Artykuły w czasopismach na temat „Count of Dunois”

John Dunn’s provocative interview in Contention volume 5, issue 2 inspired an array of responses from the scholarly and practitioner communities. In the original interview, Dunn suggested that the era of modern revolutions has come to a close and that we are now witnessing a phenomenon better described as “regime collapse.” In this response to Dunn’s conception of revolution, Hugo Slim, an expert on non-international armed conflicts, challenges Dunn’s claims with examples of revolutionary liberation movements in Nepal, Uganda, Ethiopia, Rwanda, and Venezuela, as well as Islamist revolutionary movements in the Middle East.

Drawing on Aristotle's concepts of energeia, dunamis, and ergon, this article attempts to articulate a typology of the different works described in Édouard Levé’s Œuvres (2002 (French); 2014 (English)). This is carried out in the context of post-literary literature, i.e. following an aesthetics driven by the dismantling of ‘qualities’, understood as ‘accidents’, of literature's essence (literature's definition). It studies how Levé’s work, and particularly his opus magnum Œuvres (Works), displays a series of short descriptive texts that intend to remain in their potentiality, while, at the same time, actualising this very potentiality (a potentiality ‘in act’, by an operation triggered in the reader's imagination). The question is therefore less the nature of fiction or ‘what makes literature literature’ than ‘how does literature actualise its negation’.

In Contention volume 5, issue 2, Benjamin Abrams interviewed the political theorist John Dunn on the topic of modern revolutions. In the interview, Dunn advanced the view that the “Epoch of Revolution” had ended by 1989 and that what many scholars called revolutions today were simply instances of regime collapse. The interview received a lot of attention from scholars and practitioners including Hugo Slim. Slim challenged Dunn’s concept of revolution in this issue, and Dunn responded defending his ideas. This article attempts to tease out the differences underlying the two scholars’ disagreement as to whether the Epoch of Revolution has truly passed. The article proposes that while processual approaches (such as Slim’s) conceive of revolution primarily as a political means, Dunn’s “programmatic” approach to revolution conceives of it as not only a means but also a political end. The article also considers the implications of Dunn’s theory of revolution, and the representative challenges of academic interviewing.

The Dunkin Hartley is the most common guinea pig strain used in biomedical research, particularly for studies of asthma, allergy, infectious disease, reproduction, and osteoarthritis. Minimally invasive blood tests, such as complete blood counts and serum biochemistry profiles, are often collected for diagnostics and laboratory analyses. However, reference intervals for these assays have not yet been well-documented in this strain. The purpose of this study was to establish reference intervals for hematologic and biochemical parameters of Dunkin Hartley guinea pigs and determine age- and sex-related differences. Hematologic and biochemical parameters were retrospectively obtained from 145 male and 68 female guinea pigs between 2 and 15 months of age. All blood parameters were analyzed by a veterinary clinical pathology laboratory. Reference intervals were established according to the American Society for Veterinary Clinical Pathology guidelines. Age- and sex-related differences were determined using unpaired t-tests or nonparametric Mann-Whitney tests. Hematocrit, red blood cell distribution width, mean platelet volume, white blood cell count, heterophils, monocytes, eosinophils, glucose, blood urea nitrogen, creatinine, calcium, magnesium, total protein, albumin, globulin, cholesterol, aspartate aminotransferase, gamma glutamyl transferase, and bicarbonate increased with age. Mean corpuscular hemoglobin concentration, cellular hemoglobin concentration mean, platelets, lymphocytes, phosphorus, albumin/globulin ratio, alkaline phosphatase, anion gap, and calculated osmolality decreased with age. Males had higher hemoglobin, hematocrit, red blood cell count, mean corpuscular hemoglobin concentration, white blood cell count, heterophils, Foa-Kurloff cells, alanine aminotransferase, and bicarbonate and lower mean corpuscular volume, red blood cell distribution width, platelets, mean platelet volume, eosinophils, total protein, albumin, globulin, cholesterol, potassium, anion gap, calculated osmolality, and iron compared to females. Establishing age and sex differences in hematologic and biochemical parameters of Dunkin Hartley guinea pigs provides valuable insight into their physiology to better evaluate diagnostics and experimental results.

Kleptoparasitism, or food piracy, is common in a wide range of taxa, particularly among predators, with the larger species forcing smaller species to surrender their catch. The Bald Eagle (Haliaeetus leucocephalus) is known to rob Peregrine Falcons (Falco peregrinus) of just-caught prey. We present time series of kleptoparasitic interactions between eagles and peregrines hunting Dunlin (Calidris alpina) that were wintering at Boundary Bay in the Fraser River valley, British Columbia. In 1108 hours of observation during January, intermittently between 1994 and 2014, we recorded 667 sightings of Peregrine Falcons, including 817 attacks on Dunlin resulting in 120 captures. The population of wintering Bald Eagles in the study area increased from about 200 in 1994 to 1800 in 2014, while the rate of kleptoparasitism at the expense of peregrines increased from 0.05 to 0.20. The increase in the number of Bald Eagles coincided with a decline in January sightings of Peregrine Falcons, which suggests that some falcons may have left the study area because of interference from eagles. The decrease in Peregrine Falcon numbers can be expected to have led to reduced predation risk for Dunlins. Christmas Bird Counts conducted in the Fraser River Valley have underscored the fluctuation in eagle and peregrine numbers reported here.

Abstract Introduction: The differential diagnosis of hereditary and acquired thrombocytopenias can be challenging, especially when between immune thrombocytopenia (ITP) and less well characterized hereditary thrombocytopenias (HT) such as MYH9-related disorders. Fundamental differences in the management of these two conditions add clinical relevance to the search for novel parameters that differentiate these conditions. The immature platelet count (IPF) represents the fraction of platelets with higher RNA content, and in analogy to the reticulocyte count for erythropoiesis is a biomarker of thrombopoietic activity. In a recent report (Miyazaki et al, 2015), IPF values that were more than 5-fold higher than those observed in ITP patients were reported in a population of 15 patients with HT. However, whether this increased values represented a real increase in thrombopoietic activity, or reflected a technical limitation of IPF determination in large platelets could not be clarified. Here, we aimed to evaluate the role of IPF determination in the differential diagnosis between HT and several forms of acquired thrombocytopenia in a larger and more diverse population of patients. We also evaluated thrombopoietin (TPO) levels in HT compared to ITP, to further investigate the mechanisms by which extremely large IPF values are observed in HT. Methods: IPF and mean platelet volume (MPV) were prospectively determined using a Sysmex XE5000 hematologic analyzer (as part of the complete blood count) in a cohort of patients with post-chemotherapy thrombocytopenia (n=56), bone marrow failure (myelodysplastic syndromes and aplastic anemia; n=22), ITP (ITP; n=105) and inherited thrombocytopenias (n=27). The latter population consists of a well-defined cohort of individuals with HT thrombocytopenia characterized by clinical, familial, laboratory and molecular data. TPO levels were determined by ELISA (R&D Systems) in 21 HT patients and 22 ITP patients matched for platelet count and age. A group of 178 healthy volunteers were used to determine normal IPF and MPV values. Results: Median platelet counts were similar in post-chemotherapy patients (CTx) (32.0*109/L), bone marrow failure (BMF) (33.5*109/L), ITP (52.0*109/L) and HT (52.0*109/L) (P=0.15). Similar IPF levels were observed in CTx and BMF patients (5.6%; IQR 3.4-8.8% and 6.5%; IQR 3.5-13.7%. Compared to these two groups, higher IPF values were observed in both ITP (12.3%; 7.0-21.0%) and HT patients (29.8%; 17.5-56.4%) (both P values < 0.05). In addition, IPF were significantly higher in HT compared to ITP (Kruskall-Wallis test and Dunn's post test,P=0.001). MPV values were different between HT and CTx/BMF groups, but could not differentiate ITP from HT. TPO levels. The accuracy of IPF to discriminate HT from all other causes of thrombocytopenia estimated by ROC analysis was 0.88 (CI95%0.8-0.96, p<0.0001). Similar TPO levels were observed in platelet count-matched ITP, HT patients and healthy volunteers without thrombocytopenia. Interestingly, TPO presented marked correlations with both platelet count (Rs = - 0.61, P=0.002) and IPF (Rs= 0.59, P=0.003), even with TPO levels in the same range of healthy individuals. In contrast, no significant correlation could be observed between TPO and IPF or platelet count in HT patients. Conclusions: IPF represents an informative biomarker for the differential diagnosis of hereditary and acquired thrombocytopenias, and accurately differentiates ITP from the most common HT. As expected, TPO levels in patients with ITP were not higher than in individuals with normal platelets counts. The inverse correlation between TPO and platelet count in these patients confirm a blunted TPO response to thrombocytopenia in these patients. Similarly, patients with HT did not present increased TPO levels compared to healthy individuals. Accordingly, increased IPF levels in these patients cannot be attributed to higher TPO levels. Disclosures No relevant conflicts of interest to declare.

Jeffrey L. Dunoff and Mark A. Pollack's article is an important and very welcome contribution to the discussion about judicial values. The authors argue that with respect to judicial independence, transparency, and accountability “judicial systems face inherent trade-offs, such that any given court can maximize two, but not all three, of these features.” In our eyes, the article's most important contribution is its holistic view: it shows why these three judicial values can only be understood in their interconnectedness. It is, for instance, not meaningful to make a statement about the correlation between transparency and independence without also taking accountability into the equation. This is because the effect of transparency on independence can only be understood if information about judicial accountability is at one's disposal. In the past, these judicial values have often been analyzed in an isolated manner, thereby leading to wrong conclusions. The Judicial Trilemma will hopefully help in shifting the discourse from isolated to holistic views on independence, transparency, and accountability. Moreover, Dunoff and Pollack lay the groundwork for a meaningful normative discussion of these three judicial values. Any debate about how to structure (international) courts should henceforth take Dunoff and Pollack's holistic view as a basis for discussion.

Tuberculosis is an infectious disease of global concern caused of bacterium Mycobacterium tuberculosis. It can attack lung, liver, kidneys, bones or skin. If a person infected by tuberculosis, the body will begin the mechanism of inflammation as a form of haematological manifestation. The purpose of this study was to describe the number of leukocytes and Blood Sedimentation Rate (BSR) in tuberculosis patients. The research design used is non-analytic descriptive. The population in this study were all tuberculosis patients at the Dungus Madiun Lung Hospital in 2018Using the Quota Sampling technique, the sample in this study was 30 respondents. This research was conducted on May 2018. The results of the study on tuberculosis patients showed that the number of leukocytes in TB patients was 9120 cells/�L blood, 11 (37%) patients had leukocytosis and 19 (63%) sufferers have a nominal leukocyte count. The lowest leukocyte count was 4100 cells/�L of blood and the highest was 24700 cells/�L of blood. The average value of BSR in TB patients was 71 mm/hour I, 29 (96.6%) patients experienced an increase in BSR values and 1 (3.4%) patients had normal BSR values. The lowest value of BSR is 11 mm/hour I and the highest value of BSR is 106 mm/hour I. Prevention of tuberculosis infection can be done by conducting laboratory diagnosis to find out how far the disease goes and choose the right OAT for patients. With intensive treatment, it will reduce the number of leukocytes and reduce the risk for MDR TB

Abstract We conducted the first systematic inventory of birds in the lowlands (areas ≤100 m above sea level) of the Alaska Peninsula during summers of 2004–2007 to determine their breeding distributions and habitat associations in this remote region. Using a stratified random survey design, we allocated sample plots by elevation and land cover with a preference for wetland cover types used by shorebirds, a group of particular interest to land managers. We surveyed birds during 10-min counts at 792 points across 52, 5 km × 5 km sample plots distributed from south of the Naknek River (58.70°N,157.00°W) to north of Port Moller (56.00°N,160.52°W). We detected 95 bird species including 19 species of shorebirds and 34 species (36% of total) considered at the time to be of conservation concern for the land managers in the region. The most numerous shorebirds on point counts were dunlin Calidris alpina, short-billed dowitcher Limnodromus griseus, and Wilson's snipe Gallinago delicata. We found the breeding-season endemic marbled godwit Limosa fedoa beringiae at 20 plots within a 3,000-km2 area from north of Ugashik Bay to just north of Port Heiden and east to the headwaters of the Dog Salmon and Ugashik rivers. The most abundant passerines on point counts were American tree sparrow Spizelloides arborea, Lapland longspur Calcarius lapponicus, and savannah sparrow Passerculus sandwichensis. Sandhill crane Antigone canadensis, glaucous-winged gull Larus glaucescens, and greater scaup Aythya marila were also relatively abundant. We categorized habitat associations for 30 common species and found that lowland herbaceous vegetation supported wetland-focused species including sandhill crane, marbled godwit, short-billed dowitcher, and dunlin; whereas, dwarf shrub-ericaceous vegetation supported tundra-associated species such as willow ptarmigan Lagopus lagopus, rock sandpiper Calidris ptilocnemis, and American pipit Anthus rubescens. Tall shrub vegetation was important to several species of warblers and sparrows, as well as one species of shorebird (greater yellowlegs Tringa melanoleuca). We found that point counts augmented with incidental observations provided an almost complete inventory of lowland-breeding species on the study area. These data form a baseline to monitor any future changes in bird distribution and abundance on the Alaska Peninsula.

The Judicial Trilemma, by Jeff Dunoff and Mark Pollack, studies the dynamic relations between accountability, transparency, and independence, and suggests that designers can only maximize two of these three values at once. They can create a court that has high levels of (1) independence and accountability, (2) transparency and independence, or (3) accountability and transparency, but only at the cost of having a low level of the third value. The article explores these ideas using four different international tribunals, but its insights are not limited to international courts. Domestic designers also have to decide what levels of accountability, independence, and transparency their courts should have, and in making a decision they will face the Judicial Trilemma and confront the hard choice of selecting primarily two out of three values.

In Peninsula Securities, the Supreme Court held that a restrictive covenant, granted in a lease to an anchor tenant of a shopping centre not to allow any retail unit in the centre to be leased to competing shops, does not engage the doctrine of restraint of trade. The question of its enforceability therefore hinges on whether the relevant covenant breaches competition law, and specifically whether it is anti-competitive by object or effect. This relatively straightforward conclusion of the Supreme Court in Peninsula Securities masks over 50 years of conflicting judgments and uncertainty in the area. Prior to Peninsula Securities, the majority decision of the House of Lords in Esso Petroleum v Harper's Garage gave rise to a ‘battle of the tests’: the majority opined that the doctrine of restraint of trade would only be engaged if the covenantor contracts to give up a freedom they already had (what has come to be known as the ‘pre-existing freedom test’; Lord Wilberforce, dissenting, formulated what came to be known as the ‘trading society test’ which is basically a rule of reason test. In Peninsula Securities, the Supreme Court clearly sided with the latter, but in reality neither test is likely to be considered in future challenges to an anchor tenancy restrictive covenant – the key question is whether it is anti-competitive, something which only the relevant facts of the case will determine.

