Idiosyncratic Cases Research Articles

Plasma Sphingoid Base Profiles of Patients Diagnosed with Intrinsic or Idiosyncratic Drug-induced Liver Injury.

Sphingolipids are exceptionally diverse, comprising hundreds of unique species. The bulk of circulating sphingolipids are synthesized in the liver, thereby plasma sphingolipid profiles represent reliable surrogates of hepatic sphingolipid metabolism and content. As changes in plasma sphingolipid content have been associated to exposure to drugs inducing hepatotoxicity both in vitro and in rodents, in the present study the translatability of the preclinical data was assessed by analyzing the plasma of patients with suspected drug-induced liver injury (DILI) and control subjects. DILI patients, whether intrinsic or idiosyncratic cases, had no alterations in total sphingoid base levels and profile composition compared to controls, whereby cardiovascular disease (CVD) was a confounding factor. Upon exclusion of CVD individuals, elevation of 1-deoxysphingosine (1-deoxySO) in the DILI group emerged. Notably, 1-deoxySO values did not correlate with ALT values. While 1-deoxySO was elevated in all DILI cases, only intrinsic DILI cases concomitantly displayed reduction of select shorter chain sphingoid bases. Significant perturbation of the sphingolipid metabolism observed in this small exploratory clinical study is discussed and put into context, in the consideration that sphingolipids might contribute to the onset and progression of DILI, and that circulating sphingoid bases may function as mechanistic markers to study DILI pathophysiology.

Indeterminacy in L1 French grammars: the case of gender and number agreement

AbstractAlthough L1 French speakers (FS) acquire the formal features of gender and number early, agreement appears to take longer, leading to persistent difficulties even for cases of straightforward agreement within a nominal or verbal phrase. This begs the questions of how adult FSs (n = 168) may fare with idiosyncratic cases of agreement such as nominal affective constructions and past participles as measured by a written grammaticality judgment /correction task and preference/grammaticality judgment task. The findings showing that participants performed better at correctly accepting than rejecting stimuli, are consistent with an increasing number of empirical studies revealing individual differences among adult L1 speakers. The findings are discussed from a generative perspective and the usage-based perspective of the Basic Language Cognition-High Language Cognition theory of L1 proficiency (Hulstijn, 2015).

Australian SME's experience in transitioning to circular economy

Small and medium-sized enterprises (SMEs) are becoming increasingly aware of the values of the Circular Economy (CE) as a sustainable alternative to the traditional linear economic model. However, the academic discussion thus far mostly clusters around conceptualisation and idiosyncratic cases challenging to replicate and generalise. Based on 16 case studies of Australian SMEs' success stories, this paper narrates their vision, alignment with 3R concepts, and critical success factors through transitioning to Circular Economy. Leaders' vision of embracing CE, rather than directly seeking financial outcomes, has led to their success. While aligning towards a singular aspect of 3R (reduce, reuse, or recycle), SMEs demonstrate an attempt to blend all 3Rs into their frugal business model. The leadership's passion and finding a practical solution are the essential internal critical factors for SMEs successfully implementing CE. Collaboration is the key external factor, suggesting persuasive public, private, and academic partnerships to address CE challenges.

Mechanism of idiosyncratic drug induced liver injury (DILI): unresolved basic issues.

Clinical features of idiosyncratic drug induced liver injury (DILI) are well described in cases that have been assessed for causality using the Roussel Uclaf Causality Assessment Method (RUCAM), but our understanding of the mechanistic steps leading to injury is fragmentary. The difficulties describing mechanistic events can be traced back to the lack of an animal model of experimental idiosyncratic DILI that can mimic the genetic requirements of human idiosyncratic DILI. However, immune tolerance plays a dominant role in the immune response of the liver, and impairment of immune tolerance with immune checkpoint inhibitors increases DILI in both humans and animals. This may provide one method to study the individual steps involved. In general. the human DILI liver is a secret keeper providing little insight into what occurs in the diseased organ. Sufficient evidence exists that most idiosyncratic cases are mediated by the adaptive immune system, which depends on stimulation of the innate immune system, but the triggering factors are unknown. It is attractive to hypothesize that the gut microbiome plays a role; however, it is very difficult to study. Similarly, exosomes are likely to play an important role in communication between hepatic cells and the immune system, but there is a lack of data on blood exosomes in affected patients. Reactive metabolites are likely to play an important role. This is supported by the current analysis, which revealed an association between metabolism by cytochrome P450 and drugs most commonly involved in causing idiosyncratic DILI with causality verified by RUCAM. Circumstantial evidence suggests that reactive oxygen species (ROS) generated by cytochrome P450 could be responsible for the initial steps of injury, but details are unknown. In conclusion, most of the mechanistic steps leading to idiosyncratic DILI remain unclear.

