Exploration of Shared Genetic Architecture Between Subcortical Brain Volumes and Anorexia Nervosa

In MRI scans of patients with anorexia nervosa (AN), reductions in brain volume are often apparent. However, it is unknown whether such brain abnormalities are influenced by genetic determinants that partially overlap with those underlying AN. Here, we used a battery of methods (LD score regression, genetic risk scores, sign test, SNP effect concordance analysis, and Mendelian randomization) to investigate the genetic covariation between subcortical brain volumes and risk for AN based on summary measures retrieved from genome-wide association studies of regional brain volumes (ENIGMA consortium, n = 13,170) and genetic risk for AN (PGC-ED consortium, n = 14,477). Genetic correlations ranged from − 0.10 to 0.23 (all p > 0.05). There were some signs of an inverse concordance between greater thalamus volume and risk for AN (permuted p = 0.009, 95% CI: [0.005, 0.017]). A genetic variant in the vicinity of ZW10, a gene involved in cell division, and neurotransmitter and immune system relevant genes, in particular DRD2, was significantly associated with AN only after conditioning on its association with caudate volume (pFDR = 0.025). Another genetic variant linked to LRRC4C, important in axonal and synaptic development, reached significance after conditioning on hippocampal volume (pFDR = 0.021). In this comprehensive set of analyses and based on the largest available sample sizes to date, there was weak evidence for associations between risk for AN and risk for abnormal subcortical brain volumes at a global level (that is, common variant genetic architecture), but suggestive evidence for effects of single genetic markers. Highly powered multimodal brain- and disorder-related genome-wide studies are needed to further dissect the shared genetic influences on brain structure and risk for AN

How context factors influence lean production practices in manufacturing cells

Factors influencing the implementation of Lean Production (LP) in the company as a whole have been widely studied; however, there is a gap in the literature about the factors that affect LP in smaller units of the manufacturing system, such as Manufacturing Cells (MC). Hence, the objective of this study is to identify the factors that affect the implementation of lean practices in MC. We conducted four in-depth case studies, and the MCs were fully using 39 % (case 1), 6 % (case 2), 39 % (case 3) and 56 % (case 4) of the lean practices. Results suggest that there are seven factors that affect the use of LP practices in MC: (i) the reason for adopting LP, (ii) the experience of the company with LP, (iii) the need for involvement of the supporting areas in some LP practices, (iv) the interdependence of some practices, (v) the variety of product models produced bin the MC, (vi) the synergy between LP and MC attributes, and (vii) the size of the equipment used in the MC. We recommend testing the association of those proposed contextual factors with LP practices and performance metrics empirically with large samples of MCs or with mathematical modelling as future research

Hemodynamic and respiratory effects of medium-chain and long-chain triglyceride fat emulsions: A prospective, randomized study

Background: Intravenous fat emulsions (IVFE) containing long-chain triglycerides (LCTs) (chain length 20 carbon atoms) have been associated with adverse hemodynamic and respiratory effects in postoperative on intensive care unit patients. Recently, medium-chain triglycerides (MCTs) (chain length 6 to 12 carbons atoms) have been introduced as a component of IVFE. Objectives: The study was aimed at comparing cardiopulmonary effects of IVFE with different composition (MCTs + LCTs vs LCT-based IVFE). Design: Prospective, double-blind, randomized, parallel-group controlled trial. Setting: Heart surgery postoperative intensive care unit. Patients: With approval of the Institutional Review Board of Human Studies, and after obtaining written informed consent, twenty-six spontaneously breathing patients were enrolled in the study 24 hours after open heart surgery for mitral valve replacement (22 females, 4 males, mean age 57 years, range 35-73). Interventions: Patients were randomized into two groups, to receive 1 mL/kg/hour for two hours (3.3 mg/kg/min) of the LCT-based IVFE or the IVFE containing a physical mixture of MCTs + LCTs (50:50%). Group comparisons were made using repeated measures of ANOVA; main statistical comparisons were made in each group between baseline values and data collected during and after two hours of IVFE infusion (Dunnett multiple comparison test). A p < .05 level was used to establish statistical significance. Measurements and main results: In each group hemodynamic measurements and arterial blood gases were obtained before, during and after (for another two hours) IVFE infusion, at 30' intervals; oxygen transport/utilization parameters and intrapulmonary shunt fraction were also calculated. No change in heart rate, cardiac index, systemic and pulmonary pressures or resistance, central venous and pulmonary capillary pressures, nor in arterial blood gases was observed in the MCTs + LCTs group, as compared to pre-infusion values. IVFE administration reduced the cardiac index (-15% at 60' and 120' of infusion) only in the group receiving the LCT-based IVFE; significant increases in both pulmonary artery pressures and vascular resistances were observed in the same group, with PaO2 decrease during IVFE administration. Oxygen consumption was constantly increased (+15% vs baseline values) during and after MCTs + LCTs infusion. Oxygen delivery was unmodified by LCTs + MCTs, but it was significantly reduced by the LCT-based IVFE. Neither changes in the intrapulmonary shunt fraction nor arrhythmias or adverse clinical reactions were observed during or after the infusion of either IVFE. Conclusions: Unlike IVFE based on LCTs only, MCTs + LCTs IVFE do not exert adverse cardiopulmonary effects at clinically useful doses following valvular heart surgery and could represent a safe source of rapidly metabolized substrates

