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Introduction: The risk of complications associated with transvenous ICDs make the subcutaneous implantable cardiac defibrillator (S-ICD) a valuable alternative in patients with adult congenital heart disease (ACHD). However, higher S-ICD ineligibility and higher inappropriate shock rates-mostly caused by T wave oversensing (TWO)- are observed in this population. We report a novel application of deep learning methods to screen patients for S-ICD eligibility over a longer period than conventional screening. Methods: Adult patients with ACHD and a control group of normal subjects were fitted with a 24-h Holters to record their S-ICD vectors. Their T:R ratio was analysed utilising phase space reconstruction matrices and a deep learning-based model to provide an in-depth description of the T: R variation plot for each vector. T: R variation was compared statistically using t-test. Results: 13 patients (age 37.4 ± 7.89 years, 61.5 % male, 6 ACHD and 7 control subjects) were enrolled. A significant difference was observed in the mean and median T: R values between the two groups (p

**Background:** Medical management of patients with type 2 diabetes mellitus (T2DM) is complex because of the chronic nature of the disease and its associated comorbidities. Injectable once-weekly semaglutide for diabetes (OW sema T2D) is a type of glucagon-like peptide–1 receptor agonist approved for the treatment of patients with T2DM. **Objectives:** To describe patient characteristics and HbA1c changes for patients prescribed 1.0 mg maintenance dose OW sema T2D. **Methods:** This retrospective study included adult patients with T2DM with a pre-index glycated hemoglobin (HbA1c) of at least 7%, initiating treatment with OW sema T2D between January 1, 2018, and December 31, 2019, and prescribed a 1.0 mg maintenance dose. Patients were identified in the Optum Research Database and were included if they had continuous health plan enrollment for at least 12 months prior to (pre-index) and at least 12 months following (post-index) the date of the first OW sema T2D claim (index). Dose at initiation and prescriber specialty were captured. Change in HbA1c between the latest post-index and pre-index HbA1c measurement was calculated among all patients and among those with at least 90 days of continuous treatment (persistent patients). **Results:** A total of 2168 patients were included in this study. On average, patients were taking 13.5 different classes of medications. The majority of patients had lipid metabolism disorder (90.8%), hypertension (86.6%), diabetes with complications (86.8%), or other nutritional/endocrine/metabolic disorders (72.5%). The mean HbA1c reduction was 1.2% (P

In the United States, the annual revenue attributable to tomato production is $1 billion. However, tomato production can cause negative environmental impacts, such as water pollution, often in the form of eutrophication-causing nutrient pollution. Hydroponic production can decrease excess nutrient leaching; however, optimization of nutrient management and cultivar choices could further decrease excess nutrient discharges. The objectives of this study were as follows: to evaluate and compare the responses of tomato growth characteristics, yield, and yield components to two nutrient management regimes (varying nutrient solution concentrations by growth stage and the use of a constant nutrient solution concentration from transplant to termination), and to analyze the effects of growth habits among six cultivars (Big Beef, Cherokee Purple, Heatmaster, Legend, Mountain Fresh Plus, and Tropic) on tomato yield and yield-correlated morphological characteristics. The nutrient management strategies were applied to tomato plants, and data regarding yield and related morphological characteristics were obtained. Data were analyzed using SAS PROC GLM. An analysis revealed no significant difference in the total fruit weight/plant between nutrient management regimes (P = 0.05); however, the mean fruit weight (164.26 g) and diameter (71.70 mm) were significantly greater (P < 0.0001) for plants that received the constant concentration nutrient regime. Indeterminate plants had a significantly greater (P < 0.0001) mean fruit weight (192.76 g) and mean fruit diameter (76.42 mm). Among cultivars, Big Beef had a significantly greater (P < 0.05) total fruit weight/plant (9.25 kg). Applying a constant nutrient concentration to indeterminate cultivars, particularly Big Beef and Cherokee Purple, improved the factors analyzed and could decrease negative environmental impacts while increasing profits of the producers.

Abstract Large‐scale disturbances such as wildfire can have profound impacts on the composition, structure, and functioning of ecosystems. Bees are critical pollinators in natural settings and often respond positively to wildfires, particularly in forests where wildfire leads to more open conditions and increased floral resources. The use of Light Detection and Ranging (LiDAR) provides opportunities for quantifying habitat features across large spatial scales and is increasingly available to scientists and land managers for post‐fire habitat assessment. We evaluated the extent to which LiDAR‐derived forest structure measurements can predict forest bee communities after a large, mixed‐severity fire. We hypothesized that LiDAR measurements linked to post‐fire forest structure would improve our ability to predict bee abundance and species richness when compared to satellite‐based maps of burn severity. To test this hypothesis, we sampled wild bee communities within the Douglas Fire Complex in southwestern Oregon, USA. We then used LiDAR and Landsat data to quantify forest structure and burn severity, respectively, across bee sampling locations. We found that the LiDAR forest structure model was the best predictor of abundance, whereas the Landsat burn severity model had better predictive ability for species richness. Furthermore, the Landsat burn severity model was better at predicting the presence and species richness of bumble bees (Bombus spp.), an ecologically distinct and economically important group within the Pacific Northwest. We posit that the divergent responses of the two modeling approaches are due to distinct responses by bee taxa to variation in forest structure as mediated by wildfire, with bumble bees in particular depending on closed‐canopy forest for some portions of their life cycle. Our study demonstrates that LiDAR data can provide information regarding the drivers of bee abundance in post‐wildfire conifer forest, and that both remote sensing approaches are useful for predicting components of wild bee diversity after large‐scale wildfire.

Ageing of rechargeable batteries is routinely characterized in the frequency domain by electrochemical impedance spectroscopy, but the technique requires laboratory measurements to be made on a time scale of days. However, the normal cycling of a battery as it is used in situ provides equivalent information in the time domain, though extracting robust frequency information from a time series is challenging. In this work, we explore, in the time domain, the relationship between instantaneous voltage-current phase difference and cycle efficiency. Moreover, we demonstrate that phase measures can be used to identify battery ageing. We have cycled a 250 mA h Nickel-Cobalt cell several hundred times and used Hilbert Transforms to identify phase difference between voltage and current. This phase difference becomes closer to zero as the battery ages, commensurate with a drop in energy cycle efficiency. In another experiment, we applied a synthetic current profile mimicking behaviour of an electric car cell, to a 3.2 A h LiNiMnCoO2 cell, for ~100 days. For this more complicated profile with a wide range of frequency content, we used wavelet analysis to identify changes in phase difference and impedance as the battery aged. For this cell, drop in cycle efficiency was associated with a rise in internal resistance. The results imply that time-series analysis of in situ measurements of voltage and current, when applied with equivalent circuit models and underlying theory, can identify markers of battery ageing.

