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The complexity of global anthropogenic change makes forecasting species responses and planning effective conservation actions challenging. Additionally, important components of a species’ adaptive capacity, such as evolutionary potential, are often not included in quantitative risk assessments due to lack of data. While genomic proxies for evolutionary potential in at-risk species are increasingly available, they have not yet been included in extinction risk assessments at a species-wide scale. In this study, we used an individual-based, spatially explicit, dynamic eco-evolutionary simulation model to evaluate the extinction risk of an endangered desert songbird, the southwestern willow flycatcher (Empidonax traillii extimus), in response to climate change. Using data from long-term demographic and habitat studies in conjunction with genome-wide ecological genomics research, we parameterized simulations that include 418 sites across the breeding range, genomic data from 225 individuals, and climate change forecasts spanning 3 generalized circulation models and 3 emissions scenarios. We evaluated how evolutionary potential, and the lack of it, impacted population trajectories in response to climate change. We then investigated the compounding impact of drought and warming temperatures on extinction risk through the mechanism of increased nest failure. Finally, we evaluated how rapid action to reverse greenhouse gas emissions would influence population responses and species extinction risk. Our results illustrate the value of incorporating evolutionary, demographic, and dispersal processes in a spatially explicit framework to more comprehensively evaluate the extinction risk of threatened and endangered species and conservation actions to promote their recovery.

The evolution of multicellular life spurred evolutionary radiations, fundamentally changing many of Earth’s ecosystems. Yet little is known about how early steps in the evolution of multicellularity transform eco-evolutionary dynamics, e.g., via niche expansion processes that may facilitate coexistence. Using long-term experimental evolution in the snowflake yeast model system, we show that the evolution of multicellularity drove niche partitioning and the adaptive divergence of two distinct, specialized lineages from a single multicellular ancestor. Over 715 daily transfers, snowflake yeast were subject to selection for rapid growth in rich media, followed by selection favoring larger group size. Both small and large cluster-forming lineages evolved from a monomorphic ancestor, coexisting for over ~4,300 generations. These small and large sized snowflake yeast lineages specialized on divergent aspects of a trade-off between growth rate and survival, mirroring predictions from ecological theory. Through modeling and experimentation, we demonstrate that coexistence is maintained by a trade-off between organismal size and competitiveness for dissolved oxygen. Taken together, this work shows how the evolution of a new level of biological individuality can rapidly drive adaptive diversification and the expansion of a nascent multicellular niche, one of the most historically-impactful emergent properties of this evolutionary transition.

Video telehealth experienced rapid growth throughout the COVID-19 pandemic in many healthcare sectors, including mental health. The Veterans Health Administration’s video telehealth platform, VA Video Connect, has been widely used to reach veterans who may have experienced difficulty accessing care, such as those living in rural areas or other barriers (e.g., transportation). Implementing VVC requires a multifaceted approach, including training providers on technical skills, increasing access to equipment for providers and veterans, and integrating VVC within the culture and processes of the clinic unit. Prior successful VVC implementation efforts in rural areas have focused on simultaneous one-on-one provider and leadership engagement using implementation facilitation (IF). However, given the rapid need for VVC expansion in light of limits and dangers associated with in-person care during the pandemic, our team developed group facilitation to increase the reach of VVC implementation through IF. Group facilitation combined training in technical and policy elements of VVC with IF with groups of providers from clinic units. This approach was designed to rapidly disseminate the necessary knowledge to conduct VVC combined with collaborative problem solving as a team to improve the ability of the clinical team to sustain VVC. Attendees were asked for feedback on the session through multiple choice and open-ended questions. Participants (N = 26) reported being highly satisfied with the training and reported a high degree of confidence in their ability to use VVC. Based on evaluation data and interview feedback, providers and clinic leaders were satisfied with group facilitation. Group facilitation may be a helpful tool in rapidly training clinical teams to implement and sustain video telemental health.

Objective: This study aims to assess the safety and efficacy of the use of popliteal nerve block (PNB) in the endovascular management of patients with critical limb threatening ischaemia. Design: Single-centre retrospective observational study. Methods: All patients with rest pain who received PNB from March 2018 to August 2021 were included. Pain scores were recorded before and after block using a visual analogue scale (VAS). Requirements for analgesia or sedation, complications related to nerve block, and level of intervention were recorded. Results were compared with a historical cohort of patients prior to implementation of nerve blocks. Results: 68 nerve blocks were performed in 63 patients (M:F 46:17) of mean age 71.7 years (range 43–91). All patients were Fontaine classification III–IV. Sonographically, all nerve blocks were technically successful. The mean VAS pain score was 8.2 pre-block, reducing to 0.3 (p

