'For this I was made': conflict and calling in the role of a woman priest

There has been an increasing focus on ‘work as calling’ in recent years, but relatively few empirical sociological accounts that shed light on the experience of performing calling work. Although callings have generally been referred to as positive and fulfilling to the individual and as beneficial to society, researchers have also suggested there is a ‘dark side’ to calling, and have drawn attention to the potential conflicts and tensions inherent in the pursuit of calling, especially for women. This article explores these themes through the first-hand experiences of one woman who felt called to work as a priest. Her narrative illustrates how callings draw the individual irresistibly towards a particular line of work. It also shows how calling work can be both satisfying individually and beneficial to the wider community but, at the same time, involves sacrifice, compromise and a willingness to defer personal rewards

Southern Africa Consortium for Research Excellence (SACORE): successes and challenges

Copyright © Mandala et al. Open access article distributed under the terms of CC BY.Published Online November 13, 2014 http://dx.doi.org/10.1016/S2214-109X(14)70321-

Medicinal importance of grapefruit juice and its interaction with various drugs

Grapefruit juice is consumed widely in today's health conscious world as a protector against cardiovascular diseases and cancers. It has however, been found to be an inhibitor of the intestinal cytochrome P – 450 3A4 system, which is responsible for the first pass metabolism of many drugs. The P – glycoprotein pump, found in the brush border of the intestinal wall which transports many of these cytochrome P – 450 3A4 substrates, has also been implicated to be inhibited by grapefruit juice. By inhibiting these enzyme systems, grapefruit juice alters the pharmacokinetics of a variety of medications, leading to elevation of their serum concentrations. Most notable are its effects on the calcium channel antagonist and the statin group of drugs. In the case of many drugs, the increased serum concentration has been found to be associated with increased frequency of dose dependent adverse effects. In this review, we have discussed the phytochemistry of grapefruit juice, the various drugs involved in the drug – grapefruit juice eraction with their mechanisms of action and have presented the clinical implications of these interactions

Prospective study of grapefruit intake and risk of breast cancer in postmenopausal women: the Multiethnic Cohort Study

In vitro and in vivo studies have shown that cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of oestrogens. There is evidence that grapefruit, an inhibitor of CYP3A4, increases plasma oestrogen concentrations. Since it is well established that oestrogen is associated with breast cancer risk, it is plausible that regular intake of grapefruit would increase a woman's risk of breast cancer. We investigated the association of grapefruit intake with breast cancer risk in the Hawaii–Los Angeles Multiethnic Cohort Study, a prospective cohort that includes over 50 000 postmenopausal women from five racial/ethnic groups. A total of 1657 incident breast cancer cases were available for analysis. Grapefruit intake was significantly associated with an increased risk of breast cancer (relative risk=1.30, 95% confidence interval 1.06–1.58) for subjects in the highest category of intake, that is, one-quarter grapefruit or more per day, compared to non-consumers (Ptrend=0.015). An increased risk of similar magnitude was seen in users of oestrogen therapy, users of oestrogen+progestin therapy, and among never users of hormone therapy. Grapefruit intake may increase the risk of breast cancer among postmenopausal women

Scallop swimming kinematics and muscle performance: modelling the effects of "within-animal" variation in temperature sensitivity

Escape behaviour was investigated in Queen scallops (Aequipecten opercularis) acclimated to 5, 10 or 15 degrees C and tested at their acclimation temperature. Scallops are active molluscs, able to escape from predators by jet-propelled swimming using a striated muscle working in opposition to an elastic hinge ligament. The first cycle of the escape response was recorded using high-speed video ( 250 Hz) and whole-animal velocity and acceleration determined. Muscle shortening velocity, force and power output were calculated using measurements of valve movement and jet area, and a simple biomechanical model. The average shortening speed of the adductor muscle had a Q(10) of 2.04, significantly reducing the duration of the jetting phase of the cycle with increased temperature. Muscle lengthening velocity and the overall duration of the clap cycle were changed little over the range 5 - 15 degrees C, as these parameters were controlled by the relatively temperature-insensitive, hinge ligament. Improvements in the average power output of the adductor muscle over the first clap cycle ( 222 vs. 139 W kg(-1) wet mass at 15 and 5 degrees C respectively) were not translated into proportional increases in overall swimming velocity, which was only 32% higher at 15 degrees C ( 0.37m s(-1)) than 5 degrees C (0.28 m s(-1))

Single-Cell Lipidomics Using Analytical Flow LC-MS Characterizes the Response to Chemotherapy in Cultured Pancreatic Cancer Cells

In this work, we demonstrate the development and first application of nanocapillary sampling followed by analytical flow liquid chromatography–mass spectrometry for single-cell lipidomics. Around 260 lipids were tentatively identified in a single cell, demonstrating remarkable sensitivity. Human pancreatic ductal adenocarcinoma cells (PANC-1) treated with the chemotherapeutic drug gemcitabine can be distinguished from controls solely on the basis of their single-cell lipid profiles. Notably, the relative abundance of LPC(0:0/16:0) was significantly affected in gemcitabine-treated cells, in agreement with previous work in bulk. This work serves as a proof of concept that live cells can be sampled selectively and then characterized using automated and widely available analytical workflows, providing biologically relevant outputs

Nanocapillary sampling coupled to liquid chromatography mass spectrometry delivers single cell drug measurement and lipid fingerprints

This work describes the development of a new approach to measure drug levels and lipid fingerprints in single living mammalian cells. Nanocapillary sampling is an approach that enables the selection and isolation of single living cells under microscope observation. Here, live single cell nanocapillary sampling is coupled to liquid chromatography for the first time. This allows molecular species to be separated prior to ionisation and improves measurement precision of drug analytes. The efficiency of transferring analytes from the sampling capillary into a vial was optimised in this work. The analysis was carried out using standard flow liquid chromatography coupled to widely available mass spectrometry instrumentation, highlighting opportunities for widespread adoption. The method was applied to 30 living cells, revealing cell-to-cell heterogeneity in the uptake of different antibiotics. Using this system, we detected 14-158 lipid features per single cell, revealing the association between bedaquiline uptake and lipid fingerprints

Modulation of erlotinib pharmacokinetics in mice by a novel cytochrome P450 3A4 inhibitor, BAS 100

Administration of BAS 100, a novel mechanism-based CYP3A4 inhibitor isolated from grapefruit juice, resulted in a 2.1-fold increase in erlotinib exposure following oral administration to wild-type and humanised CYP3A4 transgenic mice. This study illustrates the potential of BAS 100 to increase the low and variable oral bioavailability of erlotinib in cancer patients