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Background Despite disproportionate rates of mental ill-health compared with non-Indigenous populations, few programs have been tailored to the unique health, social, and cultural needs and preferences of young Aboriginal and Torres Strait Islander males. This paper describes the process of culturally adapting the US-based Young Black Men, Masculinities, and Mental Health (YBMen) Project to suit the needs, preferences, culture, and circumstances of Aboriginal and Torres Strait Islander males aged 16–25 years in the Northern Territory, Australia. YBMen is an evidence-based social media-based education and support program designed to promote mental health, expand understandings of gender and cultural identities, and enhance social support in college-aged Black men. Methods Our adaptation followed an Extended Stages of Cultural Adaptation model. First, we established a rationale for adaptation that included assessing the appropriateness of YBMen’s core components for the target population. We then investigated important and appropriate models to underpin the adapted program and conducted a non-linear, iterative process of gathering information from key sources, including young Aboriginal and Torres Strait Islander males, to inform program curriculum and delivery. Results To maintain program fidelity, we retained the core curriculum components of mental health, healthy masculinities, and social connection and kept the small cohort, private social media group delivery but developed two models: ‘online only’ (the original online delivery format) and ‘hybrid in-person/online’ (combining online delivery with weekly in-person group sessions). Adaptations made included using an overarching Aboriginal and Torres Strait Islander social and emotional wellbeing framework and socio-cultural strengths-based approach; inclusion of modules on health and wellbeing, positive Indigenous masculinities, and respectful relationships; use of Indigenous designs and colours; and prominent placement of images of Aboriginal and Torres Strait Islander male sportspeople, musicians, activists, and local role models. Conclusions This process resulted in a culturally responsive mental health, masculinities, and social support health promotion program for young Aboriginal and Torres Strait Islander males. Next steps will involve pilot testing to investigate the adapted program’s acceptability and feasibility and inform further refinement. Keywords: Aboriginal, Torres Strait Islander, Indigenous, Australia, male, cultural adaptation, social media, mental health, masculinities, social support.

Abstract Background Poor sleep quality has been associated with changes in brain volume among veterans, particularly those who have experienced mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD). This study sought to investigate (1) whether poor sleep quality is associated with decreased cortical thickness in Iraq and Afghanistan war veterans, and (2) whether these associations differ topographically depending on the presence or absence of mTBI and PTSD. Methods A sample of 440 post-9/11 era U.S. veterans enrolled in the Translational Research Center for Traumatic Brain Injury and Stress Disorders study at VA Boston, MA from 2010 to 2022 was included in the study. We examined the relationship between sleep quality, as measured by the Pittsburgh Sleep Quality Index (PSQI), and cortical thickness in veterans with mTBI (n = 57), PTSD (n = 110), comorbid mTBI and PTSD (n = 129), and neither PTSD nor mTBI (n = 144). To determine the topographical relationship between subjective sleep quality and cortical thickness in each diagnostic group, we employed a General Linear Model (GLM) at each vertex on the cortical mantle. The extent of topographical overlap between the resulting statistical maps was assessed using Dice coefficients. Results There were no significant associations between PSQI and cortical thickness in the group without PTSD or mTBI (n = 144) or in the PTSD-only group (n = 110). In the mTBI-only group (n = 57), lower sleep quality was significantly associated with reduced thickness bilaterally in frontal, cingulate, and precuneus regions, as well as in the right parietal and temporal regions (β = −0.0137, P

Abstract Retinol is a fat-soluble vitamin that plays an essential role in many biological processes throughout the human lifespan. Here, we perform the largest genome-wide association study (GWAS) of retinol to date in up to 22,274 participants. We identify eight common variant loci associated with retinol, as well as a rare-variant signal. An integrative gene prioritisation pipeline supports novel retinol-associated genes outside of the main retinol transport complex (RBP4:TTR) related to lipid biology, energy homoeostasis, and endocrine signalling. Genetic proxies of circulating retinol were then used to estimate causal relationships with almost 20,000 clinical phenotypes via a phenome-wide Mendelian randomisation study (MR-pheWAS). The MR-pheWAS suggests that retinol may exert causal effects on inflammation, adiposity, ocular measures, the microbiome, and MRI-derived brain phenotypes, amongst several others. Conversely, circulating retinol may be causally influenced by factors including lipids and serum creatinine. Finally, we demonstrate how a retinol polygenic score could identify individuals more likely to fall outside of the normative range of circulating retinol for a given age. In summary, this study provides a comprehensive evaluation of the genetics of circulating retinol, as well as revealing traits which should be prioritised for further investigation with respect to retinol related therapies or nutritional intervention.

Abstract Argyle is the world’s largest source of natural diamonds, yet one of only a few economic deposits hosted in a Paleoproterozoic orogen. The geodynamic triggers responsible for its alkaline ultramafic volcanic host are unknown. Here we show, using U-Pb and (U-Th)/He geochronology of detrital apatite and detrital zircon, and U-Pb dating of hydrothermal titanite, that emplacement of the Argyle lamproite is bracketed between 1311 ± 9 Ma and 1257 ± 15 Ma (2σ), older than previously known. To form the Argyle lamproite diatreme complex, emplacement was likely driven by lithospheric extension related to the breakup of the supercontinent Nuna. Extension facilitated production of low-degree partial melts and their migration through transcrustal corridors in the Paleoproterozoic Halls Creek Orogen, a rheologically-weak rift zone adjacent to the Kimberley Craton. Diamondiferous diatreme emplacement during (super)continental breakup may be prevalent but hitherto under-recognized in rift zones at the edges of ancient continental blocks.

We present a simple and effective method to create highly entangled spin states on a faster timescale than that of the commonly employed one-axis twisting (OAT) model. We demonstrate that by periodically driving the Dicke Hamiltonian at a resonance frequency, the system effectively becomes a two-axis countertwisting Hamiltonian, which is known to quickly create Heisenberg limit scaled entangled states. For these states we show that simple quadrature measurements can saturate the ultimate precision limit for parameter estimation determined by the quantum Cramér-Rao bound. An example experimental realization of the periodically driven scheme is discussed with the potential to quickly generate momentum entanglement in a recently described experimental vertical cavity system. We analyze effects of collective dissipation in this vertical cavity system and find that our squeezing protocol can be more robust than the previous realization of OAT.

Estimating a quantum phase is a necessary task in a wide range of fields of quantum science. To accomplish this task, two well-known methods have been developed in distinct contexts, namely, Ramsey interferometry (RI) in atomic and molecular physics and quantum phase estimation (QPE) in quantum computing. We demonstrate that these canonical examples are instances of a larger class of phase estimation protocols, which we call reductive quantum phase estimation (RQPE) circuits. Here, we present an explicit algorithm that allows one to create an RQPE circuit. This circuit distinguishes an arbitrary set of phases with a smaller number of qubits and unitary applications, thereby solving a general class of quantum hypothesis testing to which RI and QPE belong. We further demonstrate a tradeoff between measurement precision and phase distinguishability, which allows one to tune the circuit to be optimal for a specific application.

Sheep management and production enhancement are difficult for farmers due to the lack of dynamic response and poor welfare of the sheep. Poor welfare needs to be mitigated, and each farm must receive an expert-level assessment of critical importance. To mitigate poor welfare, researchers have conducted machine learning-based studies to automate the sheep health behavior monitoring process instead of using manual assessment. However, failure to recognize some sheep health behaviors degrades the performance of the model. In addition, behavior challenges, parameters, and analysis must be considered when conducting a study based on machine learning. In this paper, we discuss the different challenges: what are the parameters of the sheep health behaviors, and how to analyze the sheep health behaviors for automated machine learning systems to be helpful in the long term? The hypothesis is based on a different review of the literature of precision-based animal welfare monitoring systems with the potential to improve management and production.

