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PubMed1993

The method of public morality versus the method of principlism.

Two years ago in two articles in a thematic issue of this journal the three of us engaged in a critique of principlism. In a subsequent issue, B. Andrew Lustig defended aspects of principlism we had criticized and argued against our own account of morality. Our reply to Lustig's critique is also in two parts, corresponding with his own. Our first part shows how Lustig's criticisms are seriously misdirected. Our second and philosophically more important part picks up on Lustig's challenge to us to show that our account of mortality is more adequate than principlism. In particular we show that recognition of mortality as public and systematic enables us to provide a far better description of morality than does principlism. This explains why we adopt the label "Dartmouth Descriptivism."

Beneficence↗

PubMedDate not supplied

Testing green coffee for ochratoxin A, part II: Observed distribution of ochratoxin A test results.

The suitability of 4 theoretical distributions (normal, lognormal, negative binomial, and gamma) to predict the observed distribution of ochratoxin A (OTA) in green coffee was investigated. One symmetrical and 3 positively skewed theoretical distributions were each fitted to 25 empirical distributions of OTA test results for green coffee beans. Parameters of each theoretical distribution were calculated by using Methods of Moments. The 3 skewed theoretical distributions provided acceptable fits to each of the 25 observed distributions. Because of its simplicity, the lognormal distribution was selected to model OTA test results for green coffee. Using variance equations determined in previous studies, mathematical expressions were developed to calculate the parameters of the log normal distribution for a given OTA lot concentration and test procedure. Observed acceptance probabilities were compared to an operating characteristic curve predicted from the lognormal distribution, and all 25 observed acceptance probabilities were found to lie within the 95% confidence band associated with the predicted operating characteristic curve. The parameters of compound gamma distribution were used to calculate the fraction of OTA contamination beans within a contaminated lot. The percent-contaminated beans were a function of the lot concentration and increased with lot concentration. At a lot concentration of 5 microg/kg, approximately 6 beans per 10,000 beans are contaminated.

Buffers↗

PubMed1998

A new protocol for the measurement of picomole quantities of magnesium in rat renal tubular fluid.

The analysis of picomolar quantities of magnesium by electrothermal atomic absorption spectrophotometry (EAAS) was studied using a Perkin-Elmer-Zeeman 3030 spectrophotometer. The absorbance signal was not heavily dependent on the atomization temperature, but was greatly reduced when ashing temperatures in excess of 1200 degrees C were applied. The magnesium signal was significantly depressed in the presence of excess chloride in the sample matrix. However, use of NH4NO3 as a matrix modifier was sufficient to overcome this artefact. The analytical sensitivity was 0.15 absorbance units pmol-1 and the detection limit was 0.04 pmol. Using nanolitre constriction pipettes to dispense standards, the mean coefficient of variation was 5%. Measurement of magnesium handling in the rat proximal convoluted tubule revealed a significant correlation between the tubular fluid-to-plasma ultrafiltrate (TF/UF) concentration ratio for magnesium and the tubular fluid-to-plasma (TF/P) concentration ratio for [3H]inulin (r2 = 0.56, n = 17). This indicated that magnesium is concentrated during its passage along the proximal tubule. In contrast, this was not the case for sodium (r2 = 0.11, n = 16). Mean (TF/UF)Mg (1.16 +/- 0.07, n = 17) for random punctures was significantly greater than that for sodium ((TF/UF)Na = 1.02 +/- 0.02, n = 16). Despite concentration of magnesium in the lumen, significant net reabsorption of magnesium was observed along the length of the tubule (fractional reabsorption, FRMg = 19.4 +/- 3.0%, n = 17). In conclusion, EAAS provides a highly sensitive, reproducible and technically simple method for measuring picomolar quantities of magnesium in renal tubular fluid.

Animals↗

PubMedDate not supplied

Enzyme-linked immunosorbent assay for microcystins in blue-green algal blooms.

