing in which all are to participate before Yahweh. According to this model, the eucharistic celebrative joy of the first Jerusalem congregation (Acts 2:44-46) reveals its community-changing force in the fact that "no poor were to be found any more" among the believers (Dt 15:4 in Acts 4:32-34).

ABSTRACT Acinetobacter species encounter cycles of feast and famine in nature. We show that populations of A cinetobacter baylyi strain ADP1 remain dynamic for 6 weeks in batch culture. We created a library of lacZ reporters inserted into SalI sites in the genome and then isolated 30 genes with lacZ insertions whose expression was induced by starvation during long-term stationary phase compared with their expression during exponential growth. The genes encode metabolic, gene expression, DNA maintenance, envelope, and conserved hypothetical proteins.

Medieval funerals combined the accumulation of merit for the soul of the deceased with social display. During the late medieval period funerary practice became more elaborate, formalised and expensive, a reflection of its eschatological and social importance. An extended funeral lasting several weeks, comprising a vigil, procession, liveried mourners, a hearse, heraldic elements, almsgiving and a feast, developed. Several of these elements were repeated a week, a month and a year after death. The late medieval higher clergy shared the same funeral culture as the wealthy laity but with significant differences, particularly greater liturgical sophistication and more generous charity.

Nineteen patients (16 - 49 years) with scaphoid pseudarthrosis were treated using vascularized bone autograft from medial femoral epicondyle. Mean term since scaphoid fracture made up 30.5 ± 21.2 months. In all cases avascular necrosis of the proximal fragment, scaphoid humpbach deformity and dorsal intercalated segment instability (DISI) were present. In 16 (84.2%) consolidation in the zone of scaphoid pseudarthrosis was achieved at terms from 8 to 12 weeks after operation. In 3 (15.8%) unsatisfactory results were observed. Average scapholunate angle correction made up 13°. Average force of feast and pinch grasps increased on the average by 2.5 and 1.5 times, respectively. One year after surgery the average estimation by DASH scale decreased by 9.6 points at average, from 27 to 13.4 points.

Nineteen patients (16 - 49 years) with scaphoid pseudarthrosis were treated using vascularized bone autograft from medial femoral epicondyle. Mean term since scaphoid fracture made up 30.5 ± 21.2 months. In all cases avascular necrosis of the proximal fragment, scaphoid humpbach deformity and dorsal intercalated segment instability (DISI) were present. In 16 (84.2%) consolidation in the zone of scaphoid pseudarthrosis was achieved at terms from 8 to 12 weeks after operation. In 3 (15.8%) unsatisfactory results were observed. Average scapholunate angle correction made up 13°. Average force of feast and pinch grasps increased on the average by 2.5 and 1.5 times, respectively. One year after surgery the average estimation by DASH scale decreased by 9.6 points at average, from 27 to 13.4 points.

The 2012 Globe to Globe Festival proved a great success. Actors, directors, musicians, dancers, designers and technicians travelled from all over the world to perform on the Globe stage. Visitors to London’s Cultural Olympiad enjoyed six jam-packed weeks of Shakespeare, presented in an array of international languages. The Globe’s Artistic Director, Dominic Dromgoole, and his Festival Director, Tom Bird, had achieved what seemed, to many, the impossible. Nonetheless, filmed interviews with Dromgoole and Bird, conducted during the festival by the American documentary-maker Steve Rowland, offer tantalizing insights into the genesis of the festival venture. These candid interviews confirm the sometimes farcical, often exhausting, but invariably serendipitous truth behind the Globe to Globe Festival’s short, intense history. Although the Globe was “flying completely blind,” it still succeeded in hosting a glorious feast of Shakespearean delights, seasoned with the strong spice of multiculturality.

The food at the All-College Dining Commons (ACDC) at Vassar College stinks. Not that is literally smells foul; it just isn’t very good. The high-achieving community college students in the Exploring Transfer Program (ET) eat breakfast and dinner there for the five weeks that they are studying at Vassar. Ironically, the course I co-taught in ET for two summers, with the Chair of Environmental Studies, is entitled Feast or Famine: Food, Society, Environment. This course is a survey of issues concerning food systems, such as industrial farming, the role of agricultural lobbyists in Washington, overfishing, food sovereignty in developing countries, food stamps, food deserts, the USDA, FDA, WTO, IMF, etc. And yet, with all of the knowledge the students are gleaning from authors like Marion Nestle, Michael Pollan, Wendell Berry and myriad others, they have to eat the crappy food at ACDC. We have had students in this course from Argentina, Bosnia, Bourkina Faso, China, El Salvador, Ghana, Guyana, Haiti, Italy, Mexico, Pakistan, Poland, the Philippines, Sweden, Uzbekistan, and Vietnam. They come from community colleges mostly in the New York area, but also from as far away as Boston, Maine, Los Angeles, and Diné Community College, which is on a Navajo reservation in Northern Arizona. This program—over 30 years old and with over 1,000 alumni—is a sort of academic boot camp for community college students who hope to transfer to an elite liberal arts college, a Research 1 university, or an Ivy League school. It’s a full scholarship program during which they take two courses in five weeks, each team-taught by a community college professor and a Vassar professor. “AC/DC” seems an apt metaphor for the ET program; not for its pop-metal connotations but because of the fact that it demands that students that are accustomed to operating in one current suddenly adjust to quite another. The question that arises out of the experience of eating ACDC, though—of being low-income, immigrant, first-generation college students, studying at one of the whitest and most expensive schools in the country and yet being forced to eat poor food—is “how do they develop a sense of personal agency,” since that is what the transition through community college and onto a school like Vassar requires.

Right at the time of national financial difficulties, the Provisional Government of the Democratic Republic of Vietnam launched the Golden Week in the framework of the Independence Fund, exhorting the entire people to raise money and wealth to help the country. Golden Week became one of the events that started Vietnam's modern history with feats and meanings that surpass the time. This article reproduces the progress and results of the event based on contemporary media sources, especially the Cuu Quoc newspaper, the Government's daily mouthpiece and propaganda agency. The concrete facts have contributed to restoring the face and stature of the event, correcting perceptions that contain many erroneous information that has been defaults before, through some scientific manipulations of quantification, statistics, matching, etc. The results of the study showed that Golden Week was conducted in two spaces associated with two diffirent time periods, including Hanoi capital from September 16, 1945 to September 30, 1945 and the whole country from September 16, 1945 to January 9, 1946; the activities of Golden Week in Hanoi capital are actually organized in seven different locations, of which there was Bac Bo palace, which gathered dozens of capitalists and landlords with the value of donations up to half of the total value of 7 million Indochina of Golden Week, demonstrating the leading role in the financial support of the rich and patriotic classes at the beginning of the consolidation of national independence.

During his time spent in the Wartburg Castle, Martin Luther experienced an intense exile and a crisis of identity that played a distinct role in the formation of his theology. This crisis of identity was brought about by his loss of friends, family, and purpose. My attestation in this article is that this exilic crisis quickly moved Luther to a radical rejection of monastic celibacy, thus preparing him for his own marriage three years later, and also created the perfect conditions in which Luther was able to accomplish the astounding feat of translating the New Testament into German in the course of only eleven weeks. Understanding Luther’s experience at the Wartburg as an exile allows us to properly assess the intense transformation of identity that Luther underwent and better understand how this radical shift of theology and impressive feat of translation were possible.

Isolates of Claviceps africana from Australia, Africa, Asia, and America were tested for the production of dihydroergosine (DHES), and its biogenic precursors dihydroelymoclavine (DHEL) and festuclavine (FEST), in culture. Several growth media were evaluated to optimise alkaloid production with little success. The best of these involved 2-stage culturing on high-sucrose substrate. Australian C. africana isolates varied widely and inconsistently in alkaloid production, with DHES concentrations in mycelium ranging from: <0.1 to 9 mg DHES/kg; <0.1 to 1.6 mg DHEL/kg; and <0.1 to 0.4 mg FEST/kg. In a separate experiment using similar culturing techniques, DHES was produced by 2 of 3 Australian isolates, 1 of 3 USA isolates, 1 of 4 Indian isolates, the sole Puerto Rican isolate, the sole Japanese isolate, but not the sole South African isolate. In this experiment, DHES concentrations detected in mycelium of Australian isolates (0.1–1.0 mg DHES/kg) were of similar magnitude to isolates from other countries (0.2–1.8 mg DHES/kg). Three C. africana isolates, including one that produced only traces of alkaloid in culture after 8 weeks, were inoculated onto panicles of sterile male sorghum plants. After 8 weeks, all 3 isolates produced 10–19 mg DHES/kg in the panicles, demonstrating that the growing plant favoured more consistent alkaloid production than culture medium.

The aim of the study was to evaluate power performance and muscle morphology adaptations in response to 5 weeks of fast-eccentric squat training (FEST) performed twice per week, with three different training volumes. Twenty-five moderately trained females were assigned into three groups performing eight repetitions of FEST of either four sets (4 × 8 group; N = 9), 6 sets (6 × 8 group; N = 8) or eight sets (8 × 8 group, N = 8). Before and after the intervention, countermovement jumping height (CMJh) and power (CMJp), half squat maximal strength (1-RM), quadriceps cross-sectional area (QCSA) and vastus lateralis (VL) architecture and fiber type composition were evaluated. Significant increases (p < 0.05) were found for all groups, with no differences among them in 1-RM (4 × 8: 14.8 ± 8.2%, 6 × 8: 13.1 ± 9.2% and 8 × 8: 21.6 ± 7.0%), CMJh (4 × 8: 12.5 ± 8.5%, 6 × 8: 11.3 ± 9.3% and 8 × 8: 7.0 ± 6.2%), CMJp (4 × 8: 9.1 ± 6.0%, 6 × 8: 7.1 ± 5.2% and 8 × 8: 5.0 ± 3.9%) and QCSA (4 × 8: 7.7 ± 4.7%, 6 × 8: 9.0 ± 6.8% and 8 × 8: 8.2 ± 6.5%). Muscle fiber type distribution remained unaltered after training in all groups. VL fascicle length increased and fascicle angle decreased only in 6 × 8 and 8 × 8 groups. In conclusion, four sets of eight fast-eccentric squats/week increase lower body power and strength performance and maintain type IIX muscle fibers after 5 weeks, at least in moderately trained females.

By describing where animals go, biologging technologies (i.e. animal attached logging of biological variables with small electronic devices) have been used to document the remarkable athletic feats of wild animals since the 1940s. The rapid development and miniaturization of physiologging (i.e. logging of physiological variables such as heart rate, blood oxygen content, lactate, breathing frequency and tidal volume on devices attached to animals) technologies in recent times (e.g. devices that weigh less than 2 g mass that can measure electrical biopotentials for days to weeks) has provided astonishing insights into the physiology of free-living animals to document how and why wild animals undertake these extreme feats. Now, physiologging, which was traditionally hindered by technological limitations, device size, ethics and logistics, is poised to benefit enormously from the on-going developments in biomedical and sports wearables technologies. Such technologies are already improving animal welfare and yield in agriculture and aquaculture, but may also reveal future pathways for therapeutic interventions in human health by shedding light on the physiological mechanisms with which free-living animals undertake some of the most extreme and impressive performances on earth. This article is part of the theme issue ‘Measuring physiology in free-living animals (Part I)’.

One of the apparent pillars of consistency in the medieval Latin liturgy is the divine, alias daily, office. Although scholars convincingly postulate forms of the office that both antedate the specific provisions for it which bulk large in the Rule of Benedict and reflect an urban secular (the so-called cathedral office) rather than a monastic context, in terms of actual books out of which the office was performed, not a great deal survives until roughly the eleventh century. By that time, if not before, thought is clearly being given as to how to present the contents of the office - given that much of it consists in the recitation of psalms - in a way that, while clear, minimizes repetition. This can most readily be done in the long stretch of the weeks after Pentecost and the shorter stretch (sometimes very short indeed, depending on when Easter falls) of the weeks between the octave of Epiphany and the beginning of Lent or pre-Lent (that is, from Septuagesima on). Although the structure of the office in this, to use the current phrase, ‘ordinary time’, remains the same as in the more exciting seasons of Advent, Christmastide, Lent, and Eastertide (plus, of course, the individual feasts of the Proper of Saints), the content of the various services is not driven by a particular time or saint, and so there is a somewhat abstract quality about it quite lacking from the great seasons and occasions of the liturgical year.

Calcium phosphate cement is a bioceramic with potential applications for bone-tissue engineering. In this work, controlled porous calcium phosphate scaffolds with interconnected pores were computationally designed by an image-based approach and fabricated by indirect solid freeform fabrication (ISFF) or ‘lost mold’ technique. Voxel finite-element analysis (FEA) showed that mechanical properties of design and fabricated scaffold can be predicted computationally. Scaffolds were then implanted subcutaneously to demonstrate tissue in-growth. Previously, we showed the ability of porous calcium phosphate cement scaffolds to have sufficiently strong mechanical properties for bone tissue engineering applications. This work shows the image-based FEAs from micro-CT scans in vivo (four- and eight weeks). Extensive new bone apposition was noted with micro-CT technique after four- and eight weeks. FEA models of the original design and scaffolds with newly bone formed were compared.

