RESUMEN
BACKGROUND: Clinical Dementia Rating (CDR) global (CDR-G) and sum of box scores (CDR-SB) are commonly used as primary outcome variables to measure progression or treatment effects in symptomatic Alzheimer disease (AD) clinical trials. OBJECTIVES: We sought to determine whether the CDR is sensitive to change in pre-symptomatic AD and whether there are specific CDR boxes that are dynamic during the multi-year Anti-Amyloid in Asymptomatic Alzheimer's Disease (A4) secondary prevention study. DESIGN: All participants entered the study with a CDR-G of 0. Box scores were examined individually and as composites of cognition (memory, orientation and judgment /problem solving) and function (community affairs and home/ hobbies). A progression in box score was tabulated only when the change occurred at two consecutive visits. SETTING: The A4 study took place at 67 sites in Australia, Canada, Japan and the United States. PARTICIPANTS: 1,147 individuals, ages 65-85, were randomized to either placebo (n= 583) or solanezumab (n= 564). All participants received a baseline flobetapir PET scan, an annual CDR, and cognitive testing every 6 months with the Primary Alzheimer Cognitive Composite (PACC) over the course of 240 weeks. MEASUREMENTS: Generalized estimating equations and generalized least square models were used to explore the modeled mean progression rate in the CDR-G, CDR-SB, individual CDR boxes, and CDR composite scores in the combined solanezumab and placebo groups. Models were refitted to explore the probability of CDR progression in centiloid tertiles of amyloid at baseline (< 46.1 CL, 46.1 to 77.2 CL, > 77.2 CL). All models included effects for age, education, APOEε4 carrier status, baseline amyloid with flobetapir PET, treatment, and time-by-treatment. RESULTS: There were no statistical differences between the placebo or solanezumab groups in CDR-G, CDR-SB, specific CDR boxes or CDR composite scores over the course of the trial. Changes in judgment/ problem solving were present at baseline and persisted over time, but progression on the CDR memory box and the CDR cognitive composite quickly predominated. Community affairs and home/ hobbies showed little progression. Personal care remained stable. The probability of cognitive and functional progression in CDR boxes began either at the intermediate or advanced amyloid level (46.1 to 77.2 CL, > 77.2 CL), while amyloid at the lowest level (< 46.1 CL) showed relatively little CDR progression. CONCLUSIONS: The findings suggest that the CDR memory box and the CDR cognitive composite progressed over 240 weeks and were associated with intermediate and advanced stages of amyloid at baseline. Functional changes in community affairs and home/hobbies were relatively stable. These finding suggest that specific CDR box score changes may help refine our measurement of expected treatment effects in future AD prevention trials.
Asunto(s)
Enfermedad de Alzheimer , Anticuerpos Monoclonales Humanizados , Progresión de la Enfermedad , Tomografía de Emisión de Positrones , Humanos , Anciano , Femenino , Masculino , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/uso terapéutico , Encéfalo/diagnóstico por imagen , Pruebas de Estado Mental y Demencia , Cognición/fisiología , Cognición/efectos de los fármacos , Método Doble Ciego , Compuestos de Anilina , Glicoles de EtilenoRESUMEN
BACKGROUND: Blood-based AD biomarkers such as plasma P-tau217 are increasingly used in clinical trials as a screening tool. OBJECTIVES: To assess the utility of an electrochemiluminescence (ECL) immunoassay in predicting brain amyloid PET status in cognitively unimpaired individuals. SETTING: Plasma samples collected at baseline, week 12, and week 240 or endpoint originated from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) trial and the companion Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) study. PARTICIPANTS: Both A4 and LEARN enrolled eligible cognitively unimpaired persons 65 to 85 years. Individuals with elevated brain amyloid PET levels were eligible for the A4 Study, while those without elevated brain amyloid PET levels were eligible for the LEARN Study. INTERVENTION: Participants in the A4 Study received intravenous solanezumab (up to 1600 mg) or placebo every 4 weeks. The LEARN Study is an observational study without intervention. MEASUREMENTS: Plasma P-tau217 concentration levels from A4 Study participants were measured using an ECL immunoassay. Receiver Operating Characteristic (ROC) curve analysis was performed for each biomarker against amyloid positivity, defined by ≥22 CL and ≥ 33 CL. RESULTS: Receiver operating characteristic curve (ROC) analysis indicates high diagnostic value of P-tau217 in individuals with amyloid PET ≥ 20 (Area under the ROC (AUROC): 0.87) and ≥ 33 CL (AUROC: 0.89). Repeated testing with the placebo group taken 12 weeks apart (range: 68 to 143 days) and the LEARN participants taken between 1.4 and 1.75 years resulted in a strong positive correlation (Corr. 0.91 (0.90 to 0.92)). CONCLUSION: An ECL immunoassay testing plasma P-tau217 accurately predicts amyloid PET positivity in cognitively unimpaired individuals. Our future analyses aim to determine if use of this assay may reduce the screening burden of preclinical individuals into anti-amyloid clinical trials.
