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Spatial maps of the air and ground thermal regime were generated for four Yukon valleys. The aim was to model air, ground surface, and ground temperature (at fine spatial resolution) using locally measured inverted surface lapse rates (SLR) to better predict temperature along an elevation gradient. These local models were then compared to a regional permafrost probability model, which utilized differing inversion assumptions, as well as circumpolar and national models generated without considering inversions. Overall, permafrost probability in the regional model matched well with the local models where assumptions of treeline and inverted SLRs held true. When normal SLRs were assumed, permafrost presence was overestimated in each valley. This discrepancy was greatest at high elevations where permafrost was predicted to be the coldest and most widespread. However, the difference between valleys was dependent on surface and subsurface characteristics such as higher snow cover, mature forest, or thick organic layers which show a greater disassociation from the air temperature overall. Appropriate characterization of the SLR is essential for accurate predictions of the ground thermal regime’s spatial distribution and permafrost presence. These models also provide a starting point for better predictions of warming in these valleys and other areas subject to inversions of similar magnitudes.

Permafrost landscapes are becoming increasingly susceptible to widespread thaw due to climate change. Collating historical and ongoing data are critical for assessing permafrost conditions and spatiotemporal changes. Electrical resistivity tomography (ERT) is a geophysical technique that has become standard practice for characterizing permafrost. However, resistivity data—particularly raw measurements—often go unpublished and unshared, resulting in missed opportunities for knowledge exchange and collaboration. To fill this gap, we created the Canadian Permafrost Electrical Resistivity Survey database and established clear guidelines for data archival and reuse. Here, we present the first release of the database, which currently houses 280 ERT datasets, including standardized metadata, collected between 2008 and 2022 in British Columbia, Labrador, Northwest Territories, Québec, Yukon, and Alaska. These data present unique opportunities to better understand spatial and temporal variability of permafrost conditions across North America.

Rock glaciers have been the subject of extensive research in recent years due to their potential to serve as indicators of past and present climate conditions and their potential impacts on water resources. Location and descriptive rock glacier data within the Mackenzie Mountains were used to build a rock glacier inventory that will serve as a valuable resource for future research and monitoring efforts. Additionally, this study maps the likelihood of rock glacier presence using extracted variables in a generalized additive model (GAM). The model incorporates attribute data, including potential incoming solar radiation (PISR), topographic position index (TPI), slope, elevation, and lithology as controls for rock glacier development. Topographic data were compiled for three study regions of the Mackenzie Mountains from a 30 m digital elevation model (DEM). The analysis of the GAM showed that the most significant explanatory variables were PISR, elevation, slope, and TPI. The GAM model had an accuracy of 0.87 with a sensitivity of 0.92. This study provides important insights into the controls, distribution, and dynamics of rock glaciers in the Mackenzie Mountains, as well as both the limitations and the potential of statistical models in predicting their occurrence.

A scenario-based approach was used to test air and ground response to warming with and without changes to inverted surface lapse rates in four Yukon valleys. Generally, climate warming coupled with weakening of temperature inversions resulted in the greatest increase in air temperature at low elevations. However, ground temperatures at high elevations showed the greatest response to warming and variability between scenarios due to increased connectivity between air and ground. Low elevations showed less of a response to warming and permafrost was largely preserved in these locations. Local models also predicted higher permafrost occurrence compared to a regional permafrost probability model, due to the inclusion of differential surface and thermal offsets. Results show that the spatial warming patterns in these mountains may not follow those predicted in other mountain environments following elevation-dependent warming (EDW). As a result, the concept of EDW should be expanded to become more inclusive of a wider range of possible spatial warming distributions. The purpose of this paper is not to provide exact estimations of warming, but rather to provide hypothetical spatial warming patterns, based on logical predictions of changes to temperature inversion strength, which may not directly follow the distribution projected through EDW.

Abstract Flagella propel pathogens through their environments, yet are expensive to synthesize and are immunogenic. Thus, complex hierarchical regulatory networks control flagellar gene expression. Spirochetes are highly motile bacteria, but peculiarly, the archetypal flagellar regulator σ28 is absent in the Lyme spirochete Borrelia burgdorferi. Here, we show that gene bb0268 (flgV) in B. burgdorferi, previously and incorrectly annotated to encode the RNA-binding protein Hfq, is instead a structural flagellar component that modulates flagellar assembly. The flgV gene is broadly conserved in the flagellar superoperon alongside σ28 in many Spirochaetae, Firmicutes and other phyla, with distant homologs in Epsilonproteobacteria. We find that B. burgdorferi FlgV is localized within flagellar basal bodies, and strains lacking flgV produce fewer and shorter flagellar filaments and are defective in cell division and motility. During the enzootic cycle, flgV-deficient B. burgdorferi survive and replicate in Ixodes ticks but are attenuated for infection and dissemination in mice. Our work defines infection timepoints when spirochete motility is most crucial and implicates FlgV as a broadly distributed structural flagellar component that modulates flagellar assembly.

Current permafrost models in Canadian boreal forests are generally of low spatial resolution as they cover regional or continental scales. This study aims to understand the viability of creating a temperature at the top of permafrost (TTOP) model on a local scale in the boreal wetland environment of Whatì, Northwest Territories from short-term field-collected temperature data. The model utilizes independent variables of vegetation, topographic position index, and elevation, with the dependent variables being ground surface temperature collected from 60 ground temperature nodes and 1.5 m air temperature collected from 10 temperature stations. In doing this, the study investigates the relationship vegetation and disturbance have on ground temperature and permafrost distribution. The model predicts that 31% of the ground is underlain by permafrost, based on a mean annual temperature at TTOP of