A large area of feat soil as available across Aceh Singkil province of Aceh. The possibility of thearea for upland rice farming is a necessary tube evaluated. This study aims to evaluate the growth andyield of upland rice varieties on peat soil with different thickness of soil. The research useda randomized block design with 2 (two) factors. The first factor was rice varieties (V) were consistof (1) Local variety (Siliam varieties), (2) Situ Bagendit varieties, (3) Situ Patenggang varieties and(4) Batutegi varieties. Whereas the second-factor thickness of mineral soil applied on peat whichconsists of 5 cm, 10 cm, 15 cm, 20 cm and no mineral soil as a control. The results indicated thatvarieties of upland rice showed a significant effect on the growth and production variables such asplant height 4, 6, 8 and 10 weeks after planting, where Situ Bagendit variety was the highest amongthe varieties. Similarly, the number of tillers 4, 6, 8 and 10 weeks after planting, the highest number oftillers was found on Situ Bagendit variety, while for the highest number of grain per panicle was inBatutegi varieties. The thickness of mineral soil applicated on peat soil indicated a significant effecton the growth and production variables such as plant height 4 weeks after planting. The highestyield of upland rice was fond on Situ Bagendit variety followed by Batutegi variety, SituPatenggang variety and local variety (Siliam variety).

For centuries, Santa Claus has proved to be a pervasive, persistent and influential mythic figure who dominates children’s lives for several weeks each year. But unlike most other fantasy figures, Santa Claus is presented as a real entity, a feat achieved through the widespread deception of children. This deception primarily involves a child’s family, but is also encouraged and maintained by wider society and its institutions. That educators could involve themselves in such a deception seems particularly controversial. Given their role as providers of epistemic goods, it appears like a dereliction of duty for them to seemingly encourage credulity and to deceive their students to maintain their false beliefs. However, I argue that there are epistemic benefits that can reaped by children through their experience of believing in Santa Claus and the process of independently disabusing themselves of these beliefs. For these benefits to be attained, educators must reluctantly engage in low-level paternalistic deception to keep their students in the dark about the truth, before then actively helping them to learn important epistemic lessons and foster key intellectual virtues as a result of their experiences. This justifies educators’ modest involvement in the Santa Claus deception.

Abstract Myelodysplastic Syndrome (MDS) is rarely concomitant with Sjögren's syndrome (SS) with only 9 previously reported cases in the literature. A case of a previously healthy 31-year-old Chinese female presenting with dysplasia affecting all three lineages without blasts excess showed by bone marrow examination is reported. Autoimmune workup revealed positive antinuclear antibodies and Anti-SSA. Lip biopsy revealed findings consistent with SS. A diagnosis of SS associated with MDS of the refractory cytopenia with multilineage dysplasia (RCMD) subtype was established, and decitabine for five days at 20mg/m2 per day was initiated with only slight increase in platelet counts. Four weeks later, another cycle of decitabine for five days at 20mg/m2 per day was performed. Unfortunately, infection occurred, and the patient suffered from thrombocytopenia and leucopenia. Then the patient received the treatment of Biapenem and Vancomycin Hydrochloride along with granulocyte colony stimulating factor followed by platelet infusion for two weeks. Significant clinical and laboratory response was achieved. In hopes of improving both response rates and durability of response, the third cycle of decitabine for five days at 20mg/m2 per day was performed with again an excellent clinical and laboratory response. However the patient refused further cycle of decitabine due to cost consideration, then prednisone at 10mg per day was used as a basic treatment for SS. It was an amazing feat that the patient was in a state of remission for two years. MDS with SS tends to be incurable. Decitabine alone with prednisone may serve as an effective option to those patients. Disclosures No relevant conflicts of interest to declare.

A parenting education program delivered to a sample of parents of young children aged 3–12 years who often used negative behavior control strategies to discipline their children was evaluated for effectiveness using a quasi-experimental design. Parents ( n = 150) who received parenting education program intervention program for 8 weeks (weekly 2 hr session) were compared with parents ( n = 150) who did not go through the program. The program’s effectiveness was evaluated with regard to changes in parental disciplinary behavior through observation of parent–child interactions during home visits. Data were collected across three time periods using home observation checklist. Significant improvements in parenting skills were observed as many parents were seen using verbal praise and other positive strategies in dealing with their children; a feat that was lacking before to intervention. The analysis of covariance revealed a significant treatment effect on parenting behavior F(2, 248) = 23.39, p < .05, with the intervention parents demonstrating greater ability to use positive behavior control strategies than did the comparison parents. The magnitude of the effect size was medium (partial η² = .072). This effect persisted over a 12-week follow-up period. These findings indicated that the parenting education program could be effective in helping parents improve their parenting skills and support the parents in creating a safe and supportive home environment that prevent children’s exposure to physical abuse.

Peru is mining country with a great diversity of mineral resource. The high grade ores are declining, and there is a need to implement new techniques for recycling metals (Cu, Au, Zn, Pb, etc) from low-grade ores. In order to answer this question, the bioleaching of copper from sulphide ore (FeS2 45.30%, CuFeS2 1.90%, ZnS 8.90%, FeAsS 13.12%, PbS 3.69%) was evaluated with different concentrations of Fe2+ using an iron-oxidizing native microbial consortium.The samples were collected from drainage acid mine (4100 m.a.s.l.) located in the south of Huancavelica region and the sample of ore from middle Huaraz region (3200 m.a.s.l.). Microorganisms were isolated in 9k medium at pH 1.8, 22oC. Bioleaching test were performed in two consecutive steps to 150 rpm at 22oC, monitoring pH, ORP (mV). Assays varying the concentration of Fe2+ (0 mM – 53 mM) were performed with a pulp density of 1% and 2% at each step, and with an inoculum 10% (v/v) to a microbial concentration of 108 cel/mL.We isolated a microbial consortium after 8 weeks with presence of bacteria Acidithiobacillus ferrooxidans-like. In assays, copper was solubilized. The microbial concentration in the tests was (2x107- 4x107cel/mL). In the first stage, the test with 21 mM Fe2+ recovered 62% copper. In the next step, with the bacterial concentration of the first step, bioleaching time is reduced by 22% for copper recovery (63%) in absence of Fe2+.With these data, we observed that the addition of iron is not necessary in a stage adaptation when the mineral contain iron.

Background:Inhibition of interleukin-1 (IL-1) represents a promising treatment option in adult-onset Still’s disease (AOSD). Canakinumab is approved for treatment of systemic juvenile idiopathic arthritis and has a marked impact on systemic as well as articular activity of the disease.Objectives:To investigate the efficacy and safety of canakinumab in patients with AOSD and active joint involvement by means of a multi-centre, double-blinded, randomized, placebo controlled trial over a period of 24 weeks with the option of a long-term extension.Methods:Patients with AOSD and active joint involvement (tender and swollen joint count ≥4 each) were stratified by pre-treatment status with biologic DMARDs to canakinumab (4 mg/kg, maximum 300 mg s.c. q4w) or placebo. After approval of canakinumab for AOSD by the European Medicines Agency, recruitment was stopped prematurely with enrollment of 35 out of 68 planned patients. The primary endpoint was the proportion of patients with a clinically-relevant reduction in disease activity at week 12 as determined by the change in disease activity score (ΔDAS28 >1.2).Results:At enrollment, patients had high active disease with a mean DAS28(ESR) of 5.4 in the canakinumab group (n=18, [CI 43.1; 85.2]) and 5·3 in the placebo group (n=17, [CI 20.1; 65.0]). In the intention-to-treat analysis, 12 (67%) canakinumab and 7 (41%) placebo patients fulfilled the primary outcome criterion (p=0.18). Figure 2 shows the DAS28-ESR disease activity by treatment groups and visits with imputation. In the per-protocol analysis, significantly higher ACR30 (61% vs. 33% p=0.033), ACR50 (50% vs. 6.7% p= 0.009) and ACR70 (28% vs. 0% p=0.049) response rates were observed in the canakinumab group compared with placebo (Figure 1). Two patients in the canakinumab group experienced an SAE.Figure 1.Response rates (PP)Figure 2.DAS28-ESR disease activity by treatment groups and visits with imputationConclusion:Although the study was terminated prematurely and the primary endpoint was not achieved, treatment with canakinumab led to an improvement of several outcome measures in AOSD. The overall safety findings were consistent with the known profile of canakinumab. Thus, our data support indication for IL-1 inhibition with canakinumab in AOSD.References:[1]Nirmala N et al. Gene-expression analysis of AOSD and SJIA is consistent with a continuum of a single disease entity. Pediatr Rheumatol Online J. 2015P-values are shown above each pair of bars; P-values in red are significant ACR, American College of Rheumatology; CRP, C-reactive protein; DAS, disease activity score; EULAR, European League Against Rheumatism; PP, per-protocolDisclosure of Interests:Claudia Kedor Consultant of: Advisory Board for Novartis Pharma GmbH, Joachim Listing: None declared, Jan Zernicke: None declared, Anja Weiß: None declared, Frank Behrens Grant/research support from: Abbvie, Pfizer, Roche, Chugai, Janssen, Consultant of: Abbvie, Pfizer, Roche, Chugai, UCB, BMS, Celgene, MSD, Novartis, Biotest, Janssen, Genzyme, Lilly; Boehringer; Sandoz, Speakers bureau: Abbvie, Pfizer, Roche, Chugai, UCB, BMS, Celgene, MSD, Novartis, Biotest, Janssen, Genzyme, Lilly; Boehringer; Sandoz, Norbert Blank Grant/research support from: Novartis, Sobi, Consultant of: Novartis, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Actelion, UCB, Boehringer-Ingelheim, Roche, Jörg Henes Grant/research support from: Novartis, Roche-Chugai, Consultant of: Novartis, Roche, Celgene, Pfizer, Abbvie, Sanofi, Boehringer-Ingelheim,, Jörn Kekow Speakers bureau: BMS, MSD, Pfizer, Roche, Andrea Rubbert-Roth Consultant of: Abbvie, BMS, Chugai, Pfizer, Roche, Janssen, Lilly, Sanofi, Amgen, Novartis, Hendrik Schulze-Koops Grant/research support from: Pfizer Inc, Eva Seipelt: None declared, Christof Specker Consultant of: Abbvie, Boehringer Ingelheim, Chugai, Lilly, Novartis, Sobi, UCB, Celgene, Janssen-Cilag, MSD, Pfizer, Roche, UCB, Toshiba, Eugen Feist Consultant of: Novartis, Roche, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Sanofi, Speakers bureau: Novartis, Roche, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Sanofi

There are relatively few written records of medieval eating habits available today. However, archaeological evidence, the examination of plant remains, and of the people’s teeth who lived that time, further stable isotope analysis can help to reconstruct the diet of that era. Most of the ingredients used in the Middle Ages are also available today, but cooking methods were less sophisticated. Back then, only a few methods were known for storing or long-time preserving of food, thus hygienic problems were often emerging. Strict religious rules affected all areas of life, thus eating habits too. Fasting days were commanded week by weeks as red meat was banned to consume or any food of animal origin. There was a big difference in the diets of poorer and richer people. For the poor, even essential food was often not available, or only in very poor quality, and people were often plagued by famine in this era. In contrast, the rich had an ample supply of food and acquired special ingredients imported from other countries. The nobility often arranged lavish feasts while serving strange foods from our contemporary point of view only to dazzle the guests. They also consumed a significant amount of wine, while poorer peasants preferred rather a drinking beer. This may be traced back to the poor quality of drinking water thus alcoholic beverages were considered safer from a hygienic point of view. Adequate nutrient supply depended also significantly on social status but in an overall frame, it can be said that the majority of inhabitants suffered from some form of nutrient deficiency, including the rich too due to unilateral unbalanced diets.

Background Professional and amateur soccer players often perform dramatic on-field feats of celebration after scoring a goal. Injuries may occur during these activities. Purpose With the aim of preventing such “score-celebration injuries” in the future, the authors examine these events in professional soccer players and discuss potential avenues for prevention. Study Design Case series; Level of evidence, 4. Methods Over the course of 2 seasons (1996-1998), 152 soccer players were evaluated at an orthopaedic clinic for injuries incurred during matches. Nine players (6%) had injured themselves while celebrating after scoring goals in a match. The type of celebration, injury type, treatment, and mean duration of recovery were noted. Results Seven of the 9 patients were male professional soccer players with ages ranging between 17 and 29 years (mean age, 24 years). The injuries occurred when the playing ground was natural turf in 8 cases; most injuries occurred in the second half of the game. The types of celebration maneuvers were sliding (prone or supine) and sliding while kneeling in 5 cases, piling up on jubilant teammates in 3 cases, and being tackled while racing away in 1 case. Injuries included ankle, clavicle, and rib fractures; medial collateral ligament sprain; low back strain; hamstring and adductor muscle strain; quadriceps muscle sprain; and coccyx contusion. The mean duration for recovery was 6.2 weeks. Rival team players were usually not responsible for such trauma. Conclusion Exaggerated celebrations after making a goal, such as sliding, piling up, and tackling a teammate when racing away, can result in serious injury. In addition to general measures for preventing soccer injuries, coaches and team physicians should teach self-control and behavior modification to minimize the risk of such injuries. More restrictive rules, which penalize such behavior, may assist in the prevention of score-celebration injuries.

Arsenopyrite (FeAsS) is the principal arsenic (As) mineral in mineralised mesothermal veins (typically 5,000 mg/kg As) in southeastern New Zealand. Groundwater in contact with arsenopyrite-bearing rocks has elevated As concentrations (up to 0.1 mg/l). The arsenopyrite decomposes slowly on oxidation in soils and historic mine workings in a cool semiarid climate. Dissolved As is predominantly As(III) in association with arsenopyrite, but this is rapidly oxidised over days to weeks to As(V) in the vadose zone. Oxidation is facilitated by particulate Fe and/or Mn oxyhydroxides, and by bacteria in surface waters. Evaporative concentration of dissolved As(V) in the vadose zone causes precipitation of scorodite (Fe(III)As(V)O4.2H2O). Adsorption of As(V) to Fe oxyhydroxides in soils and groundwater pathways lowers dissolved As concentrations. Soils over mineralised veins typically have <200 mg/kg As, as most As is removed in solution on geological time scales. Most plants on the mineralised rocks and soils do not take up As, although some inedible species can fix up to 18 mg/kg As. Hence, bioavailability of As(V) is low in this environment, despite the substantial As flux.Similar As mobility is seen in an active gold mine processing plant and tailings. Arsenopyrite dissolves more rapidly on agitation, and mine waters can have dissolved As >200 mg/l, predominantly as As(V). This dissolved As decreases in tailings waters to near 2 mg/l, mainly as As(III) when in contact with arsenopyrite. Weak oxidation of evaporatively dried tailings causes cementation with scorodite and iron oxyhydroxides, and scorodite precipitation exerts some control on dissolved As(V) concentrations. High dissolved As in mine waters is lowered by adsorption to iron oxyhydroxides, and waters discharged from the mine site have negligible dissolved As.