Abstract Visual evoked potentials (VEPs) are an important prognostic indicator of visual ability in patients with nystagmus. However, VEP testing requires stable fixation, which is impossible with nystagmus. Fixation instability reduces VEP amplitude, and VEP reliability is therefore low in this important patient group. We investigated whether VEP amplitude can be increased using an eye tracker by triggering acquisition only during slow periods of the waveform. Data were collected from 10 individuals with early-onset nystagmus. VEP was obtained under continuous (standard) acquisition, or triggered during periods of low eye velocity, as detected by an eye tracker. VEP amplitude was compared using Bonferroni corrected paired samples t-tests. VEP amplitude is significantly increased when triggered during low eye velocity (95% CI 1.42–6.83 µV, t(15) = 3.25, p = 0.0053). This study provides proof-of-concept that VEP amplitude (and therefore prognostic reliability) can be increased in patients with early onset nystagmus by connecting an eye tracker and triggering acquisition during periods of lower eye velocity.

Abstract Striatal dysfunction has been implicated in the pathophysiology of schizophrenia, a disorder characterized by positive symptoms such as hallucinations and delusions. Haloperidol is a typical antipsychotic medication used in the treatment of schizophrenia that is known to antagonize dopamine D2 receptors, which are abundantly expressed in the striatum. However, haloperidol’s delayed therapeutic effect also suggests a mechanism of action that may go beyond the acute blocking of D2 receptors. Here, we performed proteomic analysis of striatum brain tissue and found more than 400 proteins significantly altered after 30 days of chronic haloperidol treatment in mice, namely proteins involved in glutamatergic and GABAergic synaptic transmission. Cell-type specific electrophysiological recordings further revealed that haloperidol not only reduces the excitability of striatal medium spiny neurons expressing dopamine D2 receptors (D2-MSNs) but also affects D1-MSNs by increasing the ratio of inhibitory/excitatory synaptic transmission (I/E ratio) specifically onto D1-MSNs but not D2-MSNs. Therefore, we propose the slow remodeling of D1-MSNs as a mechanism mediating the delayed therapeutic effect of haloperidol over striatum circuits. Understanding how haloperidol exactly contributes to treating schizophrenia symptoms may help to improve therapeutic outcomes and elucidate the molecular underpinnings of this disorder.

Background: Despite a number of states in the U.S. enacting medical marijuana policies, there is currently a lack of research outlining the role that individual-level factors play in predicting medical marijuana use, especially regarding use and misuse of prescription pain relievers. The overall aim of this study was to assess the prevalence of medical marijuana use in the U.S. and to identify clinical, social, and demographic predictors. Methods: A retrospective secondary database analysis was conducted utilizing five years of the National Survey on Drug Use and Health (NSUDH). A multivariable logistic regression model assessed the association between prescription pain reliever use and medical marijuana in the adult U.S. population while adjusting for substance use factors, psychiatric factors, and demographic characteristics. Results: Within the U.S. adult population from 2015 to 2019, medical marijuana use increased from 1.6% to 2.4%, while appropriate prescription pain reliever use decreased from 33.4% to 27.5%, and prescription pain reliever misuse decreased from 4.7% to 3.7%. Of all marijuana users, 15.1% resided within non-medical marijuana states. Medical marijuana users are more likely to have a serious mental illness (14.0% vs. 4.4%) and a non-marijuana related substance dependence (5.3% vs. 1.2%). Past-year medical marijuana use was significantly more likely to be reported among appropriate users of prescription pain relievers (OR = 1.99, p

Abstract Background The postulated benefits of the ketogenic diet in the management of multiple medical conditions have seen more patients who are in therapeutic ketosis attending 18F-FDG PET scans. This study aimed to investigate the effect of ketosis on cerebral glucose metabolism in a clinical PET scanning environment using 18F-FDG uptake as a surrogate marker. Methods A retrospective audit was conducted of the brain 18F-FDG uptake in 52 patients who underwent PET scans for possible cardiac sarcoidosis or suspected intracardiac infection, following a ketogenic diet and prolonged fasting. SUVbw for whole brain and separate brain regions was compared with serum glucose and serum ketone body (beta-hydroxybutyrate) levels. Results The expected negative association between serum glucose levels and whole brain 18F-FDG uptake was confirmed. A reduction in SUVbw due to increasing serum ketones levels was also observed that was independent of and in addition to the effects of glucose. The magnitude of the reduction in SUVbw related to serum glucose level and serum ketone level was found to be greater in the precuneus than in the cerebellum or whole brain. Conclusion In a real-world clinical PET setting, cerebral 18F-FDG uptake appears to be affected by glycaemia and ketonaemia. This means when assessing the brain, both serum glucose and ketone levels need to be considered when SUVs are used to distinguish between pathologic and physiologic states. The magnitude of this effect appears to vary between different brain regions. This regional difference should be taken into consideration when selecting the appropriate brain region for SUV normalisation, particularly when undertaking database comparison in the assessment of dementia.

Abstract Background Machine learning methods are used in the classification of various cardiovascular diseases through ECG data analysis. The concept of varying subcutaneous implantable cardiac defibrillator (S‐ICD) eligibility, owing to the dynamicity of ECG signals, has been introduced before. There are practical limitations to acquiring longer durations of ECG signals for S‐ICD screening. This study explored the potential use of deep learning methods in S‐ICD screening. Methods This was a retrospective study. A deep learning tool was used to provide descriptive analysis of the T:R ratios over 24 h recordings of S‐ICD vectors. Spearman's rank correlation test was used to compare the results statistically to those of a “gold standard” S‐ICD simulator. Results A total of 14 patients (mean age: 63.7 ± 5.2 years, 71.4% male) were recruited and 28 vectors were analyzed. Mean T:R, standard deviation of T:R, and favorable ratio time (FVR)—a new concept introduced in this study—for all vectors combined were 0.21 ± 0.11, 0.08 ± 0.04, and 79 ± 30%, respectively. There were statistically significant strong correlations between the outcomes of our novel tool and the S‐ICD simulator (p

The Gemini South telescope is now equipped with a new high-resolution spectrograph called the Gemini High-resolution Optical SpecTrograph (GHOST). This instrument provides high-efficiency, high-resolution spectra covering 347–1060 nm in a single exposure of either one or two targets simultaneously, along with precision radial velocity spectroscopy utilizing an internal calibration source. It can operate at a spectral element resolving power of either 76,000 or 56,000, and can reach a signal-to-noise ratio of ∼5 in a 1 hr exposure on a V ∼ 20.8 mag target in median site seeing and dark skies (per resolution element). GHOST was installed on-site in 2022 June, and we report performance after full integration to queue operations in 2023 November, in addition to scientific results enabled by the integration observing runs. These results demonstrate the ability to observe a wide variety of bright and faint targets with high efficiency and precision. With GHOST, new avenues to explore high-resolution spectroscopy have opened up to the astronomical community. These are described, along with the planned and potential upgrades to the instrument.