Oxidative stress is one of the most important environmental exposures associated with psychiatric disorders, but the underlying molecular mechanisms remain to be elucidated. In a previous study, we observed a substantial alteration of the gene expression landscape in neuron-like cells that were differentiated from SH-SY5Y cells after or during exposure to oxidative stress, with a subset of dysregulated genes being enriched for neurodevelopmental processes. To further explore the regulatory mechanisms that might account for such profound perturbations, we have now applied small RNA-sequencing to investigate changes in the expression of miRNAs. These molecules are known to play crucial roles in brain development and response to stress through their capacity to suppress gene expression and influence complex biological networks. Through these analyses, we observed more than a hundred differentially expressed miRNAs, including 80 previously reported to be dysregulated in psychiatric disorders. The seven most influential miRNAs associated with pre-treatment exposure, including miR-138-5p, miR-96-5p, miR-34c-5p, miR-1287-5p, miR-497-5p, miR-195-5p, and miR-16-5p, supported by at least 10 negatively correlated mRNA connections, formed hubs in the interaction network with 134 genes enriched with neurobiological function, whereas in the co-treatment condition, miRNA-mRNA interaction pairs were enriched in cardiovascular and immunity-related disease ontologies. Interestingly, 12 differentially expressed miRNAs originated from the DLK1-DIO3 location, which encodes a schizophrenia-associated miRNA signature. Collectively, our findings suggest that early exposure to oxidative stress, before and during prenatal neuronal differentiation, might increase the risk of mental illnesses in adulthood by disturbing the expression of miRNAs that regulate neurodevelopmentally significant genes and networks.

The central nervous system (CNS) influences the immune system generally by regulating the systemic concentration of humoral substances (e.g., cortisol and epinephrine), whereas the peripheral nervous system (PNS) communicates specifically with the immune system according to local interactions/connections. An imbalance between the components of the PNS might contribute to pathogenesis and the further development of certain diseases. In this review, we have explored the “thread” (hardwiring) of the connections between the immune system (e.g., primary/secondary/tertiary lymphoid tissues/organs) and PNS (e.g., sensory, sympathetic, parasympathetic, and enteric nervous systems (ENS)) in health and disease in vitro and in vivo. Neuroimmune cell units provide an anatomical and physiological basis for bidirectional crosstalk between the PNS and the immune system in peripheral tissues, including lymphoid tissues and organs. These neuroimmune interactions/modulation studies might greatly contribute to a better understanding of the mechanisms through which the PNS possibly affects cellular and humoral-mediated immune responses or vice versa in health and diseases. Physical, chemical, pharmacological, and other manipulations of these neuroimmune interactions should bring about the development of practical therapeutic applications for certain neurological, neuroimmunological, infectious, inflammatory, and immunological disorders/diseases.

Hydrogen production via methane pyrolysis is projected to have a key role in achieving net zero GHG emission by 2050. Carbon makes up to 75% by mass of the products of methane pyrolysis, indicating the importance of a thorough characterization to find its potential applications. A new approach is methane pyrolysis utilizing microwaves, where the carbon product serves as receptors for the microwave energy. In this method, methane decomposes and forms solid carbon. In this study, we evaluated the morphological and structural features of the produced carbon using SEM, XRD, XPS, Raman spectroscopy, and thermogravimetric analysis. The analysis indicates that the pyrolytic carbon produced through this process is highly pure and exhibits a semi-graphitic structure with localized defects. Additionally, the surface morphology of the carbon material was observed to possess a rough cauliflower-like texture. A thorough characterization of carbon revealed several potential applications, including the utilization of granular carbon in electric arc furnace for steelmaking, the feedstock for graphene production, and serving as an anode material in Na-ion batteries with further optimization of the production process. Safe sequestration of the carbon due to limited demand is feasible as the carbon is pure and oxygen-free, indicating its potential to remain unreacted over a long period after sequestration.

Methane pyrolysis is a widely used technique for producing hydrogen and valuable carbon materials. Among these materials are carbon films, which have a diverse range of properties that make them useful for various applications. This study focuses on synthesizing a new type of carbon film through a microwave-driven methane pyrolysis process. The resulting metallic-like carbon film deposits on a polished quartz substrate and detaches as it thickens. We conducted a thorough characterization of the film's properties, using different techniques to study its surface morphology and structural features. Our findings show that the carbon film has a smooth surface texture and a semi-graphitic internal structure, with 78% of the carbon atoms exhibiting sp2 bonding as revealed by X-ray photoelectron spectroscopy. X-ray diffraction analysis further confirms the presence of microcrystalline carbon fragments within the film. Additionally, conductivity measurements using a conductive-atomic force microscope demonstrate the carbon film's remarkable electrical conductivity, comparable to that of gold and silver metals. The electrochemical measurements indicate that the carbon film's high conductivity and free-standing nature make it a promising candidate for use as a direct active material in sodium-ion batteries. This is because the film does not require binders or conductive agents, which can improve battery performance.

Abstract The application of single-cell RNA sequencing (scRNA-seq) in biomedical research has advanced our understanding of the pathogenesis of disease and provided valuable insights into new diagnostic and therapeutic strategies. With the expansion of capacity for high-throughput scRNA-seq, including clinical samples, the analysis of these huge volumes of data has become a daunting prospect for researchers entering this field. Here, we review the workflow for typical scRNA-seq data analysis, covering raw data processing and quality control, basic data analysis applicable for almost all scRNA-seq data sets, and advanced data analysis that should be tailored to specific scientific questions. While summarizing the current methods for each analysis step, we also provide an online repository of software and wrapped-up scripts to support the implementation. Recommendations and caveats are pointed out for some specific analysis tasks and approaches. We hope this resource will be helpful to researchers engaging with scRNA-seq, in particular for emerging clinical applications.

Abstract Almost half of individuals diagnosed with schizophrenia also present with a substance use disorder, however, little is known about potential molecular mechanisms underlying this comorbidity. We used genetic analyses to enhance our understanding of the molecular overlap between these conditions. Our analyses revealed a positive genetic correlation between schizophrenia and the following dependence phenotypes: alcohol (r g = 0.368, SE = 0.076, P = 1.61 × 10−6), cannabis use disorder (r g = 0.309, SE = 0.033, P = 1.97 × 10−20) and nicotine (r g = 0.117, SE = 0.043, P = 7.0 × 10−3), as well as drinks per week (r g = 0.087, SE = 0.021, P = 6.36 × 10−5), cigarettes per day (r g = 0.11, SE = 0.024, P = 4.93 × 10−6) and life-time cannabis use (r g = 0.234, SE = 0.029, P = 3.74 × 10−15). We further constructed latent causal variable (LCV) models to test for partial genetic causality and found evidence for a potential causal relationship between alcohol dependence and schizophrenia (GCP = 0.6, SE = 0.22, P = 1.6 × 10−3). This putative causal effect with schizophrenia was not seen using a continuous phenotype of drinks consumed per week, suggesting that distinct molecular mechanisms underlying dependence are involved in the relationship between alcohol and schizophrenia. To localise the specific genetic overlap between schizophrenia and substance use disorders (SUDs), we conducted a gene-based and gene-set pairwise meta-analysis between schizophrenia and each of the four individual substance dependence phenotypes in up to 790,806 individuals. These bivariate meta-analyses identified 44 associations not observed in the individual GWAS, including five shared genes that play a key role in early central nervous system development. The results from this study further supports the existence of underlying shared biology that drives the overlap in substance dependence in schizophrenia, including specific biological systems related to metabolism and neuronal function.