AbstractBetween April 2012 and October 2017, 18 southern black racers,Coluber constrictor priapus, were collected from nine counties of Arkansas (n= 13) and McCurtain County, Oklahoma (n= 5) and their faeces examined for coccidian parasites. One of 18 (6%)C. c. priapusharboured an eimerian that we describe here as new. Oocysts ofEimeria dunnisp. nov. were subspheroidal with a lightly pitted bi-layered wall measuring L × W 24.0 × 21.1 and L/W ratio of 1.2. A micropyle was absent but an oocyst residuum and polar granule were present. Sporocysts were ovoidal and measured 11.9 × 8.1 with L/W of 1.5. A Stieda body was present but substieda and parastieda bodies were absent. The sporocyst residuum was composed of medium-sized granules aligned along perimeter of sporocyst or in a dispersed mass. This represents the first valid eimerian reported from the southern black racer.

The population of the far North Coast of New South Wales is growing rapidly. It is estimated that the number of people served by the Rous County water supply will increase threefold in the next fifty years. Steps are being taken to manage demand and to provide an additional source of water by pumping from the Wilson River at Lismore. It is recognised that a new dam will eventually be required. The dam currently providing the bulk of the Rous County supply is on Rocky Creek near Dorroughby. A second dam is planned for Rocky Creek about 10 km downstream from the existing dam. This will be built near Dunoon about 20 km to the north of Lismore. A preliminary study of the distribution of platypuses in the affected area has been carried out using a program of passive observation. Of the nine pools observed in the program platypuses have been seen in seven. No attempt has been made to estimate the actual size of the platypus population. There appears to be sufficient evidence that the building of the proposed dam could have an impact on the platypus. Recommendations have been addressed to the planners of the dam urging that special provision be made to minimise its impact on the platypus population.

The Pichavaram Mangrove Forest (PMF) is one of the important wetlands in southern India. The PMF is harboring numerous species of shorebirds seasonally. The current study assessed the population characteristics of small wading birds by using direct count method from 2015 to 2016. In total, 27 species of small wading birds were recorded, in which the Little stint showed highest density 177.24±20.515 (No./ha.) and the Bar-tailed godwit showed lowest density 0.13±0.099 (No./ha.). Indeed the Little stint was only species turned highest density across the three different seasons studied. However, the bar-tailed godwit not recorded during the pre-monsoon and post-monsoon seasons, the Dunlin, Grey plover and Great sand plover not sighted during the post-monsoon season. The density, diversity and species richness of small wading birds showed significant differences among the seasons (P<0.001). The study inferred that the population characteristics of small wading birds are declining when compared to the previous studies. However exhaustive studies are essential to explore the quality of the PMF which is need of the hour since it is supporting various species of shorebirds seasonally.

Autumn Passage of Waders (Charadrii) in the Middle Vistula Valley (Kaliszany, Central Poland) The phenology and dynamics of wader migration were studied at a stopover area in the middle Vistula Valley (Kaliszany ringing station, 51°05'N, 21°48'E, central Poland). The study was conducted during autumn passage seasons of 1993-1996 and 1999-2001. At this time 364 counts were done from mid-July to the end of October. Altogether 23 030 waders of 27 species were recorded within the study period. The most numerous species observed were: the Northern Lapwing (Vanellus vanellus) — 49% of all birds, Common Sandpiper (Actitis hypoleucos) — 16% and Greenshank (Tringa nebularia) — 9%. Species constituting ca 2-4% of all noted waders each were: the Dunlin (Calidris alpina), Spotted Redshank (T. erythropus), Wood Sandpiper (T. glareola), Curlew (Numenius arquata), Ruff (Philomachus pugnax) and Green Sandpiper (T. ochropus). The proportion of the remaining species did not exceed 2%. The pattern of autumn migration dynamics is presented for the dominant species.

This study investigated the effects of Brazilian Red Propolis (BRP) extract on seven-day-old multispecies subgingival biofilms. Mixed biofilm cultures containing 31 species associated with periodontal health or disease were grown for six days on a Calgary device. Then, mature biofilms were treated for 24 h with BRP extract at different concentrations (200–1600 µg/mL), amoxicillin (AMOXI) at 54 µg/mL (positive control) or vehicle (negative control). Biofilm metabolic activity was determined by colorimetry, and bacterial counts/proportions were determined by DNA–DNA hybridization. Data were analyzed by Kruskal–Wallis and Dunn’s tests. Treatment with BRP at 1600, 800 and 400 μg/mL reduced biofilm metabolic activity by 56%, 56% and 57%, respectively, as compared to 65% reduction obtained with AMOXI. Mean total cell counts were significantly reduced in all test groups (~50–55%). Lower proportions of red, green and yellow complex species were observed upon treatment with BRP (400 µg/mL) and AMOXI, but only AMOXI reduced the proportions of Actinomyces species. In conclusion, BRP extract was as effective as AMOXI in killing seven-day-old multispecies biofilm pathogens and did not affect the levels of the host-compatible Actinomyces species. These data suggest that BRP may be an alternative to AMOXI as an adjunct in periodontal therapy. In vivo studies are needed to validate these results.

Autumn Migration of Waders (Charadrii) at the Reda Mouth (N Poland) The migration of waders was investigated at the Reda mouth (Polish Baltic coast) between 1996 and 2001. During the study 496 counts were conducted in the period between 5 July and 5 October. The most numerous species observed were: the Lapwing (Vanellus vanellus) - 39.5% and Dunlin (Calidris alpina) - 29.8% of all waders. Because of a variety of habitats in the Reda mouth region, among the waders staging numerously in the Reda mouth there were species typical both for coastal and inland habitat. It was shown that birds from tundra zone migrated later than those from more southern breeding areas, which was caused by much later beginning of egg laying in northern latitudes. Moreover, in the species from tundra zone, e.g. the Knot (Calidris canutus), Little Stint (C. minuta), Curlew Sandpiper (C. ferruginea), the migration of both age classes were well separated, whereas in those from more southern areas, e.g. the Little Ringed Plover (Charadius dubius), Common Sandpiper (Actitis hypoleucos), such difference was less pronounced and the period of common passage of adults and juveniles was much longer. A comparison of the obtained data on migration pattern with some other sites in Poland where regular counts were conducted showed several similarities and some discrepancies, which are discussed in the paper.

The common law doctrine of restraint of trade has a well-established presence in relation to contracts of employment and contracts for the sale of a business. Beyond those specific areas it reared its head from time to time, but the legal test for its applicability was not a model of clarity. Where the covenantor ceded a pre-existing freedom to engage in commercial activity, the decision of the House of Lords in Esso Petroleum Co Ltd v Harper’s Garage (Stourport) Ltd [1968] AC 269 brought it within the doctrine, but the recent decision of the Supreme Court in Peninsula Securities Ltd v Dunnes Stores (Bangor) Ltd [2020] UKSC 36, on appeal from the Northern Ireland Court of Appeal [2018] NICA 7, has discarded that test in favour of one based on the structure of a trading society. Peninsula Securities was a case concerned with the applicability of the restraint of trade doctrine to covenants affecting the ability of a landowner and its successors in title to use the land in a way that potentially competed with the business of an adjoining occupier. The decision that the restraint of trade doctrine was not engaged in these circumstances was set against the power of the Lands Tribunal to modify or extinguish covenants affecting land under article 5 of the Property (NI) Order 1978.

Abstract Abstract 3599 Poster Board III-536 Introduction P-selectin is a pro-inflammatory molecule that increases neutrophil recruitment to the vein wall at the site of thrombosis. Aptamers are short single-stranded oligonucleotides with the ability to bind small molecules and diverse proteins such as P-selectin. P-selectin could be targeted by a specific inhibitor or novel aptamer to limit inflammation following deep vein thrombosis (DVT). In this study, the effect of a novel anti-P-selectin aptamer on reducing DVT associated inflammation was evaluated. Methods Male C57BL/6J mice (20-25g) were placed into groups: anti-P-selectin aptamer ARC5690 (APSA, 2mg/kg, 5mg/kg, and 10mg/kg intraperitoneal [IP]), anti-P-selectin control aptamer “scrambled sequence” (PSCA 1mg/kg and 10 mg/kg IP), anti-P-selectin antibody (APSB 0.2mg/kg IP), ligation only (LO), or true control (TC). Inferior vena cava (IVC) ligation, below the renal vein, was performed on all groups except TC. Groups PSCA and APSA received daily injections starting two days pre-IVC ligation and continued up to 3 days post-IVC ligation. Groups TC and LO did not receive test compounds. At 3 days post-IVC ligation, mice were euthanized. The IVC was harvested and weighed or submitted for vein wall morphometric inflammatory cell histological analysis. Blood was collected via cardiac puncture for plasma soluble P-selectin (sP-sel) protein analysis. Data was analyzed using a student t-test and Kruskal-Wallace test with a Dunn's multiple comparison test. Results The total leukocyte counts in APSA groups 5 mg/kg and 10 mg/kg were significantly reduced compared to the PSCA groups and APSA group 2 mg/kg (p<0.05). The inflammatory cell count in APSA groups 5mg/kg and 10mg/kg confirmed this same trend for neutrophils, monocytes, lymphocytes versus the PSCA and APSA 2 mg/kg groups. Increased neutrophil counts were observed in the PSCA group compared to the TC group Figure 1). The thrombus weight (TW) was significantly decreased in the APSA 5mg/kg group compared to the LO group and the PSCA 1mg/kg group (p<0.05). The TW in the APSB group was significantly decreased compared to the LO group, the PSCA group (1mg/kg and 10mg/kg). There was a positive correlation between TW and sP-sel (Spearman correlation r=0.55). Conclusions ARC5690 showed a significant anti-inflammatory effect at the 5 mg/kg and 10 mg/kg doses. A reduction in TW was observed using an anti P-selectin aptamer with a positive correlation between TW and sP-sel levels, providing evidence that sP-sel could be a clinical biomarker of venous thrombosis. The reduction of venous inflammation by p-selectin blockade could have benefit in reducing the sequelae of DVT including venous fibrosis. Disclosures: Kurz: Archemix: Research Funding. Schaub:Archemix: Research Funding.

Abstract Abstract 2495 Background. The intracellular concentration of imatinib (IM) in patients with chronic myeloid leukemia (CML) is supposed to be influenced by the expression of its main cellular transporters, hOCT1 (influx) and ABCB1 (efflux). The assessment of the genes expression may be potentially important in clinical practice to effectively manage the therapy. Our recent results showed the necessity to cautiously interpret results from gene expression measurements of both transporters as their detected mRNA levels are affected by the proportion of different cell types in the sample analyzed (Racil et al. 2010 Am J Hem 85:525, Racil et al. 2011 Leuk & Lymph 52:331). Aims. In this report, we aimed to comprehensively assess differences in the expression of hOCT1 and ABCB1 in total leukocytes of peripheral blood (PB) in relation to the blood cell lineage in CML patients with different responses to IM. Methods. Kruskall Wallis's and Dunn's multiple comparison tests were applied to calculate differences in transcript levels of hOCT1 and ABCB1 in patients at diagnosis (Dg=43), in major molecular response (MMR=27), complete molecular response (BCR-ABL log 4.5 reduction; CMR4.5 =15), therapy failure (TF=13), accelerated phase (AP=12) and in 75 healthy controls. CMR4.5 is defined here as either a detectable disease ≤0.0032% BCR-ABLIS or as undetectable by nested PCR. TF is defined as non CCgR achievement. Additionally, we used the Spearman's correlation test to investigate relationship between expressions and percentage of immature cells and neutrophils in patients with non-physiological blood count (Dg and AP). In patients with normal blood count (CMR4.5, MMR, TF), we calculated correlation with BCR-ABL transcript level. Finally, we performed in vitro experiments with BCR-ABL negative (SKM-1, MOLM-13) and positive cell lines (K562, MOLM-7) treated with IM to study its effect on ABCB1 expression. Results. We found a significantly lower expression of hOCT1 and ABCB1 at Dg (P<0.001) and in AP (P<0.001 and P<0.01, respectively) in comparison to controls. The lower expression probably depends indirectly on the immature cells count (hOCT1 r = −0.4850, P=0.0002; ABCB1 r = −0.6451, P< 0.0001). Interestingly, while a significant positive correlation of neutrophil count was found with hOCT1 mRNA levels (r=0.6090, P< 0.0001), no correlation was observed with ABCB1. In patients with physiological blood count, we observed significantly elevated expression of ABCB1 in MMR and CMR4.5 in comparison to controls (P< 0.01). As MMR and CMR4.5 samples are characterized by the BCR-ABL transcript level <0.1%, this result led us to perform in vitro experiments to test the effect of IM on ABCB1 expression in BCR-ABL negative cell lines showing an elevated expression after incubation with IM. We assume this effect to be a natural defense of BCR-ABL negative cells to get rid of IM. By contrast, we found a drop in ABCB1 expression after BCR-ABL positive cell lines incubation with IM, suggesting inhibitory effects of IM. A significantly reduced expression of hOCT1 was found in TF in comparison to MMR and CMR4.5 (P< 0.01). These samples did not differ in blood count, but we observed a significant negative correlation of hOCT1 with BCR-ABL transcript levels (r= − 0.5117; P< 0.0001). Conclusion. Cell composition in PB changes during the CML treatment with IM which influences the measurement of hOCT1 and ABCB1 mRNA levels in total leukocytes. However, hOCT1 expression was found to be significantly lower in patients who failed to achieve CCgR but had normal blood count. Interestingly, our data suggest that ABCB1 is differently expressed in BCR-ABL positive and negative cells due to the inhibitory and enhancing effects of IM, respectively. Supported by IGA NT11555 and MZOUHKT2005 Disclosures: Machova Polakova: Novartis: travel grant. Ondrackova:BMS: travel grant.

The purpose of this study is to analyze and describe the National Health Insurance program in terms of the budget deficit problem and its implications for health insurance for Covid-19 patients. This study uses a qualitative method oriented to library research (library research) using secondary data sources and William N. Dunn's analytical approach. The results of this study indicate that the National Health Insurance (JKN) program has not found a bright spot in dealing with the budget deficit after the JKN rate increase through Presidential Decree Number 75 of 2019 was canceled by the Supreme Court because it was considered to have violated the provisions of the 1945 Law article 28 H paragraph 1. The handling of covid-19 patients as the health insurance is instructed to be borne by the BPJS also has legal regulatory constraints, which is contrary to Presidential Decree Number 82 of 2018 article 52 paragraph 1 letter O. Even though the efforts to service covid-19 patients, the budget comes from injecting APBN and APBD funds as effort prevention of a larger deficit, but operationally violates applicable legal provisions. For this reason, it is necessary to make new rules and revise related regulations in order to accelerate the handling of policies in accordance with applicable legal provisions.

