Climate change in the past has led to significant changes in species' distributions. However, how individual species respond to climate change depends largely on their adaptations and environmental ...tolerances. In the Quaternary, temperate-adapted taxa are in general confined to refugia during glacials while cold-adapted taxa are in refugia during interglacials. In the Northern Hemisphere, evidence appears to be mounting that in addition to traditional southern refugia for temperate species, cryptic refugia existed in the North during glacials. Equivalent cryptic southern refugia, to the south of the more conventional high-latitude polar refugia, exist in montane areas during periods of warm climate, such as the current interglacial. There is also a continental/oceanic longitudinal gradient, which should be included in a more complete consideration of the interaction between species ranges and climates. Overall, it seems clear that there is large variation in both the size of refugia and the duration during which species are confined to them. This has implications for the role of refugia in the evolution of species and their genetic diversity.
Background Peritoneal dissemination of abdominal malignancy (carcinomatosis) has a clinical course marked by bowel obstruction and death; it traditionally does not respond well to systemic therapy ...and has been approached with nihilism. To treat carcinomatosis, we use cytoreductive surgery (CS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Methods A prospective database of patients has been maintained since 1992. Patients with biopsy-proven peritoneal surface disease were uniformly evaluated for, and treated with, CS and HIPEC. Patient demographics, performance status (Eastern Cooperative Oncology Group), resection status, and peritoneal surface disease were classified according to primary site. Univariate and multivariate analyses were performed. The experience was divided into quintiles and outcomes compared. Results Between 1991 and 2013, a total of 1,000 patients underwent 1,097 HIPEC procedures. Mean age was 52.9 years and 53.1% were female. Primary tumor site was appendix in 472 (47.2%), colorectal in 248 (24.8%), mesothelioma in 72 (7.2%), ovary in 69 (6.9%), gastric in 46 (4.6%), and other in 97 (9.7%). Thirty-day mortality rate was 3.8% and median hospital stay was 8 days. Median overall survival was 29.4 months, with a 5-year survival rate of 32.5%. Factors correlating with improved survival on univariate and multivariate analysis (p ≤ 0.0001 for each) were preoperative performance status, primary tumor type, resection status, and experience quintile (p = 0.04). For the 5 quintiles, the 1- and 5-year survival rates, as well as the complete cytoreduction score (R0, R1, R2a) have increased, and transfusions, stoma creations, and complications have all decreased significantly (p < .001 for all). Conclusions This largest reported single-center experience with CS and HIPEC demonstrates that prognostic factors include primary site, performance status, completeness of resection, and institutional experience. The data show that outcomes have improved over time, with more complete cytoreduction and fewer serious complications, transfusions, and stomas. This was due to better patient selection and increased operative experience. Cytoreductive surgery with HIPEC represents a substantial improvement in outcomes compared with historical series, and shows that meaningful long-term survival is possible for selected carcinomatosis patients. Multi-institutional cooperative trials are needed to refine the use of CS and HIPEC.
Two decades ago a class of ion channels, hitherto unsuspected, was discovered. In mammals these Transient Receptor Potential channels (TRPs) have not only expanded in number (to 26 functional ...channels) but also expanded the view of our interface with the physical and chemical environment. Some are heat and cold sensors while others monitor endogenous and/or exogenous chemical signals. Some TRP channels monitor osmotic potential, and others measure cell movement, stretching, and fluid flow. Many TRP channels are major players in nociception and integration of pain signals. One member of the vanilloid sub-family of channels is TRPV6. This channel is highly selective for divalent cations, particularly calcium, and plays a part in general whole-body calcium homeostasis, capturing calcium in the gut from the diet. TRPV6 can be greatly elevated in a number of cancers deriving from epithelia and considerable study has been made of its role in the cancer phenotype where calcium control is dysfunctional. This review compiles and updates recent published work on TRPV6 as a promising drug target in a number of cancers including those afflicting breast, ovarian, prostate and pancreatic tissues.