Shakhdaraite-(Y), ideally ScYNb2O8, is a new mineral from the Leskhozovskaya miarolitic granitic pegmatite at the Shakhdara River, southwestern Pamir (Tajikistan). Shakhdaraite-(Y) occurs mainly as grains from 10 to 150 μm in size in a near-miarolitic pegmatite complex in association with quartz, albite, pyrochlore-microlite, fersmite, and an unnamed Sc-Nb oxide; only one large, single, well-shaped crystal 200 μm long was found in a small cavity with quartz, albite, bertrandite, pyrochlore, and jarosite. Shakhdaraite-(Y) is black to dark-brown, streak is brown. Luster is vitreous semi-metallic. It is brittle with conchoidal fracture. Mohs hardness is 5. VHN100 = 436 kg/mm2. Dcalc. = 5.602 g/cm3. In reflected light, it is light gray and its reflective capacity is moderate to low. Anisotropy is distinct, without color effects. Pleochroism was not observed. Internal reflections are red-brown. Reflectance values were measured in air with SiC as reference material [λ(nm), Rmax, Rmin]: 470, 14.6, 13.9; 546, 14.0, 13.4; 589, 13.9, 13.3; 650, 13.8, 13.1. Electron probe microanalysis (WDS mode, 7 points) gives (wt.%): Nb2O5 50.70; Ta2O5 4.52; TiO2 0.08; WO3 0.79; SnO2 1.54; CaO 1.01; Sc2O3 11.35; MnO 1.38; FeO 0.01; Y2O3 12.00; Ce2O3 0.21; Pr2O3 0.04; Nd2O3 0.27; Sm2O3 0.32; Eu2O3 0.07; Gd2O3 0.86; Tb2O3 0.22; Dy2O3 2.07; Ho2O3 0.29; Er2O3 1.33; Tm2O3 0.35; Yb2O3 2.80; Lu2O3 0.32; PbO 0.24; ThO2 1.90; UO2 3.30, total 97.97. The empirical formula of shakhdaraite-(Y) based on O = 8 apfu (atoms per formula unit) is (Nb1.91Sc0.83Y0.53Ta0.10Mn0.10Ca0.09 Yb0.07U4+0.06Dy0.06Sn0.05Th0.04Er0.03Gd0.02W6+0.02Pb0.01Ce0.01Nd0.01Sm0.01Tb0.01Ho0.01Tm0.01Lu0.01Ti0.01)Σ4.00O8, Z = 2. The simplified formula is Sc(Y,Yb)Nb2O8, where Yb is the dominant lanthanoid. Shakhdaraite-(Y) is monoclinic, space group P2/c, a 9.930(2), b 5.6625(11), c 5.2108(10) Å, β 92.38(3)°, V 292.7(5) Å3, Z = 2. The crystal structure was solved by direct methods [R1 = 0.0269, 878 unique reflections (F > 4σF)]. There are three cation M sites: [6]M(1) = Nb2apfu, [6]M(2) = Sc apfu, and [8]M(3) = Y apfu, ideally M = ScYNb2apfu. The M(1) and M(2) octahedra each form a brookite chain along c. The Y-dominant [8]M(3A) polyhedra form a brookite-like kinked chain, and each M(3A) polyhedron of one brookite-like chain shares two edges with the two M(3A) polyhedra from the adjacent brookite-like chain, thus forming a [Y2O8]10– layer. In the structure of shakhdaraite-(Y), M(1A) and M(2) brookite chains and a layer of [8]-coordinated M(3A) polyhedra alternate along a. Shakhdaraite-(Y) is isostructural with samarskite-(Y), ideally YFe3+Nb2O8. Shakhdaraite-(Y) [Russian Cyrillic: шахдараит-(Y)] is named after its type locality: the valley of the Shakhdara River in the southwest of the Pamir Mountains.

Species reintroductions are successful when established populations maintain both demographic stability and genetic diversity. Such a result may be obtained by ensuring both structural habitat connectivity and genetic connectivity among reintroduced and remnant populations. Nevertheless, prezygotic barriers such as assortative mating can prevent the flow of genetic material between populations, even when migration between populations is high. Limited gene flow may be particularly relevant for reintroductions that were sourced either from captive-bred populations or from disparate locations in the wild. American martens (Martes americana) have been reintroduced repeatedly in the Upper Midwestern United States in an effort to establish self-sustaining populations. We quantified levels of genetic diversity within and spatial genetic variance among four marten populations during two time periods separated by 10 years. Spatially informed and naïve discriminant analysis of principal components were used to assign individuals to populations. Results indicate that heterozygosity declined and inbreeding coefficients increased between the two collection periods, while genetic structure among populations also increased. Data are consistent with assortative mating contributing to reapportioning of genetic variation. Population assignment tests show that migration among populations is apparent, but admixture (based on cluster membership probabilities) is low and declined over time. Specifically, martens may be successfully dispersing between populations but a lack of admixture indicates a lack of reproductive contributions to genetic diversity by migrants. Because marten reintroductions in this region are well-documented and well-monitored, lessons can be derived from results to inform future reintroductions. We encourage a careful balance of supplementing genetic diversity via augmentation while avoiding translocation of animals from disparate populations that may result in reproductive isolation of migrants. In combination with the maintenance of a functionally connected landscape, this strategy would maximize the likelihood of a successful reintroduction in terms both of demography and genetics.

