Single-Phase L10-Ordered High Entropy Thin Films with High Magnetic Anisotropy.

The vast high entropy alloy (HEA) composition space is promising for discovery of new material phases with unique properties. This study explores the potential to achieve rare-earth-free high magnetic anisotropy materials in single-phase HEA thin films. Thin films of FeCoNiMnCu sputtered on thermally oxidized Si/SiO2 substrates at room temperature are magnetically soft, with a coercivity on the order of 10 Oe. After post-deposition rapid thermal annealing (RTA), the films exhibit a single face-centered-cubic phase, with an almost 40-fold increase in coercivity. Inclusion of 50 at.% Pt in the film leads to ordering of a single L10 high entropy intermetallic phase after RTA, along with high magnetic anisotropy and 3 orders of magnitude coercivity increase. These results demonstrate a promising HEA approach to achieve high magnetic anisotropy materials using RTA.

Recommendations for High-resolution Peripheral Quantitative Computed Tomography Assessment of Bone Density, Microarchitecture, and Strength in Pediatric Populations.

PURPOSE OF REVIEW: The purpose of this review is to summarize current approaches and provide recommendations for imaging bone in pediatric populations using high-resolution peripheral quantitative computed tomography (HR-pQCT). RECENT FINDINGS: Imaging the growing skeleton is challenging and HR-pQCT protocols are not standardized across centers. Adopting a single-imaging protocol for all studies is unrealistic; thus, we present three established protocols for HR-pQCT imaging in children and adolescents and share advantages and disadvantages of each. Limiting protocol variation will enhance the uniformity of results and increase our ability to compare study results between different research groups. We outline special cases along with tips and tricks for acquiring and processing scans to minimize motion artifacts and account for growing bone. The recommendations in this review are intended to help researchers perform HR-pQCT imaging in pediatric populations and extend our collective knowledge of bone structure, architecture, and strength during the growing years.

CoTe2 : A Quantum Critical Dirac Metal with Strong Spin Fluctuations.

Quantum critical points separating weak ferromagnetic and paramagnetic phases trigger many novel phenomena. Dynamical spin fluctuations not only suppress the long-range order, but can also lead to unusual transport and even superconductivity. Combining quantum criticality with topological electronic properties presents a rare and unique opportunity. Here, by means of ab initio calculations and magnetic, thermal, and transport measurements, it is shown that the orthorhombic CoTe2 is close to ferromagnetism, which appears suppressed by spin fluctuations. Calculations and transport measurements reveal nodal Dirac lines, making it a rare combination of proximity to quantum criticality and Dirac topology.

Human convalescent plasma protects K18-hACE2 mice against severe respiratory disease.

SARS-CoV-2 is the causative agent of COVID-19 and human infections have resulted in a global health emergency. Small animal models that reproduce key elements of SARS-CoV-2 human infections are needed to rigorously screen candidate drugs to mitigate severe disease and prevent the spread of SARS-CoV-2. We and others have reported that transgenic mice expressing the human angiotensin-converting enzyme 2 (hACE2) viral receptor under the control of the Keratin 18 (K18) promoter develop severe and lethal respiratory disease subsequent to SARS-CoV-2 intranasal challenge. Here we report that some infected mice that survive challenge have residual pulmonary damages and persistent brain infection on day 28 post-infection despite the presence of anti-SARS-COV-2 neutralizing antibodies. Because of the hypersensitivity of K18-hACE2 mice to SARS-CoV-2 and the propensity of virus to infect the brain, we sought to determine if anti-infective biologics could protect against disease in this model system. We demonstrate that anti-SARS-CoV-2 human convalescent plasma protects K18-hACE2 against severe disease. All control mice succumbed to disease by day 7; however, all treated mice survived infection without observable signs of disease. In marked contrast to control mice, viral antigen and lesions were reduced or absent from lungs and absent in brains of antibody-treated mice. Our findings support the use of K18-hACE2 mice for protective efficacy studies of anti-SARS-CoV-2 medical countermeasures (MCMs). They also support the use of this system to study SARS-CoV-2 persistence and host recovery.