To investigate macula and optic nerve head (ONH) mitochondrial metabolic activity using flavoprotein fluorescence (FPF) in normal, glaucoma suspect (GS), and open-angle glaucoma (OAG) eyes we performed a cross-sectional, observational study of FPF in normal, GS, and OAG eyes. The macula and ONH of each eye was scanned and analyzed with a commercially available FPF measuring device (OcuMet Beacon, OcuSciences Inc., Ann Arbor, MI). One-way analysis of variance was used to compare macula and ONH FPF scores between groups. Linear regression models investigated the correlation between FPF scores and structural and functional parameters. We included 25 normal, 16 GS, and 54 OAG eyes. The average age in years ± SD for normal, GS, and OAG groups was 60.6 ±17.4, 67.8 ± 10.3, and 67.9 ± 11.6, respectively (P = 0.064). There was no significant difference in gender, race/ethnicity, visual acuity, and intraocular pressure between groups. OAG eyes had larger cup-to-disc ratio, thinner retinal nerve fiber and macula thicknesses, and worse visual field indices compared to normal and GS eyes (P ≤ 0.018). There was no significant difference in any FPF metric between the study groups in either the macula or the ONH, despite normalizing FPF data for structural differences between groups (e.g. retinal nerve fiber layer and ganglion cell-inner plexiform layer thickness). In conclusion, no significant differences in metabolic activity as measured by FPF were found in macula and ONH FPF scores using the integrated clinician report generator between normal, GS, and OAG eyes. Further research is needed to evaluate the role of mitochondrial metabolic activity measurements in glaucoma.

Background: Posterior lumbar fusion (PLF) is frequently considered for various spinal pathologies. While many outcome metrics have been assessed, to our knowledge, there has yet to be literature specifically investigating inpatient falls (IPFs) and its risk factors. Methods: Adult patients who underwent single-level PLF were abstracted from the 2010–Q1 2022 M161Ortho PearlDiver Database. Patients who had an IPF were determined based on administrative coding. Various patient variables were extracted and variables independently associated with IPFs were assessed with multivariate logistic regression. Incidence of secondary injuries and cost incurred related to the IPF were determined. Results: Of the 342,890 patients who underwent PLF, IPF was identified for 4,379 (1.4%). Independent predictors of an IPF in decreasing odds ratio (OR) order were those with: active psychosis (OR=3.35), active delirium (OR=2.83), history of falling (OR=2.47), commercial insurance (OR=1.59 relative to Medicare), Medicaid insurance (OR=1.47 relative to Medicare), dementia (OR=1.17), older age (OR=1.12 per decade), alcohol use disorder (O=1.11), higher comorbidity (OR=1.08 per Elixhauser comorbidity index point) (p

Annually, Sierra Leone records an estimated 301 human fatalities due to rabies. Canine vaccination is crucial for rabies prevention and control efforts. However, considerable variability exists in vaccination rates. Reasons for this variation remain unclear. We conducted a cross-sectional study across 2,558 dog-owning households (HHs) to provide insights into factors influencing canine vaccination for targeted prevention and control towards elimination by 2030. First, we described dog ownership practices, then built a probabilistic model to understand factors associated with dog vaccination, and finally used a spatial scan statistic to identify spatial clusters where vaccination rates were low. Our results indicated that only 14% (358/2,558) of participating HHs had fully vaccinated their dogs against rabies. The probability of dog vaccination increased when comparing civil servants to private workers/artisans, with an Odds Ratio(OR) of 1.14 (95% credible interval (Crl) of 0.82-1.56), residing in locations with a veterinary establishment vs. none (OR = 6.43, 95% Crl (4.97-8.35), providing care to dogs vs. allowing dogs to roam freely (OR = 2.38, 95% Crl(1.80-3.17) and owning a single dog vs multiple dogs (OR = 1.20, 95 Crl (0.92-1.56). Conversely, there was a decrease in the estimated probability of vaccination when comparing dog owners located in rural vs. urban areas (OR = 0.58, CrI 95% (0.43-0.78). Latent understanding, a measure of overall understanding of rabies virus, which we estimated using participant education levels and responses to questions about rabies epidemiology, was also an important predictor of vaccination probability (OR = 1.44, 95% Crl (1.04-2.07). The spatial analysis identified high-risk clusters for low vaccination in the cities of Moyamba, with a radius of 40 km, a relative risk (RR) of 1.10, and Bo, with a radius of 19.9 km with RR of 1.11. These data do not support Sierra Leone reaching the 2030 goal of human rabies elimination caused by dogs. Our study highlights a critical need for public outreach and education, improved vaccination rates, increased accessibility to veterinary services, and targeted interventions in Bo and Moyamba to support rabies prevention and control efforts.

Rabies perpetuates in Nigeria despite initiatives like the Regional Disease Surveillance System Enhancement Project, with evidence indicating suboptimal canine vaccination rates as a contributing factor. To inform effective planning of mass dog vaccination campaigns, it is crucial to understand the factors associated with variation in canine vaccination rates. We conducted a cross-sectional study in 2022 to understand factors associated with canine vaccination. We used stratified random sampling of the streets and dog-owning households to survey 4162 households from three states and the Federal Capital Territory (FCT). We then built a joint probabilistic model to understand factors associated with dog vaccination and non-vaccination. First, we modelled rabies knowledge as a latent variable indirectly measured with several targeted survey questions. This method allowed a respondent's unobserved understanding of rabies to be estimated using their responses to a collection of survey questions that targeted different aspects of rabies epidemiology and took various possible response distributions (i.e., ordinal, categorical, binary). Second, we modelled factors influencing pet owners' decisions to vaccinate their dogs against rabies and barriers to dog vaccination among dog owners whose dogs were not vaccinated against rabies. Posterior distributions revealed that the probability of dog vaccination was positively associated with the owner's latent knowledge of rabies, civil servant service employment, residence in the FCT, ownership of a single dog, providing care to dogs, and a preference for contemporary treatment following a dog bite. Conversely, non-vaccination was positively associated with private employment, residing in Anambra and Enugu states, owning multiple dogs, allowing dogs to search for leftovers, and a preference for traditional treatment after a dog bite. Cost was the primary barrier against vaccination for dog owners in Anambra and Enugu, while mistrust posed a major challenge for those in the FCT. Owners in areas with veterinary establishments cited cost as a barrier, while those without a veterinary establishment cited access as the primary barrier. Our study underscores the need to enhance rabies knowledge, tailor vaccination campaigns to specific demographics, address financial and access barriers, and combat hesitancy to improve rabies vaccination rates in Nigeria.