Abstract Psychiatric disorders such as schizophrenia are commonly associated with structural brain alterations affecting the cortex. Recent genetic evidence suggests circulating metabolites and other biochemical traits play a causal role in many psychiatric disorders which could be mediated by changes in the cerebral cortex. Here, we leveraged publicly available genome-wide association study data to explore shared genetic architecture and evidence for causal relationships between a panel of 50 biochemical traits and measures of cortical thickness and surface area. Linkage disequilibrium score regression identified 191 genetically correlated biochemical-cortical trait pairings, with consistent representation of blood cell counts and other biomarkers such as C-reactive protein (CRP), haemoglobin and calcium. Spatially organised patterns of genetic correlation were additionally uncovered upon clustering of region-specific correlation profiles. Interestingly, by employing latent causal variable models, we found strong evidence suggesting CRP and vitamin D exert causal effects on region-specific cortical thickness, with univariable and multivariable Mendelian randomization further supporting a negative causal relationship between serum CRP levels and thickness of the lingual region. Our findings suggest a subset of biochemical traits exhibit shared genetic architecture and potentially causal relationships with cortical structure in functionally distinct regions, which may contribute to alteration of cortical structure in psychiatric disorders.

Susceptibility to pneumonia has a genetic component, but specific genes involved remain poorly understood. In this study, genetic signals associated with pneumonia susceptibility are identified, providing information about disease biology and potential targets for treatment.

Fast pyrolysis oil (FPO, also called bio-oil) is a biofuel made from thermal decomposition of renewable or waste biomass. However, the physiochemical properties of FPO have limited its widespread use in combustion applications. In this study, the impacts of FPO upgrading with multi-stage condensation, catalytic pyrolysis with ZSM-5, and ethanol blending were studied through characterization of physiochemical properties and combustion in a swirl burner. A commercially available FPO sample (COMM) and diesel were used to benchmark the upgraded FPO samples. The non-catalytic FPO (NC) sample produced with multi-stage condensation had 9.0wt% less oxygen and an HHV 2.2 MJ/kg higher than COMM. The FPO produced using ZSM-5 catalyst (CAT) had 19.0wt% less oxygen, an HHV greater by 7.4 MJ/kg, and lower viscosity than COMM. The CAT sample also had fewer low-molecular-weight compounds, showing a peak mass loss rate 70 °C higher than NC. The NC and CAT samples were also blended with 10vol% ethanol, which had minor effects on the measured physiochemical properties aside from improving volatility. Combustion was evaluated by measuring unburned hydrocarbon, CO, NOx, and particulate matter exhaust concentrations from a swirl burner as well as through flame visualization. Combustion of neat NC was stable, although compared to COMM, CO was ∼2-times higher and NOx was ∼2-times lower. In contrast, the CAT flame was unstable, resulting in the highest CO concentrations overall. Blending NC and CAT with 10vol% ethanol resulted in lower CO concentrations (NC: 88% less, CAT: 96% less) and higher NOx (NC: 2-times, CAT: 1.4-times) compared to neat FPO. Although catalytic upgrading and multi-stage condensation improved HHV, oxygen content, and viscosity, changes to these properties did not improve combustion performance. Ethanol blending emphasized the outsize role of volatility in improving furnace combustion relative to other measured physiochemical properties as reflected by the improved flame stability and exhaust composition.

Human idiopathic hypercalciuria (IH) is the most common cause of calcium oxalate nephrolithiasis with perturbed calcium metabolism with increased bone resorption and decreased renal calcium reabsorption, which can be phenotype-copied in the genetic hypercalciuric stone-forming (GHS) rat model. We previously demonstrated that high VDR expression plays important roles in the development of hypercalciuria in the GHS rats. However, the underlying mechanism through which VDR impact hypercalciuria development remains to be fully understood. Here, we sought to determine how VDR regulated its target genes that are implicated in calcium homeostasis and potentially hypercalciuria. We found that VDR expression in the GHS rats was elevated in the calcium transporting tissues, as well as in the thymus and prostate, but not in lung, brain, heart, liver and spleen, when compared with control SD rats. Snail expression in the GHS rats was significantly downregulated in kidney, intestine, thymus and testis. Intraperitoneal injection of 1,25(OH)2D3 significantly upregulated the expression of renal calcium sensing receptor (CaSR), intestinal calcium transporters transient receptor potential vanilloid type 6 (TRPV6), and VDR in GHS rats, compared with that in control SD rats. ChIP assays revealed that VDR specifically bound to the proximal promoters of target genes, followed by histone H3 hyperacetylation or hypermethylation. Collectively, our results suggest that elevated VDR expression may contribute to the development of hypercalciuria by sensitizing VDR target genes to 1,25(OH)2D3 through histone modifications at their promoter regions in a genetic hypercalciuric stone-forming (GHS) rat model.

Periosteum is a highly vascularized membrane lining the surface of bones. It plays essential roles in bone repair following injury and reconstruction following invasive surgeries. To broaden the use of periosteum, including for augmenting in vitro bone engineering and/or in vivo bone repair, we have developed an ex vivo perfusion bioreactor system to maintain the cellular viability and metabolism of surgically resected periosteal flaps. Each specimen was placed in a 3D printed bioreactor connected to a peristaltic pump designed for the optimal flow rates of tissue perfusate. Nutrients and oxygen were perfused via the periosteal arteries to mimic physiological conditions. Biochemical assays and histological staining indicate component cell viability after perfusion for almost 4 weeks. Our work provides the proof-of-concept of ex vivo periosteum perfusion for long-term tissue preservation, paving the way for innovative bone engineering approaches that use autotransplanted periosteum to enhance in vivo bone repair.

Elicitation methods are known to influence second language speech production. For teachers and language assessors, awareness of such effects is essential to accurate interpretations of testing outcomes. For speech researchers, understanding why one method gives better performance than another may yield insights into how second-language phonological knowledge is acquired, stored, and retrieved. Given these concerns, this investigation compared L2 vowel intelligibility on two elicitation tasks and determined the degree to which differences generalized across vowels, vowels in context, lexical items, and individual speakers. The dependent variable was the intelligibility of Cantonese speakers' productions of English /i I u ℧/ in varying phonetic environments. In a picture-naming task, the speakers produced responses without an auditory prompt. In a second task–interrupted repetition–they heard exemplars of the same targets without pictures, and repeated each one after counting aloud to 10, a step intended to disrupt their short-term auditory store and therefore prevent simple mimicry. For target words with scores below 80% on picture naming, mean intelligibility was more than 10 points higher on interrupted repetition. However, that difference did not generalize across conditions or across speakers. Thus, although it is technically accurate to say that, on average, interrupted repetition yielded better vowel intelligibility than did picture naming, that observation requires a great deal of qualification, particularly because of individual speaker differences. The outcomes are interpreted in terms of their relevance to language assessment and phonetic learning.

Jordan Murray,1 Kiran Garg,2 Fatema Ghasia3 1Cleveland Clinic Cole Eye Institute, Ophthalmological Research, Cleveland, OH, USA; 2Case Western Reserve University School of Medicine, Cleveland, OH, USA; 3Cleveland Clinic Cole Eye Institute, Department of Ophthalmology, Cleveland, OH, 44195-0001, USACorrespondence: Fatema GhasiaCleveland Clinic Cole Eye Institute, Department of Ophthalmology, 2022, East 105th Street, Cleveland, OH, 44195-0001, USAEmail fatemaghasia@gmail.comPurpose: The aim of the study is to examine the association between amblyopia type and the presence of nystagmus on binocular and monocular functions of the fellow (FE) and amblyopic eye (AE).Methods: We recruited 19 controls and 44 amblyopes (anisometropes=13, strabismic=10, mixed=21). We measured visual, grating, and vernier acuities and high/low spatial frequency (SF) contrast sensitivities in each eye using a staircase method. Stereoacuity was measured with the Titmus fly test. We recorded fixation eye movements (FEM) using high-resolution video-oculography. Subjects were classified as having either no nystagmus (n=18), fusion maldevelopment nystagmus syndrome (FMNS) (n=12), or nystagmus without any structural anomalies that does not meet the criteria for FMNS or infantile nystagmus (n=14).Results: Analysis of visual function by clinical amblyopia type showed that patients with strabismus/mixed amblyopia (F (2,54)=9.5, p< 0.001) were more likely to have poor stereopsis while controlling for AE grating acuity deficit. The FE of patients with anisometropia had greater contrast sensitivity deficits at low (F (2,43)=4.4, p=0.018) and high SF (F (2,42)=10.1, p< 0.001). Analysis of visual function by FEM characteristics (low SF: (F (3,43)=4.3, p=0.010) and high SF: (F (3,42)=7.1, p=0.001) showed that the FE of patients with FMNS had worse low and high SF contrast sensitivities, whereas those without FMNS had greater contrast sensitivity deficits only at high SF compared to controls. Patients with FMNS (F (3,54) = 12.9, p< 0.001) were more likely to have poor stereopsis while controlling for AE grating acuity deficit compared to patients without FMNS. All amblyopic patients had worse high SF contrast sensitivity of the AE irrespective of type or FEM characteristics (Type = F (2,43)=8.8, p=0.001; FEM characteristics= F (3,43)=5.1, p=0.004).Conclusion: The presence of FMNS in patients with strabismic/mixed amblyopia is associated with poor/absent stereopsis. FE deficits vary across amblyopia type. Like FEM abnormalities, visual function deficits are seen in the FE of patients with and without nystagmus.Keywords: amblyopia, fellow eye, contrast sensitivity, fusion maldevelopment nystagmus, stereopsis

