Robust reference intervals for Liver function test (LFT) analytes in newborns and infants

ABSTRACT: Back groundReference intervals (RIs) are ranges of upper and lower limits of a given analyte which are used for a laboratory test to determine whether a disease is present or absent or to know if the patient is at risk for future disease states. In Ethiopia, a country with highly diversified population groups and geographical sites, there are no established RIs to metabolic analytes including the liver function test (LFT) analytes for the pediatric population though it has been known that liver function assessment in this population is vital as a result of varied vulnerability to both endogenous and xenobiotic substances. METHODS: A cross sectional study was conducted in Tikur Anbessa Specialized Hospital (TASH) and Teklehaymanot Health Center (THC) from November 2010 to April 2011. 117 cord blood (from newborns) and venous blood samples (from infants) were collected and analyzed using HumaStar 300. All pre-analytical, analytical and post-analytical aspects were thoroughly controlled. A robust, CLSI/ IFCC recommended, method was used for the determination of upper and lower end points covering 95% of the reference values of each analyte with respective 90% CIs using MedCalc(R) software. RESULTS: Combined RIs for newborns and infants were established for albumin, AST, ALP, direct bilirubin and total bilirubin to be 3.88-5.82 g/dl, 16.1-55.4U/l, 130-831U/l, <0.41 mg/dl and <1.37 mg/dl respectively. But, separated RIs were indicated for ALT and GGT as 1.2-23.1U/l and 6.94-24.8U/l ALT; and 30.6-160.7U/L and 10--28.2U/l GGT for newborns and infants respectively. Some maternal and infantile factors were identified to affect the values of analytes. CONCLUSION: Almost all analytes were different from previously reported values for other target population of similar age group, kit insert values and adult values. So, interpretation of values of these analytes in newborns and infants of Ethiopian population sounds better to be performed by using such RIs taking the effect of some maternal and infantile factors in to account.     

Analysis of household's energy consumption,forest degradation and plantation requirements in Eastern Tigray,Northern Ethiopia

This study examines the link between household's energy consumption, forest degradation and plantation requirements in Eastern Tigray. Data on household's fuelwood, cow‐dung, kerosene and electricity consumption in the study sites were collected from 557 urban and 114 rural households. Deforestation rate was estimated following FAO and Woody Biomass Inventory Strategy Planning Project (WBISPP's) conversion factors. The study showed that household's fuelwood consumption in urban areas (mean = 2.5 kg/day) was about 52% lower as compared to the rural villages (mean = 3.8 kg/day). The estimated area abandoned annually in the vicinity of urban areas as the result of urban fuelwood consumption varies from 217 ha around Maichew town to 12047 ha around Mekelle City. The estimated area abandoned in rural areas annually as the result of tree cutting for fuelwood also varies from 6.5 ha around Sinkata to 127 ha around Dergajen village. It is therefore recommended that an estimated annual tree plantation of area ranging from 286 ha around Maichew town to 21,684 ha around Mekelle city is required. Moreover, an estimated annual tree plantation of area ranging from 16 ha around Sinkata village to 229 ha around the Dergajen village is required taking the existing population into account.     

Pro-fibrotic pathway activation in trabecular meshwork and lamina cribrosa is the main driving force of glaucoma

While primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide, it still does not have a clear mechanism that can explain all clinical cases of the disease. Elevated IOP is associated with increased accumulation of extracellular matrix (ECM) proteins in the trabecular meshwork (TM) that prevents normal outflow of aqueous humor (AH) and has damaging effects on the fine mesh-like lamina cribrosa (LC) through which the optic nerve fibers pass. Applying a pathway analysis algorithm, we discovered that an elevated level of TGFβ observed in glaucoma-affected tissues could lead to pro-fibrotic pathway activation in TM and in LC. In turn, activated pro-fibrotic pathways lead to ECM remodeling in TM and LC, making TM less efficient in AH drainage and making LC more susceptible to damage from elevated IOP via ECM transformation in LC. We propose pathway targets for potential therapeutic interventions to delay or avoid fibrosis initiation in TM and LC tissues.     

