Certified community forests combine local governance with forest certification and aim to serve multiple objectives including forest protection, restoration, human wellbeing and equitable governance. However, the causal pathways by which they impact these objectives remain poorly understood. The ability of protected area impact evaluations to identify complex pathways is limited by a narrow focus on top-down theoretical, quantitative perspectives and inadequate consideration of local context. We used a novel mixed-methods research design that integrates the perspectives of multiple actors to develop a generalized conceptual model of the causal pathways for certified community forests. We tested the model using a combination of statistical matching, structural equation modelling and qualitative analyses for an agroforestry landscape in Tanzania. We found certified community forests positively impacted human wellbeing, equitable governance and forest restoration. Equitable governance had the largest impact on wellbeing, followed by crop yield and forest resource availability. Timber revenues varied widely between villages and the average effect of financial benefits did not impact wellbeing due to the immature stage of the certified timber market. We identified positive interactions and trade-offs between conservation and agriculture. Our findings suggest that no simple solution exists for meeting multiple objectives. However, developing understanding of the pathways linking social and conservation outcomes can help identify opportunities to promote synergies and mitigate negative impacts to reconcile competing objectives.This article is part of the theme issue ‘Understanding forest landscape restoration: reinforcing scientific foundations for the UN Decade on Ecosystem Restoration’. However, over the last 50 years the roles of PAs have expanded to include human wellbeing and equitable governance objectives ,2. Some Certified Community Forests (CFs) represent a new generation of PAs seeking to meet the expanding role of PAs, by combining two recent trends in forest PA governance: (i) decentralization—transferring governance responsibility from central governments to local actors in efforts to enhance equitable governance; (ii) forest certification to increase the financial benefits and equitable benefit sharing to incentivize sustainable management . Forest Analysis of causal pathways can be used to explain the complex processes by which PAs impact outcomes . Win-winHowever, the presence of negative interactions between social and ecological outcomes would result in trade-offs between PA objectives. For example, if conservation governance is perceived as being unfair, this could lead to conflicts and local resistance , as occuAdvances in the field of impact evaluation have seen the mainstreaming of statistical matching to exclude alternative explanations and attribute observed differences to the intervention . Howevera priori hypotheses of how PAs impact wellbeing or conservation using exclusively quantitative approaches. This top-down framing of a study system excludes local perspectives and has been described as creating a ‘bottleneck’ in dialogue [Secondly, impact evaluations tend to test dialogue , which mdialogue ,26. GreaWe aim to advance methods to evaluate the success of conservation and restoration interventions. We identify and test the causal pathways by which certified CFs impact human wellbeing and forest restoration for a case study in Tanzania. Specifically, we evaluate win-win assumptions of PA governance by testing pathways of (i) equitable governance, (ii) financial benefits, (iii) interaction effects and (iv) trade-offs.We advance on existing evaluation methodologies by (i) combining statistical matching with a conceptual model (ii) integrating top-down theoretical perspectives with bottom-up perspectives of local actors to promote inclusive consideration of alternative explanations from marginalized actors. We thereby contribute to two key knowledge gaps of the United Nations Decade on Restoration: (i) methods for designing interventions, and monitoring restoration success; (ii) linkages between the health of ecosystems and the flow of services to communities .. 2 (a)Tanzania provides an excellent test case of the challenges to reconcile forest restoration and human wellbeing objectives as national development policies aim to expand both agricultural and PA land uses, while CFs are often established on forests already considered to be degraded and economically marginal . We focu (b)Our conceptual model aimed to integrate actor perspectives with hypothesized pathways derived from conservation science literature . We consA thematic analysis of transcripts was then undertaken to identify actor perspectives of the main pathways linking certified CFs with conservation and human wellbeing impacts by identifying logical causal statements that were similar between independent consultation sessions. Identified pathways were then converted into a connected sequence of indicators linking CF governance via one or more causally linked mechanisms to human wellbeing and conservation impacts . The overall conceptual model was then composed of these main pathways. Indicators may be connected to more than one pathway if the causal logic suggested