Deterrence, settlement, and litigation under adversarial versus inquisitorial systems

In this paper, we compare deterrence, settlement, and litigation spending under adversarial and inquisitorial systems. We present a basic litigation model with three sequential stages—care, settlement, litigation—and we test the predictions on experimental data. In line with our theoretical expectations, we fnd that, compared with the adversarial system, the inquisitorial system is associated with lower litigation spending, lower rates of cases settled, and tends to strengthen deterrenc

Incidence and predictive biomarkers of Clostridioides difficile infection in hospitalized patients receiving broad-spectrum antibiotics

Trial enrichment using gut microbiota derived biomarkers by high-risk individuals can improve the feasibility of randomized controlled trials for prevention of Clostridioides difficile infection (CDI). Here, we report in a prospective observational cohort study the incidence of CDI and assess potential clinical characteristics and biomarkers to predict CDI in 1,007 patients ≥ 50 years receiving newly initiated antibiotic treatment with penicillins plus a beta- lactamase inhibitor, 3rd/4th generation cephalosporins, carbapenems, fluoroquinolones or clindamycin from 34 European hospitals. The estimated 90-day cumulative incidences of a first CDI episode is 1.9% (95% CI 1.1-3.0). Carbapenem treatment (Hazard Ratio (95% CI): 5.3 (1.7-16.6)), toxigenic C. difficile rectal carriage (10.3 (3.2-33.1)), high intestinal abundance of Enterococcus spp. relative to Ruminococcus spp. (5.4 (2.1-18.7)), and low Shannon alpha diversity index as determined by 16 S rRNA gene profiling (9.7 (3.2-29.7)), but not nor- malized urinary 3-indoxyl sulfate levels, predicts an increased CDI risk

Genetic relatedness among isolates of Shigella sonnei carrying class 2 integrons in Tehran, Iran, 2002–2003

<p>Abstract</p> <p>Background</p> <p><it>Shigella </it>spp. are major cause of diarrhoeal disease in both developing and developed countries. <it>Shigella sonnei </it>is the serogroup of <it>Shigella </it>most frequently responsible for sporadic and epidemic enteritis in developed countries. In recent years the emergence and spread of <it>S. sonnei </it>biotype g carrying class 2 integron have been frequently reported in many countries. Recently, <it>S. sonnei </it>has been reported as the prevalent serogroup of <it>Shigella </it>in Iran.</p> <p>The present study was carried out to investigate phenotypic and genetic characteristics of <it>Shigella sonnei </it>isolates identified in the years 2002 and 2003 in Tehran, Iran.</p> <p>Methods</p> <p>Biotyping, drug susceptibility testing, pulsed field gel electrophoresis (PFGE) and analysis of class 2 integrons have been carried out on 60 <it>S. sonnei </it>isolates, including 57 sporadic isolates from paediatric cases of shigellosis occurring in 2002 and 2003, two sporadic isolates recovered in 1984 and the ATCC 9290 strain.</p> <p>Results</p> <p>Biotype g and resistance to streptomycin, sulfamethoxazole-trimethoprim and tetracycline were exhibited by 54 of the 57 recent isolates. Of the 54 biotype g isolates, 28 exhibited a class 2 integron of 2161 bp, and 24 a class 2 integron of 1371 bp, respectively. Class 2 integrons were not detected in four isolates only, including the two endemic isolates recovered in 1984 and two strains from recent sporadic cases. PFGE divided the strains into eight pulsotypes labeled A to H, three major pulsotypes – A to C – including the large majority of the recent sporadic <it>S. sonnei </it>isolates. Pulsotypes A and C were the most prevalent groups, accounting for 41.6% and 35.0%, respectively, of the isolates under study.</p> <p>Conclusion</p> <p>The results suggest that biotype g, class 2 integron carrying <it>S. sonnei </it>are prevalent in our geographic area. <it>S. sonnei </it>isolated in the years 2002 and 2003 could be attributed to a few predominant clusters including, respectively, strains with pulsotypes B and C carrying a 2161 bp class 2 integron, and those having pulsotype A and a 1371 bp class 2 integron. A few epidemic clones are responsible for the apparently endemic occurrence of shigellosis in Tehran, Iran.</p