Neuronal Spike Timing Adaptation Described with a Fractional Leaky Integrate-and-Fire Model

The voltage trace of neuronal activities can follow multiple timescale dynamics that arise from correlated membrane conductances. Such processes can result in power-law behavior in which the membrane voltage cannot be characterized with a single time constant. The emergent effect of these membrane correlations is a non-Markovian process that can be modeled with a fractional derivative. A fractional derivative is a non-local process in which the value of the variable is determined by integrating a temporal weighted voltage trace, also called the memory trace. Here we developed and analyzed a fractional leaky integrate-and-fire model in which the exponent of the fractional derivative can vary from 0 to 1, with 1 representing the normal derivative. As the exponent of the fractional derivative decreases, the weights of the voltage trace increase. Thus, the value of the voltage is increasingly correlated with the trajectory of the voltage in the past. By varying only the fractional exponent, our model can reproduce upward and downward spike adaptations found experimentally in neocortical pyramidal cells and tectal neurons in vitro. The model also produces spikes with longer first-spike latency and high inter-spike variability with power-law distribution. We further analyze spike adaptation and the responses to noisy and oscillatory input. The fractional model generates reliable spike patterns in response to noisy input. Overall, the spiking activity of the fractional leaky integrate-and-fire model deviates from the spiking activity of the Markovian model and reflects the temporal accumulated intrinsic membrane dynamics that affect the response of the neuron to external stimulation.     

The deubiquitinating gene Usp29 is dispensable for fertility in male mice

The balanced actions between ubiquitination and deubiquitination precisely control the levels of various proteins vital for spermatogenesis. Ubiquitin-specific processing proteases(USPs) are the largest family of deubiquitinatingenzymes(DUBs),containing more than 50 members. So far, the functions of only a few USPs in male fertility have been studied, the roles of the majority are yet unknown. The present study aimed to explore the function of Usp29(ubiquitin-specific protease 29) in male fertility. We found that Usp29 showed predominant expression in mouse testis, and its m RNA expression started to increase at 14 days postpartum(dpp), with a peak at 28 and 35 dpp. Using CRISPR/Cas9 technology, we generated Usp29 knockout mice(Usp29~(–/–)). Usp29~(–/–)mice exhibited no overt developmental anomalies. Further examination revealed that Usp29~(–/–)mice had normal fertility and showed no detectable difference in the testis/body weight ratio, testicular and epididymal histology as well as epididymal sperm count from the wild-type littermates. Moreover, Usp29 is not a pseudogene in mice. Taken together, our study first reported that though Usp29 is predominantly expressed in the testis, it is not essential for male fertility in mice.     

Using species distribution models to select species resistant to climate change for ecological restoration of bowé in West Africa

Bowalization is a particular form of land degradation and leads to lateral expansion of ferricrete horizons. The process occurs only in tropical regions. In this study, the most adapted and resistant species towards climate change were identified on bowé. The 15 most common bowé species of the subhumid and semi‐arid climate zones of Benin were submitted together with significant environmental variables (elevation, current bioclimatic variables, soil types) to three ecological niche modelling programmes (Maxent, Domain and GARP). For future prediction (2050), IPCC4/CIAT and IPCC5/CMIP5 climate data were applied. Asparagus africanus, Andropogon pseudapricus and Combretum nigricans were identified as the most resistant species for ecological restoration of bowé in the semi‐arid climate zone and Asparagus africanus, Detarium microcarpum and Lannea microcarpa in the subhumid climate zone. The ‘Pull’ strategies were identified as appropriate for ecological restoration of bowé in Benin.     