interactions between indicators from different pathways.All indicators in the conceptual model were included in a quantitative questionnaire to collect data on community perceptions of all indicators, which were then used to test the model. Our conceptual model emphasizes measuring ‘bottom-up’ community perceptions, rather than externally measured data sources because perceptions are important drivers of local behaviour and success of conservation interventions . (c)To improve the causal inference of our study we used statistical matching to compare certified CFs to control villages that represent the counterfactual situation—what would have happened in the absence of the intervention . This apThe questionnaire was undertaken with 955 people from the nine villages with certified CFs and 10 matched control villages, with at least 50 respondents per village stratified by gender, local elite status  and wealth category . The questionnaire was undertaken at the scale of individuals rather than whole households since the concept of wellbeing contains subjective elements which cannot be generalized across households . (d) (i)Multidimensional human wellbeing provides a comprehensive measure of social impacts. Wellbeing indicators were identified following the Wellbeing Indicator Selection Protocol  by a sub (ii)Miombo woodlands were the dominant forest type in the study landscape. Normalised difference vegetation index (NDVI) correlates with ground vegetation biomass and productivity under low to medium vegetation density conditions such as the Miombo woodlands . NDVI ch (iii)Equitable governance concerns notions of fairness , in rela (e)We tested the conceptual model by structural equation modelling using PiecewiseSEM in R . Latent We included socio-economic indicators for local elite status and gender in models to account for any systematic perception biases between actors. To account for residual imbalances in the distributions of confounding variables between treatment and control groups we included orthogonal sets of confounding variables as predictors of response variables . We thenr2 values (the variance explained by fixed effects).For continuous variables, we report standardized path coefficients, which estimate the expected change in the response variable (e.g. wellbeing) as a function of the change in the explanatory variable (e.g. equitable governance), in units of standard deviation. For categorical variables (e.g. governance treatment versus control group), we report the model-estimated means for each factor level . For allp < 0.05). Finally, we critically reviewed the conceptual model through triangulation with the qualitative data to assess whether the identified pathways and trends were representative of different village cases and actors sampled. This served as a verification check to ensure inclusive representation of pluralistic perspectives, particularly potentially marginalized or minority actors whose perspectives might otherwise be masked by reporting normative trends.We assessed the overall model fit by Shipley's test of d-separation, accepted when Fisher's C statistic is higher than a significance level , with mean scores of all equitable governance indicators  higher in villages with certified CFs than control villages. In turn, equitable governance positively impacted human wellbeing both directly (standardized estimate = 0.18) and indirectly . The indWe have a lot of forest here and we work to manage it. But we have a limited number of customers and so the villagers here have not yet felt the actual benefit of this forest. But if we could get many customers to buy our timber then every member of this village could realize the importance of managing the forest - Village Natural Resource Committee Secretary, village 11.Second, a financial benefits pathway blue, , wherebyHowever poor economic performance was not the case in all villages. Annual timber revenue was highly variable between certified CFs . The size of certified CFs was also highly variable , with larger CFs generating more revenue. Some differentiation in timber revenue spending was observed between villages; the highest timber producing village able to undertake additional, larger-scale and more diverse community development projects, including (i) building new village government offices, (ii) installing primary school sanitation facilities, (iii) improved village healthcare provision targeting facilities for pregnant women and disabled patients and health insurance for village natural resource committee members, (iv) building a village-run guesthouse, (v) payment for forest patrols, planning meetings and patrol equipment, (vi) payment for professional forestry and governance training services from the supporting NGO MCDI and the district government forest office. An FSC-certified sawmill factory run by a sustainable timber production company called Sound and Fair had also been established in this village in 2017 to further up-scale timber production and revenue generation, providing additional employment opportunities.Third, a conservation pathway green,  showed tWe are funding our own forest management activities. We pay even from our own village basket for meetings and patrols - Village Natural Resource Committee member, village 2.Fourth, positive interaction