Individuals with upper limb loss lack sensation of the missing hand, which can negatively impact their daily function. Several groups have attempted to restore this sensation through electrical stimulation of residual nerves. The purpose of this study was to explore the utility of regenerative peripheral nerve interfaces (RPNIs) in eliciting referred sensation. In four participants with upper limb loss, we characterized the quality and location of sensation elicited through electrical stimulation of RPNIs over time. We also measured functional stimulation ranges (sensory perception and discomfort thresholds), sensitivity to changes in stimulation amplitude, and ability to differentiate objects of different stiffness and sizes. Over a period of up to 54 months, stimulation of RPNIs elicited sensations that were consistent in quality (e.g. tingling, kinesthesia) and were perceived in the missing hand and forearm. The location of elicited sensation was partially-stable to stable in 13 of 14 RPNIs. For 5 of 7 RPNIs tested, participants demonstrated a sensitivity to changes in stimulation amplitude, with an average just noticeable difference of 45 nC. In a case study, one participant was provided RPNI stimulation proportional to prosthetic grip force. She identified four objects of different sizes and stiffness with 56% accuracy with stimulation alone and 100% accuracy when stimulation was combined with visual feedback of hand position. Collectively, these experiments suggest that RPNIs have the potential to be used in future bi-directional prosthetic systems.

Purpose The purpose of this study is to investigate if leading a physically active and healthy lifestyle can prevent the weight gain typically experienced during the freshman year of college – the ‘Freshman 15’. Methods Study participants ( N = 525) were from three cohorts of incoming students (2018–2020) at a mid-sized university in the West South-Central United States. The weight of each study participant was measured at three points over a year: beginning of their first semester, beginning of their second semester, and beginning of their third semester. During the study, students were encouraged to lead physically active and healthy lifestyles and to exercise daily. Weight changes at sixth months and one-year intervals were recorded as percentages. Results Freshmen weight gain/loss depended upon initial weight with freshmen who arrived on campus with relatively lower weights (≤100 kg) tending to gain weight, especially males, whilst freshmen who arrived on campus with relatively higher weights (≥100 kg) tended to lose weight. This finding was both more apparent and more statistically significant at the 1-year mark than at the 6-months mark. Conclusions Several previous studies have linked freshmen weight gain to initial weight with students with higher initial weights gaining the most. However, our results show that maintaining a physically active and healthy lifestyle when entering college reverses this trend – with students with high initial weights losing weight. Thus, living a physically active and healthy lifestyle, which includes aerobic exercise, can prevent the fat mass weight gain often experienced by college freshmen.

The long sword, a weapon first known in the Aegean Bronze Age from Middle Minoan Crete (early second millennium BC), represented the culmination of a long period of development. Several problems in both casting and forging had to be solved before the production of large implements like swords could be achieved. Very early experiments with long weapons come from Early Minoan IB Crete, early in the third millennium BC. Examples from the cemetery at Hagia Photia illustrate this early phase in the production of large implements.

During the Early Bronze Age, before the expansion in copper mining and distribution of this metal from Cyprus, Aegean metal production relied especially on local ores. An example of this industry has been excavated from only a few sites in the Aegean. One of these smelting workshops has been excavated at Chrysokamino in eastern Crete. Its smelting furnaces provide a good example of the technology in use at early copper production centers in the Aegean region.

Assumptions of linear lapse rates in regions prone to surface-based inversions (SBIs) can generate biases in the prediction of surface air temperature. Although studies of Arctic inversions are common, few regional studies of their characteristics exist in high-latitude regions with mountainous topography. To address this gap, vertical atmospheric temperature profiles for five sites in northwestern Canada were analysed using archived radiosonde data from 1990 to 2016. We present monthly, seasonal, and annual SBI characteristics including the occurrence of transient and persistent SBIs. A novel metric, surface-based inversion impact (SBIimp), was developed by combining the traditional inversion characteristics of depth, strength, and frequency, and was used to quantify the impact of SBIs on cooling the surface air temperature. SBIimp values of >5 °C yr−1 and ∼10 °C winter−1 occur locally. A weak linear relationship between sea ice coverage in the Beaufort Sea and SBIimp manifests across parts of the study area, though this relationship does not persist after detrending the datasets. Topographic analysis of areas surrounding each radiosonde location reveals highly variable SBIimp in complex mountain areas and more consistent SBIimp across areas of low relief. Our results can help interpret the role of inversions in climatic conditions maintaining cryospheric elements such as permafrost.

Abstract Introduction Endometrial lesions are morphologically diverse and uncommon on cervical smears, with its detection rate and associated diagnostic categories uncharacterized. In this study, cervical smears matched to histologically proven endometrial hyperplasias and carcinomas were reviewed and compared with cervical in‐situ‐carcinomas/carcinomas, aiming to detail the diagnostic performance of cervical smears for upper tract and glandular lesions. Methods Pathology reports of cervical smears, hysterectomies, endometrial and cervical biopsies from 1995 to 2021 were retrieved. Diagnoses of cervical smears were matched to endometrial hyperplasias and carcinomas, or cervical carcinomas and reviewed. Results Totally 832 cervical smears (272 cervical carcinomas, 312 endometrial carcinomas, and 248 hyperplasias) were included. Considering all cytologic glandular diagnosis as positive, the detection rate of cervical adenocarcinoma‐in‐situ was the highest (64.3%), followed by cervical adenocarcinoma (63.8%), endometrial carcinoma (31.7%), and hyperplasia (with atypia–8.5%; without atypia–2.3%) (p