Asunto(s)
Enfermedad de Alzheimer , Biomarcadores , Tomografía de Emisión de Positrones , Proteínas tau , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/diagnóstico , Anciano , Proteínas tau/sangre , Masculino , Femenino , Biomarcadores/sangre , Anciano de 80 o más Años , Estudios Longitudinales , Anticuerpos Monoclonales Humanizados/uso terapéutico , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Péptidos beta-Amiloides/sangre , Péptidos beta-Amiloides/metabolismoRESUMEN
BACKGROUND: Converging evidence suggests that markers of Alzheimer's disease (AD) pathology in cognitively unimpaired older individuals are associated with high risk of cognitive decline and progression to functional impairment. The Anti-Amyloid Treatment in Asymptomatic Alzheimer's disease (A4) and Longitudinal Evaluation of Amyloid and Neurodegeneration Risk (LEARN) Studies enrolled a large cohort of cognitively normal older individuals across a range of baseline amyloid PET levels. Recent advances in AD blood-based biomarkers further enable the comparison of baseline markers in the prediction of longitudinal clinical outcomes. OBJECTIVES: We sought to evaluate whether biomarker indicators of higher levels of AD pathology at baseline predicted greater cognitive and functional decline, and to compare the relative predictive power of amyloid PET imaging, tau PET imaging, and a plasma P-tau217 assay. DESIGN: All participants underwent baseline amyloid PET scan, plasma P-tau217; longitudinal cognitive testing with the Primary Alzheimer Cognitive Composite (PACC) every 6 months; and annual functional assessments with the clinical dementia rating (CDR), cognitive functional index (CFI), and activities of daily living (ADL) scales. Baseline tau PET scans were obtained in a subset of participants. Participants with elevated amyloid (Aß+) on screening PET who met inclusion/exclusion criteria were randomized to receive placebo or solanezumab in a double-blind phase of the A4 Study over 240+ weeks. Participants who did not have elevated amyloid (Aß-) but were otherwise eligible for the A4 Study were referred to the companion observational LEARN Study with the same outcome assessments over 240+ weeks. SETTING: The A4 and LEARN Studies were conducted at 67 clinical trial sites in the United States, Canada, Japan and Australia. PARTICIPANTS: Older participants (ages 65-85) who were cognitively unimpaired at baseline (CDR-GS=0, MMSE 25-30 with educational adjustment, and Logical Memory scores within the normal range LMIIa 6-18) were eligible to continue in screening. Aß+ participants were randomized to either placebo (n=583) or solanezumab (n=564) in the A4 Study. A subset of Aß+ underwent tau PET imaging in A4 (n=350). Aß- were enrolled into the LEARN Study (n=553). MEASUREMENTS: Baseline 18-F Florbetapir amyloid PET, 18-F Flortaucipir tau PET in a subset and plasma P-tau217 with an electrochemiluminescence (ECL) immunoassay were evaluated as predictors of cognitive (PACC), and functional (CDR, CFI and ADL) change. Models were evaluated to explore the impact of baseline tertiles of amyloid PET and tertiles of plasma P-tau217 on cognitive and functional outcomes in the A4 Study compared to LEARN. Multivariable models were used to evaluate the unique and common variance explained in longitudinal outcomes based on baseline predictors, including effects for age, gender, education, race/ethnic group, APOEε4 carrier status, baseline PACC performance and treatment assignment in A4 participants (solanezumab vs placebo). RESULTS: Higher baseline amyloid PET CL and P-tau217 levels were associated with faster rates of PACC decline, and increased likelihood of progression to functional impairment (CDR 0.5 or higher on two consecutive measurements), both across LEARN Aß- and A4 Aß+ (solanezumab and placebo arms). In analyses considering all baseline predictor variables, P-tau217 was the strongest predictor of PACC decline. Among participants in the highest tertiles of amyloid PET or P-tau217, >50% progressed to CDR 0.5 or greater. In the tau PET substudy, neocortical tau was the strongest predictor of PACC decline, but plasma P-tau217 contributed additional independent predictive variance in commonality variance models. CONCLUSIONS: In a large cohort of cognitively unimpaired individuals enrolled in a Phase 3 clinical trial and companion observational study, these findings confirm that higher baseline levels of amyloid and tau markers are associated with increased rates of cognitive decline and progression to functional impairment. Interestingly, plasma P-tau217 was the best predictor of decline in the overall sample, superior to baseline amyloid PET. Neocortical tau was the strongest predictor of cognitive decline in the subgroup with tau PET, suggesting that tau deposition is most closely linked to clinical decline. These findings indicate that biomarkers of AD pathology are useful to predict decline in an older asymptomatic population and may prove valuable in the selection of individuals for disease-modifying treatments.