pathways were hypothesized from social to conservation outcomes yellow,  with posThe government extended the national forest reserve boundary and so we have been left with a small area for farming. That land, it was very fertile, it was supporting us to have high production and we had a lot of food surplus. But now we have little food because we harvest very little – Community member, village 1.Fifth, trade-off pathways were hypothesized between conservation and agriculture red, . Focus gLarger certified CFs were also suggested by MCDI to have more economic potential for timber revenue, creating a trade-off between land uses. However, testing of our conceptual model did not show an impact of certified CFs on perceived land availability or knock-on impacts of perceived land availability for farming on crop yield or timber revenue.. 4We found evidence of both win-win and trade-off pathways from certified CF governance to forest recovery and human wellbeing. Certified CFs positively impacted (i) equitable governance and (ii) forest recovery and both pathways positively impacted wellbeing, supporting win-win assumptions that positive social and conservation outcomes can occur together and are causally linked. However, additional hypothesized win-win pathways of (iii) financial benefits from certified CFs and (iv) improved attitudes towards conservation did not impact either wellbeing or forest restoration, suggesting that the importance of these pathways was limited in our case study. The limitation of the economic pathway linking forest governance to wellbeing may be due to the FSC timber market being at an early stage of development and operating sub-optimally. While some villages were able to generate significant FSC timber revenue, which was used to deliver integrated programmes to improve human wellbeing, concerns were raised by other villages about the challenges of accessing timber markets. Nevertheless, these findings agree with other research suggesting that equitable governance can be a more important driver of successful conservation than financial incentives . FinallyBy disaggregating the impacts of PA governance into multiple pathways it is possible to identify which aspects of an intervention are performing well and which aspects are failing. In our case study, the governance equity component of certified CFs had a positive impact, in contrast to other CF programmes in Tanzania . HoweverBy comparing quantitative and qualitative findings it is possible to explore how variation in contextual factors can lead to alternative outcomes. Not all CFs showed poor financial performance. The village that  established the largest CF, was also generating the most timber revenue, which was spent on diverse community projects, including additional income generation schemes such as a village-run guesthouse. The economic potential of this village had also attracted the establishment of an FSC-certified sawmill, in contrast to other villages which struggled to attract timber buyers. This more economically successful village, contrary to the general trend identified by modelling analyses, suggests that improved financial performance may require villages to dedicate significant land area to CFs and that strategies are needed to improve engagement with timber markets.The positive interaction pathways suggest the potential for virtuous cycles to occur over time , where pThe trade-off pathways, whereby forests provide both ecosystem benefits and costs for agriculture and potential agricultural land-shortages caused by expansion of PAs, suggest that the study landscape represents a microcosm of global challenges to reconcile forest conservation with rural development objectives ,5. We diOur research design sort to embrace a complex systems perspective. However, several simplifications were necessary to aid interpretation. To support a statistical comparison, we employed a binary distinction between the governance approaches of certified CFs and control villages. However, we recognize that within this overarching governance grouping, varying governance arrangements exist. To move beyond a coarse binary description of governance approaches, we employed qualitative methods to highlight outlying cases that contrasted with the normative quantitative trends reported. However further exploration of the within-group variation in governance approach would be possible through more in-depth case study research . Both huOur novel methodology illustrates the utility of a mixed methods approach for developing and testing theory of complex systems, with quantitative analyses showing overall trends, while qualitative analyses identifying alternative pathways missed by normative analyses. The integration of multiple actor perspectives provided a more comprehensive and contextualized understanding of pathways that balanced assumed positive and negative impacts of forest governance on people and forest recovery. By integrating views of actors from the global south our methodology makes progress in operationalizing calls for a pluralistic perspective of conservation challenges , to impr