CD4+ T cell activation is driven by five-module receptor complexes. The T cell receptor (TCR) is the receptor module that binds composite surfaces of peptide antigens embedded within MHCII molecules (pMHCII). It associates with three signaling modules (CD3γε, CD3δε, and CD3ζζ) to form TCR-CD3 complexes. CD4 is the coreceptor module. It reciprocally associates with TCR-CD3-pMHCII assemblies on the outside of a CD4+ T cells and with the Src kinase, LCK, on the inside. Previously, we reported that the CD4 transmembrane GGXXG and cytoplasmic juxtamembrane (C/F)CV+C motifs found in eutherian (placental mammal) CD4 have constituent residues that evolved under purifying selection (Lee et al., 2022). Expressing mutants of these motifs together in T cell hybridomas increased CD4-LCK association but reduced CD3ζ, ZAP70, and PLCγ1 phosphorylation levels, as well as IL-2 production, in response to agonist pMHCII. Because these mutants preferentially localized CD4-LCK pairs to non-raft membrane fractions, one explanation for our results was that they impaired proximal signaling by sequestering LCK away from TCR-CD3. An alternative hypothesis is that the mutations directly impacted signaling because the motifs normally play an LCK-independent role in signaling. The goal of this study was to discriminate between these possibilities. Using T cell hybridomas, our results indicate that: intracellular CD4-LCK interactions are not necessary for pMHCII-specific signal initiation; the GGXXG and (C/F)CV+C motifs are key determinants of CD4-mediated pMHCII-specific signal amplification; the GGXXG and (C/F)CV+C motifs exert their functions independently of direct CD4-LCK association. These data provide a mechanistic explanation for why residues within these motifs are under purifying selection in jawed vertebrates. The results are also important to consider for biomimetic engineering of synthetic receptors.

Background Little is known about treatment variability across US hospitals for patients with chronic limb‐threatening ischemia (CLTI). Methods and Results Data were collected from the 2016 to 2018 National Inpatient Sample. All patients aged ≥18 years, admitted to nonfederal US hospitals with a primary diagnosis of CLTI, were identified. Patients were classified according to their clinical presentation (rest pain, skin ulceration, or gangrene) and were further characterized according to the treatment strategy used. The primary outcome of interest was variability in CLTI treatment, as characterized by the median odds ratio. The median odds ratio is defined as the likelihood that 2 similar patients would be treated with a given modality at 1 versus another randomly selected hospital. There were 15 896 (weighted n=79 480) hospitalizations identified where CLTI was the primary diagnosis. Medical therapy alone, endovascular revascularization ± amputation, surgical revascularization ± amputation, and amputation alone were used in 4057 (25%), 5390 (34%), 3733 (24%), and 2716 (17%) patients, respectively. After adjusting for both patient‐ and hospital‐related factors, the median odds ratio (95% CI) for medical therapy alone, endovascular revascularization ± amputation, surgical revascularization ± amputation, any revascularization, and amputation alone were 1.28 (1.19–1.38), 1.86 (1.77–1.95), 1.65 (1.55–1.74), 1.37 (1.28–1.45), and 1.42 (1.27–1.55), respectively. Conclusions Significant variability in CLTI treatment exists across US hospitals and is not fully explained by patient or hospital characteristics.

Abstract Transcription termination is an essential and dynamic process that can tune gene expression in response to diverse molecular signals. Yet, the genomic positions, molecular mechanisms, and regulatory consequences of termination have only been studied thoroughly in model bacteria. Here, we use several RNA-seq approaches to map RNA ends for the transcriptome of the spirochete Borrelia burgdorferi – the etiological agent of Lyme disease. We identify complex gene arrangements and operons, untranslated regions and small RNAs. We predict intrinsic terminators and experimentally test examples of Rho-dependent transcription termination. Remarkably, 63% of RNA 3′ ends map upstream of or internal to open reading frames (ORFs), including genes involved in the unique infectious cycle of B. burgdorferi. We suggest these RNAs result from premature termination, processing and regulatory events such as cis-acting regulation. Furthermore, the polyamine spermidine globally influences the generation of truncated mRNAs. Collectively, our findings provide insights into transcription termination and uncover an abundance of potential RNA regulators in B. burgdorferi.

Abstract Promoter-proximal pausing by RNA Pol II is a rate-determining step in gene transcription that is hypothesized to be a prominent point at which regulatory factors act. The pausing factor NELF is known to induce and stabilize pausing, but not all kinds of pausing are NELF-mediated. Here, we find that NELF-depleted Drosophila melanogaster cells functionally recapitulate the NELF-independent pausing we previously observed in fission yeast (which lack NELF). Critically, only NELF-mediated pausing establishes a strict requirement for Cdk9 kinase activity for the release of paused Pol II into productive elongation. Upon inhibition of Cdk9, cells with NELF efficiently shutdown gene transcription, while in NELF-depleted cells, defective, non-productive transcription continues unabated. By introducing a strict checkpoint for Cdk9, the evolution of NELF was likely critical to enable increased regulation of Cdk9 in higher eukaryotes, as Cdk9 availability can be restricted to limit gene transcription without inducing wasteful, non-productive transcription.

Abstract Rabies is an ancient disease. Two centuries since Pasteur, fundamental progress occurred in virology, vaccinology, and diagnostics—and an understanding of pathobiology and epizootiology of rabies in testament to One Health—before common terminological coinage. Prevention, control, selective elimination, and even the unthinkable—occasional treatment—of this zoonosis dawned by the twenty-first century. However, in contrast to smallpox and rinderpest, eradication is a wishful misnomer applied to rabies, particularly post-COVID-19 pandemic. Reasons are minion. Polyhostality encompasses bats and mesocarnivores, but other mammals represent a diverse spectrum of potential hosts. While rabies virus is the classical member of the genus, other species of lyssaviruses also cause the disease. Some reservoirs remain cryptic. Although global, this viral encephalitis is untreatable and often ignored. As with other neglected diseases, laboratory-based surveillance falls short of the notifiable ideal, especially in lower- and middle-income countries. Calculation of actual burden defaults to a flux within broad health economic models. Competing priorities, lack of defined, long-term international donors, and shrinking local champions challenge human prophylaxis and mass dog vaccination toward targets of 2030 for even canine rabies impacts. For prevention, all licensed vaccines are delivered to the individual, whether parenteral or oral–essentially ‘one and done’. Exploiting mammalian social behaviors, future ‘spreadable vaccines’ might increase the proportion of immunized hosts per unit effort. However, the release of replication-competent, genetically modified organisms selectively engineered to spread intentionally throughout a population raises significant biological, ethical, and regulatory issues in need of broader, transdisciplinary discourse. How this rather curious idea will evolve toward actual unconventional prevention, control, or elimination in the near term remains debatable. In the interim, more precise terminology and realistic expectations serve as the norm for diverse, collective constituents to maintain progress in the field.