Quantitative wildfire risk assessments increasingly are used to prioritize areas for investments in wildfire risk mitigation actions. However, current assessments of wildfire risk derived from fire models built primarily on biophysical data do not account for socioeconomic contexts that influence community vulnerability to wildfire. Research indicates that despite accounting for only a small proportion of high wildfire hazard areas, communities with fewer socioeconomic resources to devote to wildfire prevention and response may experience outsized exposure and impacts. We examined the distribution of simulated wildfire risk versus observed wildfire experience relative to social vulnerability across communities in the Pacific Northwest region of the United States. Using three decades of wildfire occurrence data, we investigated whether socially vulnerable communities were more likely to experience ignitions, fires that escaped initial attack (hereafter ‘escaped fires’) (>121 hectares), and large fires (>404 hectares), reasoning that each may reveal key insights into the effectiveness of current wildfire risk mitigation and response efforts. We found that communities located in areas with higher wildfire risk or hazard tended to have lower social vulnerability, but that across landscapes east of the Cascade Range, communities with higher social vulnerability were more likely to be exposed to ignitions, escaped fires, and large fires. Our results draw into question whether the current reliance on biophysical data in wildfire risk assessments, absent consideration of community socioeconomic conditions, may perpetuate social inequities by leading to over-investment in well-resourced communities and under-investment in socially vulnerable communities subject to disproportionate wildfire exposure.

Kaposi sarcoma is a vascular endothelial neoplasm caused by human herpesvirus 8. Although it is a well-studied disease, little is known about the specific characteristics or epidemiology of Kaposi sarcoma in Afghanistan. The data consist primarily of anecdotal reports and epidemiological studies extrapolated from neighboring countries. In this case series, we summarize existing data about Kaposi sarcoma in Afghanistan and present seven histologically confirmed cases with associated clinical features to shed light on the characteristics of Kaposi sarcoma in this unique geographic setting.

Abstract Background Individuals with 22q11.2 deletion are at considerably increased risk of neurodevelopmental and psychiatric conditions. There have been very few studies investigating how this risk manifests in early childhood and what factors may underlie developmental variability. Insights into this can elucidate transdiagnostic markers of risk that may underlie later development of neuropsychiatric outcomes. Methods Thirty two children with 22q11.2 Deletion Syndrome (22q11.2DS) (mean age = 4.1 [SD = 1.2] years) and 12 sibling controls (mean age = 4.1 [SD = 1.5] years) underwent in‐depth dimensional phenotyping across several developmental domains selected as being potential early indicators of neurodevelopmental and psychiatric liability. Comparisons were conducted of the dimensional developmental phenotype of 22q11.2DS and sibling controls. For autistic traits, both parents and children were phenotyped using the Social Responsiveness Scale. Results Young children with 22q11.2DS exhibited large impairments (Hedge's g ≥ 0.8) across a range of developmental domains relative to sibling controls, as well as high rates of transdiagnostic neurodevelopmental and psychiatric traits. Cluster analysis revealed a subgroup of children with 22q11.2DS (n = 16; 53%) in whom neurodevelopmental and psychiatric liability was particularly increased and who differed from other children with 22q11.2DS and non‐carrier siblings. Exploratory analyses revealed that early motor and sleep impairments indexed liability for neurodevelopmental and psychiatric outcomes. Maternal autism trait scores were predictive of autism traits in children with 22q11.2DS (intraclass correlation coefficients = 0.47, p = 0.046, n = 31). Conclusions Although psychiatric conditions typically emerge later in adolescence and adulthood in 22q11.2DS, our exploratory study was able to identify a range of early risk indicators. Furthermore, findings indicate the presence of a subgroup who appeared to have increased neurodevelopmental and psychiatric liability. Our findings highlight the scope for future studies of early risk mechanisms and early intervention within this high genetic risk patient group.

Summary: Development of spatial-integrative pre-clinical models is needed for glioblastoma, which are heterogenous tumors with poor prognosis. Here, we present an optimized protocol to generate three-dimensional ex vivo explant slice glioma model from orthotopic tumors, genetically engineered mouse models, and fresh patient-derived specimens. We describe a step-by-step workflow for tissue acquisition, dissection, and sectioning of 300-μm tumor slices maintaining cell viability. The explant slice model allows the integration of confocal time-lapse imaging with spatial analysis for studying migration, invasion, and tumor microenvironment, making it a valuable platform for testing effective treatment modalities.For complete details on the use and execution of this protocol, please refer to Comba et al. (2022).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

It is essential to improve our understanding of the features that influence aggressiveness and invasion in high grade gliomas (HGG). Here, the authors characterize dynamic anatomical structures in HGG called oncostreams, which are associated with tumor growth and are regulated by COL1A1.

Abstract Few technologies have been mired in hype more than blockchain, which is the underlying peer-to-peer network protocol for cryptocurrencies such as Bitcoin. Given the technology’s emphasis on purported “immutable ledgers” and trust-less sharing models, there has been a great deal of interest in applying blockchain to democratic reforms. From localized decision-making to national-scale voting systems, blockchain has spurred a surge of interest in how democracy might “get a software update”. While significant research exists on socio-technological imaginaries (perceptions) and potential applications (experiments) within the Global North, few studies have looked at more dynamic contexts, particularly Central Asia. In light of the violence surrounding elections in October 2020 and previous revolutions against the country’s central government, the status of democracy in Kyrgyzstan is, at best, fragile and, at worst, non-existent. This article explores alternative futures scenarios for localized, blockchain-driven governance futures in Kyrgyzstan and concludes with a proposal for deeper investigation.

