HIV-1 Subtype Diversity and Factors Affecting Drug Resistance among Patients with Virologic Failure in Antiretroviral Therapy in Hainan Province,China,2014–2020

Objective This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance(HIVDR)in patients with ART failure from 2014 to 2020 in Hainan,China.Methods A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan.We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences.Drug resistance mutations(DRMs)were analyzed using the Stanford University HIV Drug Resistance Database.Results A total of 307 HIV-infected patients with ART failure were included,and 241 available pol sequences were obtained.Among 241 patients,CRF01_AE accounted for 68.88%,followed by CRF07_BC(17.00%)and eight other subtypes(14.12%).The overall prevalence of HIVDR was 61.41%,and the HIVDR against non-nucleoside reverse transcriptase inhibitors(NNRTIs),nucleotide reverse transcriptase inhibitors(NRTIs),and protease inhibitors(PIs)were 59.75%,45.64%,and 2.49%,respectively.Unemployed patients,hypoimmunity or opportunistic infections in individuals,and samples from 2017 to 2020 increased the odd ratios of HIVDR.Also,HIVDR was less likely to affect female patients.The common DRMs to NNRTIs were K103N(21.99%)and Y181C(20.33%),and M184V(28.21%)and K65R(19.09%)were the main DRMs against NRTIs.Conclusion The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.

Tuning microstructures of TC4 ELI to improve explosion resistance

A reasonable heat treatment process for TC4 ELI titanium alloy is crucial to tune microstructures to improve its explosion resistance.However,there is limited investigation on tuning microstructures of TC4 ELI to improve explosion resistance.Moreover,the current challenge is quantifying microstructural changes'effects on explosion resistance and incorporating microstructural changes into finite element models.This work aims to tune microstructures to improve explosion resistance and elucidate their anti-explosion mechanism,and find a suitable method to incorporate microstructural changes into finite element models.In this work,we systematically study the deformation and failure characteristics of TC4 ELI plates with varying microstructures using an air explosion test and LS-DYNA finite element modeling.The Johnson-Cook(JC)constitutive parameters are used to quantify the effects of microstructural changes on explosion resistance and incorporate microstructural changes into finite element models.Because of the heat treatment,one plate has equiaxed microstructure and the other has bimodal microstructure.The convex of the plate after the explosion has a quadratic relationship with the charge mass,and the simulation results demonstrate high reliability,with the error less than 17.5%.Therefore,it is feasible to obtain corresponding JC constitutive parameters based on the differences in microstructures and mechanical properties and characterize the effects of microstructural changes on explosion resistance.The bimodal target exhibits excellent deformation resistance.The response of bimodal microstructure to the shock wave may be more intense under explosive loading.The well-coordinated structure of the bimodal target enhances its resistance to deformation.

Effects of cement-enhanced soil on the ultimate lateral resistance of composite pile in clayey soil

The composite pile consisting of core-pile and surrounding cement-enhanced soil is a promising pile foundation in recent years.However,how and to what extent the cement-enhanced soil influences the ultimate lateral resistance has not been fully investigated.In this paper,the ultimate lateral resistance of the composite pile was studied by finite element limit analysis(FELA)and theoretical upper-bound analysis.The results of FELA and theoretical analysis revealed three failure modes of laterally loaded composite piles.The effects of the enhanced soil thickness,strength,and pile-enhanced soil interface characteristics on the ultimate lateral resistance were studied.The results show that increasing the enhanced soil thickness leads to a significant improvement on ultimate lateral resistance factor(N P),and there is a critical thickness beyond which the thickness no longer affects the N P.Increasing the enhanced soil strength induced 6.2%-232.6%increase of N P.However,no noticeable impact was detected when the enhanced soil strength was eight times higher than that of the natural soil.The maximum increment of N P is only 30.5%caused by the increase of interface adhesion factor(a).An empirical model was developed to calculate the N P of the composite pile,and the results show excellent agreement with the analytical results.