Abstract The myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, peripheral blood cytopenias, dysplasia and a propensity for transformation to acute myeloid leukemia (AML). MDS is frequently associated with epigenetic gene silencing via methylation of cytosine residues in gene regulatory regions, and DNA methyl-transferase 1 (DNMT1) inhibitors, such as 5'azacytidine and 5-aza-2'-deoxycytidine (decitabine, DAC), are two of the three agents that are FDA approved for treatment of MDS. Although these drugs are not curative, they induce hematological improvement or improved survival in a significant fraction of MDS patients. Two novel, thiol-substituted 2'-deoxycytidine (dCyd) analogs designated T-dCyd (4'-thio-2'-deoxycytidine) and Aza-T-dCyd (5-aza-4'-thio-2'-deoxycytidine) were synthesized and shown to be potent DNMT1 inhibitors in vitro. We evaluated these drugs in vivo using the NUP98-HOXD13 (NHD13) mouse model for MDS. To mimic human MDS hematopoiesis, in which a portion of the hematopoietic output is provided by the MDS clone, and a portion provided by normal, non-MDS cells, we transplanted wild-type (WT) mice with a mixture of WT murine hematopoietic cells and NHD13 (MDS) hematopoietic cells. This bone marrow transplant (BMT) produces chimaeric recipients with bone marrow comprised of hematopoietic cells derived from both the MDS clone as well as normal hematopoietic precursors. WT and MDS cells in the mice can be distinguished by differential CD45 alleles (CD45.1 and CD45.2, respectively), which enables analysis and purification of the MDS and WT cells; this feat is not easily achieved with human MDS patient samples, which lack cell surface antigens specific for the MDS clone. At 8 weeks post-transplant; engraftment of MDS cells was documented by the presence of CD45.2+ cells in the peripheral blood, and the starting CBCs showed signs consistent with MDS including peripheral blood cytopenia and macrocytosis. Mice were randomly assigned to one of the three groups. 1) PBS, 2) T-dCyd, 3) Aza-T-dCyd. T-Cyd was dosed at 4 mg/kg/d intraperitoneally (IP) on weekdays for 2 weeks (10 doses), followed by three weeks rest; this constituted one cycle of therapy. Aza-T-dCyd was administered on the same schedule at 4 mg/kg/d IP. Flow cytometry and CBC were assessed on day 21 of each cycle, and treatment continued for up to one year, or until mice were humanely euthanized due to tachypnea, lethargy, or other signs of AML. Between four and six mice were treated per group, and the entire experiment was repeated three times and results pooled for T-dCyd, once for Aza-T-dCyd. The T-dCyd treated chimaeric mice showed significantly enhanced overall survival associated with hematological improvement including hemoglobin concentration, platelet and absolute neutrophil count compared to PBS treated mice (median survival 45.4 vs 28 weeks, p=0.0187). In addition to a survival advantage, AML onset was significantly delayed in the T-dCyd treated mice (median time to AML transformation 35 weeks for PBS vs unreached for T-dCyd, p=0.0111), although there was no significant change in MDS (CD45.2) engraftment between the T-dCyd and PBS treated mice. For Aza-T-dCyd group, we did not detect a survival benefit nor hematologic improvement, although we suspect this may have been secondary to unexpected toxicity at the selected dose. In sum, these results demonstrate the utility of chimaeric WT/MDS mice as a pre-clinical model for human MDS, and show that treatment with T-dCyd, a new DNMT1 inhibitor, leads to a survival advantage, hematologic improvement, and delayed transformation to AML. Disclosures Aplan: NIH Office of Technolgy Transfer: Employment, Patents & Royalties: NUP98-HOXD13 mice.

94 Background: Bortezomib is a novel first-in-class proteasome inhibitor and received it’s FDA approval with twice weekly dosing on day 1, 4, 8 and 11 of a 21-day cycle with weekly complete blood count (CBC). However, subsequent studies have shown that weekly dosing has equal drug efficacy. Our clinical practice at Feist-Weiller cancer center is to administer weekly subcutaneous bortezomib injection after reviewing the CBC. Objective: To analyze hematological toxicities with weekly bortezomib and assess the need for CBC prior to administration of bortezomib. Methods: A retrospective analysis of CBC results was done for every patient receiving bortezomib as part of bortezomib and dexamethasone +/- lenalidomide regimens in a 2-year period (2017-2018). The data extraction was done using Epic Clarity database using an SQL script which identified each treatment duration in minutes between check in and check out, Absolute neutrophil count (ANC) and platelet count on each treatment day. Results: A total of 38 patients received 626 treatment doses of bortezomib. The average patient stay between check-in and check-out was 227 mins. There was very low incidence of grade 3 thrombocytopenia (0.64%) and grade 3 neutropenia (0.32%). There is no evidence of grade 4 cytopenia’s or any dose changes from cytopenia’s. This data suggests that weekly lab monitoring may not be necessary prior to drug administration. Conclusions: Using this data, we have streamlined our approach for monitoring patients receiving weekly bortezomib. During weekly bortezomib administration, we propose to obtain a CBC on day 1 of every 4 weeks. If either platelet count is less than 75,000 /μl and ANC is less than 1000/μl on day 1, we will monitor labs weekly until count recovery. We believe that this new protocol may result in 75% reduction in the average patient stay for the treatment. It will reduce the need for phlebotomy and lab services. We believe that this change will improve patient satisfaction and an another step forward to efficient and safe patient care at our institute.

Background:Still’s disease is a systemic auto-inflammatory disease with a pediatric form, sJIA, and an analogous condition in adults, adult-onset Still’s disease (AOSD). The role of interleukin-1 (IL-1) in the pathophysiology of Still’s disease is well established. Canakinumab, a monoclonal antibody against IL-1ß, is approved to treat patients with Still’s disease in Europe (sJIA and AOSD) and the United States (sJIA).Objectives:To study the efficacy of canakinumab in sJIA patients categorized by age, we performed an intention-to-treat analysis of pooled data from 5 clinical trials, as an addition to a previously communicated analysis including 3 of the studies1Methods:The age categories were children (2-<12 years), young adolescents (12-<16 years) and older adolescents and young adults (16-<20 years). We pooled efficacy results from patients with active disease at baseline treated during a 12-week period with canakinumab (4mg/kg every 4 weeks), including the presence of intermittent fever, serum concentrations of C reactive protein (CRP), improvement of sJIA (adapted pediatric ACR 30, 70 and 100 responses) and JIA ACR inactive disease status. Safety was assessed by analysis of reported adverse events (AEs).Results:302 children, 82 young adolescents and 34 older adolescents and young adults were included in the analysis, with a mean disease duration of 922, 1708 and 2615 days, respectively. Prior therapy with other biologics was common, with anakinra used in 33%, 35% and 47% of patients in each group. Disease severity was comparable among groups, with the mean number of active joints ranging from 11.8 to 13.7. Adapted pediatric ACR responses revealed a rapid response to canakinumab, with all groups showing similar rates of responders at most time points (Table 1). In each age group, the proportion of patients with inactive disease progressively increased to Day 57. At all time points after Day 15, the 16-<20 years group presented the highest proportion of patients with inactive disease. Median CRP levels decreased from baseline to reach values in the normal range (<10 mg/L) from Day 29 onwards in the three groups, with improvements more marked in the 16-<20 years group. The safety profile was similar in the three age groups analyzed, with a lower proportion of 16-<20 years old patients experiencing serious AEs (28%) as compared to children (35%) and young adolescents (42%).Table 1.Percentages of patients with Adapted pediatric ACR responses and inactive disease status over time*Time of treatment(Days)2 - <12 yearsa12 - <16 yearsb16-<20 yearscACR301572.781.783.9 (%)2977.584.182.45776.282.988.28565.574.583.3ACR701551.558.364.5 (%)2961.962.270.65765.258.579.48558.661.875.0ACR1001521.625.012.9 (%)2929.530.535.35736.134.138.28534.130.933.3Inactive disease1519.030.019.4 (%)2934.134.147.15739.436.655.98536.743.452.2*Some studies did not include visits at Day 15 and/or 85. For Day 15, 29, 57 and 85 the respective denominators for each age group were:aN = 231, 302, 302, 232;bN = 60, 82, 82, 55;cN = 31, 34, 34, 24.Conclusion:The efficacy and safety profile of canakinumab was consistent in children, adolescents and young adults with sJIA. Since sJIA and AOSD represent pediatric- and adult- onset variants of the Still’s disease continuum, these results further support the therapeutic effect of canakinumab 4 mg/kg every 4 weeks in both children and adults with Still’s disease.References:[1]Feist et al.Clin Exp Rheumatol.2018;36(4):668-75.Disclosure of Interests:Pierre Quartier Consultant of: AbbVie, Chugai-Roche, Lilly, Novartis, Sanofi, Sobi, Speakers bureau: AbbVie, BMS, Chugai-Roche, Novartis, Pfizer, Sobi, Eugen Feist Consultant of: Novartis, Roche, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Sanofi, Speakers bureau: Novartis, Roche, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Sanofi, Daniel J Lovell Consultant of: Abbott (consulting and PI), AbbVie (PI), Amgen (consultant and DSMC Chairperson), AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb (PI), Celgene, Forest Research (DSMB Chairman), GlaxoSmithKline, Hoffman-La Roche, Janssen (co-PI), Novartis (consultant and PI), Pfizer (consultant and PI), Roche (PI), Takeda, UBC (consultant and PI), Wyeth, Employee of: Cincinnati Children’s Hospital Medical Center, Speakers bureau: Wyeth, Hiroaki Umebayashi: None declared, Nicolino Ruperto Grant/research support from: Bristol-Myers Squibb, Eli Lily, F Hoffmann-La Roche, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sobi (paid to institution), Consultant of: Ablynx, AbbVie, AstraZeneca-Medimmune, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lily, EMD Serono, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sanofi, Servier, Sinergie, Sobi, Takeda, Speakers bureau: Ablynx, AbbVie, AstraZeneca-Medimmune, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lily, EMD Serono, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sanofi, Servier, Sinergie, Sobi, Takeda, Hermine Brunner Consultant of: Hoffman-La Roche, Novartis, Pfizer, Sanofi Aventis, Merck Serono, AbbVie, Amgen, Alter, AstraZeneca, Baxalta Biosimilars, Biogen Idec, Boehringer, Bristol-Myers Squibb, Celgene, EMD Serono, Janssen, MedImmune, Novartis, Pfizer, and UCB Biosciences, Speakers bureau: GSK, Roche, and Novartis, Cornelia Dunger-Baldauf Employee of: Novartis, Stephanie Noviello Employee of: Novartis, sarah whelan Employee of: Novartis

