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Background: Busulfan is widely used in conditioning regimens to prepare patients for hematopoietic stem cell transplantation. Therapeutic drug monitoring (TDM) is critical due to large inter- and intra-individual variability in busulfan pharmacokinetics, and the risk of adverse consequences of toxicity including hepatic veno-occlusive disease. Busulfan is most commonly measured by liquid chromatography–mass spectrometry (LC-MS/MS), which is not as widely available in clinical laboratories as automated routine clinical chemistry analyzers. The objective was to perform analytical verification of a busulfan immunoassay on the Abbott Alinity c platform. Methods: The MyCare Oncology busulfan immunoassay was configured as a third-party reagent on the Abbott Alinity c. Imprecision, linearity, sample carryover, and onboard stability of reagent studies were evaluated. The performance of the busulfan immunoassay using the Abbott Alinity c was compared to the Beckman Coulter AU480 using sodium heparinized plasma, as well as to LC-MS/MS using lithium heparinized plasma. Results: The imprecision goal of 8% was met, and linearity within the analytical measurement range of 240 to 1700 ng/mL was verified. Sample carryover was negligible, and the reagents were stable onboard for at least 84 days. The busulfan immunoassay correlated well with LC-MS/MS (slope = 0.949, y-intercept = −7.8 ng/mL, r2 = 0.9935) and the Beckman Coulter AU480 (slope = 1.090, y-intercept = −34.5 ng/mL, r2 = 0.9988). Conclusions: This study demonstrated successful analytical verification of a busulfan third-party immunoassay on the Abbott Alinity c platform. The ability to perform TDM of busulfan on a routine clinical chemistry analyzer will positively impact turnaround times to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Sometimes, the fact that an attitude is fitting seems like a demand to have that attitude. But in other cases, the fact that an attitude is fitting seems more like a permission to have the attitude. I defend a proposal that can accommodate both of these appearances. I argue that there is a kind of emotionlessness, which I call apathy, that can be fitting or unfitting in just the same way that emotion can. I further argue that, in some cases, it can be fitting to respond a single object either with emotion or with apathy. When both apathy and emotion are fitting options, the fittingness of the emotion is a permission-like status; failures to have the fitting emotion are not failures of fit. But when an emotion is fitting and apathy is unfitting, the fittingness of the emotion is a demand-like status; failures to have the emotion are failures of fit. [ABSTRACT FROM AUTHOR]

This paper investigates the ethics of regarding others as epistemically hopeless. To regard a person as epistemically hopeless with respect to p is, roughly, to regard her as unable to see the truth of p through rational means. Regarding a person as epistemically hopeless is a stance that has surprising and nuanced moral implications. It can be a sign of respect, and it can also be a way of giving up on someone. Whether it is morally problematic to take up this stance, I argue, depends on the choices that one faces (or is likely to face). I close the paper by arguing against the view that there are standing moral reasons against regarding others as epistemically hopeless. [ABSTRACT FROM AUTHOR]

This paper introduces a novel form of pragmatic encroachment: one that makes a difference to the status of emotion rather than the status of belief. I begin by isolating a distinctive standard in terms of which we can evaluate emotion – one sometimes called "subjective fittingness," "epistemic justification," or "warrant." I then show how this standard for emotion could face a kind of pragmatic encroachment importantly similar to the more familiar encroachment on epistemic standards for belief. Encroachment on warranted emotion is a striking proposal that deserves attention. In fact, there are good reasons to think that encroachment on warranted emotion deserves to be considered the default view for those who already accept pragmatic encroachment on the epistemic status of belief. I support this parity claim by arguing for a principle that establishes a limited coordination between the conditions that warrant emotion and the conditions that justify belief. [ABSTRACT FROM AUTHOR]

