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Alternating current (ac) and direct current (dc) conductivities have been measured in polymer-nanotube composite thin films. This was carried out for a range of concentrations of multiwall nanotubes in two polymer hosts, poly(m-phenylenevinylene-co-2,5-dioctyloxyp-phenylenevinylene) (PmPV) and polyvinylalcohol (PVA). In all cases the dc conductivity σ[sub DC] was ohmic in the voltage range studied. In general the ac conductivity displayed two distinct regions, a frequency independent region of magnitude σ[sub 0] at low frequency and a frequency dependent region at higher frequency. Both σ[sub DC] and σ[sub 0] followed a percolation scaling law of the form σ∝(p-p[sub c])[sup t] with p[sub c] = 0.055% by mass and t = 1.36. This extrapolates to a conductivity of 1 × 10[sup -3] S/m for 100% nanotube content. Such a low value reflects the presence of a thick polymer coating, resulting in poor electrical connection between tubes. This leads to the suggestion that charge transport is controlled by fluctuation induced tunneling. In the high frequency regime the conductivity increases with frequency according to an approximate power law with exponent s ≈ 0.92, indicative of hopping transport. The onset of this frequency independent conductivity scales with mass fraction for the PmPV composite due to the variation of correlation length with nanotube content. This behavior is discussed in terms of a biased random walk in three dimensions. In addition ac universality is demonstrated by the construction of a mastercurve. [ABSTRACT FROM AUTHOR]

A series of polymer nanotube composite thin films with different nanotube mass fraction is evaluated by measuring the alternating current (ac) and direct current (dc) conductivities. The presence of a thick polymer coating is indicated by the low values of conductivity.

Objective: Cabotegravir long-acting (CAB-LA) administered every 2 months was approved in the USA as pre-exposure prophylaxis (PrEP) for individuals at risk of acquiring human immunodeficiency virus (HIV)-1 infection based on the HIV Prevention Trials Network (HPTN) 083 and HPTN 084 clinical trials, which demonstrated superior reduction in HIV-1 acquisition compared with daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in men who have sex with men (MSM), transgender women (TGW), and cisgender women. A decision-analytic model was developed to assess the lifetime cost-effectiveness of initiating CAB-LA versus generic oral FTC/TDF for HIV PrEP in the USA from a healthcare sector perspective., Methods: PrEP-eligible adults entered the Markov model receiving CAB-LA or FTC/TDF and could continue initial PrEP, transition to a second PrEP option, or discontinue PrEP over time. Efficacy was taken from the HPTN 083 and HPTN 084 clinical trials. Individuals who acquired HIV-1 infection incurred lifetime HIV-related costs, could transmit HIV onwards, and could develop PrEP-related resistance mutations. Input parameter values were obtained from public and published sources. Model outcomes were discounted at 3%., Results: The model estimated that the CAB-LA pathway prevented 4.5 more primary and secondary HIV-1 infections per 100 PrEP users than the oral PrEP pathway, which yielded 0.2 fewer quality-adjusted life-years (QALYs) lost per person. Additional per-person lifetime costs were $9476 (2022 US dollars), resulting in an incremental cost-effectiveness ratio of $46,843 per QALY gained. Results remained consistent in sensitivity and scenario analyses, including in underserved populations with low oral PrEP usage., Conclusions: Our analysis suggests that initiating CAB-LA for PrEP is cost-effective versus generic daily oral FTC/TDF for individuals at risk of acquiring HIV-1 infection., (© 2024. The Author(s).)