Impacts of a mineral lick‐centred land use system on woody vegetation cover in an East African Savannah

Evaluation of woody vegetation changes with distance from a salt crater was conducted in the semi‐arid rangelands of southern Ethiopia. Data on live woody plants were collected over three seasons at 0, 1, 4, 6, 9 and 12 km from the salt crater. The density and diversity of woody plants differed significantly (p < .01) along the distance gradient. Six woody plant families were identified of which Fabaceae and Burseraceae were the dominant families. Acacia drepanolobium, Acacia nilotica, Commiphora africana and Acacia mellifera were among the severely encroaching woody species. There were high proportions of seedlings and saplings recorded closer to the salt crater showing a vigorous recruitment by woody plants. Woody plant encroachment along the 12‐km transect ranged from a low to severe encroachment, which could be translated into poor rangeland condition. Changes in soil characteristics increased grazing pressure and sedentary settlement around the salt crater, and the breakdown of traditional institutions seems to be major contributing factors to these vegetation changes. We suggest that severely encroached areas could be improved through a combination of methods such as bush clearing, prescribed fire, browsing animals and proper grazing management.     

Identification of recent cases of hepatitis C virus infection using physical-chemical properties of hypervariable region 1 and a radial basis function neural network classifier

Background

Identification of acute or recent hepatitis C virus (HCV) infections is important for detecting outbreaks and devising timely public health interventions for interruption of transmission. Epidemiological investigations and chemistry-based laboratory tests are 2 main approaches that are available for identification of acute HCV infection. However, owing to complexity, both approaches are not efficient. Here, we describe a new sequence alignment-free method to discriminate between recent (R) and chronic (C) HCV infection using next-generation sequencing (NGS) data derived from the HCV hypervariable region 1 (HVR1).

Results

Using dinucleotide auto correlation (DAC), we identified physical-chemical (PhyChem) features of HVR1 variants. Significant (p?<?9.58?×?10^?4) differences in the means and frequency distributions of PhyChem features were found between HVR1 variants sampled from patients with recent vs chronic (R/C) infection. Moreover, the R-associated variants were found to occupy distinct and discrete PhyChem spaces. A radial basis function neural network classifier trained on the PhyChem features of intra-host HVR1 variants accurately classified R/C-HVR1 variants (classification accuracy (CA)?=?94.85%; area under the ROC curve, AUROC?=?0.979), in 10-fold cross-validation). The classifier was accurate in assigning individual HVR1 variants to R/C-classes in the testing set (CA?=?84.15%; AUROC?=?0.912) and in detection of infection duration (R/C-class) in patients (CA?=?88.45%). Statistical tests and evaluation of the classifier on randomly-labeled datasets indicate that classifiers’ CA is robust (p?<?0.001) and unlikely due to random correlations (CA?=?59.04% and AUROC?=?0.50).

Conclusions

The PhyChem features of intra-host HVR1 variants are strongly associated with the duration of HCV infection. Application of the PhyChem biomarkers to models for detection of the R/C-state of HCV infection in patients offers a new opportunity for detection of outbreaks and for molecular surveillance. The method will be available at https://webappx.cdc.gov/GHOST/ to the authenticated users of Global Hepatitis Outbreak and Surveillance Technology (GHOST) for further testing and validation.

     

From Plateau to Pseudo-Plateau Bursting: Making the Transition

Bursting electrical activity is ubiquitous in excitable cells such as neurons and many endocrine cells. The technique of fast/slow analysis, which takes advantage of time scale differences, is typically used to analyze the dynamics of bursting in mathematical models. Two classes of bursting oscillations that have been identified with this technique, plateau and pseudo-plateau bursting, are often observed in neurons and endocrine cells, respectively. These two types of bursting have very different properties and likely serve different functions. This latter point is supported by the divergent expression of the bursting patterns into different cell types, and raises the question of whether it is even possible for a model for one type of cell to produce bursting of the type seen in the other type without large changes to the model. Using fast/slow analysis, we show here that this is possible, and we provide a procedure for achieving this transition. This suggests that the design principles for bursting in endocrine cells are just quantitative variations of those for bursting in neurons.