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Featured Application: Magnesium-doped carbonated hydroxyapatite and tricalcium phosphate anodized coatings are applied in alpha, beta, and duplex titanium alloys to improve osseointegration. The rising demand for dental and orthopedic implants and their frequent aseptic loosening failure mode necessitate the drive to continue modifying implant surfaces to improve osseointegration outcomes. Plasma-sprayed hydroxyapatite coatings are widely used but are prone to delamination. This study involves a single-step anodization process utilizing a novel electrolyte to produce Mg-doped carbonated hydroxyapatite and tricalcium phosphate-containing coatings on four titanium alloy surfaces. XRD confirmed hydroxyapatite and tricalcium phosphate formation, with FTIR examination revealing carbonate substitutions indicative of bone-like apatite formation in each oxide. SEM analyses revealed micro- and nano-scaled surface features on each oxide. SEM and EDS analyses of the oxide coating cross-sections showed each group to be bi-layered with an inner titanium dioxide-rich layer and an outer hydroxyapatite/tricalcium phosphate-rich layer. The oxide layer adhesion quality was shown to be good on CPTi, TAV, and TiMo α + β implant alloy surfaces. Unfortunately, the anodization process also resulted in an undesirable and embrittling omega phase at the substrate–oxide interface due to the migration of molybdenum into the inner oxide. Nonetheless, the anodized coatings on the CPTi and TAV alloy substrates, which are the most widely used titanium alloys for implant applications, show much potential for improving future patient outcomes. [ABSTRACT FROM AUTHOR]

A manager's prior experience may affect an organization's resource allocation decisions and its performance. I examine this issue in the context of National Football League (NFL) franchises. I find that teams with coaches from an offensive background spend 5.5% points more of their salary cap space on offensive personnel, while a defensive background does not significantly affect the share of resources allocated to defensive personnel. While additional salary resources committed to offensive and defensive personnel do improve team performance in those respective areas, marginal improvements in offensive and defensive performance associated with greater spending are generally unaffected by the coach's background, a finding suggesting that a coach's background does not confer an informational advantage on certain types of personnel. I further find no evidence of significant differences in the effects that spending on offence and defence respectively have on team performance, suggesting efficiency within this labour market. [ABSTRACT FROM AUTHOR]

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Formalin-fixed paraffin-embedded (FFPE) samples are valuable but underutilized in single-cell omics research due to their low RNA quality. In this study, leveraging a recent advance in single-cell genomic technology, we introduce snPATHO-seq, a versatile method to derive high-quality single-nucleus transcriptomic data from FFPE samples. We benchmarked the performance of the snPATHO-seq workflow against existing 10x 3' and Flex assays designed for frozen or fresh samples and highlighted the consistency in snRNA-seq data produced by all workflows. The snPATHO-seq workflow also demonstrated high robustness when tested across a wide range of healthy and diseased FFPE tissue samples. When combined with FFPE spatial transcriptomic technologies such as FFPE Visium, the snPATHO-seq provides a multi-modal sampling approach for FFPE samples, allowing more comprehensive transcriptomic characterization. A combination of an FFPE nuclei preparation protocol and a probe-based transcriptomic profiling technique enables snRNA-seq characterization of archival human FFPE tissues, holding promise for retrospective studies involving aged clinical cohorts. [ABSTRACT FROM AUTHOR]

Periapical radiographs are routinely used in dental practice for diagnosis and treatment planning purposes. However, they often suffer from artifacts, distortions, and superimpositions, which can lead to potential misinterpretations. Thus, an automated detection system is required to overcome these challenges. Artificial intelligence (AI) has been revolutionizing various fields, including medicine and dentistry, by facilitating the development of intelligent systems that can aid in performing complex tasks such as diagnosis and treatment planning. The purpose of the present study was to verify the diagnostic performance of an AI system for the automatic detection of teeth, caries, implants, restorations, and fixed prosthesis on periapical radiographs. A dataset comprising 1000 periapical radiographs collected from 500 adult patients was analyzed by an AI system and compared with annotations provided by two oral and maxillofacial radiologists. A strong correlation (R > 0.5) was observed between AI perception and observers 1 and 2 in carious teeth (0.7–0.73), implants (0.97–0.98), restored teeth (0.85–0.89), teeth with fixed prosthesis (0.92–0.94), and missing teeth (0.82–0.85). The automatic detection by the AI system was comparable to the oral radiologists and may be useful for automatic identification in periapical radiographs. [ABSTRACT FROM AUTHOR]

West Tasmania has a complex geological history, including a Cambrian tectonic collision and related orogenesis, which formed ore deposits in a volcanic hosted massive sulfide (VHMS) setting. While the topography and dense vegetation covering the area presents challenges for on-ground investigations, the area is relatively well-studied such that 3D geological models are available. This contribution presents results of a broadband magnetotelluric (MT) 2D transect across the area (∼30 stations over a $ \sim 80\,{\rm km} $ ∼ 80 km line, deployed in early 2016) that enables a combined interpretation of regional-scale geoelectric and geological structures. After accounting for noise, distortion and geoelectric strike; we produce 2D resistivity models using OCCAM2D inversion. We infer low resistivity anomalies in the shallow ( $ \lt 3\,{\rm km} $ < 3 km ), mid (3–8 km) and deeper crust. Along this MT transect the shallow and mid crust low resistivity zones correspond to major crustal faults. Deep low resistivity features in the east of the transect suggest fluid pathways associated with metamorphism along the western boundary of the Tyennan block during the Cambrian Tyennan Orogeny, while others potentially represent the metasomatism of lower crustal rocks and fluid pathways converging into the mid crust. [ABSTRACT FROM AUTHOR]