Effect of Interface Form on Creep Failure and Life of Dissimilar Metal Welds Involving Nickel-Based Weld Metal and Ferritic Base Metal

For dissimilar metal welds(DMWs)involving nickel-based weld metal(WM)and ferritic heat resistant steel base metal(BM)in power plants,there must be an interface between WM and BM,and this interface suffers mechanical and microstructure mismatches and is often the rupture location of premature failure.In this study,a new form of WM/BM interface form,namely double Y-type interface was designed for the DMWs.Creep behaviors and life of DMWs containing double Y-type interface and conventional I-type interface were compared by finite element analysis and creep tests,and creep failure mechanisms were investigated by stress-strain analysis and microstructure characterization.By applying double Y-type interface instead of conventional I-type interface,failure location of DMW could be shifted from the WM/ferritic heat-affected zone(HAZ)interface into the ferritic HAZ or even the ferritic BM,and the failure mode change improved the creep life of DMW.The interface premature failure of I-type interface DMW was related to the coupling effect of microstructure degradation,stress and strain concentrations,and oxide notch on the WM/HAZ interface.The creep failure of double Y-type interface DMW was the result of Type IV fracture due to the creep voids and micro-cracks on fine-grain boundaries in HAZ,which was a result of the matrix softening of HAZ and lack of precipitate pinning at fine-grain boundaries.The double Y-type interface form separated the stress and strain concentrations in DMW from the WM/HAZ interface,preventing the trigger effect of oxide notch on interface failure and inhibiting the interfacial microstructure cracking.It is a novel scheme to prolong creep life and enhance reliability of DMW,by means of optimizing the interface form,decoupling the damage factors from WM/HAZ interface,and then changing the failure mechanism and shifting the failure location.

Evaluation of chronic kidney disease in chronic heart failure: From biomarkers to arterial renal resistances

Chronic kidney disease and its worsening are recurring conditions in chronic heart failure(CHF) which are independently associated with poor patient outcome.The heart and kidney share many pathophysiological mechanisms which can determine dysfunction in each organ. Cardiorenal syndrome is the condition in which these two organs negatively affect each other, therefore an accurate evaluation of renal function in the clinical setting of CHF is essential. This review aims to revise the parameters currently used to evaluate renal dysfunction in CHF with particular reference to the usefulness and the limitations of biomarkers in evaluating glomerular dysfunction and tubular damage. Moreover, it is reported the possible utility of renal arterial resistance index(a parameter associated with abnormalities in renal vascular bed) for a better assesment of kidney disfunction.

Increased index of microcirculatory resistance in older patients with heart failure with preserved ejection fraction

Objective To study the coronary microvascular function in older patients with heart failure with preserved ejection fraction (HFpEF) using an invasive pressure–temperature sensor guidewire. Methods Patients undergoing echocardiography and cardiac catheterization examinations for exertional dyspnea and a positive stress test were retrospectively enrolled from January 2014 to November 2017, and were allocated into the control group or HFpEF group. The HFpEF group was secondary divided into two groups according to the age of 65 years. Comparing the clinical features and values obtained in examinations between the three groups, multivariate regression analysis was used to analyze the predictors of left ventricle end diastolic pressure (LVEDP). Results There were 87 patients enrolled in this study. The older HFpEF patients (n = 32) were more likely to be female;and had the most comorbidities, such as diabetes mellitus, atrial fibrillation, and chronic kidney dysfunction (CKD) with a low estimated glomerular filtration rate (eGFR), and had a similar hypertensive prevalence as the adult HFpEF group (n = 24), whose mean LVEDP and index of microcirculatory resistance (IMR) were highest in comparison to the adult HFpEF patients and controls (n = 31). The coronary flow reserve (CFR) in the older HFpEF and adult HFpEF groups was similarly reduced. In the regression analysis, the IMR linearly correlated to LVEDP, and was the only independent predictor of LVEDP. Conclusions An increased IMR and reduced CFR were characteristics of microvascular dysfunction in older HFpEF patients. The IMR independently had a positive linear correlation with LVEDP. Microvascular rarefaction might be a subsequent pathological progression in the development of HFpEF.

