Urothelial carcinoma (UC) of the lower urinary tract and prostatic carcinoma (PC) are aggressive genitourinary cancers in dogs, characterized by invasion to surrounding tissues and high metastatic ...potential. Current diagnosis of canine UC and PC requires histopathological examination of a biopsy. Such specimens require specialized medical equipment and are invasive procedures, limiting the availability of diagnosis by histopathology for many canine patients. Access to a non-invasive means to confirm diagnosis is currently an unmet need. Recently, the canine BRAF V595E mutation was detected in ~80% of canine UCs and PCs. In this study, we developed a droplet digital PCR (ddPCR) assay for detection of the canine BRAF V595E mutation in canine urogenital tumors. The assay was evaluated in DNA samples prepared from biopsy specimens of UC (n = 48) and PC (n = 27), as well and non-neoplastic bladder epithelium (n = 38). In addition the assay was assessed for use with DNA isolated from free catch urine samples derived from canine patients with UC (n = 23), PC (n = 3), as well as from dogs with cystitis and healthy controls (n = 37). In all cases the sensitivity to detect the mutant allele was compared with conventional Sanger sequencing. ddPCR had superior sensitivity for detection of the V595E mutation: 75% of UC, 85% of PC, and 0% of control samples were mutation positive, respectively, and the V595E mutation was detected at a level as low as just 1 in 10,000 alleles (~0.01%). Furthermore, the ddPCR assay identified the mutation in free catch urine samples from 83% of canine UC and PC patients, demonstrating its utility as a non-invasive means of diagnosis. We have shown that ddPCR is a sensitive molecular technique with the potential to facilitate accurate and non-invasive means of canine UC and PC diagnosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BRAF Mutations in Canine Cancers Mochizuki, Hiroyuki; Kennedy, Katherine; Shapiro, Susan G ...
PloS one,
06/2015, Letnik:
10, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Activating mutations of the BRAF gene lead to constitutive activation of the MAPK pathway. Although many human cancers carry the mutated BRAF gene, this mutation has not yet been characterized in ...canine cancers. As human and canine cancers share molecular abnormalities, we hypothesized that BRAF gene mutations also exist in canine cancers. To test this hypothesis, we sequenced the exon 15 of BRAF, mutation hot spot of the gene, in 667 canine primary tumors and 38 control tissues. Sequencing analysis revealed that a single nucleotide T to A transversion at nucleotide 1349 occurred in 64 primary tumors (9.6%), with particularly high frequency in prostatic carcinoma (20/25, 80%) and urothelial carcinoma (30/45, 67%). This mutation results in the amino acid substitution of glutamic acid for valine at codon 450 (V450E) of canine BRAF, corresponding to the most common BRAF mutation in human cancer, V600E. The evolutional conservation of the BRAF V600E mutation highlights the importance of MAPK pathway activation in neoplasia and may offer opportunity for molecular diagnostics and targeted therapeutics for dogs bearing BRAF-mutated cancers.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Agency Theory Shapiro, Susan P.
Annual review of sociology,
01/2005, Letnik:
31, Številka:
1
Journal Article
Recenzirano
In an agency relationship, one party acts on behalf of another. It is curious that a concept that could not be more profoundly sociological does not have a niche in the sociological literature. This ...essay begins with the economics paradigm of agency theory, which casts a very long shadow over the social sciences, and then traces how these ideas diffuse to and are transformed (if at all) in the scholarship produced in business schools, political science, law, and sociology. I cut a swathe through the social fabric where agency relationships are especially prevalent and examine some of the institutions, roles, forms of social organization, deviance, and strategies of social control that deliver agency and respond to its vulnerabilities, and I consider their impact. Finally, I suggest how sociology might make better use of and contribute to agency theory.
As part of the ongoing reassessment of Xenophon's philosophical works, scholars have taken a renewed interest in the relationship between Xenophon and Plato, who occasionally criticize one another's ...works. Although ancient commentators assumed that the two men must have been rivals, a closer look at each one's comments on the other's work reveals that their criticisms were more philosophical than personal. After discussing two examples in which Plato and Xenophon criticize one another's works, in this paper I suggest that an unusual comment made by Xenophon about Lycurgus, the legendary Spartan lawgiver, is an oblique but critical reference to a statement in Plato's Symposium about Lycurgus' wisdom.
