55 research outputs found
The Safety of EXPAREL ® (Bupivacaine Liposome Injectable Suspension) Administered by Peripheral Nerve Block in Rabbits and Dogs
A sustained-release DepoFoam injection formulation of bupivacaine (EXPAREL, 15 mg/mL) is currently being investigated for postsurgical analgesia via peripheral nerve block (PNB). Single-dose toxicology studies of EXPAREL (9, 18, and 30 mg/kg), bupivacaine solution (Bsol, 9 mg/kg), and saline injected around the brachial plexus nerve bundle were performed in rabbits and dogs. The endpoints included clinical pathology, pharmacokinetics, and histopathology evaluation on Day 3 and Day 15 (2/sex/group/period). EXPAREL resulted in a nearly 4-fold lower Cmax versus Bsol at the same dose. EXPAREL was well tolerated at doses up to 30 mg/kg. The only EXPAREL-related effect seen was minimal to mild granulomatous inflammation of adipose tissue around nerve roots (8 of 24 rabbits and 7 of 24 dogs) in the brachial plexus sites. The results indicate that EXPAREL was well tolerated in these models and did not produce nerve damage after PNB in rabbits and dogs
Safety Evaluation of EXPAREL (DepoFoam Bupivacaine) Administered by Repeated Subcutaneous Injection in Rabbits and Dogs: Species Comparison
EXPAREL (bupivacaine extended-release liposome injection), DepoFoam bupivacaine, is in development for prolonged postsurgical analgesia. Repeat-dose toxicity studies were conducted in rabbits and dogs to compare the potential local and systemic toxicities of EXPAREL and bupivacaine HCl (Bsol), and the reversibility of any effects. Dogs tolerated much larger doses than rabbits. EXPAREL-related minimal-to-moderate granulomatous inflammation was noted at the injection sites. In recovery animals, the granulomatous inflammation was observed less frequently and was characterized by an increased number of multinucleated giant cells. These effects were considered a normal response to liposomes and nonadverse. Rabbits are more sensitive than dogs. In rabbits, convulsions were noted with EXPAREL and more frequently with Bsol; a NOAEL was not identified. In dogs, EXPAREL was well tolerated (NOAEL > 30 mg/kg/dose). The cumulative exposure of EXPAREL in these studies is well in excess of the proposed maximum single-dose exposure that is intended in humans
Application benchmark results for Big Red, an IBM e1350 BladeCenter Cluster
The purpose of this report is to present the results of benchmark tests with Big Red, an IBM e1350 BladeCenter Cluster. This report is particularly focused on providing details of system architecture and test run results in detail to allow for analysis in other reports and comparison with other systems, rather than presenting such analysis here
Espectro de gotas de pulverização e controle da ferrugem-asiática-da-soja em cultivares com diferentes arquiteturas de planta
Finishing the euchromatic sequence of the human genome
The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead
Cross-Gendering the Racial Memory
When Ernest Gaines chooses a woman as the individual subject for collective memorialization and the ideal medium of racial memory in his 1971 novel, The Autobiography of Miss Jane Pittman, he participates in a significant but overlooked genre of black masculine discourse, the composition of black authorship as historical/national authority through the voice and viewpoint of a female protagonist. This cross-gendering of the racial imaginary, introjecting a male vision of racial collectivity and history through a female’s frame of reference, though not exactly a form of cross-dressing, can be usefully analyzed as such. Erecting a feminine monument to emblematize and materialize highly abstract notions like nationhood, justice, peace, warfare, virtue, democracy, pro/creativity, and truth has a long history in many cultures across the globe. It is a long-standing practice within many patriarchal cultures, in other words, to project highly abstract masculine visions of established power onto a female form, draped in feminine attire. Whether this occurs metaphorically, as in the case of gendering the nation-state as feminine (Britannia for the United Kingdom, Columbia for the United States, St. Joan for France, etc.), or through more literal iconography, such as the Statue of Liberty, the feminine form serves to purify, emblematize, and collectivize—and thus to transcendentalize—concepts of rightful dis/empowerment that are otherwise fraught with cultural-historical strife. The static nature of such imagery distances us from the contentiousness of the act of cross-gendering that occurs ideologically in the enunciation or re-erection of patriarchal power through an objectified, if celebrated, feminine icon.We can find evidence of this conventionally patriarchal kind of feminine iconography in black cultural practice. For instance, in black nationalist discourse of the 1960s and ’70s (whether in the Black Power movement in the United States or the post-colonial movements in the West Indies and Africa), there is a tendency to emblematize the rising black nation as a fecund black mother, frequently figured more transcendently as “Mother Africa” herself, even as the battle for and leadership of these emerging nations is assumed to be the purview of militant big men. Ironically, to index the greatness of the emerging nation, and the bigness of the male freedom fighters and founders, both figuratively and materially the female icon must be giganticized, making her a presence so massive as to become a queer she-male—masculine in size and intent, feminine in spirit and form. In European-American iconography, there is a drive to materialize this gigantic feminine figure not only by super-sizing her but also by casting her in the hardest stones—again the Statue of Liberty providing a perfect instance. Lacking the economic resources for such a luxury of patriarchal imagination, black nationalist practice most frequently resorts to more figurative embodiments of the gigantic feminine in art, poetry, song, and dance.Gaines’s gigantic female who voices and embodies black American epochal and epical history, Miss Jane Pittman, is cast as novel and film (1974) at the height of the black nationalist moment, when metaphorical she/males emblematizing the masculine heroism of black nation-building are proliferating all over the place in black popular culture. This paper analyzes Miss Jane Pittman in this historical context of the black nationalist gigantic female icon. I argue that while Gaines draws on this black nationalist image as context and subtext, he diverts attention away from this militant and often violent black nationalist iconography of cross-gendering to figure instead a strong, enduring black woman as a pacifying emblem of cross-racial American nation-building. Opting to follow the lead of other black male cross-gendering writers—most notably James Weldon Johnson, W. E. B. Du Bois, Walter White, and Wallace Thurman—Gaines erects Miss Jane as a she/male icon who prophesies the integrated, interracial, harmonious United States nation that emerges ironically out of black folk’s capacity to endure and transcend an entrenched history of state-endorsed racial violence and abjection. Gaines chooses a woman as his medium/subject both to envelope the image of the gigantic black feminine as black nationalist icon and to counter that image in favor of a conscientious black nation within a bloody white nation, the black (wo)man as the purifying conscience of the historically compromised American nation-state. On the one hand, Gaines’s iconography has the benefit of disturbing and subverting the normatively masculine stance of black nationalism by figuring a she/male whose cross-gendering is less aggressively patriarchal in size and intent, more ambivalently feminine in spirit and form. On the other hand, it has the effect of “softening” and thus blunting the militant agency of a defiant black collective conscience and consciousness
Preclinical Analyses Support Clinical Investigation of Combined PD-L1 Blockade and Anti-CD19 CAR T Cell Therapy for the Treatment of NHL
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