Investigation of failure mechanism and mechanical properties of resistance spot welded magnesium alloy joints

Resistance .spot u,e/ded magnesium alloy joints can fail in two markedly different failure modes （interfiscialfitilure and button pullout failure） under tensile shear loading conditions. For button pullottt failure, the crack first propagates along cellular dendritic structure of the nugget circumference, and then passes through heat-affected zone （HAZ） and base metal in sequence. The tensile shear load has smaller values under the interracial failure occurring in a small weld nugget as compared to the button pullout failure appearing in a large weld nugget. The tensile shear load increases with the increasing nugget diameter for expulsion free joints. However, for joints which experienced expulsion, the tensile shear load decreases in spite of nugget diameter increasing. Under the equivalent nugget diameter （5. g mm）, the tensile shear load of joints with 9 × 10^-4 g KBF4 addition was increased by around 20% as compared to that of joints without KBF4 addition.

Hepatitis C virus treatment failure:Clinical utility for testing resistance-associated substitutions

The hepatitis C virus has a high mutation capacity that leads to the emergence of resistance-associated substitutions(RAS).However,the consequence of resistance selection during new direct-acting antiviral drug(DAA)treatment is not necessarily the therapeutic failure.In fact,DAA treatment has shown a high rate(>95%)of sustained virological response even when high baseline RAS prevalence has been reported.In the context of RAS emergence and high rates of sustained viral response,the clinical relevance of variants harboring RAS is still controversial.Therefore,in order to summarize the data available in international guidelines,we have reviewed the clinical utility of testing RAS in the era of new pangenotypic DAA drugs.

Protecting future antimalarials from the trap of resistance:Lessons from artemisinin-based combination therapy (ACT) failures

Having faced increased clinical treatment failures with dihydroartemisinin-piperaquine(DHA-PPQ),Cambodia swapped the first line artemisinin-based combination therapy(ACT)from DHA-PPQ to artesunate-mefloquine given that parasites resistant to piperaquine are susceptible to mefloquine.However,triple mutants have now emerged,suggesting that drug rotations may not be adequate to keep resistance at bay.There is,therefore,an urgent need for alternative treatment strategies to tackle resistance and prevent its spread.A proper understanding of all contributors to artemisinin resistance may help us identify novel strategies to keep artemisinins effective until new drugs become available for their replacement.This review highlights the role of the key players in artemisinin resistance,the current strategies to deal with it and suggests ways of protecting future antimalarial drugs from bowing to resistance as their predecessors did.

The change of plasma leptin level and its correlation study with insulin resistance or TNF-αin patients with congestive heart failure

Objectives To determine thechange of plasma leptin levels and the correlation be-tween hyperleptinaemia and insulin resistance orTNF -α in patients with congestive heart failure(CHF). Methods The levels of plasma leptin, fastingplasma insulin (FINS) and TNF-α in 64 male patientswith CHF and 30 healthy male people were measuredby ELISA. Body mass index (BMI), waist/hip ratio(WHR) and insulin resistance index (Homa-IR) werecalculated respectively. Results The plasma leptinlevels in CHF group were higher compared with con-trol group (P<0.00l). There was a increased trend ofplasma leptin levels in CHF group with the increaseof NYHA class (r_s=0.884, P<0.001), according to dif-ferent etiology,there was no significant difference ofplasma leptin levels in CHF group (P>0.05); FINS,Homa-IR and TNF-α levels in CHF group were high-er than in control group (all P<0.001); in CHF groupplasma leptin levels correlated with FINS (r=0.652, P<0.001),Homa-IR (r=0.561,P<0.001) and TNF-α (r=0.629,P<0.001); in multiple stepwise regression anal-ysis BMI, FINS and TNF-α were isolated factors af-fecting plasma leptin levels in CHF group, Y=-3.466+0.456 (BMI)+ 0.162 (FINS)+4.487(TNF-α), F=38.405,P<0.001. Conclusions plasma leptin levels wereraised and correlated with disease severity in patientswith CHF; FINS and TNF-α were isolated factor af-fecting plasma leptin level in CHF patients; hyper-leptinaemia may play a role in the pathophysiology ofCHF such as catabolic process and activation of neu-rohormonal.