Background:Personalization of RA treatment is not optimal due to lack of predictors. We previously demonstrated in RA patients that central nervous system (CNS) pain response to tender joint compression, measured by using functional MRI (fMRI) of the brain rapidly wanes after 24 hours of anti-TNF administration and that a higher pre-treatment BOLD signal volume seems to predict clinical response to treatment with certolizumab-pegol (CZP)1,2. We therefore hypothesized that the CNS pain response upon compression of a painful joint could predict subsequent anti-TNF treatment response.Objectives:To compare disease activity after 12-weeks of CZP treatment to that of placebo in DMARD-refractory RA patients based on pre-treatment baseline CNS pain response measured using BOLD fMRI.Methods:Adult RA patients fulfilling the 2010 ACR/EULAR classification criteria with a DAS28>3.2 under stable DMARD treatment for at least 3 months were eligible. Patients underwent fMRI scanning of the brain at screening for stratification by CNS pain response. Whole brain BOLD-signal-voxel-count of 700 units classifying between low and high, and were randomized to CZP or placebo (2:1) The primary outcome was low disease activity (LDA, DAS28 ≤3.2) after 12 weeks of treatment.Results:156 RA patients, inadequate responders to csDMARD, signed the informed consent. 139 patients (46/47, 46/49 and 42/43) (99 females, 71%) with moderate-high disease activity (mean (SD) DAS-28: 4.83 (1.03)) could be included respectively and completed the 12-week study treatment. Geometric mean (SD) numbers of baseline BOLD signal positive voxels were 559 (10), 81 (12) and 2498 (3) in the 3 arms respectively. The mean DAS28 (SD) scores after 12 weeks of study treatment were Placebo: 3.89 (1.29), CZP-L: 3.42 (1.06) and CZP-H: 3.06 (1.04). LDA was achieved in 12/47 patients (25.5 %) in placebo, 22/49 (44.9%) in the CZP-L, and 25/43, (58.1%) in the CZP-H arm. The linear effect term for the ordinal study group variable supported a linear trend of increasing CZP treatment effect with increasing baseline CNS pain response. RR (95% CI) for achieving LDA with each unit increase in treatment category over placebo was 1.79 (1.24 to 2.74, p=0.003).Conclusion:A higher pre-treatment brain activity in response to pain measured with fMRI predicts the chance of achieving low disease activity with CZP treatment.References:[1] Hess, A.et al.PNAS (2011)[2] Rech, J.et al. Arthritis & Rheumatism(2013).Acknowledgments :The study was supported by an unrestricted grant from UCB Biopharma SPRL, Brussels, BelgiumDisclosure of Interests:Jürgen Rech Consultant of: BMS, Celgene, Novartis, Roche, Chugai, Speakers bureau: AbbVie, Biogen, BMS, Celgene, MSD, Novartis, Roche, Chugai, Pfizer, Lilly, Koray Tascilar: None declared, Hannah Schenker: None declared, Marina Sergeeva: None declared, Mageshwar Selvakumar: None declared, Laura Konerth: None declared, Jutta Prade: None declared, Sandra Strobelt: None declared, Melanie Hagen: None declared, Verena Schönau: None declared, Larissa Valor: None declared, Axel Hueber Grant/research support from: Novartis, Lilly, Pfizer, EIT Health, EU-IMI, DFG, Universität Erlangen (EFI), Consultant of: Abbvie, BMS, Celgene, Gilead, GSK, Lilly, Novartis, Speakers bureau: GSK, Lilly, Novartis, David Simon Grant/research support from: Else Kröner-Memorial Scholarship, Novartis, Consultant of: Novartis, Lilly, Arnd Kleyer Consultant of: Lilly, Gilead, Novartis,Abbvie, Speakers bureau: Novartis, Lilly, Frank Behrens Grant/research support from: Abbvie, Pfizer, Roche, Chugai, Janssen, Consultant of: Abbvie, Pfizer, Roche, Chugai, UCB, BMS, Celgene, MSD, Novartis, Biotest, Janssen, Genzyme, Lilly; Boehringer; Sandoz, Speakers bureau: Abbvie, Pfizer, Roche, Chugai, UCB, BMS, Celgene, MSD, Novartis, Biotest, Janssen, Genzyme, Lilly; Boehringer; Sandoz, José Antonio P. da Silva Grant/research support from: Pfizer, Abbvie, Consultant of: Pfizer, AbbVie, Roche, Lilly, Novartis, Christoph Baerwald Consultant of: CGB received speaker or consulting fees from AbbVie, Paid instructor for: CGB received speaker or consulting fees from AbbVie, Speakers bureau: CGB received speaker or consulting fees from AbbVie, Stephanie Finzel: None declared, Reinhard Voll: None declared, Eugen Feist Consultant of: Novartis, Roche, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Sanofi, Speakers bureau: Novartis, Roche, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Sanofi, Arnd Doerfler: None declared, Nemanja Damjanov Grant/research support from: from AbbVie, Pfizer, and Roche, Consultant of: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche, Speakers bureau: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche, Andreas Hess: None declared, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB

Abstract Abstract 3829 Therapies for the treatment of myelodysplastic syndromes (MDS) are limited. The only known curative therapy for MDS is allogeneic hematopoietic stem cell transplantation. MDS is frequently associated with epigenetic gene silencing via methylation of cytosine residues in gene regulatory regions. Clinical trials with DNA methyl-transferase inhibitors 5'azacytidine and 5-aza-2'-deoxycytidine (Decitabine, DAC) have shown hematologic responses and a survival benefit. Both azanucleosides have recently been approved for use in the clinic. However, responses are typically not durable, thus further characterization of response to treatment is required, as is the identification of new drugs to better treat MDS. Using bone marrow cells from NUP98-HOXD13 (NHD13) transgenic mice, which have previously been shown to faithfully recapitulate key features of MDS, we co-transplanted MDS and wild type (WT) bone marrow cells into WT irradiated recipient mice. The chimaeric bone marrow transplant (BMT) produces a recipient that mimics the human condition, with patient bone marrow comprised of hematopoietic cells derived from both the MDS clone as well as normal hematopoietic precursors. WT and MDS cells in the mice can be distinguished by differential CD45 alleles (CD45.1 and CD45.2, respectively), which enables analysis and purification of the MDS and normal cells; this feat is not easily achieved with human MDS patient samples, which lack cell surface antigens specific for the MDS clone. We treated mice with 0.018mg DAC (or saline) daily for 5 days, given every 4–5 weeks, to approximate MDS patient dosing schedules. Three trial groups were divided into saline (total n=19) and DAC (total n=24) treatment cohorts. Successful treatment of the chimeric MDS mice resulted in increasing levels of WT cells in the peripheral blood, with a concomitant reduction or eradication of the MDS cells. For instance, in trial #1, DAC treated chimaeric WT/MDS mice showed less severe anemia (2.0 g/dL higher Hgb), normalized neutrophil counts (57– 85% of mice vs 20–60%) and a significant survival benefit (median 27 vs 20 weeks, p=0.004) compared to saline treated mice. The response to treatment varied within individual mice and between trials, analogous to the variability in response seen in human MDS patients. We purified WT and MDS cells from treated mice and evaluated CpG island (CGI) DNA methylation in Chd13, a gene aberrantly methylated in MDS patients. Chd13 was hypermethylated in the murine MDS cells compared to WT cells (42–59% vs 10–16%, respectively). Of note, there was considerable variability between mice in the response to DAC treatment; half of the DAC treated mice showed a normalization of Chd13 methylation (14–20%) and half had a modest decrease in Chd13 methylation (38–40%). We next assayed global CGI methylation using a deep sequencing technique (DREAM, Digital Restriction Enzyme Analysis of Methylation). 8.2% of all CGI sites assayed were hypermethylated in MDS cells compared to WT; this increase in methylation was reduced to only 2.0% following DAC treatment of the MDS cells. This genome wide approach documented extensive hypermethylation in the NHD13 mice, similar to findings in a subset of MDS patients. Chimaeric WT/MDS mice demonstrated variable hematologic outcomes and cytosine demethylation in response to DAC treatment, as seen in human MDS patients. Successful treatment resulted in depletion of MDS cells allowing reconstitution of the bone marrow with WT cells as would happen in the successful treatment of patients. Durable responses were seen in several recipients, including one long-term survivor with no evidence of MDS cells in the bone marrow at 24 months of age (16 months post treatment). The chimaeric WT/MDS mice therefore represent a useful pre-clinical model of human MDS, which can be used to better characterize current treatments and test novel therapies. Disclosures: Issa: Johnson & Johnson: Consultancy; Astex: Consultancy. Aplan:NIH Office of Technology Transfer: Patents & Royalties.

Background:Abatacept (CTLA4-Ig) is a biological DMARD (bDMARD) for treatment of rheumatoid arthritis (RA) and selectively modulates the co-stimulatory signal by CD28: CD80/CD86 interaction required for T cell activation. CD28 mediated signaling regulates many T cell functions including cytokine production. The role of proteasome was approved in many autoimmune diseases, and the effect of Abatacept on modifying cytokines including interferon-γ that alters proteasome proteolytic activities was shown in RA.Objectives:To characterize the effect of Abatacept on the expression and proteolytic activity of the immunoproteasome.Methods:Effects of Abatacept on the proteasome system were investigated in 39 patients with rheumatoid arthritis over a period of 24 weeks. Using real time PCR, transcript expression levels of constitutive and corresponding immunoproteasome catalytic subunits were investigated at baseline (T0), week 16 (T16) and week 24 (T24) in sorted blood cells. Proteasomal activity and induction of apoptosis after proteasome inhibition were also evaluated in cellular subsets.Results:Upon treatment with Abatacept, remission or low disease activity according to DAS28 was achieved in 55 % of patients at T16 and in 70 % at T24. By Two- (time and type of response) way ANOVA, a significant reduction of proteasome immunosubunit β1i expression was shown only in CD4+ and CD8+ T cells of prolonged responders at both T16 and T24 (P= 0.0390 andP= 0.0198, respectively). One-way ANOVA analysis for each response group separately confirmed the results and showed significant reduction at T24;P= 0.0396 difference between T0 and T24,P= 0.0260 between T16 and T24 in CD4+ T cells of the same group. Abatacept did not influence chymotrypsin like activity of proteasome, which is carried out by the subunit β5i and had no effect on induction of apoptosis under exposure to a proteasome inhibitor in-vitro.Conclusion:Treatment with Abatacept showed a clear effect on the expression of the proteasome immunosubunit β1i. This phenomenon was only seen in CD4+ and CD8+ T cells of prolonged responding patients with RA suggesting an association between persistent induction of β1i and failure to the T cell directed therapy with Abatacept.References:[1]Keating, G.M., Abatacept: A Review of its Use in the Management of Rheumatoid Arthritis. Drugs, 2013. 73(10): p. 1095-1119.[2]Ferrington, D.A. and D.S. Gregerson, Immunoproteasomes: Structure, Function, and Antigen Presentation. Progress in molecular biology and translational science, 2012. 109: p. 75-112.[3]Marti, L., et al., Alterations in Cytokine Profile and Dendritic Cells Subsets in Peripheral Blood of Rheumatoid Arthritis Patients before and after Biologic Therapy. Annals of the New York Academy of Sciences, 2009. 1173: p. 334-42.Disclosure of Interests:Khetam Ghannam: None declared, Lorena Martinez Gamboa: None declared, Claudia Kedor Consultant of: Advisory Board for Novartis Pharma GmbH, Lydia Spengler: None declared, Gerd Rüdiger Burmester Consultant of: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Speakers bureau: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Eugen Feist Consultant of: Novartis, Roche, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Sanofi, Speakers bureau: Novartis, Roche, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Sanofi

Abstract Abstract 975 Every second, a healthy human body produces ∼2 million red blood cells (RBCs), an impossible feat for patients suffering from certain anemias not alleviated by erythropoietin (EPO) therapy. Instead, they rely on blood transfusions. Currently, all blood supplies are from donors, with inherent infection risks and supply uncertainty. Furthermore, some patients (such as those with sickle cell anemia) need frequent transfusion of RBC concentrates from best-matched donors, which are difficult to find. The production of cultured human RBCs in the quantities required for transfusion therapy (about 2 trillion RBCs in one transfusion unit of blood) will have great potential for improving healthcare worldwide. Large-scale production of cultured RBCs from isolated human CD34+ post-natal hematopoietic stem/progenitor cells (HSPCs) has achieved some success in the past decade. However, many challenges remain, such as determining the best method to enhance the cell number expansion and improve the efficiency of terminal maturation. CD34+ mononuclear cells (MNCs) contain HSPCs that have high proliferative capacity, but are very rare (<1% in PB MNC and <5% in CB MNC) and unable to be expanded substantially by existing culture methods. Although ESC/iPSC can be expanded in culture unlimitedly, their differentiation into mature RBCs remains inefficient. In addition to the approach of inducing erythroid-restricted precursors (erythroblasts) in unfractionated blood MNCs to iPSCs by reprogramming factors and then differentiate back to erythropoietic cells, we also attempted to use the same or similar reprogramming factors to induce expansion (and ideally immortalization) of erythroblasts. We first culture unfractionated CB MNCs in a serum-free culture condition with several cytokines and hormones that have been shown to specifically stimulate the proliferation of immature erythroblasts (pro-basophilic erythroblasts), as we did previously to prime these cells for reprogramming them to iPSCs. While this culture condition can achieve a substantial expansion of primary erythroblasts, their expansion is still limited (about 1 million fold starting from CB MNCs) and not enough for large-scale production of cultured RBCs for repeated transfusion patients. We reasoned that some reprogramming factors that we used to derive iPSCs may be able to induce an unlimited self-renewal capability of cultured erythroblasts in combination with specific culture conditions, without stepping into a pluripotent state. To this end, we have derived several immortalized erythroblast (iE) cell lines from CB MNCs after gene transfer of specific combinations of reprogramming factors. These iE cells can be expanded exponentially in serum-free suspension culture for over 1022 fold in a period of at least 5 months. They resemble pro-basophilic erythroblasts that had a large nucleus and basophilic cytoplasm. The iE cells express immature erythroblast cell surface markers (CD235+CD36+CD45+) and intracellular fetal hemoglobin in either culture flasks or a spin and high-density culture system. The vastly expanded iE cells are karyotypically normal, growth-factor dependent, and non-leukemic. We also developed a co-culture system with stromal cells to induce the terminal maturation and enucleation of iE cells. After switching to the termination culture condition, iE cells gradually stopped growing, decreased cell size and condensed nuclei, after 2 weeks we detected enucleated erythrocytes (CD235+DRAQ5−) at about 10% to 30% of the final maturated iE cells by FACS and fluorescence microscope. Coupled with about 5 to 10 fold expansion of cell number during terminal maturation, we can get approximately the same number of enucleated erythrocytes as the input cell number of iE cells. Since mature and enucleated RBCs are devoid of DNA, the genetic modification or potential genomic alterations in the iE cells are not likely to be a main concern for clinical uses. Our result may ultimately lead to the development of unlimited sources of cultured RBCs for optimally-matched or personalized transfusion medicine. Disclosures: No relevant conflicts of interest to declare.