Background: Nonalcoholic fatty liver disease (NAFLD) has reached high prevalence, paralleling the obesity pandemic. The aggressive form of the disease, nonalcoholic steatohepatitis (NASH), is characterized by fatty infiltration and inflammation of the liver, can progress to compensated cirrhosis (CC) and end-stage liver disease (ESLD: decompensated cirrhosis [DCC] and hepatocellular carcinoma [HCC]), and may ultimately require liver transplantation (LT). Real-world data on the burden of NAFLD/NASH are limited. This study aimed to evaluate the clinical and economic burden of NAFLD/NASH to the French hospital system., Methods: This retrospective cohort study used data from the French PMSI-MCO database. Adults with NAFLD/NASH diagnosis identified between 2009 and 2015 were categorized into disease severity cohorts (NAFLD/NASH, CC, DCC, HCC, and LT). Demographic and clinical data were assessed at the index (diagnosis) date. Hospitalization resource utilization and costs were assessed in the pre- and post-index periods. Rates of liver disease progression and death were evaluated for each cohort., Findings: During the median follow-up of 34.8 months, of the 131,656 patients included, 1491 patients developed CC (1.1%), 7846 developed DCC (5.9%), 1144 developed HCC (0.9%), and 52 required LT (0.04%). The diagnosis of NAFLD/NASH was associated with increasing annual costs: €7736 vs €5076 before the diagnosis. Rates of comorbidities, hospitalization resource utilization, and costs increased with disease progression. The rate of death at seven-year follow-up was 7.9% in NAFLD/NASH, CC: 18.0%, DCC: 34.9%, and HCC: 48.8%., Interpretation: NAFLD/NASH is associated with high economic burden and imparts substantial risk of negative clinical outcomes and mortality at all stages of disease., Competing Interests: Jérôme Boursier has received research grants, honoraria and fees from the following companies Abbvie, Allergan, Bio-Rad, Diafir, Echosens, Gilead, Intercept, Novo Nordisk, Pfizer, Siemens Jeremy Fraysse and Sanatan Shreay are employees of Gilead Sciences Cecile Fabron and Elodie Torreton are employees of CEMKA and worked as consultants for Gilead Sciences, (© 2020 The Authors.)

Background: Risk factors and timing associated with disease progression and mortality in nonalcoholic fatty liver disease (NAFLD) are poorly understood., Aims: To evaluate the impact of disease severity, demographics and comorbidities on risk of mortality and time to progression in a large, real-world cohort of diagnosed NAFLD patients., Methods: Claims data from a 20% Medicare representative sample between 2007 and 2015 were analysed retrospectively. Adults were categorised into disease severity groups: NAFLD/nonalcoholic steatohepatitis (NASH) alone, compensated cirrhosis, decompensated cirrhosis, liver transplant or hepatocellular carcinoma. Cumulative incidence of mortality and disease progression were calculated for each group and multivariate analyses performed adjusting for demographics, comorbidities and disease severity., Results: A total of 10 826 456, patients were assessed and the prevalence of NAFLD was 5.7% (N = 621 253). Among patients with NAFLD, 71.1% had NAFLD/NASH alone and 28.9% had NAFLD cirrhosis. Overall, 85.5% of patients had hypertension, 84.1% dyslipidemia, 68.7% had cardiovascular disease and 55.5% diabetes. The cumulative risk of progression of NAFLD to cirrhosis, and compensated cirrhosis to decompensated cirrhosis was 39% and 45%, respectively, over 8 years of follow-up. The independent predictors of progression included cardiovascular disease, renal impairment, dyslipidemia and diabetes. The cumulative risk of mortality for NAFLD, NAFLD cirrhosis, decompensated cirrhosis and hepatocellular carcinoma was 12.6%, 31.1%, 51.4% and 76.2%, respectively., Conclusions: The present report (a) demonstrates that NAFLD is grossly underdiagnosed in real-world clinical settings and (b) provides new evidence on the progression rates of NAFLD and risk factors of mortality across the spectrum of severity of NAFLD and cirrhosis., (© 2020 John Wiley & Sons Ltd.)

Objectives: As the prevalence of nonalcoholic steatohepatitis (NASH) in the elderly population increases, healthcare resource utilization (HCRU) and costs are also predicted to rise substantially., Methods: This retrospective, observational cohort study used the Medicare 20% sample data set to evaluate the impact of NASH severity on HCRU and costs over 8 years (2007-2015). The sample included 255,681 patients with nonalcoholic fatty liver disease (NAFLD)/NASH: 185,407 (72.5%) with NAFLD/NASH and no further progression to advanced liver disease, 3,454 (1.3%) with compensated cirrhosis (CC), 65,926 (25.8%) with decompensated cirrhosis (DCC), 473 (0.2%) with liver transplant (LT), and 421 (0.2%) with hepatocellular carcinoma (HCC)., Results: Rates of comorbid diabetes, hypertension, hyperlipidemia, and cardiovascular disease were significantly higher in patients with CC or more severe liver disease compared with NAFLD/NASH and no progression. The annual mean number of all-cause healthcare visits increased from 32.1 for NAFLD/NASH with no progression to 37.3 for CC, 59.8 for DCC, 74.1 for LT, and 59.3 for HCC (P < 0.05). Total annual costs for inpatient, outpatient, physician, and pharmacy services rose from $19,908 in NAFLD/NASH with no progression to $129,276 for LT (P < 0.05). Generalized linear model adjusted for patient characteristics and comorbidities revealed that costs were 1.19, 3.15, 5.02, and 3.33 times significantly higher in patients diagnosed with CC, DCC, LT, or HCC, respectively, compared with NAFLD/NASH and no progression., Discussion: These results confirm the substantial impact of NASH, particularly more severe disease, on HCRU and costs and identify patients who may benefit from interventions to prevent progression and subsequently reduce HCRU and costs.

