Value-based analysis of routine pathologic septal and inferior turbinate specimens.

This article was presented at the 2012 AAO-HNSF Annual Meeting & OTO EXPO; September 9-12, 2012; Washington, DC. Objective To determine the frequency and clinical relevance of unanticipated histopathologic results in routine sinonasal surgery and evaluate the necessity for histologic processing of nasal septal cartilage, bone, and inferior turbinate specimens. Study Design Case series with chart review. Setting Tertiary care academic medical center. Subjects and Methods A retrospective review of surgical pathology reports on adult patients undergoing sinonasal surgery during a 5-year period from 2005 to 2010 was performed. All cases with the preoperative diagnosis of sinonasal neoplasia, autoimmune disease, or directed septal biopsies were excluded from review. Results A total of 1194 pathology reports were reviewed from 1172 individual patients. This included histopathologic evaluation of 1194 septal cartilage and bone specimens and 714 inferior turbinate specimens. None of the patients had unanticipated histopathologic findings that were clinically significant. Conclusion Many surgeons obtain histopathologic diagnoses on all tissue removed from a patient. Based on our institutional case series, histopathology of the septum and inferior turbinates in routine sinonasal cases may not be necessary. A value-based approach to processing grossly unremarkable septal and turbinate tissue by waiving histologic processing and subsequent microscopic evaluation could provide significant cost savings

Impaired hepatic drug and steroid metabolism in congenital adrenal hyperplasia due to P450 oxidoreductase deficiency

Objective: Patients with congenital adrenal hyperplasia due to P450 oxidoreductase (POR) deficiency(ORD) present with disordered sex development and glucocorticoid deficiency. This is due to disruption of electron transfer from mutant POR to microsomal cytochrome P450 (CYP) enzymes that play a key role in glucocorticoid and sex steroid synthesis. POR also transfers electrons to all major drugmetabolizing CYP enzymes, including CYP3A4 that inactivates glucocorticoid and oestrogens. However, whether ORD results in impairment of in vivo drug metabolism has never been studied. Design:We studied an adult patient with ORD due to homozygous POR A287P, the most frequent POR mutation in Caucasians, and her clinically unaffected, heterozygous mother. The patient had received standard dose oestrogen replacement from 17 until 37 years of age when it was stopped after she developed breast cancer. Methods: Both subjects underwent in vivo cocktail phenotyping comprising the oral administration of caffeine, tolbutamide, omeprazole, dextromethorphan hydrobromide and midazolam to assess the five major drug-metabolizing CYP enzymes. We also performed genotyping for variant CYP alleles known to affect drug metabolism. Results: Though CYP enzyme genotyping predicted normal or high enzymatic activities in both subjects, in vivo assessment showed subnormal activities of CYP1A2, CYP2C9, CYP2D6 and CYP3A4 in the patient and of CYP1A2 and CYP2C9 in her mother. Conclusions: Our results provide in vivo evidence for an important role of POR in regulating drug metabolism and detoxification. In patients with ORD, in vivo assessment of drug-metabolizing activities with subsequent tailoring of drug therapy and steroid replacement should be considered

Microplastic in the stomachs of open-ocean and deep-sea fishes of the North-East Atlantic

This is the author accepted versionThe presence of microplastic in marine fishes has been well documented but few studies have directly examined differences between fishes occupying contrasting environmental compartments. In the present study, we investigated the gut contents of 390 fishes belonging to three pelagic (blue jack mackerel, chub mackerel, skipjack tuna) and two deep-sea species (blackbelly rosefish, blackspot seabream) from the Azores archipelago, North-East Atlantic for microplastic contamination. Our results revealed that pelagic species had significantly more microplastic than the deep-water species. In all of the species studied, fragments were the most common plastic shape recovered and we found a significant difference in the type of polymer between the pelagic and deep-water species. In deep-sea fish we found almost exclusively polypropylene, whereas in the pelagic fish, polyethylene was the most abundant polymer type. Overall, the proportion of fish containing plastic items varied across our study species from 3.7% to 16.7% of individuals sampled, and the average abundance of plastic items ranged from 0.04 to 0.22 per individual (the maximum was 4 items recovered in one stomach). Despite the proximity of the Azores archipelago to the North Atlantic subtropical gyre, a region of elevated plastic abundance, the proportion of individuals containing plastic (9.49%) were comparable with data reported elsewhere.Natural Environment Research Council (NERC