Xenopus laevis, have revealed that efference copies (ECs) of the spinal motor program that generates axial- or limb-based propulsion directly drive compensatory eye movements. During fictive locomotion in larvae, ascending ECs from rostral spinal central pattern generating (CPG) circuitry are relayed through a defined ascending pathway to the mid- and hindbrain ocular motor nuclei to produce conjugate eye rotations during tail-based undulatory swimming in the intact animal. In post-metamorphic adult frogs, this spinal rhythmic command switches to a bilaterally-synchronous burst pattern that is appropriate for generating convergent eye movements required for maintaining image stability during limb kick-based rectilinear forward propulsion. The transition between these two fundamentally different coupling patterns is underpinned by the emergence of altered trajectories in spino-ocular motor coupling pathways that occur gradually during metamorphosis, providing a goal-specific, morpho-functional plasticity that ensures retinal image stability irrespective of locomotor mode. Although the functional impact of predictive ECs produced by the locomotory CPG matches the spatio-temporal specificity of reactive sensory-motor responses, rather than contributing additively to image stabilization, horizontal vestibulo-ocular reflexes (VORs) are selectively suppressed during intense locomotor CPG activity. This is achieved at least in part by an EC-mediated attenuation of mechano-electrical encoding at the vestibular sensory periphery. Thus, locomotor ECs and their potential suppressive impact on vestibular sensory-motor processing, both of which have now been reported in other vertebrates including humans, appear to play an important role in the maintenance of stable vision during active body displacements.Vertebrate locomotion presents a major challenge for maintaining visual acuity due to head movements resulting from the intimate biomechanical coupling with the propulsive musculoskeletal system. Retinal image stabilization has been traditionally ascribed to the transformation of motion-related sensory feedback into counteracting ocular motor commands. However, extensive exploration of spontaneously active semi-intact and isolated brain/spinal cord preparations of the amphibian  Gaze stabilization during both self-generated and passive motion is essential for constantly maintaining retinal image acuity as a prerequisite for stable perception of the visual world . During While the sensory-motor transformations subserving gaze stabilization are well documented for passive head/body motion, the processes operating during self-generated movements have remained more elusive. Over the last decade, however, evidence has accumulated that intrinsic copies of the actual motor commands responsible for an animal’s propulsive axial or limb movements may also provide a source of neuronal signals for retinal image stabilization . Due to Xenopus laevis, consisting of the head—including inner ears, eyes and eye muscles—along with the still-attached and isolated spinal cord  may provide a functional blueprint that extends to other vertebrates, including humans.Here, we review evidence for the involvement of this novel mechanism during rhythmic undulatory and limb-based swimming in larval and juvenile Xenopus, which occurs mostly in the horizontal plane, both eyes oscillate in conjugation during left-right head excursions resulting from undulatory tail movements  pathway that is known to be involved in producing conjugate eye movements , the ocular motor performance remains exclusively coordinated with the tail undulations, without any evident VOR contributions to eye motion . The strThe suppression of vestibular afferent influences during high-intensity larval swimming might be spatially specific to inputs from the horizontal semicircular canals, or might represent a generalized filtering process that applies to all vestibular signals irrespective of their peripheral origin. To distinguish between these two possibilities, the influence of locomotor ECs on inputs from vestibular endorgans other than the horizontal semicircular canals was tested during passive motion around the longitudinal (roll) axis. In fact, an imposed left-right head roll motion caused a strong modulation of the LR nerve discharge that increased and decreased in strength during contra- and ipsiversive movements, respectively. The directionality of these evoked ocular motor responses and the low frequency (0.1 Hz) of the motion stimulus were consistent with the activation of vestibular signals predominantly arising from the gravitoinertial stimulation of utricular hair cells . SignifiXenopus tadpoles can be conferred by locomotor ECs rather than by VOR-producing sensory-motor transformations, this mechanism also has hitherto unsuspected implications for issues ranging from the evolution of the horizontal semicircular canals to the maintenance of postural stability during locomotion in human patients with vestibular disorders  synapse in the vestibular nuclei, or peripherally, at the synaptic connection between hair cells and vestibular nerve afferent fibers in the inner ear endorgans themselves  at which the suppression of spatially-specific signals in the VOR circuitry occurs, nor the underlying neurophysiological mechanism(s), have been fully established. Such an understanding requires identifying the anatomical pathways that convey the intrinsic CPG-derived signals and the suppressive processes