ABSTRACT: This study aimed to determine the occurrence of gastrointestinal and pulmonary parasites in calves and to evaluate seasonal and age patterns in parasitism. For this, we used 140 clinically healthy crossbreed calves (two to 12 months old) that belonged to two private farms in the municipalities of Botucatu (n=53) and Manduri (n=87), São Paulo state, Brazil. The calves were monitored for 12 months (from September 2014 to August 2015). Fecal samples were collected directly from the rectum every three months. Fecal egg counts were determined using the modified McMaster technique with a sensitivity of 50 eggs per gram of feces (EPG). Coproculture was performed on pooled samples to identify Strongylida infective larvae. First-stage larvae of Dictyocaulus viviparus were extracted by a modified Baermann method. The data showed non-normal distribution (Shapiro-Wilk) and the nonparametric Kruskall-Wallis test was employed to evaluate the EPG data by seasons and age groups. Dunn’s post-test was used for multiple comparisons (P<0.05). The calves from Manduri farm showed significantly higher fecal egg counts (P<0.0001) in the winter when compared to other seasons. At Botucatu farm, young calves (2-3 months old) showed significantly higher EPG than old calves (8-12 months) (P=0.01). The prevalence and overall mean of animals positive for Strongylida type-eggs were 81.1% and 340 in Botucatu, respectively, versus 83.9% and 854 in Manduri, respectively. Furthermore, we found Strongyloides spp., Moniezia spp., and Trichuris spp. eggs and Eimeria spp. oocysts. The prevalent genera in all coprocultures in decreasing order were: Cooperia spp., Haemonchus spp., Oesophagostomum spp., and Trichostrongylus spp. First-stage larvae of Dictyocaulus viviparus were found only in Botucatu farm samples throughout the year, except in spring.

Antifreeze proteins (AFP) have been included in extenders for sperm cryopreservation to prevent ice crystal formation. Thus, this study assessed the effects of supplementing semen extender with two concentrations of AFP types I and III on the quality of frozen–thawed ram sperm. The hypothesis is that various types and concentrations of AFP enhance cryopreservation of ram sperm. Semen was collected from 4 rams, pooled in 6 replicates, and allocated into 1 of 5 treatments: Control (CONT, without AFP); AFP type I [0.1 (AFPI-0.1) or 0.5 (AFPI-0.5) µg±mL−1]; or AFP type III [0.1 (AFPIII-0.1) or 0.5 (AFPIII-0.5) µg±mL−1]. Straws were placed on a metal wire net frame at 37°C and placed in a refrigerator for 2h to cool them to 5°C (−0.25°C/min). After 2h for stabilisation, straws were cooled in liquid nitrogen vapor (−15.3°C/min) and subsequently immersed (−196°C). After thawing, samples from each treatment were evaluated microscopically (sperm kinetics, plasma membrane integrity, capacitation, hypoosmotic test, acrosome status and mitochondrial activity, chromatin condensation, morphology, binding to egg perivitelline membrane, and lipoperoxidation quantification). The normal distribution of residuals was determined by Shapiro-Wilk test and homoscedasticity by Levene’s test. Normally distributed variables were analysed with one-way analysis of variance (ANOVA), followed by Tukey’s test. The non-normally distributed were analysed by Kruskal–Wallis and Dunn’s test. The repeated-measures ANOVA in general linear model (GLM) was used to effects of concentration for each AFP type in paired samples. The Greenhouse-Geisser test was applied when sphericity was not considered, followed by the Sidak test. Values of P&lt;0.05 were considered significant. Treatments affected (P&lt;0.05) kinetic parameters, plasma membrane integrity, and morphology. Linearity was greater in AFPI-0.1 (56.6±3.1%, mean±s.e.m.), AFPI-0.5 (56.9±2.2%), and AFPIII-0.5 (64.7±6.2%) than in CONT (36.8±3.0%). Straightness was greater in all AFP-supplemented extenders (overall mean, 78.6±2.8%) than in CONT (63.2±0.8%). Plasma membrane integrity was greater in AFPI-0.1 (49.1±4.6%) and AFPI-0.5 (36.6±7.3%) compared with CONT (13.0±4.4%). All AFP groups had a greater percentage of normal sperm (overall mean: 74.3±1.3%) than CONT (65.3±1.9%). There were no significant differences in percentage of sperm with functional membrane (overall mean: 16.1±3.3%), normal acrosome (11.5±4.5%), mitochondrial activity (24.5±6.5%), chromatin condensation (98.8±0.4%), perivitelline membrane binding rate (194.0±44.5 sperm/mm2), and lipoperoxidation (556.7±20.5 TBARS ng±mL−1). In conclusion, the use of AFP, predominantly type I, had potential as a cryoprotectant for ram sperm, increasing sperm cell protection, with no adverse effects on potential fertilization capacity and did not increase reactive oxygen species. This research was funded by FAPERJ, CNPq, and CAPES (Finance Code 001).

Antifreeze proteins (AFP) have been included in extenders for sperm cryopreservation to prevent ice crystal formation. Thus, this study assessed the effects of supplementing semen extender with two concentrations of AFP types I and III on the quality of frozen–thawed ram sperm. The hypothesis is that various types and concentrations of AFP enhance cryopreservation of ram sperm. Semen was collected from 4 rams, pooled in 6 replicates, and allocated into 1 of 5 treatments: Control (CONT, without AFP); AFP type I [0.1 (AFPI-0.1) or 0.5 (AFPI-0.5) µg±mL−1]; or AFP type III [0.1 (AFPIII-0.1) or 0.5 (AFPIII-0.5) µg±mL−1]. Straws were placed on a metal wire net frame at 37°C and placed in a refrigerator for 2h to cool them to 5°C (−0.25°C/min). After 2h for stabilisation, straws were cooled in liquid nitrogen vapor (−15.3°C/min) and subsequently immersed (−196°C). After thawing, samples from each treatment were evaluated microscopically (sperm kinetics, plasma membrane integrity, capacitation, hypoosmotic test, acrosome status and mitochondrial activity, chromatin condensation, morphology, binding to egg perivitelline membrane, and lipoperoxidation quantification). The normal distribution of residuals was determined by Shapiro-Wilk test and homoscedasticity by Levene’s test. Normally distributed variables were analysed with one-way analysis of variance (ANOVA), followed by Tukey’s test. The non-normally distributed were analysed by Kruskal–Wallis and Dunn’s test. The repeated-measures ANOVA in general linear model (GLM) was used to effects of concentration for each AFP type in paired samples. The Greenhouse-Geisser test was applied when sphericity was not considered, followed by the Sidak test. Values of P&lt;0.05 were considered significant. Treatments affected (P&lt;0.05) kinetic parameters, plasma membrane integrity, and morphology. Linearity was greater in AFPI-0.1 (56.6±3.1%, mean±s.e.m.), AFPI-0.5 (56.9±2.2%), and AFPIII-0.5 (64.7±6.2%) than in CONT (36.8±3.0%). Straightness was greater in all AFP-supplemented extenders (overall mean, 78.6±2.8%) than in CONT (63.2±0.8%). Plasma membrane integrity was greater in AFPI-0.1 (49.1±4.6%) and AFPI-0.5 (36.6±7.3%) compared with CONT (13.0±4.4%). All AFP groups had a greater percentage of normal sperm (overall mean: 74.3±1.3%) than CONT (65.3±1.9%). There were no significant differences in percentage of sperm with functional membrane (overall mean: 16.1±3.3%), normal acrosome (11.5±4.5%), mitochondrial activity (24.5±6.5%), chromatin condensation (98.8±0.4%), perivitelline membrane binding rate (194.0±44.5 sperm/mm2), and lipoperoxidation (556.7±20.5 TBARS ng±mL−1). In conclusion, the use of AFP, predominantly type I, had potential as a cryoprotectant for ram sperm, increasing sperm cell protection, with no adverse effects on potential fertilization capacity and did not increase reactive oxygen species. This research was funded by FAPERJ, CNPq, and CAPES (Finance Code 001).

Abstract The aim of this study was to evaluated the root surfaces modifications resulted by application of different chemicals agents, and their influence on the fibrin network and fibroblasts attachment. From 96 anterior mandibular human extracted incisor teeth, 192 dentin blocks of buccal and lingual surface were obtained and randomly divided into 6 groups: Cont- control group, which received no treatment; Root surface scaling and root planing (Srp); Citric acid-Srp; EDTA-Srp; Tetracycline capsule-Srp; Tetracycline gel-Srp. After dentin treatments the specimens were analyzed as follows: 1) demineralization level and residues of the product by scanning electron microscopy (SEM); 2) adhesion of blood components after 20 min of surface treatment by SEM; 3) fibroblast attachment after 24 h by SEM; 4) cell metabolism after 24 h by MTT assay. Data were analyzed using Fisher Exact, One-way ANOVA test followed by Dunn's test, Tukey test and Dunnett test (α=0.05). Citric acid, EDTA and Tetracycline gel resulted in adequate demineralization with no completely smear layer and smear plug removal on root dentin surface. Tetracycline capsule produced great tetracycline residues with several demineralization areas. Tetracycline gel and EDTA groups presented more fibroblast fixation than other experimental groups. The highest mean blood clot adhesion score was observed in roots treated with tetracycline gel. EDTA and Tetracycline gel surface treatment removed the smear layer over dentin surface and promoted adhesion of fibrin network and fibroblast cells attachment.

Background: The mechanisms mediating the impacts of fetal growth restriction (FGR) on follicular development are commonly studied in mouse/rat models, where ovarian development occurs largely during the early postnatal period. These models have shown that FGR is associated with premature follicle loss, early pubertal onset, and accelerated ovarian aging. Whether the same occurs in precocious species is unknown. Objective: Since guinea pig follicle development occurs in utero in a manner consistent with human ovarian development, we sought to determine whether FGR had similar impacts on guinea pig ovarian development. Methods: Dunkin-Hartley guinea pig dams were randomized to receive a control (CON) or a nutrient-restricted diet (FGR) prior to conception until weaning. Offspring ovaries were collected at prepubertal (postnatal day [P] 25) and young adult (P110) time points. Results: Prepubertal offspring exposed to FGR showed little differences in ovarian transcript levels and follicle counts. Young adult FGR offspring, however, showed reductions in the number of transitioning, primary, and antral follicles, as well as corpora lutea. This loss in follicles was associated with reduced insulin-like growth factor receptor and growth differentiation factor-9 messenger RNA levels in FGR P110 offspring compared to CON. Conclusion: We demonstrate that FGR in guinea pigs is accompanied by perturbations in signaling pathways essential for proper follicle growth and manifests as reductions in growing follicles in offspring, but these changes do not manifest until postpuberty. These data support the fact that accelerated reproductive maturation/aging is a conserved phenotype that is associated with in utero nutritional adversity.

The abundance of the New Zealand sea lion, Phocarctos hookeri, was estimated using a model that incorporated estimated pup production. Pups are born at only five sites, four of which are at the sub-Antarctic Auckland Islands, which lie to the south of New Zealand. The remaining breeding site is at Campbell Island in the same region. Pup production was estimated during the 1994/95 and 1995/96 breeding seasons from mark–recapture studies at the two largest sea lion rookeries, at the Auckland Islands (Sandy Bay and Dundas Island), which account for almost 90% of total pup production for the species. Pup production for the other sites was estimated from direct counts or, in the case of Campbell Island, from recent tagging data. Total pup production estimates for all sites during the 1994/95 and 1995/96 breeding seasons are 2640 and 2807 respectively. During the four-week pupping season, pup mortality at most sites was estimated to be about 10%. The estimates of absolute abundance based on pup production for the two breeding seasons were 11 700 (95% confidence interval (CI): 10 500–13 100) and 12 500 (95% CI: 11 100–14 000) respectively. This population abundance is among the smallest reported for a species within the Otariidae. The highly localised, and historically reduced distribution make this species vulnerable to impact and warrants particular attention from conservation managers. In particular, the potential impact of the annual bycatch of P. hookeri in a trawl fishery requires close monitoring and, ideally, some mitigation action.

Abstract: Introduction: The 8th edition of the Tumor-Node-Metastasis (TNM) based staging of breast cancer introduces a prognostic stage influenced by biomarkers along the traditional T, N and M categories. Aim: To retrospectively assess stage influencing prognostic variables; and the anatomic and prognostic stages on the basis of the overall survival (OS) of a cohort of deceased patients once diagnosed with breast cancer. Method: We included patients with known causes of death certified at the Bács-Kiskun County Teaching Hospital and having a history of breast cancer diagnosed on a resection specimen at the same institution. Prognostic factors were obtained from the histopathological reports. Statistics included one-way ANOVA, Dunn’s post hoc test and Kaplan-Meier curve analyses. Results: The 303 patients grouped as breast cancer related death (n = 168) or unrelated (n = 135) showed significant differences in most stage defining prognostic factors and the anatomic and prognostic stages. Significant differences in 5-year OS were observed between pT and pN categories, histological grades and estrogen receptor statuses. Except for stages I and II, significant differences were found between both different anatomic and prognostic stages (p<0.001). Stage IV is by definition uniform, but we identified survival differences between biomarker based subgroups: triple negative carcinomas had worse OS than estrogen receptor positive and HER2 negative carcinomas. Conclusions: Our analysis based on real survival data suggests that the prognostic stages separate patients according to OS similarly to the anatomic stages. The results validate the prognostic stages, but also suggest that separating stage IV disease according to biomarkers makes sense. Orv Hetil. 2017; 158(35): 1373–1381.

Deteriorating financial condition of a company may lead to insolvency. As a result, the company may be declared bankrupt or undergo restructuring. The first goal of the study described in the paper is to compare the financial condition of Poland-based non-financial companies undergoing restructuring and bankruptcy processes. In the empirical study, a tool for forecasting the future financial situation of a company was constructed. The second goal is the assessment of the effectiveness of restructuring processes on the basis of a comparative analysis of companies subjected to varios forms of this procedure. An attempt was made to identify the determinants of the success or failure of the restructuring process. The study was based on the information from the Coface Poland, EMIS Professional and the Court and Commercial Gazette (Pol. ‘Polski Monitor Sądowy i Gospodarczy’) databases. The empirical research was conducted on a random sample of financial data of 1740 non-financial companies (580 companies that were declared bankrupt, 580 companies undergoing a restructuring, and 580 companies in a good financial condition) in 2015–2019. The Kruskal-Wallis test, Dunn’s test, Mann-Whitney’s test and the random forest classifier were used for the purpose of the study. Companies that were declared bankrupt or underwent a restructuring process have more in common with each other than with companies efficiently operating in the market. It was possible to create a classifier which enabled forecasting whether a company will have financial problems. The results of the study demonstrated that the efficiency of the restructuring process does not depend on financial factors. Moreover, restructuring often fails to protect companies from bankruptcy and does not have a significant impact on the financial condition of restructured entities.

