Analytical considerations for accurately capturing the relevant species contributing to vitamin D status in liquid chromatography-tandem mass spectrometry assays

This tutorial review focuses on analytical challenges encountered with the liquid chromatography-tandem mass spectrometry determination of 25-hydroxyvitamin D, which is currently still considered the metabolite that is most representative of vitamin D status. It describes how multiple binding states of circulating 25-hydroxyvitamin D (phase II metabolites, epimers, free/bioavailable/protein-bound species) can influence the accuracy of the analytical determination. It also summarizes important chemical species that can inadvertently contribute to vitamin D status and thus cause systematic errors. These interfering endogenous and exogenous compounds might be isomers of vitamin D, constitutional isomers or isobars and the article outlines techniques to eliminate or minimize these interferences, including chromatographic separations, ion mobility spectrometry, and high-resolution mass spectrometry.Peer Reviewe

Analysis of vitamin D metabolic markers by mass spectrometry: Recent progress regarding the “gold standard” method and integration into clinical practice

Liquid chromatography/tandem mass spectrometry is firmly established today as the gold standard technique for analysis of vitamin D, both for vitamin D status assessments as well as for measuring complex and intricate vitamin D metabolic fingerprints. While the actual mass spectrometry technology has seen only incremental performance increases in recent years, there have been major, very impactful changes in the front- and back-end of MS-based vitamin D assays; for example, the extension to new types of biological sample matrices analyzed for an increasing number of different vitamin D metabolites, novel sample preparation techniques, new powerful chemical derivatization reagents, as well the continued integration of high resolution mass spectrometers into clinical laboratories, replacing established triple-quadrupole instruments. At the same time, the sustainability of mass spectrometry operation in the vitamin D field is now firmly established through proven analytical harmonization and standardization programs. The present review summarizes the most important of these recent developments.Peer Reviewe

Noninvasive monitoring of liver fat during treatment with GLP‐1 analogues and SGLT‐2 inhibitors in a real‐world setting

Introduction: Patients with NAFLD have a two‐fold increased risk of diabetes, and conversely, NAFLD affects up to 80% of patients with type 2 diabetes. Due to the co‐occurrence of both diseases and the lack of approved pharmacotherapy for NAFLD, the anti‐steatogenic potential of diabetes‐related drugs is being explored. In this study, we aim to monitor liver fat noninvasively during treatment with SGLT‐2 inhibitors or GLP‐1 analogues in a real‐world setting. Methods: Overall, 39 patients (49% women, age 57.7 ± 10.9 years) with type 2 diabetes and hepatic steatosis (defined by controlled attenuation parameter [CAP] values ≥ 215 dB/m) were observed for 6 months and routinely monitored with respect to hepatic fat contents and liver stiffness (VCTE); body composition (BIA); and blood biochemistry, including liver function tests (LFTs), serum lipids and glucose metabolism markers. Results: Median liver fat contents were significantly (P = .026) reduced by 9% in patients taking either SGLT‐2 (n = 22) or GLP‐1 (n = 17) for 6 months (absolute median CAP decrease: −32 dB/m [−58 to 32 dB/m]). In parallel, serum ALT and γ‐GT activities decreased significantly (P = .002 and P = .049, respectively). These improvements were accompanied by significant (P < .0001) changes to body weight and BMI (−2.5 ± 3.3 kg and −0.9 ± 1.2 kg/m2, respectively) and glucose homeostasis, with significant reductions in HbA1c and fasting plasma glucose (FDG) (both P < .0001). Of note, significant reductions of intrahepatic lipid contents occured in patients receiving SGLT‐2 inhibitors only. Conclusions: In this real‐world observational evaluation of fatty liver monitored noninvasively in patients with type 2 diabetes treated with either SGLT2 or GLP‐1, improvements in measures of hepatic steatosis, glucose and weight parameters were observed after 6 months, with significant reductions of intrahepatic lipid contents seen specifically in the SGLT2 subgroup

Dark open innovation in a criminal organizational context: the case of Madoff’s Ponzi fraud