A direct competitive enzyme-linked immunosorbent assay (ELISA) for the freshwater blue-green algal toxin microcystin (MCYST) in algae and water was developed. The assay involves coating anti-MCYST-variant leucine-arginine (LR) antibody to the ELISA plate and the use of MCYST-LR-peroxidase as the enzyme marker. The linear portion of the standard curve for MCYST in phosphate buffer containing saline (PBS) was 0.5-10.0 ng/mL (25-500 pg/assay). The minimum detection level for MCYST-LR was 0.20 ng/mL (10 pg/assay). Contaminated water could be directly used in the ELISA. The overall analytical recoveries for MCYST-LR added to water at levels of 1-20 ng/mL was 83.4%. For analysis of cellular MCYST, the toxin was first extracted from the algae with 0.1M ammonium bicarbonate, diluted with PBS to less than 0.5 mg dried algae/mL (less than 5.0 mg wet weight/mL) and directly used in the ELISA. C-18 reverse-phase Sep-Pak cartridges effectively adsorbed MCYST from the toxin-containing solutions. The toxin could be recovered from the cartridge by eluting with 60% methanol. Using this approach, an algae extract that was relatively free of MCYST was prepared and was used in a recovery study. The overall analytical recovery of MCYST added to the algae extract in the range of 0.25-20 ppm was 83% with a coefficient of variation of 11.9%. The detection limit for MCYST in dried algae was about 0.25-0.5 microgram/g (0.25-0.5 ppm) lyophilized algae sample. This method was applied for the analysis of several naturally occurring algal blooms. Limited samples were also analyzed for MYCST by liquid chromatography.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, Liquid↗

PubMed2005

Challenges and strategies in developing nursing research capacity: a review of the literature.

OBJECTIVES: This paper reports the findings of a critical overview of the development of nursing research capacity in academic departments. It examines the major barriers to developing research capacity, the capacity building strategies adopted (or proposed) within the literature, and considers the wider context within which such endeavours take place. DESIGN: The literature review forms part of a longitudinal project utilising case study methodology. A key word search was used to locate relevant journal articles for the period 1999-2004, derived from the project's research question and an earlier literature review. A number of manual 'shelf searches' were conducted. DATA SOURCES: Bibliographic data were retrieved from The Cumulative Index of Nursing and Allied Health literature, The Social Science Citation Index, and Medline. REVIEW METHODS: Approximately 150 articles were retrieved, of which 47 were included in the study. Given the paucity of work in this area papers were not excluded on the grounds of methodological weakness. Major themes were identified in each paper and an analytical framework was developed. RESULTS: Two main challenges affecting research capacity development were identified-material constraints and organisational contexts, and the changing roles and expectations of nurse educators. The importance of developing an overall strategic approach, clearly communicated, and accompanied by effective leadership was a point of common agreement. Debate existed on how research support should be managed, particularly the merits of inclusivity and the reconcilement of individual and organisational needs. Specific capacity strategies identified in the literature were the creation of infrastructures, the fostering of research cultures and environments, and the facilitation of training and collaboration. CONCLUSIONS: The literature offers many examples of capacity building strategies. However, more empirical studies are needed to understand the situated process of implementing and evaluating capacity building in individual academic departments, and how this process differs between geographical settings.

Education, Nursing, Continuing↗

PubMedDate not supplied

New methods for determination of cinnarizine in mixture with piracetam by spectrodensitometry, spectrophotometry, and liquid chromatography.

Four new methods were developed and validated for the determination of cinnarizine HCl in its binary mixture with piracetam in pure and pharmaceutical preparations. The first one was a densitometric analysis that provides a simple and rapid method for the separation and quantification of cinnarizine HCI. The method depends on the quantitative densitometric evaluation of thin-layer chromatograms of cinnarizine HCI at 252 nm over concentration range of 1-6 microg/spot, with a mean accuracy of 100.05 +/- 0.91%. The second method was determination of the drug using a colorimetric method that utilizes the reaction of 3-methyl-benzothiazolin-2-one in the presence of FeCl3 as an oxidant. The green color of the resulting product was measured at 630 nm over concentration range 10-40 microg/mL, with a mean accuracy of 100.10 +/- 1.13%. The third method was a direct spectrophotometric determination of cinnarizine HCI at 252 nm over the concentration range 7-20 microg/mL, while piracetam was determined by derivative ratio spectrophotometry at 221.6 nm over concentration range 5-30 microg/mL, with a mean accuracy of 100.14 +/- 0.79 and 100.26 +/- 1.24% for cinnarizine HCI and piracetam, respectively. The last method was a liquid chromatography analysis of both cinnarizine HCI and piracetam, depending on quantitative evaluation of chromatograms of cinnarizine HCI and piracetam at 252 and 212 nm, respectively, over the concentration range 10-200 microg/mL for cinnarizine HCI and 20-500 microg/mL for piracetam, with a mean accuracy of 100.03 +/- 0.89 and 100.40 +/- 0.94% for cinnarizine HCI and piracetam, respectively. The proposed procedures were checked using laboratory-prepared mixtures and successfully applied for the analysis of their pharmaceutical preparations. The validity of the proposed procedures was further assessed by applying the standard addition technique. Recoveries were quantitative, and the results obtained agreed with those obtained by other reported methods.