Human knockouts and phenotypic analysis in a cohort with a high rate of consanguinity

A major goal of biomedicine is to understand the function of every gene in the human genome. Loss-of-function mutations can disrupt both copies of a given gene in humans and phenotypic analysis of such 'human knockouts' can provide insight into gene function. Consanguineous unions are more likely to result in offspring carrying homozygous loss-of-function mutations. In Pakistan, consanguinity rates are notably high. Here we sequence the protein-coding regions of 10,503 adult participants in the Pakistan Risk of Myocardial Infarction Study (PROMIS), designed to understand the determinants of cardiometabolic diseases in individuals from South Asia. We identified individuals carrying homozygous predicted loss-of-function (pLoF) mutations, and performed phenotypic analysis involving more than 200 biochemical and disease traits. We enumerated 49,138 rare (<1% minor allele frequency) pLoF mutations. These pLoF mutations are estimated to knock out 1,317 genes, each in at least one participant. Homozygosity for pLoF mutations at PLA2G7 was associated with absent enzymatic activity of soluble lipoprotein-associated phospholipase A2; at CYP2F1, with higher plasma interleukin-8 concentrations; at TREH, with lower concentrations of apoB-containing lipoprotein subfractions; at either A3GALT2 or NRG4, with markedly reduced plasma insulin C-peptide concentrations; and at SLC9A3R1, with mediators of calcium and phosphate signalling. Heterozygous deficiency of APOC3 has been shown to protect against coronary heart disease; we identified APOC3 homozygous pLoF carriers in our cohort. We recruited these human knockouts and challenged them with an oral fat load. Compared with family members lacking the mutation, individuals with APOC3 knocked out displayed marked blunting of the usual post-prandial rise in plasma triglycerides. Overall, these observations provide a roadmap for a 'human knockout project', a systematic effort to understand the phenotypic consequences of complete disruption of genes in humans.D.S. is supported by grants from the National Institutes of Health, the Fogarty International, the Wellcome Trust, the British Heart Foundation, and Pfizer. P.N. is supported by the John S. LaDue Memorial Fellowship in Cardiology from Harvard Medical School. H.-H.W. is supported by a grant from the Samsung Medical Center, Korea (SMO116163). S.K. is supported by the Ofer and Shelly Nemirovsky MGH Research Scholar Award and by grants from the National Institutes of Health (R01HL107816), the Donovan Family Foundation, and Fondation Leducq. Exome sequencing was supported by a grant from the NHGRI (5U54HG003067-11) to S.G. and E.S.L. D.G.M. is supported by a grant from the National Institutes of Health (R01GM104371). J.D. holds a British Heart Foundation Chair, European Research Council Senior Investigator Award, and NIHR Senior Investigator Award. The Cardiovascular Epidemiology Unit at the University of Cambridge, which supported the field work and genotyping of PROMIS, is funded by the UK Medical Research Council, British Heart Foundation, and NIHR Cambridge Biomedical Research Centre ... Fieldwork in the PROMIS study has been supported through funds available to investigators at the Center for Non-Communicable Diseases, Pakistan and the University of Cambridge, UK