A diagnostic evaluation of a molecular assay used for testing and treating anorectal chlamydia and gonorrhoea infections at the point-of-care in Papua New Guinea.

OBJECTIVES: Papua New Guinea has among the highest prevalences of sexually transmissible infections (STIs) globally with no services able to accurately test for anorectal Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections. Here we prospectively evaluated the diagnostic performance of a molecular CT/NG assay used at the point-of-care (POC) with the aim of enhancing anorectal STI screening and same-day treatment. METHODS: Men who have sex with men, transgender women and female sex workers taking part in Papua New Guinea's first large-scale biobehavioural study were enrolled and asked to provide a self-collected anorectal swab for POC GeneXpert CT/NG testing. Same-day treatment was offered if positive. A convenience sample of 396 unique and randomly selected samples were transported to Australia for comparison using the Cobas 4800 CT/NG test (Roche Molecular Diagnostics, Pleasanton, CA, USA). RESULTS: A total of 326 samples provided valid results by Cobas whereas 70 samples provided invalid results suggesting inhibition. The positive, negative and overall percentage agreements of GeneXpert CT/NG for the detection of C. trachomatis were 96.7% (95% CI 92.3%-98.9%), 95.5% (95% CI 91.3%-98.0%) and 96.0% (95% CI 93.3%-97.8%), and for N. gonorrhoeae were 93.0% (95% CI 86.1%-97.1%), 100.0% (95% CI 98.3%-100.0%) and 97.8% (95% CI 95.6%-99.1%), respectively. CONCLUSIONS: The overall rate of agreement between the GeneXpert and Cobas CT/NG assays was high with 96.0% for C. trachomatis and 97.8% for N. gonorrhoeae. Results from this study data suggest that the GeneXpert CT/NG assay is suitable for testing self-collected anorectal specimens at the POC and that same-day treatment was feasible.

Standard method for microCT-based additive manufacturing quality control 4: Metal powder analysis.

X-ray micro computed tomography (microCT) can be applied to analyse powder feedstock used in additive manufacturing. In this paper, we demonstrate a dedicated workflow for this analysis method, specifically for Ti6Al4V powder typically used in commercial powder bed fusion (PBF) additive manufacturing (AM) systems. The methodology presented includes sample size requirements, scan conditions and settings, reconstruction and image analysis procedures. We envisage this method will support standardization in powder analysis in the additive manufacturing community. This is aimed at ultimately improving the quality of additively manufactured parts, through the identification of impurities and defects in powders. •MicroCT analysis of metal powders for additive manufacturing•Method describes a standard workflow simplifying usage of the technique•Sample requirements and image analysis workflow is described.

Bias-Dependent Scanning Tunneling Microscopy Signature of Bridging-Oxygen Vacancies on Rutile TiO2(110).

The rutile TiO2(110) surface has long-served as a well-characterized, prototypical transition-metal oxide surface used in heterogeneous catalysis and photocatalytic water splitting. Naturally occurring defects on this surface, called bridging-oxygen (BO) vacancies, are important as they determine the overall reactivity of the surface. Herein, we report a bias-dependent, scanning tunneling microscopy (STM) signature of the BO vacancies on TiO2(110): for sample bias voltages past a threshold of +3 V, the bright vacancies are flanked on either side (along the oxygen row) by two dark spots approximately shaped like half-moons. The BO vacancies have a bright aspect below the threshold bias also but are not surrounded by half-moon dark depressions. Using generalized gradient approximation calculations with Hubbard correction (GGA + U) for projected density of states (DOS) and simulated STM images, we find that the bias-dependent STM signature originates from (i) local DOS maxima of all BOs (lighter background that occurs above the threshold bias) and (ii) the increased separation between the first and second BO atoms neighboring the vacancy which leads to an apparent dip between these neighboring oxygens. These results offer a new striking example of the STM signature that appears without switching the polarity of the bias. Similar approaches can be employed for seeking distinguishing features on the surfaces of other large band gap semiconductors and insulators.

Association of Toll-like receptor polymorphisms with HIV status in North Americans.