Healthspan and healthy aging are areas of research with potential socioeconomic impact. Here, the authors present the Medical Genome Reference Bank (MGRB) which consist of over 4,000 individuals aged 70 years and older without a history of the major age-related diseases and report on results from whole-genome sequencing and association analyses.

Category: Hindfoot Introduction/Purpose: TTC fusions are often performed as a salvage procedure in patient with severe hindfoot arthritis or hindfoot deformity. Comorbidities in this patient collective are frequent, leading to increased risk of postoperative complication. The purpose of this study was to evaluate the surgical outcome regarding union rate, reoperation rate and adverse events using a retrograde hindfoot fusion nail. Methods: Patient records of a single center were retrospectively reviewed in which a retrograde hindfoot fusion nail was utilized for hindfoot fusion between July 1st, 2009 and August 31st, 2018. These records included age, gender, BMI, comorbidities, indications for surgery, non-union, re-operation rates and adverse events related to the surgery. The fusions were performed by 4 fellowship trained foot and ankle surgeons at a tertiary care teaching hospital. 58 cases were identified consecutively, in 51 cases a TTC fusion was performed, in 7 cases a tibiotalar fusion with preexisting talocalcaneal fusion. 22 fusions were arthroscopic and 36 open. The average age of patients was 59 years, the average BMI 29. Main indication for the hindfoot fusion were arthritis (55%) and complex hindfoot deformity (43%). Results: An overall union rate of 89.66% was achieved, 5 non-union tibiotalar and 1 non-union tibiotalar + talocalcaneal was documented. In the group of arthroscopic fusion the non-union rate was 9.09%, in the open group 11.11% respectively. The non- union group included patient with elevated BMI (50%), Diabetes mellitus (33%) and smoking (33%). Adverse events were documented in 21%. The reoperation rate was 17%, mostly due to deep infection or wound complication requiring surgical debridement. No patient in the arthroscopic fusion group needed a reoperation due to deep infection or wound complication, whereas in open surgery this rate was 27.78%. Conclusion: A union rate of 89.66% was achieved using a retrograde hindfoot fusion nail in a high risk patient population for non- union. Arthroscopic preparation of the tibiotalar and the subtalar joint seem to prevent postoperative wound complications.

Category: Ankle; Ankle Arthritis; Arthroscopy Introduction/Purpose: End-stage ankle arthritis has long been managed surgically with open ankle arthrodesis (OAA). More recently, arthroscopic ankle arthrodesis (AAA) is thought to be associated with improved patient-reported outcome measures (PROMs) and fewer complications. The objective of this study was to systematically compare these two approaches in long-term PROMs, major complication rates and survivorship of the ankle fusion. Methods: In this retrospective longitudinal cohort study, all patients with an ankle fusion done at our institution and a minimum two-year follow-up were screened for inclusion. Patients demographics at baseline were collected including: age, gender, BMI, smoking status, diabetes status as well as preoperative ankle arthritis COFAS (Canadian Orthopedic Foot and Ankle Society) type. The following PROMs were completed preoperatively, at 6-months and annually thereafter to five years: AAS, AOS, SF-36, expectation, satisfaction and swelling scores. PROMs were compared at all timepoints using a mixed-effects regression model adjusted for baseline patients' demographics, COFAS type and PROMs. Major postoperative complications and survival analysis/rate of revision of the ankle fusions were also compared. Results: Of 874 patients screened for inclusion, 351 ankle fusions done between 2003 and 2019 were eligible for the study, 223 AAA and 128 OAA. The two groups were similar at baseline with respect to demographics, but COFAS type was higher in the OAA group and AAS and AOS scores were better in the AAA group. At one-year post-operatively, there was a higher mean AAS score in the AAA group, but there were no other differences in outcomes at any other timepoint. Survivorship of the ankle fusion in the arthroscopic group was lower (ie higher rate of revision) due to a higher rate of amputation or fusion. Deep infection and wound complications were more common with OAA and accounted for most ankle fusion revisions in this group. Conclusion: There were no consistent differences in PROMs of patients who underwent AAA versus OAA patients up to five- years postoperatively. Ankle fusions done arthroscopically had a lower survivorship rate compared to those done with the open approach due to a higher rate of major complications. Previously proposed advantages of AAA over OAA may therefore need to re-assessed and weighed against the technical challenges and associated complications of the arthroscopic technique.

Category: Bunion Introduction/Purpose: Hallux valgus can be corrected by a variety of procedures. The Lapidus procedure corrects the first ray position in three planes using a first tarsometatarsal fusion (TMTF) and distal release and realignment. In a single surgeon practice the procedure was performed open until 2017, when burrs became available to perform the procedure percutaneously. This study compares the early radiographic results and complications of the percutaneous procedure with the open procedure. Methods: 47 patients undergoing the percutaneous procedure were compared with 44 patients undergoing the open procedure prior to July 2017. Radiographic measures preoperatively were compared to the postoperative measures for intermetataral angle (IMA), Hallux valgus angle (HVA), foot width (FW), distal metatarsal articular angle (DMMA), sesamoid station, metatarsus adductus angle (MAA), first metatarsal to second metatarsal length, and elevation of the first metatarsal. Early 30 day complications were recorded, as well as repeat surgeries. Demographics: There were 81 female and 10 male patients; The average age was MIS 58+/- 13, open 62+/-13. BMI was 28.4 vs 25.1. 1% of patients had diabetes, and 15% were smokers. Statistical analysis was performed using ANOVA. Because of multiple comparisons p0.005). The change was 9.5 o compared to 12.9 o. HVA in the MIS group went from 34.6 o +/- 9.1 o to 14.5 o +/- 7.9 o (20.1 o change) compared to the open group where HVA went from 40.7 o +/- 10.5 o down to 11.6 o +/- 6.1 o (29.1 o change) (p0.05). The nonunion rate was higher in the open group (0 MIS vs 4). The revision rate for deformity correction was the same in both groups (2 versus 2). Conclusion: In this single surgeon series between the two cohorts the MIS group showed a trend towards less correction than the open group. In particular the correction of the Hallux valgus angle was less. At the current time the distal release and realignment may not be as effective as in the open surgery, so more Aitken osteotomies may be required.However there was a trend for less wound complications and less non unions in the MIS group. The comparison included the initial experience with MIS as so the correction may not be as good as the technique evolves.