Probabilistic Presumptions in Fourth Amendment Decisionmaking

For decades, the Supreme Court has maintained a rhetorical commitment to an ad hoc, case-by-case, totality of the circumstances approach to evaluating probable cause and reasonable suspicion. Despite the Court’s insistence that there are so many factors involved in the assessment of Fourth Amendment probabilities that one case will seldom be useful precedent for future cases, it has with increasing frequency endorsed the use of presumptive rules in this context. Such presumptions provide an appealing balance between the often competing imperatives of providing clear guidance to lower courts and law enforcement officers, on the one hand, and retaining the flexibility to ensure results consistent with Fourth Amendment principles in idiosyncratic cases, on the other. Additionally, although courts might evaluate the suitability of some such presumptions using quantitative analysis, in other cases, the use of qualitative, intuition-based judgment is necessary.

Breaking Conventions: The Lebanese Civil War

Over the years, political scientists have largely come to accept four assumptions about civil wars. These assumptions are useful when applied to civil war as a concept. Unfortunately, they are invalid when applied to idiosyncratic cases like the Lebanese Civil War, and one must therefore exercise caution before generalizing from them. This essay discusses why the Lebanese Civil War defied political scientists’ usual assumptions about civil conflict. It suggests that countries sharing Lebanon’s idiosyncrasies will also resist the four assumptions. Finally, it uses survey data to undercut a view commonly held by the media and public—that different ethnic groups do not socialize with one another during times of conflict.

Neither Fish, nor Fowl: Honeybees and the Parameters of Current Legal Frameworks for Animals, Wildlife and Biodiversity

The regulation of animals falls into three main paradigms; animal health, animal welfare and conservation. This article argues that in the modern context there are several regulatory challenges which are not accommodated within those parameters including those presented by contemporary issues such as animal diseases and hybrid and feral animals. A case study of honeybees is used to explore these frameworks and their parameters and limitations in detail. The difficulties arising are not confined to idiosyncratic cases such as honeybees however, but also apply at a broader level. While some of these difficulties might be tackled through incremental changes to existing legislation, a more holistic framework which moves beyond historical assumptions about the nature of animals and their relationship with people therefore, will ultimately be needed.

Characteristics and host country drivers of Chinese FDI in Europe: a company-level analysis

The present study of direct investment from mainland China into Europe complements and extends prior studies by building on a firm-level database comprising of 548 Chinese subsidiaries in 26 countries in EU and EFTA. The study identifies and characterises three segments of subsidiaries, predominantly related, respectively, to private companies' market-seeking activities, state-owned companies' production- and technology-seeking activities, and efficiency-seeking activities in Eastern Europe. Through multivariate regression the study confirms that potentials for market exploitation are particularly important host country factors for attracting Chinese FDI. There is no strong correlation between aggregate national R&D spending and Chinese knowledge-seeking investments, reflecting that such investments tend to be individual and highly idiosyncratic cases. Rather than a wholesale adoption or dismissal of extant FDI-theories vis-a-vis new ones, extant theories are found to apply differentially to the different identified segments of Chinese outward FDI.

Abstracts from the In Vitro Toxicology Society Annual Meeting Radisson Blu Hotel Glasgow, United Kingdom November 14–15, 2016

Abstracts from the In Vitro Toxicology Society Annual Meeting Radisson Blu Hotel Glasgow, United Kingdom November 14–15, 2016

Perioperative risk factors for vascularized composite allotransplantation: A systematic review and proposal of identity‐defining VCA

Vascularized composite allotransplantation (VCA) is a new dimension in reconstructive surgery. Generally, these procedures are offered for quality of life and functional indications rather than life-saving indications. Controversy exists, therefore, over the indications and risk/benefit ratios of VCA. Transplantation failure is a basic measurable risk of VCA. In this report we attempt to analyze perioperative factors associated with failures. Such factors are generally independent of technical performance and can be assessed to better define regulations applied to VCA. Ninety-one VCA procedures were identified, and 18 (19.8%) of them failed. Significant (P < 0.05) failure rates were associated with idiosyncratic cases (100%), cases performed without psychological screening (56.3%), cases performed without competent social support systems (44%), and cases done in developing countries (52.4%). A substantial but not significant failure rate was observed in cases performed without institutional review (36.4%). These findings suggest that institutional, professional, social, and ethical standards applied to VCA should require clarification of perioperative risk managements for any clinical VCA program, because such managements can be critical factors in determining outcome. The special character of these transplantation procedures suggest the concept of identity-defining vascularized composite allotransplantation (IVCA), for which psychological screening and third-party supervision is recommended.