This article reviews the fate of truth and falsehood outside of the courtroom, largely-but not exclusively-in the United States. Describing opportunities and techniques to mislead or deceive on and ...off the Internet and social media, it focuses on the evolving social control response undertaken by institutions and increasingly by distributed networks: government regulators, private actors, self-regulators, crowds, third parties, platform architecture, and technology. The review highlights the turbulent legal and regulatory challenges encountered as existing rules do not quite fit the virtual world, free speech protections tie the hands of legislators and regulators in some parts of the world, and massive private corporations-whose profitability is maximized by user engagement with inflammatory and often false messages-control much of what can and cannot be said. Competing media, platforms, and regulators usher in a post-truth era with contested arbiters of truth and dire warnings of an epistemological crisis.
A growing literature addresses the poor fit of classic agency theory to management settings. For example, where classic theory considers discretion the avenue through which agents exercise ...self-interest at the expense of their principals, alternative perspectives identify discretion as the reason some principals enter an agency relationship in the first place--to take advantage of agent expertise and to respond to uncertain contingent events. This paper examines relationships in which agents enjoy considerable discretion and have limited, conflicting, or ambiguous guidance from their principals, characteristic of many governance and organizational settings and professional relationships. It draws on observational research in two intensive care units, where principals (patients) lack capacity to specify their objectives and cannot control, monitor, incentivize, converse with, or fire the agent charged with making life-and-death medical decisions on their behalf. Observing agents at the bedside provides a rare opportunity to understand—in real time—how agents fashion appropriate actions to take on behalf of principals with whom they cannot communicate and who rarely gave them sufficient guidance. Managers not infrequently must act for another without clear or authoritative direction. Insights from the study of medical decision-makers inform diverse literatures that feature extreme delegation to the agent.
Optimal prophylactic and therapeutic management of thromboembolic disease in patients with COVID-19 remains a major challenge for clinicians. The aim of this study was to define the incidence of ...thrombotic and haemorrhagic complications in critically ill patients with COVID-19. In addition, we sought to characterise coagulation profiles using thromboelastography and explore possible biological differences between patients with and without thrombotic complications.
We conducted a multicentre retrospective observational study evaluating all the COVID-19 patients received in four intensive care units (ICUs) of four tertiary hospitals in the UK between March 15, 2020, and May 05, 2020. Clinical characteristics, laboratory data, thromboelastography profiles and clinical outcome data were evaluated between patients with and without thrombotic complications.
A total of 187 patients were included. Their median (interquartile (IQR)) age was 57 (49-64) years and 124 (66.3%) patients were male. Eighty-one (43.3%) patients experienced one or more clinically relevant thrombotic complications, which were mainly pulmonary emboli (n = 42 (22.5%)). Arterial embolic complications were reported in 25 (13.3%) patients. ICU length of stay was longer in patients with thrombotic complications when compared with those without. Fifteen (8.0%) patients experienced haemorrhagic complications, of which nine (4.8%) were classified as major bleeding. Thromboelastography demonstrated a hypercoagulable profile in patients tested but lacked discriminatory value between those with and without thrombotic complications. Patients who experienced thrombotic complications had higher D-dimer, ferritin, troponin and white cell count levels at ICU admission compared with those that did not.
Critically ill patients with COVID-19 experience high rates of venous and arterial thrombotic complications. The rates of bleeding may be higher than previously reported and re-iterate the need for randomised trials to better understand the risk-benefit ratio of different anticoagulation strategies.
Nursing Policies and Protocols Kelly, Ursula; Edwards, Geneva; Shapiro, Susan E.
Journal of nursing care quality,
07/2021, Letnik:
36, Številka:
3
Journal Article
Recenzirano
BACKGROUNDNursing policies and protocols exist to promote high-quality, safe, and effective nursing practice; however, there is little evidence demonstrating how nurses actually use them to inform ...their everyday, routine practice. PURPOSEThe purposes were to explore the extent to which nurses use nursing policies and protocols to guide their routine practice, and identify barriers and facilitators affecting the frequency with which nurses use nursing policies and protocols. METHODSLicensed nurses (N = 235) providing direct care to inpatients and outpatients in a large medical center participated in an 18-question online survey. RESULTSMost nurses access policies and protocols once a month or more; the greatest barrier to more frequent access was length of the policy or protocol. CONCLUSIONSOrganizations should make policies and protocols succinct, current, and easily accessible. Studies are needed to determine how policies and procedures can best meet the needs of stakeholders, including health care organizations, staff, and patients.
PDF