Schizophrenia-associated anomalies in gene expression in postmortem brain can be attributed to a combination of genetic and environmental influences. Given the small effect size of common variants, it is likely that we may only see the combined impact of some of these at the pathway level in small postmortem studies. At the gene level, however, there may be more impact from common environmental exposures mediated by influential epigenomic modifiers, such as microRNA (miRNA). We hypothesise that dysregulation of miRNAs and their alteration of gene expression have significant implications in the pathophysiology of schizophrenia. In this study, we integrate changes in cortical gene and miRNA expression to identify regulatory interactions and networks associated with the disorder. Gene expression analysis in post-mortem prefrontal dorsolateral cortex (BA 46) (n = 74 matched pairs of schizophrenia, schizoaffective, and control samples) was integrated with miRNA expression in the same cohort to identify gene–miRNA regulatory networks. A significant gene–miRNA interaction network was identified, including miR-92a, miR-495, and miR-134, which converged with differentially expressed genes in pathways involved in neurodevelopment and oligodendrocyte function. The capacity for miRNA to directly regulate gene expression through respective binding sites in BCL11A, PLP1, and SYT11 was also confirmed to support the biological relevance of this integrated network model. The observations in this study support the hypothesis that miRNA dysregulation is an important factor in the complex pathophysiology of schizophrenia.

Hierarchies of difficulty in second-language (L2) phonology have long played a role in the postulation and evaluation of learning models. In L2 pronunciation teaching, hierarchies are assumed to be helpful in the development of instructional strategies based on anticipated areas of difficulty. This investigation addressed the practicality of defining a pedagogically useful hierarchy of difficulty for English tense and lax close vowels (/i I u ʊ/) produced by Cantonese speakers. Unlike their English counterparts, Cantonese close tense-lax pairs are allophonic variants with [i u] occurring before alveolars and [I ʊ] before velars. Each tense-lax pair represents a “phonemic split” in which members of a single L1 category are realized contrastively in L2. Despite evidence that English tense-lax distinctions are challenging for Cantonese speakers, no previous empirical work has closely considered the problem from the standpoint of vowel intelligibility across multiple phonetic contexts and in different words sharing the same rhyme. In a picture-based word-elicitation task, 18 Cantonese-speaking participants produced 31 high-frequency CV and CVC words. Vowels were evaluated for intelligibility by phonetically-trained judges. A series of mixed-effects binary logistic models were fitted to the scores, with vowel quality, phonetic context (rhyme) and word as factors, and length of Canadian residence and daily use of English as co-variates. As expected, the general hierarchy of difficulty for vowels that emerged (/i/ > /u/ > /ʊ/ > /I/) was complicated by large differences across phonetic contexts. Results were not readily explicable in terms of transfer; moreover, different words with the same rhyme were not produced with equal intelligibility. The most serious modeling complication was the sizeable inter-speaker variability in difficulties, which could not be accounted for by model co-variates. Although some difficulties were roughly systematic at the group level, it is argued that establishing a pedagogically useful hierarchy on such data would prove intractable. Rather, L2 learners might be better served by assessment and instructional targeting of their individual problem areas than by a focus on errors predicted from hierarchies of difficulty.

While there are many demonstrations of self-propelled synthetic particles, there are fewer realisations of multimode swimming for the same particle. Here the authors demonstrate two swimming behaviours in magnetically manipulated microtori and show that these can manipulate other active particles.

Abstract Background Different definitions of constipation have been used to estimate its prevalence in the community but this creates difficulties when comparing results from various studies. This study explores the impact of different definitions on prevalence estimates in the same population and compares the performance of simple definitions with the Rome III criteria. Methods The prevalence of constipation in a large nationally representative sample of community-dwelling adults was estimated using five simple definitions of constipation and compared with definitions based on the Rome III criteria. The sensitivity, specificity, and positive and negative predictive values, were calculated for each definition using the Rome III criteria as the gold standards for chronic and sub-chronic constipation. Results Prevalence estimates for the five simple definitions ranged from 9.4 to 58.9%, while the prevalence estimates using the Rome III criteria were 24.0% (95%CI: 22.1, 25.9) for chronic constipation and 39.6% (95%CI: 37.5, 41.7) for sub-chronic constipation. None of the simple definitions were adequate compared to the Rome III criteria. Self-reported constipation over the past 12 months had the highest sensitivity (91.1%, 95%CI: 88.8, 93.4) and negative predictive value (94.5%, 95%CI: 93.1, 96.1) compared to the Rome III criteria for chronic constipation but an unacceptably low specificity (51.3%, 95%CI: 48.8, 53.8) and positive predictive value (37.1%, 95%CI: 34.4, 39.9). Conclusions The definition used to identify constipation within a population has a considerable impact on the prevalence estimate obtained. Simple definitions, commonly used in research, performed poorly compared with the Rome III criteria. Studies estimating population prevalence of constipation should use definitions based on the Rome criteria where possible.

Shelterbelt agroforestry systems inventory is challenging given their narrow linear feature and extensive distribution. The objective of this study was to evaluate the capability of Sentinel-2A Multispectral Instrument (MSI) and Sentinel-1B Synthetic Aperture Radar (SAR) imagery in (i) delineating shelterbelt tree rows on managed agricultural land in Saskatchewan, Canada, and (ii) detecting shelterbelt removal during the period 2008–2016. Contrast split segmentation for the normalized difference vegetation index and Gaussian filter (line filter) data sets from SAR were used to delineate feature borders. Several feature variables from the spectral bands of MSI were used as inputs for an object-based classification using the random forest classifier. A resulting land cover map, including the linear features of existing shelterbelts, was created with an overall accuracy of 80% and kappa value of 0.69. Shelterbelt change detection analysis using the land cover map (2016) and a legacy shelterbelt inventory map (2008) showed that 354 km of shelterbelts were removed within the study area (1,400 km2), accounting for 29.8% of the total shelterbelt length present in 2008. Our results demonstrated that the combination of Sentinel SAR and MSI imagery can provide sufficient information for mapping future shelterbelt planting, as well as allow the detection of shelterbelt removal.

The combustion performance and pollutant emissions of a pyrolysis bio-oil (also called pyrolysis oil) upgraded with a thermo-catalytic reforming process were investigated experimentally in a micro-gas turbine burner and compared with those of a conventional bio-oil, ethanol (EtOH), and diesel fuel. The upgraded intermediate pyrolysis bio-oil called thermo-catalytic reforming bio-oil (TCRBO) has lower water and oxygen contents, suspended solid particulates, and non-volatile residue, along with higher carbon content, physical and chemical stability, and compatibility with fossil oils compared to the conventional fast pyrolysis bio-oil (FPBO). A stable flame with 100% TCRBO was possible in the present burner, whereas 50% by volume fraction EtOH had to be added to FPBO to improve its ignition and combustion characteristics. The original externally-mixed twin-fluid nozzle of the micro-gas turbine was replaced with an internally-mixed one which exhibited a superior performance with bio-oils. Over the practical range of air-to-liquid mass flow ratio for bio-oils, 0.3

Measures of lung function are heritable, and thus, we sought to utilise genetics to propose drug-repurposing candidates that could improve respiratory outcomes. Lung function measures were found to be genetically correlated with seven druggable biochemical traits, with further evidence of a causal relationship between increased fasting glucose and diminished lung function. Moreover, we developed polygenic scores for lung function specifically within pathways with known drug targets and investigated their relationship with pulmonary phenotypes and gene expression in independent cohorts to prioritise individuals who may benefit from particular drug-repurposing opportunities. A transcriptome-wide association study (TWAS) of lung function was then performed which identified several drug–gene interactions with predicted lung function increasing modes of action. Drugs that regulate blood glucose were uncovered through both polygenic scoring and TWAS methodologies. In summary, we provided genetic justification for a number of novel drug-repurposing opportunities that could improve lung function.