Background:Tumor necrosis factor inhibitors have revolutionized the treatment of rheumatoid arthritis (RA). However, only about 50% of the patients respond well to TNF inhibitors. Therefore, markers that predict response to TNF inhibitors are valuable. Previously we demonstrated that central nervous system (CNS) response to nociceptive stimuli, measured by fMRI of the brain as blood oxygen level dependent (BOLD) signals, decreases already after 24 hours of anti-TNF administration a higher pre-treatment BOLD signal volume seems to predict clinical response to treatment with certolizumabpegol (CZP)1,2. We therefore hypothesized that the baseline volume of BOLD signal in the CNS could predict anti-TNF treatment response.Objectives:To perform a randomized placebo controlled trial in active RA patients to test the effect of TNF inhibition on arthritis induced pain activity in the brain and to test whether patients with high-level RA-related brain activation react differently to TNF-inhibitors than patients with low-level brain activation.Methods:Adult RA patients fulfilling the 2010 ACR/EULAR classification criteria with a DAS28>3.2 receiving stable DMARD treatment for at least 3 months were eligible. Patients underwent the first fMRI at screening measuring BOLD signal upon MCP joint compression and were stratified into low (< 700 units) and high (>700 units) voxel counts. Then patients were randomized to CZP or placebo with a 2:1 ratio. The second and third fMRI were performed after 12 and 24 weeks, respectively. Control stimulation was done by measuring brain activation after non-painful finger tapping.Results:156 RA patients with moderate-to-high disease activity participated in the study. In the finger tapping control, fMRI showed no significant changes in BOLD signal in the CZP-L and CZP-H arms, but a slight but significant decrease (p=0.043) was observed. After joint compression, the CZP-L group showed significant increase in the BOLD signal volume (p=0.043) in fMRI-2 as compared to fMRI-1 with no further significant changes. In contrast, in the CZP-H group, the BOLD signal volume significantly decreased (p=0.037) in fMRI-2 and continued to decrease further, p=0.007. No significant changes were observed in the placebo arm over time.Conclusion:TNF inhibition improves arthritis-related brain activity in the subgroup of RA patients with high baseline BOLD activity in the fMRI.References:[1]Hess, A.et al.PNAS (2011).[2]Rech, J. et al. Arthritis & Rheumatism (2013).Fig 1.BOLD fMRI responses to painful stimulationAcknowledgments:The study was supported by an unrestricted grant of UCB Biopharma SPRL Brussels, BelgiumDisclosure of Interests:Jürgen Rech Consultant of: BMS, Celgene, Novartis, Roche, Chugai, Speakers bureau: AbbVie, Biogen, BMS, Celgene, MSD, Novartis, Roche, Chugai, Pfizer, Lilly, Koray Tascilar: None declared, Hannah Schenker: None declared, Melanie Hagen: None declared, Marina Sergeeva: None declared, Mageshwar Selvakumar: None declared, Laura Konerth: None declared, Jutta Prade: None declared, Sandra Strobelt: None declared, Verena Schönau: None declared, Larissa Valor: None declared, Axel Hueber Grant/research support from: Novartis, Lilly, Pfizer, EIT Health, EU-IMI, DFG, Universität Erlangen (EFI), Consultant of: Abbvie, BMS, Celgene, Gilead, GSK, Lilly, Novartis, Speakers bureau: GSK, Lilly, Novartis, David Simon Grant/research support from: Else Kröner-Memorial Scholarship, Novartis, Consultant of: Novartis, Lilly, Arnd Kleyer Consultant of: Lilly, Gilead, Novartis, Abbvie, Speakers bureau: Novartis, Lilly, Frank Behrens Grant/research support from: Abbvie, Pfizer, Roche, Chugai, Janssen, Consultant of: Abbvie, Pfizer, Roche, Chugai, UCB, BMS, Celgene, MSD, Novartis, Biotest, Janssen, Genzyme, Lilly; Boehringer; Sandoz, Speakers bureau: Abbvie, Pfizer, Roche, Chugai, UCB, BMS, Celgene, MSD, Novartis, Biotest, Janssen, Genzyme, Lilly; Boehringer; Sandoz, Christoph Baerwald Consultant of: CGB received speaker or consulting fees from AbbVie, Paid instructor for: CGB received speaker or consulting fees from AbbVie, Speakers bureau: CGB received speaker or consulting fees from AbbVie, Stephanie Finzel: None declared, Reinhard Voll: None declared, Eugen Feist Consultant of: Novartis, Roche, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Sanofi, Speakers bureau: Novartis, Roche, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Sanofi, José Antonio P. da Silva Grant/research support from: Pfizer, Abbvie, Consultant of: Pfizer, AbbVie, Roche, Lilly, Novartis, Arnd Doerfler: None declared, Nemanja Damjanov Grant/research support from: from AbbVie, Pfizer, and Roche, Consultant of: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche, Speakers bureau: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche, Andreas Hess: None declared, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB

AbstractThe 2012 Globe to Globe Festival proved a great success. Actors, directors, musicians, dancers, designers and technicians travelled from all over the world to perform on the Globe stage. Visitors to London’s Cultural Olympiad enjoyed six jam-packed weeks of Shakespeare, presented in an array of international languages. The Globe’s Artistic Director, Dominic Dromgoole, and his Festival Director, Tom Bird, had achieved what seemed, to many, the impossible. Nonetheless, filmed interviews with Dromgoole and Bird, conducted during the festival by the American documentary-maker Steve Rowland, offer tantalizing insights into the genesis of the festival venture. These candid interviews confirm the sometimes farcical, often exhausting, but invariably serendipitous truth behind the Globe to Globe Festival’s short, intense history. Although the Globe was “flying completely blind,” it still succeeded in hosting a glorious feast of Shakespearean delights, seasoned with the strong spice of multiculturality.

Functional electrical stimulation therapy (FEST) can improve motor function after neurological injuries. However, little is known about cortical changes after FEST and weather it can improve motor function after traumatic brain injury (TBI). Our study examined cortical changes and motor improvements in one male participant with chronic TBI suffering from mild motor impairment affecting the right upper-limb during 3-months of FEST and during 3-months follow-up. In total, 36 sessions of FEST were applied to enable upper-limb grasping and reaching movements. Short-term assessments carried out using transcranial magnetic stimulation (TMS) showed reduced cortical silent period (CSP), indicating cortical and/or subcortical inhibition after each intervention. At the same time, no changes in motor evoked potentials (MEPs) were observed. Long-term assessments showed increased MEP corticospinal excitability after 12-weeks of FEST, which seemed to remain during both follow-ups, while no changes in CSP were observed. Similarly, long-term assessments using TMS mapping showed larger hand MEP area in the primary motor cortex (M1) after 12-weeks of FEST as well as during both follow-ups. Corroborating TMS results, functional magnetic resonance imaging (fMRI) data showed M1 activations increased during hand grip and finger pinch tasks after 12-weeks of FEST, while gradual reduction of activity compared to after the intervention was seen during follow-ups. Widespread changes were seen not only in the M1, but also sensory, parietal rostroventral, supplementary motor, and premotor areas in both contralateral and ipsilateral hemispheres, especially during the finger pinch task. Drawing test performance showed improvements after the intervention and during follow-ups. Our findings suggest that task-specific and repetitive FEST can effectively increase cortical activations by integrating voluntary motor commands and sensorimotor network through functional electrical stimulation (FES). Overall, our results demonstrated cortical re-organization in an individual with chronic TBI after FEST.

The mesoscale variability in the Mediterranean Sea is investigated through eddy detection techniques. The analysis is performed over 24 years (1993–2016) considering the three-dimensional (3D) fields from an ocean re-analysis of the Mediterranean Sea (MED-REA). The objective is to achieve a fit-for-purpose assessment of the 3D mesoscale eddy field. In particular, we focus on the contribution of eddy-driven anomalies to ocean dynamics and thermodynamics. The accuracy of the method used to disclose the 3D eddy contributions is assessed against pointwise in-situ measurements and observation-based data sets. Eddy lifetimes ≥ 2 weeks are representative of the 3D mesoscale field in the basin, showing a high probability (> 60%) of occurrence in the areas of the main quasi-stationary mesoscale features. The results show a dependence of the eddy size and thickness on polarity and lifetime: anticyclonic eddies (ACE) are significantly deeper than cyclonic eddies (CE), and their size tends to increase in long-lived structures which also show a seasonal variability. Mesoscale eddies result to be a significant contribution to the ocean dynamics in the Mediterranean Sea, as they account for a large portion of the sea-surface height variability at temporal scales longer than 1 month and for the kinetic energy (50–60%) both at the surface and at depth. Looking at the contributions to ocean thermodynamics, the results exhibit the existence of typical warm (cold) cores associated with ACEs (CEs) with exceptions in the Levantine basin (e.g., Shikmona gyre) where a structure close to a mode-water ACE eddy persists with a positive salinity anomaly. In this area, eddy-induced temperature anomalies can be affected by a strong summer stratification in the surface water, displaying an opposite sign of the anomaly whether looking at the surface or at depth. The results show also that temperature anomalies driven by long-lived eddies (≥ 4 weeks) can affect up to 15–25% of the monthly variability of the upper ocean heat content in the Mediterranean basin.

Study of the mechanical response of rock slopes to moderate earthquakes is important for understanding the local rheology of landslide and earthquake interactions and for mitigating the risks associated with subsurface geological processes in tectonically active mountainous belts. To complement existing point measurements from surface observations (e.g., global positioning system and interferometric synthetic-aperture radar measurements), measuring the ambient noise-based velocity change (δv/v) allows for remote observations of mechanical state changes of the slope, at depth and continuously in time. We herein investigate the seismic responses of the Pubugou rock slope, a typical steep rock slope in south-west China, to the 2019 Mw 5.7 Changning earthquake. We apply ambient noise interferometry to the slope and measure the coda wave velocity changes at frequencies from 2 to 20 Hz with a 1-h temporal resolution, 2 days before and 14 days after the earthquake. We observe a significant co-seismic wave velocity decrease caused by the Changning earthquake of up to 0.9% followed by a gradual logarithmic recovery process over 2 weeks. The earthquake-induced stress sensitivity of δv/v on the slope is estimated as ∼3.2×10−8 Pa−1. Through the analysis of the co-seismic and post-seismic δv/v with different time lapses of the coda, we characterize the healing process on the slope and also constrain such changes to 75 m in depth. This study highlights the possibility of quantitatively characterizing the slope weakness using moderate earthquakes in mountainous areas in the future.

Lake Afdera is a hypersaline endorheic lake situated at 112 m below sea-level in the Danakil Depression. The Danakil Depression is located in the northern part of the Ethiopian Afar and features an advanced stage of continental rifting. The remoteness and inhospitable environment explain the limited scientific research and knowledge about this lake. Bathymetric data were acquired during 2 weeks expeditions in January/February 2016 and 2017 using an easily deployable echosounder system mounted on an inflatable motorized boat. This study presents the first complete bathymetric map of the lake Afdera. Bathymetric results show that the lake has an average depth of 20.9 m and a total volume of 2.4 km3. The maximum measured depth is 80 m, making Lake Afdera the deepest known lake in Afar and the lowest elevation of the Danakil Depression. Comparison with historical reports shows that the lake level did not fluctuate significantly during the last 50 years. Two distinct tectonic basins to the north and the south are recognized. Faults of different orientations control the morphology of the northern basin. In contrast, the southern basin is affected by volcano-tectonic processes, unveiling a large submerged caldera. Comparison between the orientation of faults throughout the lake with the regional fault pattern indicates that the lake is part of two transfer zones: the major Alayta–Afdera Transfer Zone and the smaller Erta Ale–Tat’Ali Transfer Zone. The interaction between these Transfer Zones and the rift axis forms the equivalent of a developing nodal basin which explains the lake’s position as the deepest point of the depression. This study provides evidence for the development of an incipient transform fault on the floor of the Afar depression.

Precipitation change, which is closely related to drought and flood disasters in China, affects billions of people every year, and the demand for subseasonal forecasting of precipitation is even more urgent. Subseasonal forecasting, which is more difficult than weather forecasting, however, has remained as a blank area in meteorological service for a long period of time. To improve the accuracy of subseasonal forecasting of China precipitation, this work introduces the machine learning method proposed by Hwang et al. in 2019 to predict the precipitation in China 2–6 weeks in advance. The authors used a non-linear regression model called local linear regression together with multitask feature election (MultiLLR) model and chosen 21 meteorological elements as candidate predictors to integrate diverse meteorological observation data. This method automatically eliminates irrelevant predictors so as to establish the forecast equations using multitask feature selection process. The experiments demonstrate that the pressure and Madden–Julian Oscillation (MJO) are the most important physical factors. The average prediction skill is 0.11 during 2011–2016, and there are seasonal differences in forecasting skills, evidenced by higher forecast skills of winter and spring seasons than summer and autumn seasons. The proposed method can provide effective and indicative guidance for the subseasonal prediction of precipitation in China. By adding another three factors, Arctic Oscillation (AO) index, Western North Pacific Monsoon (WNPM) index and Western North Pacific Subtropical High (WNPSH) index into the MultiLLR model, the authors find that AO can improve the forecast skill of China precipitation to the maximum extent from 0.11 to 0.13, followed by WNPSH. Moreover, the ensemble skill of our model and CFSv2 is 0.16. This work shows that our subseasonal prediction of China precipitation should be benefited from the MultiLLR model.

Wildfire is one of the most common natural hazards in the world. Fire risk estimation for the purposes of risk reduction is an important aspect in disaster studies around the world. The aim of this research was to develop a machine learning workflow process for South East China to monitor fire risks over a large region by learning from a grid file database containing a time series of several of the important environmental parameters largely extracted from remote sensing data products, and highlight areas as fire risk or non-fire risk over a couple of weeks in the future. The study employed fire threshold and the transductive PU learning method to identify reliable non-fire/negative training samples from the grid file database using fire/positive training samples, labeled using the MODIS MCD14ML fire location product. Different models were trained for the three natural vegetation land covers, namely evergreen broadleaf forest, mixed forest, and woody savannas in the study area. On the test dataset, the three models exhibited high sensitivity (>80%) by identifying the majority of fires in the test dataset for all land covers. The use of the reliable negatives identified though the fire threshold and PU learning process resulted in low precision and accuracy. During the model verification process, the model for the mixed forest land cover performed the best with 70% of verification fires falling within the classified fire zone. It was found that the better representation of mixed forest in the training samples made this model perform more reliably as compared to others. Improving the individual models constructed for different land covers and combining them can provide fire classification for a larger region. There is room to improve the spatial precision of fire cell classification. Introducing finer scale features that have higher correlation with fire activity and exhibit high spatial variability seems a viable way forward.