BackgroundTotal hip arthroplasty (THA) is a common procedure following which postoperative visits are important to optimize outcomes. The associated global billing period includes the 90 postoperative days (or approximately 13 weeks), during which professional billing is included with the surgery itself. The current study assessed clinical practice patterns relative to the global billing period.MethodsUsing the PearlDiver M91Ortho dataset, the incidence and timing of Evaluation and Management (E&M) codes in the 26 weeks following THA were assessed. The follow-up visits within and beyond the global billing period, and those conducted by surgeons versus non-surgeon advanced practice providers (APPs) were determined.Results77,843 THAs were identified. Follow-up visits peaked at postoperative weeks 3, 7, and 14. The greatest week-to-week variation in the number of follow-ups was from weeks 13 to 14 immediately following the global billing period (representing a greater than 4-fold increase in visits.) During the first 13 postop weeks, 73.8% of patients were seen by orthopedic surgeons (as opposed to APPs). In the following 13 weeks, a significantly greater percentage of visits were with surgeons (86.8%, pConclusionsFollowing the THA global billing period, there was marked increase in the number of follow-ups and transition to a greater percentage being performed by the surgeons. These results provide interesting insight into the potential impact of the billing structure on how practice is pursued.

Background: End-stage ankle osteoarthritis is a condition that can be treated with ankle arthrodesis (AA) or total ankle arthroplasty (TAA). The goal of this study is to estimate the 2016-2017 United States’ utilization of TAA and AA in specific ambulatory settings and delineate patient and hospital factors associated with the selection of TAA vs AA for treatment of ankle osteoarthritis. Methods: TAA and AA procedures performed for ankle osteoarthritis were identified in the 2016-2017 Nationwide Ambulatory Surgery Sample (NASS) Database. Notably, the NASS database only examines instances of ambulatory surgery encounters at hospital-owned facilities. As such, instances of TAA and AA performed at privately owned or freestanding ambulatory surgical centers or those performed inpatient are excluded from this analysis. Cases were weighted using nationally representative discharge weights. Univariate analyses and a combined multiple logistic regression model were used to compare demographic, hospital-related, and socioeconomic factors associated with TAA vs AA. Results: In total, 6577 cases were identified, which represents 9072 cases after weighting. Of these, TAA was performed for 2233 (24.6%). Based on the logistic regression model, several factors were associated with increased utilization of TAA vs AA. With regard to patient factors, older patients were more likely to undergo TAA, as well as females. Conversely, patients with a higher comorbidity burden were less likely to receive TAA over AA. With regard to socioeconomic factors, urban teaching and urban nonteaching hospitals were significantly more likely to use TAA compared to rural hospitals. Similarly, privately insured patients and those with a median household income of $71 000 or more were also more likely to receive TAA over AA. Private hospitals (“not-for-profit” and “investor-owned”) were significantly more likely to offer TAA over AA. Conclusion: Using a large nationally representative cohort, the current data revealed that during 2016-2017, 24.6% of operatively treated cases of end-stage ankle osteoarthritis in the ambulatory setting are treated with TAA. Associations between socioeconomic and hospital-level factors with TAA utilization suggest that nonclinical factors may influence surgical treatment choice for ankle osteoarthritis. Level of Evidence: Level III, retrospective cohort study.

Category: Ankle Arthritis Introduction/Purpose: Total ankle replacement (TAR) surgery has steadily increased in recent decades. The aim of the current study was to investigate the evolving burden of revision surgery and risk factors and timing of revision or implant removal. We hypothesized that there has been an increase in revision TAR and explant surgeries in the past decade and that younger age and higher comorbidity burden are risk factors for revision and explant. Methods: Using the 2010-2020 PearlDiver M151Ortho dataset, this retrospective cohort study identified primary TAR, TAR revision, and TAR explant patients. This is a large national database containing billing claims information on over 151 million patients in the United States across all payer types and sites of care. Patient factors investigated included age, sex, and Elixhauser Comorbidity Index (ECI, a longitudinal measure of patient comorbidity burden generated using ICD-9 and ICD-10 diagnosis codes). Annual incidence for primary and revision TAR, and explant were recorded. Multivariate logistic regression analyses were performed to determine independent risk factors for revision TAR or explant relative to primary TAR. For explants, the eventual intervention by two years was analyzed. Ten-year timing and survival to revision or explant surgery following patient-matched unilateral TAR were characterized. Results: Over the study period, there were 10,531 primary, 1,218 revision, and 1,735 explant TARs (increasing by 310%, 398%, and 9.6%, respectively). Independent predictors of revision TAR included: younger age (odds ratio [OR] 1.29 per decade decrease) and higher ECI (OR 1.23 per 2-point increase) (p < 0.0001 for both). Independent predictors of explant surgery included: younger age (OR 1.80 per decade decrease, p< 0.0001), female sex (OR 1.17, p=0.0011), and higher ECI (OR 1.35 per 2-point increase, p< 0.0001). Explanted patients went on to arthrodesis (37.7%), amputation (26.1%), revision TAR (14.7%), or no identified procedure/other procedures (21.5%) within the subsequent two years. The 10-year implant survival rate following primary TAR was 91.8%. 73% and 83% of revisions and explants occurred in the first three years following index TAR, respectively. Conclusion: The burden of TAR revision has grown substantially over the past decade. Younger age, female sex, and higher patient comorbidity burden were associated with increased risk of revision or explant surgery. If explant is pursued, most went on to arthrodesis or amputation. These results suggest that care should be taken in patient selection for TAR to minimize the occurrence of revision and explant surgery. Treatment algorithms should be modified to optimize outcomes among patients who undergo explant or revision surgery.

