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Nevin Manimala Statistics

Diagnostic accuracy of lung ultrasonography in childhood pneumonia: a meta-analysis

Eur J Emerg Med. 2021 Oct 6. doi: 10.1097/MEJ.0000000000000883. Online ahead of print.

ABSTRACT

OBJECTIVE: This meta-analysis aimed to assess the diagnostic accuracy of lung ultrasonography in pneumonia-affected pediatric patients.

METHODS: Literature search of published articles in Medline, Web of Science, Scopus, Embase and Journal of Web till September 2020 were reviewed for the predescribed accuracy assessors. In compliance with the inclusion and exclusion criteria, two researchers independently screened the literature, collected the results and assessed the risks of bias using the quality assessment of diagnostic accuracy studies-2 tool. The pooled sensitivity and specificity, pooled positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio were estimated for the meta-analysis. The overall efficiency of LUS was evaluated using a summary receiver operating characteristic curve. Q and I2 statistics were used to determine heterogeneity. Meta disc software was used for the analysis of the study.

RESULTS: Out of 1182 studies, only 29 articles were chosen; 25 of them were prospective studies and 4 studies were retrospective. The overall pooled sensitivity was 0.83 [95% confidence intervals (CI), 0.81-0.84] and specificity was 0.84 (95% CI, 0.81-0.86), depicting good diagnostic performance.

CONCLUSION: LUS is an efficient imaging technique for detecting childhood pneumonia with a high accuracy rate. It is an appealing alternative to chest X rays to detect and follow-up pneumonia in children because it is simple to do, widely available, comparatively cheap and free of radiation hazards.

PMID:34619690 | DOI:10.1097/MEJ.0000000000000883

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Estimation of electric field impact in deep brain stimulation from axon diameter distribution in the human brain

Biomed Phys Eng Express. 2021 Oct 7. doi: 10.1088/2057-1976/ac2dd4. Online ahead of print.

ABSTRACT

OBJECTIVE: Finite element method (FEM) simulations of the electric field magnitude (EF) are commonly used to estimate the affected tissue surrounding the active contact of deep brain stimulation (DBS) leads. Previous studies have found that DBS starts to noticeably activate axons at approximately 0.2 V/mm, corresponding to activation of 3.4 µm axons in simulations of individual axon triggering. Most axons in the brain are considerably smaller however, and the effect of the electric field is thus expected to be stronger with increasing EF as more and more axons become activated. The objective of this study is to estimate the fraction of activated axons as a function of electric field magnitude.

APPROACH: The EF thresholds required for axon stimulation of myelinated axon diameters between 1 and 5 µm were obtained from a combined cable and Hodgkin-Huxley model in a FEM-simulated electric field from a Medtronic 3389 lead. These thresholds were compared with the average axon diameter distribution from literature from several structures in the human brain to obtain an estimate of the fraction of axons activated at EF levels between 0.1 and 1.8 V/mm.

MAIN RESULTS: The effect of DBS is estimated to be 47∙EF – 8.8 % starting at a threshold level EFt0 = 0.19 V/mm.

SIGNIFICANCE: The fraction of activated axons from DBS in a voxel is estimated to increase linearly with EF above the threshold level of 0.19 V/mm. This means linear regression between EF above 0.19 V/mm and clinical outcome is a suitable statistical method when doing improvement maps for DBS.

PMID:34619674 | DOI:10.1088/2057-1976/ac2dd4

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Nevin Manimala Statistics

The Regional Specificity of Mucosa-Associated Microbiota in Patients with Distal Colorectal Cancer

Digestion. 2021 Oct 7:1-9. doi: 10.1159/000519487. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: Recent studies have demonstrated that the populations of several microbes are significantly increased in fecal samples from patients with colorectal cancer (CRC), suggesting their involvement in the development of CRC. The aim of this study was to identify microbes which are increased in distal CRCs and to identify the specific location of microbes increased in mucosal tissue around the tumor.

METHODS: Tissue specimens were collected from surgical resections of 28 distal CRCs. Five samples were collected from each specimen (location A: tumor, B: adjacent normal mucosa, C: normal mucosa 1 cm proximal to the tumor, D: normal mucosa 3 cm proximally, and E: normal mucosa 6 cm proximally). The microbiota in the sample were analyzed using 16S rRNA gene amplicon sequencing and the relative abundance (RA) of microbiota compared among the 5 locations.