Calcium Channel Blockers↗

PubMed2006

Factors influencing female registered nurses' work behavior.

OBJECTIVE: To analyze factors that are related to whether registered nurses (RNs) work (WK) or do not work (NW) in nursing; and if the RN works, whether she works full- (FT) or part-time (PT). DATA SOURCES: Secondary data from National Sample Survey of Registered Nurses 2000 (NSSRN), the InterStudy Competitive Edge Part III Regional Market Analysis (2001), and the Area Resource File (2002). STUDY DESIGN: Using a cross-sectional design we tested the relationship between WK or NW and FT or PT; and demographic, job-related, and metropolitan statistical area (MSA)-level variables. DATA COLLECTION/EXTRACTION METHODS: We combined the data sources noted above to produce the analytic sample of 25,471 female RNs. PRINCIPAL FINDINGS: Working in nursing is not independent of working FT or PT. Age (55 and older), other family income, and prior other work experience in health care are negatively related to working as an RN. The wage is not related to working as an RN, but negatively influences FT work. Age, children, minority status, student status, employment status, other income, and some job settings have a negative impact on working FT. Previous health care work has a positive effect on whether married RNs worked. Married RNs who are more dissatisfied are less likely to work FT. A greater number of market-level factors influence FT/PT than WK/NW behavior. CONCLUSIONS: An important contribution of this study is demonstrating that MSA-level variables influence RN work behavior. The market environment seems to have little effect on whether a nurse works, but is influential on how much the nurse works, and has differential effects on married versus single nurses.

Adult↗

PubMed2006

Analysis of subcellular surface structure, function and dynamics.

Analytics of single biological cells allows quantitative investigation from a structural, functional and dynamical point of view and opens novel possibilities to an unamplified subcellular analysis. In this article, we report on three different experimental methods and their applications to single cellular systems with a subcellular sensitivity down to the single molecule level. First, the subcellular surface structure of living bacteria (Corynebacterium glutamicum) was investigated with atomic force microscopy (AFM) at the resolution of individual surface layer (S-layer) proteins; discrimination of bacterial strains that lack the expression of hexagonally packed surface layer proteins was possible. Second, quantitative measurement of individual recognition events of membrane-bound receptors on living B-cells was achieved in single cell manipulation and probing experiments with optical tweezers (OT) force spectroscopy. And third, intracellular dynamics of translocating photoactivatable GFP in plant protoplasts (Nicotiana tabacum BY-2) was quantitatively monitored by two-photon laser scanning microscopy (2PLSM).

Animals↗

PubMed2005

Simultaneous determination of myristyl nicotinate, nicotinic acid, and nicotinamide in rabbit plasma by liquid chromatography-tandem mass spectrometry using methyl ethyl ketone as a deproteinization solvent.

Myristyl nicotinate (Nia-114) is an ester prodrug being developed for delivery of nicotinic acid (NIC) into the skin for prevention of actinic keratosis and its progression to skin cancer. To facilitate dermal studies of Nia-114, a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method using methyl ethyl ketone (MEK) as a deproteinization solvent was developed and validated for the simultaneous determination of Nia-114, NIC, and nicotinamide (NAM) in rabbit plasma. NAM is the principal metabolite of NIC, which is also expected to have chemopreventive properties. The analytes were chromatographically separated using a Spherisorb Cyano column under isocratic conditions, and detected by multiple reaction monitoring (MRM) in positive-ion electrospray ionization mode with a run time of 9 min. The method utilized a plasma sample volume of 0.2 ml and isotope-labeled D4 forms of each analyte as internal standards. The method was linear over the concentration range of 2-1000, 8-1000, and 75-1000 ng/ml, for Nia-114, NIC, and NAM, respectively. The intra- and inter-day assay accuracy and precision were within +/-15% for all analytes at low, medium, and high quality control standard levels. The relatively high value for the lower limit of quantitation (LLOQ) of NAM was demonstrated to be due to the high level of endogenous NAM in the rabbit plasma (about 350 ng/ml). Endogenous levels of NIC and NAM in human, dog, rat, and mouse plasma were also determined, and mean values ranged from <2 ng/ml NIC and 38.3 ng/ml NAM in human, to 233 ng/ml NIC and 622 ng/ml NAM in mouse. Nia-114 was generally unstable in rabbit plasma, as evidenced by loss of 44-50% at room temperature by 2 h, and loss of 64-70% upon storage at -20 degrees C for 1 week, whereas it was stable (<7% loss) upon storage at -80 degrees C for 1 month.