Chronic hepatitis B (CHB) comorbidity data are limited. Using insurance claims databases, our aims were to determine the prevalence and incidence of nonliver comorbidities in CHB patients over time and the predictors of select comorbidities in CHB patients. Patients were adults with continuous coverage (commercial/Medicare or Medicaid) 6 months prior to and after the first CHB diagnosis and matched non-CHB patients. Deyo-Charlson Comorbidity Index (DCCI) and comorbidities were analyzed (cardiovascular disease [CVD], carcinoma, diabetes mellitus [DM], obesity, hypertension [HTN], hyperlipidemia, alcohol use, renal impairment, chronic kidney disease [CKD], and osteoporosis/fracture [OF]). The study population included 44,026 CHB cases and 121,568 matched controls. CHB patient mean age increased from 48.1 ± 11.9 years in 2006 to 51.8 ± 12.4 years in 2015 for commercial/Medicare and from 44.1 ± 11.1 years to 50.2 ± 10.2 years for Medicaid (P < 0.001 for both). The Medicaid CHB cohort was the sickest (DCCI, 2.6, P < 0.001). The commercial/Medicare 2006 CKD prevalence rate was 36.1/1,000 in CHB patients and 10.2/1,000 in controls, increasing to 97.6 and 38.8 in 2015, respectively. The 2006 CKD incidence (per 1,000 person-years) was 10.3 and 4.8 and 15.2 and 11.3 by 2015, respectively (P < 0.05 for all). The strongest predictors for CKD were DM (hazard ratio [HR], 2.48), HTN (HR, 3.29), and CVD (HR, 2.61) (all P < 0.0001). Similar prevalence and incidence changes were observed for OF. The strongest predictors for OF were female gender (HR, 2.22), alcohol use (HR, 2.02), and viral coinfection (HR, 1.37) (all P < 0.0001). Conclusion: Insured CHB patients were older, had more comorbidities, and experienced higher incidence and prevalence of CKD and OF than controls., (© 2018 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.)

Vanadium oxides, such as V2O5, are promising for lithium-ion batteries, catalysis, electrochromic devices and sensors. Vanadium oxides were proposed more than a decade ago for another redox-dependent application: the direct conversion of electrical energy to mechanical energy in actuators (artificial muscles). Although related conducting polymer and carbon nanotube actuators have been demonstrated, electromechanical actuators based on vanadium oxides have not be realized. V2O5 nanofibres and nanotubes provide the potential advantages of low-cost synthesis by sol-gel routes and high charging capacity and long cycle life. Here, we demonstrate electromechanical actuation for obtained high modulus V2O5 sheets comprising entangled V2O5 nanofibres. The high surface area of these V2O5 sheets facilitates electrochemical charge injection and intercalation that causes the electromechanical actuation. We show that the V2O5 sheets provide high Young's modulus, high actuator-generated stress, and high actuator stroke at low applied voltage.

Despite the major improvement in immunosuppressive therapy, noninvasive detection of heart graft rejection remains a challenge. As lipoproteins are involved in several immunomodulation mechanisms, we studied their proton NMR spectra in plasma from patients after heart transplantation. NMR data were compared to clinical and functional evaluation of rejection process. The total linewidth (TLW) of methyl and methylene peaks, mainly arising from lipoproteins, were significantly lower for patients without a rejection process than for patients before surgery and patients with evidences of a rejection process. When TLW values are referred to TLW on the 8th day for each patient, the sensitivity and the specificity of the test are increased, with resulting positive and negative predictive values of 90 and 91%, respectively. The results obtained on more than 400 samples from 46 patients justify the use of proton NMR spectroscopy as a clinical tool.

We investigated the influence of the experimenter's attitude on children's performance in a classification task. We chose 96 children (M age: 5 years, 9 months) on the basis of their performance in a spontaneous classification task. Forty-eight children made partial alignments on the basis of a link established from one object to the next (O-level group); 48 looked for objects having one common property (P-level group). The children had to perform a dichotomy task in two testing situations: one with a caring experimenter, and one with an indifferent experimenter. In the O-level group, the children's performance was superior when the experimenter was caring even though they did not seem to notice the difference between the two attitudes. P-level children clearly distinguished the experimenter attitudes, but their performance remained the same. To determine children's actual abilities accurately, researchers must take into account children's interactions with both objects and partners.

