Effects of atmospheric environmental conditions on fatigue crack growth rates

Corrosion has a significant impact on the fatigue of aging aircraft. In service, an airframe will be exposed not only to a spectrum of mechanical loading due to variations in flight profile and mission types, but also to a spectrum of environmental conditions. The detrimental influence of chlorides on fatigue performance for metallic materials has been well-documented in mechanical tests typically performed in an aqueous solution. In studying aircraft alloys, however, the environmental influence is that of a multifarious non-stationary gaseous atmosphere, making an aqueous exposure a poor predictor of in-service corrosion phenomena. Temperature, humidity, atmospheric gas composition, salt concentration, pollution, and UV light exposure all vary as a complex function of geographical location, seasonal weather patterns, diurnal cycle, and flight mission profiles. Research in accelerated corrosion testing has resulted in noteworthy advances in understanding the kinetics of atmospheric corrosion. Current test methodologies, such as the salt fog described in ASTM B117, often correlate poorly with field exposure. The addition of ozone, UV light, and control of relative humidity was shown to create corrosion in highly pure Ag samples similar to outdoor exposures due to the formation of reactive oxidizing species. AA 5083 and carbon steel samples demonstrated similar discrepancies between lab simulated and actual field exposures that were mitigated in lab testing with the addition of ozone and UV light. Chlorides in conjunction with strong oxidizers like ozone react to create species that attack the substrate material. Furthermore, the aerosols that deposit chlorides on field exposure samples can vary in size, composition and acidity. These variations have proven in recent experiments to influence corrosion morphologies and rates. When considering environmental influences on fatigue crack growth rates (FCGR), investigations have focused on a more limited set of parameters. The effects of water vapor on FCGR have been examined in tests under vacuum, partial vacuum, dry inert gas, lab air, and at climatic low temperatures by numerous investigators. At low temperatures, air has little capacity to hold water. Indeed, experiments with AA 2024-T3 and AA 7075-T6 at -75°C demonstrated FCGR much lower than that at room temperature. Similar results were obtained with AA 2024-T351 and AA 7475-T7651 at room temperature and at -54°C though the FCGR difference was clearly sensitive to stress ratio, R, and stress intensity factor range, ΔK. Further evidence for the role of water vapor was demonstrated by research exhibiting decreasing FCGR with decreasing relative humidity and tests exhibiting the same behavior with decreasing water vapor pressure, both with AA 7075-T651. Since systems to apply and control multiple environmental parameters in conjunction with mechanical loading are not readily available, such a system has been developed to apply and control relative humidity (2% to 100%), specimen temperature (-57°C to 121°C), ozone (30 ppb to 50 ppm), salt spray (NaCl, CaCO3, NaHCO3), background gas (CO2 and N2) and UV light. The chamber is designed to fit 245 kN and some larger servo-hydraulic test frames. The current test program is designed to elucidate the effects of the individual environmental parameters before moving onto combinations of parameters to enable a better understanding of the underlying mechanisms. Baseline FCGR tests are underway on center-cracked AA 7075-T651 specimens at a range of R values between -1 and 0.9. Constant amplitude sine wave decreasing ΔK, increasing ΔK tests are used to generate full FCGR curves to characterize behavior from threshold to stable tearing, but constant K-gradient test control will be investigated as a means of accelerating testing efforts. Tests at various ozone levels and chloride loading levels are to follow. The effects of ozone levels at 1-3 orders of magnitude higher (0.5 – 50 ppm) than typical ground level ozone values will be examined to determine at what combinations of ozone concentration and testing frequency an effect can be seen. Salt loading will focus primarily on the effects of relative humidity variations near the deliquescence point. There is some evidence to suggest that FCGR may decrease at relative humidity levels above the deliquescence point presumably due to significant corrosion products influencing crack closure. These effects will be of significant interest. Testing will eventually transition into the simultaneous application of a spectrum of environmental conditions with a mechanical loading spectrum. The resulting test data will ultimately be used to improve fatigue life prediction models that typically rely upon laboratory air FCGR data

Comparing clinical outcomes of piperacillin-tazobactam administration and dosage strategies in critically ill adult patients : a systematic review and meta-analysis

