Dose equivalence for metaraminol and noradrenaline - A retrospective analysis.

BACKGROUND: Noradrenaline and metaraminol are commonly used vasopressors in critically ill patients. However, little is known of their dose equivalence. METHODS: We conducted a single centre retrospective cohort study of all ICU patients who transitioned from metaraminol to noradrenaline infusions between August 26, 2016 and December 31, 2020. Patients receiving additional vasoactive drug infusion were excluded. Dose equivalence was calculated based on the last hour metaraminol dose (in µg/min) and the first hour noradrenaline dose (in µg/min) with the closest matched mean arterial pressure (MAP). Sensitivity analyses were performed on patients with acute kidney injury (AKI), sepsis and mechanical ventilation. RESULTS: We studied 195 patients. The median conversion ratio of metaraminol to noradrenaline was 12.5:1 (IQR 7.5-20.0) for the overall cohort. However, the coefficient of variation was 77% and standard deviation was 11.8. Conversion ratios were unaffected by sepsis or mechanical ventilation but increased (14:1) with AKI. One in five patients had a MAP decrease of >10 mmHg during the transition period from metaraminol to noradrenaline. Post-transition noradrenaline dose (p < 0.001) and AKI (p = 0.045) were independently associated with metaraminol dose. The proportion of variation in noradrenaline dose predicted from metaraminol dose was low (R2 = 0.545). CONCLUSIONS: The median dose equivalence for metaraminol and noradrenaline in this study was 12.5:1. However, there was significant variance in dose equivalence, only half the proportion of variation in noradrenaline infusion dose was predicted by metaraminol dose, and conversion-associated hypotension was common.

The effect of age on clinical dose equivalency of fentanyl and morphine analgosedation in mechanically ventilated patients: Findings from the ANALGESIC trial.

BACKGROUND: The dose equivalency of fentanyl vs. morphine is widely considered to be approximately 1:100. However, little is known about the effect of age on this ratio when these agents are used as infusions for analgosedation. OBJECTIVES: To assess the impact of age on the clinical dose equivalency of fentanyl and morphine when used as infusions for analgosedation in mechanically ventilated intensive care unit patients. METHODS: We performed a post hoc analysis of the Assessment of Opioid Administration to Lead to Analgesic Effects and Sedation in Intensive Care (ANALGESIC) cluster randomised crossover trial of fentanyl and morphine infusions for analgosedation. Dose and analgosedative clinical equivalency of fentanyl and morphine were assessed by age and by using different body-size descriptors. RESULTS: We studied 663 patients (338 fentanyl, 325 morphine). Median (interquartile range) hourly dose of fentanyl and morphine were 58.1 (40.0-89.2) mcg and 3400 (2200-5000) mcg, respectively. The ratio of total dose of fentanyl:morphine was 1:93 in the 18- to 29-year-old group and 1:25 in the ≥80-year-old group (p = 0.015), respectively, with fentanyl becoming relatively less clinically effective as age increased. This effect was also seen when comparing dosing by different body-size descriptors with the strongest age-related change when using body surface area as body-size descriptor (p = 0.009). CONCLUSION: The analgosedative clinical dose equivalency of fentanyl vs. morphine is heterogeneous when used as infusions for analgosedation, with fentanyl becoming relatively less clinically effective as age increases. This information can help guide prescription of these agents during transition from one agent to the other in critically ill patients.

Natural language processing diagnosed behavioural disturbance phenotypes in the intensive care unit: characteristics, prevalence, trajectory, treatment, and outcomes.