What we talk about when we talk about "global mindset": managerial cognition in multinational corporations

Recent developments in the global economy and in multinational corporations have placed significant emphasis on the cognitive orientations of managers, giving rise to a number of concepts such as “global mindset” that are presumed to be associated with the effective management of multinational corporations (MNCs). This paper reviews the literature on global mindset and clarifies some of the conceptual confusion surrounding the construct. We identify common themes across writers, suggesting that the majority of studies fall into one of three research perspectives: cultural, strategic, and multidimensional. We also identify two constructs from the social sciences that underlie the perspectives found in the literature: cosmopolitanism and cognitive complexity and use these two constructs to develop an integrative theoretical framework of global mindset. We then provide a critical assessment of the field of global mindset and suggest directions for future theoretical and empirical research

The use of microbubbles to target drug delivery

Ultrasound-mediated microbubbles destruction has been proposed as an innovative method for noninvasive delivering of drugs and genes to different tissues. Microbubbles are used to carry a drug or gene until a specific area of interest is reached, and then ultrasound is used to burst the microbubbles, causing site-specific delivery of the bioactive materials. Furthermore, the ability of albumin-coated microbubbles to adhere to vascular regions with glycocalix damage or endothelial dysfunction is another possible mechanism to deliver drugs even in the absence of ultrasound. This review focuses on the characteristics of microbubbles that give them therapeutic properties and some important aspects of ultrasound parameters that are known to influence microbubble-mediated drug delivery. In addition, current studies involving this novel therapeutical application of microbubbles will be discussed

Building Babies - Chapter 16

In contrast to birds, male mammals rarely help to raise the offspring. Of all mammals, only among rodents, carnivores, and primates, males are sometimes intensively engaged in providing infant care (Kleiman and Malcolm 1981). Male caretaking of infants has long been recognized in nonhuman primates (Itani 1959). Given that infant care behavior can have a positive effect on the infant’s development, growth, well-being, or survival, why are male mammals not more frequently involved in “building babies”? We begin the chapter defining a few relevant terms and introducing the theory and hypotheses that have historically addressed the evolution of paternal care. We then review empirical findings on male care among primate taxa, before focusing, in the final section, on our own work on paternal care in South American owl monkeys (Aotus spp.). We conclude the chapter with some suggestions for future studies.Deutsche Forschungsgemeinschaft (HU 1746/2-1) Wenner-Gren Foundation, the L.S.B. Leakey Foundation, the National Geographic Society, the National Science Foundation (BCS-0621020), the University of Pennsylvania Research Foundation, the Zoological Society of San Dieg

A unique serum IgG glycosylation signature predicts development of Crohn’s disease and is associated with pathogenic antibodies to mannose glycan

