Reduced healthcare utilisation following successful HCV treatment in HIV co-infected patients with mild liver disease

New direct-acting antivirals (DAA) for hepatitis C virus (HCV) infection have achieved high cure rates in many patient groups previously considered difficult-to-treat, including those HIV/HCV co-infected. The high price of these medications is likely to limit access to treatment, at least in the short term. Early treatment priority is likely to be given to those with advanced disease, but a more detailed understanding of the potential benefits in treating those with mild disease is needed. We hypothesized that successful HCV treatment within a co-infected population with mild liver disease would lead to a reduction in the use and costs of healthcare services in the 5 years following treatment completion. We performed a retrospective cohort study of HIV/HCV-co-infected patients without evidence of fibrosis/cirrhosis who received a course of HCV therapy between 2004 and 2013. Detailed analysis of healthcare utilization up to 5 years following treatment for each patient using clinical and electronic records was used to estimate healthcare costs. Sixty-three patients were investigated, of whom 48 of 63 (76.2%) achieved sustained virological response 12 weeks following completion of therapy (SVR12). Individuals achieving SVR12 incurred lower health utilization costs (£5000 per-patient) compared to (£10 775 per-patient) non-SVR patients in the 5 years after treatment. Healthcare utilization rates and costs in the immediate 5 years following treatment were significantly higher in co-infected patients with mild disease that failed to achieve SVR12. These data suggest additional value to achieving cure beyond the prevention of complications of disease

ATR based infrared spectroscopy for the diagnosis of neonatal respiratory distress syndrome

Optical spectroscopy offers a potential non-invasive, label free and rapid method to assist clinicians to diagnose diseases for which biomarkers are known. Neonatal respiratory distress syndrome (nRDS) diagnosis in preterm infants is known to be correlated with the lecithin/sphingomyelin ratio (LS ratio) in gastric aspirates, with a ratio less than 2.2 indicating that surfactant replacement therapy is needed. Currently no widespread method exists that can give clinically relevant answers in less than 2 hours from the point of sample collection as it is difficult to identify those who could benefit from prompt surfactant treatment. Various LS ratios were generated using pure dipalmitoylphosphatidylcholine (DPPC) and sphingomyelin (SM) dissolved in dichloromethane and infrared spectra generated using Attenuated Total Reflection (ATR) assisted Fourier Transform InfraRed spectrometry (FTIR). Subsequent analysis obtained the LS ratio using the spectra alone. Further, we demonstrate the application of principal component regression (PCR) and partial least squares (PLS) fits to measured spectra to assist in the determination of the LS ratio using a model trained with multiple runs of the different batches of the same concentration

Resting-state Networks in Tinnitus: A Scoping Review

Chronic subjective tinnitus is the constant perception of a sound that has no physical source. Brain imaging studies show alterations in tinnitus patients’ resting-state networks (RSNs). This scoping review aims to provide an overview of resting-state fMRI studies in tinnitus, and to evaluate the evidence for changes in different RSNs. A total of 29 studies were included, 26 of which found alterations in networks such as the auditory network, default mode network, attention networks, and visual network; however, there is a lack of reproducibility in the field which can be attributed to the use of different regions of interest and analytical methods per study, and tinnitus heterogeneity. Future studies should focus on replication by using the same regions of interest in their analysis of resting-state data, and by controlling adequately for potential confounds. These efforts could potentially lead to the identification of a biomarker for tinnitus in the future

Prediction of Neonatal Respiratory Distress Biomarker Concentration by Application of Machine Learning to Mid-Infrared Spectra

The authors of this study developed the use of attenuated total reflectance Fourier transform infrared spectroscopy (ATR–FTIR) combined with machine learning as a point-of-care (POC) diagnostic platform, considering neonatal respiratory distress syndrome (nRDS), for which no POC currently exists, as an example. nRDS can be diagnosed by a ratio of less than 2.2 of two nRDS biomarkers, lecithin and sphingomyelin (L/S ratio), and in this study, ATR–FTIR spectra were recorded from L/S ratios of between 1.0 and 3.4, which were generated using purified reagents. The calibration of principal component (PCR) and partial least squares (PLSR) regression models was performed using 155 raw baselined and second derivative spectra prior to predicting the concentration of a further 104 spectra. A three-factor PLSR model of second derivative spectra best predicted L/S ratios across the full range (R2: 0.967; MSE: 0.014). The L/S ratios from 1.0 to 3.4 were predicted with a prediction interval of +0.29, −0.37 when using a second derivative spectra PLSR model and had a mean prediction interval of +0.26, −0.34 around the L/S 2.2 region. These results support the validity of combining ATR–FTIR with machine learning to develop a point-of-care device for detecting and quantifying any biomarker with an interpretable mid-infrared spectrum

Organelles in Blastocystis that blur the distinction between mitochondria and hydrogenosomes.