Heat flow data obtained in connection with geothermal resource exploration suggests anomalous upper crustal structure and processes in parts of central east Tasmania. The regional scale crustal geology of the Midlands of Tasmania is, however, mostly obscured at the surface by the Permo-Triassic sedimentary sequences of the Tasmania Basin together with extensive exposures of Jurassic dolerite. We investigate controls on undercover crustal processes in this region by combining long period and broadband magnetotelluric (MT) datasets in 3D inversions for the geoelectric structure; followed by an interpretation that is informed by aspects of the pre-existing 3D regional geological and geophysical model. The new 3D model allows improved resolution of low resistivity anomalies together with a qualitative appraisal of spatially variable model sensitivity. The most robust features ( $ \lt 1\,\Omega {\rm m} $ < 1 Ω m ) in the 2–3 km depth interval occur where N–S and E–W faults intersect with a high point in the topography of the upper surface of a deep seated granite body. Enhancement of conductivity in this zone by clay, graphite or mineralisation, or a combination thereof, is likely. Other low resistivity features suggest that conductive pathways exist where major or multiple faults are present. These interpretations provide support for continued exploration in the Midlands of Tasmania for a variety of resources related to crustal fluids and fracturing. [ABSTRACT FROM AUTHOR]

Medication-related osteonecrosis of the jaw (MRONJ) is an adverse reaction caused by the use of antiresorptive antiangiogenic medication. The most commonly affected areas are posterior regions of mandible and maxilla. However, a simultaneous occurrence in both jaws is rarely observed. We present an interesting case of MRONJ affecting both jaws. A 47-year-old female presented with pain and swelling in the left posterior region of the mandible. The patient’s medical history was significant for breast cancer with ongoing bisphosphonate therapy. Cone-beam computerized tomography (CBCT) confirmed the presence of an extraction socket at the site of complaint. There was evidence of a diffuse sclerotic bone reaction in the maxillary posterior region bilaterally. The mandible showed presence of diffuse sclerotic bone only in the left para-symphysis and posterior region in addition to association with a periosteal bone reaction in the left para-symphysis region. Considering these findings and a history of exposure to bisphosphonate medication, the final diagnosis was conclusive of MRONJ. Management was aimed at suppressing the symptoms of pain and infection. The present case study reinforces the importance of correlating clinical and radiographic findings. Early diagnosis of MRONJ may lead to a more conservative treatment approach, greatly improving the patient’s prognosis. [ABSTRACT FROM AUTHOR]

Early stage technology startups rely critically on talented scientists and engineers to commercialize new technologies. And yet these startups compete with established technology firms to hire the best workers. Theories of ability sorting predict that high-ability workers will choose jobs in established firms that offer greater complementary assets and higher pay, leaving low-ability workers to take lower paying and riskier jobs in startups. We propose an alternative view in which heterogeneity in both worker ability and preferences enable startups to hire talented workers who have a taste for a startup work environment even at lower pay. Using a longitudinal survey that follows 2,394 science and engineering PhDs from graduate school into their first industrial employment, we overcome common empirical challenges by observing ability and stated preferences prior to entry into the labor market. We find that both ability and career preferences strongly predict startup employment with high-ability workers who prefer startup employment being the most likely to work in a startup. We show that this partly reflects dual selection effects whereby worker preferences result in a large pool of startup job applicants and startups make job offers to the most talented workers. Additional analyses confirm that startup employees earn approximately 17% lower pay. This gap is greatest for high-ability workers and persists over workers' early careers, suggesting that they accept a negative compensating differential in exchange for the nonpecuniary benefits of startup employment. Data on job attributes and stated reasons for job choice further support this interpretation. This paper was accepted by Toby Stuart, entrepreneurship and innovation. Funding: This work was supported by the National Science Foundation SciSIP Award [Grant 1262270] and the Ewing Marion Kauffman Foundation (Junior Faculty Fellowship). Supplemental Material: The online appendix and data are available at https://doi.org/10.1287/mnsc.2023.4868. [ABSTRACT FROM AUTHOR]

Titanium has a long history of clinical use, but the naturally forming oxide is not ideal for bacterial resistance. Anodization processes can modify the crystallinity, surface topography, and surface chemistry of titanium oxides. Anatase, rutile, and mixed phase oxides are known to exhibit photocatalytic activity (PCA)-driven bacterial resistance under UVA irradiation. Silver additions are reported to enhance PCA and reduce bacterial attachment. This study investigated the effects of silver-doping additions to three established anodization processes. Silver doping showed no significant influence on oxide crystallinity, surface topography, or surface wettability. Oxides from a sulfuric acid anodization process exhibited significantly enhanced PCA after silver doping, but silver-doped oxides produced from phosphoric-acid-containing electrolytes did not. Staphylococcus aureus attachment was also assessed under dark and UVA-irradiated conditions on each oxide. Each oxide exhibited a photocatalytic antimicrobial effect as indicated by significantly decreased bacterial attachment under UVA irradiation compared to dark conditions. However, only the phosphorus-doped mixed anatase and rutile phase oxide exhibited an additional significant reduction in bacteria attachment under UVA irradiation as a result of silver doping. The antimicrobial success of this oxide was attributed to the combination of the mixed phase oxide and higher silver-doping uptake levels. [ABSTRACT FROM AUTHOR]

Titanium alloys are commonly used for implants, but the naturally forming oxides are bioinert and not ideal for bacterial resistance or osseointegration. Anodization processes are a modification technique that can crystallize the oxides, alter oxide surface topography, and introduce beneficial chemistries. Crystalline titanium oxides are known to exhibit photocatalytic activity (PCA) under UVA light. Anodization was used to create mixed-phase oxides on six titanium alloys including commercially pure titanium (CPTi), Ti-6Al-4V (TAV), Ti-6Al-7Nb (TAN), two forms of Ti-15Mo (TiMo-β and TiMo-αβ), and Ti-35Nb-7Zr-5Ta (TNZT). Combined EDS and XPS analyses showed uptake of the electrolyte and substrate alloying elements into the oxides. The relative oxide PCA was measured using methylene blue degradation assays. CPTi and TAN oxides exhibited increased PCA compared to other alloys. Combined XRD and EBSD oxide phase analyses revealed an unfavorable arrangement of anatase and rutile phases near the outermost surfaces, which may have reduced PCA for other oxides. The relative Staphylococcus aureus attachment to each oxide was also assessed. The CPTi and TiMo-αβ oxides showed significantly reduced S. aureus attachment after 1 h of UVA compared to un-anodized CPTi. Cell culture results verified that the UVA irradiation did not negatively influence the MC3T3-E1 attachment or proliferation on the mixed-phase oxides. [ABSTRACT FROM AUTHOR]