If there is pragmatic encroachment in epistemology, whether a person knows that p can vary with normative facts about her actions—including facts that do not bear on the truth or likelihood of p. This paper raises an underappreciated question for defenders of pragmatic encroachment: which of the many norms on action are distinctively connected to knowledge? To the extent that contemporary defenders of pragmatic encroachment address this question, they do so by citing norms of 'practical rationality.' I show that this approach can only be made to work on the assumption that all immorality involves some form of incoherence. I then suggest a pluralist strategy for pragmatic encroachers who seek to answer my question without making this heavyweight metaethical assumption: they should agree that multiple distinct norms on action play a difference-making role in epistemology. I close the paper by sketching three ways in which pragmatic encroachers might pursue this strategy. [ABSTRACT FROM AUTHOR]

Most agree that, in some special scenarios, prudence can speak against feeling a fitting emotion. Some go further, arguing that the tension between fittingness and prudence afflicts some emotions in a fairly general way. (Perhaps, for instance, it's best for human well-being that we generally grieve much less than is fitting.) This paper goes even further: it argues that, when it comes to anxiety, the tension between fittingness and prudence is nearly inescapable. On any plausible theory, an enormous array of possible outcomes are both bad and epistemically uncertain in the right way to ground fitting anxiety. What's more, the fittingness of an emotion is a demanding, not a permissive, normative status. So the norms of fitting emotion demand a great deal of anxiety. For almost any realistic agent, it would be deeply imprudent to feel anxiety in a way that meets the demands set by norms of fitting emotion. [ABSTRACT FROM AUTHOR]

Radical moral encroachment is the view that belief itself is morally evaluable, and that some moral properties of belief itself make a difference to epistemic rationality. To date, almost all proponents of radical moral encroachment hold to an asymmetry thesis: the moral encroaches on rational belief, but not on rational credence. In this paper, we argue against the asymmetry thesis; we show that, insofar as one accepts the most prominent arguments for radical moral encroachment on belief, one should likewise accept radical moral encroachment on credence. We outline and reject potential attempts to establish a basis for asymmetry between the attitude types. Then, we explore the merits and demerits of the two available responses to our symmetry claim: (1) embracing radical moral encroachment on credence and (2) denying radical moral encroachment on belief. [ABSTRACT FROM AUTHOR]

In this paper, I defend an epistemic requirement on fitting hopes and worries: it is fitting to hope or to worry that p only if one's epistemic position makes it rational to suspend judgment as to whether p. This view, unlike prominent alternatives, is ecumenical; it retains its plausibility against a variety of different background views of epistemology. It also has other important theoretical virtues: it is illuminating, elegant, and extensionally adequate. Fallibilists about knowledge have special reason to be friendly to my view; it can help them explain why it can be unfitting to hold on to hope and worry in the face of overwhelming evidence, and it can also help them explain the sense in which knowledge that p and hope that –p are in tension with one another. [ABSTRACT FROM AUTHOR]

This essay provides a novel argument for impurism, the view that certain non-truth-relevant factors can make a difference to a belief's epistemic standing. I argue that purists, unlike impurists, are forced to claim that certain 'high-stakes' cases rationally require agents to be akratic. Akrasia is one of the paradigmatic forms of irrationality. So purists, in virtue of calling akrasia rationally mandatory in a range of cases with no obvious precedent, take on a serious theoretical cost. By focusing on akrasia, and on the nature of the normative judgments involved therein, impurists gain a powerful new way to frame a core challenge for purism. They also gain insight about the way in which impurism is true: my argument motivates the claim that there is moral encroachment in epistemology. [ABSTRACT FROM AUTHOR]

According to the view that there is moral encroachment in epistemology, whether a person has knowledge of p sometimes depends on moral considerations, including moral considerations that do not bear on the truth or likelihood of p. Defenders of moral encroachment face a central challenge: they must explain why the moral considerations they cite, unlike moral bribes for belief, are reasons of the right kind for belief (or withheld belief). This paper distinguishes between a moderate and a radical version of moral encroachment. It shows that, while defenders of moderate moral encroachment are well-placed to meet the central challenge, defenders of radical moral encroachment are not. The problem for radical moral encroachment is that it cannot, without taking on unacceptable costs, forge the right sort of connection between the moral badness of a belief and that belief's chance of being false. [ABSTRACT FROM AUTHOR]