Purpose The purpose of this paper is to investigate the processes of open innovation in the context of a fraudulent organization and, using the infamous Bernie L. Madoff Investment Securities fraud case, introduces and elaborates upon the concept of dark open innovation. The paper’s conceptual framework is drawn from social capital theory, which is grounded on the socio-economics of Bourdieu, Coleman and Putnam and is employed in order to make sense of the processes that occur within dark open innovation. Design/methodology/approach Given the self-evident access issues, this paper is necessarily based on archival and secondary sources taken from the court records of Madoff v. New York – including victim impact statements, the defendant’s Plea Allocution, and academic and journalistic commentaries – which enable the identification of the processes involved in dark open innovation. Significantly, this paper also represents an important inter-disciplinary collaboration between academic scholars variously informed by business and history subject domains. Findings Although almost invariably cast as a positive process, innovation can also be evidenced as a negative or dark force. This is particularly relevant in open innovation contexts, which often call for the creation of extended trust and close relationships. This paper outlines a case of dark open innovation. Research limitations/implications A key implication of this study is that organizational innovation is not automatically synonymous with human flourishing or progress. This paper challenges the automatic assumption of innovation being positive and introduces the notion of dark open innovation. Although this is accomplished by means of an in-depth single case, the findings have the potential to resonate in a wide spectrum of situations. Practical implications Innovation is a concept that applies across a range of organization and management domains. Criminals also innovate; thus, the paper provides valuable insights into the organizational innovation processes especially involved in relation to dark open innovation contexts. Social implications It is important to develop and fully understand the possible wider meanings of innovation and also to recognize that innovation – particularly dark open innovation – does not always create progress. The Caveat Emptor warning is still relevant. Originality/value The paper introduces the novel notion of dark open innovation

The Effect of the Paleolithic Diet vs. Healthy Diets on Glucose and Insulin Homeostasis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Recently, the Paleolithic diet became popular due to its possible health benefits. Several, albeit not all, studies suggested that the consumption of the Paleolithic diet might improve glucose tolerance, decrease insulin secretion, and increase insulin sensitivity. Therefore, the aim of this meta-analysis was to compare the effect of the Paleolithic diet with other types of diets on glucose and insulin homeostasis in subjects with altered glucose metabolism. Four databases (PubMed, Web of Sciences, Scopus, and the Cochrane Library) were searched to select studies in which the effects of the Paleolithic diet on fasting glucose and insulin levels, glycated hemoglobin (HbA1c), homeostasis model assessment of insulin resistance (HOMA-IR), and area under the curve (AUC 0–120) for glucose and insulin during the oral glucose tolerance test were assessed. In total, four studies with 98 subjects which compared the effect of the Paleolithic diet with other types of diets (the Mediterranean diet, diabetes diet, and a diet recommended by the Dutch Health Council) were included in this meta-analysis. The Paleolithic diet did not differ from other types of diets with regard to its effect on fasting glucose (standardized mean difference (SMD): −0.343, 95% confidence interval (CI): −0.867, 0.181, p = 0.200) and insulin (SMD: −0.141; 95% CI: −0.599, 0.318; p = 0.548) levels. In addition, there were no differences between the Paleolithic diet and other types of diets in HOMA-IR (SMD: −0.151; 95% CI: −0.610, 0.309; p = 0.521), HbA1c (SMD: −0.380; 95% CI: −0.870, 0.110; p = 0.129), AUC 0–120 glucose (SMD: −0.558; 95% CI: −1.380, 0.264; p = 0.183), and AUC 0–120 insulin (SMD: −0.068; 95% CI: −0.526, 0.390; p = 0.772). In conclusion, the Paleolithic diet did not differ from other types of diets commonly perceived as healthy with regard to effects on glucose and insulin homeostasis in subjects with altered glucose metabolism

Resilience and the (Micro-)Dynamics of Organizational Ambidexterity: Implications for Strategic HRM

In the twenty-first century, resilience has emerged as an important topic linked to calls for adaptability, well-being and organizational performance. Extant strategic human resource management (HRM) literature and practices have developed many insights into resilience. However, overall, they have a propensity to conceptualise resilience as being associated with ‘macro-’ and ‘extreme’ situations. This paper complements the prevailing perspective by developing a micro-focus on resilience through the conceptual framework of organizational ambidexterity surfacing under-examined individual resilience in connection with HRM practices. Methodologically, the paper adopts a qualitative approach presenting data from two illustrative contexts: an ‘everyday’ quasi-governmental institution and a prima facie ‘extreme’ pan-international military organization. Using template analysis, a number of valuable themes and similarities are identified. The findings and discussion underline the managerial challenges in handling organizational ambidextrous dynamics and tensions surrounding resilience, positive and sceptical approaches in relation to individual and organizational stances towards HRM practices. As such, the results point at value in HRM managers and practices recontextualising and appreciating ‘extremes’ and resilience more as an everyday (rather than exceptional) phenomenon wherein myriad micro-moments are highly significant in constructing and influencing macro-contexts. This also implies a need to see cynical resistance as normative rather than automatically negatively

Design and validation of a German version of the GSRS-IBS - an analysis of its psychometric quality and factorial structure

