This study uses a business network perspective to investigate the industry 4.0 context with the internet of things (IoT) as its enabling technology and product-use data as its core network resource. ...A three-stage qualitative methodology (interviews, focus group, Delphi-based inquiry) was used to examine the case of an emergent IoT-based business network in the UK road transport industry to examine: (i) how aspects of product use data influence the benefit opportunities the data provide to the different network actors; (ii) how capturing of the benefit opportunities in a network context is impacted by key barriers; and (iii) how network capabilities can overcome these barriers to capture benefits from product-use data. The study, thereby, contributes to an understanding of the industry 4.0 context from a resource dependency theory perspective and provides concrete recommendations for management operating in this context.
Background
Interferon-inducible protein-10 (IP-10) and monokine induced by interferon-gamma (MIG) are chemokines recognized as inflammatory biomarkers during HIV-1 infection. We assessed their early ...and long-term dynamics after initiation of antiretroviral treatment (ART).
Methods
Persons with HIV-1 (PWH) aged>18 years starting their first ART in 2015-2021 in a prospective cohort (n=73) were included. IP-10 and MIG plasma levels were quantified using a multiplexed bead-based assay.
Results
IP-10 and MIG plasma levels showed a significant and consistent reduction following ART (80% integrase inhibitor INSTI-based) initiation, starting at day 20 and maintained throughout the study period (48 months), paralleling the HIV-1 RNA decay and CD4+ count recovery (p<0·001). At baseline, PWH≥ 50 years, CDC stage C and CD4+ count<350cells/mm
3
had higher levels of IP-10 (p=0·022, p=0·001 and p=0·002, respectively) and MIG (p<0·001, p=0·024 and p=0·069, respectively). All of them matched their counterparts several months following ART initiation. MIG levels showed a greater decrease at day 10 in those treated with INSTI (p=0·038). Low-level HIV-1 viremia did not impact MIG or IP-10 levels.
Conclusion
Plasma IP-10 and MIG showed an early significant decline following ART initiation, with greater early declines in MIG levels in INSTI-based regimens. These findings suggest a strong impact of HIV-1 viremia on IP-10 and MIG levels.
The lack of the recovery of CD4
T-cells (CD4
recovery) among immunodeficiency virus (HIV)-infected patients on antiretroviral therapy (ART) is not well known. We aimed to analyze the association ...between single nucleotide polymorphisms (SNPs) underlying vitamin D metabolism and the CD4
recovery in naïve HIV-infected patients who started ART with low baseline CD4
.
We conducted a retrospective study in 411 naïve individuals with plasma HIV load >200 copies/mL and CD4
<200 cells/mm
. During 24 months of follow-up, all patients had plasma HIV load <50 copies/mL. DNA genotyping was performed using the Sequenom MassARRAY platform. The outcome variable was the change in CD4
during the study.
CD4
recovery was higher in patients carrying
rs7041 AA genotype (AA versus CC/AC) and
rs3829251 AA genotype (AA versus GG/AG) (
-value < 0.05).
rs7041 AA genotype was linked to increase in CD4
(adjusted arithmetic mean ratio (aAMR) = 1.22;
-value = 0.011), increase in CD4
≥P75th adjusted odds ratio (aOR) = 2.31;
-value = 0.005, slope of CD4
recovery (aAMR = 1.25;
-value = 0.008), slope of CD4
recovery ≥ P75th (aOR = 2.55;
-value = 0.005) and achievement of CD4
≥500 cells/mm
(aOR = 1.89;
-value = 0.023). Besides,
rs3829251 AA genotype was related to increase in CD4
(aAMR = 1.43;
-value = 0.031), increase in CD4
≥P75th (aOR = 3.92;
-value = 0.030), slope of CD4
recovery (aAMR = 1.40;
-value = 0.036), slope of CD4
recovery ≥ P75th (aOR = 3.42;
-value = 0.031) and achievement of CD4
≥500 cells/mm
(aOR = 5.68;
-value = 0.015).
In summary,
rs3829251 and
rs7041 polymorphisms were associated with CD4
recovery in HIV-infected patients who started cART with low CD4
T-cell counts.
Because inflammation is associated with mortality and has been linked to HIV transcription in lymphoid tissues during ART, it is necessary to address the long-term effects of switching 3-drug (3DR) ...to 2-drug regimens (2DR) on inflammation.
Nested study in the Spanish AIDS Research Network. We selected PWH ART-naive initiating 3DR who achieved viral suppression in the first 48 weeks and either remained on 3DR or switched to 2DR (3TC+bPI; 3TC+DTG; DTG+RPV). We assessed the trajectories on inflammatory markers during ART using multivariate piecewise mixed models.