BackgroundPrediction of the dynamics of new SARS-CoV-2 infections during the current COVID-19 pandemic is critical for public health planning of efficient health care allocation and monitoring the effects of policy interventions. We describe a new approach that forecasts the number of incident cases in the near future given past occurrences using only a small number of assumptions.MethodsOur approach to forecasting future COVID-19 cases involves 1) modeling the observed incidence cases using a Poisson distribution for the daily incidence number, and a gamma distribution for the series interval; 2) estimating the effective reproduction number assuming its value stays constant during a short time interval; and 3) drawing future incidence cases from their posterior distributions, assuming that the current transmission rate will stay the same, or change by a certain degree.ResultsWe apply our method to predicting the number of new COVID-19 cases in a single state in the U.S. and for a subset of counties within the state to demonstrate the utility of this method at varying scales of prediction. Our method produces reasonably accurate results when the effective reproduction number is distributed similarly in the future as in the past. Large deviations from the predicted results can imply that a change in policy or some other factors have occurred that have dramatically altered the disease transmission over time.ConclusionWe presented a modelling approach that we believe can be easily adopted by others, and immediately useful for local or state planning.

Evidence exists for the use of high-flow nasal oxygen (HFNO) in the general critical care population for acute hypoxemic respiratory failure. There is discord between guidelines for hypoxemia management in COVID-19. Both noninvasive management and intubation present risk to patients and staff and potentially overwhelm hospital mechanical ventilator capacity. The use of HFNO has been particularly controversial in the UK, with oxygen infrastructure failure. We discuss our experience of managing COVID-19 with HFNO and awake self-prone positioning. We focus upon the less-usual case of an eighteen-year-old female to illustrate the type of patient where HFNO may be used when perhaps earlier intubation once was. It is important to consider the wider implications of intubation. We have used HFNO as a bridge to intubation or as definitive management. As we await clinical trial evidence, HFNO with self-prone positioning has a role in COVID-19 for certain patients. Response parameters must be set and reviewed, oxygen infrastructure considered, and potential staff droplet exposure minimised.

In the field of light-matter interactions, it is often assumed that a classical light field that interacts with a quantum particle remains almost unchanged and thus contains nearly no information about the manipulated particles. To investigate the validity of this assumption, we develop and theoretically analyze a simple Gedanken experiment, which involves the interaction of a coherent state with a quantum particle in an optical cavity. We quantify the resulting alteration of the light field by calculating the fidelity of its initial and equilibrium states. Using Bayesian inference, we demonstrate the information transfer through photon statistics. In addition, we employ the concepts of quantum entropy and mutual information to quantify the entropy transfer from the particle to the light field. In the weak coupling limit, we validate the usually assumed negligible alteration of the light field and entropy transfer. In the strong coupling limit, however, we observe that the information of the initial particle state can be fully encoded in the light field, even for large photon numbers. Nevertheless, we show that spontaneous emission is a sufficient mechanism for removing the entropy initially stored in the particle. Our analysis provides a deeper understanding of the entropy exchange between quantum matter and classical light.

Category: Ankle; Ankle Arthritis Introduction/Purpose: To understand the role of total ankle replacement (TAR) in treating the spectrum of arthritis of the ankle, a clear understanding of the epidemiology of ankle arthritis is required. The largest pools of epidemiologic data available to date come from international registries. In the USA, the largest market for TAR, where an estimated 10,000 TARs are implanted per year, the largest pool of demographic data on patients undergoing TAR is comprised of just 805 cases collected over 6 years. With the advent of patient-specific instrumentation (PSI), detailed demographic and CT scan data can now be collected. These data on 21,222 cases undergoing CT scan-based PSI planning were reviewed to define the demographics of a very large cohort of TAR patients. Methods: The cohort contained 21,222 patients from the USA and Canada, with surgery dates from 2012 - 2019. Data analysed included deformity measures, presence of existing hardware and joint fusion status. To date, a subset sample of 4800 cases was available for analysis. Extraction is ongoing and data for the full cohort will soon be available. This subset described cases with surgery dates ranging from November 2015 through May 2019. Summary statistics to describe age, gender, ankle size, and tibio- talar deformity were calculated. Of the 4800 patients analyzed, 53% were male. Mean age 63.6 years (SD 10.4) (Age distribution in Figure 1a). The deformity distribution is shown in Figure 1b, with varus more common than valgus. The mean degree of deformity increased with every decade of patient age from 6.1° (age 30-39) to 9.2° (age 80-89), and over time from 9.3°(2016) to 11.8° (2019) [in stemmed- implant cases]. Results: Tibia size varied with gender. Females ranged between 34-38mm in 85% of cases; males from 41-48mm in 79%. Of 21,222 cases, 5964 (28%) had adjacent hardware (screws, etc) in situ and pre-existing ankle fusions were present in 517 (2.4%), increasing from 1.2% in 2013 to 2.9% in 2019.The mean age of TAR patients is similar to that reported in smaller series. Tibia size was significantly greater in males than females, a finding not previously reported in demographic literature. In contrast to knee arthritis, intra-articular deformity >5° is common, present in > 51% of cases (varus > valgus). This is the first series to show the degree of deformity increases with age. Over time, TAR is being used in cases with greater deformity. Conclusion: Hardware is seen to be commonly present in TAR, increasing complexity. Conversion of fusion to TAR, while rare, is more common than existing literature suggests, with the rate increasing each year, suggesting this may be an increasingly important role for TAR in the future. This study presents the largest set of demographic data on TAR patients in the literature. The demographics of USA patients undergoing TAR are similar to those seen in non-USA registries. Deformity is common, increasing with age. The severity of deformity treated with TAR and conversion of fusion to TAR are increasing over time.

A common limitation of neuroimaging studies is their small sample sizes. To overcome this hurdle, the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium combines neuroimaging data from many institutions worldwide. However, this introduces heterogeneity due to different scanning devices and sequences. ENIGMA projects commonly address this heterogeneity with random-effects meta-analysis or mixed-effects mega-analysis. Here we tested whether the batch adjustment method, ComBat, can further reduce site-related heterogeneity and thus increase statistical power. We conducted random-effects meta-analyses, mixed-effects mega-analyses and ComBat mega-analyses to compare cortical thickness, surface area and subcortical volumes between 2897 individuals with a diagnosis of schizophrenia and 3141 healthy controls from 33 sites. Specifically, we compared the imaging data between individuals with schizophrenia and healthy controls, covarying for age and sex. The use of ComBat substantially increased the statistical significance of the findings as compared to random-effects meta-analyses. The findings were more similar when comparing ComBat with mixed-effects mega-analysis, although ComBat still slightly increased the statistical significance. ComBat also showed increased statistical power when we repeated the analyses with fewer sites. Results were nearly identical when we applied the ComBat harmonization separately for cortical thickness, cortical surface area and subcortical volumes. Therefore, we recommend applying the ComBat function to attenuate potential effects of site in ENIGMA projects and other multi-site structural imaging work. We provide easy-to-use functions in R that work even if imaging data are partially missing in some brain regions, and they can be trained with one data set and then applied to another (a requirement for some analyses such as machine learning).