Hemodynamic and respiratory effects of medium-chain and long-chain triglyceride fat emulsions: A prospective, randomized study

Background: Intravenous fat emulsions (IVFE) containing long-chain triglycerides (LCTs) (chain length 20 carbon atoms) have been associated with adverse hemodynamic and respiratory effects in postoperative on intensive care unit patients. Recently, medium-chain triglycerides (MCTs) (chain length 6 to 12 carbons atoms) have been introduced as a component of IVFE. Objectives: The study was aimed at comparing cardiopulmonary effects of IVFE with different composition (MCTs + LCTs vs LCT-based IVFE). Design: Prospective, double-blind, randomized, parallel-group controlled trial. Setting: Heart surgery postoperative intensive care unit. Patients: With approval of the Institutional Review Board of Human Studies, and after obtaining written informed consent, twenty-six spontaneously breathing patients were enrolled in the study 24 hours after open heart surgery for mitral valve replacement (22 females, 4 males, mean age 57 years, range 35-73). Interventions: Patients were randomized into two groups, to receive 1 mL/kg/hour for two hours (3.3 mg/kg/min) of the LCT-based IVFE or the IVFE containing a physical mixture of MCTs + LCTs (50:50%). Group comparisons were made using repeated measures of ANOVA; main statistical comparisons were made in each group between baseline values and data collected during and after two hours of IVFE infusion (Dunnett multiple comparison test). A p < .05 level was used to establish statistical significance. Measurements and main results: In each group hemodynamic measurements and arterial blood gases were obtained before, during and after (for another two hours) IVFE infusion, at 30' intervals; oxygen transport/utilization parameters and intrapulmonary shunt fraction were also calculated. No change in heart rate, cardiac index, systemic and pulmonary pressures or resistance, central venous and pulmonary capillary pressures, nor in arterial blood gases was observed in the MCTs + LCTs group, as compared to pre-infusion values. IVFE administration reduced the cardiac index (-15% at 60' and 120' of infusion) only in the group receiving the LCT-based IVFE; significant increases in both pulmonary artery pressures and vascular resistances were observed in the same group, with PaO2 decrease during IVFE administration. Oxygen consumption was constantly increased (+15% vs baseline values) during and after MCTs + LCTs infusion. Oxygen delivery was unmodified by LCTs + MCTs, but it was significantly reduced by the LCT-based IVFE. Neither changes in the intrapulmonary shunt fraction nor arrhythmias or adverse clinical reactions were observed during or after the infusion of either IVFE. Conclusions: Unlike IVFE based on LCTs only, MCTs + LCTs IVFE do not exert adverse cardiopulmonary effects at clinically useful doses following valvular heart surgery and could represent a safe source of rapidly metabolized substrates

Pediatric idiopathic intracranial hypertension and the underlying endocrine-metabolic dysfunction: a pilot study

AIM:To unravel the potential idiopathic intracranial hypertension (IIH) endocrine-metabolic comorbidities by studying the natural (and targeted drug-modified) history of disease in children. IIH is a disorder of unclear pathophysiology, characterized by raised intracranial pressure without hydrocephalus or space-occupying lesion coupled with normal cerebrospinal fluid (CSF) composition. METHODS: Retrospective study (years 2001-2010) of clinical records and images and prospective follow-up (years 2010-2013) in 15 children (11 girls, 4 boys; aged 5-16 years) diagnosed previously as "IIH", according to the criteria for pediatric IIH proposed by Rangwala, at four university pediatric centers in northern, central, and southern Italy. RESULTS: We identified six potential endocrine-metabolic comorbidities including, weight gain and obesity (n=5), recombinant growth hormone therapy (n=3), obesity and metabolic syndrome (n=1), secondary hyperaldosteronism (n=1), hypervitaminosis A (n=1), and corticosteroid therapy (n=1). Response to etiologically targeted treatments (e.g., spironolactone, octreotide) was documented. CONCLUSIONS: IIH is a protean syndrome caused by various potential (risk and) associative factors. Several conditions could influence the pressure regulation of CSF. An endocrine-metabolic altered homeostasis could be suggested in some IIH patients, and in this context, etiologically targeted therapies (spironolactone) should be considere

Lean and Digitalization—Contradictions or Complements?

Part 1: Lean ProductionInternational audienceLean has been the dominant production paradigm for the past few decades. With its focus on reducing complexity, lean suggests to limit the use of digital technologies on the shop floor. Recent advancements in digital technologies, however, promise significant improvements through its ability to manage complexity. This apparent conflict raises the question as to whether these two paradigms—lean and digitalization—contradict or complement each other. Furthermore, there is ambiguity about whether or not firms should excel in lean before investing in digitalization. This paper contributes to this discussion through an empirical investigation of this relationship. It draws on survey data from Swiss manufacturers as well as consecutive interviews with selected firms. The analyses indicate a positive correlation between the digital maturity and the lean maturity of firms. This relationship is discussed from two perspectives: first, how digitalization can support lean and, second, how lean can support digitalization. Furthermore, the different characteristics of companies of different maturities in lean and digitalization are examined. It is concluded that a favorable organizational culture and some specific continuous improvement practices help the mature implementers of lean and digitalization to achieve superior operational performance