A decrease in the myocardial level of the mRNA encoding the Ca2(+)-ATPase of the sarcoplasmic reticulum (SR) has been recently reported during experimental cardiac hypertrophy and failure. To determine if such a deficit occurs in human end-stage heart failure, we compared the SR Ca2(+)-ATPase mRNA levels in left (LV) and right ventricular (RV) specimens from 13 patients undergoing cardiac transplantation (6 idiopathic dilated cardiomyopathies; 4 coronary artery diseases with myocardial infarctions; 3 diverse etiologies) with control heart samples using a rat cardiac SR Ca2(+)-ATPase cDNA probe. We observed a marked decrease in the mRNA for the Ca2(+)-ATPase relative to both the 18S ribosomal RNA and the myosin heavy chain mRNA in LV specimens of patients with heart failure compared to controls (-48%, P less than 0.01 and -47%, P less than 0.05, respectively). The LV ratio of Ca2(+)-ATPase mRNA to 18S RNA positively correlated with cardiac index (P less than 0.02). The RV ratio correlated negatively with systolic, diastolic and mean pulmonary arterial pressures (P less than 0.02, P less than 0.02, and P less than 0.01, respectively). We suggest that a decrease of the SR Ca2(+)-ATPase mRNA in the myocardium plays an important role in alterations of Ca2+ movements and myocardial relaxation reported during human end-stage heart failure.

The transplantable pituitary tumor MtT-F4 secretes several pituitary hormones in Fisher rats, resulting in severe cardiovascular disease with a mineralocorticoid type of hypertension and hyperlipidemia. The mineralocorticoid-dependent hypertension possesses particular characteristics in humans and animals. It was of interest to study cyclic nucleotides and platelet aggregation in the Fisher rat with an MtT-F4 tumor in order to evaluate the type of abnormalities in this form of hypertension. The effect of administration of an anti-hyperlipidemic agent (clofibrate) was also evaluated. The animals bearing the tumor showed anomalies of platelet aggregation induced by the divalent cation ionophore A 23187, in that there was an apparent enhanced change in shape and a decreased rate of aggregation. Although the basal concentrations of cyclic nucleotides were normal, as were the increases in cyclic GMP induced by epinephrine, cyclic AMP concentrations increased less (about 2.7-fold) in response to PGE1 than in control Fisher rats (about 6-fold). A decreased stimulation of adenylate cyclase activity by PGE1 was observed in platelets of tumor-bearing rats. The administration of clofibrate to sham-operated animals somewhat lowered the increase of cyclic AMP in response to PGE1. In tumor-bearing animals, clofibrate considerably reduced plasma lipids, blood pressure and the degree of abnormalities in platelet aggregation and cyclic AMP in platelets. Thus, the abnormalities of platelet aggregation and regulation of cyclic nucleotides in the mineralocorticoid-type of hypertension induced by MtT-F4 were opposite to those found previously in spontaneous hypertension in rats. Hyperlipidemic and hypertensive rats with MtT-F4 tumor may provide a useful model for the study of the relatioship between hyperlipidemia and hypertension.

In healthy humans glucagon infusion resulted in a significant increase in blood sugar and in plasma cyclic AMP. No discernible hemodynamic effects were found. Isoproterenol infusion on a mole per mole basis in the same subjects induced a significant, although less pronounced rise in plasma cyclic AMP, heart rate, and a fall in diastolic blood pressure but had no effect on blood sugar. Propranolol administration abolished the hemodynamic effects of isoproterenol and significantly decreased the response of plasma cyclic AMP; the same blocking dosage had little effect on plasma cyclic AMP changes induced by glucagon wheras the response in blood sugar was significantly reduced. These data in vivo are compatible with the in vitro demonstration of separate receptors for glucagon and isoproterenol.

Urinary excretion and plasma concentrations of adenosine 3',5'-monophosphate were determined in idiopathic edema patients both at rest and after assumption of the upright position. Patients and normal subjects responded similarly to upright posture with decreases in urinary volume and creatine excretion and their urinary excretion of cyclic AMP was not significantly different. The plasma concentration of cyclic AMP was high in patients, both in the recumbent and upright positions, and its renal clearance (unlike that of creatinine) was low. Plasma cyclic AMP increased in response to upright posture both in patients and normal subjects. Even if the significance of elevated plasma cyclic AMP is unknown, its presence without an increase in urinary cyclic AMP suggests that the renal handling of cyclic AMP is abnormal is idiopathic edema; this may be related to an excessive beta-adrenergic tone.