The materials traditionally used for implant applications, such as titanium alloys, cobalt chromium, and zirconium, often require surface modifications to achieve the desired osseointegration. These materials still have the problematic stress-shielding effect. To limit stress shielding, PEEK is the superior alternative to fulfill implant needs. However, the traditional methods of modifying and functionalizing the surface of PEEK are often expensive, time consuming, and are not easily translated into commercialization. Sulfonation is a process, which is dependent on controllable factors. Thus far, no research has been performed to optimize the sulfonation process. Our data suggest that the process factors can be controlled and optimized. Cellular activity was examined on the optimized PEEK surfaces through testing with pre-osteoblast MC3T3-E1 cells through cell viability (MTT assay), cell proliferation (DNA assay), cell differentiation (ALP assay), and cell mineralization (Alizarin red assay). Overall, sulfonated and heat-treated PEEK exhibited a statistically significant increase in DNA content over the course of 21 days, indicating more cell proliferation and viability for that surface. In vitro testing results showed that the optimized sulfonated and heat-treated PEEK exhibited superior cell proliferation and mineralization performance over smooth PEEK and sulfonated-only PEEK. [ABSTRACT FROM AUTHOR]

We utilize play-by-play data from the National Football League to examine coaching decisions on fourth down and how sensitive they are to information on situational success and their competitive environment. Prior fourth down successes and failures within a game influence coaches in a way consistent with the notion that recent information is more salient to these coaches when making decisions and a belief in in-game momentum. Coaches are more sensitive to fourth down failures than successes, and our findings suggest this sensitivity to prior failures leads to suboptimal fourth down decisions later in the game. This finding is generally driven by the behavior of coaches with a background in coaching offense, suggesting the availability heuristic is particularly potent for managers who are more involved and, perhaps, more accountable for the details of fourth down plays. We suspect these patterns are prevalent in a wide range of managerial contexts. [ABSTRACT FROM AUTHOR]

Background Modern sequencing technologies offer extraordinary opportunities for virus discovery and virome analysis. Annotation of viral sequences from metagenomic data requires a complex series of steps to ensure accurate annotation of individual reads and assembled contigs. In addition, varying study designs will require project-specific statistical analyses. Findings Here we introduce Hecatomb, a bioinformatic platform coordinating commonly used tasks required for virome analysis. Hecatomb means "a great sacrifice." In this setting, Hecatomb is "sacrificing" false-positive viral annotations using extensive quality control and tiered-database searches. Hecatomb processes metagenomic data obtained from both short- and long-read sequencing technologies, providing annotations to individual sequences and assembled contigs. Results are provided in commonly used data formats useful for downstream analysis. Here we demonstrate the functionality of Hecatomb through the reanalysis of a primate enteric and a novel coral reef virome. Conclusion Hecatomb provides an integrated platform to manage many commonly used steps for virome characterization, including rigorous quality control, host removal, and both read- and contig-based analysis. Each step is managed using the Snakemake workflow manager with dependency management using Conda. Hecatomb outputs several tables properly formatted for immediate use within popular data analysis and visualization tools, enabling effective data interpretation for a variety of study designs. Hecatomb is hosted on GitHub (github.com/shandley/hecatomb) and is available for installation from Bioconda and PyPI. [ABSTRACT FROM AUTHOR]

Motivation Microbial communities have a profound impact on both human health and various environments. Viruses infecting bacteria, known as bacteriophages or phages, play a key role in modulating bacterial communities within environments. High-quality phage genome sequences are essential for advancing our understanding of phage biology, enabling comparative genomics studies and developing phage-based diagnostic tools. Most available viral identification tools consider individual sequences to determine whether they are of viral origin. As a result of challenges in viral assembly, fragmentation of genomes can occur, and existing tools may recover incomplete genome fragments. Therefore, the identification and characterization of novel phage genomes remain a challenge, leading to the need of improved approaches for phage genome recovery. Results We introduce Phables, a new computational method to resolve phage genomes from fragmented viral metagenome assemblies. Phables identifies phage-like components in the assembly graph, models each component as a flow network, and uses graph algorithms and flow decomposition techniques to identify genomic paths. Experimental results of viral metagenomic samples obtained from different environments show that Phables recovers on average over 49% more high-quality phage genomes compared to existing viral identification tools. Furthermore, Phables can resolve variant phage genomes with over 99% average nucleotide identity, a distinction that existing tools are unable to make. Availability and implementation Phables is available on GitHub at https://github.com/Vini2/phables. [ABSTRACT FROM AUTHOR]

The gut virome is an incredibly complex part of the gut ecosystem. Gut viruses play a role in many disease states, but it is unknown to what extent the gut virome impacts everyday human health. New experimental and bioinformatic approaches are required to address this knowledge gap. Gut virome colonization begins at birth and is considered unique and stable in adulthood. The stable virome is highly specific to each individual and is modulated by varying factors such as age, diet, disease state, and use of antibiotics. The gut virome primarily comprises bacteriophages, predominantly order Crassvirales, also referred to as crAss-like phages, in industrialized populations and other Caudoviricetes (formerly Caudovirales). The stability of the virome's regular constituents is disrupted by disease. Transferring the fecal microbiome, including its viruses, from a healthy individual can restore the functionality of the gut. It can alleviate symptoms of chronic illnesses such as colitis caused by Clostridiodes difficile. Investigation of the virome is a relatively novel field, with new genetic sequences being published at an increasing rate. A large percentage of unknown sequences, termed 'viral dark matter', is one of the significant challenges facing virologists and bioinformaticians. To address this challenge, strategies include mining publicly available viral datasets, untargeted metagenomic approaches, and utilizing cutting-edge bioinformatic tools to quantify and classify viral species. Here, we review the literature surrounding the gut virome, its establishment, its impact on human health, the methods used to investigate it, and the viral dark matter veiling our understanding of the gut virome. [ABSTRACT FROM AUTHOR]