We analyzed 619 plasma samples from 148 patients (3DR, N=90; 2DR, N=58), the median follow-up was 4.6 (IQR 3.2-6.2) years. There were no significant differences in baseline characteristics between groups. After adjusting for potential confounders, patients with 3DR experienced a slow decline of IL6, hs-CRP, sCD14, sCD163, and D-dimer over time. In contrast, compared to 3DR, switching to 2DR was associated with increases in IL-6 (p=0.001), hs-CRP (p=0.003), and D-dimer (p=0.001) after year 3 from virologic suppression. 2DR was associated with a higher risk of hs-CRP quartile increase (aOR 3.3, 95%CI 1.1-10) and D-dimer quartile increase (aOR 3.7, 95%CI 1.1-13). The adjusted biomarker trajectories did not reveal a distinct pattern according to the type of 2DR used (bPI
DTG).
In this study in virally suppressed individuals, maintaining 3DR was associated with a more favorable long-term inflammatory profile than switching to 2DR. The potential clinical implications of these findings on the development of non-AIDS events deserve further investigation.
A eficácia não inferior a longo prazo do regime de 2 medicamentos foi demonstrada em estudos de 144 semanas em virgens de tratamento e pacientes experimentados com um bom perfil de segurança e uma ...alta barreira à resistência. Avaliamos a eficácia e segurança da mudança para combinação de dose fixa DTG/3TC em adultos com HIV-1 em uso de qualquer regime antirretroviral (CAR) atual. SALSA é um estudo randomizado, controlado e aberto. Os participantes com RNA de HIV-1 <50 c/mL por> 6 meses em um esquema de 3/4DR sem falha virológica anterior ou mutações associadas à resistência a inibidor da transcriptase reversa de nucleosídeo (NRTI) ou DTG foram randomizados 1:1 (estratificado pela classe de terceiro agente da linha de base ) para mudar para DTG/3TC ou continuar CAR por 52 semanas. O desfecho primário foi a proporção de participantes com RNA de HIV-1 plasmático ≥50 c/mL na semana 48 (população exposta por intenção de tratamento ; falha virológica instantânea). Estimativas e intervalos de confiança foram baseados em análise estratificada usando o teste Cochran-Mantel-Haenszel ajustados para a terceira classe de agente da linha de base. No geral, 493 participantes foram randomizados (59% brancos; 39% mulheres; 39% com idade ≥50 anos; 50%/40%/10% com não NRTI/inibidor da integrase/inibidor da protease no início do estudo). DTG/3TC não foi inferior ao CAR contínuo na semana 48 usando análise de falha virológica instantânea (DTG / 3TC, 1/246 0,4%; CAR, 3/247 1,2%; diferença de tratamento ajustada IC de 95%, -0,8% -2,4%, 0,8%); os resultados foram consistentes com a análise de resposta virológica instantânea (DTG/3TC, 232/246 94,3%; CAR, 229/247 92,7%; diferença de tratamento ajustada IC de 95%, 1,6% -2,8%, 5,9% ). Nenhuma retirada virológica confirmada ou resistência observada ocorreu em nenhum dos grupos. Os resultados gerais de segurança foram comparáveis entre os grupos DTG/3TC e CAR quanto à frequência de quaisquer eventos adversos (AEs; 73% vs 70%), AEs que levam à retirada (2% vs 1%) e AEs graves (3% vs 6% ), respectivamente. Conclusão: No SALSA, a mudança para DTG/3TC foi não inferior à continuação da CAR na manutenção da supressão virológica na semana 48, com um perfil de segurança consistente com as bulas de DTG e 3TC. Ao longo de 48 semanas, o esquema com 2DR (DTG/3TC) oferece uma opção de troca com menos drogas antirretrovirais em comparação com 3/4DRs tradicionais, sem aumento do risco de falha virológica ou resistência.
Liver stiffness (LS) at sustained virological response (SVR) after direct-acting antivirals (DAA)-based therapy is a predictor of liver events in hepatitis C virus (HCV)-infected patients. The study ...aim was to identify genetic factors associated with LS changes from the moment of starting anti-HCV therapy to SVR. This prospective study included HCV-infected patients from the GEHEP-011 cohort who achieved SVR with DAA-based therapy, with LS pre-treatment ≥ 9.5 kPa and LS measurement available at SVR. Plink and Magma software were used to carry out genome-wide single-nucleotide polymorphism (SNP)-based and gene-based association analyses, respectively. The ShinyGO application was used for exploring enrichment in Gene Ontology (GO) categories for biological processes. Overall, 242 patients were included. Median (quartile 1, quartile 3) LS values at pre-treatment and at SVR were 16.8 (12, 28) kPa and 12.0 (8.5, 19.3) kPa, respectively. Thirty-five SNPs and three genes reached suggestive association with LS changes from the moment of starting anti-HCV therapy to SVR. GO categories related to DNA packaging complex, DNA conformation change, chromosome organization and chromatin organization were significantly enriched. Our study reports possible genetic factors associated with LS changes during HCV-infection cure. In addition, our results suggest that processes related to DNA conformation are also involved in these changes.