The Cascades back-arc in northern California is dominated by monogenetic tholeiitic basalts that erupted throughout the Pleistocene. Elucidating their eruptive history and processes is important for understanding potential future eruptions here. We focus on the well-exposed monogenetic volcano that emplaced the Brushy Butte flow field, which constructed a ∼150 m tall edifice, has flow lobes up to >10 km long, and in total covers ∼150 km2 with an eruptive volume of 3.5 km3. We use a multidisciplinary approach of field mapping, petrography, geochemistry, paleomagnetism, geochronology, and lidar imagery to unravel the eruptive history and processes that emplaced this flow field. Tholeiitic basalts in northern California have diverse surface morphology and vegetation cover but similar petrographic appearances, which makes them hard to distinguish in the field. Geochemistry and paleomagnetism offer an independent means of distinguishing tholeiitic basalts. Brushy Butte flow field lavas are similar in major-oxide and trace-element abundances but differ from adjacent tholeiitic basalts. This is also apparent in remanent magnetic directions. Additionally, paleomagnetism indicates that the flow field was emplaced during a geologically brief time interval (10–20 years), which 36Cl cosmogenic dating puts at 35.7 ± 1.7 ka. Lidar imagery shows that these flows erupted from at least 28 vents encompassing multiple scoria cones, spatter cones, and craters. Flows can be grouped into four pulses using stratigraphic position and volume. Pulse 1 is the most voluminous, comprising eight eruptions and ∼2.3 km3. Each subsequent pulse started rapidly but decayed quickly, and each successive pulse erupted less lava (i.e., 2.3 km3 for pulse 1, 0.6 km3 for pulse 2, 0.3 km3 for pulse 3, and 0.2 km3 for pulse 4). Many of these flows host well-established lava channels and levees (with channel breakouts) that lead to lava fans, with some flows hosting lava ponds. Similar flow features from tholeiitic eruptions elsewhere demonstrate that these morphologies generally occur over weeks, months, or longer (e.g., Puʻu ʻŌʻō eruption at K–llauea, Hawaiʻi). This multidisciplinary study shows the range of eruptive styles and durations of a Cascades back-arc eruption and illustrates how potential future tholeiitic eruptive activity in the western United States might progress.

This study provides an attempt to analyze the pre-eruptive seismicity events for volcano eruption forecasting. After more than 50 years of slumber, Agung volcano on Bali Island erupted explosively, starting on November 21, 2017. The eruption was preceded by almost 2 months of significant increase of recorded seismicity, herein defined as “seismic crisis.” Our study provides the first analysis of VT events using data from eight local seismic stations deployed by the Center for Volcanology and Geological Hazard Mitigation of Indonesia (CVGHM) to monitor the Agung Volcano activity. In total, 2,726 Volcano-Tectonic (VT) events, with 13,023 P waves and 11,823 S wave phases, were successfully identified between October 18 and November 30, 2017. We increased the accuracy of the hypocenter locations of these VT events using a double-difference (DD) relative relocation and a new velocity model appropriate to the subsurface geological conditions of Agung volcano. We found two types of seismicity during the recording period that represent the VT events relating to fracture network reactivation due to stress changes (during the seismic crisis) and magma intrusion (after the seismic crisis). The characteristics of each event type are discussed in terms of Vp/Vs values, phase delay times, seismic cluster shapes, and waveform similarity. We interpret that the upward migrating magma reached a barrier (probably a stiff layer) which prohibited further ascent. Consequently, magma pressurized the zone above the magma chamber and beneath the barrier, reactivated the fracture zone between Agung and Batur volcanoes, and caused the seismic crisis since September 2017. In early November 2017, the barrier was finally intruded, and magma and seismicity propagated toward the Agung summit. This reconstruction provides a better depth constraint as to the previous conceptual models and explains the long delay (∼10 weeks) between the onset of the seismic crisis and the eruption. The distinction between the fracture reactivation and magma intrusion VT events observed in this study is significant for eruption forecasting and understanding the subsurface structure of the magmatic system. Based on the results obtained in this study, we emphasize the importance of prompt analysis (location and basic seismic characteristics) of the seismic crisis preceding the Agung eruption.

In 2017, Mount Agung produced a small (VEI 2) eruption that was preceded by an energetic volcano-tectonic (VT) swarm (>800 earthquakes per day up to M4.9) and two months of declining activity. The period of decreased seismic activity complicated forecasting efforts for scientists monitoring the volcano. We examine the time history of earthquake families at Mount Agung in search of additional insight into the temporal changes in the shallow crust prior to eruption. Specifically, we analyze the period of declining seismic activity about five weeks prior to the eruption when forecasting uncertainty was greatest. We use REDPy (Hotovec-Ellis and Jeffries, 2016) to build a catalog of 6,508 earthquakes from 18 October 2017–15 February 2018 and group them into families of repeating earthquakes based on waveform similarity using a cross-correlation coefficient threshold of 0.8. We show that the evolution of earthquake families provides evidence that Mount Agung was progressing toward eruption even though overall earthquake rates and seismic-energy-release declined. We find that earthquake families that dominated seismicity during the beginning of the crisis ceased near the onset of tremor on 12 November 2017. Then, earthquake families took on characteristics commonly observed during effusive phases of eruptions on 15 November—a full six days before the first phreatomagmatic eruption on 21 November 2017 and a full ten days before the actual onset of lava effusion on 25 November 2017. We interpret the transitions in seismicity as the manifestation of a three-phase physical model including an Intrusion Phase, a Transition Phase, and a Eruptive Phase. During the Intrusion Phase, seismicity was dominated by VT earthquakes with a relatively high percentage of repeaters (59%) grouped into numerous (65) simultaneous families. During the Eruptive Phase, seismicity included both VT and low frequency earthquakes that grouped into relatively long-lived families despite a low overall percentage of repeaters (14%). The Transition Phase exhibited characteristics of earthquake families between the Intrusion Phase and Eruptive Phase. We conclude that the time history of earthquake families provides insight into the evolution of the stress distribution in the volcanic edifice, the development of the volcanic conduit, and seismogenesis of magma effusion. Finally, we discuss the role that repeating earthquakes could play in real-time monitoring at restless volcanoes. Our work suggests eruption forecasts can be improved by incorporating automatic processing codes to assist seismologists during sustained periods of high earthquake rates, even at sparsely monitored volcanoes.

This short report captures the week-by-week reflections of a group of family physicians who joined the clinical and operational management teams tasked with providing the in-patient service of an 862-bed COVID-19 field hospital. The ‘Hospital of Hope’ at the Cape Town International Convention Centre (CTICC) was established as an intermediate care facility specifically to cope with the effects of the COVID-19 pandemic in Cape Town metropole. In an extraordinary feat of engineering, the conference centre floor was transformed within a matter of weeks into wards with piped oxygen at each bed. Whilst the emergency medicine specialists took the lead in designing and commissioning the facility, the medical management and staff were drawn mostly from family physicians. This report is a short reflection on the experience of the first 4 weeks of managing patients in this repurposed space. Our insights evolved during various formal and informal learning conversations as the in-patient service became more organised over time. We hope that these insights, as well as the process of reaching them, will assist other colleagues in serving their communities during this difficult moment in history; moreover, it may reflect a renewed appreciation for team-based interdisciplinary efforts in achieving person-centred care.

Abstract Background Little is known about the influence on outcome of exploration of the patient-therapist relationship (that is, transference work) in psychoanalytic psychotherapy. We hypothesized that depressed adolescents would have better long-term effects from psychoanalytic psychotherapy with than without transference work. Methods Depressed adolescent (16 to 18 years) were recruited in health authority funded out-patient clinics in Oslo and Vestfold County, Norway. They were randomized to 28 weeks of treatment with psychoanalytic psychotherapy with or without transference work. Change was assessed using linear-mixed models. The primary outcome measure was the Psychodynamic Functioning Scale (pre- post-, and 1-year post-treatment). Level of depression was measured at the same time points and during therapy (week 12, and 20). Results 69 adolescents were treated with (N = 39) or without (N = 31) transference work. The mean number of sessions was 18.6 (SD = 8,6) in the transference work group and 18.0 (SD = 10.9) in the non-transference work group. Both groups showed large and significant improvement on Psychodynamic Functioning Scale during the whole study period. The difference between the two groups was not significant during the treatment period (95% CI −.79 to 1.2, p = .674, F = .18), or from post-treatment to one-year follow-up (95% CI −.13 to .96; p = .134; F = 2.3). For the secondary outcome measures the transference work group had significantly better outcomes from 12 weeks in treatment to one-year follow-up (Beck Depression Inventory, 95% CI − 1.7 to −.14, p = .022; Montgomery and Åsberg Depression Rating Scale, 95% CI − 1.6 to −.23, p = .009). Conclusion The findings suggest that exploration of the adolescents’ relations to the therapist amplify the effects of short-term psychoanalytic psychotherapy on their depressive symptoms for adolescents with a Major Depressive Disorder. Trial registration ClinicalTrials.gov. Id: NCT01531101. Registered 8 February 2012.

Abstract Background/Aims Olokizumab (OKZ) is a new humanised monoclonal antibody targeting IL-6 directly. Here we present the results of a global randomised clinical trial (RCT) in patients (pts) with RA. Methods This double-blind, placebo (PBO) and active controlled, RCT in pts with moderately to severely active RA despite MTX (ClinicalTrials.gov Identifier NCT02760407, CREDO2) was carried out in 18 counties. Pts were randomized 2:2:2:1 to receive subcutaneous injections of OKZ 64 mg every 2 weeks (q2w), OKZ 64 mg once every 4 weeks (q4w), adalimumab (ADA) 40mg q2w or PBO for 24 weeks, plus MTX. After week 24, subjects either rolled over into an open-label study or entered the Safety Follow-Up Period for another 20 weeks. The primary endpoint was ACR 20% (ACR20) response rate at week 12. Secondary endpoints included: percentage of subjects with DAS28-CRP <3.2 and improvement of HAQ-DI from baseline at week 12, ACR50 and percentage of subjects with remission (CDAI) ≤2.8 at week 24. Safety outcomes, including adverse events, serious adverse events and laboratory abnormalities were assessed. Results 1,648 subjects were randomised to OKZ 64mg q2w (n = 464), OKZ 64mg q4w (n = 479), ADA 40mg (n = 462) or PBO (n = 243). Baseline characteristics were comparable across treatment arms. The vast majority of the pts completed 24 weeks treatment period 421 (90.7%) in q2w, 437 (91.2%) in q4w, 413 (89.4%) in ADA and 208 (85.6%) in PBO arms and enrolled to open-label extension study: 410 (88.4%), 422 (88.1%), 397 (85.9%) and 199 (81.9%) pts, respectively. Both regimens of OKZ were significantly better than PBO in all primary and secondary endpoints. Furthermore, non-inferiority to ADA was demonstrated for the pre-defined endpoints of ACR20 and DAS28-CRP<3.2 for both OKZ treatment groups. The efficacy outcomes were maintained throughout the 24-week period of the study. Overall incidence of treatment-emergent adverse events (TEAEs) was 70.0% in OKZ q2w arm; 70.9% in OKZ q4w arm, 65.4% in ADA arm and 63.4% in PBO, TEAEs leading to study treatment discontinuation were reported in 4.5%, 6.3%, 5.6% and 3.7% pts, respectively. The number of deaths were comparable among arms: 3 (0.6%; 2 infections, 1 cerebrovascular accident) in the OKZ q2w arm, 2 (0.4%; 1 infection, 1 myocardial ischemia) in OKZ q4w arm, 1 (0.2%; infection) in ADA arm and 1 (0.4%; sudden death) in PBO. The most common treatment-emergent serious adverse events (TESAEs) were infections. Conclusion In this global Phase III trial, treatment with OKZ plus MTX in both regimes (OKZ 64 mg q2w and OKZ 64 mg q4w) was associated with significant improvements in the signs, symptoms and physical function of RA compared to PBO plus MTX and non-inferior to ADA plus MTX over a 24-week period. OKZ was well tolerated and no new safety signals were observed. Disclosure E. Feist: Consultancies; R-Pharm, Abbvie, BMS, Celgene, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche/Chugai, Sanofi. Honoraria; R-Pharm, Abbvie, AB2Bio, BMS, Celgene, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche/Chugai, Sanofi, Sobi, UCB. Member of speakers’ bureau; R-Pharm, Abbvie, AB2Bio, BMS, Celgene, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche/Chugai, Sanofi, Sobi, UCB. Grants/research support; Lilly, Novartis, Pfizer, Roche/Chugai. S. Chohan: None. S. Fatenejad: Consultancies; RPharm International. Shareholder/stock ownership; Pfizer. S. Grishin: Corporate appointments; Employed by R-Pharm. E. Korneva: Corporate appointments; Employed by R-Pharm. E.L. Nasonov: Honoraria; Lilly, Abbnie, Prizer, Biocad, R-Pharm. Member of speakers’ bureau; Lilly, Abbnie, Prizer, Biocad, R-Pharm. A. Rowińska-Osuch: Consultancies; R-Pharm. M. Samsonov: Corporate appointments; Employed by R-Pharm.