Voluntary flutter (sometimes known as “voluntary nystagmus”) is a conjugate saccadic oscillation of the eyes that occurs in some healthy individuals. It has no relation to pathological nystagmus, which can manifest in infancy or become acquired later in life. This report presents an unusual case of voluntary flutter that presented in a 20-year-old male with autism spectrum disorder during ocular examination via direct ophthalmoscopy. Refraction and ocular motor balance were normal, and visual acuity was good in each eye (−0.10 logMAR). During direct ophthalmoscopy, a fine intermittent tremor was initiated. The patient was referred for further assessment, and eye movements were recorded at 1,000 Hz with an EyeLink 1000 eye tracker. Upon request, the patient could manifest voluntary flutter again and sustain the eye movements with effort during convergence. The voluntary flutter consisted of back-to-back saccadic oscillations in a predominantly horizontal direction, with an average frequency of 13 Hz and an amplitude of ∼8°, both reducing over time. We speculate that the discomfort induced by the proximity of the clinician during direct ophthalmoscopy examination may have triggered the eye oscillations. Although the oscillations typically manifest during convergence, atypical forms of voluntary flutter can also occur during divergence. Voluntary flutter can be a useful differential diagnosis in patients with a recently onset apparent “nystagmus,” and no other neurological signs and symptoms.

ABSTRACT: Transportation is a stressful event for cattle, as it may involve various handling practices, commingling, deprivation of food and water, and fluctuating temperatures. Calves are particularly susceptible to these stressors because their physiological and immune systems are still developing. There has been no formal synthesis of the scientific literature evaluating the effect of transportation on young dairy calf health and performance; the aim of this scoping review is to describe and characterize this body of work. We targeted both descriptive and analytic studies examining transport of calves, including listing how the effect of transport has been evaluated. Eight databases were searched for relevant articles with eligible studies being primary research articles investigating transportation of calves of either sex who were younger than 60 d of age or weighed less than 100 kg. Two reviewers independently screened the title and abstracts of 6,859 articles with 361 potentially relevant articles screened at full text. Of these, 46 were relevant and had data extracted. Articles reporting study location were conducted in the United States (n = 5), Australia (n = 3), Japan (n = 3), and New Zealand (n = 3). Common transport-related variables evaluated included time in transit (n = 13), distance of transportation (n = 8), vehicle-related factors (n = 8), and age at time of transportation (n = 4). Outcome measures varied greatly, including blood parameters (n = 28), health assessments (n = 20), weight (n = 17), behavioral metrics (n = 14), mortality (n = 7), feed intake following transportation (n = 4), salivary cortisol concentrations (n = 3), morbidity (n = 3), and isolation of Salmonella Dublin in fecal samples (n = 2). Outcome parameters were measured during transport or ranged from immediately after to one year following transportation. As the transport-related risk factors and outcomes measured assessed varied widely between studies, future quantitative synthesis (e.g., meta-analysis) in this area may be limited. Several knowledge gaps were identified, including methods to prepare calves for transportation, such as improving nutrition, administering medication, or transporting calves at an older age or weight. Further research could also focus on consistent and clear reporting of key items related to study conduct and analysis, as well as the development of a core outcome set for calf transport studies.

Abstract Wildfires in the western United States (US) are increasingly expensive, destructive, and deadly. Reducing wildfire losses is particularly challenging when fires frequently start on one land tenure and damage natural or developed assets on other ownerships. Managing wildfire risk in multijurisdictional landscapes has recently become a centerpiece of wildfire strategic planning, legislation, and risk research. However, important empirical knowledge gaps remain regarding cross-boundary fire activity in the western US. Here, we use lands administered by the US Forest Service as a study system to assess the causes, ignition locations, structure loss, and social and biophysical factors associated with cross-boundary fire activity over the past three decades. Results show that cross-boundary fires were primarily caused by humans on private lands. Cross-boundary ignitions, area burned, and structure losses were concentrated in California. Public lands managed by the US Forest Service were not the primary source of fires that destroyed the most structures. Cross-boundary fire activity peaked in moderately populated landscapes with dense road and jurisdictional boundary networks. Fire transmission is increasing, and evidence suggests it will continue to do so in the future. Effective cross-boundary fire risk management will require cross-scale risk co-governance. Focusing on minimizing damages to high-value assets may be more effective than excluding fire from multijurisdictional landscapes.

ABSTRACT Multidrug resistance (MDR) plasmids drive the spread of antibiotic resistance between bacterial lineages. The immediate impact of MDR plasmid acquisition on fitness and cellular processes varies among bacterial lineages, but how the evolutionary processes enabling the genomic integration of MDR plasmids vary is less well understood, particularly in clinical pathogens. Using diverse Escherichia coli lineages experimentally evolved for ~700 generations, we show that the evolutionary response to gaining the MDR plasmid pLL35 was dominated by chromosomal mutations affecting metabolic and regulatory functions, with both strain-specific and shared mutational targets. The expression of several of these functions, such as anaerobic metabolism, is known to be altered upon acquisition of pLL35. Interactions with resident mobile genetic elements, notably several IS-elements, potentiated parallel mutations, including insertions upstream of hns that were associated with its upregulation and the downregulation of the plasmid-encoded extended-spectrum beta-lactamase gene. Plasmid parallel mutations targeted conjugation-related genes, whose expression was also commonly downregulated in evolved clones. Beyond their role in horizontal gene transfer, plasmids can be an important selective force shaping the evolution of bacterial chromosomes and core cellular functions. IMPORTANCE Plasmids drive the spread of antimicrobial resistance genes between bacterial genomes. However, the evolutionary processes allowing plasmids to be assimilated by diverse bacterial genomes are poorly understood, especially in clinical pathogens. Using experimental evolution with diverse E. coli lineages and a clinical multidrug resistance plasmid, we show that although plasmids drove unique evolutionary paths per lineage, there was a surprising degree of convergence in the functions targeted by mutations across lineages, dominated by metabolic functions. Remarkably, these same metabolic functions show higher evolutionary rates in MDR-lineages in nature and in some cases, like anaerobic metabolism, their expression is directly manipulated by the plasmid. Interactions with other mobile elements resident in the genomes accelerated adaptation by disrupting genes and regulatory sequences that they inserted into. Beyond their role in horizontal gene transfer, plasmids are an important selective force driving the evolution of bacterial genomes and core cellular functions.

As contemporary wildfire activity intensifies across the western United States, there is increasing recognition that a variety of forest management activities are necessary to restore ecosystem function and reduce wildfire hazard in dry forests. However, the pace and scale of current, active forest management is insufficient to address restoration needs. Managed wildfire and landscape-scale prescribed burns hold potential to achieve broad-scale goals but may not achieve desired outcomes where fire severity is too high or too low. To explore the potential for fire alone to restore dry forests, we developed a novel method to predict the range of fire severities most likely to restore historical forest basal area, density, and species composition in forests across eastern Oregon. First, we developed probabilistic tree mortality models for 24 species based on tree characteristics and remotely sensed fire severity from burned field plots. We applied these estimates to unburned stands in four national forests to predict post-fire conditions using multi-scale modeling in a Monte Carlo framework. We compared these results to historical reconstructions to identify fire severities with the highest restoration potential. Generally, we found basal area and density targets could be achieved by a relatively narrow range of moderate-severity fire (roughly 365-560 RdNBR). However, single fire events did not restore species composition in forests that were historically maintained by frequent, low-severity fire. Restorative fire severity ranges for stand basal area and density were strikingly similar for ponderosa pine (Pinus ponderosa) and dry mixed-conifer forests across a broad geographic range, in part due to relatively high fire tolerance of large grand (Abies grandis) and white fir (Abies concolor). Our results suggest historical forest conditions created by recurrent fire are not readily restored by single fires and landscapes have likely passed thresholds that preclude the effectiveness of managed wildfire alone as a restoration tool.