Abstract Abstract 3227 Background: Sickle cell anemia (SCA) patients present an elevated rate of thrombotic complications and increased biological markers of hemostatic activation. Hemoglobin SC disease (HbSC) is the second most prevalent hemoglobinopathy after SCA (homozygous HbSS), has specific clinical and pathological characteristics that may differ from SCA, and viscosity appears to be a hallmark of the disease. Studies have shown an increase in thrombotic events in HbSC patients, especially pulmonary embolism, however, not much is known about the coagulation activation in this population. We herein aimed to evaluate the hypercoagulability markers in HbSC disease and their associations with patients' clinical and laboratory characteristics. Patients and Methods: This was a cross-sectional study performed on a cohort of 41 adult HbSC (mean age of 43 years) and 58 adult HbSS patients (mean age of 36 years), all in steady-state, and 25 healthy age-matched controls. We evaluated the expression of tissue factor (TF), the physiological initiator of coagulation, and thrombin-antithrombin complex (TAT), a final marker of coagulation activation. Leukocyte TFmRNA expression was analyzed by real time quantitative PCR and TAT plasma levels were measured by ELISA. Comparisons between the two patient groups and controls were performed using Kruskal-Wallis test followed by Dunn's Multiple Comparisons test. Fisher's exact test and Mann-Whitney's U test were used to compare patients' clinical complications and laboratory characteristics. Spearman's rank test was used for correlations analysis. Results: Relative TF mRNA expression was significantly up-regulated in HbSC patients when compared to controls (2.6 vs. 1.2), however levels of TF were lower in HbSC than HbSS patients (2.6 vs. 3.3) (P<0.0001). Confirming the biological relevance of TF expression, TAT plasma levels were also higher in HbSC patients in comparison to controls (4.2 vs. 2.4), and lower in HbSC than HbSS patients (4.2 vs. 7.3); (P<0.0001). In the analyses of the HbSC cohort, TAT levels presented significant positive correlations with inflammation markers: leukocyte (r=0.5; P=0.001), monocyte (r=0.4; P=0.01), and platelet counts (r=0.5; P=0.002); and hemolysis markers: reticulocyte counts (r=0.4; P=0.01) and lactate dehydrogenase levels (r=0.6, P=0.0001). We also evaluated associations between TAT levels and clinical complications: stroke, pulmonary arterial hypertension, acute thoracic syndrome, retinopathy, osteonecrosis, leg ulcers, autosplenectomy and microalbuminuria. HbSC patients with retinopathy had significantly higher TAT levels (4.7 vs. 3.9; P=0.03) when compared with patients without this complication. TAT levels were also higher in patients with autosplenectomy (4.8 vs. 3.8; P=0.004), and in patients with osteonecrosis, although this had borderline statistical significance (4.6 vs. 3.9; P=0.06). TF expression significantly correlated with monocyte counts (r=0.6; P=0.01). Conclusions: Our results indicate that HbSC disease patients present elevated coagulation activation markers when compared to controls, although not as intense as seen in SCA. Thrombotic complications in HbSC patients have been mainly linked to the hyperviscosity present in this disease. Our data suggest that inflammation and hemolysis are also important factors contributing to hemostatic activation, which may participate in the pathophysiology of very prevalent chronic complications of HbSC disease: retinopathy and osteonecrosis. Interestingly, in our cohort, patients with autosplenectomy had higher levels of pro-coagulant markers, possibly due to a higher intravascular hemolytic rate and elevated peripheral blood counts. Although HbSC disease is considered a milder form of SCA, autopsy studies have shown that mortality by pulmonary embolism is more frequent in HbSC disease than in SCA, being the second cause of mortality in these patients (Manci et al, 2003). Studies addressing the pathophysiology of coagulation activation in HbSC disease are lacking. Low numbers of cases of HbSC disease are usually included in studies focusing mainly in SCA, and the results are very variable, probably due to the small numbers of patients. In view of the high prevalence and morbimortalilty of thrombotic complications in this population, we believe that future studies should focus on a better understanding of hypercoagulability in HbSC disease. Disclosures: No relevant conflicts of interest to declare.

Abstract Background: Pneumocystis spp. are the obligate pathogenic fungi that cause PCP in immunocompromised mammalian hosts. The life cycle of Pneumocystis is thought to be biphasic with asexual replication by trophic forms and sexual production leading to formation of asci/cysts. There is evidence to suggest that infection is initiated by cyst inhalation and asci formation may be essential for the Pneumocystis life cycle. We have previously reported (Cushion, et al. 2010; 5:e8524) that currently available echinocandins are not suitable for monotherapy as large numbers of trophic forms remained after 3 weeks of treatment and asci re-appeared and replication resumed after treatment discontinuation. We evaluated the effects of CD101, a novel long-acting echinocandin, on trophic and cyst forms of Pneumocystis murina and its efficacy in preventing infection in a mouse model of PCP. Methods: Mice (C3H/HeN) were immunosuppressed throughout this 6-week study by dexamethasone (4 mg/L) in acidified drinking water. Infection with P. murina was by intranasal inoculation (2 x 106/50 µL). Mice were divided into groups to receive either vehicle (untreated control), trimethoprim/sulfamethoxazole (TMP/SMX 50/250 mg/kg x 3 per week), or CD101 (20, 2, or 0.2 mg/kg once or 3x per week) intraperitoneally at the time mice were inoculated. After 6 weeks, mice were humanely euthanized and lungs were processed for analysis by homogenization. Slides made from the lung homogenates were prepared for quantification of trophic forms by rapid Wright-Giemsa stain and of asci by cresyl echt violet staining. The reduction in P. murina burden (nuclei of trophic forms and asci) in treatment and untreated control groups was evaluated. The nuclei and asci counts for each lung were log transformed and analyzed by ANOVA. Individual groups were compared by Dunn's test for multiple comparisons (GraphPadPrismv.6). Results: The reduction in nuclei and asci counts for all groups are shown in the Figure. Statistically significant reductions in nuclei levels compared with untreated controls were demonstrated with all CD101-treated groups except for the 0.2 mg/kg once weekly group. CD101 efficacy was comparable to that of TMP/SMX for 3 of the CD101 dose groups; no nuclei were observed by microscopic evaluation following CD101 dosages of 2 or 20 mg/kg 3x per week or 20 mg/kg once weekly. In terms of asci reduction, all CD101 groups demonstrated statistically significant reductions compared with untreated controls. CD101 efficacy was comparable to that of TMP/SMX for 5 of the CD101 dose groups (all but the 0.2 mg/kg once weekly group), with no asci observed by microscopic evaluation. Conclusion: Asci/cysts appear to be critical for replication as well as transmission of Pneumocystis. CD101 inhibited the formation of both trophic forms and asci of P. murina in thismouse model of PCP in immunocompromised mice. These data demonstrate that CD101 is a viable candidate for prophylactic therapy of PCP. Figure Figure. Disclosures Cushion: Univ. of Cincinnati: Employment; Cincinnati VAMC: Research Funding; Cidara Therapeutics, Inc.: Research Funding. Bartizal:Cidara Therapeutics, Inc.: Employment, Other: Stockholder.

586 Background: PARP inhibitors (PARPi) such as talazoparib and olaparib, have demonstrated an improvement in progression-free survival (PFS) amongst metastatic HER2-negative breast cancer patients with germline mutations in BRCA1/2 (BRCA-MUT). Clinical trials have evaluated PARPi in combination with carboplatin, but with mixed results. Earlier trials studied the combination of carboplatin and a low-dose PARPi of low potency, veliparib. The concomitant combination of carboplatin and talazoparib, a higher-potency PARPi, was also evaluated in solid tumors, using a heavily pre-treated population. Here, we perform a comparative evaluation of different sequencing strategies of talazoparib and carboplatin to determine efficacy and toxicity in BRCA-MUT and BRCA wild-type (WT) TNBC models. Methods: We used three orthotopic xenograft models in NSG (NOD scid gamma) mice, with 7-14 mice in each treatment group: MDAMB231 (BRCA-WT), HCC1806 (BRCA-WT), and MX1 (BRCA-MUT). We treated mice with carboplatin (C) (35 mg/kg intraperitoneally) in combination with talazoparib (T) (0.33 mg/kg oral gavage) using 2 dosing strategies: a) concomitant administration of C + T; and b) T first, followed by C three days later, each compared to vehicle control. We evaluated primary tumor inhibition and hematologic toxicity. Kruskal-Wallis test and Dunn’s multiple comparison test was used to assess statistical significance. Results: Using the MDAMB231 xenograft, we found the T-first approach led to a 66.7% (P < 0.0001), and the concomitant approach resulted in a 51.4% decrease in primary tumor volume, (P = 0.08), in comparison to control. In HCC1806, the T-first approach resulted in a 62.0% decrease in tumor volume (P < 0.0001), whereas the concomitant combination showed a 54.4% decrease (P = 0.002). In MX1, the T-first and concomitant approaches resulted in 72.7% (P < 0.0001) and 81.4% (P < 0.0001) decrease in tumor volume, respectively. With regards to neutrophil counts, T-first approach decreased neutrophils by 66.2% and 43.0% in MDAMB231 and HCC1806 xenografts respectively, similar to the trend with concomitant T + C: 61.4% and 38.0%. In the MX1 cohort, the T-first approach resulted in a 66.2% decrease in neutrophils (P = 0.001), and the concomitant approach led to a 77.5% decrease in neutrophils (P = 0.006). Conclusions: Our results demonstrate that the talazoparib-first approach is effective in two BRCA-WT models with no statistically significant neutropenia. While the concomitant combination approach demonstrated greater tumor inhibition in the BRCA-MUT model, this was also associated with significant neutropenia. This is suggestive that sequencing of talazoparib and carboplatin may have differential effect in BRCA-WT and BRCA-MUT tumors and may play an important role in improving efficacy in BRCA-WT tumors.

Abstract Background: Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated low platelet count and a skewed proinflammatory Th1/Th17 profile. However, little is known about the involvement of CD8+ cytotoxic T cells in ITP pathophysiology and whether they are regulated by regulatory T cells (Treg). Immunosuppressive therapy has been the mainstay treatment in ITP. More recently, Thrombopoietin receptor agonists (TPO-RA); Romiplostim (Romi) and Eltrombopag (EPAG), have been increasingly used to stimulate megakaryocytopoiesis to produce more platelets. TPO-RAs are reported to induce complete remission in up to 30% of cases, with limited understanding of their impact on the immune system. Here we describe changes in T cell subsets in patients with ITP: how these changes are affected by disease activity and how TPO-RA may induce remission through modulating the immune system. Methods: Multi-color flow cytometric panels were designed to characterize peripheral blood T cell subsets, including CD8+ T cell and Treg subsets, phenotypically as well as functionally through intracellular cytokine expression. To determine whether CD8+ cells were platelet specific, an IFNγ ELISpot assay was performed using platelets from a healthy donor and PBMC from both HC and patients. Forty patients with ITP were included: 13 were on Romi, 11 on EPAG and 16 on no treatment at the time of analysis. Of these 40 patients, 15 patients had active disease (AD) (platelet-count less than 30 x 109/L) and 25 had stable disease (SD) (> 30 x 109/L). These patients were compared with 26 age and gender-matched healthy controls (HC). Data were presented as median values; Mann Whitney U and Kruskal Wallis tests were used with Dunn's multiple comparisons correction; a P value of < 0.05 was considered significant. Results: CD4/CD8 T cell ratio was significantly lower in patients compared to HC [1.77 vs. 3.97; P value < 0.001]. CD45RA+CD62L- Terminally-differentiated CD8+ T cells were significantly higher in patients compared to HC [66.3% vs. 8.56%; P value < 0.001]. This finding was more prominent in AD patients than those with SD [66% vs. 44.4%; P value < 0.05]. This effector population is polyfunctional, expressing high levels of proinflammatory cytokines including TNFα, IFNγ and Granzyme B when compared to HC [P value < 0.05]. Additionally, this population lacks the exhaustion markers PD-1 and Tim-3. Furthermore, these cells were reactive to platelets showing higher IFNγ-producing cells when co-cultured with platelets. CD3+CD4+CD25hiCD127lo Treg frequency did not differ between patients and HC [P value>0. 05]. Treg functionality was preserved in these patients; no important changes were observed in their capacity to express interlukin2 intracellularly, nor in the cell surface receptor (CD25) [P value > 0. 05]. However, Tregs were significantly lower in AD patients with compared to SD patients [2.32% vs. 4.46%; P value < 0.05]. Treg function is interactive with other T cell subsets and depends on its relative abundance in relation to other subsets; The Treg/effector CD8+ T cell ratio was significantly lower in patients compared to HC [0.06 vs. 0.16; P value < 0.01] and was also significantly lower in AD compared to SD patients [0.03 vs. 0.09 ; P value < 0.05]. EPAG-treated patients had a significantly lower effector CD8+ T cells compared to Romi-treated patients [42.4% vs 76.8%; P value <0.01]. Although EPAG did not have a direct effect on the frequency of Treg, the Treg/effector CD8+ T cell ratio was significantly lower than that in patients on Romi [0.04 vs. 0.11; P value < 0.05] because of the CD8+.T cell difference. The Treg/effector CD8+ T cell ratio in EPAG-treated patients was comparable to the ratio of HC [0.11 vs. 0.16; P value > 0.05]. Conclusion: While Th1/Th2 cell ratio is often considered as driving ITP, these results demonstrate the involvement of cytokine secreting effector CD8+ T cells in the disease pathogenesis. The imbalance in immune tolerance is also highlighted in the form of a significant reduction in the Treg/effector CD8 T cell ratio. The differences seen in T cell subsets between EPAG- and Romi-treated patients suggest the potential for an additional, differential immunomodulatory effect between the two agents which is currently being explored. Acknowledgment: The authors wish to thank Prof James B Bussel for his insightful comments and support of this work. Disclosures Cooper: Amgen, Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Background:Inflammatory joint diseases, such as psoriatic arthritis (PsA), are frequently treated by biologics. Assessment of treatment efficacy is based upon change in clinical activity scores and in tender and swollen joint counts. Although the response to these agents may be attributed to their central anti-inflammatory effects, synovial response may be operating in parallel. The potential beneficial role of intra-articular injection of tumor necrosis factor (TNF) blockers compared to glucocorticoids (GCs) in reducing synovitis was shown by means of clinical and instrumental validated measures (1). The inflamed synovial fluid is rich in mononuclear cells, however, the different mode of action of the in vitro response of these cells to drugs may contribute to the understanding of cellular response to therapeutic agents in central as opposed to peripheral compartments.Objectives:To evaluate the effect of biologics used in the management of PsA on synovial fluid mononuclear cells (SFMCs) in vitro, and to compare their modes of action to GCs that are used to locally alleviate synovial inflammation.Methods:SFMCs were obtained from PsA patients (n=11) during therapeutic knee arthrocentesis. The cells were cultured in vitro for 7 days in the presence of biologics (adalimumab, infliximab, secukinumab and ustekinumab, 10ug/ml) and GCs (betamethasone and methylprednisolone, 1 ug/ml and 10ug/ml) or medium as control. Levels of the secreted TNF were measured by ELISA. Changes in %CD14+CD16+ monocytes were analyzed by flow cytometry.Results:Both TNF inhibitors (adalimumab p<0.01, infliximab p=0.0003) and GCs (betamethasone and methylprednisolone at 1ug/ml p<0.01 and at 10ug/ml p<0.04) significantly reduced TNF levels in cultured media derived from SFMCs of PsA patients (n=8) compared to medium. None of the other biologics reduced TNF levels in culture (Fig. 1A). Additionally, %CD14+CD16+ SFMCs derived from PsA patients (n=11) were significantly reduced by TNF inhibitors (p=0.0003) compared to medium, however, other biologics and GCs did not display similar activity (Fig. 1B).Figure 1.Both TNF inhibitors and GCs block TNF secretion but exhibit different activity on inflammatory CD14+CD16+ monocytes derived from SFMCs of PsA patients. SFMCs were co-cultured for 7 days in the presence of adalimumab, infliximab, secukinumab and ustekinumab at 10ug/ml or with betamethasone and methylprednisolone at 1ug/ml and 10ug/ml. Medium alone was used as a control. (A) Culture supernatants were analyzed for TNF levels by ELISA (n=8). (B) Cells were analyzed for %CD14+CD16+ monocytes by flow cytometry (n=11). All p values were calculated by the non-parametric one-way ANOVA Kruskal-Wallis test and Dunn’s multiple comparison test, *p<0.04, **p<0.01 and ***p=0.0003.Conclusion:Our data demonstrated marked activity mediated by TNF inhibitors in comparison with other biologics tested for their ability to suppress TNF secretion and inflammatory CD14+CD16+ monocytes. In contrast, GCs suppressed TNF secretion but did not significantly change the proportion of inflammatory CD14+CD16+ monocytes. These findings suggest an additional mechanism of action exerted directly by TNF inhibitors on synovial monocytes and which differs from that of GCs. These results warrant further studies of the therapeutic potential of local peripheral activity of TNF inhibitors for clinical application.Reference:[1]Carubbi F, Zugaro L, Cipriani P, Conchiglia A, Gregori L, Danniballe C, et al. Safety and efficacy of intra-articular anti-tumor necrosis factor alpha agents compared to corticosteroids in a treat-to-target strategy in patients with inflammatory arthritis and monoarthritis flare. Int J Immunopathol Pharmacol. 2016;29:252-66.Disclosure of Interests:None declared