Single-nucleotide polymorphisms (SNPs) in Toll-like receptor (TLR) genes TLR2-4 and TLR7-9, but not in TLR1 and TLR6, have been previously evaluated regarding human immunodeficiency virus (HIV) acquisition and disease progression in various populations, most of which were European. In this study, we examined associations between a total of 41 SNPs in 8 TLR genes (TLR1-4, TLR6-9) and HIV status in North American subjects (total n=276 (Caucasian, n=102; African American, n=150; other, n=24)). Stratification of the data by self-identified race revealed that a total of nine SNPs in TLR1, TLR4, TLR6 and TLR8 in Caucasians, and two other SNPs, one each in TLR4 and TLR8, in African Americans were significantly associated with HIV status at P<0.05. Concordant with the odds ratios of these SNPs, significant differences were observed in the SNP allele frequencies between HIV+ and HIV- subjects. Finally, in Caucasians, certain haplotypes of single (TLR1 and TLR4) and heterodimer (TLR2_TLR6) genes may be inferred as 'susceptible' or 'protective'. Our study provides in-depth insight into the associations between TLR variants, particularly TLR1 and TLR6, and HIV status in North Americans, and suggests that these associations may be race specific.

Notch pathway inhibition controls myeloma bone disease in the murine MOPC315.BM model.

Despite evidence that deregulated Notch signalling is a master regulator of multiple myeloma (MM) pathogenesis, its contribution to myeloma bone disease remains to be resolved. Notch promotes survival of human MM cells and triggers human osteoclast activity in vitro. Here, we show that inhibition of Notch through the γ-secretase inhibitor XII (GSI XII) induces apoptosis of murine MOPC315.BM myeloma cells with high Notch activity. GSI XII impairs murine osteoclast differentiation of receptor activator of NF-κB ligand (RANKL)-stimulated RAW264.7 cells in vitro. In the murine MOPC315.BM myeloma model GSI XII has potent anti-MM activity and reduces osteolytic lesions as evidenced by diminished myeloma-specific monoclonal immunoglobulin (Ig)-A serum levels and quantitative assessment of bone structure changes via high-resolution microcomputed tomography scans. Thus, we suggest that Notch inhibition through GSI XII controls myeloma bone disease mainly by targeting Notch in MM cells and possibly in osteoclasts in their microenvironment. We conclude that Notch inhibition is a valid therapeutic strategy in MM.

Rodent animal models of delayed bone healing and non-union formation: a comprehensive review.

Despite the growing knowledge on the mechanisms of fracture healing, delayed healing and non-union formation remain a major clinical challenge. Animal models are needed to study the complex process of normal and impaired fracture healing and to develop new therapeutic strategies. Whereas in the past mainly large animals have been used to study normal and impaired fracture healing, nowadays rodent models are of increasing interest. New osteosynthesis techniques for rat and mice have been developed during the last years, which allowed for the first time stable osteosynthesis in these animals comparable to the standards in large animals and humans. Based on these new implants, different models in rat and mice have been established to study delayed healing and non-union formation. Although in humans the terms delayed union and non-union are well defined, in rodents definitions are lacking. However, especially in scientific studies clear definitions are necessary to develop a uniform scientific language and allow comparison of the results between different studies. In this consensus report, we define the basic terms "union", "delayed healing" and "non-union" in rodent animal models. Based on a review of the literature and our own experience, we further provide an overview on available models of delayed healing and non-union formation in rats and mice. We further summarise the value of different approaches to study normal and delayed fracture healing as well as non-union formation, and discuss different methods of data evaluation.

Small animal bone healing models: standards, tips, and pitfalls results of a consensus meeting.

Small animal fracture models have gained increasing interest in fracture healing studies. To achieve standardized and defined study conditions, various variables must be carefully controlled when designing fracture healing experiments in mice or rats. The strain, age and sex of the animals may influence the process of fracture healing. Furthermore, the choice of the fracture fixation technique depends on the questions addressed, whereby intra- and extramedullary implants as well as open and closed surgical approaches may be considered. During the last few years, a variety of different, highly sophisticated implants for fracture fixation in small animals have been developed. Rigid fixation with locking plates or external fixators results in predominantly intramembranous healing in both mice and rats. Locking plates, external fixators, intramedullary screws, the locking nail and the pin-clip device allow different degrees of stability resulting in various amounts of endochondral and intramembranous healing. The use of common pins that do not provide rotational and axial stability during fracture stabilization should be discouraged in the future. Analyses should include at least biomechanical and histological evaluations, even if the focus of the study is directed towards the elucidation of molecular mechanisms of fracture healing using the largely available spectrum of antibodies and gene-targeted animals to study molecular mechanisms of fracture healing. This review discusses distinct requirements for the experimental setups as well as the advantages and pitfalls of the different fixation techniques in rats and mice.