Objective: The goal of this study was to (1) Describe the patient population of a newly implemented addiction medicine consult service (AMCS); (2) Evaluate referrals to community-based addiction support services and acute health service use, over time; (3) Provide lessons learned. Methods: A retrospective observational analysis was conducted at Health Sciences North in Sudbury, Ontario, Canada, with a newly implemented AMCS from November 2018 and July 2021. Data were collected using the hospital's electronic medical records. The outcomes measured included the number of emergency department visits, inpatient admissions, and re-visits over time. An interrupted time-series analysis was performed to measure the effect of AMCS implementation on acute health service use at Health Sciences North. Results: A total of 833 unique patients were assessed through the AMCS. A total of 1,294 referrals were made to community-based addiction support services, with the highest proportion of referrals between August and October 2020. The post-intervention trend for ED visits, ED re-visits, ED length of stay, inpatient visits, re-visits, and inpatient length of stay did not significantly differ from the pre-intervention period. Conclusion: Implementation of an AMCS provides a focused service for patients using with substance use disorders. The service resulted in a high referral rate to community-based addiction support services and limited changes in health service usage. [ABSTRACT FROM AUTHOR]

Titanium anodization has been shown to produce crystalline oxides exhibiting photocatalytic reactions that form reactive oxygen species (ROS) when exposed to UV light. The ROS subsequently attack bacteria cells, and thus reduce bacteria attachment on titanium implant surfaces. Polyaniline (PANI) is a conductive polymer that has shown antibacterial properties when electropolymerized onto titanium. Our research group hypothesized the addition of PANI to crystalline titanium oxide surfaces would increase the available free electrons and thus increase photocatalytic activity (PCA). This research led to the development of a novel single‐step anodization approach for PANI doping crystalline titanium oxide layers. The objective of the present study was to determine the proper aniline electrolyte concentration needed to maximize the PCA and reduce bacterial attachment on the formed oxides. Aniline concentrations up to 1 M were added into a 1 M sulfuric acid electrolyte. The formed oxides exhibited increased PANI surface coverage but decreased anatase and rutile crystalline titanium oxide phase formation with increasing aniline electrolyte concentrations. Despite exhibiting the lowest levels of anatase and rutile formation, the 0.75 M and 1 M aniline oxides with the greatest PANI surface coverage also exhibited the highest PCA levels. 1 M aniline oxides showed significantly higher PCA under UVA irradiation compared to oxides formed from aniline concentrations up to 0.5 M (p < 0.001). 0.75 M aniline oxides exhibited significant reductions in Staphylococcus aureus attachment with or without UVA irradiation compared to control oxides without PANI. MTT and live/dead assays confirmed cytocompatibility and nearly 100% cell viability for the PANI doped oxides. [ABSTRACT FROM AUTHOR]

Interestingly, many existing bioinformatics command line tools are wrappers for a series of other software, but since that is the goal of workflow managers, they can be used instead. Package managers such as Conda and the package installer for Python (pip) will automatically download and install software and represent the easiest avenue for accessing command line applications. Conda and pip are two popular cross-platform package managers used in bioinformatics for command line applications. Rule 8: Include a simple test dataset After installing a new command line tool, users will want a way to quickly and easily verify that a command line tool is working correctly. [Extracted from the article]

Studies of financial markets have shown markets inefficiently underreacting to surprise information, discounting it too heavily in the short term. This paper explores this phenomenon in a new but analogous setting: Major League Baseball. I analyze how surprise information – the deviation between a team's realized win total and the preseason expectations of betting markets – is incorporated into the teams' personnel investments and into betting markets. Using fixed effect panel regressions, I find that higher win totals are associated with increased investment in the following season (as measured by team payroll and investment in free agents) and that, conditional on win totals, underperforming (overperforming) expectations in the prior season is associated with more (less) investment. This is consistent with teams discounting some of the surprise information. The effect is more pronounced for teams near the threshold of a playoff appearance. I find that some discounting is rational since roughly 27% of the gap between realized performance and expected performance does not persist into the following season. I find no evidence that betting markets are inefficient in their incorporation of surprise information. However, estimates suggest that teams significantly underreact to surprise information, an inefficiency analogous to those observed in financial markets. [ABSTRACT FROM AUTHOR]

The epidermal microbiome is a critical element of marine organismal immunity, but the epidermal virome of marine organisms remains largely unexplored. The epidermis of sharks represents a unique viromic ecosystem. Sharks secrete a thin layer of mucus which harbors a diverse microbiome, while their hydrodynamic dermal denticles simultaneously repel environmental microbes. Here, we sampled the virome from the epidermis of three shark species in the family Carcharhinidae: the genetically and morphologically similar Carcharhinus obscurus (n = 6) and Carcharhinus galapagensis (n = 10) and the outgroup Galeocerdo cuvier (n = 15). Virome taxonomy was characterized using shotgun metagenomics and compared with a suite of multivariate analyses. All three sharks retain species-specific but highly similar epidermal viromes dominated by uncharacterized bacteriophages which vary slightly in proportional abundance within and among shark species. Intraspecific variation was lower among C. galapagensis than among C. obscurus and G. cuvier. Using both the annotated and unannotated reads, we were able to determine that the Carcharhinus galapagensis viromes were more similar to that of G. cuvier than they were to that of C. obscurus, suggesting that behavioral niche may be a more prominent driver of virome than host phylogeny. [ABSTRACT FROM AUTHOR]

