Tempest Technologies (United States)

Through an examination of his core doctrinal points, I argue that Shinran’s conception of Pure Land Buddhism (Jōdo Shinshū) should not be so readily dismissed as one that is only salvific in an otherworldly sense, with no relevance to contemporary, everyday life, nor should it be reduced to a purely ethnic form of Buddhism without any reference to its universal dimension. Through this analysis, we will find that Shinran’s adoption of a unique and honest evaluation of our inner lives through receiving the wisdom and compassion of Amida Buddha can offer people of today’s world a way to embrace a spirit of self-acceptance so that one can live with confidence, integrity, and a modest joy, despite the manifold shortcomings of the human condition. Through the radical transformation of one’s dissatisfaction and suffering, an uncontrived ethical impulse is able to emerge, accompanied by a keen awareness of deep empathy for others, leading to an existence informed by empathy instead of animosity.

<div>AbstractPurpose:<p>TPST-1120 is a first-in-class oral inhibitor of peroxisome proliferator-activated receptor α (PPARα), a fatty acid ligand-activated transcription factor that regulates genes involved in fatty acid oxidation, angiogenesis, and inflammation, and is a novel target for cancer therapy. TPST-1120 displayed antitumor activity in xenograft models and synergistic tumor reduction in syngeneic tumor models when combined with anti-PD-1 agents.</p>Experimental Design:<p>This phase I, open-label, dose-escalation study (NCT03829436) evaluated TPST-1120 as monotherapy in patients with advanced solid tumors and in combination with nivolumab in patients with renal cell carcinoma (RCC), cholangiocarcinoma (CCA), or hepatocellular carcinoma. Objectives included evaluation of safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity (RECIST v1.1).</p>Results:<p>A total of 39 patients enrolled with 38 treated (20 monotherapy, 18 combination; median 3 prior lines of therapy). The most common treatment-related adverse events (TRAE) were grade 1–2 nausea, fatigue, and diarrhea. No grade 4–5 TRAEs or dose-limiting toxicities were reported. In the monotherapy group, 53% (10/19) of evaluable patients had a best objective response of stable disease. In the combination group, 3 patients had partial responses, for an objective response rate of 20% (3/15) across all doses and 30% (3/10) at TPST-1120 ≥400 mg twice daily. Responses occurred in 2 patients with RCC, both of whom had previously progressed on anti-PD-1 therapy, and 1 patient with late-line CCA.</p>Conclusions:<p>TPST-1120 was well tolerated as monotherapy and in combination with nivolumab and the combination showed preliminary evidence of clinical activity in PD-1 inhibitor refractory and immune compromised cancers.</p>Significance:<p>TPST-1120 is a first-in-class oral inhibitor of PPARα, whose roles in metabolic and immune regulation are implicated in tumor proliferation/survival and inhibition of anticancer immunity. This first-in-human study of TPST-1120 alone and in combination with nivolumab supports proof-of-concept of PPARα inhibition as a target of therapeutic intervention in solid tumors.</p></div>

SOMMARIO: 1. La questione dell’aborto e la perdita di credibilità della Corte Suprema statunitense - 2. Una tempesta perfetta? - 3. La partita della fiducia.
 The case of abortion: a slippery slope for SCOTUS?
 ABSTRACT: The case of the right of abortion in the United States is going to represent much more than a mere legal question. The upcoming decision of the Supreme Court of the United States (SCOTUS) on the matter involves its own credibility as a third party institution in a check and balance system where the SCOTUS is increasingly perceived as a political player. In this paper the A. tries to explore why it is so.