Abstract Introduction S‐ICD eligibility is assessed at pre‐implant screening where surface ECG traces are used as surrogates for S‐ICD vectors. In heart failure (HF) patients undergoing diuresis, electrolytes and fluid shifts can cause changes in R and T waves. Subsequently, T:R ratio, a major predictor of S‐ICD eligibility, can be dynamic. Methods This is a prospective study of patients with structurally normal hearts and HF patients undergoing diuresis. All patients were fitted with Holters® to record their S‐ICD vectors. Our deep learning model was used to analyze the T:R ratios across the recordings. Welch two sample t‐test and Mann–Whitney U were used to compare the data between the two groups. Results Twenty‐one patients (age 58.43 ± 18.92, 62% male, 14 HF, 7 normal hearts) were enrolled. There was a significant difference in the T:R ratios between both groups. Mean T: R was higher in the HF group (0.18 ± 0.08 vs 0.10 ± 0.05, p

Abstract Wildfires devastated communities in Oregon and Washington in September 2020, burning almost as much forest west of the Cascade Mountain crest (“the westside”) in 2 weeks (~340,000 ha) as in the previous five decades (~406,00 ha). Unlike dry forests of the interior western United States, temperate rain forests of the Pacific Northwest have experienced limited recent fire activity, and debates surrounding what drove the 2020 fires, and management strategies to adapt to similar future events, necessitate a scientific evaluation of the fires. We evaluate five questions regarding the 2020 Labor Day fires: (1) How do the 2020 fires compare with historical fires? (2) How did the roles of weather and antecedent climate differ geographically and from the recent past (1979–2019)? (3) How do fire size and severity compare to other recent fires (1985–2019), and how did forest management and prefire forest structure influence burn severity? (4) What impact will these fires have on westside landscapes? and (5) How can we adapt to similar fires in the future? Although 5 of the 2020 fires were much larger than any others in the recent past and burned ~10 times the area in high‐severity patches >10,000 ha, the 2020 fires were remarkably consistent with historical fires. Reports from the early 1900s, along with paleo‐ and dendro‐ecological records, indicate similar and potentially even larger wildfires over the past millennium, many of which shared similar seasonality (late August/early September), weather conditions, and even geographic locations. Consistent with the largest historical fires, strong east winds and anomalously dry conditions drove the rapid spread of high‐severity wildfire in 2020. We found minimal difference in burn severity among stand structural types related to previous management in the 2020 fires. Adaptation strategies for similar fires in the future could benefit by focusing on ignition prevention, fire suppression, and community preparedness, as opposed to fuel treatments that are unlikely to mitigate fire severity during extreme weather. While scientific uncertainties remain regarding the nature of infrequent, high‐severity fires in westside forests, particularly under climate change, adapting to their future occurrence will require different strategies than those in interior, dry forests.

Abstract Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cerebral small vessel disease caused by mutations in the NOTCH3 gene. Our laboratory has been undertaking genetic diagnostic testing for CADASIL since 1997. Work originally utilised Sanger sequencing methods targeting specific NOTCH3 exons. More recently, next-generation sequencing (NGS)-based technologies such as a targeted gene panel and whole exome sequencing (WES) have been used for improved genetic diagnostic testing. In this study, data from 680 patient samples was analysed for 764 tests utilising 3 different sequencing technologies. Sanger sequencing was performed for 407 tests, a targeted NGS gene panel which includes NOTCH3 exonic regions accounted for 354 tests, and WES with targeted analysis was performed for 3 tests. In total, 14.7% of patient samples (n = 100/680) were determined to have a mutation. Testing efficacy varied by method, with 10.8% (n = 44/407) of tests using Sanger sequencing able to identify mutations, with 15.8% (n = 56/354) of tests performed using the NGS custom panel successfully identifying mutations and a likely non-NOTCH3 pathogenic variant (n = 1/3) identified through WES. Further analysis was then performed through stratification of the number of mutations detected at our facility based on the number of exons, level of pathogenicity and the classification of mutations as known or novel. A systematic review of NOTCH3 mutation testing data from 1997 to 2017 determined the diagnostic rate of pathogenic findings and found the NGS-customised panel increases our ability to identify disease-causing mutations in NOTCH3.

The objective of this scoping review was to describe the literature on the characteristics and management practices of colostrum feeding and their associations with the level of transfer of passive immunity (TPI) in dairy calves. Observational and experimental studies were searched in 5 electronic databases and 3 conference proceedings. Two reviewers independently screened primary studies, either analytic observational or experimental studies written in English. Studies on dairy or dual-purpose calves with passive immunity analyzed by blood sampling between 1 to 9 days of age were included. All studies had to compare at least one colostrum intervention or risk factor and their association with passive immunity. Of the 3,675 initially identified studies, 256 were included in this synthesis. One hundred and ninety-five were controlled trials, 57 were cohort studies, and 4 were cross-sectional studies. The effect of colostral quantity at first feeding was investigated in 30 controlled studies including studies that were comparable to each other. The effect of colostral quality was explored in 24 controlled studies with inconsistent criteria used to define the quality. The effect of the timing of first feeding of colostrum was investigated in 21 controlled studies, where the timing of feeding ranged widely from immediately after birth to 60 h of age. Only 4 controlled studies evaluated the relationship between bacterial load in the colostrum and TPI in dairy calves. Of the 256 total studies, 222 assessed blood IgG concentration while 107 measured blood total protein concentration. We identified a gap in knowledge on the association between passive immunity in dairy calves and the bacterial load in colostrum, or the timing of harvesting colostrum from the dam. A possible quantitative synthesis could be conducted among the studies that evaluated colostral quantity at the first feeding in relation to TPI in dairy calves.