Marine Protected Areas (MPAs) are key tools in addressing the global decline of sharks and rays, with "marine parks" and "shark sanctuaries" of various configurations established to conserve shark populations. There is also a rapidly growing body of telemetry research used to assess MPA performance in shark protection. However, assessments of MPA efficacy in shark and ray conservation are compromised by inconsistent terminology, a lack of standardised approaches to assess how MPAs contribute to the overall conservation of sharks and rays, and ambiguity about integrating movement data into assessment processes. This paper presents a conceptual framework that standardises key terms and uses the concept of Portfolio Risk to fully describe how an MPA may contribute to shark and ray conservation. The framework also demonstrates how movement data can be integrated into the process and presents eight key questions that provide guidance for applying the framework. Understanding an MPA's contribution to shark and ray protection requires explicit consideration of the assessment scope, MPA type and purpose, the range of existing and potential threats, the species biology and ecology, and management and operational contexts. Ultimately, MPA contributions to shark and ray conservation differ according to a complex set of human and natural factors and interactions which should be carefully considered in MPA design, implementation and evaluation. Article Impact statement: Standardization of key terms and use of the portfolio risk concept describe how protected areas contribute to shark and ray conservation. This article is protected by copyright. All rights reserved.

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease in urgent need of disease biomarkers for the assessment of promising therapeutic candidates in clinical trials. Raman spectroscopy is an attractive technique for identifying disease related molecular changes due to its simplicity. Here, we describe a fibre optic fluid cell for undertaking spontaneous Raman spectroscopy studies of human biofluids that is suitable for use away from a standard laboratory setting. Using this system, we examined serum obtained from patients with ALS at their first presentation to our centre ( n = 66) and 4 months later ( n = 27). We analysed Raman spectra using bounded simplex-structured matrix factorization (BSSMF), a generalisation of non-negative matrix factorisation which uses the distribution of the original data to limit the factorisation modes (spectral patterns). Biomarkers associated with ALS disease such as measures of symptom severity, respiratory function and inflammatory/immune pathways (C3/C-reactive protein) correlated with baseline Raman modes. Between visit spectral changes were highly significant ( p = 0.0002) and were related to protein structure. Comparison of Raman data with established ALS biomarkers as a trial outcome measure demonstrated a reduction in required sample size with BSSMF Raman. Our portable, simple to use fibre optic system allied to BSSMF shows promise in the quantification of disease-related changes in ALS over short timescales.

The research-practice gap is an ongoing concern for sport and exercise science researchers. Despite ongoing efforts to ‘bridge’ the gap between research and practice, a know-do gap remains. Drawing...

Removal of non-native fish populations can be crucial to the conservation of native species, but often presents a complex challenge for managers. The goal of Trojan Y chromosome (TYC) programs is to skew the non-native sex ratio until only males remain, leading to eradication. We present results from a simulation model used to explore effects of alternative management approaches on an in-progress mechanical removal and TYC program to eradicate non-native brook trout (Salvelinus fontinalis). Simulation results indicated that stocking fingerling YY males (∼137 mm) was more effective than stocking catchable-sized YY males (∼230 mm), although questions about intercohort competition warrant further investigation. Increasing the proportion of mature fingerling YY males reduced treatment time by increasing the number of YY male spawners and increasing density-dependent mortality on young, mature wild brook trout. Maximizing the spatial distribution of YY male releases may be crucial to program success but is also dependent upon immediate dispersal movements. Principles derived from our results can be broadly applied to the management of other aquatic invaded systems using TYC programs to eradicate non-native species.