ABSTRACT To study human idiopathic hypercalciuria (IH), we developed an animal model, genetic hypercalciuric stone‐forming (GHS) rats, whose pathophysiology parallels that in IH. All GHS rats form kidney stones and have decreased BMD and bone quality compared with the founder Sprague–Dawley (SD) rats. To understand the bone defect, we characterized osteoclast and osteoblast activity in the GHS compared with SD rats. Bone marrow cells were isolated from femurs of GHS and SD rats and cultured to optimize differentiation into osteoclasts or osteoblasts. Osteoclasts were stained for TRAcP (tartrate resistant acid phosphatase), cultured to assess resorptive activity, and analyzed for specific gene expression. Marrow stromal cells or primary neonatal calvarial cells were differentiated to osteoblasts, and osteoblastic gene expression as well as mineralization was analyzed. There was increased osteoclastogenesis and increased resorption pit formation in GHS compared with SD cultures. Osteoclasts had increased expression of cathepsin K, Tracp, and MMP9 in cells from GHS compared with SD rats. Osteoblastic gene expression and mineralization was significantly decreased. Thus, alterations in baseline activity of both osteoclasts and osteoblasts in GHS rats, led to decreased BMD and bone quality, perhaps because of their known increase in vitamin D receptors. Better understanding of the role of GHS bone cells in decreased BMD and quality may provide new strategies to mitigate the low BMD and increased fracture risk found in patients with IH. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Abstract Background Adapting promising health care interventions to local settings is a critical component in the dissemination and implementation process. The Veterans Health Administration (VHA) rural transitions nurse program (TNP) is a nurse-led, Veteran-centered intervention designed to improve transitional care for rural Veterans funded by VA national offices for dissemination to other VA sites serving a predominantly rural Veteran population. Here, we describe our novel approach to the implementation and evaluation = the TNP. Methods This is a controlled before and after study that assesses both implementation and intervention outcomes. During pre-implementation, we assessed site context using a mixed method approach with data from diverse sources including facility-level quantitative data, key informant and Veteran interviews, observations of the discharge process, and a group brainstorming activity. We used the Practical Robust Implementation and Sustainability Model (PRISM) to inform our inquiries, to integrate data from all sources, and to identify factors that may affect implementation. In the implementation phase, we will use internal and external facilitation, paired with audit and feedback, to encourage appropriate contextual adaptations. We will use a modified Stirman framework to document adaptations. During the evaluation phase, we will measure intervention and implementation outcomes at each site using the RE-AIM framework (Reach, Effectiveness, Adoption, Implementation, and Maintenance). We will conduct a difference-in-differences analysis with propensity-matched Veterans and VA facilities as a control. Our primary intervention outcome is 30-day readmission and Emergency Department visit rates. We will use our findings to develop an implementation toolkit that will inform the larger scale-up of the TNP across the VA. Discussion The use of PRISM to inform pre-implementation evaluation and synthesize data from multiple sources, coupled with internal and external facilitation, is a novel approach to engaging sites in adapting interventions while promoting fidelity to the intervention. Our application of PRISM to pre-implementation and midline evaluation, as well as documentation of adaptations, provides an opportunity to identify and address contextual factors that may impede or enhance implementation and sustainability of health interventions and inform dissemination.

Category: Ankle, Ankle Arthritis, Hindfoot, Midfoot/Forefoot Introduction/Purpose: Bone graft and bone graft substitutes may affect fusion rates and have been advocated to reduce the risk of nonunion particularly in patients with risk factors for failure of fusion. However historically they have not been used in all patients but tend to be used in patients at risk for nonunion. This paper analyses the union rates of patients with and without graft for a large retrospective cohort in which no graft, autograft and bone graft substitute, and summarizes the risk factors for nonunion. Methods: 2301 fusions performed in 1320 patients were reviewed with a minimum of 2 years follow up to determine the risk of repeat surgery for nonunion. The records were reviewed to determine which patients underwent revision surgery of the primary site for nonunion. Demographic factors and risk factors for nonunion were recorded. The nonunion rate for each joint (ankle, subtalar, talonavicular, calcaneocuboid, navicular cuneiform and tarsometatarsal joints) was determined. The mean age of the patients was 56, BMI 27.83, 32% were male, diabetes was present in 8.9%, smoking present in 10.9%, rheumatoid arthritis present in 10%. No graft was used in 1249 fusions, Autograft in 644, PDGF with TCP (regular) in 113, and PDGF injectable (TCP and collagen) formula in 110. Combinations were used in 159 patients. Odds ratios were used with 95% confidence intervals and p values. Results: No graft was used in 1249 fusions with 34 revisions for nonunion (2.7%) and graft was used in 1052 patients with 59 non unions (5.6%). The odds ratio for nonunion with graft was 2.2x, and was not significant. The odds ratio for PDGF with TCP for nonunion was higher than the PDGF injection, at 5 x versus 1 x. However the difference was not significant. The demographics of patients receiving graft were different than those not receiving graft, and were more likely to be older, male, have a higher BMI, be smokers and have diabetes. The appended figure shows the odds ratios for risk factors for receiving graft. Conclusion: Bone graft substitute and bone grafts result in a similar union rate for patients undergoing foot and ankle fusions. However patients receiving graft have higher risk factors for nonunion compared to those not receiving graft. This paper demonstrates that the concept of using graft for at risk patients is merited, with similar fusion rates being achieved. Larger patient numbers would be required to reach statistical conclusions.

Category: Ankle, Ankle Arthritis Introduction/Purpose: Recent advances in arthroplasty for the hip and the knee have motivated modern foot and ankle research to perfect the implant and technique for the optimal total ankle replacement. Unlike in the hip where different approaches can be done with the same implants, the approach of a total ankle is intimately associated to the prosthetic design. The anterior and lateral approaches have pros and cons regarding their respective soft tissue complications, osteotomy necessity, orientation of the bone cut and gutter visualization. While both have been studied independently, very few reports have compared both in the same setting. We set out to quantify the PROs and re-operations of both groups. Methods: A prospective study was conducted from a single center between 2014 and 2018 including a total of 64 total ankles performed by one of four fellowship-trained foot and ankle surgeon. A baseline dataset of their demographic as well as baseline scores (AOS, AAS & SF-36) was documented as well as at the 6 months and yearly mark post-operatively. Re-operations were also reported and coded in the local database. The approach was determined by the surgeon’s practice preference and patients were referred to surgeons as part of a central intake. Patients were included when they had a primary TAR in the timeframe noted and had a complete dataset up to at least the one year outcome. This cohort comprised 27 anterior and 37 lateral with balanced demographic for age (95%CI 63-67 yo) and gender (47% F). The lateral group had higher COFAS type arthritis, longer intraoperative time and adjunct procedures. Results: Comparing the two groups, it was noted that the anterior group had superior SF-36 scores at the one-year post- operative mark on both the physical and mental components. The difference was statistically significant and greater than the MCID. Otherwise, the two groups had similar AOS and AAS post-operative scores that were not statistically different. A total of 8 patients had a reoperation, 7 were from the lateral cohort and 1 from the anterior approach group. The lateral group had 3 surgical debridement for deep infection/wound complication, 2 ankle gutter/HO debridement and 2 lateral hardware removal. The anterior group had one ankle gutter/ HO debridement. Two of the above patients had two re-operations and one had three. Conclusion: This prospective pilot study outlines the early results of lateral versus anterior total ankle replacements. The risk of deep infection requiring reoperation was higher in the lateral group and the SF-36 scores one year after surgery were inferior to the anterior group. The lateral cohort had however significantly more pre-operative peritalar disease which was not balanced and likely affected those results. Patient experience based on PROs (AAS, AOS) otherwise is comparable. Future studies with longer prospective data need to be considered to have the power to draw significant conclusions.

Category: Ankle, Ankle Arthritis Introduction/Purpose: Ankle replacements (TAR) have evolved significantly over the past 10 years. While most TAR systems reference the medial gutter to set axial tibial component rotation, newer CT scan-based patient specific instrumentation (PSI) allows any rotational position to be set, and this is commonly set to bisect the medial and lateral gutter lines. It is still not yet known which alignment technique is optimal. Methods: We initiated a prospective cohort analysis of 22 consecutive cases using the Prophecy® 3D PSI guide (Wright Medical Technologies, Memphis, TN). There were four foot and ankle fellowship trained surgeons practicing from two referral centers. Every procedure had an intra-operative photograph taken from the knee looking down to the ankle after both the attachment of the PSI guide to the tibia and the insertion of the standard medial gutter fork. The axial rotational angle between both was measured and compared to the Prophecy® pre-operative plan. Statistical analysis was performed using the student’s T-test for paired distribution and descriptive statistics given the number of cases (N=22). Results: The primary outcome of this study was to assess the correlation between the pre-operative medial gutter line drawn on the Prophecy plan and the intra-operative medial gutter fork angle. The Pearson R correlation value was 0.54 (p = 0.53). The average difference between the pre-operative medial gutter line on the Prophecy® plan and the intra-operative gutter fork was -0.46 [95% CI -2.04 – 1.10]. This could mean that the medial gutter fork is on average slightly more internally rotated than templated medial gutter line. However, the average of the absolute differences between the preoperative medial gutter line and the intraoperative medial gutter fork was 2.69 degrees. Of the 22 cases, 11 were within 2 degrees and 17 were within 4 degrees. Conclusion: The medial gutter line on Prophecy® PSI pre-operative TAR plans is a moderately good representation of the intra- operative medial gutter fork position used in standard TAR instrumentation. Based on this, using the Prophecy® default which sets the tibial implant axial rotation to bisect the medial and lateral gutter lines will typically lead to greater external rotation of the tibial component compared to standard TAR instrumentation which aligns the tibial component to the medial gutter fork. Further work needs to be done to better understand which of these axial alignment options, or potentially others, is optimal.