Animals↗

PubMed2006

Evaluation of the cost-effectiveness of drotrecogin alfa (activated) for the treatment of severe sepsis in the United Kingdom.

OBJECTIVES: The aim of this study was to assess the cost-effectiveness of drotrecogin alfa (activated) compared with best supportive care in a UK cohort of adult intensive-care patients with severe sepsis. METHODS: A systematic review of evidence on the clinical- and cost-effectiveness of drotrecogin alfa (activated) was undertaken, and a decision-analytic model was developed to estimate the cost-effectiveness of treatment in the United Kingdom. Trial data from the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study have been synthesized with other data, including UK data on severe sepsis, to estimate the costs and consequences of treatment over time. RESULTS: For patients with severe sepsis and multiple organ dysfunction, the estimates of cost per life year and cost per quality-adjusted life year (QALY) are pounds 4931 and pounds 8228, respectively. For patients with severe sepsis alone, the cost per life-year and cost per QALY are pouhds 5495 and pounds 9161, respectively. CONCLUSIONS: Whereas the therapeutic cost for drotrecogin alfa (activated) appears high (at around pounds 5000 per patient) and the potential impact on the provider budget is considerable, drotrecogin alfa (activated) is clinically effective, represents a cost-effective use of resources, and is a significant advance in the treatment of severe sepsis in patients requiring intensive care.

Acute Disease↗

PubMed2006

Novel transparent poly(silazane) derived solvent-resistant, bio-compatible microchannels and substrates: application in microsystem technology.

In this report we have described fabrication of preceramic polymer-derived transparent, solvent-resistant, thermally stable and bio-compatible microchannels and substrates using soft-lithography methods such as micromolding in capillary (MIMIC) and micromolding. The micromolding technique was preferred in the current work to fabricate channels by thermal and photo crosslinking of a commercially available poly(vinyl silazane) (VL 20, KION Corporation, USA). Both thermal and photo cured preceramic polymer channels were found to possess unique glass-like characteristics, such as transparency and chemical inertness. However, their surfaces were identified to be hydrophobic with a contact angle of 101 degrees . To have an insight on the nature of the surface groups present on the surface of the cured preceramic polymer, ATR-IR was carried out. The hydrophobic nature of the cured polymer was best utilized for direct patterning of protein by nonspecific binding.

Animals↗

PubMedDate not supplied

A comparison of intensive behavior analytic and eclectic treatments for young children with autism.

We compared the effects of three treatment approaches on preschool-age children with autism spectrum disorders. Twenty-nine children received intensive behavior analytic intervention (IBT; 1:1 adult:child ratio, 25-40 h per week). A comparison group (n=16) received intensive "eclectic" intervention (a combination of methods, 1:1 or 1:2 ratio, 30 h per week) in public special education classrooms (designated the AP group). A second comparison group (GP) comprised 16 children in non-intensive public early intervention programs (a combination of methods, small groups, 15 h per week). Independent examiners administered standardized tests of cognitive, language, and adaptive skills to children in all three groups at intake and about 14 months after treatment began. The groups were similar on key variables at intake. At follow-up, the IBT group had higher mean standard scores in all skill domains than the AP and GP groups. The differences were statistically significant for all domains except motor skills. There were no statistically significant differences between the mean scores of the AP and GP groups. Learning rates at follow-up were also substantially higher for children in the IBT group than for either of the other two groups. These findings are consistent with other research showing that IBT is considerably more efficacious than "eclectic" intervention.

Adaptation, Psychological↗

PubMedDate not supplied

Rapid identification of hemoglobin variants by electrospray ionization mass spectrometry.