Factors associated with DAA virological treatment failure and resistance-associated substitutions description in HIV/HCV coinfected patients

AIM To describe factors associated with treatment failure and frequency of resistance-associated substitutions(RAS).METHODS Human immunodeficiency virus(HIV)/hepatitis C virus(HCV) coinfected patients starting a first direct-acting antiviral(DAA) regimen before February 2016 and included in the French ANRS CO13 HEPAVIH cohort were eligible. Failure was defined as:(1) non-response [HCV-RNA remained detectable during treatment, at end of treatment(EOT)]; and(2) relapse(HCVRNA suppressed at EOT but detectable thereafter). Sequencing analysis was performed to describe prevalence of drug class-specific RAS. Factors associated with failure were determined using logistic regression models.RESULTS Among 559 patients, 77% had suppressed plasma HIV-RNA < 50 copies/mL at DAA treatment initiation, 41% were cirrhotic, and 68% were HCV treatmentexperienced. Virological treatment failures occurred in 22 patients and were mainly relapses(17, 77%) then undefined failures(3, 14%) and non-responses(2, 9%). Mean treatment duration was 16 wk overall. Posttreatment NS3, NS5 A or NS5 B RAS were detected in 10/14 patients with samples available for sequencing analysis. After adjustment for age, sex, ribavirin use, HCV genotype and treatment duration, low platelet count was the only factor significantly associated with a higher risk of failure(OR: 6.5; 95%CI: 1.8-22.6). CONCLUSION Only 3.9% HIV-HCV coinfected patients failed DAA regimens and RAS were found in 70% of those failing. Low platelet count was independently associated with virological failure.

Risk of control failure to insecticides malathion,profenophos+cypermethrin mixture,and fipronil in boll weevil(Coleoptera:Curculionidae)populations from Bahia,Brazil

Background To control the boll weevil Anthonomus grandis grandis(Coleoptera:Curculionidae),a key pest of cotton in the Americas,insecticides have been intensively used to manage their populations,increasing selection pressure for resistant populations.Thus,this study aimed to detect insecticide resistance and assess insecticide control failure likelihood of boll weevil populations exposed to malathion,profenophos+cypermethrin,and fipronil insecticides.Results Twelve populations of the boll weevil were collected from commercial cotton fileds of the state of Bahia,northeastern Brazil.These populations were exposed to malathion,profenophos+cypermethrin mixture,and fipronil,at their respective maximum label dose for field applications.Three replicates of 10 adult beetles were exposed to the insecticides and mortality was recorded after 24 h treatment.The control failure likelihood was determined after 48 h.Highest median lethal times(LT_(50))were observed for malathion and the profenophos+cypermethrin mixture.Resistance to at least one insecticide was detected in 11 populations;three populations were resistant to malathion and profenophos+cypermethrin;seven were resistant to all insecticides tested.The resistance levels were low(<10-fold)for the three insecticides.Among 12 populations tested,58%of them exhibited significant risk of control failure for the insecticides malathion and profenophos+cypermethrin.The insecticide fipronil was efficient for the control of the boll weevil in 83%of the populations.Conclusions The results confirm the significant risk of insecticide control failure in the boll weevil populations to the main compounds used in the region.Thus,proper insecticide resistance management plans are necessary for the boll weevil in the region,particularly for malathion and profenophos+cypermethrin insecticides.

The use of diuretics in acute heart failure: Evidence based therapy?

The evidence base for the use of diuretics in acute heart failure is limited, with no large double-blind placebo-controlled randomized trials. However, their use as a first line treatment of acute heart failure is firmly established in clinical practice, and endorsed in clinical guidelines. Loop diuretics are typically the first line diuretic strategy for the treatment of acute heart failure. For patients with considerable fluid retention, there is some evidence that initial treatment with continuous infusion or boluses of high dose loop diuretic is superior to an initial lower dose strategy. In patients who are diuretic resistant, the addition of an oral thiazide or thiazide-like diuretic to induce sequential nephron blockade can be beneficial. Intravenous low-dose dopamine has also been used to assist diuresis and preserve renal function in such circumstances, but trials are underway to confirm the clinical value of this agent. Mechanical ultrafiltration has been used to treat patients with heart failure and fluid retention, but the evidence base is not secure, and its place in clinical practice is yet to be established.