Background: Currently, a suitable questionnaire in German language is not available to monitor the progression and evaluate the severity of irritable bowel syndrome (IBS). Therefore, this study aimed to translate the Gastrointestinal Symptom Rating Scale for Irritable Bowel Syndrome (GSRS-IBS) into German and to evaluate its psychometric qualities and factorial structure. Methods: This study is based on a total sample of 372 participants [62.6% female, mean age = 41 years (SD = 17 years)]. 17.5% of the participants had a diagnosis of IBS, 19.9% were receiving treatment for chronic inflammatory bowel disease, 12.1% of the participants were recruited from a psychosomatic clinic, and 50.5% belonged to a control group. All participants completed the German version of GSRS-IBS (called Reizdarm-Fragebogen, RDF), as well as the Gießen Subjective Complaints List (GBB-24) and the Hospital Anxiety and Depression Scale - German version (HADS-D). Results: The internal consistency of the RDF total scale was at least satisfactory in all subsamples (Cronbach’s Alpha between .77 and .92), and for all subscales (Cronbach’s Alpha between .79 and .91). The item difficulties (between .25 and .73) and the item-total correlations (between .48 and .83) were equally satisfactory. Principal axis analysis revealed a four-factorial structure of the RDF items, which mainly resembled the structure of the English original. Convergent validity was established based on substantial and significant correlations with the stomach-complaint scale of the GBB-24 (r = .71; p &lt; .01) and the anxiety (r = .42; p &lt; .01) and depression scales (r = .43; p &lt; .01) of the HADS-D. Conclusion: The German version of the GSRS-IBS RDF proves to be an effective, reliable, and valid questionnaire for the assessment of symptom severity in IBS, which can be used in clinical practice as well as in clinical studies

Hepatic steatosis in patients with acromegaly

Objective Comorbid NAFLD is increasingly being diagnosed in patients with diabetes and nondiabetic endocrinopathies. The aim of this study was to assess hepatic steatosis noninvasively by transient elastography in patients with acromegaly. Design A cross‐sectional study including 22 patients with acromegaly. Methods Hepatic steatosis was quantified using controlled attenuation parameter (CAP) during elastography. Anthropometric measurements were obtained, serum liver function tests and lipid and hormone profiles were measured, and prosteatogenic gene variants were genotyped using standard assays. Results In total, 41% of patients were women (mean age 60 ± 14.7 years, mean BMI 31.2 ± 4.6 kg/m2). Hepatic steatosis, as defined by CAP > 248 dB/m, was present in 66% of patients. Five (45%) of the patients with hepatic steatosis also had fibrosis, and one presented with cirrhosis. Nine patients were carriers of the PNPLA3 p.I148M prosteatogenic [M] risk allele, eight of whom were heterozygotes. CAP values were significantly (P = .045) higher in these patients and corresponded to advanced steatosis, as compared to patients with the wild‐type genotype, who demonstrated CAP values consistent with mild steatosis (311 ± 33 dB/m. vs 254 ± 62 dB/m). CAP values did not differ significantly in carriers of distinct TM6SF2 and MBOAT7 genotypes; however, carriers of the risk alleles displayed higher CAP as compared to wild‐type patients. Conclusions This study shows that in patients with acromegaly, carriers of the PNPLA3 susceptibility allele are at risk of developing hepatic steatosis, as assessed by CAP. Comorbid NAFLD might compound prognosis in such patients; thus, further research into the pathomechanisms and treatment of NAFLD in acromegaly is warranted

Making Sense of a New Transport System: An Ethnographic Study of the Cambridgeshire Guided Busway

An increase in public transport use has the potential to contribute to improving population health, and there is growing interest in innovative public transport systems. Yet how new public transport infrastructure is experienced and integrated (or not) into daily practice is little understood. We investigated how the Cambridgeshire Guided Busway, UK, was used and experienced in the weeks following its opening, using the method of participant observation (travelling on the busway and observing and talking to passengers) and drawing on Normalization Process Theory to interpret our data. Using excerpts of field notes to support our interpretations, we describe how the ease with which the new transport system could be integrated into existing daily routines was important in determining whether individuals would continue to use it. It emerged that there were two groups of passengers with different experiences and attitudes. Passengers who had previously travelled frequently on regular bus services did not perceive the new system to be an improvement; consequently, they were frustrated that it was differentiated from and not coherent with the regular system. In contrast, passengers who had previously travelled almost exclusively by car appraised the busway positively and perceived it to be a novel and superior form of travel. Our rich qualitative account highlights the varied and creative ways in which people learn to use new public transport and integrate it into their everyday lives. This has consequences for the introduction and promotion of future transport innovations. It is important to emphasise the novelty of new public transport, but also the ways in which its use can become ordinary and routine. Addressing these issues could help to promote uptake of other public transport interventions, which may contribute to increasing physical activity and improving population health. © 2013 Jones et al