The precise identification of human hemoglobin variants, over 700 human hemoglobin variants are known, is essential for prediction of their clinical and genetic significance. A systematic approach to their rapid identification is described. Traditionally this requires protein or DNA characterization which entails lengthy analytical procedures. To overcome these obstacles a rapid approach to variant hemoglobin identification has been developed using conventional phenotypic methods combined with electrospray ionization-mass spectrometry (ESI-MS). The latter requires only a small amount of whole blood (10 microl) but in most cases 2 microl would have been sufficient and no preanalytical steps, such as separation of red cells or globin chains, are necessary. Aged, hemolyzed blood samples can also be analyzed. This approach has been used to positively identify 95% of the variants in over 250 samples. The remaining 5% in which a variant was detected by phenotypic techniques were not resolved by mass spectrometry. Ninety-nine different abnormalities comprising 36 alpha-chain variants, 59 beta-chain variants (including 2 extensions), and 4 hybrid hemoglobins were identified. These include 15 novel variants. The application of ESI-MS described requires approximately 1 h to prepare and analyze each sample and has minimal reagent costs. The turnaround time on a single sample can be as little as 2 h. This technique can now be considered a useful additional tool for reference laboratories.

Amino Acid Substitution↗

PubMed1995

Relations between heart failure, ejection fraction, arrhythmia suppression and mortality: analysis of the Cardiac Arrhythmia Suppression Trial.

OBJECTIVES: We studied the relations between heart failure, ejection fraction, arrhythmia suppression and mortality. BACKGROUND: Both left ventricular ejection fraction and functional class of heart failure are strongly associated with mortality after acute myocardial infarction. Both are also related to the presence of ventricular arrhythmias and have been identified as factors related to the ability to suppress ventricular arrhythmias. Little has been reported about the relations between these two factors and arrhythmia suppression or mortality. METHODS: Baseline data from the Cardiac Arrhythmia Suppression Trial were used to define several categories of heart failure and to relate both the resulting categories and ejection fraction to arrhythmia suppression and mortality using logistic and survival regression analytic methodologies. RESULTS: Regardless of the prospective baseline definition of heart failure used, the data consistently showed that heart failure was a more powerful predictor of subsequent congestive heart failure events and arrhythmia suppression and was equally powerful in predicting death. However, each variable provided incremental information when included in the prediction model. Heart failure and ejection fraction appeared to be independent predictors of death. Interactions were observed: A low ejection fraction was more predictive of failure of arrhythmia suppression in patients with than without evidence of heart failure before or at baseline; a low ejection fraction was more predictive of subsequent congestive heart failure events in patients without than with evidence of heart failure before or at baseline. CONCLUSIONS: Although heart failure as a prognostic feature appears to be somewhat superior to ejection fraction, both are powerful predictors of arrhythmia suppression and cardiac events in patients with ventricular arrhythmia after myocardial infarction. Each provides incremental prediction.

Arrhythmias, Cardiac↗

PubMed2001

Ornithine carbamoyltransferase deficiency: improved sensitivity of testing for protein tolerance in the diagnosis of heterozygotes.

The most direct test of functional capacity of the liver in nitrogen disposal is to stress the urea cycle with a high protein load. This has been used in the diagnosis of heterozygosity for ornithine carbamoyltransferase deficiency for many years by measuring the subsequent excretion of orotic acid in urine. Reports have shown some ambiguity in both this and the more recent allopurinol test. We investigated the effects of different foods as the protein load and of different analytical methods. A standardized protocol was developed, giving 35 g protein per m2 surface area as steamed fat-free chicken breast to be eaten within 30 min. Urine was collected at zero time and over 0-2, 2-4 and 4-6 h. Compliance was checked by assessing excretion of amino acids. Diagnostic sensitivity was improved by reference to the change in excretion, i.e. the ratio of excretions 2-4 h/0-2 h. Extension of the test to 6 h gave no diagnostic advantage over a 4 h test. Comparison of the analysis of total orotic acids by the photometric method of Harris and Oberholtzer, the reference method for this study, with that by the method of Goldstein and colleagues showed that the latter gave erratic results with some false positives. However, comparison of the method of Harris and Oberholtzer with specific orotic acid analysis by a modification of the stable-isotope internal standard method of Rimoldi and colleagues yielded the same diagnoses. The improved protein load test gave a clearly positive result in all 16 obligate heterozygotes and 2 possible heterozygotes tested from 14 kindred, and a clearly negative result in all 18 control subjects and all 6 of the possible heterozygotes who were later shown by DNA studies not to carry the family mutation. The test appears at least as sensitive and specific as the allopurinol test, and is more convenient because of the short period of sample collection.