Comparison between the electrical resistance and the shear strength of brazed cemented carbides

Brazing is a suitable technology to join different materials such as cemented carbides and steel. Even though this technology has been investigated for many years, insufficient joints can occur easily, as the brazing process is very sensitive concerning the handling parameters. Defects such as voids and cracks are hard to detect by commonly used visual inspection methods. Other nondestructive methods such as radiography or ultrasonic testing are usually not economical for the examination of these joints. Studies proved that the electrical resistance has the potential to serve as an effective alternative for the evaluation of brazed joints. In this study, the authors have compared the electrical resistance and the shear strength. For this, cemented carbides were brazed to steel by means of induction heating at an ambient atmosphere. A silver-based filler metal （ BrazeTec 4900 / Ag 449 ） and a flux （ BrazeTec spezial h / FH12） were selected to enable the brazing process. The brazing time and the temperature were varied in order to produce different joint qualities. After brazing, the resistance was measured on each joint with the 4-point probe method to facilitate a high accuracy. The results underline the possibility to use electrical resistance measurements as an effective tool for a quality control of brazed joints.

Failure mechanism of Mesozoic soft rock roadway in Shajihai coal mine and its surrounding rock control

In view of the buckling failure caused by large deformation of Mesozoic soft rock roadway in Shajihai mining area, such as serious roof fall, rib spalling, floor heave, etc., based on the detail site investigation,theoretical analysis, mineral composition test, microstructure test, water-physical property test and field experiments were carried out. And we revealed the compound failure mechanism of Mesozoic soft rock roadway in Shajihai mining area, namely the molecule expansion-shear slip of weak structural plane-construction disturbance. On this basis, the coupling support technology whose core is constant resistance with large deformation bolt was proposed. The feature of this supporting technology is that a new type of structural composite material was used, which makes the supporting system not only has the ideal deformation characteristics, but also has high supporting resistance. Thus the fully release of plastic energy within surrounding rock and reasonable control of the thickness of the plastic ring were realized. Then the differential deformation between the surrounding rock and support was eliminated by the secondary coupling support of bolt–mesh–cable, and the bolt with high strength was applied in the base angle to control floor. Eventually the collaborative bearing system of surrounding rock–support was formed. Through field tests the validity and rationality of support was also verified.

High-resistance controlled yielding supporting technique in deep-well oil shale roadways

In order to avoid the deep-well oil shale roadway being deformed, damaged, or difficult to maintain after excavating and supporting in Haishiwan coal mine, this paper has analyzed the characteristics of the deformed roadway and revealed its failure mechanism by taking comprehensively the methods of field geological investigation, displacement monitoring of surrounding rock, rock properties and hydration properties experiments and field application tests. Based on this work, the high-resistance controlled yielding supporting principle is proposed, which is: to ‘‘resist'' by high pre-tightening force and high stiffness in the early stage, to ‘‘yield'' by making use of the controlled deformation of a yielding tube in the middle stage, and to ‘‘fix'' by applying total-section Gunite in the later stage. A high-resistance controlled yielding supporting technique of ‘‘high pre-tightening force yielding anchor bolt + small-bore pre-tightening force anchor cable + rebar ladder beam + rhombic metal mesh + lagging gunite'' has been established, and industrial on site testing implemented. The practical results show that the high-resistance controlled yielding supporting technique can effectively control the large deformation and long-time rheology of deep-well oil shale roadways and can provide beneficial references for the maintenance of other con-generic roadways.

RESEARCH ON DIRECT CURRENT ELECTRIC FIELD CHARACTERISTICS OF OVERBURDEN FAILURE AND ITS APPLICATIONS

The overburden failure causes the changes of the constant electric field, and the resistivity is the main parameter in these changes. The experimental simulation about tbe response relation between the overburden failure and its electrical parameter changes is made by building the similar material physics model of mining. The experiment results are used to analyze and test the in-situ detection. The research indicates that the resistivity changes with the electric characteristic of the rock in cracked zone and caving zone caused by overburden failure, the response characteristics of resistivity vary with the failure degrees at different overburden failure zone and that they are corresponding. The resistivity method used in monitoring the overburden failure can determine the height and the affecting scopes of the cracked zone and caving zone. This can provide reliable techaological guarantee for mining design and safe production.