Urban stressors represent strong selective gradients that can elicit evolutionary change, especially in non‐native species that may harbor substantial within‐population variability. To test whether urban stressors drive phenotypic differentiation and influence local adaptation, we compared stress responses of populations of a ubiquitous invader, reed canary grass (Phalaris arundinacea). Specifically, we quantified responses to salt, copper, and zinc additions by reed canary grass collected from four populations spanning an urbanization gradient (natural, rural, moderate urban, and intense urban). We measured ten phenotypic traits and trait plasticities, because reed canary grass is known to be highly plastic and because plasticity may enhance invasion success. We tested the following hypotheses: (a) Source populations vary systematically in their stress response, with the intense urban population least sensitive and the natural population most sensitive, and (b) plastic responses are adaptive under stressful conditions. We found clear trait variation among populations, with the greatest divergence in traits and trait plasticities between the natural and intense urban populations. The intense urban population showed stress tolerator characteristics for resource acquisition traits including leaf dry matter content and specific root length. Trait plasticity varied among populations for over half the traits measured, highlighting that plasticity differences were as common as trait differences. Plasticity in root mass ratio and specific root length were adaptive in some contexts, suggesting that natural selection by anthropogenic stressors may have contributed to root trait differences. Reed canary grass populations in highly urbanized wetlands may therefore be evolving enhanced tolerance to urban stressors, suggesting a mechanism by which invasive species may proliferate across urban wetland systems generally., We tested whether populations of a ubiquitous wetland invader, reed canary grass (Phalaris arundinacea), differed phenotypically across an urbanization gradient, suggesting evolutionary responses to common urban stressors. We found clear trait and trait plasticity variation among populations, suggesting reed canary grass may be evolving enhanced tolerance to anthropogenic stressors.

Introduction Pre-eclampsia (PE) is a dangerous placental condition that can lead to premature labour, seizures and death of mother and infant. Several studies have identified altered placental DNA methylation in PE; however, there is widespread inconsistency between studies and most findings have not been replicated. This study aimed to identify and validate consistent differences in methylation across multiple PE cohorts. Methods Seven publicly available 450K methylation array datasets were analysed to identify consistent differentially methylated positions (DMPs) in PE. DMPs were identified based on methylation difference (≥10%) and significance (p-value ≤ 1 × 10−7). Targeted deep bisulfite sequencing was then performed to validate a subset of DMPs in an additional independent PE cohort. Results Stringent analysis of the seven 450K datasets identified 25 DMPs (associated with 11 genes) in only one dataset. Using more relaxed criteria confirmed 19 of the stringent 25 DMPs in at least four of the remaining six datasets. Targeted deep bisulfite sequencing of eight DMPs (associated with three genes; CMIP, ST3GAL1 and DAPK3) in an independent PE cohort validated two DMPs in the CMIP gene. Seven additional CpG sites in CMIP were found to be significantly differentially methylated in PE. Discussion The identification and validation of significant differential methylation in CMIP suggests that the altered DNA methylation of this gene may be associated with the pathogenesis of PE, and may have the potential to serve as diagnostic biomarkers for this dangerous condition of pregnancy.

This paper reviews the concept of governance in protected areas, providing details about nine key principles of governance as they relate to marine protected areas (MPAs). Following a theoretical description of each principle, real-world examples of the principles are presented from the Great Barrier Reef (GBR) Marine Park, where marine governance has evolved over 45 years as part of adaptive management. Examples of good governance in the GBR include the intergovernmental arrangements that enable both federal and state governments to co-operate effectively across adjoining marine jurisdictions. In addition, the application of multiple layers of management adds to an effective integrated approach, considered to be the most appropriate for managing a large MPA. The nine governance principles discussed in the paper are applicable to all MPAs, but how they are applied will vary in dissimilar settings because of differing environmental, social, economic, cultural, and political contexts - clearly, one size does not fit all. The analogy of the nine principles being part of an interlaced or woven ‘lattice’ is also introduced. Collectively the lattice is stronger than any individual principle, and together all principles contribute to the totality of effective governance. The paper provides information for those involved in MPA management who are keen to understand marine governance and how it might apply to their MPA, recognising there will be differences in how the principles will apply.

Objective Prostaglandins (PGs) use for cervical ripening with small for gestational age (SGA) fetuses is controversial since it remains uncertain if use increases the chance of cesarean delivery (CD). We aimed to assess the association between PG use for cervical ripening and mode of delivery between SGA and appropriate for gestational age (AGA) neonates. Study Design Secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b), a prospective observational cohort study of 10,038 nulliparas. We included women undergoing induction with nonanomalous fetuses in the cephalic presentation. Women with >2 cm cervical dilation or prior uterine scar were excluded. We assessed the association of PG use with CD among women with SGA and AGA neonates. SGA was defined as birth weight Results Among 2,353 women eligible, PGs were used in 54.8%, SGA occurred in 15.1%, and 35.0% had CD. The association between PG use and CD differed significantly (interaction p = 0.018) for SGA versus AGA neonates; CD occurred more often in SGA neonates exposed to PGs than not (35 vs. 22%, p = 0.009). PG use was not associated with CD among AGA neonates (36 vs. 36%, p = 0.8). This effect remained significant when adjusting for body mass index, race/ethnicity, and cervical dilation. Among SGA neonates, CD for “nonreassuring fetal status” was similar between PG groups. Among SGA neonates, PG use was not associated with adverse neonatal outcomes or postpartum hemorrhage but had a higher rate of chorioamnionitis (7.0 vs. 2.1%, p = 0.048). Conclusion PG use was associated with a higher rate of CD in SGA but not AGA neonates; however, further studies are needed before PG use is discouraged with SGA neonates. Key Points