BACKGROUND: Natural language processing (NLP) may help evaluate the characteristics, prevalence, trajectory, treatment, and outcomes of behavioural disturbance phenotypes in critically ill patients. METHODS: We obtained electronic clinical notes, demographic information, outcomes, and treatment data from three medical-surgical ICUs. Using NLP, we screened for behavioural disturbance phenotypes based on words suggestive of an agitated state, a non-agitated state, or a combination of both. RESULTS: We studied 2931 patients. Of these, 225 (7.7%) were NLP-Dx-BD positive for the agitated phenotype, 544 (18.6%) for the non-agitated phenotype and 667 (22.7%) for the combined phenotype. Patients with these phenotypes carried multiple clinical baseline differences. On time-dependent multivariable analysis to compensate for immortal time bias and after adjustment for key outcome predictors, agitated phenotype patients were more likely to receive antipsychotic medications (odds ratio [OR] 1.84, 1.35-2.51, p < 0.001) compared to non-agitated phenotype patients but not compared to combined phenotype patients (OR 1.27, 0.86-1.89, p = 0.229). Moreover, agitated phenotype patients were more likely to die than other phenotypes patients (OR 1.57, 1.10-2.25, p = 0.012 vs non-agitated phenotype; OR 4.61, 2.14-9.90, p < 0.001 vs. combined phenotype). This association was strongest in patients receiving mechanical ventilation when compared with the combined phenotype (OR 7.03, 2.07-23.79, p = 0.002). A similar increased risk was also seen for patients with the non-agitated phenotype compared with the combined phenotype (OR 6.10, 1.80-20.64, p = 0.004). CONCLUSIONS: NLP-Dx-BD screening enabled identification of three behavioural disturbance phenotypes with different characteristics, prevalence, trajectory, treatment, and outcome. Such phenotype identification appears relevant to prognostication and trial design.

Insulin therapy associated relative hypoglycemia during critical illness.

PURPOSE: In critically ill diabetes patients, relative hypoglycemia (RH) (a decrease in glucose ≥30% below pre-admission levels, as estimated by HbA1c) is associated with greater mortality and absolute hypoglycemia. We investigated the epidemiology and outcomes of RH when it was associated with insulin therapy. METHODS: We performed retrospective analysis of a cohort of critically ill patients with diabetes who received insulin in the intensive care units (ICUs) of a tertiary hospital. The primary outcome was 28-day mortality with respect to insulin therapy associated relative hypoglycemia (ITARH). RESULTS: ITARH occurred in 184 (42%) of insulin-treated patients. ITARH was associated with a higher HbA1c (8.6% vs 6.6%, p < 0.001), a higher glycemic variability index (121 vs 75.1 mmol2/L2/h/week, p < 0.001) and more absolute hypoglycemia (18.5% vs 3.94%, p < 0.001). Its frequency peaked about 5 h after initiation of insulin therapy. ITARH was associated with a greater risk of subsequent hypoglycemia (adjusted HR 3.5, 95% CI 1.7-6.8) but not mortality (HR 1.2, 95% CI 0.7-2.2). CONCLUSIONS: ITARH is common in insulin treated critically ill diabetes patients and associated with poorer glycemic control. Unlike reports of RH in general, it is not associated with mortality, suggesting that the prognostic implications of RH differ according to its context.

Natural language processing diagnosed behavioral disturbance vs confusion assessment method for the intensive care unit: prevalence, patient characteristics, overlap, and association with treatment and outcome.