Asunto(s)
Biomarcadores , Disfunción Cognitiva , Tomografía de Emisión de Positrones , Proteínas tau , Humanos , Femenino , Anciano , Masculino , Proteínas tau/sangre , Estudios Longitudinales , Biomarcadores/sangre , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/tratamiento farmacológico , Actividades Cotidianas , Anticuerpos Monoclonales Humanizados/uso terapéutico , Péptidos beta-Amiloides/sangre , Péptidos beta-Amiloides/metabolismo , Anciano de 80 o más Años , Progresión de la Enfermedad , Compuestos de AnilinaRESUMEN
BACKGROUND: Increased white matter hyperintensity (WMH) volume visible on MRI is a common finding in Alzheimer's disease (AD). We hypothesized that WMH in preclinical AD is associated with the presence of advanced vessel amyloidosis manifested as microhemorrhages (MCH). OBJECTIVES: 1) To assess the relationship between baseline WMH volume and baseline MCH. 2) To assess the relationship between longitudinal WMH accumulation and last MRI MCH during the double-blind phase of the A4 trial. DESIGN: A multicenter, randomized, double-blind, placebo-controlled, Phase 3 study comparing solanezumab with placebo given as infusions once every 4 weeks over 4.5 years in subjects with preclinical AD, defined as having evidence of elevated brain amyloid before the stage of clinically evident cognitive impairment, with an optional open-label extension period. SETTING: Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study. PARTICIPANTS: A sample of 1157 cognitively unimpaired older adults (mean age = 71.9 years [SD = 4.8 years], 59% women, 59% APOE ε4 carriers). MEASUREMENTS: A linear regression model was used to assess the impact of baseline MCH amount (0, 1, 2+) on WMH volume. A linear mixed-effects model was used to assess the impact of last MRI MCH on longitudinal WMH. All models were corrected for age, sex, grey matter volume, cortical amyloid PET, APOE ε4 status, and treatment group. RESULTS: Baseline WMH volume was greater in individuals with more than one MCH compared to those with no MCH (t=4.8, p<0.001). The longitudinal increase in WMH amongst individuals with one (t=2.3, p=0.025) and more than one MCH (t=6.7, p<0.001) at the last MRI was greater than those with no MCH. CONCLUSION: These results indicate a strong association between WMH and MCH, a common manifestation of cerebral amyloid angiopathy and ARIA-H. These results suggest that increased WMH volume may represent an early sign of vessel amyloidosis, likely prior to the emergence of MCH.