To examine the association of alcohol consumption and type of alcoholic beverage with incident cataract surgery in 2 large cohorts.Longitudinal, observational study.We included 469 387 participants of UK Biobank with a mean age of 56 years and 23 162 participants of European Prospective Investigation of Cancer (EPIC)-Norfolk with a mean age of 59 years.Self-reported alcohol consumption at baseline was ascertained by a touchscreen questionnaire in UK Biobank and a food-frequency questionnaire in EPIC-Norfolk. Cases were defined as participants undergoing cataract surgery in either eye as ascertained via data linkage to National Health Service procedure statistics. We excluded participants with cataract surgery up to 1 year after the baseline assessment visit or those with self-reported cataract at baseline. Cox proportional hazards models were used to examine the associations of alcohol consumption with incident cataract surgery, adjusted for age, sex, ethnicity, Townsend deprivation index, body mass index (BMI), smoking, and diabetes status.Incident cataract surgery.There were 19 011 (mean cohort follow-up of 95 months) and 4573 (mean cohort follow-up of 193 months) incident cases of cataract surgery in UK Biobank and EPIC-Norfolk, respectively. Compared with nondrinkers, drinkers were less likely to undergo cataract surgery in UK Biobank (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.85-0.93) and EPIC-Norfolk (HR, 0.90; 95% CI, 0.84-0.97) after adjusting for covariables. Among alcohol consumers, greater alcohol consumption was associated with a reduced risk of undergoing cataract surgery in EPIC-Norfolk (P0.001), whereas a U-shaped association was observed in the UK Biobank. Compared with nondrinkers, subgroup analysis by type of alcohol beverage showed the strongest protective association with wine consumption; the risk of incident cataract surgery was 23% and 14% lower among those in the highest category of wine consumption in EPIC-Norfolk and UK Biobank, respectively.Our findings suggest a lower risk of undergoing cataract surgery with low to moderate alcohol consumption. The association was particularly apparent with wine consumption. We cannot exclude the possibility of residual confounding, and further studies are required to determine whether this association is causal in nature.

Neuromuscular diseases result in muscle weakness, disability, and, in many instances, death. Preclinical models form the bedrock of research into these disorders, and the development of in vivo and potentially translational biomarkers for the accurate identification of disease is crucial. Spontaneous Raman spectroscopy can provide a rapid, label-free, and highly specific molecular fingerprint of tissue, making it an attractive potential biomarker. In this study, we have developed and tested an in vivo intramuscular fiber optic Raman technique in two mouse models of devastating human neuromuscular diseases, amyotrophic lateral sclerosis, and Duchenne muscular dystrophy (SOD1G93A and mdx, respectively). The method identified diseased and healthy muscle with high classification accuracies (area under the receiver operating characteristic curves (AUROC): 0.76-0.92). In addition, changes in diseased muscle over time were also identified (AUROCs 0.89-0.97). Key spectral changes related to proteins and the loss of α-helix protein structure. Importantly, in vivo recording did not cause functional motor impairment and only a limited, resolving tissue injury was seen on high-resolution magnetic resonance imaging. Lastly, we demonstrate that ex vivo muscle from human patients with these conditions produced similar spectra to those observed in mice. We conclude that spontaneous Raman spectroscopy of muscle shows promise as a translational research tool.

INTRODUCTION/AIMS: Raman spectroscopy is an emerging technique for the evaluation of muscle disease. In this study we evaluate the ability of in vivo intramuscular Raman spectroscopy to detect the effects of voluntary running in the mdx model of Duchenne muscular dystrophy (DMD). We also compare mdx data with muscle spectra from human DMD patients.METHODS: Thirty 90-day-old mdx mice were randomly allocated to an exercised group (48-hour access to a running wheel) and an unexercised group (n = 15 per group). In vivo Raman spectra were collected from both gastrocnemius muscles and histopathological assessment subsequently performed. Raman data were analyzed using principal component analysis-fed linear discriminant analysis (PCA-LDA). Exercised and unexercised mdx muscle spectra were compared with human DMD samples using cosine similarity.RESULTS: Exercised mice ran an average of 6.5 km over 48 hours, which induced a significant increase in muscle necrosis (P = .03). PCA-LDA scores were significantly different between the exercised and unexercised groups (P DISCUSSION: Raman spectroscopy provides a readout of the biochemical alterations in muscle in both the mdx mouse and human DMD muscle.