operating at single or multiple synaptic levels. In principle, establishing these underlying features benefits from the simple organization of the VOR circuitry, which is comprised of a three-neuronal reflex arc for integrating angular and translational/gravitoinertial sensory signals . This shemselves .Xenopus, such an efferent neuron activation was indeed revealed by multi-unit recordings from the central severed ends of the anterior and posterior branches of a vestibular  nerve  nerve . During l) nerve , that thl) nerve .2+ transients were recorded in practically all efferent neuronal somata (of which there are 10–15 per side located in rhombomere 4), with onsets and durations that were strictly correlated with those of the accompanying spinal Vr bursting  burst discharge recorded in vestibular nerve branches indicated that the latter activity precisely encodes swim episode duration and any changes in Vr burst cycle frequency and intensity. This faithful coupling thereby ensures that the major parameters of propulsive motor commands are conveyed to the sensory periphery.The proportion of efferent neurons that are activated during locomotion was assessed by somatic calcium imaging during episodes of fictive swimming monitored by spinal Vr recordings. During swim episodes, Cabursting . FurtherXenopus preparations with intact vestibular endorgans and preserved peripheral and central nerve connections (en passant during rotational stimuli applied in different spatial planes alone, and during the occurrence of spontaneous fictive swimming (The impact of locomotor-related efferent neuron bursting on vestibular sensory encoding of head/body motion was evaluated in semi-intact larval nections . Vestibuswimming . In the swimming , left. Hswimming , the measwimming . HoweverThe functional significance of the differential effects of efferent neuronal activity on the spontaneous firing of vestibular afferents and their sensitivity to motion stimuli might be related to the push-pull operation of the vestibular system itself. Here, the encoding of immobility relies on bilaterally-balanced population resting discharge rates throughout the afferent neuronal assemblage . AccordiAnother potential site for a suppressive action of locomotor ECs on sensory-motor processing resides within the central circuitry of the vestibular nuclei . Since vAlthough the selective suppression of ocular motor output in tadpoles during horizontal, but not vertical, head rotation is based on a spatial specificity, likely related to the plane of head undulations during axial swimming, an alternative explanation might involve a difference in the dynamic spectrum of activated vestibular afferent units during motion in the two rotational planes. Roll motion stimulation in the vertical plane activates sensory elements in the vertical semicircular canals but is also a highly effective gravito-inertial stimulus for the utricle, thereby activating a large proportion of hair cells/afferent vestibular fibers with more tonic response dynamics . This isAn involvement of cerebellar and local vestibular circuits in the gating of body motion-related sensory signals during locomotion would not be unexpected given previous knowledge of their roles in the control of gaze stabilization . In contIn an evolutionary context, locomotor EC-driven eye movements might constitute a vestige of an ancestral mechanism, appearing in early vertebrates before rotational motion-encoding semicircular canals had appeared . AlthougXenopus laevis, considerably less is known for such a role in other vertebrates. In lamprey, an extant jawless vertebrate species, the use of semi-intact, head-immobilized preparations after optic nerve transection and labyrinth ablation has very recently provided direct evidence that spinal CPG-derived ECs contribute to compensatory eye movements, coordinated with swimming undulations in the horizontal plane (Xenopus. This idea has been further supported by experimental galvanic stimulation of bilateral inner ear endorgans in human patients, which caused smaller trajectory deviations during running than walking (While the functional processes and underlying neuronal pathways by which locomotor ECs can stabilize gaze have been unequivocally demonstrated in the amphibian al plane . Howeveral plane . Furtheral plane . The remal plane  or pre-pal plane  and animal plane . In addial plane  and humaal plane , resultaal plane , then ECal plane , 2022. A walking , again c walking , 2022.ex vivo brain-spinal cord preparations of neonatal mice with spatio-temporal characteristics reminiscent of those described in Xenopus. This ocular motoneuronal pattern complied with rhythmic eye movements, mostly in the horizontal plane, which occurred in phase with the forelimb gait pattern during treadmill-elicited locomotion in decerebrated animals. Moreover, the ascending locomotor signals were likely to derive from cervical cord neurons that connect directly with abducens motoneurons, similar to the situation found in amphibians (More direct evidence for locomotor EC-driven eye movements has recently been discovered in mice, where the existence of a comparable spino-ocular motor coupling has been established by multi-methodological approaches . Brieflyphibians . Thus, sphibians .in vitro experiments on larval