Abstract Abstract 904 Introduction: We previously reported that Pomalidomide (PL), a novel thalidomide-derived immunomodulatory drug (IMiD), is capable of enhancing erythropoiesis and fetal hemoglobin (HbF) production in a knockout-transgenic (KT) mouse model of sickle cell anemia (SCA). In addition to these hematological properties, PL is known to modulate specific effector functions of the innate and adaptive immune system. PL and other IMiDs potently inhibit the output of the inflammatory mediators TNF-α, IL-1β, and IL-6 in activated monocytes/macrophages, whereas their ability to promote T helper 1 (Th1) lymphocyte differentiation and co-stimulation of both CD4+ and CD8+ T lymphocytes can lead to increased TNF-α, IL-2, and IFN-γ secretion in both cell culture and human subjects. SCA is an inflammatory disease. It is therefore conceivable that PL could diminish disease severity in SCA by targeting vascular endothelial and innate immune cell activation, whereas preferential induction of a Th1-biased lymphocyte program could have unwanted effects. To test these possibilities in SCA, we evaluated PL's immunomodulatory activities in a relevant KT mouse model. Methods: Animals. Six week old KT homozygous sickle mice were treated daily (Mon-Fri; i.p. injections) for eight weeks with Vehicle (n=8) or PL (10 mg/kg; n=9). Mice were maintained in an accredited pathogen-free animal facility according to NIH and institutional guidelines. Mice were anesthetized with Ketamine/Xylazine and blood collected by intracardiac puncture into 0.5 ml vacutainer EDTA tubes (Becton-Dickinson). Soluble plasma adhesion molecules (sVCAM-1, sICAM-1, and sE-Selectin) and cytokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL-17, IFN-γ, TNF-α, G-CSF, and GM-CSF) were measured by ELISA (R&D Systems and SABiosciences). Organ analysis. We focused our analysis on the liver of KT mice because this organ manifests severe sickle cell-related pathology. Livers were removed and divided for H&E paraffin sections, immunohistochemistry, and RNA analysis (storage at -80°C). The area of liver ischemic infarcts (ALI) was measured on H&E tissue sections using an image processing program (Image J, NIH) and averaged from four randomly selected low power optical fields (5x) / animal. Whole liver RNA was pooled from PL animals with low ALI scores (n=2) and vehicle animals (n=3) using Trizol followed by RNeasy column purification. RNA was submitted to SABioscience for analysis using the 440 gene Inflammatory Response and Autoimmunity GEArray. Statistical analysis. One-Way ANOVA/Student-Newman-Kuels and Kruskal-Wallis One-Way ANOVA/Dunn's Method (Sigma Stat). Data are reported as the mean ± SE. A P-value of < 0.05 was considered significant. Results: The peritoneal cavity of all animals was free of adhesions, exudates and drug, suggesting that daily i.p. injections did not inflame the peritoneal membranes and resulted in complete absorption of the active compound. PL significantly reduced the level of the endothelial cell marker of inflammation, sVCAM-1 (sVCAM-1[ng/ml]: Veh: 1202±36; PL: 962±48; P<0.01), but did not affect sICAM-1 or sE-Selectin. Plasma cytokines in vehicle animals were measured at the assay's lower limit of detection and were not significantly modified by PL, suggesting that PL did not induce overt activation of the TH1 lymphocyte program. Liver histology in vehicle controls revealed scattered tissue infarcts surrounded by a mixed inflammatory cell infiltrate (macrophages [F4/80+], T-lymphocytes [CD3+]). PL reduced the ALI by 60 % (ALI [mm2/LPF: Veh: 0.30±0.05; PL: 0.12±0.06; P=0.01). The ALI score of eight out of nine PL mice was lower than the lowest score in the vehicle group (89% responder rate). Gene array data were consistent with decreased organ inflammation (serum amyloid A2 [-3.57 fold]), modifications in antigen presentation (CD74 [-2.12 fold]), inhibition of T-cell signaling (SLAP-2 [+5.68 fold]; SLP-76 [-1.92 fold]), and reduced T-cell migration (MIP-3β [-2.56 fold]). Tissue protection in the PL group did not correlate with HbF expression, total WBC count, or any other hematological variable. Summary & Conclusions: Pomalidomide modulates vascular and tissue markers of inflammation and protects from sickle cell-induced organ damage in a HbF-independent manner. These data suggest that PL, in addition to its HbF-inducing properties, may exert beneficial anti-inflammatory effects in SCA. Disclosures: Meiler: Celgene: Research Funding. Wade:Celgene: Research Funding. Moutouh de Parseval:Celgene: Employment. Corral:Celgene: Employment. Swerdlow:Celgene: Research Funding. Kutlar:Celgene: Research Funding.

Abstract Abstract 2651 Background: LIGHT (TNFSF14; CD258), a recently-identified member of the TNF superfamily, is found associated with and produced from platelets, amongst other immune cells. Increased circulating levels of this protein have been observed in patients with myocardial infarction and acute atherothrombotic stroke and LIGHT has been proposed as a potential therapeutic target in atherosclerosis, due to its reported pro-thrombotic and pro-inflammatory effects upon human endothelial cells. This study evaluated whether production of LIGHT is altered in patients with sickle cell anemia (SCA), and the participation that the platelets (PLTs) may have in this production, since SCA is characterized by a significant chronic inflammation and endothelial activation that may initiate the vaso-occlusive process. Patients and Methods: Soluble LIGHT (sLIGHT) was determined in PLT-free plasma (obtained by sequential centrifugations and ultrafiltration) from healthy control individuals (CON), SCA patients in steady state (SCA) and SCA patients on hydroxyurea therapy (SCAHU; 20–30 mg/kg/day HU) by ELISA. Expressions of PLT-membrane LIGHT and PLT activation markers were evaluated by flow cytometry using anti-CD258-PE, anti-CD62P-FITC or anti-PAC1-FITC. Subjects had not taken ASA during the previous 14 days. Results: sLIGHT was significantly elevated in the plasma of SCA and SCAHU individuals, compared to CONs (SCA; 35.4 ± 9.4 pg/ml; SCAHU, 37.3 ± 7.5 pg/ml; CON, 9.7 ± 1.5 pg/ml, n=27, 27, 19, resp.; P<0.01 for SCA/SCAHU, compared to CON; Kruskal-Wallis/Dunn's). Plasma sLIGHT in SCA/SCAHU individuals presented no correlation with hematological variables, such as PLT counts (rs=-0.079, P=0.65) and fetal hemoglobin (rs=0.107, P=0.51). In contrast, plasma sLIGHT levels in SCA patients presented an impressive correlation with plasma levels of CD40L, another important PLT-derived inflammatory protein (rs=0.817, P<0.0001 for SCA group and rs=0.651, P<0.0001 for SCA+SCAHU) and correlated with IL-8, an endothelium-derived inflammatory mediator (rs=0.900, P<0.05 for SCA and rs=0.455, P=0.06 for SCA+ SCAHU). Expression of LIGHT protein (CD258) was significantly higher on the membrane of PLTs from SCA and SCAHU individuals, compared to CON PLTs (SCA, 27.1 ± 4.5 %; SCAHU, 33.7 ± 5.8 %; CON, 5.5 ± 1.6 % positive PLTs, n=15, 20, 15, resp.; P<0.001 for SCA/SCAHU comp. CON). Notably, when PLTs were activated by incubation with ADP (20 μM, 30 min), PLTs from SCA/SCAHU individuals still expressed significantly more surface LIGHT than CON PLT (SCA, 41.8 ± 4.5 %; SCAHU, 41.3 ± 5.4 %; CON, 11.1 ± 2.3 % positive PLTs; n=15, 20, 14, resp. P<0.001 for SCA/SCAHU comp. CON); successful activation of PLTs from all groups was confirmed by increased PAC-1 (anti-activated αIIbß3 integrin) binding and increased P-selectin (CD62P, a PLT activation marker) expression (data not shown); furthermore LIGHT expression on ADP-activated cells correlated significantly with both PAC-1 binding (rs=0.483, P=0.03) and P-selectin expression (rs=0.502, P=0.02, n=20) on SCA PLTs. sLIGHT release from SCA PLTs during 90 min (37°C, 5% CO2 in Krebs) was evaluated and demonstrated that PLTs of SCA individuals may be an important source of circulating sLIGHT, releasing 22.2 ± 4.7 pg LIGHT/108 PLTs (n=10); release of sLIGHT from SCA PLT was significantly augmented by incubation with collagen (P<0.01), but not ADP (P>0.05); basal and collagen-stimulated sLIGHT release correlated significantly with CD40L release (rp=0.654; rp=0.764, resp. P<0.05). Conclusion: The pro-inflammatory and atherogenic protein, LIGHT, is found significantly elevated in the plasma of SCA patients. The correlation of plasma LIGHT with IL-8 indicates that LIGHT may participate in, or reflect, endothelial activation, whilst the correlation of circulating LIGHT and PLT release of LIGHT with CD40L indicates that the production of these two proteins may be tightly coupled. LIGHT protein is highly expressed on the PLT surface in SCA and this expression appears to be associated with PLT activation, rather than PLT number. Interestingly, HU therapy was not associated with any significant alteration in circulating LIGHT, nor PLT surface LIGHT. Future investigations will determine the extent of the contribution of LIGHT to endothelial activation, inflammation and vaso-occlusion in SCA and whether this protein holds promise as a potential therapeutic target for the disease. Disclosures: No relevant conflicts of interest to declare.

Introduction: During the Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), 3 distinct phenotypes have emerged in children. The majority of children have mild or no symptoms. Similar to adults, a minority of children can be severely affected with respiratory distress requiring intensive care. Finally, they may develop a phenomenon presumed unique to children termed Multisystem Inflammatory Syndrome in Children (MIS-C). MIS-C is a hyperinflammatory syndrome characterized by fever and organ dysfunction (particularly cardiac) in the setting of recent COVID-19 infection. Reports from the adult literature have invoked thrombotic microangiopathy (TMA) and complement activation as a potential cause for severe manifestations of COVID-19 (Zhang et al. NEJM. 2020; Campbell et al. Circulation 2020). Soluble C5b9 (sC5b-9), the terminal complement complex, has been implicated as a marker of hematopoietic stem cell transplant associated TMA (HSCT-TMA; Jodele et al. Blood 2014). We sought to elucidate the role of terminal complement activation and TMA in the different pediatric disease phenotypes. Methods: We enrolled children admitted to the Children's Hospital of Philadelphia during the COVID-19 pandemic who had evidence of SARS-CoV-2 infection on reverse transcriptase polymerase chain reaction (RT-PCR) from mucosa, or met clinical criteria for MIS-C. Patients (pts) were classified in to 3 categories: minimal COVID-19 symptoms or incidental finding of SARS-CoV-2 infection, severe COVID-19 requiring ventilatory support, or MIS-C. To investigate the role of TMA in children with COVID-19 we measured sC5b-9 in plasma of pts with the 3 manifestations of SARS-CoV-2, and in healthy controls. sC5b9 was measured in triplicate at two dilutions by ELISA. Proinflammatory cytokines were measured using V-Plex Pro-inflammatory Panel 1 Human Kits and analyzed on a QuickPlex SQ120. P-values were computed using Dunn's multiple comparisons test after Kruskal-Wallis testing. Blood smears were examined by a hematologist and hematopathologist for schistocytes. Results: 50 pts were enrolled on whom complete sC5b9 data were available: minimal COVID-19 (N=18), severe COVID-19 (N=11), and MIS-C (N=21). Plasma was obtained on healthy controls (N=26). The median sC5b9 level in healthy controls (57 ng/mL) differed significantly (p&lt;0.001 in each case; Figure 1A) from that in pts with minimal disease (392 ng/mL), severe disease (646 ng/mL), and MIS-C (630 ng/mL); differences between MIS-C, minimal, and severe were not statistically significant. Elevations in sC5b9 correlated in a statistically significant manner with the maximum creatinine and blood urea nitrogen (BUN) measured during hospitalization (Figure 1B&C), but not age (p=0.512). sC5b9 did not correlate with lactate dehydrogenase (LDH), nor with the lowest levels of fibrinogen, hemoglobin or platelet counts. Of pts with available data, 19/26 (73.1%) had elevated LDH, 2/31 (6.4%) had hypofibrinogenemia, 35/47 (74.5%) were anemic, and 28/47 (59.6%) were thrombocytopenic. Pro-inflammatory cytokines were measured. Of particular interest to TMA is the neutrophil chemotactic factor IL-8, because of its role as a marker of endothelial damage (Dvorak et al. Front Pediatr 2019). Levels of IL-8 differed significantly between pts with MIS-C (p=0.0166) or pts with severe COVID-19 (p=0.0079), when compared to minimal COVID-19 pts; but not between pts with MIS-C and severe disease (p = 0.99). Blood smears were available on 34 patients. Schistocytes were present in 13/15 (87%) patients with MIS-C, 7/8 (87%) patients with severe COVID-19 and 5/11 (45%) patients with minimal COVID-19 (χ2=6.59, p=0.037). Conclusions: We demonstrate derangements of the final common pathway of complement activation in children with the 3 presentations of SARS-CoV-2. Strikingly, sC5b9s were abnormal even in children with minimal disease or incidental infection. Renal dysfunction correlated with elevations in sC5b9, strengthening the evidence that TMA plays a role in the pathophysiology of SARS-CoV-2 infection. Future work is aimed at further characterizing the role of the complement cascade in the pathogenesis of MIS-C and COVID-19 in children. The long-term complications of endothelial damage and complement activation are unknown and extended follow-up is warranted. Figure 1 Disclosures Diorio: Children's Hospital of Philadelphia: Research Funding; University of Pennsylvania: Research Funding. Lambert:22qSociety: Consultancy; RDMD ITP study: Consultancy; Octapharma: Consultancy, Research Funding; Educational Concepts in Medicine: Consultancy; Shionogi: Consultancy; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Argenix: Consultancy; CdLS Foundation: Consultancy; Sysmex: Research Funding; Dova: Consultancy, Membership on an entity's Board of Directors or advisory committees; Principia: Consultancy, Membership on an entity's Board of Directors or advisory committees; ClinGen: Honoraria; Platelet Disorder Support Association (PDSA): Consultancy; AstraZeneca: Research Funding; Bayer: Consultancy; ITP Australia: Consultancy. Henrickson:Horizon Pharma: Other: ad hoc board meeting. Odom John:Burroughs Wellcome: Research Funding; NIAID: Research Funding. Bassiri:CSL Behring: Other: Spouse receives stocks . Behrens:NIH/NIAID: Research Funding. Teachey:Janssen: Consultancy; Amgen: Consultancy; La Roche: Consultancy; Sobi: Consultancy.