Category: Ankle Introduction/Purpose: Patients perspective and experience is heavily modulated by their understanding of their pre-operative disability along with their overall coping strategy and life philosophy. It is well appreciated that patient’s catastrophization and emphasis on outcomes can affect their outcome. Given that we are relying on patient-reported outcomes more and more, the orthopedic community must be diligent in differencing patients that may have the same objective outcome vary widely on a patient-centered subjective basis. Catastrophization has been reported to affect outcomes in the arthroplasty litterature and this was the first study to look at its effect in the foot and ankle world. Methods: This current study set out to look at a cohort of complex consecutive foot and ankle cases and describe the relationship between Patient Catastrophizing Score (PCS) and multiple functional outcomes that are used routinely. The PCS has three subcategory rumination, helplessness and magnification. In the end, 46 patients were found to be eligible in the study with an average age of 54.72 ± 14.41 years-old, a majority female 30 / 46 (65.22%), a minority employed at the pre-operative visit 19/46 (41%) and with an average BMI of 26.2 ± 5.56. We used univariate and multivariate regression analysis for further statistical analysis. Results: We found that the mental component of the SF12 had a statistically significant negative effect with the rumination score (-1.03) and the helplessness score (-1.05). There was no statistically significant effect for the physical component of the SF-12. Looking at the FAOS Pain component, it correlated with the PCS rumination and helplessness. Otherwise the FAOS ADL component showed correlation as well with the PCS rumination (M -4.67 (p=0.02) U: -1.85 (0.01)), helplessness (M -5.89 (p = 0.01) U -1.81 (p = 0.001)) and total score (M: 3.74 (p=0.02) U -0.75 (p=0.01)). The FAOS Quality of life component was statistically significant for the rumination score (-11.59) (p > 0.05) and the helplessness score (-9.65) (p = 0.002) also the PCS total (8.54). Conclusion: This study confirms that post-operative patient reported outcome (SF- 12MCS, FAOS) are affected by pre-operative catastrophization scores. This has extensive implications in the patient selection, counselling and tailoring of surgeries offered to patients. This is also a symbolic finding highlighting that certain outcomes measure need to be adjusted or updated. This was a pilot study to capture the initial trend and within the limits of our methodology we would recommend future larger study trials and careful pre-operative selection based on PCS scores.

Category: Ankle, Ankle Arthritis, Hindfoot, Midfoot/Forefoot Introduction/Purpose: Nonunion after fusion results in ongoing pain and a request for repeat surgery in many patients. Nonunion is therefore a failure of the primary surgery. Patients undergoing fusion surgery need to understand the risk for nonunion and the risk for repeat surgery. This is a review of fusions performed at a single institution by 4 foot and ankle surgeons to outline the nonunion rate after foot and ankle fusion for different joints. Methods: Data on fusions performed between January 1, 2010 to July 31, 2006 were retrospectively extracted from database. The records were reviewed to determine the union status of each fusion. Demographic and clinic risk factors of nonunion were recorded. The nonunion rate for each joint (ankle, subtalar, talonavicular, calcaneocuboid, navicular cuneiform, tarsometatarsal and metatssophalengeal joints) was estimated. Due to multiple surgeries performed on individual patient and fusions in the same surgery, random effects logistic regression models were conducted to assess the impact of risk factor on nonunion. The study include 2301 fusions preformed on 1320 patients. The minimum follow up was two years. The majority of patients were female (70%), with mean age of 57 years old and mean body mass index (BMI) of 28. There were 9% of patients with diabetes, 11% being smokers, 18% having lung disease, 8% with renal disease, and 29% with high blood pressure. Results: The risk of nonunion by joint is outlined in figure 1. The ankle showed the highest nonunion rate at 8%, and the calcaneocuboid joint had the lowest rate at 2%. Comparing to ankle, the nonunion rate was significantly lower at Talocalcaneal (Subtalar) joint (Odd ratio [OR]=0.05, p-value= 0.02) and Tarsometatarsal (OR=0.03, p-value=0.01). Across all joints the nonunion rate was higher in males, smokers, having a higher BMI and diabetes Age had a minimal effect. Conclusion: Union rate varied among fusion sites. Patient’s demographic and clinic characteristics might be potential risk factors for nonunion. This paper assists surgeons in determining the risk factors for nonunion after foot and ankle fusions. The ankle joint is at highest risk for nonunion, and the tarsometatarsal joint and the subtalar joints the lowest risk.

Colonies of the opportunistic pathogen Proteus mirabilis can distinguish self from non-self: in swarming colonies of two different strains, one strain excludes the other from the expanding colony edge. Predominant models characterize bacterial kin discrimination as immediate antagonism towards non-kin cells, typically through delivery of toxin effector molecules from one cell into its neighbor. Upon effector delivery, receiving cells must either neutralize it by presenting a cognate anti-toxin as would a clonal sibling, or suffer cell death or irreversible growth inhibition as would a non-kin cell. Here we expand this paradigm to explain the non-lethal Ids self-recognition system, which stops access to a social behavior in P. mirabilis by selectively and transiently inducing non-self cells into a growth-arrested lifestyle incompatible with cooperative swarming. This state is characterized by reduced expression of genes associated with protein synthesis, virulence, and motility, and also causes non-self cells to tolerate previously lethal concentrations of antibiotics. We show that temporary activation of the stringent response is necessary for entry into this state, ultimately resulting in the iterative exclusion of non-self cells as a swarm colony migrates outwards. These data clarify the intricate connection between non-lethal recognition and the lifecycle of P. mirabilis swarm colonies.

Oleanolic acid (OA) and ursolic acid (UA) are the major chemical constituents in Fructus Ligustri Lucidi (FLL), a kidney-tonifying Chinese herb that is previously shown to improve bone properties and enhance calcium balance in aged female rats. The present study was designed to study if OA and UA act as the active ingredients in FLL to exert the positive effects on bone and mineral metabolism in aged rats. Aged (13-month-old) Sprague-Dawley female rats were randomly assigned to four groups with oral administration of drug or vehicle treatment for 12 weeks: medium calcium diet (MCD, 0.6% calcium), high calcium diet (HCD, 1.2% calcium), MCD + FLL (700 mg/kg/day), MCD + OA (23.6 mg/kg/day) + UA (8.6 mg/kg/day). A group of mature (3-month-old) female rats fed with MCD was included as positive control. The results demonstrated that FLL and OA+UA increased bone mineral density and improved microarchitectural properties of aged female rats. The osteoprotective effects of FLL and OA+UA might be, at least in part, associated with their actions on enhancing calcium balance and suppressing age-induced secondary hyperparathyroidism in aged female rats. FLL and OA+UA also significantly induced renal CYP27B1 protein expression and OA+UA treatment decreased CYP24A1 mRNA and protein expressions in aged female rats. In addition, FLL and OA+UA significantly increased the promoter activity, mRNA and protein expressions of renal CYP27B1 in vitro in human proximal tubule HKC-8 cells. The present findings suggest that OA+UA can be regarded as the active ingredients of FLL and might be a potential drug candidate for prevention and treatment of osteoporosis.