Selivanovaite, ideally NaFe3+Ti4(Si2O7)2O4(H2O)4, is a murmanite-group (seidozerite supergroup) TS-block mineral from the Lovozero massif, Kola Peninsula, Russia. The crystal structure of selivanovaite was refined in space group C, a 10.524(6), b 13.815(6), c 12.213(14) Å, α 99.74(6), β 107.45(8), γ 90.15(10)°, V 1666.8(26) Å3, R1 = 21.40%. The previously given chemical analysis has been modified to better fit the crystal structure: Nb2O5 8.51, ZrO2 2.94, TiO2 31.96, SiO2 30.62, Al2O3 0.05, Fe2O3 5.08, FeO 3.23, MnO 3.36, CaO 2.14, MgO 0.75, Na2O 2.47, H2O 8.88, sum 99.99 wt.%; H2O was determined from structure-refinement results: H2O = 3.34 pfu, OH = 1.05 pfu. The empirical formula calculated on 22 O apfu is: (Na0.63Ca0.30Mn0.36)Σ1.29(Fe3+0.50Fe2+0.35)Σ0.85(Ti3.14Nb0.50Zr0.19Mg0.15Mn0.01Al0.01)Σ4.00Si3.99O22.00H7.73, Z = 4. The crystal structure of selivanovaite [basic structure type B1(MG)] is an array of TS blocks (Titanium Silicate) connected via hydrogen bonds. The TS block consists of HOH sheets (H = heteropolyhedral, O = octahedral) parallel to (001). In the O sheet, the Ti-dominant MO(1,2) sites, Na-dominant MO(3) site, and □-dominant MO(4) sites give ideally Na□Ti2pfu. In the H sheet, the Ti-dominant MH(1,2) sites, Fe3+-dominant AP(1) site, and vacant AP(2) sites give ideally Fe3+□Ti2pfu. The MH and AP(1) polyhedra and Si2O7 groups constitute the H sheet. The ideal structural formula of selivanovaite of the form AP2MH2MO4(Si2O7)2(XOM,A)4(XPM,A)4 is Fe3+□Ti2Na□Ti2(Si2O7)2O4(H2O)4. Selivanovaite is a Fe3+-bearing and OH-poor analogue of vigrishinite, ideally Zn□Ti2Na□Ti2(Si2O7)2O2O(OH)(H2O)4. Vigrishinite and selivanovaite are related by the following substitution: O(OH)–vig + H(Zn2+)vig ↔ O(O2–)sel + H(Fe3+)sel. Selivanovaite is a Fe3+-bearing and Na-poor analogue of murmanite, ideally Na2Ti2Na2Ti2(Si2O7)2O4(H2O)4. Murmanite and selivanovaite are related by the following substitution: O(Na+)mur + H(Na+2)mur ↔ O(□)sel + H(Fe3+)sel + H(□)sel. The doubling of the t1 and t2 translations of selivanovaite compared to those of murmanite is due to the ordering of Fe3+ and □ in the H sheet and Na and □ in the O sheet of selivanovaite.

IMPORTANCE: If an anatomic narrow angle is not appropriately diagnosed and treated, it can result in acute angle-closure crisis (AACC) and lead to substantial vision loss. OBJECTIVE: To identify patients who presented with AACC and assess for factors that may have been associated with risk of developing it. DESIGN, SETTING, AND PARTICIPANTS: This population-based retrospective cohort study conducted from January 1, 2001, to December 31, 2015, included a 20% nationwide sample of 1179 Medicare beneficiaries. Patients aged 40 years or older with AACC were identified with billing codes. A 2-year lookback period from the date of initial presentation of AACC was used to identify patients who had at least 1 eye care visit, received a diagnosis of open-angle glaucoma (OAG) or suspected OAG, or received at least 1 medication associated with risk of AACC. Of the patients who had at least 1 eye care visit, those who underwent gonioscopy, received a diagnosis of an anatomic narrow angle before developing AACC, or both were identified. MAIN OUTCOMES AND MEASURES: Proportions of patients who had at least 1 eye care visit, had OAG or suspected OAG, received at least 1 medication associated with risk of AACC, underwent gonioscopy, or received a diagnosis of an anatomic narrow angle before development of AACC. RESULTS: A total of 1179 patients had a confirmed diagnosis of AACC. The mean (SD) age of patients with AACC was 66.7 (11.8) years (range, 40-96 years), 766 were women (65.0%), 57 were Asian (4.8%), 109 were Black (9.2%), 126 were Latino (10.7%), 791 were White (67.1%), and 96 were other race and ethnicity (8.1%). Of these patients, only 796 (67.5%) consulted an optometrist or ophthalmologist at least once during the 2-year lookback period. A total of 464 individuals (39.4%) had OAG or suspected OAG, and 414 (35.1%) had received at least 1 medication associated with increased risk of AACC before developing it. Of the 796 patients who consulted an optometrist or ophthalmologist in the lookback period, less than one-third underwent gonioscopy in the 2 years before developing AACC (n = 264 [33.2%]), and less than one-half of all patients undergoing gonioscopy received a diagnosis of an anatomic narrow angle (n = 113 [42.8%]). Most patients underwent gonioscopy in the 1 to 4 weeks preceding the AACC. CONCLUSIONS AND RELEVANCE: In this group of Medicare patients, there appear to have been multiple opportunities for interventions that may have averted AACC. Interventions aimed at addressing risk factors associated with AACC and improving performance of gonioscopy might be associated with reduced risk for ocular morbidity.