Objectives Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.Setting Prospective, international, multicentre, observational cohort study.Participants Patients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome 30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.Results This study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).Conclusions Patients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration number NCT04323644

Background A positive circumferential resection margin (CRM) has been associated with higher rates of locoregional recurrence and worse survival in oesophageal cancer. The aim of this study was to establish if clinicopathological and radiological variables might predict CRM positivity in patients who received neoadjuvant chemotherapy before surgery for oesophageal adenocarcinoma. Methods Multivariable analysis of clinicopathological and CT imaging characteristics considered potentially predictive of CRM was performed at initial staging and following neoadjuvant chemotherapy. Prediction models were constructed. The area under the curve (AUC) with 95% confidence intervals (c.i.) from 1000 bootstrapping was assessed. Results A total of 223 patients were included in the study. Poor differentiation (odds ratio (OR) 2·84, 95 per cent c.i. 1·39 to 6·01) and advanced clinical tumour status (T3–4) (OR 2·93, 1·03 to 9·48) were independently associated with an increased CRM risk at diagnosis. CT‐assessed lack of response (stable or progressive disease) following chemotherapy independently corresponded with an increased risk of CRM positivity (OR 3·38, 1·43 to 8·50). Additional CT evidence of local invasion and higher CT tumour volume (14 cm3) improved the performance of a prediction model, including all the above parameters, with an AUC (c‐index) of 0·76 (0·67 to 0·83). Variables associated with significantly higher rates of locoregional recurrence were pN status (P = 0·020), lymphovascular invasion (P = 0·007) and poor response to chemotherapy (Mandard score 4–5) (P = 0·006). CRM positivity was associated with a higher locoregional recurrence rate, but this was not statistically significant (P = 0·092). Conclusion The presence of advanced cT status, poor tumour differentiation, and CT‐assessed lack of response to chemotherapy, higher tumour volume and local invasion can be used to identify patients at risk of a positive CRM following neoadjuvant chemotherapy.

Abstract Background Global RNA sequencing technologies have revealed widespread RNA polymerase II (Pol II) transcription outside of gene promoters. Small 5′-capped RNA sequencing (Start-seq) originally developed for the detection of promoter-proximal Pol II pausing has helped improve annotation of Transcription Start Sites (TSSs) of genes as well as identification of non-genic regulatory elements. However, apart from the most well studied genomes of human and mouse, mammalian transcription has not been profiled with sufficiently high precision. Results We prepared and sequenced Start-seq libraries from rat (Rattus norgevicus) primary neural progenitor cells. Over 48 million uniquely mappable reads from two independent biological replicates allowed us to define the TSSs of 7365 known genes in the rn6 genome, reannotating 2503 TSSs by more than 5 base pairs, characterize promoter-associated antisense transcription, and profile Pol II pausing. By combining TSS data with polyA-selected RNA sequencing, we also identified thousands of potential new genes producing stable RNA as well as non-genic transcripts representing possible regulatory elements. Conclusions Our study has produced the first Start-seq dataset for the rat. Apart from profiling transcription initiation, our data reaffirm the prevalence of Pol II pausing across the rat genome and indicate conservation of pausing mechanisms across metazoan genomes. We suggest that pausing location, at least in mammals, is constrained by a distance from initiation of transcription, whether it occurs at or outside of a gene promoter. Abundant antisense transcription initiation around protein coding genes indicates that Pol II recruited to the vicinity of a promoter is distributed to available start sites of transcription at either DNA strand. Transcriptome profiling of neural progenitors presented here will facilitate further studies of other rat cell types as well as other organisms.

Background Mycoplasma genitalium is a sexually transmitted infection (STI) pathogen. There have been no published studies concerning symptomatology, prevalence data, antibiotic resistance profiling or reports of co-infection with other STI in pregnant women.Objective To describe these characteristics among pregnant women attending prenatal clinics in a large tertiary care centre.Design Remnant genital samples collected from pregnant women between August 2018 and November 2019 were tested for M. genitalium and Trichomonas vaginalis by the transcription-mediated amplification technique. Specimens with detectable M. genitalium RNA were sequenced for 23S rRNA mutations associated with azithromycin resistance and parC and gyrA mutations associated with resistance to moxifloxacin. Demographic, obstetric and STI co-infection data were recorded.Results Of the 719 samples, 41 (5.7 %) were positive for M. genitalium. M. genitalium infection was associated with black race, Hispanic ethnicity and young age (p=0.003, p=0.008 and p=0.004, respectively). M. genitalium infection was also associated with T. vaginalis co-infection and Streptococcus agalactiae (group B Streptococcus) colonisation (p≤0.001 and p=0.002, respectively). Of the 41 positive samples, 26 (63.4%) underwent successful sequencing. Eight (30.8%) had 23S rRNA mutations related to azithromycin resistance. One of 26 (3.8%) positive samples with sequencing results had the gyrA gene mutation and 1 of 18 sequenced samples (5.6%) had the parC gene mutation associated with moxifloxacin resistance.Conclusions Prevalence rates of M. genitalium in pregnant women was 5.7%. M. genitalium infection disproportionately affects young black women co-infected with T. vaginalis. Pregnant women remain at risk for persistent infection with M. genitalium due to decreased azithromycin susceptibility.

Vagally mediated heart rate variability (vmHRV), a measure of the parasympathetic nervous system’s control over the heart, is often negatively related to maladaptive emotional outcomes. Recent work suggests that quadratic relationships involving these factors may be present; however, research has not investigated gender differences in these nonlinear functions. To address this gap, the current study tested for quadratic relationships between resting vmHRV and depression and positive affect while investigating gender differences in these relationships. Significant quadratic effects were found between resting vmHRV and reports of both depression symptoms and positive affect in women but not men. Specifically, the lowest levels of depression and the highest levels of positive affect were found at moderate vmHRV in women. These results suggest that examinations of vmHRV’s nonlinear associations require the consideration of gender. Our findings are interpreted based on proposed differential neuropsychological mechanisms of vmHRV in men versus women.

[This corrects the article DOI: 10.1371/journal.pntd.0008413.].

Tuberculosis is an infectious disease caused by the bacterium Mycobacterium tuberculosisMycobacterium bovis

Infectious fungal species are often treated uniformly despite clear evidence of genotypic and phenotypic heterogeneity being widespread across strains. Identifying the genetic basis for this phenotypic diversity is extremely challenging because of the tens or hundreds of thousands of variants that may distinguish two strains.