Abstract Background: Recently, continuous administration of piperacillin-tazobactam has been proposed as a valuable alternative to traditional intermittent administration especially in critically ill patients. However, antibiotic dosing remains a challenge for clinicians as antibiotic dosing regimens are usually determined in non-critically-ill hospitalized adult patients. The aim was to conduct a systematic review to identify and highlight studies comparing clinical outcomes of piperacillin tazobactam dosing regimens, continuous/prolonged infusion vs intermittent infusion in critically ill patients. Meta-analyses were performed to assess the overall effect of dosing regimen on clinical efficacy. Methods: Studies were identified systematically through searches of PubMed and Science Direct, in compliance with PRISMA guidelines. Following the systematic literature review, meta-analyses were performed using Review Manager. Results: Twenty-three studies were included in the analysis involving 3828 critically ill adult participants in total (continuous/prolonged infusion = 2197 and intermittent infusion = 1631) from geographically diverse regions. Continuous/prolonged resulted in significantly: higher clinical cure rates (OR 1.56, 95% C.I 1.28-1.90, P = 0 .0001), lower mortality rates (OR 0.68, 95% C.I 0.55-0.84, P = 0 .0003), higher microbiological success rates (OR 1.52, 95% C.I 1.10-2.11, P = 0.01) and decreasing the length of hospital stay (OR -1.27, 95% C.I -2.45—0.08, P = 0.04) in critically ill patients. Conclusion: There is a significant level of evidence that clinical outcome in critically ill patients is improved in patients receiving piperacillin-tazobactam via continuous/prolonged infusion. Therefore, this alternative infusion strategy could be recommended in clinical practice

Comparing clinical outcomes of piperacillin-tazobactam administration and dosage strategies in critically ill adult patients : a systematic review and meta-analysis

Abstract: Background: Recently, continuous administration of piperacillin-tazobactam has been proposed as a valuable alternative to traditional intermittent administration especially in critically ill patients. However, antibiotic dosing remains a challenge for clinicians as antibiotic dosing regimens are usually determined in non-critically ill hospitalized adult patients. The aim was to conduct a systematic review to identify and highlight studies comparing clinical outcomes of piperacillin tazobactam dosing regimens, continuous/prolonged infusion vs intermittent infusion in critically ill patients. Meta-analyses were performed to assess the overall effect of dosing regimen on clinical efficacy. Methods: Studies were identified systematically through searches of PubMed and Science Direct, in compliance with PRISMA guidelines. Following the systematic literature review, meta-analyses were performed using Review Manager. Results: Twenty-three studies were included in the analysis involving 3828 critically ill adult participants in total (continuous/prolonged infusion = 2197 and intermittent infusion = 1631) from geographically diverse regions. Continuous/prolonged resulted in significantly: higher clinical cure rates (Odds Ratio 1.56, 95% Confidence Interval 1.28–1.90, P = 0 .0001), lower mortality rates (Odds Ratio 0.68, 95% Confidence Interval 0.55–0.84, P = 0 .0003), higher microbiological success rates (Odds Ratio 1.52, 95% Confidence Interval 1.10–2.11, P = 0.01) and decreasing the length of hospital stay (Mean Difference − 1.27, 95% Confidence Interval − 2.45—0.08, P = 0.04) in critically ill patients. Conclusion: Results from this study show that there is a significant level of evidence that clinical outcome in critically ill patients is improved in patients receiving piperacillin-tazobactam via continuous/prolonged infusion. However, more rigorous scientific studies in critically ill patients are warranted to reach a sufficient level of evidence and promote further implementation of C/PI as a dosing strategy