PURPOSE: To compare the prevalence, characteristics, drug treatment for delirium, and outcomes of patients with Natural Language Processing (NLP) diagnosed behavioral disturbance (NLP-Dx-BD) vs Confusion Assessment Method for intensive care unit (CAM-ICU) positivity. METHODS: In three combined medical-surgical ICUs, we obtained data on demographics, treatment with antipsychotic medications, and outcomes. We applied NLP to caregiver progress notes to diagnose behavioral disturbance and analyzed simultaneous CAM-ICU. RESULTS: We assessed 2313 patients with a median lowest Richmond Agitation-Sedation Scale (RASS) score of - 2 (- 4.0 to - 1.0) and median highest RASS score of 1 (0 to 1). Overall, 1246 (53.9%) patients were NLP-Dx-BD positive (NLP-Dx-BDpos) and 578 (25%) were CAM-ICU positive (CAM-ICUpos). Among NLP-Dx-BDpos patients, 539 (43.3%) were also CAM-ICUpos. In contrast, among CAM-ICUpos patients, 539 (93.3%) were also NLP-Dx-BDpos. The use of antipsychotic medications was highest in patients in the CAM-ICUpos and NLP-Dx-BDpos group (24.3%) followed by the CAM-ICUneg and NLP-Dx-BDpos group (10.5%). In NLP-Dx-BDneg patients, antipsychotic medication use was lower at 5.1% for CAM-ICUpos and NLP-Dx-BDneg patients and 2.3% for CAM-ICUneg and NLP-Dx-BDneg patients (overall P < 0.001). Regardless of CAM-ICU status, after adjustment and on time-dependent Cox modelling, NLP-Dx-BD was associated with greater antipsychotic medication use. Finally, regardless of CAM-ICU status, NLP-Dx-BDpos patients had longer duration of ICU and hospital stay and greater hospital mortality (all P < 0.001). CONCLUSION: More patients were NLP-Dx-BD positive than CAM-ICU positive. NLP-Dx-BD and CAM-ICU assessment describe partly overlapping populations. However, NLP-Dx-BD identifies more patients likely to receive antipsychotic medications. In the absence of NLP-Dx-BD, treatment with antipsychotic medications is rare.

An Exploratory Analysis of the Association between Hypercapnia and Hospital Mortality in Critically Ill Patients with Sepsis.

Rationale: Hypercapnia may affect the outcome of sepsis. Very few clinical studies conducted in noncritically ill patients have investigated the effects of hypercapnia and hypercapnic acidemia in the context of sepsis. The effect of hypercapnia in critically ill patients with sepsis remains inadequately studied. Objectives: To investigate the association of hypercapnia with hospital mortality in critically ill patients with sepsis. Methods: This is a retrospective study conducted in three tertiary public hospitals. Critically ill patients with sepsis from three intensive care units between January 2011 and May 2019 were included. Five cohorts (exposure of at least 24, 48, 72, 120, and 168 hours) were created to account for immortal time bias and informative censoring. The association between hypercapnia exposure and hospital mortality was assessed with multivariable models. Subgroup analyses compared ventilated versus nonventilated and pulmonary versus nonpulmonary sepsis patients. Results: We analyzed 84,819 arterial carbon dioxide pressure measurements in 3,153 patients (57.6% male; median age was 62.5 years). After adjustment for key confounders, both in mechanically ventilated and nonventilated patients and in patients with pulmonary or nonpulmonary sepsis, there was no independent association of hypercapnia with hospital mortality. In contrast, in ventilated patients, the presence of prolonged exposure to both hypercapnia and acidemia was associated with increased mortality (highest odds ratio of 16.5 for ⩾120 hours of potential exposure; P = 0.007). Conclusions: After adjustment, isolated hypercapnia was not associated with increased mortality in patients with sepsis, whereas prolonged hypercapnic acidemia was associated with increased risk of mortality. These hypothesis-generating observations suggest that as hypercapnia is not an independent risk factor for mortality, trials of permissive hypercapnia avoiding or minimizing acidemia in sepsis may be safe.

A Phase II Cluster-Crossover Randomized Trial of Fentanyl versus Morphine for Analgosedation in Mechanically Ventilated Patients.

Rationale: The continuous infusion of fentanyl or morphine is often prescribed to assist with analgesia and sedation (analgosedation) during mechanical ventilation. Objectives: To compare the effect of fentanyl versus morphine on patient-centered outcomes in ventilated patients. Methods: We conducted a cluster-randomized, cluster-crossover trial between July 2019 and August 2020 in two adult ICUs. We compared two continuous infusion regimens (fentanyl versus morphine). One ICU was randomized to the fentanyl-morphine sequence and the other to the morphine-fentanyl sequence. The primary outcome was the number of ventilator-free days at Day 28. Secondary outcomes included, among others, duration of mechanical ventilation in survivors and ICU-free days at Day 28. Measurements and Main Results: Via cluster allocation, we randomized 737 patients. Of these, 56 were excluded because of the opt-out consent process, leaving 681 (344 to fentanyl and 337 to morphine) for primary analysis (median [interquartile range] age, 59 [44-69] years). Median ventilator-free days at Day 28 were 26.1 (20.7-27.3) in the fentanyl versus 25.3 (19.1-27.2) in the morphine group (median difference, 0.79 [95% confidence interval, 0.31 to 1.28], P = 0.001). ICU-free days were greater (P < 0.001) and length of stay in the ICU for survivors shorter (P < 0.001) in the fentanyl group. All other secondary outcomes were not statistically different by treatment group. Conclusions: Among adult patients requiring mechanical ventilation, compared with morphine, fentanyl infusion significantly increased the median number of ventilator-free days at Day 28. The choice of opioid infusion agent may affect clinical outcomes and requires further investigation.