Asunto(s)
Enfermedad de Alzheimer , Anticuerpos Monoclonales Humanizados , Imagen por Resonancia Magnética , Sustancia Blanca , Humanos , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/tratamiento farmacológico , Femenino , Masculino , Anciano , Sustancia Blanca/patología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/efectos de los fármacos , Método Doble Ciego , Anticuerpos Monoclonales Humanizados/uso terapéutico , Síntomas ProdrómicosRESUMEN
BACKGROUND: Individuals from diverse racial and ethnic groups are severely underrepresented in Alzheimer's disease trials in part due to disproportionate biomarker ineligibility. Evidence from recent studies support plasma phosphorylated tau 217 (P-tau217) as an early marker for brain Aß pathology and a reliable marker in predicting elevated brain amyloid PET in cognitively unimpaired adults. OBJECTIVES: To examine whether the relationship between P-tau217 and 18-F florbetapir PET standard uptake value ratios (SUVR) is influenced by race and ethnicity in the Anti-Amyloid treatment in Asymptomatic Alzheimer's disease (A4) preclinical AD studies. DESIGN: We conducted a retrospective analysis of A4 clinical trial and the LEARN natural history companion study data to evaluate the relationship between baseline P-tau217 and PET SUVR concentration levels by race and ethnicity. SETTING: The analysis was conducted on samples from participants enrolled across 65 study sites in the United States and Canada. PARTICIPANTS: Cognitively unimpaired adults aged 65-85 enrolled at North American sites in the A4 preclinical AD trial, pre-dose, (N=1018), and the LEARN (N=480) study. Participants were grouped into 2 categories, racial and ethnic underrepresented group (RE-URG) and non-RE-URG (nRE-URG) based on self-identification. MEASUREMENTS: A mixed-effects regression model was fit to determine differences in the relationship between P-tau217 and PET SUVR by race and ethnicity, adjusting for age, and APOE ε4 carrier status. RESULTS: Results from the linear mixed-effects model support that there was no statistically significant effect of race and ethnicity on the relationship between P-tau217 and PET SUVR. CONCLUSION: These findings suggest that the relationship between plasma P-tau217 and PET SUVR is the same across race and ethnicity. Future analyses should corroborate these findings in a larger sample and examine whether plasma P-tau217 reflects the differential amyloid prevalence previously reported for other biomarkers of amyloid.
Asunto(s)
Enfermedad de Alzheimer , Tomografía de Emisión de Positrones , Proteínas tau , Humanos , Anciano , Femenino , Masculino , Proteínas tau/metabolismo , Proteínas tau/sangre , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/diagnóstico por imagen , Anciano de 80 o más Años , Estudios Retrospectivos , Compuestos de Anilina , Etnicidad , Biomarcadores/sangre , Biomarcadores/metabolismo , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Grupos Raciales , Estados Unidos , Canadá , Glicoles de Etileno , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/sangre , FosforilaciónRESUMEN
BACKGROUND: Participant discontinuation from study treatment in a clinical trial can leave a trial underpowered, produce bias in statistical analysis, and limit interpretability of study results. Retaining participants in clinical trials for the full study duration is therefore as important as participant recruitment. OBJECTIVE: This analysis aims to identify associations of pre-randomization characteristics of participants with premature discontinuation during the blinded phase of the Anti-Amyloid treatment in Asymptomatic AD (A4) Study. DESIGN: All A4 trial randomized participants were classified as having prematurely discontinued study during the blinded period of the study for any reason (dropouts) or completed the blinded phase of the study on treatment (completers). SETTING: The trial was conducted across 67 study sites in the United States, Canada, Japan and Australia through the global COVID-19 pandemic. PARTICIPANTS: The sample consisted of all 1169 A4 trial randomized participants. MEASUREMENTS: Pre-randomization demographic, clinical, amyloid PET and genetic predictors of study discontinuation were evaluated using a univariate generalized linear mixed model (GLMM), with discontinuation status as the binary outcome, each predictor as a fixed effect, and site as a random effect to account for differences among study sites in the trial. Characteristics significant at p<0.10 were then included in a multivariable GLMM. RESULTS: Among randomized participants, 339 (29%) discontinued the study during the blinded period (median follow-up time in trial: 759 days). From the multivariable analysis, the two main predictors of study discontinuation were screening State-Trait Anxiety Inventory (STAI) scores (OR = 1.07 [95%CI = 1.02; 1.12]; p=0.002) and age (OR = 1.06 [95%CI = 1.03; 1.09]; p<0.001). Participants with a family history of dementia (OR = 0.75 [95%CI = 0.55; 1.01]; p=0.063) and APOE ε4 carriers (OR = 0.79 [95%CI = 0.6; 1.04]; p=0.094) were less likely to discontinue from the study, with the association being marginally significant. In these analyses, sex, race and ethnicity, cognitive scores and amyloid/tau PET scores were not associated with study dropout. CONCLUSIONS: In the A4 trial, older participants and those with higher levels of anxiety at baseline as measured by the STAI were more likely to discontinue while those who had a family history of dementia or were APOE ε4 carriers were less likely to drop out. These findings have direct implications for future preclinical trial design and selection processes to identify those individuals at greatest risk of dropout and provide information to the study team to develop effective selection and retention strategies in AD prevention studies.