Titanium alloys provide excellent corrosion resistance and favorable mechanical properties well suited for a variety of biomaterial applications. The native oxide surface on titanium alloys has been shown to be less than ideal and surface modification is often needed. Previously, an optimized anodization process was shown to form a porous phosphorus‐enhanced anatase oxide layer on commercially pure Ti grade 4. The anodized layer was shown to improve osseointegration and to reduce bacteria attachment when photocatalytically activated with UVA preillumination. The primary objective of the present study was to create a similar phosphorus‐enhanced anatase oxide layer on series of titanium alloys including commercially pure Ti grade 4, Ti‐6Al‐7Nb, Ti‐6Al‐4V ELI, alpha + beta Ti‐15Mo, beta Ti‐15Mo, and Ti‐35Nb‐7Zr‐5Ta. Phosphorus‐enhanced anatase oxide layers were formed on each titanium substrate. Anatase formation was shown to generally increase with oxide thickness, except on substrate alloys containing niobium. Phosphorus uptake was shown to be dependent on the titanium alloy chemistry or microstructure. Anodized layers formed on beta‐structured titanium alloys revealed the lowest phosphorus uptake and the most nanosized surface porosity. A methylene blue degradation assay showed anodized layers on commercially pure Ti and both Ti‐15Mo alloys to exhibit the highest levels of photocatalytic activity. Given the range of mechanical properties available with the commercially pure Ti and Ti‐15Mo alloys, the results of this study indicate the benefits of phosphorus‐enhanced anatase oxide coatings may be applicable to a wide variety of biomaterial applications. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii is an opportunistic human pathogen responsible for numerous severe nosocomial infections. Genome analysis on the A. baumannii clinical isolate 04117201 revealed the presence of 13 two-component signal transduction systems (TCS). Of these, we examined the putative TCS named here as StkSR. The stkR response regulator was deleted via homologous recombination and its progeny, ΔstkR, was phenotypically characterized. Antibiogram analyses of ΔstkR cells revealed a two-fold increase in resistance to the clinically relevant polymyxins, colistin and polymyxin B, compared to wildtype. PAGE-separation of silver stained purified lipooligosaccharide isolated from ΔstkR and wildtype cells ruled out the complete loss of lipooligosaccharide as the mechanism of colistin resistance identified for ΔstkR. Hydrophobicity analysis identified a phenotypical change of the bacterial cells when exposed to colistin. Transcriptional profiling revealed a significant up-regulation of the pmrCAB operon in ΔstkR compared to the parent, associating these two TCS and colistin resistance. These results reveal that there are multiple levels of regulation affecting colistin resistance; the suggested 'cross-talk' between the StkSR and PmrAB two-component systems highlights the complexity of these systems. [ABSTRACT FROM AUTHOR]

The global expansion of offshore windfarms (OWF), whilst seen as a tool to combat climate change, can often be of concern to fishing communities already challenged by spatial restrictions. Static gear fisheries, due to their strong fidelity to specific sites, can be particularly affected by spatial conflict with OWF. Here we investigate, using four sampling efforts over a six-year period, the effects of the development of the Westermost Rough OWF (UK) on a commercially important European Lobster (Homarus gammarus) population. A collaborative study was developed and conducted by the local fishery and the developer. A baseline potting survey was conducted ∼ every 4 days over the summer months of 2013 (pre-construction) and post-construction surveys were conducted in 2015, 2017, and 2019. Size, catch, and landings per unit of effort (CPUE & LPUE) of all lobsters were recorded and compared between sites and between years. Size structure and catch rates differed between years, however differences were not observed in comparisons of the windfarm and export cable to their associated control sites within each year, although there were compounding factors associated with the proximity of the control sites to the treatment sites. There was a short-term increase in size and catch rates of lobsters associated with the construction phase of the windfarm site, but this was not observed during the subsequent operational phase surveys. Although the impacts of windfarms on fisheries will vary on a case-by-case basis, this study has implications for the expansion of offshore wind developments on other static gear crustacean fisheries. [ABSTRACT FROM AUTHOR]

Sports franchises often value prior head coaching experience as they evaluate head coaching candidates. This paper empirically tests whether prior head coaching experience affects team performance in the National Football League. Accounting for individual coach effects and other relevant factors, I find that team performance is significantly worse beyond a given coach's initial head coaching spell. These results hold for a variety of outcome measures. While coaches with the lowest levels of success in their initial head coaching spell have the most pronounced negative experience effects, significant negative effects are estimated for coaches at all levels of initial success. One explanation for these results is that human capital acquired through head coaching experience is to a large extent firm specific, so while learning does occur within a given head coaching job, it does not carry over to future coaching spells. This can lead to an erosion of any relative human capital advantage. [ABSTRACT FROM AUTHOR]