RESULTS: At the genus level, the RA of Fusobacterium and Streptococcus at location A was the highest among the 5 locations, significantly different from that in location E. The dominant species of each genus was Fusobacterium nucleatum and Streptococcus anginosus. The RAs of these species gradually decreased from locations B to E with a statistically significant difference in F. nucleatum. The genus Peptostreptococcus also showed a similar trend, and the RA of Peptostreptococcus stomatis in location A was significantly associated with depth of tumor invasion and tumor size.

CONCLUSION: Although the clinical relevance is not clear yet, these results suggest that F. nucleatum, S. anginosus, and P. stomatis can spread to the adjacent normal tissues and may change the surrounding microenvironment to support the progression of CRC.

PMID:34619680 | DOI:10.1159/000519487

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Correlation of in-vivo imaging with histopathology: A review

Eur J Radiol. 2021 Sep 21;144:109964. doi: 10.1016/j.ejrad.2021.109964. Online ahead of print.

ABSTRACT

Despite tremendous advancements in in vivo imaging modalities, there remains substantial uncertainty with respect to tumor delineation on in these images. Histopathology remains the gold standard for determining the extent of malignancy, with in vivo imaging to histopathologic correlation enabling spatial comparisons. In this review, the steps necessary for successful imaging to histopathologic correlation are described, including in vivo imaging, resection, fixation, specimen sectioning (sectioning technique, securing technique, orientation matching, slice matching), microtome sectioning and staining, correlation (including image registration) and performance evaluation. The techniques used for each of these steps are also discussed. Hundreds of publications from the past 20 years were surveyed, and 62 selected for detailed analysis. For these 62 publications, each stage of the correlative pathology process (and the sub-steps of specimen sectioning) are listed. A statistical analysis was conducted based on 19 studies that reported target registration error as their performance metric. While some methods promise greater accuracy, they may be expensive. Due to the complexity of the processes involved, correlative pathology studies generally include a small number of subjects, which hinders advanced developments in this field.

PMID:34619617 | DOI:10.1016/j.ejrad.2021.109964

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The best strategy for metastatic colorectal cancer (mCRC) patients in second-line treatment: A network meta-analysis

Cancer Treat Res Commun. 2021 Sep 17;29:100455. doi: 10.1016/j.ctarc.2021.100455. Online ahead of print.

ABSTRACT

BACKGROUND: Varieties of systemic treatments in second-line treatment for metastatic colorectal cancer (mCRC) patients have showed an improvement on survival. In this study, we performed a systematic review with a pairwise and bayesian network meta-analysis to rank the best strategy for mCRC patients in second-line treatment.

METHODS: A systematic literature search through 2007 was performed to evaluate the association between several treatment combinations and overall survival (OS), progression-free survival (PFS) and disease control rate (DCR) in mCRC patients. Data were carried out and pooled into a statistical indirect comparison with Bayesian network meta-analysis (NMA).

RESULTS: 10 trials totally comprised 4183 patients were included in our study. In NMA, For PFS, Doublet+Bev showed benefits in comparing with Doublet, Doulblet+placebo and Doublet+Ramucirumab. Also, Doublet+Aflibercept demonstrated its superiority in comparing with Doulblet+placebo. For OS, Doublet+Bev represented its superiority when comparing with Double and Doublet+placebo. Doublet+Aflibercept and Doublet+Ramucirumab also done well when opposed to Doublet+placebo. For DCR, Doublet+bev showed unique superiority when compared with Doublet, And Doublet+targeted agent did not represent benefits to each other in DCR. Doublet+bev ranked highest in terms of PFS, OS and DCR followed by Doublet+panitumumab, Doublet+placebo was the lowest in terms of PFS and OS.

CONCLUSIONS: Our study shows that Doublet+Bev has the major probability to provide an improvement of survival in patients with mCRC.

PMID:34619647 | DOI:10.1016/j.ctarc.2021.100455

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Changes in Escherichia coli to enteric protozoa ratios in rivers: Implications for risk-based assessment of drinking water treatment requirements

Water Res. 2021 Sep 25;205:117707. doi: 10.1016/j.watres.2021.117707. Online ahead of print.