Effects of Additive CeO_2 on Thermal Shock Resistance of Plasma-Sprayed Cr_2O_3 Coating

The influence of CeO2 with different content on the thermal shock resistance of plasmasprayed Cr2O3 coating was investigated. The thermal shock failure mechanism of coating was also studied. It is found that the thermal shock failure mechanism of coating is thermal stress fatigue destruction, and the destruction takes place at interface of ceramic and bond coating. The experimental results show that the lifetime of coating fracture and failure increase considerably when 3% CeO2 is added into the plasma-sprayed Cr2O3 coating. The suitable content of CeO2 makes the microcracks exist in network form. The microcrack net can release internal stress in coating, delay the crack forming and expanding and decrease holes in coating. Thus the thermal shock resistance increase largely.

Quality Evaluation of Diffusion Bonded Joints by Electrical Resistance Measuring and Microscopic Fatigue Testing

Micro-structure related behavior of diffusion bonding joints is a crucial issue in device and reactor fabrication of Micro Chemo Mechanical Systems.However,the previous studies have been focused on the macro mechanical performance of diffusion bonded joint,especially diffusion bonding conditions effects on tensile strength,shearing strength and fatigue strength.The research of interfacial micro-voids and microstructures evolution for failure mechanism has not been carried out for diffusion-bonded joints.An interfacial electrical resistance measuring method is proposed to evaluate the quality of bonded joints and verified by using two-dimensional finite-element simulation.The influences of micro void geometry on increments of resistance are analyzed and the relationship between bonded area fraction and resistance increment is established by theoretical analysis combined with simulated results.Metallographic inspections and micro-hardness testing are conducted near the interface of diffusion bonded joints.For the purpose of identifying the failure mechanisms of the joints,both microscopic tensile and fatigue tests are conducted on the self-developed in-situ microscopic fatigue testing system.Based on the microscopic observations,the mechanism of interfacial failure is addressed.The observation result shows that for 316LSS diffusion-bonded joints,microstructure evolution and effect of micro-voids play a key role in interfacial failure mechanism.Finally,a new life prediction model in terms of the increment of electrical resistance is developed and confirmed by the experimental results.The proposed study is initiated that constituted a primary interfacial failure mechanism on micron scale and provide the life prediction for reliability of components sealed by diffusion bonding.

Involvement of the Genetic Diversity of HIV-1 in the Virological Treatment Failure of First Line Antiretroviral in Kinshasa

Background: Genetic diversity of human immunodeficiency virus affects the treatment and the emergence of resistance. Some subtypes would develop resistance more frequently than others. The aim of this study is to determine the rate of virological treatment failure and the involvement of genetic diversity and different mutations in this failure in Kinshasa. Methods: Of the 153 Antiretroviral-naive patients who were included in the cohort, 138 patients have been received for the appointment of the 6th month. Clinical parameters were recorded on individual patient charts. The determination of Viral Load (VL) was done at the Laboratory of Molecular Biology. Clinical and biological parameters of the 6th month were compared with those taken at baseline of the cohort to determine the evolution of patients under treatment. Results: At the consultation of the 6th month, 138 patients (90.2%) had returned out of the 153 included. Eighty-one (58.7%) patients were women and 57 (41.3%) men. The age of patients is between 18 and 65 with an average of 37 years. Ten deaths (6.5%) and 5 (3.3%) lost have been reported. One hundred twenty-five patients (90.5%) were in clinical stage 3 and 13 (9.5%) in clinical stage 4. The median CD4 T cells is 560 cells mm3. The median VLs of patients was 0.90 log10 RNA copies/ml. Of the 34 patients in virological failure, 8 (23.5%) are minimal failure, 23 (67.7%) in moderate failure and 3 (8.8%) in severe failure. According to the Pearson’s test, VLs at 6th months were highly correlated with that of inclusion, with V75 and K70 mutations for NRTIs, with V108 mutation for NNRTI well as the virological failure of treatment. Conclusion: Our results confirmed the hypothesis that high Viral Load at the start of the treatment is a poor prognosis for the development of therapy. Transmitted mutations are involved in treatment failure.