This paper is an attempt to describe how strong the covariation is between systematic counts and spontaneous reporting of staging waders at the Getterön Nature Reserve in southwestern Sweden. The material is based on systematic and spontaneous observations of twelve species of waders, made on the same days during the autumn migration in July–October 2010–2019. There is a significant positive correlation between the two methods for nine of twelve species. However, there is a large variation in the strength of the correlations, with the strongest correlation seen for Dunlin Calidris alpina. The Wood Sandpiper Tringa glareola, Green Sandpiper Tringa ochropus, and Little Stint Calidris minuta, on the other hand, show no significant correlations. This shows the difficulties in evaluating quantitative data of the wader occurrence at stopover areas such as Getterön. The variation in correlation between count methods between different species entails an uncertainty, which is probably due to low reliability in the spontaneous reporting. Thus, in the case of studies of staging waders based solely on spontaneous data, caution should be exercised.

Background: The clinical course of Kawasaki disease (KD), which is self-limiting and immune-mediated, is controlled by the host’s immune system. The incidence of incomplete KD is increasing in Korea. We evaluate the changes in the platelet count and immunoglobulin (Ig) levels (IgG, IgM, IgA, and IgE) during hospitalization and the relationships among these parameters. Methods: We examined the platelet count and levels of the four above-mentioned Igs twice at presentation and at discharge (mean of 6.2 days apart) in 43 patients with complete KD who received intravenous Ig at 2 g/kg. The relationships across all parameters were evaluated. Results: The mean patient age was 29.9 ± 16.4 months, and there were 28 male and 15 female patients. The mean platelet count and IgG, IgM, IgA, and IgE levels at presentation and at discharge were 366 ± 92 and 548 ± 135 х10 3 /μL, 718 ± 317 and 2433 ± 426 mg/dL, 125 ± 45 and 234 ± 71 mg/dL, 63 ± 57 and 98 ± 79 mg/dL, and 69 ± 70 and 57 ± 64 IU/mL, respectively. The values of these parameters were correlated with the time of examination from fever onset, in comparing three groups with fever duration of the <5 days, the 5-10 days, and the 11-16 days (Nonparametric Kruskal Wallis test and Dunn’s mehod for each post-hoc pair-wise test). A correlation was also noted in the degree of increase calculated at the two time points between the platelet count and IgG ( P = 0.002), IgM ( P = 0.01) or IgA level ( P = 0.002), respectively (Spearman correlation coefficient). Conclusions: The platelet count and Ig levels (IgG, IgM, and IgA) increased in the early convalescent stage of KD and were correlated with each other. This finding suggests that the host’s immune/repair system is involved in recovery from KD and may help to differentiate KD, especially incomplete KD, from other KD-like diseases if these phenomena do not occur in other diseases.

O presente trabalho teve por objetivo fazer uma análise comparativa de viabilidade econômica de projetos florestais com Pinus taeda e Eucalyptus dunnii localizados no município de Prudentópolis, PR. Na análise econômica foram utilizados os critérios do Valor Presente Líquido (VPL), Razão Benefício Custo (B/C), Taxa Interna de Retorno (TIR) e Valor Periódico Equivalente (VPE). A taxa de juros usada foi de 6,75% ao ano. Para o projeto de Pinus taeda os dados de custos e receitas corrigidos totalizaram R$ 4.344,71/ha e R$36.143,99/ha, respectivamente. Os valores calculados dos critérios de avaliação econômica foram um VPL de R$31.799,28/ha; Razão Beneficio/Custo de 8,32, TIR de 27.23% e VPE de R$ 3.200,87/ha/ano. Para o povoamento de Eucalyptus dunnii, a correção dos valores para o momento zero totalizaram R$ 5.767,75/ha, de custos e R$43.842,46/ha de receitas. Os valores calculados dos critérios de avaliação econômica foram um VPL de R$ 38.074,71/ha; Razão Beneficio/Custo de 7,60; TIR de 35,83% e um VPE de R$ 3.832,55/ha/ano. Para os dois projetos foi realizada análise de sensibilidade do VPL. Os resultados mostraram que ambos os projetos são economicamente viáveis.Palavras-chave: Análise comparativa; viabilidade econômica; custos; receitas. AbstractComparative analysis of the economic viability of Pinus taeda and Eucalyptus dunnii plantations in the south-center region of Parana State, Brazil. The objective of this research was to carry out a comparative analysis of economic viability of afforestation projects with Pinus taeda and Eucalyptus dunnii located in Prudentópolis County, State of Paraná, Brazil. In the economic analysis the criteria of Net Present Value (NPV), Benefit Cost rate (B/C), Internal Return Rate (IRR) and Periodic Equivalent Value (PEV) were used. The interest rate used was of 6.75% per the year. For the Pinus taeda plantations the data of rectified costs and income totalized R$ 4.344,71/ha and R$ 36.143,99/ha, respectively. The calculated values of the of economic evaluation criteria presented a NPV of R$ 31,799.28/ha, a Benefit Cost rate of 8,32, an IRR of 27.23% and a PEV of R$ 3.200,87/ha. For the Eucalyptus dunnii plantations the rectified values totalized R$5.767,75 and R$43.842,46/ha for the costs and income, respectively. The calculated values of the economic evaluation criteria showed a NPV of R$38.074,71/ha, a Benefit Cost rate of 7.60, an IRR of 35,83%, and a PEV of R$3.832,55/ha. A sensitivity analysis of the NPV for the two plantations was carried out. The results showed that both afforestation projects are economically viable.Keywords: Comparative analysis; economic viability; costs; income.

Objectives The aims of this study were to determine if stable chronic kidney disease (CKD) cats and uremic crisis cats have altered platelet function, and to determine the prevalence of positive fecal occult blood in CKD cats. Methods Platelet function in normal cats, clinically stable International Renal Interest Society (IRIS) stage 2–4 CKD cats and CKD cats experiencing a uremic crisis were evaluated using impedance aggregometry. Area under the curve (AUC) at 6 mins was calculated for saline, adenosine diphosphate (AUCADP) and arachidonic acid (AUCASPI). The AUC in addition to hematocrit, platelet count and mean platelet volume (MPV) were compared between groups using the Kruskal–Wallis test followed by Dunn’s post-hoc analysis. Guaiac fecal occult blood tests were performed on fecal samples and results were compared between groups using a χ2 for trend test. Results AUCADP ( P = 0.04) and AUCASPI ( P = 0.05) were significantly higher in uremic crisis cats compared with normal cats at 6 mins. Hematocrit was significantly higher in normal cats when compared with IRIS stage 3 and 4 ( P = 0.002) and uremic crisis ( P = 0.0008) cats, with no difference among groups for platelet count or MPV. The proportion of cats with positive fecal occult blood samples was significantly different between groups ( P = 0.0017); 50% uremic crisis cats, 33% IRIS stage 3 and 4 cats, and 10% IRIS stage 2 cats were positive, while no normal cats were positive. The proportion of cats with platelet clumping was significantly different between groups ( P = 0.03). Conclusions and relevance Platelet hyper-reactivity may be occurring in CKD cats experiencing a uremic crisis. The etiology of positive fecal occult blood samples in CKD cats is unclear and did not appear to be related to decreased platelet function as measured in this study and requires further investigation.

There is a collection of plain and decorated ceramic sherds in the Gregg County Historical Museum from a feature, described as either a fire pit or a hearth, excavated by Buddy Calvin Jones in March 1956 at the Cherokee Lake site (41RK132) on Toawichi Creek in northern Rusk County, Texas. This assemblage is discussed in this article. The Cherokee Lake site is best known for its early 18th century Nadaco Caddo component, but it also has a Middle Caddo period (ca. A.D. 1200–1400) component. In Jones’ discussion of work he conducted at the Cherokee Lake site, he mentions the excavation of an Historic Caddo burial as well as a large “refuse pit” of prehistoric age, both in Area A of the site. The excavation of a fire pit or hearth in any area at the site is not mentioned by Jones, but it seems likely that the “fire pit/hearth” may be the same feature as the aforementioned refuse pit. In any case, this “fire pit/hearth” feature at the Cherokee Lake site contained a considerable number of plain and decorated ceramic sherds, as did the “refuse pit.” According to Jones, the refuse pit had “Hickory Engraved, Dunkin Incised, variant types, unidentified types of punctated and incised wares,” as well as a small Bullard Brushed jar, a fragment of a second Bullard Brushed jar, both from the upper part of the pit, and fragments of a plain bowl from the floor of the pit.

The Cherokee Lake site (41RK132), also called the Tiawichi Creek Burial site, was discovered by Buddy Calvin Jones in 1956, on a terrace area along Tiawichi Creek at its confluence with Mill Creek, inundated by the construction of Lake Cherokee in 1947, that had been graded for the construction of fish hatcheries there. Tiawichi Creek is a tributary stream in the mid–Sabine River basin. Jones identified a single burial and a large storage pit in Area A at the southern end of the terrace, where there was a shallow (0–30 cm bs) midden deposit. The burial in Area A is an Historic Nadaco Caddo grave that probably dates to the early 18th century based on the recovery of 15 blue glass beads. This strand of beads was placed near the legs of the deceased individual. The Caddo person had been placed in an extended supine position in a pit that was 1.83 m long and 0.76 cm in width, with the head facing towards the west. The estimated depth of the grave was 0.76 m, and its fill was a dark charcoal–stained midden. In addition to the strand of glass beads, three ceramic vessels had been placed as funerary offerings in the grave along with a Fresno arrow point by the upper left leg. One Simms Engraved vessel was on the left side of the body, near the foot of the grave, while a second Simms Engraved vessel had been placed by the individual’s right foot, along with a Maydelle Incised jar. A plain clay elbow pipe had been placed inside the jar. A storage pit excavated by Jones in Area A at the Cherokee Lake site appears to have been primarily associated with a pre–A.D. 1200 Caddo occupation, based on the recovery of Hickory Engraved and Dunkin Incised pottery sherds, long–stemmed Red River clay pipe sherds, and Catahoula, Alba, and Bonham arrow points. This occupation probably created the midden deposits found in Area A. In this article, I discuss ceramic sherds collected by Jones from Area A at the Cherokee Lake site. Some of the sherds were surface collected in March 1956 from the midden deposits, but it is not clear if this ceramic sherd assemblage is part of the sample of 300 sherds discussed by Jones from an Area A surface collection. The present ceramic sherd assemblage is curated at the Gregg County Historical Museum (GCHM).

Abstract Aim: This work aimed to evaluate a pre/post-reform pilot study from 2015 to 2018 in a rural county of Zhejiang Province, China to realign the provider payment system for primary health care (PHC). Methods: Data were extracted from the National Health Financial Annual Reports for the 21 township health centers (THCs) in Shengzhou County. An information system was designed for the reform. Differences among independent groups were assessed using Kruskal–Wallis H-test. Dunn’s post hoc test was used for multiple comparisons. Differences between paired groups were tested by Wilcoxon signed-rank test. Two-tailed P < 0.05 indicated statistical significance. Data were processed and analyzed using R 3.6.1 for Windows. Findings: First, payments to THCs shifted from a “soft budget” to a mixed system of line-item input-based and categorized output-based payments, accounting for 17.54% and 82.46%, respectively, of total revenue in 2017. Second, providers were more motivated to deliver services after the reform; total volumes increased by 27.80%, 19.22%, and 30.31% for inpatient visits, outpatient visits, and the National Essential Public Health Services Package (NEPHSP), respectively. Third, NEPHSP payments were shifted from capitation to resource-based relative value scale (RBRVS) payments, resulting in a change in the NEPHSP subsidy from 36.41 to 67.35 per capita among the 21 THCs in 2017. Fourth, incentive merit pay to primary health physicians accounted for 38.40% of total salary, and the average salary increased by 32.74%, with a 32.45% increase in working intensity. A small proportion of penalties for unqualified products and pay-for-performance rewards were blended with the payments. The reform should be modified to motivate providers in remote areas. Conclusion: In the context of a profit-driven, hospital-centered system, add-on payments – including categorized output-based payments to THCs and incentive merit pay to primary care physicians (PCPs) – are probably worth pursuing to achieve more active and output/outcome-based PHC in China.