Optimising antibiotic therapy for inpatient and outpatient settings

Background: Not only have antibiotics saved countless patients’ lives but they have also played a crucial role in supporting major advances in modern medicine. However, precipitously emerging resistant bacterial strains jeopardise the remarkable advances achieved with antibiotics. In the past, the development of new antibiotics was an effective strategy to combat resistant bacteria. However, with the discovery of new antibiotics diminishing, optimising the administration of currently available antibiotics has become a necessity. A strategy of particular interest involves applying pharmacokinetic and pharmacodynamic concepts to optimise time-dependant antibiotics dosing regimens. The latter is a growing area of interest for reducing the development of antibiotic resistance, and it involves differential dosing regimens such as prolonged or continuous infusions of beta-lactam antibiotics. Aim: The overarching aim of this research is to optimise antibiotic therapy for inpatient and outpatient use. This thesis consists of literature-based, practice-based, and laboratory-based research. Literature-based: The aim of the literature-based research category was to review existing literature to compare the clinical outcomes of continuous vs intermittent infusion beta-lactam antibiotics and appraise the strengths and the weaknesses of current evidence. Overall, literature-based research demonstrated a wealth of studies in terms of systematic reviews, meta-analysis as well as primary studies. Despite the literature exhibiting favourable outcomes towards prolonged/continuous infusions, the literature review and systematic reviews conducted support the need for better conducted, definitive trials and systematic reviews given the variability in scope of the available studies. Practice-based: The aim of the practice-based research category was to provide a snapshot of beta-lactam antibiotic use in clinical practice. The first study was single-centre retrospective cohort practice review conducted to Investigate the prescribing patterns of beta-lactam antibiotics in critical care wards. The second study was a cross sectional survey investigating nurse’s knowledge, perceptions, and experiences regarding differential antibiotic dosing. Findings show that prolonged/continuous infusions as dosing strategies are implemented in practice to improve patient outcomes, however, healthcare XI professionals implementing this practice have not received sufficient training to support the administration of differential antibiotic dosing. This was evident from both practice based studies that disclose beta-lactam antibiotics are not used to their full potential or are inaccurately used. There is a need for tailored education and training to improve health care professional’s knowledge of prolonged/continuous infusions. Laboratory-based: Despite the advantages that prolonged/continuous infusions beta-lactam antibiotics offer, in order to use these dosing regimens efficiently, infusion solutions should remain stable for the preparation, storage and infusion time. Concerns regarding stability present a challenge in practice as most stability information is based on administration via bolus injection or an intermittent infusion. Therefore, the aim of the laboratory-based research category was to determine the feasibility of prolonged/continuous infusion beta-lactam antibiotics for hospital and outpatient settings. Findings from the conducted studies aid in ameliorating current dosing regimens to optimise antibiotic efficacy. Results obtained from stability studies assist in resolving challenges experienced in practice in terms of preparation, storage, and administration as they indicate the effects of temperature, diluent, and pre-preparation of infusion solutions. Studies demonstrated that stability data generated in all studies are an improvement to the stability data presented in the British, American, and European pharmacopoeias. Conclusion: Findings of this PhD research are supportive of the beneficial role of differential antibiotic dosing. Overall, the gathered data indicate that prolonged/continuous infusions are feasible, advantageous and could potentially improve patient clinical outcomes