addresses: Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, B3H 1X5, Canada. [email protected]: PMCID: PMC2428068types: Journal Article; Research Support, Non-U.S. Gov'tOpen Access Article. This is a copy of an article published in Current Biology © Elsevier. Current Biology is available online at: http://www.sciencedirect.com/science/journal/09609822Blastocystis is a unicellular stramenopile of controversial pathogenicity in humans. Although it is a strict anaerobe, Blastocystis has mitochondrion-like organelles with cristae, a transmembrane potential and DNA. An apparent lack of several typical mitochondrial pathways has led some to suggest that these organelles might be hydrogenosomes, anaerobic organelles related to mitochondria. We generated 12,767 expressed sequence tags (ESTs) from Blastocystis and identified 115 clusters that encode putative mitochondrial and hydrogenosomal proteins. Among these is the canonical hydrogenosomal protein iron-only [FeFe] hydrogenase that we show localizes to the organelles. The organelles also have mitochondrial characteristics, including pathways for amino acid metabolism, iron-sulfur cluster biogenesis, and an incomplete tricarboxylic acid cycle as well as a mitochondrial genome. Although complexes I and II of the electron transport chain (ETC) are present, we found no evidence for complexes III and IV or F1Fo ATPases. The Blastocystis organelles have metabolic properties of aerobic and anaerobic mitochondria and of hydrogenosomes. They are convergently similar to organelles recently described in the unrelated ciliate Nyctotherus ovalis. These findings blur the boundaries between mitochondria, hydrogenosomes, and mitosomes, as currently defined, underscoring the disparate selective forces that shape these organelles in eukaryotes

Who gains from information asymmetry?

This article considers an asymmetric contest with incomplete information. There are two types of players: informed and uninformed. Each player has a different ability to translate effort into performance in terms of the contest success function. While one player's type is known to both players, the other is private information and known only to the player himself. We compare the Bayesian Nash equilibrium outcome of a one-sided private information contest to the Nash equilibrium with no private information, in which both players know the type of the other player. We show conditions under which uncertainty increases the investment of the uninformed player and the rent dissipation of the contest, while decreasing the expected net payoff of the informed player. In addition, we consider conditions under which the informed player - before knowing his own type - prefers that the uninformed player knows his type. Moreover, we show conditions for the existence/non-existence of equilibrium in a two-stage contest in which the informed player declares his type (or does not declare) in the first stage and in the second stage the two players play according to the information available to them

Nietzsche’s meta-axiology: against the skeptical readings

In this paper, I treat the question of the meta-axiological standing of Nietzsche's own values, in the service of which he criticizes morality. Does Nietzsche, I ask, regard his perfectionistic valorization of human excellence and cultural flourishing over other ideals to have genuine evaluative standing, in the sense of being correct, or at least adequate to a matter-of-fact? My goal in this paper is modest, but important: it is not to attribute to Nietzsche some sophisticated meta-axiological view, because I am doubtful that he has one. It is, however, to show that Nietzsche's texts do not necessitate the sceptical meta-axiological positions that have been attributed to him in the recent secondary literature. And it is thereby to suggest that we need not give up on the idea that Nietzsche takes the values he champions to have genuine evaluative standing – not because he has some sophisticated realist theory to this effect, but in a more philosophically unreflective way

Successful new product development by optimizing development process effectiveness in highly regulated sectors: the case of the Spanish medical devices sector

Rapid development and commercialization of new products is of vital importance for small and medium sized enterprises (SME) in regulated sectors. Due to strict regulations, competitive advantage can hardly be achieved through the effectiveness of product concepts only. If an SME in a highly regulated sector wants to excell in new product development (NPD) performance, the company should focus on the flexibility, speed, and productivity of its NPD function: i.e. the development process effectiveness. Our main research goals are first to explore if SMEs should focus on their their development process effectiveness rather than on their product concept effectiveness to achieve high NPD performance; and second, to explore whether a shared pattern in the organization of the NPD function can be recognized to affect NPD performance positively. The medical devices sector in Spain is used as an example of a\ud highly regulated sector. A structured survey among 11 SMEs, of which 2 were studied also as in in-depth case studies, led to the following results. First of all, indeed the companies in the dataset which focused on the effectiveness of their development process, stood out in NPD performance. Further, the higher performing companies did have a number of commonalities in the organisation of their NPD function: 1) The majority of the higher performing firms had an NPD strategy characterized by a predominantly incremental project portfolio.\ud 2) a) Successful firms with an incremental project portfolio combined this with a functional team structure b) Successful firms with a radical project portfolio combined this with a heavyweight or autonomous team structure.\ud 3) A negative reciprocal relationship exists between formalization of the NPD processes and the climate of the NPD function, in that a formalized NPD process and an innovative climate do not seem to reinforce each other. Innovative climate combined with an informal NPD process does however contribute positively to NPD performance. This effect was stronger in combination with a radical project portfolio. The highest NPD performance was measured for companies focusing mainly on incremental innovation. It is argued that in highly regulated sectors, companies with an incremental product portfolio would benefit from employing a functional structure. Those companies who choose for a more radical project portfolio in highly regulated sectors should be aware\ud that they are likely to excell only in the longer term by focusing on strategic flexibility. In their NPD organization, they might be well advised to combine informal innovation processes with an innovative climate