and young adult Xenopus laevis provided the initial demonstration that efference copies of axial- as well as limb-based locomotor commands are able to elicit retinal image-stabilizing eye movements. This intrinsic feed-forward mechanism is spatio-temporally specific, functionally appropriate and dynamically adaptive, being capable of initiating gaze-stabilizing eye movements according not only to the immediate strength of ongoing locomotion but also to its mode, even throughout the transitional period of metamorphic development as one locomotor strategy progressively replaces the other. The ability to provide retinal image stability during the change in body format, propulsive motion profile and associated visual demands derives from a remarkable rewiring plasticity of spino-ocular motor coupling pathways that co-exist in the metamorphosing animal. While the impact of predictive locomotor efference copies matches the specificity of reactive sensory-motor transformations, the two fundamentally different signals do not simply summate in the production of image-stabilizing ocular motor commands. Rather, depending on the intensity of spinal CPG activity, the horizontal VOR is selectively suppressed, at least in part by an attenuation of the motion signal encoding at the sensory periphery in the inner ear. Significantly, this gaze-stabilizing mechanism that relies on locomotor EC signaling is not merely idiosyncratic to amphibians with their simpler and more stereotyped locomotor movement profiles, but evidently is also employed by other vertebrates, including humans. Recent studies in both Xenopus and mice (Maintaining visual world stability during locomotion is a major challenge for all vertebrates. Avoiding retinal image slip due to passive or self-generated head/body motion is traditionally ascribed to the transformation of mechanosensory feedback signals into ocular motor commands that offset perturbing head movements to ensure stable eye position in space. However, this generally acknowledged concept has been challenged over the past decade by increasing evidence that ascending neuronal pathways enable the propulsive CPG circuitry in the spinal cord to directly access and drive the brainstem ocular motor system during locomotion. Various types of and mice  suggest and mice . This meHS and JS wrote the first draft of the manuscript. FL made the figures. HS, FL, and JS reviewed and edited the final version of the manuscript. All authors contributed to the article and approved the submitted version.


Due to antibiotic overutilization, development of antimicrobial stewardship (AMS) in the outpatient setting has become a necessary focus for AMS programs. The cornerstone of AMS is utilization of antimicrobial prescribing data to provide feedback to individual providers and compare providers to each other in order to promote improved prescribing practices. Respiratory infections, especially conditions that never require antimicrobials, are a common target for this feedback. We aimed to create interactive data visualization dashboards of end-users prescribing for these respiratory and otic conditions in order for AMS and urgent/quick care program staff to identify potential areas of intervention.A multidisciplinary work group consisting of data analysts, infectious diseases physicians, urgent/quick care physicians, and infectious diseases pharmacists determined dashboard content, layout, and comparison charts. Graph types were tested to determine optimal visual output. Using the electronic medical record ICD10 and antimicrobial prescription data was extracted for the encounter with focus on ICD10 codes for respiratory and otic conditions which never require antimicrobials. Rates were calculated as number of antimicrobial prescriptions over total number of visits for these conditions.A multi-faceted dashboard was developed in Tableau® to view antimicrobial prescribing rates. Dashboard capabilities include the option to view individual provider prescribing rates compared to other de-identified providers, overall clinic prescribing rate, or individual rate compared to clinic rate. This allows for quick direct comparison of antimicrobial prescribing on the same graph by clinic to identify outliers  and allows visualization of trends in prescribing rates by clinics and providers over time .Never Antimicrobial Prescribing Rate ComparisonScatter plot comparing individual prescribers rate of prescribing for never antimicrobial eventsClinic Antimicrobial Prescribing Rate TrendClinic prescribing rate trend over time for never antimicrobial eventsPrescriber and Clinic Antimicrobial Prescribing Rate TrendIndividual prescriber rate compared to clinic rate over time for never antimicrobial eventsWe developed an interactive outpatient AMS dashboard to visualize prescribing of antimicrobials for never respiratory and otic conditions. These dashboards can be used by providers along with AMS and clinic leadership to determine areas of intervention in the urgent/quick care setting.Kelly M. Percival, PharmD, Gilead Sciences Inc: Advisor/Consultant Patrick M. Kinn, PharmD, MPH, Gilead Sciences: Advisor/Consultant Dilek Ince, MD, Evergreen: Member of data monitoring board|Gilead Sciences: Grant/Research Support|Leidos: Grant/Research Support|Moderna: Grant/Research Support.