Background Personality traits are known factors that may influence levels of physical activity and other healthy lifestyle measures and behaviors that ultimately lead to health problems later in life. Participants and procedure The aim of this study was to examine the association between personality traits (HEXACO) and levels of physical activity and resting heart rate (RHR) – measured using Fitbits, BMI, and a self-reported whole-person healthy lifestyle score for N = 2580 college students. Data were collected and analyzed for students enrolled in a University Success type course from August 2017 to May 2021. The relationships between HEXACO personality traits and various physical activity and healthy lifestyle behaviors were analyzed by building several multiple regression models using R version 4.0.2. Results In general, students who are extraverted were more physically active and students who are more open to experience had a higher RHR, even when controlling for gender. Females and males however had different profiles as to how personality influenced physical activity and other health-related measures. Male extraverts with high negative emotionality scores tend to be more physically active, whereas females tend to be more physically active when they were high in extroversion and conscientiousness, and low in openness to experience. BMI values were higher for female participants with high honesty-humility and low agreeableness and conscientiousness scores. Females also had a lower RHR for high honesty-humility and emotionality and low conscientiousness scores. Conclusions Personality can influence levels of physical activity, RHR, and BMI. This is especially true of women. Being aware of one’s personality and the relationship of personality traits to levels of physical activity and other measures of leading a healthy lifestyle can be beneficial in determining strategies to improve long-term health outcomes.

Mites act as the vectors of zoonotic vector-borne disease scrub typhus caused by the rickettsial pathogen Orientia tsutsugamushi. In India, scrub typhus is transmitted by the mite Leptotrombidium deliense. Rodents are the reservoirs and support the spread of this disease. Sarcoptes scabiei or the itch mite is causing scabies which is a common skin infection in India. Dermatitis, trombiculosis, and mite dust allergy are common mite-borne diseases transmitted by Pyemotidae family. D. brevis folliculorum and Demodex brevis are two major mite species found on humans also causing a disease; “Demodicosis”, common in India. Dermanyssus gallinae, fowl mite causes pruritis in poultry birds, transmits infections to poultry workers when they come into contact with birds. There is a re-emergence of mite-borne diseases, especially scrub typhus, in many parts of India requiring urgent attention for its control. This review is aimed to update the available information on mites and mite transmitted diseases prevalent in India to highlight the importance of rodent and chigger mite vector control to prevent forthcoming mite-borne diseases in India.

Active layer thicknesses (ALTs) from sites along a transect through the Mackenzie Valley, Northwest Territories, Canada, were analyzed to explore variation in thickness within and between ecoregions. At an ecoregional scale the relation between ALT, latitude, freezing and thawing degree-days, and snowfall were examined to determine the presence of trends. Site-specific variables including dominant vegetation and substrate were explored to explain spatial variability in ALT within ecoregions. Generally, average ALT increases moving southward through the comprising ecoregions (68 cm to 126 cm), following the increase in air temperature. Spatial variability in ALT within ecoregions was greater than that between ecoregions (up to 145 cm), which may be attributed to site-specific conditions (vegetation and snow cover). Most notable, sites with shrubs had thicker than average active layers likely because of increased snow retention leading to warmer overall ground conditions. Despite a warming trend in air temperatures, only one northern ecoregion showed a corresponding thickening trend in ALT. Sites located in southern ecoregions with mature forests showed limited response to changes in air temperature. For these locations, disturbance, specifically changes in thermally protective vegetation cover, rather than changing air temperature could potentially have a larger impact on ALT into the future.

Permafrost distribution in high-latitude continental mountains is a product of both latitudinal and elevationally controlled attributes. Frequently occurring surface-based temperature inversions (SBIs) significantly modify surface lapse rates (SLRs) annually. We aim to identify and quantify patterns of SBI characteristics in two proximal yet morphologically and vegetatively dissimilar central Yukon valleys. Elevational transect analysis is applied by using sensors in valley bottoms and 100 m upslope to determine in situ SLRs for the study period (August 2017 – August 2021). SLRs were shown to vary significantly between these dissimilar valleys. Climate reanalysis products (ClimateNA and Globsim) underestimated or almost entirely missed the presence of strong SBIs which produce annual average SLRs that range from 0.46 to 1.2 °C 100 m−1. The magnitude of these hyper-inversions was grossly underpredicted by previous surface air temperature modelling that attempted to account for SBIs across Yukon. Our results support the previously conceptualized framework that strong SBIs influence surface air temperatures and the pattern of permafrost distribution.

Objective: Administrative claims data offer a rich data source for clinical research. However, its application to the study of diabetic lower extremity ulceration is lacking. Our objective was to create a widely applicable framework by which investigators might derive and refine the International Classification of Diseases, 9th and 10th revision (ICD-9 and ICD-10, respectively) codes for use in identifying diabetic, lower extremity ulceration. Methods: We created a seven-step process to derive and refine the ICD-9 and ICD-10 coding lists to identify diabetic lower extremity ulcers. This process begins by defining the research question and the initial identification of a list of ICD-9 and ICD-10 codes to define the exposures or outcomes of interest. These codes are then applied to claims data, and the rates of clinical events are examined for consistency with prior research and changes across the ICD-9 to ICD-10 transition. The ICD-9 and ICD-10 codes are then cross referenced with each other to further refine the lists. Results: Using this method, we started with 8 ICD-9 and 43 ICD-10 codes used to identify lower extremity ulcers in patients with known diabetes and peripheral arterial disease and examined the association of ulceration with lower extremity amputation. After refinement, we had 45 ICD-9 codes and 304 ICD-10 codes. We then grouped the codes into eight clinical exposure groups and examined the rates of amputation as a rudimentary test of validity. We found that the rate of lower extremity amputation correlated with the severity of lower extremity ulceration. Conclusions: We identified 45 ICD-9 and 304 ICD-10 ulcer codes, which identified patients at risk of amputation from diabetes and peripheral artery disease. Although further validation at the medical record level is required, these codes can be used for claims-based risk stratification for long-term outcomes assessment in the treatment of patients at risk of limb loss.