Asunto(s)
Enfermedad de Alzheimer , Humanos , Masculino , Femenino , Anciano , Pacientes Desistentes del Tratamiento/estadística & datos numéricos , COVID-19 , Síntomas Prodrómicos , Australia , Estados Unidos , Canadá , Tomografía de Emisión de Positrones , Anciano de 80 o más AñosRESUMEN
This paper forms part of an ongoing investigation into the tools required in linear elastic fracture mechanics (LEFM) for evaluating the durability of components designed for limited life replacement. In this study, we demonstrate that the USAF 'Characteristic K' method, when combined with the Hartman-Schijve adaptation of the NASGRO crack growth formula, can predict the impact of underloads on the propagation of small cracks in aluminum alloy AA7050-T7451 with reasonable accuracy. The published da/dN versus ΔK small crack growth curves associated with five specific underload spectra are examined. It is found that, in each case, there is reasonably good agreement between the predicted and the measured curves. To the best of the author's knowledge, this paper is the first to highlight the ability of the USAF Characteristic K approach, when coupled with the Hartman-Schijve equation, to reasonably accurately predict the growth of small cracks subjected to a range of underload spectra.
RESUMEN
This paper presents the results of an extensive investigation into the durability of cold spray repairs to corrosion damage in AA7075-T7351 aluminium alloy specimens where, prior to powder deposition, the surface preparation involved grit blasting. In this context, it is shown that the growth of small naturally occurring cracks in cold spray repairs to simulated corrosion damage can be accurately computed using the Hartman-Schijve crack growth equation in a fashion that is consistent with the requirements delineated in USAF Structures Bulletin EZ-SB-19-01, MIL-STD-1530D, and the US Joint Services Structural Guidelines JSSG2006. The relatively large variation in the da/dN versus ΔK curves associated with low values of da/dN highlights the fact that, before any durability assessment of a cold spray repair to an operational airframe is attempted, it is first necessary to perform a sufficient number of tests so that the worst-case small crack growth curve needed to perform the mandated airworthiness certification analysis can be determined.
RESUMEN
The present study examines the high-temperature (500-800 °C) oxidation behavior of Fe-10Cr-(3,5) Al alloys and studies the effect of nanocrystalline structure and Al content on their resistance to oxidation. The nanocrystalline (NC) alloy powder was synthesized via planetary ball milling. The prepared NC alloy powder was consolidated using spark plasma sintering to form NC alloys. Subsequently, an annealing of the NC alloys was performed to transform them into microcrystalline (MC) alloys. It was observed that the NC alloys exhibit superior resistance to oxidation compared to their MC counterparts at high temperatures. The superior resistance to oxidation of the NC alloys is attributed to their considerably finer grain size, which enhances the diffusion of those elements to the metal-oxide interface that forms the protective oxide layer. Conversely, the coarser grain size in MC alloys limits the diffusion of the oxide-forming components. Furthermore, the Fe-10Cr-5Al alloy showed greater resistance to oxidation than the Fe-10Cr-3Al alloy.