Pelvic fractures are common in cases of blunt trauma, which is strongly associated with mortality. Transcatheter arterial embolization is a fundamental treatment strategy for fatal arterial injuries caused by blunt pelvic trauma. However, vascular injuries due to blunt pelvic trauma can show various imaging findings other than arterial hemorrhage. We present a pictorial review of common and uncommon vascular injuries, including active arterial bleeding, pseudoaneurysm, arteriovenous fistula, arterial occlusion, vasospasm, and active venous bleeding. Knowledge of these vascular injuries can help clinicians select the appropriate therapeutic strategy and thus save lives. Pelvic fractures are not rare and account for approximately 3% of skeletal injuries . Pelvic Transcatheter arterial embolization (TAE) is the fundamental treatment strategy for patients with fatal arterial injuries caused by blunt pelvic trauma , 5. HoweTAE is the fundamental treatment strategy for active arterial bleeding due to pelvic fractures . Embolizn-butyl cyanoacrylate (NBCA) is useful for both selective and non-selective embolization; however, an experienced operator is desirable to prevent NBCA-related complications, such as reflux and non-target embolization . Ant. Ant8]. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an important method for treating severe hemorrhagic shock due to pelvic trauma. In this procedure, occlusion of the aorta with a balloon catheter is conducted to increase proximal arterial pressure and maintain organ blood flow while controlling downstream bleeding . HoweverThe formation of pseudoaneurysms in patients with blunt pelvic trauma, although rare, may occur immediately after the injury or later in the clinical course . PseudoaEndovascular treatment of traumatic pseudoaneurysm is usually effective Fig.  16]. Th. Th16]. AVF is an abnormal anastomosis between arteries and veins and does not involve capillaries. Traumatic AVF can develop if arterial bleeding influxes into an adjacent injured vein . On radiBecause traumatic AVF can cause heart failure after highly variable latency periods , AVFs shThe middle layer of blood vessels is made up of smooth muscles, and smooth muscle cells may contract and become spasmodic following external compression, stretching, or endothelial injury due to trauma . Active Arterial occlusion is caused by transmural injury or dissection with a thrombus . Active Traumatic occlusion of the main trunk of the common/external iliac artery can cause critical lower limb ischemia, making recanalization crucial . VasculaBleeding due to pelvic fractures occurs more frequently from veins (80%) than from arteries (20%); the main venous sources of bleeding are the presacral plexus and prevesical veins . PeritonActive venous bleeding can be visualized using CT as the extravasation of contrast material in venous phase images without extravasation in arterial phase images Fig.  20]. Il. Il20]. Transcatheter venous embolization with NBCA can potentially control critical bleeding from the iliac vein. However, it may cause some complications, such as leg swelling, deep vein thrombosis, and pulmonary embolism by obstruction of venous flow . EndovasWhen surgical treatment is chosen for a venous injury, balloon catheters can reduce bleeding and help obtain the necessary visualization of the operative field by occluding the proximal and distal portions of the injury .Endovascular treatment is effective for vascular injuries due to blunt pelvic trauma. Knowledge of the various forms and imaging findings of vascular injuries is essential for the astute planning of treatment strategies and life-saving maneuvers.


Events that occur in utero set the trajectory for later-life diseases and longevity. Compelling data exist for interactions between developmental programming and aging, but the underlying mechanisms are not clearly defined. Fetal exposure to glucocorticoids (GC) is associated with alteration in hepatic enzymes and metabolic function in later life. We previously reported increased hepatic lipid accumulation and obese phenotype in middle-age male baboons exposed to GC as fetuses. The mitochondria play significant roles in cellular processes including stress responses and possibly a nexus between developmental programming and aging. The present study investigated the long-term effects of in utero GC exposure on mitochondrial bioenergetics using hepatocytes derived from aging baboons . Mitochondrial bioenergetics of both left and right lobe liver hepatocytes were examined as well as potential sex differences in mitochondrial function. Cell viability following isolation was similar among sexes and liver lobes but hepatocytes from males were highly energetic compared to females. Significant bioenergetic differences were observed in hepatocytes isolated from female baboons’ left and right liver lobes, with higher basal, maximal, and ATP-linked respiration in left lobe hepatocytes compared to the right lobe. These lobe-specific bioenergetic differences were absent in males. Interestingly, H2O2-induced oxidative stress significantly modified male baboon hepatocyte bioenergetics but females were unaffected, suggesting mitochondrial resilience in females compared to males. These data demonstrate that early life exposure to GC elicits a sex-specific effect on mitochondrial function. These mitochondrial differences might drive differences in cell senescence between males and females.