This paper considers the hotly debated issue of whether one should grant moral and legal personhood to intelligent robots once they have achieved a certain standard of sophistication based on such ...criteria as rationality, autonomy, and social relations. The starting point for the analysis is the European Parliament’s resolution on Civil Law Rules on Robotics (2017) and its recommendation that robots be granted legal status and electronic personhood. The resolution is discussed against the background of the so-called Robotics Open Letter, which is critical of the Civil Law Rules on Robotics (and particularly of §59 f.). The paper reviews issues related to the moral and legal status of intelligent robots and the notion of legal personhood, including an analysis of the relation between moral and legal personhood in general and with respect to robots in particular. It examines two analogies, to corporations (which are treated as legal persons) and animals, that have been proposed to elucidate the moral and legal status of robots. The paper concludes that one should not ascribe moral and legal personhood to currently existing robots, given their technological limitations, but that one should do so once they have achieved a certain level at which they would become comparable to human beings.
Context .- As our understanding of genomic alterations underlying solid tumor malignancies continues to evolve, molecular testing of tumor samples is increasingly used to guide therapeutic ...management. Next-generation sequencing (NGS) provides a novel platform for the simultaneous screening of multiple genes using small amounts of DNA. Several recent studies have described NGS mutational analysis using cytologic specimens. The cytopathologist's role in specimen assessment and triaging is critical to effectively implementing NGS in routine cytology practice. Objectives .- To review the NGS experience and a variety of preanalytic factors that affect NGS success rates of cytologic specimens at our institution. Data Sources .- To evaluate cytology specimen adequacy rates for NGS, we reviewed a 14-month period of image-guided fine-needle aspiration and core needle biopsies, used for testing. In addition, we reviewed data from our previously published studies to evaluate preanalytic factors affecting NGS success in these specimens. Conclusions .- Identifying factors that affect NGS success rates in cytology specimens is crucial for a better understanding of specimen adequacy requirements and for proper use of limited-volume tissue samples. In our practice, which uses direct smears as well as cell block sections, NGS success rates in core needle biopsy and fine-needle aspiration samples are comparable. The chance of successful testing is further increased by procuring concurrent fine-needle aspiration and core needle biopsy samples. The type of glass slides used for direct smears and the method of tissue extraction affect our DNA yield. Validating a DNA input for cytology samples that is lower than that recommended by the manufacturer has significantly increased our NGS success rate.
Moral expertise revisited Gordon, John‐Stewart
Bioethics,
July 2023, 2023-07-00, 20230701, Letnik:
37, Številka:
6
Journal Article
Recenzirano
In recent years, there has been a lively (bio‐)ethical debate on the nature of moral expertise and the concept of moral experts. However, there is currently no common ground concerning most issues. ...Against this background, this paper has two main goals. First, in more general terms, it examines some of the problems concerning moral expertise and experts, with a special focus on moral advice and testimony. Second, it applies the results in the context of medical ethics, especially in the clinical setting. By situating the debate in the clinical setting, one arrives at some important conclusions to better understand the relevant concepts and vital problems in the general discussion on moral expertise and the requirements of who counts as a moral expert.
Pattern recognition receptors (PRRs) recognize danger signals such as PAMPs/MAMPs and DAMPs to initiate a protective immune response. TLRs, NLRs, CLRs, and RLRs are well-characterized PRRs of the ...host immune system. cGLRs have been recently identified as PRRs. In humans, the cGAS/STING signaling pathway is a part of cGLRs. cGAS recognizes cytosolic dsDNA as a PAMP or DAMP to initiate the STING-dependent immune response comprising type 1 IFN release, NF-κB activation, autophagy, and cellular senescence. The present article discusses the emergence of cGLRs as critical PRRs and how they regulate immune responses. We examined the role of cGAS/STING signaling, a well-studied cGLR system, in the activation of the immune system. The following sections discuss the role of cGAS/STING dysregulation in disease and how immune cross-talk with other PRRs maintains immune homeostasis. This understanding will lead to the design of better vaccines and immunotherapeutics for various diseases, including infections, autoimmunity, and cancers.
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