Brettanomyces bruxellensis is considered one of the most problematic microbes associated with wine production. Sulfur dioxide is commonly used to inhibit the growth of B. bruxellensis and limit the potential wine spoilage. Brettanomyces bruxellensis wine isolates can grow at higher concentrations of this preservative than isolates from other sources. Thus, it has been suggested that the use of sulfite may have selected for B. bruxellensis strains better adapted to survive in the winemaking environment. We utilized laboratory adaptive evolution to determine the potential for this to occur. Three B. bruxellensis strains, representative of known genetic variation within the species, were subjected to increasing sublethal sulfur dioxide concentrations. Individual clones isolated from evolved populations displayed enhanced sulfite tolerance, ranging from 1.6 to 2.5 times higher than the corresponding parental strains. Whole-genome sequencing of sulfite-tolerant clones derived from two of the parental strains revealed structural variations affecting 270 genes. The region containing the sulfite efflux pump encoding gene, SSU1, showed clear copy number variants in all sequenced clones. Regardless of parental strain genetic background, SSU1 copy number changes were reproducibly associated with one SSU1 haplotype. This work clearly demonstrates adaptive evolution of B. bruxellensis when exposed to sublethal sulfites and suggests that, similar to Saccharomyces cerevisiae wine yeast, the mechanism responsible involves the gene SSU1. The wine spoilage yeast Brettanomyces bruxellensis is usually inhibited by sulfur dioxide during winemaking; however, this yeast has the potential to develop increased tolerance to this preservative. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this work is to create a decision support methodology to predict when patients undergoing radiotherapy treatment for locally advanced lung cancer would potentially benefit from adaptive radiotherapy. The proposed methodology seeks to eliminate the manual subjective review by developing an automated statistical learning model to predict when tumor regression would trigger implementation of adaptive radiotherapy based on quantified anatomic changes observed in individual patients on‐treatment cone beam computed tomographies (CTs). This proposed process seeks to improve the efficacy and efficiency of both the existing manual and automated adaptive review processes for locally advanced stage III lung cancer. Methods: A predictive algorithm was developed as a decision support tool to determine the potential utility of mid‐treatment adaptive radiotherapy based on anatomic changes observed on 1158 daily CBCT images across 43 patients. The anatomic changes on each axial slice within specified regions‐of‐interest were quantified into a single value utilizing imaging similarity criteria comparing the daily CBCT to the initial simulation CT. The range of the quantified metrics for each fraction across all axial slices are reduced to specified quantiles, which are used as the predictive input to train a logistic regression algorithm. A "ground‐truth" of the need for adaptive radiotherapy based on tumor regression was evaluated systematically on each of the daily CBCTs and used as the classifier in the logistic regression algorithm. Accuracy of the predictive model was assessed utilizing both a tenfold cross validation and an independent validation dataset, with the sensitivity, specificity, and fractional accuracy compared to the ground‐truth. Results: The sensitivity and specificity for the individual daily fractions ranged from 87.9%–94.3% and 91.9%‐98.6% for a probability threshold of 0.2–0.5, respectively. The corresponding average treatment fraction difference between the model predictions and assessed ART "ground‐truth" ranged from −2.25 to −0.07 fractions, with the model predictions consistently predicting the potential need for ART earlier in the treatment course. By initially utilizing a lower probability threshold, the higher sensitivity minimizes the chance of false negative by alerting the clinician to review a higher number of questionable cases. Conclusions: The proposed methodology accurately predicted the first fraction at which individual patients may benefit from ART based on quantified anatomic changes observed in the on‐treatment volumetric imaging. The generalizability of the proposed method has potential to expand to additional modes of adaptive radiotherapy for lung cancer patients with observed underlying anatomic changes. [ABSTRACT FROM AUTHOR]

Titanium dioxide (TiO2) has been a key material in a wide range of applications such as catalysis, energy harvesting, and antibacterial surfaces. Typically, different TiO2 phases are first synthesized and then coated onto the test parts. Here, the authors demonstrate a direct method for the formation of TiO2 nanostructures and patterns with rutile, anatase, and mixed phases by a controlled laser-assisted surface modification approach on additive manufacturing titanium parts. A tunable nanosecond fiber laser coupled to a galvo scanner was employed to regulate the laser material for a controlled and localized transformation process in an oxygen environment. The influence of processing conditions such as scanning speed, laser power, laser pulse duration, frequency, and gas flow rate on the selective formation of rutile, anatase, and mixed phases was studied. The structural evolutions and morphology have been investigated using different characterization techniques, including scanning electron microscopy and Raman spectroscopy methods. The main advantage of this laser-assisted process is its ability to create selective TiO2 phases on complex titanium parts such as implants. [ABSTRACT FROM AUTHOR]

A just transition to renewable energy requires accounting for the effects of offshore wind projects (OWPs) on the fishing industry. Research on the interaction of OWPs with coastal communities and fisheries in the United Kingdom and the United States offers insights into minimizing conflict and enhancing constructive engagement between fishers and wind energy developers. Recent innovations include earlier and more meaningful inclusion of fisheries representatives in planning and decisionmaking, involving fisheries liaisons in the process, and conducting more cumulative studies and taking collaborative approaches to considering the effects of OWP on fishing. [ABSTRACT FROM AUTHOR]

Studies have shown ultraviolet-A (UVA) irradiation of crystalline titanium oxides leads to the production of reactive oxygen species (ROS) via a photocatalytic process. The ROS exhibit antimicrobial properties that may be of benefit in preventing bacterial attachment to implant devices. Recent studies have suggested a potential benefit of mixed anatase and rutile oxides and dopants on the photocatalytic properties of titanium oxides. The goal of this work was to compare the photocatalytic activity of different anodized commercially pure titanium grade 4 (CPTi4) surfaces. CPTi4 specimens were anodized in three mixed-acid electrolytes to create crystalline oxide surfaces that were either primarily anatase, primarily rutile, or a combination of anatase and rutile. Additionally, the primarily anatase and combination oxides incorporated some phosphorous from the phosphoric acid component in the electrolyte. The photocatalytic activity of the anodized specimens was measured using both methylene blue (MB) degradation assay and comparing the attachment of S. aureus under irradiation with UVA light of differing intensities (1 mW/cm2, 8 mW/cm2, and 23 mW/cm2). Primarily rutile oxides exhibited significantly higher levels of MB degradation after exposure to 1 mW/cm2 UVA lights. Primarily rutile specimens also had the largest reduction in bacterial attachment followed by the mixed phase specimens and the primarily anatase specimens at 1 mW/cm2 UVA lights. Phosphorous-doped, mixed phase oxides exhibited an accelerated MB degradation response during exposure to 8 mW/cm2 and 23 mW/cm2 UVA lights. All anodized and unanodized CPTi4 groups revealed similar S. aureus attachment at the two higher UVA intensities. Although MB degradation assay and the bacteria attachment assay both confirmed photocatalytic activity of the oxides formed in this study, the results of the MB degradation assay did not accurately predict the oxides performance against S. aureus. [ABSTRACT FROM AUTHOR]