Abstract Worldwide, shorebird populations are declining. Our objectives were to examine abundance trends of shorebirds regularly wintering at Tomales Bay, Marin County, California, accounting for the local effects of rainfall, raptors, and the restoration of part of the bay to tidal wetlands. From November 1989 to February 2019, we conducted 177 comprehensive winter shorebird surveys of Tomales Bay; we averaged 5.7 ± 0.9 (mean ± SD) winter surveys per year. In 30 yr, we counted 1,215,821 shorebirds of 31 species. We used generalized linear models and multi-model inference to evaluate trends in shorebird abundance while accounting for local sources of variation. We conducted separate analyses for 14 species seen in at least 20 of the 30 yr of monitoring and for all shorebird species combined. During the study, the abundance of all species combined declined 66% (52% in the North Bay and 81% in the South Bay) with the most rapid decline in the first 10 yr of monitoring. Of 13 species for which year was in the top model, 10 species decreased in abundance and 3 species increased. Dunlin and Western Sandpiper accounted for the greatest losses in total numbers. The best-supported models to estimate trends in shorebirds included predictors for year and North Bay vs. South Bay. Of the local variables we considered, rainfall was included in 10 of the 15 best-supported models (including all species combined), negatively affecting the numbers of all species except Willets. The wetland restoration project was included in 5 top models, with a short-term positive impact. Raptor abundance was included in 3 top models with mixed results. Our results show that effective conservation and management of local shorebird populations must be linked with regional/global efforts if we are to reverse negative shorebird trends.

Abstract Objectives The aim of this study was to evaluate the microbiological and mechanical properties of glass ionomer cement (GIC) modified by chlorhexidine (CLX) for the purpose of cementing bands to the teeth of orthodontic patients. Materials and Methods Ten patients, between the ages of 19 and 33 years, in the initial stage of orthodontic treatment, were randomly designated to two groups using the split-mouth design (n = 10). One group (GICEX) had bands cemented with GIC modified by CLX and a Control group (GIC), evaluated at time intervals before (T0), 3 months (T3), and 6 months (T6) after cementation. Total microbiological counts were performed, and color stability of tooth enamel, salivary pH, and the adhesive remnant index (ARI) were evaluated. Statistical Analysis The Friedman and Dunn’s tests, Mann–Whitney, one-way analysis of variance, and Tukey, and paired and non-paired t-tests (p< 0.05) were used. Results In T3, there was evidence of significant reduction in the quantity of colony forming unit (CFU) in GICEX group in comparison with the Control (p = 0.041). In T6, the quantity of CFU was similar to the quantity in T3 and significantly different to control (p = 0.045); Control group demonstrated a similar quantity of CFU between the experimental time intervals (p = 0.066). Salivary pH demonstrated significant difference only between the time intervals T0 and T6 (p = 0.022). The tooth enamel color (p = 0.366) and ARI (p = 0.343) values demonstrated no significant changes. Conclusion The incorporation of CLX into GIC demonstrated effective antibacterial action, allowed a good bond of the cement to the enamel, a high rate of survival of the bands, did not change the color of the tooth enamel, and maintained the salivary pH at physiological levels.

In the mid-1950s, Sam Whiteside conducted excavations at the Henry Chapman site, his site P-5 (41SM56), on Prairie Creek in eastern Smith County, Texas, some 18 miles east of Tyler, Texas. Mr. Whiteside was an amateur archaeologist who discovered and explored numerous sites up and down Prairie Creek as well as other important sites in Smith and adjoining counties. The Chapman site was one of the first sites to be investigated by Mr. Whiteside, and the major part of the work took place there in 1957 and 1958. In August 1957, the site was visited by Edward B. Jelks and Leroy Johnson, who viewed the excavations and examined artifacts collected from there. Mr. Jelks, in notes on record at the Texas Archeological Research Laboratory (TARL) at The University of Texas in Austin, Texas, on August 21, 1958, indicated after observing the artifacts from the Henry Chapman site that the ceramics indicated an Alto focus occupation. He recognized Hickory Engraved and Holly Fine Engraved wares as well as Dunkin Incised and possible Pennington Punctated-Incised sherds. He mentioned that no Crockett Curvilinear Incised or Weches Fingernail Impressed sherds were present (two common types present at the Alto focus type site, the George C. Davis site [41CE19]). E. Mott Davis also visited the site in late 1957, and in February 1959, Davis, Lathel F. Duffield, and William A. Davis collected skeletal material from the site. In a June 15, 1958, newsletter from the East Texas Archeological Society (ETAS), Mr. Whiteside described excavations at the Henry Chapman site that had revealed refuse pits, post holes, and an abundance of pottery sherds indicative of an Alto focus occupation. In the summer of 1983, Mr. Whiteside visited the University of Texas Field School at the George C. Davis site, where he loaned some of his notes and collections from the Chapman site for recording purposes (these are on file at TARL). After Mr. Whiteside’s death, his family graciously allowed me access to his notes and artifacts. Not all of the artifacts have survived, having been stored in paper bags and subjected to several moves, but thanks to Mr. Whiteside’s writing lot numbers on artifacts and listing them in a journal, a majority of them have survived, and thus are suitable for study. Although 50 years have passed since Mr. Whiteside’s work at the Henry Chapman site, it is my intent to now make that work public.

Background: Chronic kidney disease (CKD) affects both dogs and cats, mainly elderly animals, due to tubulointerstitial inflammation associated with the increase of fibrosis through the excess deposition of extracellular matrix (ECM) which leads to decrease glomerular filtration. Many different underlying renal diseases can affect the kidneys of dogs such as congenital or acquired in origin. Therefore, the main objective of this transversal study was to evaluate the epidemiology through clinical and laboratory evaluation of 225 client-owned dogs with CKD.Materials, Methods & Results: Complete blood count (CBC), urinalysis, and biochemical profile were retrospectively selected and evaluated from 225 client-owned dogs with CKD of both sexes, different ages, and breeds from the patient population of the Nephrology and Urology Small Animal Service of the Teaching Hospital of the School of Veterinary Medicine and Animal Science - São Paulo State University from 2011 to 2017. All dogs were divided in groups according to the International Renal Interest Society (IRIS) CKD grading and statistical analysis was performed according to Kruskal-Wallis non-parametric test complemented with Dunn's multiple comparisons test, and analysis of variance for the model with a factor complemented with the test of multiple comparisons of Tukey. In this retrospective study, we observed that most dogs in all groups were elderly (≥ 9 years old). CBC demonstrated lower RBC’s (P < 0.005), hemoglobin (P < 0.001), hematocrit (Ht%) [P < 0.001] at the highest stage of the disease. However, urinary specific gravity (USG) did not demonstrate significant differences between the disease stages, but urinary protein: creatinine ratio (UPC) was statistically different (P < 0.01) between IRIS-CKD stages 1 and 4. Furthermore, serum phosphate concentrations demonstrated significantly higher levels in dogs at IRI-CKD stage 4 compared with IRIS-CKD stage 3 (P < 0.001).Discussion: The analysis of 225 dogs with CKD showed that 130 animals were elderly, older than 9 years, and according to previous studies, 15% of dogs over 10 years of age are diagnosed of CKD, presenting significant morbidity and mortality. Laboratory findings such as the presence of non-regenerative anemia is expected in dogs with CKD. In our study, the degree of anemia corresponded with the stage of the disease, similarly to serum creatinine concentrations. Another important laboratory finding in diagnosing CKD is the early detection of the kidney's abilities in concentrating its tubular filtrate. In this retrospective study, isosthenuria was not significant due to all dogs presented CKD as criteria of inclusion, especially those without azotemia, although, proteinuria was reported in 90% of the population investigated. Electrolyte imbalances are also expected in CKD. However, despite serum sodium, potassium, and total calcium did not demonstrate significant results, serum phosphate had its significance between IRIS-CKD stage 3 and stage 4. Hence, despite the age factor of most dogs in all groups, with the association of laboratory results such as serum creatinine, serum phosphorus, ionized calcium, erythrogram, isosthenuria, SBP, and the degree of proteinuria, it was possible to perform early diagnosis of CKD even in dogs with IRIS-CKD Stage 1 in a stable and hydrated patient. With the proper diagnostic, staging and substaging according to IRIS guidelines, these parameters can be monitored, predicting longevity and good quality of life, or progression of the disease with a more reserved prognosis.