Local BMP-2 application can rescue the delayed osteotomy healing in a rat model.

Delayed healing is still a severe complication in the clinic. The aim of the present study was to investigate the effect of locally delivered BMP-2 incorporated in a poly(d,l-lactide) (PDLLA) implant coating in a rat model with delayed tibial healing. The healing delay in this model is not caused by mechanical instability or additional tissue manipulation and presents therefore a common and challenging clinical situation of impaired healing. Radiological, histological and biomechanical evaluations were performed at days 5, 10, 28, 42, and 84 after tibial osteotomy. The control group showed a delayed healing without complete bridging and without reaching the biomechanical stability of the contralateral tibiae after 84 days. The mechanical stability of the BMP-treated tibiae showed a significant increase at days 28 and 42 compared to the control group and exceeded the stability of the intact contralateral tibiae. Less cartilage was detected at day 28 and the mineralisation was significantly enhanced at day 42 due to the local BMP application. Looking at the early healing phase (day 10) a reduced vascularisation was seen in the BMP group. This reflects the situation seen during normal healing, whereas the delayed healing in the present model had an increased vascularisation. The present study clearly demonstrates that local BMP-2 application can stimulate delayed healing in a clinically relevant animal model.

Examining the influence of short-term implantation on oxidative degradation in retrieved highly crosslinked polyethylene tibial components.

Concerns remain regarding the oxidative resistance of highly crosslinked polyethylene (PE). The study investigated the in vivo performance of Durasul highly crosslinked PE by comparing the oxidation index, density, and percent crystallinity in the weightbearing and nonweightbearing region of retrieved components with unused time zero tibial components. Retrieved and unused Sulene conventional PE tibial components were examined for comparison and the effects of shelf age, in vivo duration, and ex vivo duration were also investigated. The oxidation index was not significantly different between unused time zero and retrieved Durasul PE components. Regression analysis data supported these findings in that neither shelf age, in vivo duration, nor ex vivo duration was a significant predictor of oxidation index in the retrieved Durasul PE components. In contrast, the retrieved conventional PE components had significantly greater oxidation index, density, and percent crystallinity compared with unused time zero PE components. Regression data suggested that in vivo and ex vivo duration, but not shelf aging, influenced the changes observed in the conventional PE components. These data also showed that in vivo loading did not significantly affect the oxidation index, density, or percent crystallinity in either the retrieved Durasul or conventional PE tibial components. This investigation demonstrates that changes in oxidation index, density, and percent crystallinity of retrieved Durasul PE components after short-term in vivo durations are likely not a clinical concern. These data should be used as a benchmark to compare with future studies examining the long-term oxidative resistance of Durasul highly crosslinked PE tibial components.

Surface damage analysis of retrieved highly crosslinked polyethylene tibial components after short-term implantation.

The use of highly crosslinked polyethylene (PE) in the knee remains controversial, because of reduced fatigue fracture properties of the material. The current study investigated postmelt surface damage as well as potential contributors to this damage in retrieved highly crosslinked PE tibial components, after short-term in vivo durations. Retrieved conventional PE tibial components were examined for comparison, as well as unused time zero highly crosslinked and conventional PE tibial components for inherent manufacturing surface characterization. Predominant surface damage modes on highly crosslinked PE components were machine mark loss and abrasion, while conventional PE components primarily had machine mark loss, abrasion, and delamination. In vivo duration, PE thickness, and conformity of the design were significant predictors of surface damage on retrieved conventional PE components. Donor weight and the conformity of the design were significant predictors of surface damage on retrieved highly crosslinked PE components. This retrieval data on highly crosslinked PE tibial components suggest that in vivo wear occurred, observed as postmelt surface damage. The highly crosslinked Durasul material examined in this retrieval study appeared to outperform the conventional PE components made from 4150 resin, ram-extruded and gamma-sterilized in air, but not the conventional components made from 1020 resin, compression molding and gamma sterilization in nitrogen. Early retrieval data of highly crosslinked PE tibial components are important to serve as a benchmark to be compared with future longer-term retrieval studies investigating whether surface damage translates to clinically relevant particulate wear debris generation and PE clinical performance.