The diagnosis of muscle disorders ("myopathies") can be challenging and new biomarkers of disease are required to enhance clinical practice and research. Despite advances in areas such as imaging and genomic medicine, muscle biopsy remains an important but time-consuming investigation. Raman spectroscopy is a vibrational spectroscopy application that could provide a rapid analysis of muscle tissue, as it requires no sample preparation and is simple to perform. Here, we investigated the feasibility of using a miniaturised, portable fibre optic Raman system for the rapid identification of muscle disease. Samples were assessed from 27 patients with a final clinico-pathological diagnosis of a myopathy and 17 patients in whom investigations and clinical follow-up excluded myopathy. Multivariate classification techniques achieved accuracies ranging between 71-77%. To explore the potential of Raman spectroscopy to identify different myopathies, patients were subdivided into mitochondrial and non-mitochondrial myopathy groups. Classification accuracies were between 74-89%. Observed spectral changes were related to changes in protein structure. These data indicate fibre optic Raman spectroscopy is a promising technique for the rapid identification of muscle disease that could provide real time diagnostic information. The application of fibre optic Raman technology raises the prospect of in vivo bedside testing for muscle diseases which would significantly streamline the diagnostic pathway of these disorders.

Tribbles proteins (TRIB1–3) are a pseudokinase-only branch of the human kinome, which recruit substrates to the COP1 ubiquitin-ligase for ubiquitination. TRIB2 was the first Tribbles ortholog to be implicated as a myeloid leukaemia oncogene, by way of recruiting the C/EBPa transcription factor for degradation by COP1. Here we report selection and characterisation of nanobodies against the TRIB2 pseudokinase domain from a synthetic yeast surface-display library. We identified nanobodies that bind the TRIB2 pseudokinase domain with low nanomolar affinity. A crystal structure of Nb4.103 in complex with TRIB2 identified a mode of binding to the N-terminal lobe of the pseudokinase, in a manner that enables specific recognition of TRIB2 over TRIB1 and TRIB3. In the nanobody-stabilised state, TRIB2 adopts an activated conformation that is remarkably similar to the C/EBPa-bound state of TRIB1. Characterization in solution revealed that Nb4.103 can stabilise a TRIB2 pseudokinase domain dimer in a face-to-face manner. Conversely, a distinct nanobody (Nb4.101) binds through a similar epitope but does not readily promote dimerization. In combination, this study identifies features of TRIB2 that could be exploited for the development of inhibitors, and nanobody tools for future investigation of TRIB2 function.

Tribbles proteins (TRIB1-3) are pseudokinases that recruit substrates to the COP1 ubiquitin ligase. TRIB2 was the first Tribbles ortholog to be implicated as a myeloid leukemia oncogene, because it recruits the C/EBPα transcription factor for ubiquitination by COP1. Here we report identification of nanobodies that bind the TRIB2 pseudokinase domain with low nanomolar affinity. A crystal structure of the TRIB2-Nb4.103 complex identified the nanobody to bind the N-terminal lobe of TRIB2, enabling specific recognition of TRIB2 in an activated conformation that is similar to the C/EBPα-bound state of TRIB1. Characterization in solution revealed that Nb4.103 can stabilize a TRIB2 pseudokinase domain dimer in a face-to-face manner. Conversely, a distinct nanobody (Nb4.101) binds through a similar epitope but does not readily promote dimerization. In combination, this study identifies features of TRIB2 that could be exploited for the development of inhibitors and nanobody tools for future investigation of TRIB2 function.