Adolescent↗

PubMed2026

Hybridization capture increases on-target nanopore sequencing of plant RNA tobamovirus- derived cDNA libraries.

High-throughput sequencing (HTS) can support plant virus surveillance, but host nucleic acids often reduce on-target read recovery. We evaluated a targeted hybridization-capture workflow in which barcoded double-stranded cDNA (ds-cDNA) libraries generated from plant RNA extracts spiked with lyophilized tobamovirus-positive controls were enriched before Oxford Nanopore sequencing. Biotinylated probes targeted conserved regions of cucumber green mottle mosaic virus (CGMMV), species Tobamovirus viridimaculae; pepper mild mottle virus (PMMoV), species Tobamovirus capsici; and tobacco mosaic virus (TMV), species Tobamovirus tabaci. Across four pairs per virus, relative target-read abundance increased after capture from 0.76 ± 0.33% to 37.62 ± 15.72% for CGMMV, 8.16 ± 3.86% to 24.68 ± 12.34% for PMMoV, and 15.62 ± 10.40% to 36.83 ± 30.33% for TMV. Exact two-sided Wilcoxon signed-rank tests yielded P = 0.125 for each virus; with four nonzero differences in a common direction, this was the minimum attainable two-sided P value. Genome-coverage breadth was maintained. Retrospective duplex qPCR supported an increased virus-to-18S ratio for CGMMV, showed a variable PMMoV response, and showed a decreased virus-to-18S ratio for TMV because the 18S signal shifted earlier by as much as or more than the TMV signal. The findings provide proof-of-concept evidence for target-dependent library enrichment but do not establish analytical sensitivity, diagnostic performance, or field validity. Validation with naturally infected, low-titer, and mixed-infection samples and comparison with simpler targeted workflows are required.

biosecurity↗

PubMed2006

Pumpless, selective docking of yeast cells inside a microfluidic channel induced by receding meniscus.

We present a simple cell docking method induced by receding meniscus to capture non-adherent yeast cells onto microwells inside a microfluidic channel. Microwells were fabricated either by capillary moulding of UV curable polyurethane acrylate (PUA) onto glass substrate or direct replica moulding of poly(dimethyl siloxane) (PDMS). A cell suspension of the budding yeast, Saccharomyces cerevisiae, was introduced into the microfluidic channel by surface tension driven capillary flow and a receding meniscus was subsequently generated by evaporation. As the meniscus progressed, one to multiple yeast cells were spontaneously captured onto microwells by lateral capillary force created at the bottom of the meniscus. Using this cell-based platform, we observed the response of yeast cells upon stimulation by a mating pheromone (alpha-factor) by monitoring the expression of green fluorescent protein (GFP) with time. It was observed that alpha-factor triggered the expression of GFP at 60 min after stimulation and the fluorescence intensity was sustained for an additional 60 min without changes.

Cells, Immobilized↗

PubMed1993

Perseverations on a critical theme.

In response to my earlier critique of recent attempts to rebut principlism as an ethical approach, Green, Gert, and Clouser (GG&C) have in turn offered their own critique of my appraisal. This essay identifies eight major criticisms GG&C raise in their response and offers a rejoinder to each. Among them, three are especially important: (1) that the label of 'deductivism' fails to capture GG&C's ethical method and should be replaced by 'descriptivism'; (2) that pluralistic accounts, including principlism, fail to offer any systematic way to resolve moral conflicts; and (3) that appeals to broader 'moral' principles beyond the moral rules are deceiving, since apparent differences in 'moral' judgment invariably involve disagreement about empirical facts rather than further moral considerations. In response to (1), I defend my earlier label by emphasizing the stipulated and invariant status of the moral rules GG&C invoke, even as I question the adequacy of their putative 'descriptivism'. In response to (2), I suggest the plausibility of pluralist approaches and reiterate the modified just-war criteria that Beauchamp and Childress invoke in situations when principles conflict. In response to (3), I suggest that a 'descriptivism' worthy of the name must systematically accommodate the appeal to moral principles that remains central to metaethical and normative discussions.

Bioethics↗