Aureobasidium pullulans is the most abundant and ubiquitous species within the genus and is also considered a core component of the grape juice microflora. So far, a small number of other Aureobasidium species have been reported, that in contrast to A. pullulans , appear far more constrained to specific habitats. It is unknown whether grape juice is a reservoir of novel Aureobasidium species, overlooked in the course of conventional morphological and meta-barcoding analyses. In this study, eight isolates from grape juice taxonomically classified as Aureobasidium through ITS sequencing were subjected to whole-genome phylogenetic, synteny and nucleotide identity analyses, which revealed three isolates to likely represent newly discovered Aureobasidium species. Analyses of ITS and metagenomic sequencing datasets show that these species can be present in grape juice samples from different locations and vintages. Functional annotation revealed the Aureobasidium isolates possess the genetic potential to support growth on the surface of plants and grapes. However, the loss of several genes associated with tolerance to diverse environmental stresses suggest a more constrained ecological range than A. pullulans. [ABSTRACT FROM AUTHOR]

Background: Yeasts of the genus Brettanomyces are of significant interest, both for their capacity to spoil, as well as their potential to positively contribute to different industrial fermentations. However, considerable variance exists in the depth of research and knowledgebase of the five currently known species of Brettanomyces. For instance, Brettanomyces bruxellensis has been heavily studied and many resources are available for this species, whereas Brettanomyces nanus is rarely studied and lacks a publicly available genome assembly altogether. The purpose of this study is to fill this knowledge gap and explore the genomic adaptations that have shaped the evolution of this genus. Results: Strains for each of the five widely accepted species of Brettanomyces (Brettanomyces anomalus, B. bruxellensis, Brettanomyces custersianus, Brettanomyces naardenensis, and B. nanus) were sequenced using a combination of long- and short-read sequencing technologies. Highly contiguous assemblies were produced for each species. Structural differences between the species' genomes were observed with gene expansions in fermentation-relevant genes (particularly in B. bruxellensis and B. nanus) identified. Numerous horizontal gene transfer (HGT) events in all Brettanomyces species', including an HGT event that is probably responsible for allowing B. bruxellensis and B. anomalus to utilize sucrose were also observed. Conclusions: Genomic adaptations and some evidence of domestication that have taken place in Brettanomyces are outlined. These new genome assemblies form a valuable resource for future research in Brettanomyces. [ABSTRACT FROM AUTHOR]

As additive manufacturing advances towards use in structural applications which can also include fatigue-critical parts, the process–structure–property relationships must be fully characterized. Currently, most additive manufactured components go through extensive postprocessing including heat treatment to improve their microstructure and resulting fatigue performance. In this study, the effect of stress relief and solution annealing on the tensile and fatigue performance in force- and strain-controlled conditions was investigated. The results reveal that, while the strain–life fatigue behavior was not significantly affected by heat treatment, stress-relieved specimens showed remarkable enhanced stress–life fatigue resistance. Microstructural analysis suggested that the as-fabricated microstructure was beneficial to enhance the crack initiation resistance by shielding process-induced defects from excessive deformation. However, after solution annealing, the crack initiation mechanism shifted from nucleating at twin and high-angle grain boundaries to defects such as lack of fusion and gas-entrapped pores, negatively affecting the fatigue resistance. [ABSTRACT FROM AUTHOR]

Ground-penetrating radar data acquired in the 2016/17 austral summer on Sørsdal Glacier, East Antarctica, provide evidence for meltwater lenses within porous surface ice that are conceptually similar to firn aquifers observed on the Greenland Ice Sheet and the Arctic and Alpine glaciers. These englacial water bodies are associated with a dry relict surface basin and consistent with perennial drainage into an interconnected englacial drainage system, which may explain a large englacial outburst flood observed in satellite imagery in the early 2016/17 melt season. Our observations indicate the rarely-documented presence of an englacial hydrological system in Antarctica, with implications for the storage and routing of surface meltwater. Future work should ascertain the spatial prevalence of such systems around the Antarctic coastline, and identify the degree of surface runoff redistribution and storage in the near surface, to quantify their impact on surface mass balance. [ABSTRACT FROM AUTHOR]

The limited understanding of additive manufacturing process-structure–property inter-relationships raises some concerns regarding the structural reliability, which limits the adoption of this emerging technology. In this study, laser beam-powder bed fusion is leveraged to fabricate an austenitic stainless steel with a microstructure containing minimal known crack initiation features. Ex-situ microstructural observations of the crack initiation features and mechanisms are carried out for interrupted fatigue tests via electron backscatter diffraction mapping of the micro-cracks. Results show that the additive manufactured stainless steel alloy has improved fatigue resistance compared to its wrought counterpart as a result of the unique microstructural features. Using an experimental ex-situ microstructural investigation, the fatigue resistance of additive manufactured 304L stainless steel was shown to be superior to the wrought counterpart by avoiding the typical failure mechanisms. [ABSTRACT FROM AUTHOR]