Examination of Factors Influencing FCG in legacy aluminum alloys

In work sponsored by the Office of Naval Research a corrosion fatigue test method to better replicate real world corrosion conditions using salt film, relative humidity, ozone and UV-light, is being developed [1]. This method is being used to evaluate the effect of atmospheric corrosion conditions in AA7075-T651 with inhibitive coatings including epoxy chromate and three chromate replacement coatings (water and epoxy based rare earth primers and an aluminum rich primer). The corrosion fatigue results are being paired with leaching studies under traditional immersion and atmospheric conditions on the primers to determine how the leaching rates relate to the ability of a primer to inhibit fatigue damage. Research shows that chromate in concentrations related to leaching rates can slow fatigue crack growth in aluminum alloys in stress ranges relevant to airframe maintainers [2,3]. The fatigue tests showing inhibition with low levels of chromate (0.05 mM) were completed with chromate added to a full immersion sodium chloride solution. It remains unclear if epoxy chromate based and other polymeric inhibitor coatings can affect corrosion fatigue under atmospheric corrosion conditions. The protection provided by corrosion inhibitors undergoing fatigue can be affected by loading conditions (∆K, frequency) and also likely by the environment due to changes in coating leaching. An improved understanding of how environmental and loading parameters influence a coating’s ability to offer protection against corrosion fatigue damage would greatly help the coating community to design more robust coating protection systems. Another focus area of the ONR sponsored research is in quantifying the corrosion damage to fatigue crack transition. A standardized specimen and testing protocol to evaluate the relative influence of material, environment, inhibitors, loading spectrum and other inputs on the pit-to-crack transition was developed [2,3]. The methodology uses a narrow plate specimen with a centrally located hole with a preferential pit (diameter approximately 150 µm) placed at the corner of the hole; current work is being completed on legacy aluminum alloy AA7075-T651. The plate thickness and hole diameter are consistent with commercial and military airframe applications. The method uses direct current potential drop (DCPD) to measure the crack length. In the current research the test methodology is being transitioned to evaluate galvanic interactions when a fastener of either stainless steel or titanium in placed in the hole. The fastener contact geometry is limited to two boundary conditions either the hole bore and starting pit are bare or only the starting pit is left unprotected. The fastener shank is left unprotected as well. The galvanic potential between the aluminum and the fastener is measured and then used to control the corrosion potential during the corrosion fatigue testing. This method allows for bench top electrochemical tests to be used to control the mechanical testing and also removes the time effect for galvanic corrosion to begin. The overarching objective of the research is to improve and transition the results on the effect of environmentally assisted fatigue in high performance metallic alloys (crack growth rate data) to the DoD research and depot maintenance activities by integrating all data into the AFGROW fatigue crack prediction software allowing for the inclusion of corrosion damage and environment effects on fatigue crack life predictions. Likewise better methods for coating and material evaluation are being produced. 1 D. Laing, et al., “Effects of Sodium Chloride Particles, Ozone, UV and Relative Humidity on Atmospheric Corrosion of Silver,” Journal of the Electrochemical Society, 2012, 157 (4) pp. C146‑C156. 2 S.E. Galyon Dorman, J.W. Rausch and S.R. Arunachalam, “Examination and Prediction of Corrosion Fatigue Damage and Inhibition,” Corrosion Reviews, ISSN (Online) 2191-0316, ISSN (Print) 0334-6005, DOI: https://doi.org/10.1515/corrrev-2017-0057. S.E. Galyon Dorman, et al, (2016) Managing Environmental Impacts of Time-Cycle Dependent Structural Integrity of High Performance DoD Alloys, SAFE Inc., SAFE-RTP-16-045

Stability of meropenem after reconstitution for administration by prolonged infusion

Objective: Meropenem is a parenteral carbapenem antibiotic which has a broad spectrum of activity against aerobes and anaerobes. Meropenem’s bactericidal activity is determined by the time during which meropenem concentration remains above the minimal inhibition concentration (MIC) during the dosing interval. Thus, prolonged infusion is the optimal way to maximize the time-dependant activity. However, studies to date have shown that carbapenems and in particular, meropenem, are relatively unstable in solution. The aims of this study were therefore (1) to establish the effects of temperature on the concentration of a generic brand reconstituted meropenem solution and (2) to determine whether 24-hour continuous infusion is possible without concentrations dropping below the recommended 90%. Method: Preliminary examination was carried out by the means of nuclear magnetic resonance (NMR) spectroscopy. Meropenem was subsequently assayed using high-performance liquid chromatography (HPLC). The method was developed and validated in compliance with International Council for Harmonisation (ICH) guidelines. Meropenem’s stability was examined at two temperatures 22°C and 33°C to mimic average and high temperature in hospital wards. Solutions were prepared aseptically at the clinically relevant concentration. Results: NMR results obtained showed an increase in open ring methyl groups peak intensity, indicating that meropenem begins to degrade upon dissolution (d=1.05 and 1.25). Results obtained from quantitative HPLC confirm that meropenem concentrations dropped to 90% of initial concentration at 7.4 hours and 5.7 hours at 22°C and 33°C, respectively. Conclusion: Although results obtained indicate that meropenem should not be continuously infused over 24 hours, it is possible that meropenem could be continuously infused for at least 7 hours if temperature does not exceed 22°C and for 5 hours if temperature does not exceed 33°C