Abstract The U.S. Forest Service is reconsidering policies that limit the size of trees that can be removed in the course of restoration treatments in dry forests of eastern Oregon. To evaluate the effects of diameter limits on the ability of managers to meet restoration objectives, we used an existing network of long‐term research plots to summarize historical and contemporary structure and composition of mixed‐conifer forests within a one million‐ha study area in eastern Oregon. Then, we used a novel thinning simulation procedure to quantify the degree to which thinning using different diameter limits restored stands to historical conditions. Contemporary mixed‐conifer forests within the study area are significantly denser, have more basal area, and have a greater proportion of shade‐tolerant species than historical conditions. Our simulations of thinning under current policy that prohibits cutting of trees ≥53 cm show that a quarter of mixed‐conifer stands cannot be restored to within the historical range of basal area or density. Those stands that could be restored to within historical basal area ranges still had a substantially higher component of shade‐tolerant trees than historical stands. Permitting larger shade‐tolerant trees to be removed allowed restoration of all or most of stands to within historical structural and compositional ranges. Forest conditions in the late 1800s may not necessarily provide the best template for management because climate and disturbance projections suggest that eastern Oregon forests will be less well suited to shade‐tolerant species in the future. Adapting stands to future conditions will require robust monitoring of forest structural and compositional response to restoration treatments.

Global Zika virus (ZIKV) outbreaks and their strong link to microcephaly have raised major public health concerns. ZIKV has been reported to affect the innate immune responses in neural stem/progenitor cells (NS/PCs). However, it is unclear how these immune factors affect neurogenesis. In this study, we used Asian-American lineage ZIKV strain PRVABC59 to infect primary human NS/PCs originally derived from fetal brains. We found that ZIKV overactivated key molecules in the innate immune pathways to impair neurogenesis in a cell stage-dependent manner. Inhibiting the overactivated innate immune responses ameliorated ZIKV-induced neurogenesis reduction. This study thus suggests that orchestrating the host innate immune responses in NS/PCs after ZIKV infection could be promising therapeutic approach to attenuate ZIKV-associated neuropathology.

Background: Complex Trauma (CT) is a term used to refer to multiple or prolonged traumatic experiences. Such experiences are often first encountered during childhood and may impact key developmental periods. CT is a risk for a broad range of deleterious physical, psychological, social, and occupational outcomes. The diagnosis of Complex Posttraumatic Stress Disorder (C-PTSD) has been proposed to capture the symptomatology resulting from CT exposure. In Australia, there are few publicly funded services that target, and are purposely designed to support, the mental health needs of young people with symptoms of complex post-traumatic stress (C-PTSD). The Tern Programme has been designed as a purpose-built model of care for providing mental health support to young people with C-PTSD. Methods: This implementation trial will involve a longitudinal examination of Tern participants for a fixed 24-month period. Participants will be recruited from the young people referred to Tern at headspace centres in regional Australia where Tern operates. Eligible participants will have reported a history of complex trauma, and present with symptoms of C-PTSD. All participants will be invited to complete a series of surveys during their participation in the programme. Survey items will assess C-PTSD symptom change, quality of life and occupational functioning. The Tern model of care is delivered in a semi-structured format to accommodate a person-centred flexible approach. Fidelity will be monitored through the completion of a clinician post-session checklist and through group supervision. Discussion: This study will provide the first quantitative data on the new Tern model of care and evaluate mental health and functional outcomes of its participants. If effective, Tern may be suitable for replication in other Australian or international youth mental health services where complex post-traumatic stress is prevalent. Trial Registration: Australia and New Zealand Clinical Trials Registry (ANZCTR): ACTRN12621000079842p. Prospectively registered on 29 January 2021. Abbreviations: CT = Complex Trauma; C-PTSD = Complex Posttraumatic Stress Disorder

Global Zika virus (ZIKV) outbreaks and their link to microcephaly have raised major public health concerns. However, the mechanism of maternal-fetal transmission remains largely unknown. In this study, we determined the role of yolk sac (YS) microglial progenitors in a mouse model of ZIKV vertical transmission. We found that embryonic (E) days 6.5-E8.5 were a critical window for ZIKV infection that resulted in fetal demise and microcephaly, and YS microglial progenitors were susceptible to ZIKV infection. Ablation of YS microglial progenitors significantly reduced the viral load in both the YS and the embryonic brain. Taken together, these results support the hypothesis that YS microglial progenitors serve as "Trojan horses," contributing to ZIKV fetal brain dissemination and congenital brain defects.

For practical and theoretical purposes, tests of second language (L2) ability commonly aim to measure one overarching trait, general language ability, while simultaneously measuring multiple sub-traits (e.g., reading, grammar, etc.). This tension between measuring uni- and multi-dimensional constructs concurrently can generate vociferous debate about the precise nature of the construct(s) being measured. In L2 testing, this tension is often addressed through the use of a higher-order factor model wherein multidimensional traits representing subskills load on a general ability latent trait. However, an alternative modeling framework that is currently uncommon in language testing, but gaining traction in other disciplines, is the bifactor model. The bifactor model hypothesizes a general factor, onto which all items load, and a series of orthogonal (uncorrelated) skill-specific grouping factors. The model is particularly valuable for evaluating the empirical plausibility of subscales and the practical impact of dimensionality assumptions on test scores. This paper compares a range of CFA model structures with the bifactor model in terms of theoretical implications and practical considerations, framed for the language testing audience. The models are illustrated using primary data from the British Council’s Aptis English test. The paper is intended to spearhead the uptake of the bifactor model within the cadre of measurement models used in L2 language testing.

Summary: Fast purinergic signaling is mediated by ATP and ATP-gated ionotropic P2X receptors (P2XRs), and it is implicated in pain-related behaviors. The properties exhibited by P2XRs vary between those expressed in heterologous cells and in vivo. Several modulators of ligand-gated ion channels have recently been identified, suggesting that there are P2XR functional modulators in vivo. Here, we establish a genome-wide open reading frame (ORF) collection and perform functional screening to identify modulators of P2XR activity. We identify TMEM163, which specifically modulates the channel properties and pharmacology of P2XRs. We also find that TMEM163 is required for full function of the neuronal P2XR and a pain-related ATP-evoked behavior. These results establish TMEM163 as a critical modulator of P2XRs in vivo and a potential target for the discovery of drugs for treating pain.