Growth Mechanisms of Nano-to Micro-Sized Lead Sulfate Particles.

PbSO4 is a key component in the charging and discharging of lead acid batteries-such as the cycling of automotive batteries. PbSO4 is a poor conductor that forms on the positive and negative electrodes during discharging and dissolves during charging of a lead acid battery. Over time, buildup of PbSO4 occurs on the electrodes, ultimately reducing the efficiency of the battery. This study aims to determine the nucleation and growth mechanisms of PbSO4 nanoparticles in various solutions to potentially reduce or control the buildup of PbSO4 on battery electrodes over time. The time dependency of particle morphology was observed using various reaction conditions. PbSO4 particles were created using premixed solutions at various times of reaction. H2O, acetone, methanol, ethanol, and isopropanol were used to stop the reaction and development of the PbSO4 particles. The structure of the nanoparticles was characterized via transmission electron microscopy, high-angle annular dark field scanning transmission electron microscopy, and selected area electron diffraction. This study provides insight into the mechanism by which PbSO4 nanoparticles form in various solutions and reveals that the degree of complexity of the solution plays a large role in the nucleation and growth of the PbSO4 nanoparticles. This insight can provide avenues to reduce unwanted buildup of PbSO4 on battery electrodes over time, which can extend battery life and performance.

Designing Better Cardiovascular Stent Materials - A Learning Curve.

Cardiovascular stents are life-saving devices and one of the top 10 medical breakthroughs of the 21st century. Decades of research and clinical trials have taught us about the effects of material (metal or polymer), design (geometry, strut thickness, and the number of connectors), and drug-elution on vasculature mechanics, hemocompatibility, biocompatibility, and patient health. Recently developed novel bioresorbable stents are intended to overcome common issues of chronic inflammation, in-stent restenosis, and stent thrombosis associated with permanent stents, but there is still much to learn. Increased knowledge and advanced methods in material processing have led to new stent formulations aimed at improving the performance of their predecessors but often comes with potential tradeoffs. This review aims to discuss the advantages and disadvantages of stent material interactions with the host within five areas of contrasting characteristics, such as 1) metal or polymer, 2) bioresorbable or permanent, 3) drug elution or no drug elution, 4) bare or surface-modified, and 5) self-expanding or balloon-expanding perspectives, as they relate to pre-clinical and clinical outcomes and concludes with directions for future studies.

Natural language processing to assess the epidemiology of delirium-suggestive behavioural disturbances in critically ill patients.