RESUMEN
BACKGROUND: The optimal timing of radiotherapy (RT) after radical prostatectomy for prostate cancer has been uncertain. RADICALS-RT compared efficacy and safety of adjuvant RT versus an observation policy with salvage RT for prostate-specific antigen (PSA) failure. PATIENTS AND METHODS: RADICALS-RT was a randomised controlled trial enrolling patients with ≥1 risk factor (pT3/4, Gleason 7-10, positive margins, preoperative PSA≥10 ng/ml) for recurrence after radical prostatectomy. Patients were randomised 1:1 to adjuvant RT ('Adjuvant-RT') or an observation policy with salvage RT for PSA failure ('Salvage-RT') defined as PSA≥0.1 ng/ml or three consecutive rises. Stratification factors were Gleason score, margin status, planned RT schedule (52.5 Gy/20 fractions or 66 Gy/33 fractions) and treatment centre. The primary outcome measure was freedom-from-distant-metastasis (FFDM), designed with 80% power to detect an improvement from 90% with Salvage-RT (control) to 95% at 10 years with Adjuvant-RT. Secondary outcome measures were biochemical progression-free survival, freedom from non-protocol hormone therapy, safety and patient-reported outcomes. Standard survival analysis methods were used; hazard ratio (HR)<1 favours Adjuvant-RT. RESULTS: Between October 2007 and December 2016, 1396 participants from UK, Denmark, Canada and Ireland were randomised: 699 Salvage-RT, 697 Adjuvant-RT. Allocated groups were balanced with a median age of 65 years. Ninety-three percent (649/697) Adjuvant-RT reported RT within 6 months after randomisation; 39% (270/699) Salvage-RT reported RT during follow-up. Median follow-up was 7.8 years. With 80 distant metastasis events, 10-year FFDM was 93% for Adjuvant-RT and 90% for Salvage-RT: HR=0.68 [95% confidence interval (CI) 0.43-1.07, P=0.095]. Of 109 deaths, 17 were due to prostate cancer. Overall survival was not improved (HR=0.980, 95% CI 0.667-1.440, P=0.917). Adjuvant-RT reported worse urinary and faecal incontinence 1 year after randomisation (P=0.001); faecal incontinence remained significant after 10 years (P=0.017). CONCLUSION: Long-term results from RADICALS-RT confirm adjuvant RT after radical prostatectomy increases the risk of urinary and bowel morbidity, but does not meaningfully improve disease control. An observation policy with salvage RT for PSA failure should be the current standard after radical prostatectomy. TRIAL IDENTIFICATION: RADICALS, RADICALS-RT, ISRCTN40814031, NCT00541047.
Asunto(s)
Prostatectomía , Neoplasias de la Próstata , Terapia Recuperativa , Humanos , Masculino , Prostatectomía/métodos , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/patología , Anciano , Terapia Recuperativa/métodos , Persona de Mediana Edad , Radioterapia Adyuvante/efectos adversos , Radioterapia Adyuvante/métodos , Antígeno Prostático Específico/sangre , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/prevención & control , Clasificación del Tumor , Factores de TiempoRESUMEN
Prompted by the unexpected observation of the pitting of the weldments of a highly corrosion- and pitting-resistant duplex stainless steel, SAF2507, in chloride solutions with nitride addition, the pitting and corrosion resistance of SAF2507 and its weldments were investigated in chloride solutions with and without different levels of nitrite. The Incoloy 825 and 316L austenitic stainless steels were included for the purpose of developing a comparative appreciation. The microstructures of the weldments were characterised, and 316L showed a profound influence of nitrite addition in inhibiting pitting, while 'meta-stable' pitting transients that were clearly visible in the chloride solution without nitrite were absent when nitrite was added. Both the parent metal and the weldment of SAF2507 had similar pitting potential (Ep) in 0.1 M NaCl without nitrite, which was the highest Ep among the three alloys tested. Additions of nitrite at low concentrations had an inhibitive effect on pitting, whereas higher nitrite contents had a deleterious effect on pitting resistance. On the other hand, Incoloy 825 showed a trend of Ep ennoblement with an increasing nitrite content of 0.1 M NaCl, and the weldment underwent greater ennoblement. Moreover, 316L showed a trend similar to Incoloy 825; however, the Ep ennoblements were significantly more pronounced for both the weldment and the base metal of 316L.
RESUMEN
Mg and its alloys are promising biodegradable materials for orthopedic implants and cardiovascular stents. The first interactions of protein molecules with Mg alloy surfaces have a substantial impact on their biocompatibility and biodegradation. We investigate the early-stage electrochemical, chemical, morphological, and electrical surface potential changes of alloy WE43 in either 154 mM NaCl or Hanks' simulated physiological solutions in the absence or presence of bovine serum albumin (BSA) protein. WE43 had the lowest electrochemical current noise (ECN) fluctuations, the highest noise resistance (Zn = 1774 Ω·cm2), and the highest total impedance (|Z| = 332 Ω·cm2) when immersed for 30 min in Hanks' solution. The highest ECN, lowest Zn (1430 Ω·cm2), and |Z| (49 Ω·cm2) were observed in the NaCl solution. In the solutions containing BSA, a unique dual-mode biodegradation was observed. Adding BSA to a NaCl solution increased |Z| from 49 to 97 Ω·cm2 and decreased the ECN signal of the alloy, i.e., the BSA inhibited corrosion. On the other hand, the presence of BSA in Hanks' solution increased the rate of biodegradation by decreasing both Zn and |Z| while increasing ECN. Finally, using scanning Kelvin probe force microscopy (SKPFM), we observed an adsorbed nanolayer of BSA with aggregated and fibrillar morphology only in Hanks' solution, where the electrical surface potential was 52 mV lower than that of the Mg oxide layer.