Abstract Background/Aims Olokizumab (OKZ) is a new humanised monoclonal antibody targeting IL-6. Here we present the results of the phase III study of OKZ in anti-TNF-IR patients. Methods Patients with moderately to severely active RA who had previously failed TNF inhibitors (ClinicalTrials.gov Identifier NCT02760433/CREDO3) were randomized in a 2:2:1 ratio to receive subcutaneous (SC) injections of OKZ 64 mg every 2 weeks (q2w), OKZ 64 mg once every 4 weeks (q4w) or placebo (PBO), plus MTX. At week 16, all subjects in the PBO group were randomized in a 1:1 ratio to receive either of OKZ regimes. The primary endpoint was ACR20 response at week 12. Results 368 subjects were randomised according to the protocol and 320 patients (87%) completed the 24-week treatment period. Baseline characteristics were comparable across arms. Both regimens of OKZ were significantly better in primary endpoint: ACR20 were 60.9% (p = 0.0029 in comparison vs. PBO) in OKZ q2w, 59.6% in OKZ q2w (p = 0.0040 in comparison vs. PBO) and 40.6% in PBO. The key efficacy outcomes were maintained throughout the 24-week period of the study. Overall incidences of treatment-emergent adverse events (TEAE) were 65.5% in OKZ q2w, 65.0% in OKZ q4w and 50.7% in PBO. Subsequent randomization of PBO arm at week 16 did not change TEAEs incidence rate per treatment group significantly: 64.3% in any OKZ q2w and 59.7% in any OKZ q4w. The majority of TEAEs in all groups were not serious and were of mild or moderate severity. Incidence of treatment-emergent serious adverse events (TESAE) were: 12 (7.0%) subjects in any OKZ q2w; 6 subjects (3.2%) in any OKZ q4w group, all in the first 16 weeks. The most frequently reported TESAEs across all treatment groups were infections and infestations: 2 (1.2%) in OKZ q2w group, 2 (1.1%) in OKZ q4w group. No opportunistic infections including active tuberculosis, major adverse cardiovascular events, gastrointestinal perforations or deaths were reported. Conclusion In this global Phase III trial in patients with moderately to severely active RA inadequately controlled by TNF-α inhibitor therapy, treatment with OKZ plus MTX in both regimes (OKZ 64 mg q2w and OKZ 64 mg q4w) was associated with significant improvements in the signs and symptoms of RA compared to PBO plus MTX over a 24-week period. Treatment with OKZ q2w and q4w in this difficult to treat population was well tolerated and consistent with the established safety profile of anti-IL-6 agents. Disclosure E. Feist: Consultancies; R-Pharm, Abbvie, BMS, Celgene, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche/Chugai, Sanofi. Honoraria; R-Pharm, Abbvie, BMS, Celgene, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche/Chugai, Sanofi, Sobi, UCB. Member of speakers’ bureau; R-Pharm, Abbvie, AB2Bio, BMS, Celgene, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche/Chugai, Sanofi, Sobi, UCB. Grants/research support; Lilly, Novartis, Pfizer, Roche/Chugai. S. Fatenejad: Consultancies; RPharm International. Shareholder/stock ownership; Pfizer. S. Grishin: Corporate appointments; Employed by R-Pharm. E. Korneva: Corporate appointments; Employed by R-Pharm. M. Luggen: Consultancies; Amgen, Sun Pharmaceuticals, R-Pharm International. Grants/research support; I havAbbvie, R-Pharm, Sun Pharmaceuticals, Pfizer, Novartis, Lilly, and GSK. E. Nasonov: Honoraria; Lilly, Abbnie, Prizer, Biocad, R-Pharm. Member of speakers’ bureau; Lilly, Abbnie, Prizer, Biocad, R-Pharm. M. Samsonov: Corporate appointments; Employed by R-Pharm.

When I think of 'flesh' at this moment in human history, it's difficult not to think of the images on television and in print news reports in recent weeks. The first pictures of Kosovo's Albanian population being purged from their homes and amassed on the borders of neighbouring countries have left an impression. While cameras have stood witness from afar, we have been confronted by images of people being shot at point-blank range. Rows of corpses have lined up after ill-executed bombing raids by NATO forces and the more systematic slaughter of pro-independence activists by wayward Indonesian military groups in East Timor. Perhaps less expected, the deaths of school students in Columbine, Colorado, and the patrons of a gay club in the Soho district of London have added force to daily reminders on the insistence of the flesh to being. The significance of flesh to being extends beyond a simple matter of physical survival. It is often our reaction to the flesh of the other upon which we stake our very sense of self. Subjectivity becomes a constant process of negotiating the borders of the self, where an individual may either identify with the other they encounter, or attempt to deny or repress the other's existence. The recent events around the world are illustrative of the attempt by some individuals to repress others, who (inadvertently) threaten their stable sense of self, by way of the very final solution of death. It is often a response to an irrational fear of the inescapable physical flesh of others in various manifestations, such as ethnicity, gender and sexuality, that provokes such violent actions. In view of the on-going perpetration of violence towards others, it is little wonder that fantasies of transcending the flesh abound in many narratives. The successes of William Gibson's Neuromancer in 1986, and now the currently-released film The Matrix are contemporary testaments to the ongoing popularity of this fantasy of human self-creation without the limits imposed by 'meat'. While it might be argued that the leap into cyberspace is a denial of the flesh, it might also be argued that emergent technologies are almost certainly embraced because they seem to offer the possibility of allowing us to be more human than we are currently. New technologies seem to offer new ways of being in the world that will refine human communication and diffuse prejudices, where you will be loved for your personality and not hated for the colour of your skin. In this issue of M/C we consider a variety of ways of thinking about the flesh amidst the effects of media and new technologies. The feature article by Sean Aylward Smith asks "Where Does the Body End?", and thus also, where does technology begin? Smith deliberates on the difficulty of working with and about technology, where common-sense suggests that one should be able to define the distinction between technology and the body before embarking on the study of "any given socio-technical imbroglio". Working through the philosophical writings of Felix Guattari, Bruno Latour and then Guattari again, this time in conjunction with Gilles Deleuze, Smith progressively confuses the apparently neat distinction between technology and the body to argue for a subjectivity, or rather "a mode of individuation" as a haecceity, where humans are "collective assemblages" of agencies and affects. Peter Chen undertakes his deliberation on flesh in terms of its existence on the Internet in the form of pornography. In "Community Without Flesh: First Thoughts on the New Broadcasting Services Amendment (Online Services) Bill 1999", Chen argues that in adapting existing regulatory paradigms to the Internet, the Australian government has overlooked the informal communities of the virtual world. He suggests that in attempting to meet a perceived social need for regulation with political and administrative expedience, the government has ignored the potentially cohesive role they might play in the development of self-regulating communities who require little government intervention to produce socially beneficial outcomes. Chen predicts the formation of a new type of community, "whose desire for a feast of flesh" will ensure they are vigilant in their evasion of the cast of the regulators' net. Alan Macdougall's article might offer some practical solutions for those members of the virtual communities of cyberspace discussed by Chen. In "'And the Word Was Made Flesh, and Dwelt amongst Us'": Towards Pseudonymous Life on the Internet", Macdougall engages in a critical discussion of pseudonymity on the Internet, where users construct untraceable identities for use online. While Chen identified the concerns private citizens have when governments implement modes of surveillance for online activities, Macdougall acknowledges the threat individuals also experience from commercial interests gathering demographic information. He iterates the emergent technologies that are being developed to counter such intrusions, and considers the ways in which this "new flesh" will dwell amongst us. Axel Bruns continues the discussion of the Internet, and concurs with Macdougall's assessment that while online activity may present itself as ephemeral, in fact it has a presence that produces very real effects. In a defense of the significance of online publishing and communication, Bruns asks "How Solid Is the Flesh?"; he wonders whether the solidity and therefore the esteem that is generally attributed to publications in the 'real world' is a convincing argument when many books and print journals languish unread on obscure library shelves. On the contrary, Bruns argues, the 'flesh' is not left behind when the leap is taken into cyberspace. The ongoing explosion in available storage space on the Internet has the effect that cyberspace is becoming increasingly anephemeral. In "How Funny?: Spectacular Ani in Animated Television Cartoons" Simon-Astley Scholfield shifts our focus to a small screen of another kind in his consideration of the popular animated American 'kidult' cartoon series Ren and Stimpy and South Park. He notes that amid the uproar about the excessive depictions of violence and viscera in these comedy cartoons, an analysis of their representations of anal flesh has been conspicuously avoided. Scholfield's article addresses this oversight in a comparison between the two programmes. He concludes that while South Park explores subversive themes, "they have been twisted into misogynist and homophobic contexts". In contrast, the narrative outcomes in Ren and Stimpy posit a challenge to the "dominant homophobic culture". The 1997 spate of dead celebrities provides the flesh in Rebecca Farley's article, "The Word Made Flesh: Media Coverage of Dead Celebrities". Noticing the absence of pictures of dead celebrities' bodies in the coverage of their deaths, Farley wonders if when alive, celebrities fill a particular function, what do they do in death? Choosing to focus specifically on the deaths of Gianni Versace, Michael Hutchence and Mother Teresa, Farley argues that the sexually transgressive personae of Versace and Hutchence in life are replaced with "a pro-social narrative" that returns them to the bosom of family in death, while Mother Teresa, whose body "caused no trouble when it was alive, and conveniently wasn't mangled to death", is allowed to be present and photographed in death. Tseen Khoo's article, "Fetishising Flesh: Asian-Australian and Asian-Canadian Representation, Porno-Culinary Genres, and the Racially Marked Body" takes full advantage of the Internet to introduce the topic of flesh. Via a tour of various Websites, Khoo introduces the Web-surfer to the issues involved in representing the Asian body in diaspora, and the politically fraught issues for racial minority populations in majority 'white' nations. Khoo considers examples from Japanese-Canadian literature, metaphors of ingestion, and racial minority identity politics in the United States. The final submission to this issue is a work of creative writing by Hamish Kaden. "The Interminable Son" is the story of a man reconciling the death of his well-known feminist mother. The un-named character resurrects the memory of his mother through a Buddhist ceremony for the dead, and by conducting library research into her life as a prominent campaigner for women's right to have safe abortions. Kaden imparts the emotions of his character, while providing insight into an important health issue that effects many lives. This issue of M/C conceives of flesh in many forms and relationships. The cover image, designed by Damian Frost, should not go without mention as it provides a fresh vision from which to embark onto the smorgasbord of 'flesh'. Enjoy! Kirsty Leishman 'Flesh' Issue Editor Citation reference for this article MLA style: Kirsty Leishman. "Editorial: 'Flesh'." M/C: A Journal of Media and Culture 2.3 (1999). [your date of access] <http://www.uq.edu.au/mc/9905/edit.php>. Chicago style: Kirsty Leishman, "Editorial: 'Flesh'," M/C: A Journal of Media and Culture 2, no. 3 (1999), <http://www.uq.edu.au/mc/9905/edit.php> ([your date of access]). APA style: Kirsty Leishman. (1999) Editorial: 'flesh'. M/C: A Journal of Media and Culture 2(3). <http://www.uq.edu.au/mc/9905/edit.php> ([your date of access]).