Background: There is no gold standard approach for delirium diagnosis, making the assessment of its epidemiology difficult. Delirium can only be inferred though observation of behavioural disturbance and described with relevant nouns or adjectives. Objective: We aimed to use natural language processing (NLP) and its identification of words descriptive of behavioural disturbance to study the epidemiology of delirium in critically ill patients. Study design: Retrospective study using data collected from the electronic health records of a university-affiliated intensive care unit (ICU) in Melbourne, Australia. Participants: 12 375 patients Intervention: Analysis of electronic progress notes. Identification using NLP of at least one of a list of words describing behavioural disturbance within such notes. Results: We analysed 199 648 progress notes in 12 375 patients. Of these, 5108 patients (41.3%) had NLP-diagnosed behavioural disturbance (NLP-Dx-BD). Compared with those who did not have NLP-Dx-DB, these patients were older, more severely ill, and likely to have medical or unplanned admissions, neurological diagnosis, chronic kidney or liver disease and to receive mechanical ventilation and renal replacement therapy (P < 0.001). The unadjusted hospital mortality for NLP-Dx-BD patients was 14.1% versus 9.6% for patients without NLP-Dx-BD. After adjustment for baseline characteristics and illness severity, NLP-Dx-BD was not associated with increased risk of death (odds ratio [OR], 0.94; 95% CI, 0.80-1.10); a finding robust to multiple sensitivity, subgroups and time of observation subcohort analyses. In mechanically ventilated patients, NLP-Dx-BD was associated with decreased hospital mortality (OR, 0.80; 95% CI, 0.65-0.99) after adjustment for baseline severity of illness and year of admission. Conclusions: NLP enabled rapid assessment of large amounts of data identifying a population of ICU patients with typical high risk characteristics for delirium. Moreover, this technique enabled identification of previously poorly understood associations. Further investigations of this technique appear justified.

Micro-/Nanotopography on Bioresorbable Zinc Dictates Cytocompatibility, Bone Cell Differentiation, and Macrophage Polarization.

Bioresorbable metals are quickly advancing in the field of regenerative medicine for their promises of tissue restoration without adverse consequences from their lifelong presence. Zn has recently risen to the top of bioresorbable metals with great potential as a medical implant. However, cell adhesion and colonization on the Zn substrate surface remains challenging, which could damper interfacial tissue-implant integration. Inspired by the fact that surface topography can regulate cell function and fate, we hypothesize that topography on bioresorbable Zn can dictate material biocompatibility, cell differentiation, and immunomodulation. To verify this, surface-engineered Zn plates with nano-, submicro-, and microtopographies were systematically investigated. The microscale topography exhibited increased adhesion, pronounced self-renewal, and enhanced osteogenic differentiation of bone cells as well as less macrophage inflammatory polarization, reduced platelet adhesion, and better hemocompatibility. Thus, surface topography could be a viable strategy to enhance bioresorbable Zn's biocompatibility and integration with surrounding tissues while reducing inflammation.

Porous zinc scaffolds for bone tissue engineering applications: A novel additive manufacturing and casting approach.

As a degradable metal, zinc (Zn) has attracted an immense amount of interest as the next generation of bioresorbable implants thanks to its modest corrosion rate and its vital role in bone remodeling, yet very few studies have thoroughly investigated its functionality as a porous implant for bone tissue engineering purposes. Zn bone scaffolds with two different pore sizes of 900 µm and 2 mm were fabricated using additive manufacturing-produced templates combined with casting. The compressive properties, corrosion rates, biocompatibility, and antibacterial performance of the bioscaffolds were examined and compared to a non-porous control. The resulting textured and porous Zn scaffolds exhibit a fully interconnected pore structure with precise control over topology. As pore size and porosity increased, mechanical strength decreased, and corrosion rate accelerated. Cell adhesion and growth on scaffolds were enhanced after an ex vivo pretreatment method. In vitro cellular tests confirmed good biocompatibility of the scaffolds. As porosity increased, potent antibacterial rates were also observed. Taken together, these results demonstrate that Zn porous bone scaffolds are promising for orthopedic applications.

Salt Preform Texturing of Absorbable Zn Substrates for Bone-implant Applications.

Surface roughness is an important factor in improving the bone-implant contact area to enhance bone regeneration, yet this aspect has not been applied to absorbable metals. Textured zinc surfaces with varying degrees of surface roughness were produced using a salt-preform method with fine- and coarse-grained salts and compared to a polished control sample. The resulting surfaces were characterized by scanning electron microscopy (SEM), surface roughness, corrosion rates, and in vitro cytotoxicity. The resulting textured surfaces exhibit micron-sized cavities and increased roughness consistent with the initial salt particle size. The corrosion rate was shown to accelerate significantly as compared to the polished control sample, and pre-osteoblasts displayed healthy morphologies on the textures. The results confirm textured zinc surfaces support cell adhesion and can be used to control the corrosion rate. This study represents an important intermediate step that can be applied to porous absorbable metal scaffolds for bone-implant applications.