Abstract
Background
The GlutenTox® ELISA Rapid G12 test kit is a quantitative method designed for the determination of the immunotoxic fraction of gluten in food samples.
Objective
To obtain AOAC ...Performance-Tested MethodsSM certification for the method for the detection and quantification of gluten from wheat, barley, and rye flours in select foods (non-heat-processed) and incurred (heat-processed) matrixes.
Methods
The method was evaluated following the Guidelines for Validation of Quantitative Gluten Methods, with Specific Examples for ELISA Assays. The validation study was conducted at Hygiena Diagnóstica España using five food matrixes (soy flour, corn bread, seasoning mix, rolled oats, and evaporated milk) artificially contaminated with gluten from wheat, barley, or rye flour at different concentrations: 0, 5, 10, and 20 mg/kg. For each matrix and gluten contamination level, five or six individually extracted test portions were analyzed. A second bread matrix was prepared by baking a gluten-free bread mix spiked at 0, 20, and 30 mg/kg gluten from wheat, barley, or rye flour for incurred matrix testing. Ten individually extracted test portions were tested for each incurred bread and contamination level of gluten.
Results
The method met the AOAC performance requirements for detection and quantification of wheat gluten in the selected food matrixes, incurred bread sample, and spike levels of wheat gluten, showing an acceptable recovery. When tested with barley and rye flours, most of the results showed acceptable recoveries or a slight overestimation, depending on the matrix and gluten concentration. Method developer and independent laboratory results were comparable.
Conclusions
The validation study demonstrated that the test kit is a reliable, accurate, quick, and easy-to-use method for the detection and quantification of gluten concentration in food and incurred matrixes from wheat, barley, and rye flours.
Highlights
Most reagents provided in the kit are at ready-to-use concentrations.
In TANGO, switching to dolutegravir/lamivudine (DTG/3TC) demonstrated long-term noninferior efficacy vs continuing tenofovir alafenamide-based regimens in treatment-experienced adults with HIV-1. The ...phase 3 SALSA study evaluated efficacy and safety of switching to DTG/3TC compared with continuing various 3-/4-drug current antiretroviral regimens (CARs).
Adults with HIV-1 RNA <50 copies/mL and no previous virologic failure were randomized (1:1, stratified by baseline third agent class) to switch to once-daily fixed-dose combination DTG/3TC or continue CAR (primary endpoint: proportion of participants with HIV-1 RNA ≥50 copies/mL at week 48; Snapshot, intention-to-treat-exposed population, 5% noninferiority margin).
Overall, 493 adults (39% women; 39% aged ≥50 years; 19% African American/African heritage; 14% Asian) were randomized to switch to DTG/3TC (n = 246) or continue CAR (n = 247). At week 48, 1 (0.4%) participant in the DTG/3TC group and 3 (1.2%) in the CAR group had HIV-1 RNA ≥50 copies/mL (Snapshot), demonstrating noninferiority (adjusted difference, -0.8%; 95% CI, -2.4%, .8%). Zero participants met confirmed virologic withdrawal criteria; therefore, no resistance testing was performed. Drug-related adverse events were more frequent with DTG/3TC (20%) than CAR (6%) through week 48 but comparable post-week 24 (5% vs 2%, respectively). Proximal tubular renal function and bone turnover biomarkers improved with DTG/3TC. Both groups had generally minimal changes in lipids and inflammatory biomarkers.
Switching to DTG/3TC was noninferior to continuing CAR for maintaining virologic suppression at week 48 with no observed resistance, supporting the efficacy, good safety, and high barrier to resistance of DTG/3TC.
www.clinicaltrials.gov, NCT04021290.
Abstract
Increasing levels of urbanisation and the rapid growth of modern cities require that particular attention be paid to ensuring the safety and protection of living conditions for their ...inhabitants. In this context, natural and human-induced disasters pose a major threat to the safety and normal operational procedures of buildings and infrastructures. In consequence, disaster management and built assets operations demand modern tools to be effectively prepared in order to better respond to such critical events. This study explores the potential of artificial intelligence in these operational fields by developing a deep learning model that is able to provide a rapid assessment of an asset’s structural condition in the case of a seismic excitation. The proposed simulation model makes an accurate prediction of the damage status of individual elements in a built asset, thus leading to operational improvements across all disaster management phases. In addition, the above development integrates the deep learning algorithm into building information modelling and then uploads the graphical information to a web dashboard. By following the framework proposed, an integrative model is designed that provides a visual and user-friendly interface that allows different stakeholders to navigate and comprehend essential information on the effects of a disaster; thus enabling quicker decision making and strengthening operational resilience in critical events.
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