ABSTRACT

Minimum treatment requirements are set in response to established or anticipated levels of enteric pathogens in the source water of drinking water treatment plants (DWTPs). For surface water, contamination can be determined directly by monitoring reference pathogens or indirectly by measuring fecal indicators such as Escherichia coli (E. coli). In the latter case, a quantitative interpretation of E. coli for estimating reference pathogen concentrations could be used to define treatment requirements. This study presents the statistical analysis of paired E. coli and reference protozoa (Cryptosporidium, Giardia) data collected monthly for two years in source water from 27 DWTPs supplied by rivers in Canada. E. coli/Cryptosporidium and E. coli/Giardia ratios in source water were modeled as the ratio of two correlated lognormal variables. To evaluate the potential of E. coli for defining protozoa treatment requirements, risk-based critical mean protozoa concentrations in source water were determined with a reverse quantitative microbial risk assessment (QMRA) model. Model assumptions were selected to be consistent with the World Health Organization (WHO) Guidelines for drinking-water quality. The sensitivity of mean E. coli concentration trigger levels to identify these critical concentrations in source water was then evaluated. Results showed no proportionalities between the log of mean E. coli concentrations and the log of mean protozoa concentrations. E. coli/protozoa ratios at DWTPs supplied by small rivers in agricultural and forested areas were typically 1.0 to 2.0-log lower than at DWTPs supplied by large rivers in urban areas. The seasonal variations analysis revealed that these differences were related to low mean E. coli concentrations during winter in small rivers. To achieve the WHO target of 10-6 disability-adjusted life year (DALY) per person per year, a minimum reduction of 4.0-log of Cryptosporidium would be required for 20 DWTPs, and a minimum reduction of 4.0-log of Giardia would be needed for all DWTPs. A mean E. coli trigger level of 50 CFU 100 mL-1 would be a sensitive threshold to identify critical mean concentrations for Cryptosporidium but not for Giardia. Treatment requirements higher than 3.0-log would be needed at DWTPs with mean E. coli concentrations as low as 30 CFU 100 mL-1 for Cryptosporidium and 3 CFU 100 mL-1 for Giardia. Therefore, an E. coli trigger level would have limited value for defining health-based treatment requirements for protozoa at DWTPs supplied by small rivers in rural areas.

PMID:34619609 | DOI:10.1016/j.watres.2021.117707

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CDT vs. GGT for the certification of the fitness to hold the driving license. A comparison based on the association of incremented values with the occurrence of alcohol-related road traffic accidents

Drug Alcohol Depend. 2021 Sep 22;228:109088. doi: 10.1016/j.drugalcdep.2021.109088. Online ahead of print.

ABSTRACT

BACKGROUND: In the context of fitness certification to hold the driving license, GGT and CDT have been used, sometimes in combination (γ-CDT), to exclude chronic alcohol abuse. The present study was carried out with the aim of comparing the power of these biomarkers as tools for the objective screening of subjects at high risk of alcohol-associated traffic injuries.

METHODS: 288 male drivers admitted to hospital after traffic accidents were examined by determination of GGT, CDT and BAC. The degree of association of GGT, CDT and γ-CDT with BAC was analysed using non-parametric statistics.

RESULTS: Partitioning the cases using the cut-off concentrations of 0.5 g/L for BAC (the legal limit adopted in most European countries), 55 U/L for GGT and 1.9% for CDT, a highly significant difference was found between the frequency of elevated GGT or CDT in cases where BAC was within the legal limits and those with elevated BAC values (Fisher’s exact test: p < 0.001). However, the calculation of the odds ratio showed a much higher increase for CDT (28 times) than for GGT (6 times) in those drivers with a BAC above the Italian legal limit in comparison with those showing a BAC within the cut-off; conversely, γ-CDT does not provide any significant advantage vs. CDT alone.

CONCLUSIONS: Both GGT and CDT provide objective evidence of an association with the occurrence of alcohol-related severe traffic accidents, but CDT shows superior association with these events. Therefore, CDT, notwithstanding higher costs, should be preferred in a forensic/certification context.

PMID:34619604 | DOI:10.1016/j.drugalcdep.2021.109088

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Impact of fenbendazole resistance in Ascaridia dissimilis on the economics of production in turkeys

Poult Sci. 2021 Aug 27;100(11):101435. doi: 10.1016/j.psj.2021.101435. Online ahead of print.