Asunto(s)
Aleaciones , Magnesio , Ensayo de Materiales , Magnesio/química , Aleaciones/química , Cloruro de Sodio , Albúmina Sérica Bovina , Stents , CorrosiónRESUMEN
Recurrent Tuberculosis patients contribute to a significant proportion of TB burden in India. A nationwide survey was conducted during 2019-2021 across India among adults to estimate the prevalence of TB. A total of 322480 individuals were screened and 1402 were having TB. Of this, 381 (27.1%) had recurrent TB. The crude prevalence (95% CI) of recurrent TB was 118 (107-131) per 100,000 population. The median duration between episodes of TB was 24 months. The proportion of drug resistant TB was 11.3% and 3.6% in the recurrent group and new TB patients respectively. Higher prevalence of recurrent TB was observed in elderly, males, malnourished, known diabetics, smokers, and alcohol users. (p<0.001). To prevent TB recurrence, all treated tuberculosis patients must be followed at least for 24 months, with screening for Chest X-ray, liquid culture every 6 months, smoking cessation, alcohol cessation, nutritional interventions and good diabetic management.
Asunto(s)
Mycobacterium tuberculosis , Tuberculosis Pulmonar , Tuberculosis , Adulto , Masculino , Humanos , Anciano , Prevalencia , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/prevención & control , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis/epidemiología , Encuestas y Cuestionarios , India/epidemiologíaRESUMEN
Wire arc additive manufacturing (WAAM) was employed to fabricate 4043 aluminum alloy walls. To investigate the effects of sinusoidal, triangular, and rectangular waveforms of alternating current (AC) and their transients on the wall geometry, microstructure evolution, hardness, and wear properties were evaluated. The root mean square (RMS) current value was maximum for the rectangular and minimum for the triangular waveform. The section produced by the triangular waveform had the highest height-to-width ratio, indicating that this waveform can be a favorable choice for creating components using WAAM. The optical micrographs of the transverse cross-section of the printed sections revealed the grain structure produced with this waveform to be heterogeneous, having a columnar dendritic structure at the bottom and equiaxed at the top portion. The waveforms also had an impact on the hardness and wear characteristics of all the walls, which were attributed to their cooling rate.
RESUMEN
This work reports on the photocatalytic activity of tin oxide (SnO2)-doped magnesium (Mg) and fluorine (F) nanoparticles for methyl orange and safranin dye degradation under sunlight irradiation. Nanocatalysis-induced dye degradation was examined using UV-visible spectroscopy and a pseudo-first-order kinetics model. The results indicate that the prepared nanoparticles exhibit superior photocatalytic activity, and the degradation of methyl orange (MO) dye is approximately 82%. In contrast, the degradation of safranin dye is 96% in the same time interval of 105 min. The calculated crystallite size of the SnO2-Mg-F nanocomposite is 29.5 nm, which respects the particle size found in the DLS analysis with a tetragonal structure and spherical morphology affirmed. The optical characteristics were assessed, and their respective bandgap energies were determined to be 3.6 eV. The influence of F in Mg and SnO2 is recognized with the XRD and FT-IR spectra of the prepared particles.