This paper presents a challenge to conciliationist views of disagreement. I argue that conciliationists cannot satisfactorily explain why we need not revise our beliefs in response to certain moral disagreements. Conciliationists can attempt to meet this challenge in one of two ways. First, they can individuate disputes narrowly. This allows them to argue that we have dispute-independent reason to distrust our opponents’ moral judgment. This approach threatens to license objectionable dogmatism. It also inappropriately gives deep epistemic significance to superficial questions about how to think about the subject matter of a dispute. Second, conciliationists can individuate disputes widely. This allows them to argue that we lack dispute-independent reason to trust our opponents’ moral judgment. But such arguments fail; our background of generally shared moral beliefs gives us good reason to trust the moral judgment of our opponents, even after we set quite a bit of our reasoning aside. On either approach, then, conciliationists should acknowledge that we have dispute-independent reason to trust the judgment of those who reject our moral beliefs. Given a conciliationist view of disagreement's epistemic role, this has the unattractive result that we are epistemically required to revise some of our most intuitively secure moral beliefs. [ABSTRACT FROM AUTHOR]

Many writers have recently argued that there is something distinctively problematic about sustaining moral beliefs on the basis of others’ moral views. Call this claim pessimism about moral deference. Pessimism about moral deference, if true, seems to provide an attractive way to argue for a bold conclusion about moral disagreement: moral disagreement generally does not require belief revision. Call this claim steadfastness about moral disagreement. Perhaps the most prominent recent discussion of the connection between moral deference and moral disagreement, due to Alison Hills, uses pessimism about the former to argue for steadfastness about the latter. This paper reveals that this line of thinking, and others like it, are unsuccessful. There is no way to argue from a compelling version of pessimism about moral deference to the conclusion of steadfastness about moral disagreement. The most plausible versions of pessimism about moral deference have only very limited implications for moral disagreement. [ABSTRACT FROM AUTHOR]

Subject-sensitive invariantism posits surprising connections between a person's knowledge and features of her environment that are not paradigmatically epistemic features. But which features of a person's environment have this distinctive connection to knowledge? Traditional defenses of subject-sensitive invariantism emphasize features that matter to the subject of the knowledge-attribution. Call this pragmatic encroachment. A more radical thesis usually goes ignored: knowledge is sensitive to moral facts, whether or not those moral facts matter to the subject. Call this moral encroachment. This article argues that, insofar as there are good arguments for pragmatic encroachment, there are also good arguments for moral encroachment. [ABSTRACT FROM AUTHOR]

A data breach occurs when sensitive data records from an organization are released either intentionally or unintentionally to an untrusted environment. This research examines mega breaches, data breaches that constitute the loss of a million records or more, and how organizations have responded to recent mega breaches. Data from 2,273 data breaches that occurred between 2005 and 2015 that involved the confirmed loss of records are analyzed. This data is used to examine recent trends in the occurrences of mega breaches as well as the different categories of breaches and the different entities affected by breaches. In addition, this research examines methods that can be employed by organizations in order to prevent data breaches, such as encryption and employee training. [ABSTRACT FROM AUTHOR]

Guided by Honig and Hatch’s conceptualization of bridging and buffering, we analyzed the first teacher collective bargaining agreements negotiated after the enactment of the Ohio Teacher Evaluation System to understand how state law has shaped provisions for teacher evaluation, compensation, reductions in force (RIF), transfers, and contract renewal. We found surprising variation in provisions across districts. Most notable was how districts defined comparable evaluations in making RIF decisions. Bridging districts provided the greatest protections for the most accomplished teachers, regardless of seniority. In contrast, buffering districts have RIF provisions based on seniority. [ABSTRACT FROM AUTHOR]