Relationship between bone ingrowth, mineral apposition rate, and osteoblast activity.

To better understand skeletal attachment of porous coated total hip and knee implants over time, this study investigated the dynamics of osteoblast populations at the interface of porous coated implants in a weight-bearing ovine model. The relationship between cancellous bone ingrowth, mineral apposition rate (MAR), and osteoblast activity indicators such as osteoblast area, relative osteoblast number, osteoid width, and osteoid area (O.Ar.) were investigated. The data demonstrated that the percent O.Ar. was a marginally significant predictor of bone ingrowth and MAR over time, suggesting that the amount of osteoid present influenced bone ingrowth and MAR in the porous coated implants. The data also demonstrated that all osteoblast activity indicators were significantly greater in the porous coated region compared to the host bone region, while controlling for in situ time (p < 0.05). This may have been due to the trauma of implantation or the influence of the implant load on the bone tissue promoting a regional acceleratory phenomenon. The localized response suggests that specific therapies may be developed to affect the physiology of osteoblasts at the interface of implants, which may allow for improve skeletal attachment of biomaterials and clinical outcomes of cementless joint replacements.

Possible explanation for the white band artifact seen in clinically retrieved polyethylene tibial components.

Studies have focused attention on the appearance of a subsurface white band in clinically retrieved polyethylene components and the possible contribution of this phenomenon to early polyethylene delamination. Unconsolidated polyethylene particles and oxidation have been suggested as possible reasons for the appearance of the white band. Calcium stearate and other additives used in processing ultra-high molecular weight polyethylene may also contribute to formation of the white band. A quantitative investigation was conducted on 11 retrieved tibial components that exhibited a subsurface white band to determine whether the amount of calcium stearate particles and additives were greater in the white band region when compared with the mid-portion of the same section of polyethylene. Calcium stearate particles and other additives were quantified using backscattered electron imaging with correlated elemental analysis. The particles were identified based on morphology and elemental patterns similar to reference calcium stearate particles and known additives. Significantly more (p < 0. 0001) calcium stearate particles and additives were present in the white band region (4578 +/- 418 particles/mm(2); mean +/- standard error) than the mid-portion region (1250 +/- 147 particles/mm(2)) of the sectioned tibial inserts. The percent area occupied by calcium stearate particles and additives was five times higher (p < 0.0001) within the white band region (0.81 +/- 0.10%) than the mid-portion region (0.16 +/- 0.03%). The increased presence of calcium stearate and other additives in the white band region suggests that they may play a role in the formation of the white band. In future investigations it may be important to consider how calcium stearate and other additives in polyethylene resins affect white band formation and the possible contribution to crazing, early delamination, and osteolysis in total joint replacement.

Elemental and morphological identification of third-body particulate and calcium stearate inclusions in polyethylene components.

Third-body particulate such as human bone chips, hydroxyapatite, and bone cement are considered contributing factors in accelerated wear in total joint replacement. Particulate wear debris is now considered the major contributing factor in aseptic loosening of total joint replacements. The ability to distinguish between different third-body particulate is necessary to better understand wear mechanisms when conducting implant retrieval analysis. The objective of this investigation is to demonstrate that backscattered electron imaging with correlated energy dispersive X-ray analysis can accurately identify third-body particulate in retrieved polyethylene components. It is important that this technique can also distinguish between third-body particulate and normal inclusions in the polyethylene such as calcium stearate, based on the distinct morphology and elemental composition of each material. Therefore, the ability to distinguish third-body particulate from calcium stearate inclusions is essential in gaining a better understanding of the contributing factors associated with coating separation and accelerated wear observed in clinically retrieved polyethylene components.