Dégueulasse is French slang for “disgusting,” derived in 1867 from the French verb dégueuler, to vomit. Despite its vulgar status, it is frequently used by almost every French speaker, including foreigners and students. It is also a term that has often been employed to describe the 1973 cult film, La Grande bouffe [Blow Out], by Marco Ferreri, which recounts in grotesque detail the gastronomic suicide of four male protagonists. This R-rated French-Italian production was booed, and the director spat on, at the 26th Cannes Film Festival—the Jury President, Ingrid Bergman, said it was the most “sordid” film she’d ever seen, and is even reported to have vomited after watching it (Télérama). Ferreri nevertheless walked away with the Prix FIPRESCI, awarded by the Federation of International Critics, and it is apparently the largest grossing release in the history of Paris with more than 700,000 entries in Paris and almost 3 million in France overall. Scandal sells, and this was especially seemingly so 1970s, when this film was avidly consumed as part of an unholy trinity alongside Bernardo Bertolucci’s Le Dernier Tango à Paris [Last Tango in Paris] (1972) and Jean Eustache’s La Maman et la putain [The Mother and the Whore] (1973). Fast forward forty years, though, and at the very moment when La Grande bouffe was being commemorated with a special screening on the 2013 Cannes Film Festival programme, a handful of University of Melbourne French students in a subject called “Matters of Taste” were boycotting the film as an unacceptable assault to their sensibilities. Over the decade that I have been showing the film to undergraduate students, this has never happened before. In this article, I want to examine critically the questions of taste that underpin this particular predicament. Analysing firstly the intradiegetic portrayal of taste in the film, through both gustatory and aesthetic signifiers, then the choice of the film as a key element in a University subject corpus, I will finally question the (dis)taste displayed by certain students, contextualising it as part of an ongoing socio-cultural commentary on food, sex, life, and death. Framed by a brief foray into Bourdieusian theories of taste, I will attempt to draw some conclusions on the continual renegotiation of gustatory and aesthetic tastes in relation to La Grande bouffe, and thereby deepen understanding of why it has become the incarnation of dégueulasse today. Theories of Taste In the 1970s, the parameters of “good” and “bad” taste imploded in the West, following political challenges to the power of the bourgeoisie that also undermined their status as the contemporary arbiters of taste. This revolution of manners was particularly shattering in France, fuelled by the initial success of the May 68 student, worker, and women’s rights movements (Ross). The democratization of taste served to legitimize desires different from those previously dictated by bourgeois norms, enabling greater diversity in representing taste across a broad spectrum. It was reflected in the cultural products of the 1970s, including cinema, which had already broken with tradition during the New Wave in the late 1950s and early 1960s, and became a vector for political ideologies as well as radical aesthetic choices (Smith). Commonly regarded as “the decade that taste forgot,” the 1970s were also a time for re-assessing the sociology of taste, with the magisterial publication of Pierre Bourdieu’s Distinction: A Social Critique of the Judgement of Taste (1979, English trans. 1984). As Bourdieu refuted Kant’s differentiation between the legitimate aesthetic, so defined by its “disinterestedness,” and the common aesthetic, derived from sensory pleasures and ordinary meanings, he also attempted to abolish the opposition between the “taste of reflection” (pure pleasure) and the “taste of sense” (facile pleasure) (Bourdieu 7). In so doing, he laid the foundations of a new paradigm for understanding the apparently incommensurable choices that are not the innate expression of our unique personalities, but rather the product of our class, education, family experiences—our habitus. Where Bourdieu’s theories align most closely with the relationship between taste and revulsion is in the realm of aesthetic disposition and its desire to differentiate: “good” taste is almost always predicated on the distaste of the tastes of others. Tastes (i.e. manifested preferences) are the practical affirmation of an inevitable difference. It is no accident that, when they have to be justified, they are asserted purely negatively, by the refusal of other tastes. In matters of taste, more than anywhere else, all determination is negation; and tastes are perhaps first and foremost distastes, disgust provoked by horror or visceral intolerance (“sick-making”) of the tastes of others. “De gustibus non est disputandum”: not because “tous les goûts sont dans la nature,” but because each taste feels itself to be natural—and so it almost is, being a habitus—which amounts to rejecting others as unnatural and therefore vicious. Aesthetic intolerance can be terribly violent. Aversion to different life-styles is perhaps one of the strongest barriers between the classes (Bourdieu). Although today’s “Gen Y” Melbourne University students are a long way from 1970s French working class/bourgeois culture clashes, these observations on taste as the corollary of distaste are still salient tools of interpretation of their attitudes towards La Grande bouffe. And, just as Bourdieu effectively deconstructed Kant’s Critique of Aesthetic Judgement and the 18th “century of taste” notions of universality and morality in aesthetics (Dickie, Gadamer, Allison) in his groundbreaking study of distinction, his own theories have in turn been subject to revision in an age of omnivorous consumption and eclectic globalisation, with various cultural practices further destabilising the hierarchies that formerly monopolized legitimate taste (Sciences Humaines, etc). Bourdieu’s theories are still, however, useful for analysing La Grande bouffe given the contemporaneous production of these texts, as they provide a frame for understanding (dis)taste both within the filmic narrative and in the wider context of its reception. Taste and Distaste in La Grande bouffe To go to the cinema is like to eat or shit, it’s a physiological act, it’s urban guerrilla […] Enough with feelings, I want to make a physiological film (Celluloid Liberation Front). Marco Ferreri’s statements about his motivations for La Grande bouffe coincide here with Bourdieu’s explanation of taste: clearly the director wished to depart from psychological cinema favoured by contemporary critics and audiences and demonstrated his distaste for their preference. There were, however, psychological impulses underpinning his subject matter, as according to film academic Maurizio Viano, Ferrari had a self-destructive, compulsive relation to food, having been forced to spend a few weeks in a Swiss clinic specialising in eating disorders in 1972–1973 (Viano). Food issues abound in his biography. In an interview with Tullio Masoni, the director declared: “I was fat as a child”; his composer Phillipe Sarde recalls the grand Italian-style dinners that he would organise in Paris during the film; and, two of the film’s stars, Marcello Mastroianni and Ugo Tognazzi, actually credit the conception of La Grande bouffe to a Rabelaisian feast prepared by Tognazzi, during which Ferreri exclaimed “hey guys, we are killing ourselves!” (Viano 197–8). Evidently, there were psychological factors behind this film, but it was nevertheless the physiological aspects that Ferreri chose to foreground in his creation. The resulting film does indeed privilege the physiological, as the protagonists fornicate, fart, vomit, defecate, and—of course—eat, to wild excess. The opening scenes do not betray such sordid sequences; the four bourgeois men are introduced one by one so as to establish their class credentials as well as display their different tastes. We first encounter Ugo (Tognazzi), an Italian chef of humble peasant origins, as he leaves his elegant restaurant “Le Biscuit à soupe” and his bourgeois French wife, to take his knives and recipes away with him for the weekend. Then Michel (Piccoli), a TV host who has pre-taped his shows, gives his apartment keys to his 1970s-styled baba-cool daughter as he bids her farewell, and packs up his cleaning products and rubber gloves to take with him. Marcello (Mastroianni) emerges from a cockpit in his aviator sunglasses and smart pilot’s uniform, ordering his sexy airhostesses to carry his cheese and wine for him as he takes a last longing look around his plane. Finally, the judge and owner of the property where the action will unfold, Philippe (Noiret), is awoken by an elderly woman, Nicole, who feeds him tea and brioche, pestering him for details of his whereabouts for the weekend, until he demonstrates his free will and authority, joking about his serious life, and lying to her about attending a legal conference in London. Having given over power of attorney to Nicole, he hints at the finality of his departure, but is trying to wrest back his independence as his nanny exhorts him not to go off with whores. She would rather continue to “sacrifice herself for him” and “keep it in the family,” as she discreetly pleasures him in this scene. Scholars have identified each protagonist as an ideological signifier. For some, they represent power—Philippe is justice—and three products of that ideology: Michel is spectacle, Ugo is food, and Marcello is adventure (Celluloid Liberation Front). For others, these characters are the perfect incarnations of the first four Freudian stages of sexual development: Philippe is Oedipal, Michel is indifferent, Ugo is oral, and Marcello is impotent (Tury & Peter); or even the four temperaments of Hippocratic humouralism: Philippe the phlegmatic, Michel the melancholic, Ugo the sanguine, and Marcello the choleric (Calvesi, Viano). I would like to offer another dimension to these categories, positing that it is each protagonist’s taste that prescribes his participation in this gastronomic suicide as well as the means by which he eventually dies. Before I develop this hypothesis, I will first describe the main thrust of the narrative. The four men arrive at the villa at 68 rue Boileau where they intend to end their days (although this is not yet revealed). All is prepared for the most sophisticated and decadent feasting imaginable, with a delivery of the best meats and poultry unfurling like a surrealist painting. Surrounded by elegant artworks and demonstrating their cultural capital by reciting Shakespeare, Brillat-Savarin, and other classics, the men embark on a race to their death, beginning with a competition to eat the most oysters while watching a vintage pornographic slideshow. There is a strong thread of masculine athletic engagement in this film, as has been studied in detail by James R. Keller in “Four Little Caligulas: La Grande bouffe, Consumption and Male Masochism,” and this is exacerbated by the arrival of a young but matronly schoolmistress Andréa (Ferréol) with her students who want to see the garden. She accepts the men’s invitation to stay on in the house to become another object of competitive desire, and fully embraces all the sexual and gustatory indulgence around her. Marcello goes further by inviting three prostitutes to join them and Ugo prepares a banquet fit for a funeral. The excessive eating makes Michel flatulent and Marcello impotent; when Marcello kicks the toilet in frustration, it explodes in the famous fecal fountain scene that apparently so disgusted his then partner Catherine Deneuve, that she did not speak to him for a week (Ebert). The prostitutes flee the revolting madness, but Andréa stays like an Angel of Death, helping the men meet their end and, in surviving, perhaps symbolically marking an end to the masculinist bourgeoisie they represent.To return to the role of taste in defining the rise and demise of the protagonists, let me begin with Marcello, as he is the first to die. Despite his bourgeois attitudes, he is a modern man, associated with machines and mobility, such as the planes and the beautiful Bugatti, which he strokes with greater sensuality than the women he hoists onto it. His taste is for the functioning mechanical body, fast and competitive, much like himself when he is gorging on oysters. But his own body betrays him when his “masculine mechanics” stop functioning, and it is the fact that the Bugatti has broken down that actually causes his death—he is found frozen in driver’s seat after trying to escape in the Bugatti during the night. Marcello’s taste for the mechanical leads therefore to his eventual demise. Michel is the next victim of his own taste, which privileges aesthetic beauty, elegance, the arts, and fashion, and euphemises the less attractive or impolite, the scatological, boorish side of life. His feminized attire—pink polo-neck and flowing caftan—cannot distract from what is happening in his body. The bourgeois manners that bind him to beauty mean that breaking wind traumatises him. His elegant gestures at the dance barre encourage rather than disguise his flatulence; his loud piano playing cannot cover the sound of his loud farts, much to the mirth of Philippe and Andréa. In a final effort to conceal his painful bowel obstruction, he slips outside to die in obscene and noisy agony, balanced in an improbably balletic pose on the balcony balustrade. His desire for elegance and euphemism heralds his death. Neither Marcello nor Michel go willingly to their ends. Their tastes are thwarted, and their deaths are disgusting to them. Their cadavers are placed in the freezer room as silent witnesses to the orgy that accelerates towards its fatal goal. Ugo’s taste is more earthy and inherently linked to the aims of the adventure. He is the one who states explicitly: “If you don’t eat, you won’t die.” He wants to cook for others and be appreciated for his talents, as well as eat and have sex, preferably at the same time. It is a combination of these desires that kills him as he force-feeds himself the monumental creation of pâté in the shape of the Cathedral of Saint-Peter that has been rejected as too dry by Philippe, and too rich by Andréa. The pride that makes him attempt to finish eating his masterpiece while Andréa masturbates him on the dining table leads to a heart-stopping finale for Ugo. As for Philippe, his taste is transgressive. In spite of his upstanding career as a judge, he lies and flouts convention in his unorthodox relationship with nanny Nicole. Andréa represents another maternal figure to whom he is attracted and, while he wishes to marry her, thereby conforming to bourgeois norms, he also has sex with her, and her promiscuous nature is clearly signalled. Given his status as a judge, he reasons that he can not bring Marcello’s frozen body inside because concealing a cadaver is a crime, yet he promotes collective suicide on his premises. Philippe’s final transgression of the rules combines diabetic disobedience with Oedipal complex—Andréa serves him a sugary pink jelly dessert in the form of a woman’s breasts, complete with cherries, which he consumes knowingly and mournfully, causing his death. Unlike Marcello and Michel, Ugo and Philippe choose their demise by indulging their tastes for ingestion and transgression. Following Ferreri’s motivations and this analysis of the four male protagonists, taste is clearly a cornerstone of La Grande bouffe’s conception and narrative structure. It is equally evident that these tastes are contrary to bourgeois norms, provoking distaste and even revulsion in spectators. The film’s reception at the time of its release and ever since have confirmed this tendency in both critical reviews and popular feedback as André Habib’s article on Salo and La Grande bouffe (2001) meticulously demonstrates. With such a violent reaction, one might wonder why La Grande bouffe is found on so many cinema studies curricula and is considered to be a must-see film (The Guardian). Corpus and Corporeality in Food Film Studies I chose La Grande bouffe as the first film in the “Matters of Taste” subject, alongside Luis Bunuel’s Le Charme discret de la bourgeoisie, Gabriel Axel’s Babette’s Feast, and Laurent Bénégui’s Au Petit Marguery, as all are considered classic films depicting French eating cultures. Certainly any French cinema student would know La Grande bouffe and most cinephiles around the world have seen it. It is essential background knowledge for students studying French eating cultures and features as a key reference in much scholarly research and popular culture on the subject. After explaining the canonical status of La Grande bouffe and thus validating its inclusion in the course, I warned students about the explicit nature of the film. We studied it for one week out of the 12 weeks of semester, focusing on questions of taste in the film and the socio-cultural representations of food. Although the almost ubiquitous response was: “C’est dégueulasse!,” there was no serious resistance until the final exam when a few students declared that they would boycott any questions on La Grande bouffe. I had not actually included any such questions in the exam. The student evaluations at the end of semester indicated that several students questioned the inclusion of this “disgusting pornography” in the corpus. There is undoubtedly less nudity, violence, gore, or sex in this film than in the Game of Thrones TV series. What, then, repulses these Gen Y students? Is it as Pasolini suggests, the neorealistic dialogue and décor that disturbs, given the ontologically challenging subject of suicide? (Viano). Or is it the fact that there is no reason given for the desire to end their lives, which privileges the physiological over the psychological? Is the scatological more confronting than the pornographic? Interestingly, “food porn” is now a widely accepted term to describe a glamourized and sometimes sexualized presentation of food, with Nigella Lawson as its star, and hundreds of blog sites reinforcing its popularity. Yet as Andrew Chan points out in his article “La Grande bouffe: Cooking Shows as Pornography,” this film is where it all began: “the genealogy reaches further back, as brilliantly visualized in Marco Ferreri’s 1973 film La Grande bouffe, in which four men eat, screw and fart themselves to death” (47). Is it the overt corporeality depicted in the film that shocks cerebral students into revulsion and rebellion? Conclusion In the guise of a conclusion, I suggest that my Gen Y students’ taste may reveal a Bourdieusian distaste for the taste of others, in a third degree reaction to the 1970s distaste for bourgeois taste. First degree: Ferreri and his entourage reject the psychological for the physiological in order to condemn bourgeois values, provoking scandal in the 1970s, but providing compelling cinema on a socio-political scale. Second degree: in spite of the outcry, high audience numbers demonstrate their taste for scandal, and La Grande bouffe becomes a must-see canonical film, encouraging my choice to include it in the “Matters of Taste” corpus. Third degree: my Gen Y students’ taste expresses a distaste for the academic norms that I have embraced in showing them the film, a distaste that may be more aesthetic than political. Oui, c’est dégueulasse, mais … Bibliography Allison, Henry E. Kant’s Theory of Taste: A Reading of the Critique of Aesthetic Judgement. 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