We report on three decades of repeat surveys of beached marine debris at two locations in the Scotia Sea, in the Southwest Atlantic sector of the Southern Ocean. Between October 1989 and March 2019 10,112 items of beached debris were recovered from Main Bay, Bird Island, South Georgia in the northern Scotia Sea. The total mass of items (data from 1996 onwards) was 101 kg. Plastic was the most commonly recovered item (97.5% by number; 89% by mass) with the remainder made up of fabric, glass, metal, paper and rubber. Mean mass per item was 0.01 kg and the rate of accumulation was 100 items km−1 month−1. Analyses showed an increase in the number of debris items recovered (5.7 per year) but a decline in mean mass per item, suggesting a trend towards more, smaller items of debris at Bird Island. At Signy Island, South Orkney Islands, located in the southern Scotia Sea and within the Antarctic Treaty area, debris items were collected from three beaches, during the austral summer only, between 1991 and 2019. In total 1304 items with a mass of 268 kg were recovered. Plastic items contributed 84% by number and 80% by mass, with the remainder made up of metal (6% by number; 14% by mass), rubber (4% by number; 3% by mass), fabric, glass and paper (

Abstract Dendroecological studies of historical tree recruitment patterns suggest mixed‐severity fire effects are common in Douglas‐fir/western hemlock forests of the Pacific Northwest (PNW), USA, but empirical studies linking observed fire severity to tree regeneration response are needed to expand our understanding into the functional role of fire in this forest type. Recent increases in mixed‐severity fires offered this opportunity, so we quantified the abundance, spatial distribution, species richness, and community composition of regenerating trees across a mixed‐severity fire gradient (unburned–high‐severity fire) 10 and 22 yr post‐fire, and use our results to inform a discussion of fire's functional role in western Oregon Cascades Douglas‐fir forests. Regeneration abundance was unimodal across the fire severity gradient such that the greatest mean abundance followed moderate‐severity fire (25–75% basal area mortality). Similarly, the greatest number of species was present within the most 25‐m2 regeneration quadrants (most extensive distribution) following moderate‐severity fire, relative to any other fire severity class. On average, species richness also exhibited a unimodal distribution across the severity gradient, increasing by 100% in stands that experienced moderate‐severity fire relative to unburned forests or following high‐severity fire, as predicted by the Intermediate Disturbance Hypothesis. Several distinct regeneration communities emerged across the fire severity gradient, including early seral tree communities indicative of those observed in initial and relay floristics successional models for this forest type. Most significantly, moderate‐severity fire alters successional trajectories and facilitates the establishment of a more diverse tree regeneration community than observed following low‐ or high‐severity fire. These communities are reflective of the diverse overstory communities commonly encountered throughout this forest type. The emergence of these diverse forests is unlikely to develop or persist in the absence of moderate‐severity fire effects, and may be perpetuated longer by recurring moderate‐severity fire relative to experiencing stand replacing fire. Therefore, moderate‐severity fire may be the most functionally important fire effect in Douglas‐fir forests and should be better represented in successional models and more prominent in ecologically based fire and forest management.

Efficient OLEDs from solution: engineering dipole alignment in polymers Dipole alignment is achieved in efficient solution-processed organic light-emitting diodes featuring a novel poly(dendrimer). A collaborative team led by Paul Burn from the Centre for Organic Photonics & Electronics, School of Chemistry & Molecular Biosciences at The University of Queensland have developed solution-processed organic light-emitting diodes (OLEDs) based on a phosphorescent poly(dendrimer)-based material with an out-coupling efficiency of around 40% and an external quantum efficiency of above 20%. The key to the enhanced light out-coupling in the devices is the favourable alignment of emissive dipoles in the poly(dendrimer), which consists of dendritic side-chains comprised of hole-transporting carbazole-based dendrons and iridium(III) complex-cores. The poly(dendrimer) is blended with a host material to ensure high efficiency in the device. Ultimately, the intelligent design of the developed poly(dendrimers) allowed the authors to utilise a simple bilayer device structure to demonstrate highly efficient solution-processed organic light-emitting diodes.

Study Design Retrospective cohort study (level of evidence: 4). Purpose To describe the potential comorbid, operative, and radiographic risk factors for the development of clinically-relevant pseudarthrosis following minimally-invasive transforaminal lumbar interbody fusion (MIS-TLIF). Overview of Literature MIS-TLIF has shown long-term clinical outcomes with decreased perioperative morbidity and earlier return to work, similar to those of open TLIF. However, unsuccessful fusion still remains a concern. The impacts of various patient, operative, and radiographic risk factors have not been evaluated for their potential association with pseudarthrosis related to MIS-TLIF. Methods Between 2012 and 2015, 204 consecutive patients underwent one or two-level MIS-TLIF at St. Joseph's University Medical Center, Paterson, NJ, USA; they had a minimum of 1 year of follow-up. The patients were divided into two cohorts: those who developed clinically-relevant pseudarthrosis and those who did not. Clinically-relevant pseudarthrosis was determined by both evidence on computed tomography and presence of continued clinical symptoms at 1-year follow-up. Results Revision surgery was the only identified non-radiographic factor associated with pseudarthrosis. Disc angle had the highest (R2=0.8), followed by anterior disc height (R2=0.79). Although posterior disc height and the ratio of anterior to posterior disc height showed a marked relationship with the outcome, the R2-values were

Abstract Background Skin and soft tissue infections (SSTIs) are a leading cause of morbidity and mortality among people who inject drugs (PWID). International data indicate up to one third of PWID have experienced an SSTI within the past month. Complications include sepsis, endocarditis and amyloid A (AA) amyloidosis. AA amyloidosis is a serious sequela of chronic SSTI among PWID. Though there is a paucity of literature reporting on AA amyloidosis among PWID, what has been published suggests there is likely a causal relationship between AA amyloidosis and injecting-related SSTI. If left untreated, AA amyloidosis can lead to renal failure; premature mortality among diagnosed PWID is high. Early intervention may reverse disease. Despite the high societal and individual burden of SSTI among PWID, empirical evidence on the barriers and facilitators to injecting-related SSTI prevention and care or the feasibility and acceptability of AA amyloidosis screening and treatment referral are limited. This study aims to fill these gaps and assess the prevalence of AA amyloidosis among PWID. Methods Care and Prevent is a UK National Institute for Health Research-funded mixed-methods study. In five phases (P1–P5), we aim to assess the evidence for AA amyloidosis among PWID (P1); assess the feasibility of AA amyloidosis screening, diagnostic and treatment referral among PWID in London (P2); investigate the barriers and facilitators to AA amyloidosis care (P3); explore SSTI protection and risk (P4); and co-create harm reduction resources with the affected community (P5). This paper describes the conceptual framework, methodological design and proposed analysis for the mixed-methods multi-phase study. Results We are implementing the Care and Prevent protocol in London. The systematic review component of the study has been completed and published. Care and Prevent will generate an estimate of AA amyloidosis prevalence among community recruited PWID in London, with implications for the development of screening recommendations and intervention implementation. We aim to recruit 400 PWID from drug treatment services in London, UK. Conclusions Care and Prevent is the first study to assess screening feasibility and the prevalence of positive proteinuria, as a marker for AA amyloidosis, among PWID accessing drug treatment services. AA amyloidosis is a serious, yet under-recognised condition for which early intervention is available but not employed.