In 2001, seventeen professionals set up the manifesto for agile software development. They wanted to define values and basic principles for better software development. On top of being brought into focus, the manifesto has been widely adopted by developers, in software-developing organizations and outside the world of IT. Agile principles and their implementation in practice have paved the way for radical new and innovative ways of software and product development. In parallel, the understanding of the manifesto's underlying principles evolved over time. This, in turn, may affect current and future applications of agile principles. This article presents results from a survey and an interview study in collaboration with the original contributors of the manifesto for agile software development. Furthermore, it comprises the results from a workshop with one of the original authors. This publication focuses on the origins of the manifesto, the contributors' views from today's perspective, and their outlook on future directions. We evaluated 11 responses from the survey and 14 interviews to understand the viewpoint of the contributors. They emphasize that agile methods need to be carefully selected and agile should not be seen as a silver bullet. They underline the importance of considering the variety of different practices and methods that had an influence on the manifesto. Furthermore, they mention that people should question their current understanding of "agile" and recommend reconsidering the core ideas of the manifesto.

In order to evaluate internal potassium balance in patients with end-stage renal disease (ESRD), epinephrine (0.015 micrograms/kg/min) was infused intravenously into normal control (N = 9) and ESRD subjects (N = 7) after a 26 hour fast. Hyperkalemia developed in ESRD patients after 16 hours of fasting, as compared with control subjects (P = 0.02). The hemodynamic response to epinephrine was similar in the two groups. During epinephrine infusion for one hour, the serum potassium decreased in normal subjects, from 4.3 +/- 0.2 mEq/liter to 3.9 +/- 0.1 mEq/liter, but did not change in ESRD patients (P = 0.005). Serum CO2 declined in ESRD, but not in control subjects, while glucose levels were not different in the two groups. Plasma aldosterone was significantly higher in fasting ESRD patients and failed to decrease during epinephrine infusion as compared to controls. Plasma insulin levels remained low in both groups even though serum glucose levels increased. These results demonstrate that hyperkalemia occurs during fasting in ESRD probably as the result of insulinopenia, and suggest that a diminished response to epinephrine may contribute to hyperkalemia.

The systemic and renal adaptations for the maintenance and correction of metabolic alkalosis generated by chloride depletion (CDA) are the focus of this review. The hypothesis that extracellular fluid (ECF) volume expansion is essential for the correction of CDA is refuted, while the concept that Cl- repletion is necessary and sufficient for correction is developed. Contraction of ECF volume probably can occur as a consequence of CDA. The principal mechanisms by which the kidney corrects CDA appear to reside primarily in the collecting duct, which is endowed with the anion exchange mechanisms and the capacity to effect the necessary changes in body anion composition. Although the remainder of the collecting duct is undoubtedly important in this response, the cortical segment appears to have the paramount role since it can either absorb or secrete HCO3-. Alterations in the delivery of Cl- or HCO3- to the collecting duct may also be important but changes in glomerular filtration rate appear to have a minor role. Major unanswered questions in the pathophysiology of CDA are the manner in which exogenous Cl- repletion is detected and the kidney is signaled to excrete HCO3- and the cellular mechanisms by which this is accomplished in the various nephron segments.

Previous studies have suggested the presence of an H(+)-K(+)-ATPase in rat cortical and medullary intercalated cells with similar properties to the gastric proton pump. The purpose of this study was to determine the functional contribution of an H(+)-K(+)-adenosinetriphosphatase(ATPase) to total CO2 (tCO2) transport along the rat collecting duct. After baseline determination of tCO2 transport in isolated perfused collecting duct segments, Sch 28080 (10 microM) was added to either the perfusate or bath. When Sch 28080 was added to the perfusate, there was no effect in the cortical collecting duct (CCD, 20.8 +/- 6.7 vs. 25.3 + 3.0 pmol.mm-1.min-1), but a marked decrease in tCO2 absorption was effected in both the outer medullary (OMCD, 37.6 + 6.2 vs. 10.7 +/- 4.1 pmol.mm-1.min-1) and initial inner medullary collecting duct (IMCD1, 34.4 +/- 8.1 vs. 16.2 +/- 5.6 pmol.mm-1.min-1). In the CCD from rats with acute alkalosis in vivo, Sch 28080 added to the bath inhibited tCO2 secretion in the CCD (-17.1 +/- 4.4 vs 3.5 + 3.3 pmol.mm-1.min-1). These findings suggest that 1) H(+)-K(+)-ATPase is important in tCO2 absorption in the OMCD and IMCD1 and in tCO2 secretion in the CCD, 2) HCO3(-)-absorbing intercalated cells differ functionally in the cortex and medulla, 3) HCO3- secretion is not the reverse process of HCO3- absorption in the CCD, and 4) H(+)-K(+)-ATPase is important in distal acidification under normal and altered acid-base conditions.

SUMMARY Glomerular bemodynamics were studied by mJcropuncture technique in the undipped kidney in rats in which modest two kidney Goldblatt hypertension was maintained for 4 weeks and in normotensive controls. Both groups ingested less than 2 mEq Na + /day. In hypertensive rats at micropuncture, mean hydrostatic pressure was elevated both systemically (128 ± 5 vs 113 ± 3 mm Hg,p < 0.05) and within glomerular capillaries (55 ± 2 vs 48 ± 1 mm Hg,p < 0.05), resulting in an Increase in the transglomerular hydrostatic pressure gradient (40 ± 2 TS 33 ± 1 mm Hg, p < 0.05). The glomerular capillary permeability coefficient, however, was decreased in the hypertensive rats (0.063 ± 0.017 vs 0.115 ± 0.011 nl/s/g kw/mm Hg, p < 0.05), resulting in no change in nephron filtration rate (38.9 ± 2.3 TS 39.9 ± 2.5 nl/min/g kw). Nephron plasma flow also remained unchanged (154 ± 10 vs 140 ± 7 ml/mln/g kw). In separate studies in this model of hypertension, saralasin infusion demonstrated a peripheral effect of circulating angiotensin II which was increased over controls. Kidney mass and GFR were not different between clipped and undipped kidneys. No consistent abnormalities were observed by light or electron microscopy either in glomeruli or in vessels in the undipped kidney. This study demonstrates that glomerular bemodynamics may be altered early In the course of modest hypertension in this model without altering blood flow or fUtration rate. The deaease in glomerular capillary area and/or permeability (LpA) in the hypertensive rats could be either a result of the increased effect of circulating angiotensin II or the direct effect of glomerular capillary hypertension. 1 "* In much of this work, marked chronic systemic hypertension has produced significant secondary focal glomerular damage, coexisting with focal "superfunctioning" glomeruli. Thus, experimental findings in these models may be influenced by the process of compensatory glomerular hypertrophy. We therefore attempted the present micropuncture study, which examines glomerular pressures, flows, resistances, and permeabilities in the undipped kidney 4 weeks after moderate systemic hypertension was es- 51tablished in the Goldblatt hypertensive MunichWistar rat. This study was undertaken 4 weeks after hypertension was established to minimize the effects of both focal glomerular obsolescence and other structural changes in the glomeruli studied, e.g., segmental sclerosis and/or glomerular hypertrophy. In this way we sought to define the initial glomerular adaptations to systemic hypertension in a model exhibiting the moderate increases in blood pressure which are most frequently encountered in clinical populations. MethodsMale Munich-Wistar rats were used; they weighed 180 to 200 g (80-90 days old) at the start of the experiment. This strain of rat, raised and housed in an isolated colony at the Veterans Administration Medical Center, San Diego, California, characteristically provides from three to eight surface glomeruli accessible to micropuncture. Three groups of rats w...