The effects of energy balance on lipid metabolism

The present dissertation focused on the effects of energy balance on postprandial triacylglycerolemia, an important and independent cardiovascular risk factor. For this purpose, we investigated 1) the effects of low energy expenditure along with mild energy intake restriction on fasting and postprandial concentrations of total triacylglycerols (TAG) and TAG in the TAG-rich lipoprotein (TRL) fraction, 2) the role of acute energy deficit induced by diet or exercise or a combination of both on fasting and postprandial TAG and TRL-TAG concentrations, 3) the effects of long-term energy deficit induced by and hypocaloric diet low in carbohydrate and saturated fat on fasting and postprandial TAG concentrations, in the absence of the acute effects of negative energy balance, and 4) whether moderate weight loss normalizes TAG metabolism in obese men compared with that of aged-matched lean healthy men. For clinical practice, the most important findings of these studies are that 1) calorie restriction and exercise may be considered as alternative and supplementary interventions for the daylong control of TAG concentrations, and that 2) moderate weight loss, induced by a low-carbohydrate and saturated fat diet, may be a feasible and valuable intervention to attenuate postprandial triacylglycerolemia in obesity, an independent risk factor for cardiovascular diseases. For research practice, the most important finding of these studies is the importance of carefully controlling for diet and exercise on the day (s) before evaluating TAG metabolism.Στην παρούσα διατριβή διερευνήθηκε η επίδραση του ενεργειακού ισοζυγίου στη μεταγευματική υπερτριακυλογλυκερολαιμία, έναν σημαντικό παράγοντα κινδύνου στεφανιαίας νόσου. Πιο συγκεκριμένα εξετάστηκε: 1) η επίδραση συνδυασμού μιας ημέρας ήπιας υποθερμιδικής δίαιτας με μια συνεδρία ήπιας άσκησης στα επίπεδα ολικών τριακυλογλυκερολών (TAG) και TAG στις λιποπρωτεΐνες που είναι πλούσιες σε τριακυλογλυκερόλες (TRL) στο μεταπορροφητικό και μεταγευματικό στάδιο, 2) ο ρόλος του βραχυχρόνιου ενεργειακού ελλείμματος από δίαιτα ή άσκηση ή συνδυασμό αυτών στα επίπεδα TAG και TRL-TAG στο μεταπορροφητικό και μεταγευματικό στάδιο 3) η επίδραση μακροχρόνιου ενεργειακού ελλείμματος που προκλήθηκε από υποθερμιδική δίαιτα χαμηλή σε υδατάνθρακες και κορεσμένα λίπη στα επίπεδα TAG στο μεταπορροφητικό και μεταγευματικό στάδιο, ανεξάρτητα από τις επιδράσεις του οξέος ενεργειακού ελλείμματος και 4) αν η μέτρια (10%) απώλεια σωματικού βάρους ομαλοποιεί το μεταβολισμό των TAG σε παχύσαρκους άνδρες συγκρινόμενοι με νορμοβαρείς υγιείς άνδρες. Από άποψη κλινικής εφαρμογής οι σημαντικότερες ίσως πληροφορίες που απορρέουν από την παρούσα διατριβή είναι ότι για την πρόληψη και θεραπεία της υπερτριακυλογλυκερολαιμίας η άσκηση και η μείωση της ενεργειακής πρόσληψης (δίαιτα) μπορούν να χρησιμοποιούνται ξεχωριστά ή να συνδυάζονται, ανάλογα με τις δυνατότητες και προτιμήσεις του ατόμου, ενώ ακόμα και μια μέτρια απώλεια βάρους μέσω περιορισμού της πρόσληψης υδατανθράκων και κορεσμένων λιπών δύναται να ομαλοποιήσει τη μεταγευματική υπερτριακυλογλυκερολαιμία ακόμα και αν οι ασθενείς παραμένουν κλινικά παχύσαρκοι. Σε ερευνητικό δε επίπεδο, σημαντικότερη ίσως πληροφορία που απορρέει από την παρούσα διατριβή είναι η αναγκαιότητα του ελέγχου του ενεργειακού ισοζυγίου (δίαιτας και άσκησης) πριν τον προσδιορισμό του μεταβολισμού των TAG

A Modified Mediterranean Diet Improves Fasting and Postprandial Glucoregulation in Adults with Overweight and Obesity: A Pilot Study

The ideal lifestyle intervention to battle both obesity and diabetes is currently unknown. The aim of this pilot uncontrolled intervention trial was to assess the effect of a modified Mediterranean diet (MedDiet) on weight loss and glucoregulation among overweight/obese adults. Eleven men and women with overweight/obesity, aged 37 &plusmn; 12 years, participated in a free-living intervention until 10% weight loss was achieved. Participants followed an individualized MedDiet high in monounsaturated fat and protein with decreased carbohydrate and saturated fat contents. Physical activity and dietary intake were monitored with pedometers and food records, respectively. Upon weight loss achievement, anthropometric measurements, blood metabolic profiles and individual responses to oral glucose and mixed-meal tests were evaluated pre- and post-intervention. The results showed significant ameliorations in body fat, waist circumference and leptin levels (p &lt; 0.01), with concomitant increases in adiponectin&ndash;leptin ratios (p &lt; 0.001). Glucoregulation was significantly improved according to glucose and insulin responses, homeostatic model assessment of insulin resistance indices and postprandial insulin sensitivity indices (p &lt; 0.05). In conclusion, the modified Mediterranean diet may induce significant improvements in body composition, adipocytokine profile and glucose metabolism in overweight/obese individuals. Notably, ameliorated glycemia and increased insulin sensitivity may be retained even at postprandial level, irrespective of the meal consumed

Effect of acute negative and positive energy balance on basal very-low density lipoprotein triglyceride metabolism in women.