Lithium and tricyclic antidepressant-induced delirium presenting with prominent dyspraxia: case report

Long-term treatment with lithium has been associated with mild cognitive impairment, mental slowing and memory impairment [Cookson, 1997]. Neurological complications such as muscle weakness, drowsiness, ataxia, confusion and dysarthria can be late signs of lithium toxicity [Tyrer, 1996], but idiosyncratic cases have also been reported [McGovern, 1983; Brown and Rosen, 1992]. In one such case, McGovern described an elderly female patient, with a history of endogenous depression, who developed tremor, vertigo, ataxia and dysphasia, following the initiation of lithium within normal therapeutic serum levels [McGovern, 1983]. In addition, Brown and colleagues described the case of a 64-year-old woman with a 25-year history of schizoaffective disorder who developed delirium following treatment with lithium, also within the therapeutic serum level [Brown and Rosen, 1992]. Tricyclic antidepressants can also cause neurological side effects such as confusion, impaired memory and paresthesia [Joint Formulary Committee, 2011]. Although, there are no case reports of dyspraxia associated with tricyclic antidepressants when used alone in the literature. However, there is an increased risk of toxicity when tricyclic antidepressants are used in combination with lithium. Worrall and colleagues published a case describing slowly developing constructional dyspraxia and mild dysphasia in a 50-year-old female patient with a 2-year history of endogenous depression [Worrall and Gillham, 1983]. After responding to a combination of lithium and amitriptyline for 14 months, she began to complain of difficulties in finding words in conversation and of memory impairment. These problems resolved completely when the lithium was stopped and amitriptyline continued. In our report, we describe a case of delirium presenting with prominent dyspraxia at therapeutic lithium serum levels, following several years of uneventful lithium administration, but within 3 months of the addition of clomipramine. The case described above [Worrall and Gillham, 1983] improved when lithium was stopped but this presentation resolved when clomipramine was withdrawn. This suggests that an idiosyncratic interaction between tricyclic antidepressants and lithium can cause delirium with dyspraxia.

Compound or phrase? Analogy in naming

In German (and other Germanic languages) both phrases and compounds are used as names for concepts (e.g. Rotwein ‘red wine’, grüner Daumen ‘green thumb/green fingers’). This study examines such kind-referring German A+N compounds and phrases. Whereas it is a widely accepted fact that compounds are inherently suitable for kind reference (or “naming”), due to their status as word formation entities, phrases used for kind reference are regarded as isolated, idiosyncratic cases. This paper presents the results of a production experiment which show that both A+N phrases and A+N compounds should be regarded as a productive means of coining names. The choice between the two constructions is largely dependent on the availability of similar constructions in the mental lexicon of the speakers. The larger the number of lexicalized compounds with the same adjective or noun, the higher the probability of the subjects choosing a compound. The larger the number of lexicalized phrases with the same adjective or noun, the higher the probability of the subjects choosing a phrase. Thus, the probability of using a compound to name a new concept positively correlates with the number of available other compounds (types) that feature one or both of the elements to be combined. This effect is stronger for adjectives than for nouns. These results cannot be accounted for in a rule-based approach to grammar and lexicon. Instead they support a constructionist approach in which differences in productivity directly relate to the (number of) existing instantiations of the respective constructions in the mental lexicon.

The Uses of Analogies in Seventeenth and Eighteenth Century Science

The object of this paper is to look at the extent and nature of the uses of analogy during the first century following the so-called scientific revolution. Using the research tool provided by JSTOR we systematically analyze the uses of “analog” and its cognates (analogies, analogous, etc.) in the Philosophical Transactions of the Royal Society of London for the period 1665–1780. In addition to giving the possibility of evaluating quantitatively the proportion of papers explicitly using analogies, this approach makes it possible to go beyond the maybe idiosyncratic cases of Descartes, Kepler, Galileo, and other much studied giants of the so-called Scientific Revolution. As a result a classification of types of uses is proposed. Relations between types of analogies and research fields are also established. In this paper we are less interested in discussing the “real nature” or “essence” or even the cognitive limitations of analogical thinking than in describing its various uses and different meanings as they changed over the course of a century.