Using language descriptors to recognise delirium: a survey of clinicians and medical coders to identify delirium-suggestive words.

OBJECTIVE: To develop a library of delirium-suggestive words. DESIGN: Cross-sectional survey. SETTING: Single tertiary referral hospital. PARTICIPANTS: Medical, nursing and allied health staff and medical coders. MAIN OUTCOME MEASURES: Frequency of graded response on a 5-point Likert scale to individual delirium-suggestive words. RESULTS: Two-hundred and three complete responses were received from 227 survey respondents; the majority were medical and nursing staff (42.4% and 43.8% respectively), followed by allied health practitioners and medical coders (10.3% and 3.4%). Words that were "very likely" to suggest delirium were "confused/ confusion", "delirious", "disoriented/disorientation" and "fluctuating conscious state". Differences in word selection were noted based on occupational background, prior knowledge of delirium, and experience in caring for intensive care unit patients. Distractor words included in the survey were rated as "unlikely" or "very unlikely" by respondents as expected. Textual responses identified several other descriptors of delirium-suggestive words. CONCLUSION: A comprehensive repertoire of delirium-suggestive words was validated using a multidisciplinary survey and new words suggested by respondents were added. The use of natural language processing algorithms may allow for earlier detection of delirium using our delirium library and be deployed for real-time decision making and clinical care.

A novel nano-particle strengthened titanium alloy with exceptional specific strength.

Various ecological and economical concerns have spurred mankind's quest for materials that can provide enhanced weight savings and improved fuel efficiency. As part of this pursuit, we have microstructurally tailored an exceptionally high-strength titanium alloy, Ti-6Al-2Sn-4Zr-6Mo (Ti6246) through friction stir processing (FSP). FSP has altered the as-received bimodal microstructure into a unique modulated microstructure comprised of fine acicular α″-laths with nano precipitates within the laths. The sequence of phase transformations responsible for the modulated microstructure and consequently for the strength is discussed with the help of scanning electron microscopy, transmission electron microscopy, and synchrotron X-ray diffraction studies. The specific strength attained in one of the conditions is close to 450 MPa m3/mg, which is about 22% to 85% greater than any commercially available metallic material. Therefore, our novel nano particle strengthened Ti alloy is a potential replacement for many structural alloys, enabling significant weight reduction opportunities.

Laboratory alerts to guide early intensive care team review in surgical patients: A feasibility, safety, and efficacy pilot randomized controlled trial.

AIM: Common blood tests can help identify patients at risk of death, unplanned intensive care unit (ICU) admission, or rapid response team (RRT) call. We aimed to test whether early ICU-team review triggered by such laboratory tests (lab alert) is feasible, safe, and can alter physiological variables, clinical management, and clinical outcomes. METHODS: In prospective pilot randomized controlled trial in surgical wards of a tertiary hospital, we studied patients admitted for >24 h. We applied a previously validated risk assessment tool to each set of common laboratory tests to identify patients at risk and generate a "lab-alert". We randomly allocated such lab-alert patients to receive early ICU-team review (intervention) or usual care (control). RESULTS: We studied 205 patients (males 54.1%; average age 79 years; 103 randomized to intervention and 102 to usual care). Intervention patients were more likely to trigger RRT activation during their first lab-alert (10.7 vs. 2.0%; P < 0.001) but less likely to receive an allied health referral (18.0% vs. 24.5%; p = 0.007). They were less likely to trigger RRT activation in the 24-h before subsequent alerts (18.4 vs. 22.4%; p = 0.008) and less likely to generate further alerts (204 vs. 320; p < 0.001), but more likely to receive a not for resuscitation or endotracheal intubation status in the 24-h before subsequent alerts (26.6 vs. 17.3%; p = 0.05). Mortality at 24 h was 1.9% for the intervention group vs. 2.9% in the control group (p = 0.63). Finally, overall mortality was 19.4% for intervention patients vs. 23.5% for control patients (p = 0.50). CONCLUSION: Among surgical patients, lab alerts identify patients with a high mortality. Lab alert-triggered interventions are associated with more first alert-associated RRT activations; more changes in resuscitation status toward a more conservative approach; fewer subsequent alert-associated RRT activations; fewer subsequent alerts, and decreased allied health interventions (ANZCTRN12615000146594).

