Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

P-glycoprotein and breast cancer resistance protein in acute myeloid leukaemia cells treated with the Aurora-B Kinase Inhibitor barasertib-hQPA

<p>Abstract</p> <p>Background</p> <p>Aurora kinases play an essential role in orchestrating chromosome alignment, segregation and cytokinesis during mitotic progression, with both aurora-A and B frequently over-expressed in a variety of human malignancies. Over-expression of the ABC drug transporter proteins P-glycoprotein (Pgp) and Breast cancer resistance protein (BCRP) is a major obstacle for chemotherapy in many tumour types with Pgp conferring particularly poor prognosis in acute myeloid leukaemia (AML). Barasertib-hQPA is a highly selective inhibitor of aurora-B kinase that has shown tumouricidal activity against a range tumour cell lines including those of leukaemic AML origin.</p> <p>Methods</p> <p>Effect of barasertib-hQPA on the pHH3 biomarker and cell viability was measured in a panel of leukaemic cell lines and 37 primary AML samples by flow cytometry. Pgp status was determined by flow cytometry and BCRP status by flow cytometry and real-time PCR.</p> <p>Results</p> <p>In this study we report the creation of the cell line OCI-AML3DNR, which over-expresses Pgp but not BCRP or multidrug resistance-associated protein (MRP), through prolonged treatment of OCI-AML3 cells with daunorubicin. We demonstrate that Pgp (OCI-AML3DNR and KG-1a) and BCRP (OCI-AML6.2) expressing AML cell lines are less sensitive to barasertib-hQPA induced pHH3 inhibition and subsequent loss of viability compared to transporter negative cell lines. We also show that barasertib-hQPA resistance in these cell lines can be reversed using known Pgp and BCRP inhibitors. We report that barasertib-hQPA is not an inhibitor of Pgp or BCRP, but by using ¹⁴[C]-barasertib-hQPA that it is effluxed by these transporters. Using phosphoHistone H3 (pHH3) as a biomarker of barasertib-hQPA responsiveness in primary AML blasts we determined that Pgp and BCRP positive primary samples were less sensitive to barasertib-hQPA induced pHH3 inhibition (p = <0.001) than samples without these transporters. However, we demonstrate that IC₅₀inhibition of pHH3 by barasertib-hQPA was achieved in 94.6% of these samples after 1 hour drug treatment, in contrast to the resistance of the cell lines.</p> <p>Conclusion</p> <p>We conclude that Pgp and BCRP status and pHH3 down-regulation in patients treated with barasertib should be monitored in order to establish whether transporter-mediated efflux is sufficient to adversely impact on the efficacy of the agent.</p

Some Aspects of the Biology and Ecology of Humble-Bees Bearing Upon the Yields of Red-Clover Seed in New Zealand

The species density, and the situation, construction, and fate of humble-bee nests in England, whence the species now present in New Zealand have come, are described. Factors that may determine populations of humble-bees in New Zealand are discussed in the light of present knowledge of factors that govern the size of nests in England. Methods are described by which further species for shipment to New Zealand may be, and have been, collected

An Overwintering Nest of the Humble-Bee: Bombus terrestris (L.) (Hymenoptera, Apidae)

This article describes a large overwintering nest of a humble-bee species taken in spring at Nelson and discusses the question of polygyny and the development of perennial colonies

The Life-Cycle of Humble-Bees in New Zealand

The life-cycles of two species of Bombus introduced into New Zealand have been determined for one district by analysing field populations. Both internal and external features of the humble-bees have been considered, and comparisons are made with the cycle found in Southern England

Studies on an Unusually Large Nest of Bombus terrestris (L.) (Hymenoptera, Apidae) Transferred to an Observation Box

An unusually large nest of Bombus terrestris (L.) comprising some 600-800 individuals was taken at Palmerston North on 9.11.60 and transferred to an observation box. The nest, which died out late in December , enabled observations to be made on the habits of guard bees, on the behaviour of aseasonally produced queens , on ovarian development, the discarding of larvae, and commensals. A technique for determining queen fertilization without dissection is described

The Biology of Humble-Bees, with Special Reference to the Production of the Worker Caste

The study of humble-bees in Buckinghamshire , Berkshire and Surrey during 1946 and 1947 has provided information relating to the problems of worker and queen production and population changes and organization. Statistical evidence on new and previously described phenomena are presented. The work has been carried out at the Imperial College of Science and Technology, and I wish to express my thanks to the staff of the Department of Zoology and Applied Entomology, especially to Dr. O. W. Richards, for advice throughout the course of the work. I wish also to thank Dr. G. Salt, of the Zoology Department, Cambridge, for his many helpful suggestions

Life Cycle of the Humble Bee

At least two hundred papers describing habits of the different humble-bee species have been written, but the majority are fragmentary. In Europe, the work of Hoffer (1882), Sladen (1912), and Friese (1923) are more comprehensive. Sladen\u27s book, The Humble-bee, Its Life History, and how to Domesticate It, which is the outstanding contribution, is well illustrated and the result of a life-long association with the subject. It contains a wealth of information gained from critical observation. The American counterpart, Bumble-bees and Their Ways by Plath (1934) contains an extensive bibliography. The many papers of Frison on the North American species are also worthy of mention. The life cycle described here is that which occurs in Southern England. The majority of humble-bee species are found in the temperate regions, but they range from the tropics to the arctic circle, and in their northern and southern limits their habits are modified. Groups of species from the temperate regions also show different habits and have been classified accordingly. There is a need for a more recent general account of the life cycle of humble-bees. The older account, although excellent, are not always accessible, and an interpretation of the cycle in the light of more recent studies would seem desirable. The present account is far too brief to fill the gap completely, but it is hoped that it will prove useful. In the years 1946-48 more than 160 nests belonging to nine species were studied in England. A large number of dissections were made, and changes in internal organs were noted and studied in relation to changes in habit. Statistical analyses were made of nests of different sizes in order to obtain a true picture of the changes taking place. Some of the information gained is incorporated in the present account. The importance of humble-bees in agriculture has been realized since Darwin\u27s time. The unsatisfactory red-clover seed yields in this country have been mainly responsible for our interest in them. The life cycle and ecology of the introduced species is now being studied, but as a prerequisite to studies in New Zealand, the life cycle found in England, whence our species came, must be fully understood if modifications from the normal are to be detected