BACKGROUND: Acute reduction in dietary energy intake reduces very low-density lipoprotein triglyceride (VLDL-TG) concentration. Although chronic dietary energy surplus and obesity are associated with hypertriglyceridemia, the effect of acute overfeeding on VLDL-TG metabolism is not known. OBJECTIVE: The aim of the present study was to investigate the effects of acute negative and positive energy balance on VLDL-TG metabolism in healthy women. DESIGN: Ten healthy women (AGE: 22.0±2.9 years, BMI: 21.2±1.3 kg/m(2)) underwent a stable isotopically labeled tracer infusion study to determine basal VLDL-TG kinetics after performing, in random order, three experimental trials on the previous day: i) isocaloric feeding (control) ii) hypocaloric feeding with a dietary energy restriction of 2.89±0.42 MJ and iii) hypercaloric feeding with a dietary energy surplus of 2.91±0.32 MJ. The three diets had the same macronutrient composition. RESULTS: Fasting plasma VLDL-TG concentrations decreased by ∼26% after hypocaloric feeding relative to the control trial (P = 0.037), owing to decreased hepatic VLDL-TG secretion rate (by 21%, P = 0.023) and increased VLDL-TG plasma clearance rate (by ∼12%, P = 0.016). Hypercaloric feeding increased plasma glucose concentration (P = 0.042) but had no effect on VLDL-TG concentration and kinetics compared to the control trial. CONCLUSION: Acute dietary energy deficit (∼3MJ) leads to hypotriglyceridemia via a combination of decreased hepatic VLDL-TG secretion and increased VLDL-TG clearance. On the other hand, acute dietary energy surplus (∼3MJ) does not affect basal VLDL-TG metabolism but disrupts glucose homeostasis in healthy women

Evaluation of automated capillary complete blood counts for routine clinical decision making in a large cohort of hematological patients, using Mindray BC-3000 Plus Auto and Sysmex XE-5000 hematology analyzers

Introduction Venous blood (VB) sampling for complete blood count (CBC) via venipuncture is the basic method for the daily evaluation of hematological patients. However, several issues during this process, such as venipuncture difficulty and repetitive attempts, may cause pain, phlebitis, hematomas, inadequate sampling, and patient discomfort. Capillary blood (CB) sampling could be an alternative and less painful solution for the patient. The purpose of this study was the comparative evaluation of basic CBC parameters, as counted from venous and capillary blood samples. Methods During the period 06/2016-06/2019 in which the study was conducted, 1634 automated counts of VB or CB were performed, derived from 425 hematological hospitalized patients. Bland-Altman plots were performed to show the agreement of VB and CB counts of common hematological parameters (Hb, Hct, WBC, absolute neutrophil count-[ANC], RBC, Plt, MCV, MCH), using two different hematology analyzers (Mindray BC-3000 Plus Auto and Sysmex XE-5000). Clinical significance of CB sampling was assessed by applying specific clinically significant cutoffs for Hb, ANC, and Plt. Results All measured parameters revealed a significant correlation (r &gt; .9) between CB and VB samples, irrelatively of the hematology analyzer used. CB measurements of Hb, ANC, and Plt, at different clinically important cutoff levels, showed excellent sensitivity (87%-100%), specificity (95%-100%), positive predictive value, and negative predictive value (87%-100% and 90%-100%, respectively). Conclusion Capillary blood and VB counts in hematological patients were equivalent for most basic hematological parameters. Hb, ANC, and Plt CB counts revealed clinically significant performance, indicating that they can reliably substitute VB sampling in the day work