Abstract Background This study illustrates the use of logistic regression and machine learning methods, specifically random forest models, in health services research by analyzing outcomes for a cohort of patients with concomitant peripheral artery disease and diabetes mellitus. Methods Cohort study using fee-for-service Medicare beneficiaries in 2015 who were newly diagnosed with peripheral artery disease and diabetes mellitus. Exposure variables include whether patients received preventive measures in the 6 months following their index date: HbA1c test, foot exam, or vascular imaging study. Outcomes include any reintervention, lower extremity amputation, and death. We fit both logistic regression models as well as random forest models. Results There were 88,898 fee-for-service Medicare beneficiaries diagnosed with peripheral artery disease and diabetes mellitus in our cohort. The rate of preventative treatments in the first six months following diagnosis were 52% (n = 45,971) with foot exams, 43% (n = 38,393) had vascular imaging, and 50% (n = 44,181) had an HbA1c test. The directionality of the influence for all covariates considered matched those results found with the random forest and logistic regression models. The most predictive covariate in each approach differs as determined by the t-statistics from logistic regression and variable importance (VI) in the random forest model. For amputation we see age 85 + (t = 53.17) urban-residing (VI = 83.42), and for death (t = 65.84, VI = 88.76) and reintervention (t = 34.40, VI = 81.22) both models indicate age is most predictive. Conclusions The use of random forest models to analyze data and provide predictions for patients holds great potential in identifying modifiable patient-level and health-system factors and cohorts for increased surveillance and intervention to improve outcomes for patients. Random forests are incredibly high performing models with difficult interpretation most ideally suited for times when accurate prediction is most desirable and can be used in tandem with more common approaches to provide a more thorough analysis of observational data.

Background: Total ankle replacement (TAR) surgery has increased in recent decades. The aim of this study was to investigate the evolving burden of revision surgery and risk factors and timing of revision or explant. Methods: Using the 2010 to 2020 PearlDiver M151Ortho data set, this retrospective cohort study identified primary TAR, TAR revision, and TAR explant patients via Current Procedural Terminology ( CPT ) and International Classification of Disease Procedural ( ICD-P ) codes. This database contains billing claims information across all payers and sites of care in the United States. Patient factors investigated included age, sex, and Elixhauser Comorbidity Index (ECI). Annual incidence for primary TAR was normalized per 100 000 covered lives in the data set for each year of study and recorded. Annual incidence of revision TAR and explant were normalized per 100 TARs performed for each year of study. Multivariate logistic regression analyses were performed to determine independent risk factors for revision TAR or explant. For explants, the eventual intervention by 2 years was analyzed. Ten-year timing and survival to revision or explant surgery following unilateral TAR were characterized. Results: A total of 10 531 primary, 1218 revision, and 1735 explant TARs were identified. After normalization, TAR utilization increased by 284% from 2010 to 2020, annual TAR revisions rose 28%, and annual TAR explants decreased 65%. Independent predictors of revision TAR were younger age (odds ratio [OR] 1.29 per decade decrease) and higher ECI (OR 1.23 per 2-point increase). Independent predictors of explant included younger age (OR 1.80 per decade decrease), female sex (OR 1.17), and higher ECI (OR 1.35 per 2-point increase). The 10-year implant survival rate was 91.8%, of which 73% of revisions and 83% of explants occurred in the first 3 years following index TAR. Conclusion: TAR utilization has grown substantially over the past decade, with minimal increases in the annual rate of revision surgery with respect to index procedures performed. Level of Evidence: Level III, retrospective cohort study.

Abstract Personalized treatment approaches for patients with limited liver metastases from colorectal cancer are critically needed. By leveraging three large, independent cohorts of patients with colorectal liver metastases (n = 336), we found that a proliferative subtype associated with elevated CIN70 scores is linked to immune exclusion, increased metastatic proclivity, and inferior overall survival in colorectal liver metastases; however, high CIN70 scores generate a therapeutic vulnerability to DNA-damaging therapies leading to improved treatment responses. We propose CIN70 as a candidate biomarker to personalize systemic treatment options for patients with metastatic colorectal cancer. These findings are potentially broadly applicable to other human cancers.

Patients with peripheral artery disease (PAD) and diabetes compose a high-risk population for development of critical limb ischemia (CLI) and amputation, although the underlying mechanisms remain poorly understood. Comparison of dysregulated microRNAs from diabetic patients with PAD and diabetic mice with limb ischemia revealed the conserved microRNA, miR–130b-3p. In vitro angiogenic assays demonstrated that miR-130b rapidly promoted proliferation, migration, and sprouting in endothelial cells (ECs), whereas miR-130b inhibition exerted antiangiogenic effects. Local delivery of miR-130b mimics into ischemic muscles of diabetic mice (db/db) following femoral artery ligation (FAL) promoted revascularization by increasing angiogenesis and markedly improved limb necrosis and amputation. RNA-Seq and gene set enrichment analysis from miR-130b–overexpressing ECs revealed the BMP/TGF-β signaling pathway as one of the top dysregulated pathways. Accordingly, overlapping downregulated transcripts from RNA-Seq and miRNA prediction algorithms identified that miR-130b directly targeted and repressed the TGF-β superfamily member inhibin-β-A (INHBA). miR-130b overexpression or siRNA-mediated knockdown of INHBA induced IL-8 expression, a potent angiogenic chemokine. Lastly, ectopic delivery of silencer RNAs (siRNA) targeting Inhba in db/db ischemic muscles following FAL improved revascularization and limb necrosis, recapitulating the phenotype of miR-130b delivery. Taken together, a miR-130b/INHBA signaling axis may provide therapeutic targets for patients with PAD and diabetes at risk of developing CLI.