Titanium surface modification by anodization has been shown to promote bone formation. However, interactions between anodized layers and bone cells depend upon the anodized layer surface composition and morphology. The present study evaluated the effect of anodized layer phosphorus content, crystallinity, surface porosity, and roughness on the MC3T3-E1 osteoblast response. Commercially pure titanium specimens were anodized in two mixed-acid electrolytes to final forming voltages of 108 V and 180 V. The oxide crystallinity, surface porosity, surface roughness, and elemental composition of each specimen type were determined by X-ray diffraction, scanning electron microscopy, atomic force microscopy, and energy dispersive spectroscopy analyses. Osteoblast-like MC3T3-E1 cell attachment, proliferation, differentiation, and mineralization were assessed using optical and fluorescence microscopy, total protein content, alkaline phosphatase activity, osteocalcin production, and alizarin red assays. Oxide crystallinity and surface roughness increased with anodization forming voltage in each electrolyte. Phosphorus (P) uptake increased with forming voltage in the phosphoric acid containing electrolyte. The total protein assay showed P-incorporated, low surface pore density oxides to exhibit initially delayed proliferation compared to non-P containing high surface pore density oxides. Alkaline phosphatase and osteocalcin assays showed trends of early differentiation and maturation for P-incorporated, low surface pore density oxides compared to non-P containing high surface pore density oxides. Highly crystalline anodized layers were shown to induce enhanced mineralization compared to non-anodized titanium specimens. Overall, the biochemical influence of P-incorporation into the oxide layers showed trends of earlier osteoblast differentiation and maturation. The combination of P-incorporation, an anatase phase oxide, a low surface pore density, and a high surface roughness showed the highest mineralization levels. [ABSTRACT FROM AUTHOR]

Visa policies to retain United States-trained STEM PhDs are of central importance to national innovation and economic competitiveness. There is also growing interest in “startup” visas that stimulate entrepreneurial activity and job creation, particularly in technology sectors. However, there is little understanding of how visa policies might influence foreign PhDs’ employment in technology startups. This study investigates differences between 2,324 foreign and US PhDs from US research universities using a longitudinal survey of individuals’ preferences and characteristics during graduate school and their subsequent employment in a startup or established firm. Among PhDs whose first job is industrial research & development, 15.8% of US PhDs work in a startup compared with 6.8% of foreign PhDs. Foreign PhDs are as likely as US PhDs to apply to and receive offers for startup jobs, but conditional on receiving an offer, they are 56% less likely to work in a startup. This disparity is partially explained by differences in visa sponsorship between startups and established firms and not by foreign PhDs’ preferences for established firm jobs, risk tolerance, or preference for higher pay. Foreign PhDs who first work in an established firm and subsequently receive a green card are more likely to move to a startup than another established firm, suggesting that permanent residency facilitates startup employment. These findings suggest that US visa policies may deter foreign PhDs from working in startups, thereby restricting startups’ access to a large segment of the STEM PhD workforce and impairing startups’ ability to contribute to innovation and economic growth. [ABSTRACT FROM AUTHOR]

Background: Adaptive magnetic resonance imaging‐guided radiation therapy (MRgRT) can escalate dose to tumors while minimizing dose to normal tissue. We evaluated outcomes of inoperable pancreatic cancer patients treated using MRgRT with and without dose escalation. Methods: We reviewed 44 patients with inoperable pancreatic cancer treated with MRgRT. Treatments included conventional fractionation, hypofractionation, and stereotactic body radiation therapy. Patients were stratified into high‐dose (biologically effective dose [BED10] >70) and standard‐dose groups (BED10 ≤70). Overall survival (OS), freedom from local failure (FFLF) and freedom from distant failure (FFDF) were evaluated using Kaplan‐Meier method. Cox regression was performed to identify predictors of OS. Acute gastrointestinal (GI) toxicity was assessed for 6 weeks after completion of RT. Results: Median follow‐up was 17 months. High‐dose patients (n = 24, 55%) had statistically significant improvement in 2‐year OS (49% vs 30%, P = 0.03) and trended towards significance for 2‐year FFLF (77% vs 57%, P = 0.15) compared to standard‐dose patients (n = 20, 45%). FFDF at 18 months in high‐dose vs standard‐dose groups was 24% vs 48%, respectively (P = 0.92). High‐dose radiation (HR: 0.44; 95% confidence interval [CI]: 0.21‐0.94; P = 0.03) and duration of induction chemotherapy (HR: 0.84; 95% CI: 0.72‐0.98; P = 0.03) were significantly correlated with OS on univariate analysis but neither factor was independently predictive on multivariate analysis. Grade 3+ GI toxicity occurred in three patients in the standard‐dose group and did not occur in the high‐dose group. Conclusions: Patients treated with dose‐escalated MRgRT demonstrated improved OS. Prospective evaluation of high‐dose RT regimens with standardized treatment parameters in inoperable pancreatic cancer patients is warranted. [ABSTRACT FROM AUTHOR]

Background: Triple negative breast cancer (TNBC) has worse prognosis than other subtypes of breast cancer, and many patients develop brain metastasis (BM). We developed a simple predictive model to stratify the risk of BM in TNBC patients receiving neo‐adjuvant chemotherapy (NAC), surgery, and radiation therapy (RT). Methods: Patients with TNBC who received NAC, surgery, and RT were included. Cox proportional hazards method was used to evaluate factors associated with BM. Significant factors predictive for BM on multivariate analysis (MVA) were used to develop a risk score. Patients were divided into three risk groups: low, intermediate, and high. A receiver operating characteristic (ROC) curve was drawn to evaluate the value of the risk group in predicting BM. This predictive model was externally validated. Results: A total of 160 patients were included. The median follow‐up was 47.4 months. The median age at diagnosis was 49.9 years. The 2‐year freedom from BM was 90.5%. Persistent lymph node positivity, HR 8.75 (1.76‐43.52, P = 0.01), and lack of downstaging, HR 3.46 (1.03‐11.62, P = 0.04), were significant predictors for BM. The 2‐year rate of BM was 0%, 10.7%, and 30.3% (P < 0.001) in patients belonging to low‐, intermediate‐, and high‐risk groups, respectively. Area under the ROC curve was 0.81 (P < 0.001). This model was externally validated (C‐index = 0.79). Conclusions: Lack of downstaging and persistent lymph node positivity after NAC are associated with development of BM in TNBC. This model can be used by the clinicians to stratify patients into the three risk groups to identify those at increased risk of developing BM and potentially impact surveillance strategies. [ABSTRACT FROM AUTHOR]