The regulatory standards of the United States Food and Drug Administration (FDA) require substantial evidence of effectiveness from adequate and well-controlled trials that typically use a valid comparison to an internal concurrent control. However, when it is not feasible or ethical to use an internal control, particularly in rare disease populations, relying on external controls may be acceptable. To better understand the use of external controls to support product development and approval, we reviewed FDA regulatory approval decisions between 2000 and 2019 for drug and biologic products to identify pivotal studies that leveraged external controls, with a focus on select therapeutic areas. Forty-five approvals were identified where FDA accepted external control data in their benefit/risk assessment; they did so for many reasons including the rare nature of the disease, ethical concerns regarding use of a placebo or no-treatment arm, the seriousness of the condition, and the high unmet medical need. Retrospective natural history data, including retrospective reviews of patient records, was the most common source of external control (44%). Other types of external control were baseline control (33%); published data (11%); and data from a previous clinical study (11%). To gain further insights, a comprehensive evaluation of selected approvals utilizing different types of external control is provided to highlight the variety of approaches used by sponsors and the challenges encountered in supporting product development and FDA decision making; particularly, the value and use of retrospective natural history in the development of products for rare diseases. Education on the use of external controls based on FDA regulatory precedent will allow for continued use and broader application of innovative approaches to clinical trial design, while avoiding delays in product development for rare diseases. Learnings from this review also highlight the need to update regulatory guidance to acknowledge the utility of external controls, particularly retrospective natural history data.

ABSTRACT: Saroyan’s The Time of Your Life (1939) employs a similar dramatic pattern of social change used in Shakespeare’s The Tempest (1611). In Shakespeare, the pattern includes the isolation of a group of characters by washing them up onto the reformer’s island by a magical tempest arranged by the reformer Prospero. He thus severs the characters from their community, and separates them on the island to undergo different healing experiences before going back to their society. Saroyan adopts a comparable, though highly modified, pattern in his play. He mainly focuses on the efforts of a reformer, who tries to help a group of depressed characters who gather in a bar, which is similar to Prospero’s island, in order to escape the difficulties of the outside world. The bar is a haven of peace surrounded by the atrocities of the urban world. In both cases there is a devoted reformer, who dedicates himself to helping his subjects. The paper aims to study the similarities of the dramatic pattern, and shows that underlying these similarities, there are major differences that reflect the cultural divergence of the twentieth century culture from that of the Renaissance. The study means to illustrate that the alterations Saroyan rendered on Shakespeare’s model helps the reader understand the meaning and the age of the modern play and, simultaneously, sheds further light on the Shakespearean play and the Renaissance in general. RESUMEN: El Tiempo de Tu Vida de Saroyan (1939) emplea un patron dramatico similar de cambio social al usado en La Tempestad de Shakespeare (1611). En Shakespeare, el patron incluye el aislamiento de un grupo de personajes al hacerlos naufragar en la isla del reformador mediante una tempestad magica organizada por el reformador Prospero. De este modo, aisla a los personajes de su comunidad y los separa en la isla para experimentar diferentes experiencias de curacion antes de regresar a su sociedad. Saroyan adopta un patron comparable, aunque altamente modificado, en su obra. Se centra principalmente en los esfuerzos de un reformador que trata de ayudar a un grupo de personajes deprimidos que se reunen en un bar, que es similar a la isla de Prospero, para escapar de las dificultades del mundo exterior. El bar es un remanso de paz rodeado de las atrocidades del mundo urbano. En ambos casos hay un devoto reformador que se dedica a ayudar a sus subditos. El documento tiene como objetivo estudiar las similitudes del patron dramatico y muestra que, subyacentes a estas similitudes, existen diferencias importantes que reflejan la divergencia entre la cultura del siglo XX y la del Renacimiento. El estudio pretende ilustrar que las alteraciones que Saroyan presento en el modelo de Shakespeare ayudan al lector a comprender el significado y la epoca de la obra moderna y, al mismo tiempo, arroja mas luz sobre la obra de Shakespeare y el Renacimiento en general.

« Très illustre seigneur, nous voulons satisfaire à la requête que nous a faite le magnifique Cicco de la part de votre Excellence, à propos de ce qui est arrivé à Tempesta de Bobbio, qui fut familier d’armes de votre Seigneurie ; il nous demande de lui dire la pure et entière vérité de la chose. Nous déclarons donc que le magnifique comte Pietro Dal Verme, notre patron, a fait détenir ici, à Pavie, dans les mains du podestat de votre Seigneurie, ledit Tempesta ; puis, il chargea Matteo Da Mo...