Examination and prediction of corrosion fatigue damage and inhibition

The United States Department of Defense (DoD) estimated that the annual cost of corrosion, the unintended material degradation due to the environment, to weapon systems and infrastructure in 2010 exceeded $21 billion, and that the number was likely to continue to rise. Unfortunately, as the warfighters demand more from their systems, corrosion prevention and control is frequently traded during the acquisition cycle for weapon system performance. As a result, the DoD remains entrenched in a find-and-fix corrosion management philosophy which is expensive and unsustainable. Better standardized fatigue laboratory procedures are need to help the DoD develop (1) a fundamental understanding of corrosion damage, (2) material performance data relevant to corrosion damage, (3) prediction methodologies to help mitigate the effects of corrosion nucleated fatigue damage and (4) to develop an understanding of how corrosion preventative coatings can slow fatigue crack propagation. All of these research area lead to developing better damage prediction methods which can account for the effect of environment on fatigue crack propagation. Aircraft structural tear-down analysis provides substantial evidence of the importance of corrosion in nucleating fatigue cracks, as such the ability to protect against such damage would be of great benefit to the DoD. While chromate and other inhibitors have been shown to slow fatigue crack growth rates when added to a bulk solution of a fully immersed sample, research has not been completed showing how these inhibitors effect crack nucleation from corrosion damage. In research funded by the Office of Naval Research (ONR) and the Office of the Secretary of Defense’s Office of Corrosion Policy and Oversight (OSD-CPO) work is being completed to develop a better understanding how to better predict and prevent environmental effects on fatigue crack propagation. While chromate has been used successfully for many years on United States Air Force (USAF) and Navy (USN) aircraft to prevent corrosion damage, the environmental and personnel risks associated with chromate have caused the DoD to pursue non-chromate containing corrosion prevention systems. To fully quantify chromate replacement coatings an understanding of the effects that chromate has on corrosion fatigue must be fully documented and understood. Some researchers have shown that high levels of inhibitors (chromate; molybdate) added to full immersion corrosion fatigue tests on aluminum alloys slow the fatigue crack growth rate substantially. The limitation of this research was that the amount of inhibitor present in the environment was not related to leach rates of chromate from polymeric coatings. For these inhibitors to slow fatigue crack propagation the inhibitors must become mobile from the polymer coating matrix. Based on this mechanism of corrosion inhibitor release, the examination of atmospheric corrosion fatigue, hydrated salt layers which better represent operating environments compared to full immersion testing, becomes important to help quantify how inhibitors affect fatigue damage in service. Another focus area of the ONR funded research is in quantifying the corrosion damage to fatigue crack transition. A standardized specimen and testing protocol to evaluate the relative influence of material, environment, inhibitors, and loading spectrum on the pit-to-crack transition was developed. The methodology uses a narrow plate specimen with a centrally located hole with a preferential pit (diameter approximately 150 µm) placed at the corner of the hole; current work is being completed on legacy aluminum alloy AA7075-T651. The plate thickness and hole diameter are consistent with commercial and military airframe applications. Current DoD engineering approaches to manage corrosion-fatigue, are incomplete in terms of the effect of service environment. Poor component life prediction results in an increased flight line inspection and maintenance burden along with premature component retirement. The overarching objective of the research is to improve and transition the results on the effect of environmentally assisted fatigue in high performance metallic alloys (crack growth rate data) to the DoD research and depot maintenance activities by integrating all data into the AFGROW fracture toughness and fatigue crack prediction software allowing for the inclusion of corrosion damage and environment effects on fatigue crack life predictions

Acceptance of Flu Vaccine among Parents of Diabetic Children in Jordan

Abstract: There is a critical need to understand vaccine decision-making in high-risk groups. This study explored flu vaccine acceptance among Jordanian parents of diabetic children. Employing a cross-sectional approach, 405 parents from multiple healthcare centers across Jordan were recruited through stratified sampling, ensuring a broad representation of socioeconomic backgrounds. A structured questionnaire, distributed both in-person and online, evaluated their knowledge, attitudes, and acceptance of the flu vaccine for their diabetic children. The results indicated that only 6.4% of the study sample reported vaccinating their children against the flu annually, and only 23% are planning to vaccinate their children this year. A multinomial logistic regression analysis revealed notable variability in responses. Specifically, parents with a positive attitude towards the flu vaccine and those with older children had less odds to reject the vaccine (OR = 0.589, 95% CI (0.518–0.670), p &lt; 0.001 and OR = 0.846, 95% CI (0.736–0.974), p = 0.02, respectively). Conversely, prevalent misconceptions regarding vaccine safety and efficacy emerged as significant barriers to acceptance.Our findings advocate for targeted educational programs that directly address and debunk these specific misconceptions. Additionally, strengthened healthcare communication to provide clear, consistent information about the flu vaccine’s safety and benefits is vital to help enhance vaccine uptake among this vulnerable population, emphasizing the need to address specific concerns and misinformation directly.</div