ABSTRACT

Feed conversion efficiency is among the most important factors affecting profitable production of poultry.Infections with parasitic nematodes can decrease efficiency of production, making parasite control through the use of anthelmintics an important component of health management. In ruminants and horses, anthelmintic resistance is highly prevalent in many of the most important nematode species, which greatly impacts their control. Recently, we identified resistance to fenbendazole in an isolate of Ascaridia dissimilis, the most common intestinal helminth of turkeys. Using this drug-resistant isolate, we investigated the impact that failure to control infections has on weight gain and feed conversion in growing turkeys. Birds were infected on D 0 with either a fenbendazole-susceptible or -resistant isolate, and then half were treated with fenbendazole (SafeGuard Aquasol) at 4- and 8-wk postinfection. Feed intake and bird weight were measured for each pen weekly throughout the study, and feed conversion rate was calculated. Necropsy was performed on birds from each treatment group to assess worm burdens at wk 7 and 9 postinfection. In the birds infected with the susceptible isolate, fenbendazole-treated groups had significantly better feed conversion as compared to untreated groups. In contrast, there were no significant differences in feed conversion between the fenbendazole-treated and untreated groups in the birds infected with the resistant isolate. At both wk 7 and 9, worm burdens were significantly different between the treated and untreated birds infected with the drug-susceptible isolate, but not in the birds infected with the drug-resistant isolate. These significant effects on feed conversion were seen despite having a rather low worm establishment in the birds. Overall, these data indicate that A. dissimilis can produce significant reductions in feed conversion, and that failure of treatment due to the presence of fenbendazole-resistant worms can have a significant economic impact on turkey production. Furthermore, given the low worm burdens and an abbreviated grow out period of this study, the levels of production loss we measured may be an underestimate of the true impact that fenbendazole-resistant worms may have on a commercial operation.

PMID:34619579 | DOI:10.1016/j.psj.2021.101435

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Introduction of the concept of diagnostic sensitivity and specificity of normothermic perfusion protocols to assess high-risk donor livers

Liver Transpl. 2021 Oct 7. doi: 10.1002/lt.26326. Online ahead of print.

ABSTRACT

Normothermic machine perfusion (NMP) allows objective assessment of donor liver transplantability. Several viability evaluation protocols have been established, consisting of parameters such as perfusate lactate clearance, pH, transaminase levels, and the production and composition of bile. The aims of this study were to assess three such protocols, namely those introduced by the teams from Birmingham (BP), Cambridge (CP) and Groningen (GP), using a cohort of high-risk marginal livers that had initially been deemed unsuitable for transplantation, and to introduce the concept of the viability assessment sensitivity and specificity. To demonstrate and quantify the diagnostic accuracy of these protocols, we used a composite outcome of organ utilisation and 24-month graft survival as a surrogate endpoint. The effects of assessment modifications, including the removal of the most stringent components of the protocols, were also assessed. Of the 31 organs, 22 were transplanted after a period of NMP, of which 18 achieved the outcome of 24-month graft survival. The BP yielded 94% sensitivity and 50% specificity when predicting this outcome. The GP and CP both seemed overly conservative, with one and zero organs, respectively, meeting these protocols. Modification of the GP and CP to exclude their most stringent components increased this to 11 and 8 organs, respectively, and resulted in moderate sensitivity (56% and 44%) but high specificity (92% and 100%, respectively) with respect to the composite outcome. This study shows that the normothermic assessment protocols can be useful in identifying potentially viable organs, but that the balance of risk of under- and overutilization varies by protocol.

PMID:34619014 | DOI:10.1002/lt.26326

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Cell-Culture Technique to Encode Glyco-nanoparticles Selectivity

Chem Asian J. 2021 Oct 7. doi: 10.1002/asia.202101015. Online ahead of print.

ABSTRACT

Nanoparticles (NPs) embedded with bioactive ligands such as carbohydrates, peptides, and nucleic acid have emerged as a potential tool to target biological processes. Traditional in vitro assays performed under statistic conditions may result in non-specific outcome sometimes, mainly because of the sedimentation and self-assembly nature of NPs. Inverted cell-culture assay allows for flexible and accurate detection of the receptor-mediated uptake and cytotoxicity of NPs. By combining this technique with glyco-gold nanoparticles, cellular internalization and cytotoxicity were investigated. Regioselective glycosylation patterns and shapes of the NPs could tune the receptors’ binding affinity, resulting in precise cellular uptake of AuNPs. Two cell lines HepG2 and HeLa were probed with galactosamine-embedded fluorescent AuNPs, revealing significant differences in cytotoxicity and uptake mechanism in upright and invert in vitro cell-culture assay, high-specificity toward uptake, and allowing for a rapid screening and optimization technique.

PMID:34619024 | DOI:10.1002/asia.202101015