In capillary electrophoresis, it is commonly considered that even a moderately high ionic concentration in the background electrolyte (BGE) leads to high currents, resulting in Joule heating and serious peak distortion. As a new approach to overcome this problem, zwitterionic (Zwittergent-3–14) and/or non-ionic (Tween 20) surfactants have been added to BGEs containing high salt concentrations (e.g. 0.3 M NaCl) and have been shown to result in acceptable separation currents (<200 µA). In turn, these BGEs could be applied to the separation of samples containing high salt concentrations (such as undiluted seawater) without the occurrence of any significant peak broadening due to electrodispersion of the sample. For example, a BGE comprising 10 mM Zwittergent-3–14, 50 mM Tween 20, 0.3 M NaCl and 5 mM phosphate (ph 7) could be used for the determination of UV-absorbing anions in seawater, giving good peak shapes and detection limits of 0.8 µM and 0.6 µM for nitrate and bromide, respectively. The beneficial effects of the non-ionic surfactant on the separation were attributed largely to suppression of the electro-osmotic flow. On the other hand, the zwitterionic surfactant was found to be capable of the incorporation of some anions in accordance with the behaviour of these same surfactants in electrostatic ion chromatography. This incorporation resulted in a decreased conductivity of the BGE and also a change in the separation selectivity of the system. [ABSTRACT FROM AUTHOR]

A new ion chromatographic (IC) system, in which n-tetradecylphosphocholine (TDPC, a phosphobetaine type of zwitterionic surfactant) was used as the stationary phase, pure water as the mobile phase, and conductivity as the method of detection, has been developed for the determination of inorganic acids. Five model acids, HCl, HNO3, HClO4, H2SO4, and H3PO4, were separated to baseline and eluted in the order H3PO4 > HCl > HNO3 > H2SO4 > HClO4. When peak areas were plotted against the concentrations of the acids in samples, linear calibration curves were obtained. Ultimate determination limits were approximately 1 mmol L–1, but the discrimination of the method between solutions of different concentration was better than 10 μmol L–1 for those model analytes. Salts of divalent cations could also be separated, but they were eluted faster than the acids. No separation was observed for the salts of monovalent cations. This newly proposed approach is applicable to the simultaneous determination of the inorganic acids (produced by reactions of NOx, SOx, and HCl with water) in aerosols. [ABSTRACT FROM AUTHOR]

Capillary electrophoresis (CE) using sulfobetaine-type zwitterionic micelles as the background electrolyte (BGE) has been used to determine inorganic anions in human saliva. The zwitterionic micelles resulted in unique migration behavior for the separation of inorganic anions. They also prevented adsorption of proteins on the inner wall of the capillary. These properties of the zwitterionic micelles enabled the direct determination of inorganic anions in human saliva. Three species of inorganic anions, NO2 –, NO3 –, and SCN–, were found in real samples and the analysis was achieved within 3 min. Direct UV-absorption was used as the detection method and the detection limits for these anions were 2.0, 1.0, and 5.0 μmol L–1, respectively (0.09, 0.06, and 0.30 μg mL–1). [ABSTRACT FROM AUTHOR]

The inability to separate fluoride, phosphate and sulfate by electrostatic ion chromatography (EIC) was overcome by using an ODS silica column coated with mixed zwitterionic-cationic surfactants as the stationary phase. The best results were obtained using the zwitterionic surfactant, 3-(N,N-dimethylmyristylammonium)-propanesulfonate (C19H41NO3S), and the cationic surfactant, myristyltrimethylammonium, CH3(CH2)13N+(CH3)3, in a 10:1 molar ratio in the column coating solution. With a dilute solution of sodium tetraborate as the eluent the model analyte anions were completely separated in the following elution order: F–, HPO4 2–, SO4 2–, Cl–, NO2 –, Br–, NO3 –. The very early elution of phosphate and sulfate is most unusual and is unique to this system. Detection limits better than 1.1 × 10–4 mM and linear calibration plots up to 7.0 mM were obtained with a suppressed conductivity system. [ABSTRACT FROM AUTHOR]

For this study, 144 subjects assumed either the role of an interviewer or the role of a respondents and then interacted under visual contact and no visual contact conditions. Under each condition the respondent was secretly instructed to answer six questions honestly and six questions deceptively. It was found that (a). deceptive answers were hesitant and lengthy, (b) visual presence increased variability in verbal response latencies and decreased response duration or length, (c) although interviewers tended to give respondents the benefit of the doubt, they still discriminated between truth and falsehoods and (d) increased hesitation and increased message length were associated with decreased believability. [ABSTRACT FROM AUTHOR]