Biological Responses and Mechanisms of Human Bone Marrow Mesenchymal Stem Cells to Zn and Mg Biomaterials.

Zn biomaterials attract strong attentions recently for load-bearing medical implants because of their mechanical properties similar to bone, biocompatibility, and degradability at a more matched rate to tissue healing. It has been shown previously that Zn alloys are beneficial for bone regeneration, but the supporting mechanisms have not been explored in detail. Here, we studied the biological responses of human bone marrow mesenchymal stem cells (hMSC) to Zn and the underlying cellular signaling mechanisms. Typical Mg material AZ31 was used as a comparative benchmark control. Direct culture of cells on the materials revealed that cell adhesion, proliferation, and motility were higher on Zn than on AZ31. Significant cytoskeletal reorganizations induced by Zn or AZ31 were also observed. Mineralization of extracellular matrix (ECM) and hMSC osteogenic differentiation, measured by Alizarin red and ALP staining and activities, were significantly enhanced when cells were cultured with Zn or AZ31. Quantitative PCR also showed the increased expression of bone-related genes including ALP, collagen I, and osteopontin. Using small RNA interference to knockdown related key molecules, we illustrated the mechanisms of Zn-induced cellular signaling. TRPM7 and GPR39 appear to be the major cellular receptors facilitating Zn2+-entry into hMSC. The intracellular Zn2+ then activates the cAMP-PKA pathway and triggers intracellular Ca2+ responses, leading to activation of MAPK. In addition, Zn2+ activates the Gαq-PLC-AKT pathway as well. Eventually, all of this signaling would lead to enhanced differential regulation of genes, cell survival/growth and differentiation, ECM mineralization, osteogenesis, and other cellular activities.

Archaeometallurgy using synchrotron radiation: a review.

Archaeometallurgy is an important field of study which allows us to assess the quality and value of ancient metal artifacts and better understand the ancient cultures that made them. Scientific investigation of ancient metal artifacts is often necessary due to their lack of well-documented histories. One important requirement of analytical techniques is that they be non-destructive, since many of these artifacts are unique and irreplaceable. Most synchrotron radiation (SR) techniques meet this requirement. In this review, the characteristics, capabilities, and advantages and disadvantages of current and future SR facilities are discussed. I examine the application of SR techniques such as x-ray imaging (radiography/microscopy and tomography), x-ray diffraction, x-ray fluorescence, x-ray spectroscopy, Fourier transform infrared spectroscopy, and lastly combined SR techniques to the field of archaeometallurgy. Previous case studies using these various SR techniques are discussed and potential future SR techniques are addressed.

Giant magnetostriction in annealed Co(1-x)Fe(x) thin-films.

Chemical and structural heterogeneity and the resulting interaction of coexisting phases can lead to extraordinary behaviours in oxides, as observed in piezoelectric materials at morphotropic phase boundaries and relaxor ferroelectrics. However, such phenomena are rare in metallic alloys. Here we show that, by tuning the presence of structural heterogeneity in textured Co(1-x)Fe(x) thin films, effective magnetostriction λ(eff) as large as 260 p.p.m. can be achieved at low-saturation field of ~10 mT. Assuming λ(100) is the dominant component, this number translates to an upper limit of magnetostriction of λ(100)≈5λ(eff) >1,000 p.p.m. Microstructural analyses of Co(1-x)Fe(x) films indicate that maximal magnetostriction occurs at compositions near the (fcc+bcc)/bcc phase boundary and originates from precipitation of an equilibrium Co-rich fcc phase embedded in a Fe-rich bcc matrix. The results indicate that the recently proposed heterogeneous magnetostriction mechanism can be used to guide exploration of compounds with unusual magnetoelastic properties.