Background: The coronavirus disease 2019 (COVID-19) pandemic adversely disrupted university student educational experiences worldwide, with consequences that included increased stress levels and unhealthy sedentary behavior. Aim: This study aimed to quantify the degree of impact that COVID-19 had on the levels of physical activity and stress of university students by utilizing wearable fitness tracker data and standard stress survey instrument scores before and during the pandemic. Methods: We collected Fitbit heart rate and physical activity data, and the results of a modified Social Readjustment Rating Scale (SRRS) stress survey from 2,987 university students during the Fall 2019 (residential instruction; before COVID-19) and Fall 2020 (hybrid instruction; during COVID-19) semesters. Results: We found indicators of increased sedentary behavior during the pandemic. There was a significant decrease in both the levels of physical activity as measured by mean daily step count (↓636 steps/day; p = 1.04 · 10-9) and minutes spent in various heart rate zones (↓58 minutes/week; p = 2.20 · 10-16). We also found an increase in stressors during the pandemic, primarily from an increase in the number of students who experienced the “death of a close family member” (38.8%), with the number even higher for the population of students who opted to stay home and attend classes virtually (41.4%). Conclusions: This study quantifies the decrease in levels of physical activity and notes an increase in the number of students who experienced the death of a close family member, a known stressor, during the first year of the COVID-19 pandemic. These findings allow for more informed student-health-focused interventions related to the COVID-19 pandemic disruptions experienced by academic communities worldwide.

Background: The aim of this study is to demonstrate whether the implementation of standardized Peer Assisted Learning (PAL) suturing workshops can aid the attainment of a technically competent interrupted suturing technique by medical students. Materials and Methods: The European University Cyprus (EUC) Division of Surgery and the students of the EUC Surgery Club compiled a standardized 1 hour and 15 minutes suturing workshop. During a one-week period 14 peer-teacher school of medicine students trained 147 fellow students. At the end of each workshop the students were assessed for the learning outcome of simple interrupted suturing with instruments by two peer-teachers, with the use of a standardized scoring rubric. The workshop primary outcomes were the rubric score and the time to complete a suture. These were correlated to student characteristics such as sex, year of studies, prior experience in suturing, previous participation in a similar workshop, previous training at home or in a hospital, and an interest in pursuing a surgical career. Univariate and multivariate statistical analysis was performed. Results: Statistical analysis showed that gender and previous suturing experience did not impact the rubric score of students, nor the time required. The student year of studies, having recently passed the course of General Surgery and having interest to pursue a surgical specialization positively affected the students’ score. Conclusions: Surgical peer teaching provided an effective method of teaching of the simple interrupted suturing technique. Interest in surgery, previous workshop experience and having recently completed the general surgery module helped students score higher in the assessment.

Patients with peripheral artery disease (PAD) and diabetes have the highest risk of critical limb ischemia (CLI) and amputation, yet the underlying mechanisms remain incompletely understood. MicroRNA (miRNA) sequencing of plasma from diabetic patients with or without CLI was compared to diabetic mice with acute or subacute limb ischemia to identify conserved miRNAs. miRNA-KO mice on high-fat diet were generated to explore the impact on CLI. Comparison of dysregulated miRNAs from diabetic individuals with PAD and diabetic mice with limb ischemia revealed conserved miR-181 family members. High-fat–fed, diabetic Mir181a2b2-KO mice had impaired revascularization in limbs due to abrogation of circulating Ly6Chi monocytes, with reduced accumulation in ischemic skeletal muscles. M2-like KO macrophages under diabetic conditions failed to produce proangiogenic cytokines. Single-cell transcriptomics of the bone marrow niche revealed that the reduced monocytosis in diabetic KO mice was a result of impaired hematopoiesis, with increased CXCR4 signaling in bone marrow Lineage–Sca1+Kit+ (LSK) cells. Exogenous Ly6Chi monocytes from nondiabetic KO mice rescued the impaired revascularization in ischemic limbs of diabetic KO mice. Increased Cxcr4 expression was mediated by the miR-181 target, Plac8. Taken together, our results show that MiR-181a/b is a putative mediator of diabetic CLI and contributes to changes in hematopoiesis, monocytosis, and macrophage polarization.

Canine-mediated rabies kills tens of thousands of people annually in lesser-developed communities of Asia, Africa, and the Americas, primarily through bites from infected dogs. Multiple rabies outbreaks have been associated with human deaths in Nigeria. However, the lack of quality data on human rabies hinders advocacy and resource allocation for effective prevention and control. We obtained 20 years of dog bite surveillance data across 19 major hospitals in Abuja, incorporating modifiable and environmental covariates. To overcome the challenge of missing information, we used a Bayesian approach with expert-solicited prior information to jointly model missing covariate data and the additive effects of the covariates on the predicted probability of human death after rabies virus exposure. Only 1155 cases of dog bites were recorded throughout the study period, out of which 4.2% (N = 49) died of rabies. The odds for risk of human death were predicted to decrease among individuals who were bitten by owned dogs compared to those bitten by free-roaming dogs. Similarly, there was a predicted decrease in the probability of human death among victims bitten by vaccinated dogs compared to those bitten by unvaccinated dogs. The odds for the risk of human death after bitten individuals received rabies prophylaxis were predicted to decrease compared to no prophylaxis. We demonstrate the practical application of a regularised Bayesian approach to model sparse dog bite surveillance data to uncover risk factors for human rabies, with broader applications in other endemic rabies settings with similar profiles. The low reporting observed in this study underscores the need for community engagement and investment in surveillance to increase data availability. Better data on bite cases will help to estimate the burden of rabies in Nigeria and would be important to plan effective prevention and control of this disease.