Inflammatory bowel disease (IBD) is characterized by chronic inflammation in the gut. There is growing evidence in Crohn’s disease (CD) of the existence of a preclinical period characterized by immunological changes preceding symptom onset that starts years before diagnosis. Gaining insight into this preclinical phase will allow disease prediction and prevention. Analysis of preclinical serum samples, up to 6 years before IBD diagnosis (from the PREDICTS cohort), revealed the identification of a unique glycosylation signature on circulating antibodies (IgGs) characterized by lower galactosylation levels of the IgG fragment crystallizable (Fc) domain that remained stable until disease diagnosis. This specific IgG2 Fc glycan trait correlated with increased levels of antimicrobial antibodies, specifically anti-Saccharomyces cerevisiae (ASCA), pinpointing a glycome–ASCA hub detected in serum that predates by years the development of CD. Mechanistically, we demonstrated that this agalactosylated glycoform of ASCA IgG, detected in the preclinical phase, elicits a proinflammatory immune pathway through the activation and reprogramming of innate immune cells, such as dendritic cells and natural killer cells, via an FcγR-dependent mechanism, triggering NF-κB and CARD9 signaling and leading to inflammasome activation. This proinflammatory role of ASCA was demonstrated to be dependent on mannose glycan recognition and galactosylation levels in the IgG Fc domain. The pathogenic properties of (anti-mannose) ASCA IgG were validated in vivo. Adoptive transfer of antibodies to mannan (ASCA) to recipient wild-type mice resulted in increased susceptibility to intestinal inflammation that was recovered in recipient FcγR-deficient mice. Here we identify a glycosylation signature in circulating IgGs that precedes CD onset and pinpoint a specific glycome–ASCA pathway as a central player in the initiation of inflammation many years before CD diagnosis. This pathogenic glyco-hub may constitute a promising new serum biomarker for CD prediction and a potential target for disease prevention.We wish to acknowledge the Gastroenterology Department of Centro Hospitalar Universitário de Santo António, in particular P. Lago, for providing samples from individuals with established CD. We kindly thank J. Rojo from the Instituto de Investigaciones Químicas (Universidad de Sevilla) for providing us with the di-GlcNAc glycodendrimer. We would also like to acknowledge J. V. Ravetch (Rockefeller University) and M. S. Cragg (University of Southampton) for kindly providing us with the FcγR-deficient mice used in the in vivo studies. S.S.P. acknowledges funding from the US Department of Defense, US Army Medical Research Acquisition Activity and FY18Peer-Reviewed Medical Research Program Investigator-Initiated Research Award (award number W81XWH1920053). S.S.P. also acknowledges funding from the European Crohn’s and Colitis Organisation (ECCO) Pioneer Award 2021, the International Organization for the study of Inflammatory Bowel Disease (IOIBD) and the Portuguese Foundation for Science and Technology (FCT; EXPL/MED-ONC/0496/2021). J.G. acknowledges funding from European Society of Clinical Microbiology and Infectious Diseases (ESCMID ResearchGrant 2022), European Crohn’s and Colitis Organisation (ECCO Grant 2023) and FCT (2020.00088.CEECIND). C.S.R. thanks FCT forfunding (2020.08422.BD). I.A. acknowledges funding from FCT (2022.00337.CEECIND) and the BIAL Foundation and PortugueseMedical Association (Maria de Sousa Award 2023). E.L.-G. thanks FCT for funding (UI/BD/152866/2022). F.P. and Z.H.G. were partially supported by the Kenneth-Rainin Foundation (20210021). B.C. acknowledges funding from FCT(CEECINST/00123/2021/CP1772/CT0001). J.T. acknowledges funding from the Portuguese Society of Gastroenterology and from Luz Saúde (Grupo dE iNvestIgação em Patologia Digestiva LUz Saúde LH.INV.F2019015). This study was also cofunded by the EuropeanUnion (GlycanTrigger, grant agreement number 101093997). The views and opinions expressed are, however, those of the author(s) only and do not necessarily reflect those of the European Union or the European Research Council Executive Agency. Neither the European Union nor the granting authority can be held responsible for them. This study was conducted under support of Peer-Reviewed Medical Research Program (PR180831P1). The views expressed in this article reflect the results of the research conducted by the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, the Henry M. Jackson Foundation for the Advancement of Military Medicine or the US Government. There are no restrictions on its use. This article was prepared while R.M.L. was employed at Henry M. Jackson Foundation for the Advancement of Military Medicine. The opinions expressed in this article are those of the authors and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services or the US Government. C.K.P. is an employee of the US Government. This work was prepared as part of official duties. Title 17 U.S.C. §105provides that ‘Copyright protection under this title is not available for any work of the United States Government.’ Title 17 U.S.C. §101 defines a US Government work as a work prepared by a military service member or employee of the US Government as part of that person’s official duties

Knowledge networks and universities : locational and organisational aspects of knowledge transfer interactions

This paper explores the nature of the significant knowledge networks universities form with external organisations through knowledge transfer activities. Focussing on the UK higher education system, the analysis focuses on examining the extent to which organisational and locational characteristics are associated with the nature of these networks, finding that the nature of the networks universities form through knowledge transfer are related to both characteristics. In particular, we find that the institution’s status is important with more established universities are likely to have a more diverse range of organisations with which they interact, as well as a higher number of non-local interactions. In terms of geographic location, we find that universities within lagging regions tend to have more locally focused networks than universities in more leading regions. Overall, the knowledge transfer networking capacity of universities is found to be associated with the regional business environment within which they are situated, with the results going someway to confirming the importance of the role of universities in regional innovation systems, However, it also the case that more established, research focussed, universities are more likely to form part of wider , and possibly even more globalised, knowledge networks. Therefore, both the flow and stock of knowledge within regions is likely to be influenced by the networks formed by its universities, which has implications for both regional innovation capability and regional competitiveness