Gray fox (Urocyon cinereoargenteus (Schreber, 1775)) populations in portions of the eastern United States have experienced declines whose trajectories differ from those of other mesocarnivore populations. One hypothesis is that gray fox declines may result from interspecific interactions, particularly competition with abundant coyotes (Canis latrans Say, 1823). Alternatively, gray foxes may respond negatively to increased urbanization and reduced forest cover. To evaluate these hypotheses, we used single-species occupancy models of camera trap data to test the effects of habitat covariates, such as the amount of urbanization and forest, on coyote and gray fox occupancy. Additionally, we test the effect of an index based on an N-mixture model of the number of coyotes at each camera trap site on gray fox occupancy. Results indicate that occupancy probabilities of coyote and gray fox relate positively to the amount of forest, but they provided no evidence urban cover impacts gray foxes. Additionally, gray fox occupancy was negatively related to the index of the number of coyotes at each site. Our models support the idea that interactions with coyotes impact gray fox occupancy across the eastern United States. These results illustrate how large-scale studies can relate mechanisms identified within specific landscapes to phenomena observed at larger scales.

Purpose To compare the clinical outcomes in femtosecond laser–assisted deep anterior lamellar keratoplasty (F-DALK) to manual non-laser deep anterior lamellar keratoplasty (M-DALK) for keratoconus in a multi-surgeon public healthcare setting. Design Single-center, comparative, retrospective interventional case series. Methods P opulation : Consecutive cases of keratoconus treated with big-bubble F-DALK from August 1, 2015, to September 1, 2018 and big-bubble M-DALK from September 1, 2012, to September 30, 2016. S etting : Moorfields Eye Hospital, London. O bservations : Data on preoperative status, operative details, intraoperative and postoperative complications, secondary interventions, and visual outcomes were archived on a customized spreadsheet for analysis. M ain O utcome M easures : Rate of intraoperative perforation and conversion to penetrating keratoplasty (PK) and the percentage of patients, post removal of sutures (ROS), with corrected distance visual acuity (CDVA) ≥20/40. Results We analyzed 58 eyes of 55 patients who underwent F-DALK and 326 eyes of 309 patients who underwent M-DALK. Intraoperative perforation of Descemet membrane occurred in 15 of 58 (25.9%) F-DALK cases compared to 148 of 326 (45.4%) M-DALK cases (P = .006). Intraoperative conversion to PK was carried out in 2 of 58 (3.4%) F-DALK cases compared to 80 of 326 (24.5%) M-DALK cases (P = .001). Post ROS, 86.5% of F-DALK eyes had a CDVA of ≥20/40 (15 ± 7.3 months after surgery) compared to 83.7% of M-DALK eyes (24.9 ± 10.6 months) (P = .825). Conclusion Laser automation of some steps in DALK for keratoconus may reduce the rate of intraoperative Descemet perforation and the conversion to PK in a multi-surgeon setting.

While many resources exist for the drug screening of bladder cancer cell lines in 2D culture, it is widely recognized that screening in 3D culture is more representative of in vivo response. Importantly, signaling changes between 2D and 3D culture can result in changes to drug response. To address the need for 3D drug screening of bladder cancer cell lines, we screened 17 bladder cancer cell lines using a library of 652 investigational small-molecules and 3 clinically relevant drug combinations in 3D cell culture. Our goal was to identify compounds and classes of compounds with efficacy in bladder cancer. Utilizing established genomic and transcriptomic data for these bladder cancer cell lines, we correlated the genomic molecular parameters with drug response, to identify potentially novel groups of tumors that are vulnerable to specific drugs or classes of drugs. Importantly, we demonstrate that MEK inhibitors are a promising targeted therapy for the basal subtype of bladder cancer, and our data indicate that drug screening of 3D cultures provides an important resource for hypothesis generation.

A distinctive fishtail feature in multifractal spectra derived from heart rate variability (HRV) data closely resembles similar features in plots of the Gibbs free energy versus reduced pressure for a van der Waals fluid below the critical temperature, and, in analogy to the nonideal fluid, signals a phase transition from one multifractal state to another. This fishtail feature, often overlooked or dismissed in previous studies, is observed most prevalently in unhealthy patients and suggests a realignment between multifractal variables and their thermodynamic analogs. The van der Waals analogy and subsequent alternate interpretation of multifractal variables and functions lead one to construct a three-dimensional heart health phase diagram reminiscent of a [Formula: see text] diagram for the van der Waals fluid. The diagram which makes use of the Maxwell width as a measure of heart health produces an orderly progression from healthy to unhealthy.

The operating temperature is a critical parameter in atom probe tomography experiments. It affects the spatial precision, mass resolving power and other key aspects of the field-evaporation process. Current commercially available atom probes operate at a minimum temperature of ∼25 K when measured at the specimen. In this paper, we explore and implement changes to the mechanical design of both the LEAP