Retrospective Evaluation of a Possible Interaction Between Warfarin and Levofloxacin

In order to clarify the clinical significance of a suspected drug interaction, we sought to determine if the international normalized ratio (INR) is affected when levofloxacin is administered in patients receiving long-term warfarin therapy. Retrospective cohort study using pharmacy and medical records. Outpatient clinic. Forty-three patients receiving long-term warfarin therapy who subsequently were prescribed either levofloxacin (22 patients) or felodipine (21 controls); felodipine was chosen as it has been shown not to interact with warfarin. Patients in both groups were required to have a documented INR before the start of levofloxacin or felodipine (pre-INR) and either during levofloxacin or felodipine therapy or within 15 days after the drug had been started (post-INR). Patient demographics were similar between the two treatment groups. The mean +/- SD age of the patients in the levofloxacin and control groups was 59.5 +/- 8.7 and 65.3 +/- 11.5 years, respectively (p=0.07). The mean change between the pre- and post-INR (primary outcome measure) was 0.31 +/- 0.82 (pre-INR 2.46, post-INR 2.76) and 0.21 +/- 0.54 (pre-INR 2.46, post-INR 2.67) in the levofloxacin and felodipine groups, respectively (p=0.65). A post hoc power analysis, based on a sample-derived, weighted standard deviation of 0.68, revealed that the study had 66% power to detect a change of 0.5 in the INR value. The percentage of patients who required a warfarin dosage adjustment based on the post-INR (secondary outcome measure) was 41% (9 of 22 patients) in the levofloxacin group and 33% (7 of 21 patients) in the felodipine group. Although our primary analysis did not detect a warfarin-levofloxacin interaction, the potential for such an interaction, especially in idiosyncratic cases, cannot be ruled out. Clinicians should closely monitor INR values when levofloxacin is administered jointly with warfarin.

Who makes economic policy in Africa and how?

To understand the considerable detorioration in the economic policies of many African countries during the 1970s, it is essential to go beyond the economist's analytical models. The pressing drive of authoritarian rulers to survive adds an important dimension to economic policy choices. Although constrained to varying degrees by ethnic, regional and class loyalties among populations they govern, African rulers enjoy a measure of autonomy in making policy. They did not react speedily to the growing economic crisis during the early 1980s, however. Most reforms were undertaken under pressure and many policy efforts failed. Some countries managed to sustain reforms, but the important question is how to go beyond these idiosyncratic cases.

GENERALIZING ABOUT MESSAGES: SUGGESTIONS FOR DESIGN AND ANALYSIS OF EXPERIMENTS

Current research practices in communication create problems for both internal and external validity. One serious design flaw, which involves use of a single message to represent a category of messages, occurs in nearly all of the experimental research on communication effects. The problem with such a design is that an observed difference between categories may reflect only differences between individual, idiosyncratic cases. A related error, the “language-as-fixed-effect fallacy,” involves use of several replications of each category, but analysis of the cases as fixed effects. The consequence is that findings cannot be generalized beyond the sample used. Future research should use multiple cases within each message category studied and treat cases as nested random effects. Since the cases cannot be true random samples from message populations, care must be taken to avoid known sources of bias or other barriers to generalization.

Ketoconazole in griseofulvin-resistant dermatophytosis

The efficacy of ketoconazole was evaluated in twenty patients with chronic dermatophyte infections who had failed to clear with griseofulvin therapy. Trichophyton rubrum was the causative organism in nineteen of the patients, and Trichophyton mentagrophytes in one patient. Three of twelve organisms tested showed in vitro resistance to griseofulvin. Duration of infection ranged from 2 to 28 years. Patients received 200 to 400 mg of ketoconazole daily for periods up to 8 months. In addition, patients were followed for 5 months post-therapy to monitor recurrences. Clearing was seen clinically as early as 2 weeks, and by 18 weeks all patients showed marked improvement or clinical clearing, though only six achieved complete mycologic cure. Improvement followed a predictable sequence of sites, with lesions of the trunk healing first, followed by hands, feet, and finally, nails. After 8 months, though all patients showed proximal nail clearing, onychomycosis persisted in thirteen of twenty affected sites. By 5 months post-therapy, four of six patients who had achieved clearing of skin and nails showed recurrences. No significant side effects were observed during therapy, though rare, apparently idiosyncratic cases of hepatotoxicity have been reported. Ketoconazole is an affective therapeutic agent for griseofulvin-resistant dermatophytosis. Apparent cures may subsequently recur after discontinuation of therapy.