Neither mere flesh nor mere thing, the yellow woman, straddling the person-thing divide, applies tremendous pressures on politically treasured notions of agency, feminist enfleshment, and human ontology. — Anne Anlin Cheng, OrnamentalismIn this (apparently) very versatile piece of clothing, she [Michelle Zauner] smokes, sings karaoke, rides motorcycles, plays a killer guitar solo … and much more. Is there anything you can’t do in a hanbok?— Li-Wei Chu, commentary, From the Intercom IntroductionAnne Anlin Cheng describes the anomaly of being “the yellow woman”, women of Asian descent in Western contexts, by underlining the haunting effects of this artificial identity on multiple politically valent forms, especially through Asian women’s conceived ambivalent relations to subject- and object-hood. Due to the entangled constructiveness conjoining Asiatic identities with objects, things, and ornaments, Cheng calls for new ways to “accommodate the deeper, stranger, more intricate, and more ineffable (con)fusion between thingness and personness instantiated by Asiatic femininity and its unpredictable object life” (14). Following this call, this essay articulates a creative combination of José Esteban Muñoz’s disidentification and Avery Gordon’s haunting theory to account for some hauntingly disidentificatory ways that the performance of diaspora sensibilities reimagines Asian American life and femininity.This essay considers “Everybody Wants to Love You” (2016) (EWLY), the music video of Michelle Zauner’s solo musical project Japanese Breakfast, as a ghostly performance, which features a celebration of the Korean culture and identity of Zauner (Song). I analyse it as a site for identifying the confrontational moments and haunting effects of the diaspora sensibilities performed by Zauner who is in fact Jewish-Korean-American. Directed by Zauner and Adam Kolodny, the music video of EWLY features the persona that I call the Korean woman orchestrated by Zauner, singing in a restroom cubicle, eating a Dunkin Donuts sandwich, shotgunning a beer, shredding a Fender electric guitar on the hood of a truck, riding a motorcycle with her queer lover, and partying with a crowd all in the traditional Korean attire hanbok that used to belong to her late mother. The story ends with Zauner waking up on a bench with a hangover and fleeing from the scene, conjuring up a journey of self-discovery, self-healing, and self-liberation through multiple sites and scenes of everyday life.What I call a ghostly performance is concerned with Avery Gordon’s creative intervention of haunting as a method of social analysis to study the intricate lingering impact of ghostly matters from the past on the present. Jacques Derrida develops hauntology to describe how Marxism continues to haunt Western societies even after its so-called failure. It refers to a status that something is neither present nor absent. Gordon develops haunting as a way of knowing and a method of knowledge production, “forcing a confrontation, forking the future and the past” (xvii). A ghostly performance is thus where ghostly matters are mobilised in “confrontational moments”:when things are not in their assigned places, when the cracks and rigging are exposed, when the people who are meant to be invisible show up without any sign of leaving, when disturbed feelings cannot be put away, when something else, something different from before, seems like it must be done. (xvi)The interstitiality that transgresses and reconfigures the geographical and temporal borders of nation, culture, and Eurocentric discourses of progression is important for understanding the diverse experiences of diaspora sensibilities as critical double consciousness (Dayal 48, 53). As Gordon suggests, confrontational moments force us to confront and expose the interstitial state of objects, subjects, feelings, and conditions. Hence, to understand this study identifies the confrontational moments in Zauner’s performance as a method to identify and deconstruct the triggering moments of diaspora sensibilities.While deconstructing the ghostly performances of diaspora sensibilities, the essay also adopts an object-oriented approach to serve as a focused entry point. Not only does this approach designate a more focused scope with regard to applying Gordon’s hauntology and Muñoz’s disidentification theory, it also taps into a less attended territory of object theories such as Graham Harman’s and Ian Bogost’s object-oriented ontology due to the overlooking of the relationship between objects and racialisation that is much explored in Asian American and critical race and ethnic studies (Shomura). Moreover, while diaspora as, or not as, an object of study has been a contested topic (e.g., Axel; Cho), the objects of diaspora have been less studied.This essay elaborates on two ghostly matters: the hanbok and the manicured nails. It uncovers two haunting effects throughout the analysis: the conjuring-up of the Korean diaspora and the troubling of everyday post-racial America. By defying the objectification of Asian bodies with objects of diaspora and refusing to assimilate into the American nightlife, Zauner’s Korean woman persona haunts a multiculturalist post-racial America that fails to recognise the specificities and historicity of Korean America and performs an alternative reality. Disidentificatory ghostly performance therefore, I suggest, thrives on confrontations between the past and the present while gesturing toward the futurities of alternative Americas. Mobilising the critical lenses of disidentification and ghostly performance, finally, I aver that disidentificatory ghostly performances have great potential for envisioning a better politics of performing and representing Asian bodies through the ghostly play of haunting objects/ghostly matters.The Embodied (Objects) and the Disembodied (Ghosts) of DisidentificationThe sonic-visual lifeworld constructed in the music video of EWLY is, first of all, a cultural public sphere, through which social norms are contested, reimagined, and reconfigured. A cultural public sphere reveals the imbricated relations between the political, the public, and the personal as contested through affective (aesthetic and emotional) communications (McGuigan 15). Considering the sonic-visual landscape as a cultural public sphere foregrounds two dimensions of Gordon’s hauntology theory: the psychological and the sociopolitical states. The emphasis on its affective communicative capacities enables the psychological reach of a cultural production. Meanwhile, the multilayered articulation of the political, the public, and the personal shows the inner-network of acts of haunting even when they happen chiefly on the sociopolitical level. What is crucial about cultural public spheres for minoritarian subjects is the creative space offered for negotiating one’s position in capacious and flexible ways that non-cultural publics may not allow. One of the ways is through imagination and disputation (McGuigan 16). The idea that imagination and disputation may cause a temporal and spatial disjunction with the present is important for Muñoz’s theorisation of disidentification. With such disjunction, Muñoz believes, queer of colour performances create future-oriented visions and coterminous temporality of the present and the future. These future-oriented visions and the coterminous temporality can be thought through disidentifications, which Muñoz identifies asa performative mode of tactical recognition that various minoritarian subjects employ in an effort to resist the oppressive and normalizing discourse of dominant ideology. Disidentification resists the interpellating call of ideology that fixes a subject within the state power apparatus. It is a reformatting of self within the social. It is a third term that resists the binary of identification and counteridentification. (97)Disidentification offers a method to identify specific moments of imagination and disputation and moments of temporal and spatial disjunction. The most distinct example of the co-nature of imagination and disputation residing in the EWLY lifeworld is the persona of the Korean woman orchestrated by Zauner, as she intrudes into the everyday field of American life in a hanbok, such as a bar, a basketball court, and a convenience store. Gordon would call these moments “confrontational moments” (xvi). When performers don’t perform in ways they are supposed to perform, when they don’t operate objects in ways they are supposed to operate, when they don’t mobilise feelings in ways they are supposed to feel, they resist and disidentify with “the oppressive and normalizing discourse of dominant ideology” (Muñoz 97).In addition to Muñoz’s disidentification and Gordon’s confrontational moments, I adopt an object-oriented approach to guide my analysis of disidentificatory ghostly performances. Object theory departs from objects and matters to rediscover identity and experience. My object-oriented approach follows new materialism more closely than object-oriented ontology because it is less about debating the ontology of Asian American experiences through the lens of objects. Instead, it is more about how re-orienting our attention towards the formation and operation of objecthood reveals and reconfigures the vexed articulation between Asian American experiences and racialised objectification. To this end, my oriented-object approach aligns particularly well with politically engaged frameworks such as Jane Bennett’s vital materialism and Eunjung Kim’s ethics of objects.Taking an object-oriented approach in inquiring Asian American identities could be paradoxically intervening because “Asian Americans have been excluded, exploited, and treated as capital because they have been more closely associated to nonhuman objects than to human subjects” (Shomura). Furthermore, this objectification is doubly performed onto the bodies of Asian American women due to the Orientalist conflations of Asia as feminine (Huang 187). Therefore, applying object theory in the case of EWLY requires special attention to the interplay between subject- and object-hood and the line between objecthood and objectification. To avoid the risk of objectification when exploring the objecthood of ghostly matters, I caution against an objects-define-subjects chain of signification and instead suggest a subjects-operate-objects route of inquiry by attending to both the haunting effects of objects and how subjects mobilise such haunting effects in their performance. From a new materialist perspective, it is also important to disassociate problems of objectification from exploration of objecthood (Kim) while excavating the world-making abilities of objects (Bennett). For diasporic peoples, it means to see objects as affective and nostalgic vessels, such as toys, food, family photos, attire, and personal items (e.g., Oum), where traumas of displacement can be stored and rehearsed (Turan 54).What is revealing from a racialised subject-object relationship is what Christopher Bush calls “the ethnicity of things”: things can have ethnicity, an identification that hinges on the articulation that “thingliness can be constituted in ways analogous and related to structures of racialization” (85). This object-oriented approach to inquiry can expose the artificial nature of the affinity between Asian bodies and certain objects, behind which is a confession of naturalised racial order of signification. One way to disrupt this chain of signification is to excavate the haunting objects that disidentify with the norms of the present, that conjure up what the present wants to be done. This “something-to-be-done” characteristic is critical to acts of haunting (Gordon xvii). Such disruptive performances are what I term as “disidentificatory ghostly performances”, connecting the embodied objects with Gordon’s disembodied ghosts through the lens of Muñoz’s disidentificatory reading with a two-fold impact: first exposing such artificial affinity and then suggesting alternative ways of knowing.In what follows, I expand upon two haunting objects/ghostly matters: the manicured nails and the hanbok. I contend that Zauner operates these haunting objects to embody the “something-to-be-done” characteristic by curating uncomfortable, confrontational moments, where the constituted affinity between Koreanness/Asianness and anomaly is instantiated and unsettled in multiple snippets of the mundane post-racial, post-globalisation world.What Can the Korean Woman (Not) Do with Those Nails and in That Hanbok?The hanbok that Zauner wears throughout the music video might be the single most powerful haunting object in the story. This authentic hanbok belonged to Zauner’s late mother who wore it to her wedding. Dressing in the hanbok while navigating the nightlife, it becomes a mediated, trans-temporal experience for both Zauner and her mother. A ghostly journey, you could call it. The hanbok then becomes a ghostly matter that haunts both the Orientalist gaze and the grieving Zauner. This journey could be seen as a process of dealing with personal loss, a process of “reckoning with ghosts” (Gordon 190). The division between the personal and the public, the historical and the present cease to exist as linear and clear-cut forces. The important role of ghosts in the performance are the efforts of historicising and specifying the persona of the Korean woman, which is a strategy for minoritarian performers to resist “the pull of reductive multicultural pluralism” (Muñoz 147). These ghostly matters haunt a pluralist multiculturalist post-racial America that refuses to see minor specificities and historicity.The Korean woman in an authentic hanbok, coupled with other objects of Korean roots, such as a traditional hairdo and seemingly exotic makeup, may invite the Orientalist gaze or the assumption that Zauner is self-commodifying and self-fetishising Korean culture, risking what Cheng calls “Oriental female objectification” operating through “the lenses of commodity and sexual fetishism” (14). However, she “fails” to do any of these. The ways Zauner acts in the hanbok manifests a self-negotiation with her Korean identity through disidentificatory sensibilities with racial fetishism. For example, in various scenes, the Korean woman appears to be drunk in a bar, gorging a sandwich, shotgunning a beer, smoking in a restroom cubicle, messing with strangers in a basketball court, rocking on a truck, and falling asleep on a bench. Some may describe what she does as abnormal, discomforting, and even disgusting in a traditional Korean garment which is usually worn on formal occasions. The Korean woman not only subverts her traditional Koreanness but also disidentifies with what the Asian fetish requires of Asian bodies: obedient, well-behaved model minority or the hypersexualised dragon lady (e.g., Hsu; Shimizu). Zauner’s performance foregrounds the sentimental, the messy, the frenetic, the aggressive, and the carnivalesque as essential qualities and sensibilities of the Korean woman. These rarely visible figurations of Asian femininities speak to the normalised public disappearance of “unwanted” sides of Asian bodies.Wavering public disappearance is a crucial haunting effect. The public disappearance is an “organized system of repression” (Gordon 72) and a “state-sponsored procedure for producing ghosts to harrowingly haunt a population into submission” (115). While the journey of EWLY evolves through ups and downs, the Korean woman does not maintain the ephemeral joy and takes offence at the people and surroundings now and then, such as at an arcade in the bar, at some basketball players, or at the audience or the camera operator. The performed disaffection and the conflicts substantiate a theory of “positive perversity” through which Asian American women claim the representation of their sexuality and desires (Shimizu), engendering a strong and visible presence of the ghostly matters operated by the Korean woman. This noticeable arrival of bodies disorients how things are arranged (Ahmed 163), revealing and disrupting whiteness, which functions as a habit and a background to actions (149). The confrontational performances of the encounters between Zauner and others cast a critique of the racial politics of disappearing by reifying disappearing into confrontational moments in the everyday post-racial world.What is also integral to Zauner’s antagonistic performance of wavering public disappearing and failure of “Oriental female objectification” is a punk strategy of negativity through an aesthetic of nihilism and a mediation of performing objects. For example, in addition to the traditional hairdo that goes with her makeup, Zauner also wears a nose ring; in addition to partying with a crowd, she adopts a moshing style of dancing, being carried over people’s heads in the hanbok. All these, in addition to her disaffectionate, aggressive, and impolite body language, express a negative punk aesthetics. Muñoz describes such a negative punk aesthetics as an energy that can be described “as chaotic, as creating a life without rhyme or reason, as quintessentially self-destructive” (97). What lies at the heart of this punk dystopia is the desire for “something else”, something “not the present time or place” (Muñoz). Through this desire for impossible time and place, utopian is reimagined, a race riot, in Mimi Thi Nguyen’s term.On the other hand, the manicured fingernails are also a major operating force, reminiscent of Korean American immigrant history along with the racialised labor relations that have marked Korean bodies as an alien anomaly (Liu). With “Japanese Breakfast” being written on the screen in neon pink with some dazzling effect, the music video begins in a warm tone. The story begins with Zauner selecting EWLY with her finger on a karaoke operation screen, the first of many shots on her carefully manicured nails, decorated with transparent nail extensions, sparkly ornaments, and hanging fine chains. These nails conjure up the nail salon business in the US that heavily depended on immigrant labor and Korean women immigrants have made significant economic contributions through the manicure business. In particular, differently from Los Angeles where nail salons have been predominantly Vietnamese and Chinese owned, Korean women immigrants in the 1980s were the first ones to open nail salons in New York City and led to the rapid growth of the business (Kang 51). The manicured nails first of all conjure up these recent histories associated with the nail salon business.Moreover, these fingernails haunt post-racial and post-globalisation America by revealing and subverting the invisible, normalised racial and ethnic nature of the labor and objects associated with fingernails cosmetic treatment. Ghostly matters inform “a method of knowledge production and a way of writing that could represent the damage and the haunting of the historical alternatives” (Gordon xvii). They function as a reminder of the damage that seems forgotten or normalised in modern societies and as an alternative embodiment of what modern societies could have become. In the universe of EWLY, the fingernails become a forceful ghostly matter by reminding us of the damage done onto Korean bodies by fixing them as service performers instead customers. The nail salon business as performed by immigrant labor has been a business of “buying and selling of deference and attentiveness”, where white customers come to exercise their privilege while not wanting anything associated with Koreaness or Otherness (Kang 134). However, as a haunting force, the fingernails subvert such labor relations by acting as a versatile agent operating varied objects, such as a karaoke machine, cigarettes, a sandwich, a Fender guitar, and a can of beer. Through such operating, an alternative labor relation is formed. This alternative is not entirely without roots. As promoted in Japanese Breakfast’s Instagram (@jbrekkie), Zauner’s look was styled by a nail artist who appears to be a white female, Celeste Marie Welch from the DnA Salon based in Philadelphia. This is a snippet of a field that is now a glocalised industry, where the racial and gender makeup is more diverse. It is increasingly easier to see non-Asian and non-female nail salon workers, among whom white nail salon workers outnumbered any other non-Asian racial/ethnic groups (Preeti et al. 23). EWLY’s alternative worldmaking is not only a mere reflection of the changing makeup of an industry but also calling out the societal tendency of forgetting histories. To be haunted, as Gordon explains, is to be “tied to historical and social effects” (190). The ghostly matters of the manicure industry haunt its workers, artists, consumers, and businesspeople of a past that prescribes racialised labor divisions, consumption relations, and the historical and social effects inflicted on the Othered bodies. Performing with the manicured nails, Zauner challenges now supposedly multicultural manicure culture by fusing oppositional, trans-temporal identities into the persona of the Korean woman. Not only does she conjure up the racialised labor relations as the child of a Korean mother, she also disidentifies with the worker identity of early Korean women immigrants as a consumer who receives service from an artist who would otherwise never perform such labor in the past.Conclusion: Toward a Disidentificatory Ghostly PerformanceThis essay suggests seeing the disidentificatory ghostly performance of the Korean woman as an artistic incarnation of her lived Othering experience, which Zauner may or may not navigate on an everyday basis. As Zauner lives through what looks like a typical Friday night in an American town, the journey represents an interrogation of the present and the past. When the ghostly matters move through public spaces – when she drinks in a bar, walks down the street, and parties with a crowd – the Korean woman neither conforms to what she is expected to do in a hanbok nor does she get fully assimilated into this American nightlife.Derrida avers that haunting, repression, and hegemony are structurally interlocked and that “haunting belongs to the structure of every hegemony” because “hegemony still organizes the repression” (46). This is why the creative capacity of disidentificatory performances is crucial for acts of haunting and for historically repressed groups of people. Conjoining the future-oriented performative mode of disidentification and the forking of the past and the present by ghostly performances, disidentificatory ghostly performances enable not only people of colour but also particularly diasporic populations of colour to challenge racial chains of signification and orchestrate future-oriented visions, where time is of the most compassion, at its utmost capacity.ReferencesAhmed, Sara. “A Phenomenology of Whiteness.” Feminist Theory 8.2 (2007): 149–168.Axel, Brian Keith. “Time and Threat: Questioning the Production of the Diaspora as an Object of Study.” History and Anthropology 9.4 (1996): 415–443.Bennett, Jane. Vibrant Matter: A Political Ecology of Things. Durham: Duke UP, 2010.Bogost, Ian. Alien Phenomenology, or, What It’s Like to Be a Thing. Minneapolis: U of Minnesota P, 2012.Bush, Christopher. “The Ethnicity of Things in America’s Lacquered Age.” Representations 99.1 (2007): 74–98. Cheng, Anne Anlin. Ornamentalism. New York: Oxford UP, 2019.Cho, Lily. “The Turn to Diaspora.” Topia: Canadian Journal of Cultural Studies 17 (2007): 11–30.Chu, Li-Wei. “MV Throwback: Japanese Breakfast – ‘Everybody Wants to Love You’.” From the Intercom, 23 Aug. 2018. <https://fromtheintercom.com/mv-throwback-japanese-breakfast-everybody-wants-to-love-you/>.Dayal, Samir. “Diaspora and Double Consciousness.” The Journal of the Midwest Modern Language Association 29.1 (1996): 46–62. Derrida, Jacques. Specters of Marx: The State of the Debt, the Work of Mourning, and the New International. London: Routledge, 1994.Gordon, Avery. Ghostly Matters: Haunting and the Sociological Imagination. Minneapolis: U of Minnesota P, 2008. Harman, Graham. Prince of Networks: Bruno Latour and Metaphysics. Melbourne: re.press, 2009.Hsu, Madeline Yuan-yin. The Good Immigrants: How the Yellow Peril Became the Model Minority. Princeton, New Jersey: Princeton UP, 2015.Huang, Vivian L. “Inscrutably, Actually: Hospitality, Parasitism, and the Silent Work of Yoko Ono and Laurel Nakadate.” Women & Performance: A Journal of Feminist Theory 28.3 (2018): 187–203.Japanese Breakfast. “Japanese Breakfast – Everybody Wants to Love You (Official Video).” YouTube, 20 Sep. 2016. <http://www.youtube.com/watch?v=KNT7wuqaykc>.Kang, Miliann. The Managed Hand: Race, Gender, and the Body in Beauty Service Work. Berkeley: U of California P, 2010.Kim, E. “Unbecoming Human: An Ethics of Objects.” GLQ: A Journal of Lesbian and Gay Studies 21.2–3 (2015): 295–320.Liu, Runchao. “Retro Objects, Alien Objects.” In Media Res. 12 Dec. 2018. <http://mediacommons.org/imr/content/retro-objects-alien-objects>.McGuigan, Jim. Cultural Analysis. Los Angeles, CA: SAGE, 2010.Muñoz, José Esteban. Disidentifications: Queers of Color and the Performance of Politics. Minneapolis: U of Minnesota P, 1999.———. “‘Gimme Gimme This ... Gimme Gimme That’: Annihilation and Innovation in the Punk Rock Commons.” Social Text 31.3 (2013): 95–110.Nguyen, Mimi Thi. “Riot Grrrl, Race, and Revival.” Women & Performance: A Journal of Feminist Theory 22.2–3 (2012): 173–196. Oum, Young Rae. “Authenticity and Representation: Cuisines and Identities in Korean-American Diaspora.” Postcolonial Studies 8.1 (2005): 109–125.Sharma, Preeti, et al. “Nail File: A Study of Nail Salon Workers and Industry in the United States.” UCLA Labor Center and California Healthy Nail Salon Collaborative, 2018.Shimizu, Celine Parrenas. The Hypersexuality of Race: Performing Asian/American Women on Screen and Scene. Durham, NC: Duke UP, 2007.Shomura, Chad. “Object Theory and Asian American Literature.” Oxford Research Encyclopedia of Literature. New York: Oxford UP, 2020.Song, Sandra. “Japanese Breakfast Is the Korean-American Songwriter Empowering Everyone to Overcome.” Teen Vogue. 14 July 2017. <http://www.teenvogue.com/story/japanese-breakfast-songwriter-empowering-everyone-overcome>.Turan, Zeynep. “Material Objects as Facilitating Environments: The Palestinian Diaspora.” Home Cultures 7.1 (2010): 43–56.