RESUMEN
This article reports the characterisation of pyrolysis of automotive shredder residue using in situ synchrotron IR, gas-phase IR, and thermal analyses to explore if the automotive shredder residue can be converted into value-added products. When heating to ~600 °C at different heating rates, thermal analyses suggested one- to two-stage pyrolysis. Transformations in the first stage, at lower temperatures, were attributed to the degradation of carbonyl, hydroxyl, or carboxyl functional stabilisers (aldehyde and ether impurities, additives, and stabilisers in the ASR). The second stage transformations, at higher temperatures, were attributed to the thermal degradation of the polymer char. Simultaneous thermal analyses and gas-phase IR spectroscopy confirmed the evolution of the gases (alkanes (CH4), CO2, and moisture). The synchrotron IR data have demonstrated that a high heating rate (such as 150 °C/min) results in an incomplete conversion of ASRs unless sufficient time is provided. The thermogravimetry data fit the linearised multistage kinetic model at different heating rates. The activation energy of reactions varied between 24.98 and 124.94 kJ/mol, indicating a surface-controlled reaction exhibiting high activation energy during the initial stages and a diffusion and mass transfer control showing lower activation energy at the final stages. The corresponding frequency factors were in the range of 3.34 × 1013-5.68 × 101 mg-1/min for different pyrolysis stages. The evolution of the functional groups decreased with an increase in the heating rate.
RESUMEN
Bipolar plates, a critical component of proton exchange membrane fuel cell (PEMFC), are constructed out of alloys of Ti, Pt, Cr, or graphitic materials that have limitations. Electrical conductivity, cost, and corrosion resistance are among the critical considerations for bi-polar plate material. Graphene, which possesses impressive conductivity and toughness, is an attractive option as coating on metallic substrates of PEMFC bipolar plates. This study investigates corrosion resistance and its durability due to graphene developed by chemical vapor deposition on a pure Ni-Cu alloy and a commercial Ni-Cu alloy in 0.5 m H2 SO4 environment, with a view to exploring use of graphene coated Ni-Cu alloys for the construction of PEMFC bipolar plates. The graphene coating on the pure alloy shows remarkably superior corrosion resistance than the commercial alloy that is attributed to the former's ability to develop considerably defect-free graphene.
RESUMEN
Alloys of magnesium, zinc or iron that do not contain toxic elements are attractive as construction material for biodegradable implants, i.e., the type of implants that harmlessly dissolve away within the human body after they have completed their intended task. The synergistic influence of mechanical stress and corrosive human body fluid can cause sudden and catastrophic fracture of bioimplants due to phenomena such as stress corrosion cracking (SCC) and corrosion fatigue (CF). To date, SCC and CF of implants based on Zn have scarcely been investigated. This article is an overview of the challenges, research needs and way forward in understanding human body-fluid-assisted fractures (i.e., SCC and CF) of Zn alloys in human body fluid.
RESUMEN
In this study, silver-functionalized bismuth oxide (AgBi2O3) nanoparticles (SBO NPs) were successfully synthesized by a highly efficient hydrothermal method. The as-synthesized SBO nanoparticles were characterized using FT-IR, P-XRD, XPS, HR-SEM, and HR-TEM analytical methods. It was found that the NPs were in spherical shape and hexagonal crystal phase. The newly prepared SBO electrode was further utilized for the detection of glucose, NO2- and H2O2 by cyclic voltammetry (CV) and amperometric methods. The electrodes exhibited high sensitivity (2.153 µA mM-1 cm-2 for glucose, 22 µA mM-1 cm-2 for NO2- and 1.72 µA mM-1 cm-2 for H2O2), low LOD (0.87 µM for glucose, 2.8 µM for NO2- and 1.15 µM for H2O2) and quick response time (3 s for glucose, 2 s for both NO2- and H2O2 respectively). The sensor exhibited outstanding selectivity despite the presence of various interferences. The developed sensor exhibited good repeatability, reproducibility, and stability. In addition, the sensor was used to measure glucose, H2O2 in human serum, and NO2- in milk and river water samples, demonstrating its potential for use in the real sample.
RESUMEN
Magnesium (Mg) alloys are a very attractive material of construction for biodegradable temporary implants. However, Mg alloys suffer unacceptably rapid corrosion rates in aqueous environments, including physiological fluid, that may cause premature mechanical failure of the implant. This necessitates a biodegradable surface barrier coating that should delay the corrosion of the implant until the fractured/damaged bone has healed. This review takes a brief account of the merits and demerits of various existing coating methodologies for the mitigation of Mg alloy corrosion. Since among the different coating approaches investigated, no single coating recipe seems to address the degradation control and functionality entirely, this review argues the need for polymer-based and biodegradable composite coatings.