This survey study uses 2020 American Hospital Association data to assess strategies of US hospitals serving vulnerable populations in addressing social needs during the COVID-19 pandemic. We used 2020 American Hospital Association (AHA) survey data to assess such strategies among rural hospitals, critical access hospitals (CAHs), and safety-net hospitals (SNHs) in the US.Hospitals may play a critical role in alleviating health inequities by addressing underlying social determinants of health (SDOH). Public interest in addressing social needs during the COVID-19 pandemic has been accompanied by substantial health system investments in SDOH.AAPOR reporting guideline.The Harvard School of Public Health Institutional Review Board approved this survey study. The AHA obtained respondent informed consent, with the agreement that hospitals would remain anonymous. The study followed the We used the 2020 AHA Annual Survey Social Determinants of Health Supplement, which surveyed hospitals’ efforts across 3 domains: screening for SDOH, programs/interventions to address SDOH, and community partnerships to address SDOH. The first domain assessed whether hospitals screened across 9 SDOH types. The second domain reported on whether hospitals had programs and/or interventions to address these SDOH. The third domain assessed whether hospitals worked with 14 types of external community partners to address SDOH, participate in community health needs assessments, and implement SDOH initiatives. We created 3 index scores across each domain  responded to the SDOH items . In adju6The results of this survey study suggest that rural hospitals, CAHs, and SNHs are not doing more and, in some cases, are engaging in fewer strategies to address the SDOH of their vulnerable populations, especially regarding community partnerships. This finding may be attributable to limited financial resources, workforce constraints, limited community resources and institutional partnerships, and lack of incentives.Study limitations include limited granularity of categorial responses of hospital efforts, potential variability and unreliability of respondent accuracy, and limited generalizability. The AHA survey also does not validate whether hospitals implemented the reported strategies or their effectiveness. Addressing resource barriers that hospitals serving vulnerable populations may face in implementing SDOH initiatives should be considered a key state and federal policy strategy for improving health equity.


In humans, various dietary and social factors led to the development of increased brain sizes alongside large adipose tissue stores. Complex reciprocal signaling mechanisms allow for a fine-tuned interaction between the two organs to regulate energy homeostasis of the organism. As an endocrine organ, adipose tissue secretes various hormones, cytokines, and metabolites that signal energy availability to the central nervous system (CNS). Vice versa, the CNS is a critical regulator of adipose tissue function through neural networks that integrate information from the periphery and regulate sympathetic nerve outflow. This review discusses the various reciprocal signaling mechanisms in the CNS and adipose tissue to maintain organismal energy homeostasis. We are focusing on the integration of afferent signals from the periphery in neuronal populations of the mediobasal hypothalamus as well as the efferent signals from the CNS to adipose tissue and its implications for adipose tissue function. Furthermore, we are discussing central mechanisms that fine-tune the immune system in adipose tissue depots and contribute to organ homeostasis. Elucidating this complex signaling network that integrates peripheral signals to generate physiological outputs to maintain the optimal energy balance of the organism is crucial for understanding the pathophysiology of obesity and metabolic diseases such as type 2 diabetes. In most mammalian species, the size of the brain and adipose depots are inversely correlated, indicating compensatory buffering strategies to protect against starvation . HoweverThis review highlights the coordinated reciprocal signaling between the CNS and white adipose tissue. We are discussing the integration of afferent signals from the periphery in neuronal populations of the mediobasal hypothalamus as well as the efferent signals from the CNS to adipose tissue and its implications for adipose tissue function. Furthermore, we are focusing on central mechanisms that regulate resident immune cell function in adipose tissue depots and subsequently contribute to organ homeostasis.The brain interacts with white adipose tissue depots through distinct efferent sympathetic nerves, releasing the catecholamine norepinephrine (NE) from their nerve terminals. In white adipose tissue (WAT), sympathetic nerve terminals are located adjacent to >90% of adipocytes, forming a dense network of sympathetic arborizations . Importaα- and β-adrenoceptors (α- and β-ARs) on adipocytes (s protein and activation of adenylate cyclase (AC), which increases intracellular cAMP levels. High cAMP levels activate protein kinase A (PKA), which phosphorylates hormone-sensitive lipase (HSL) and perilipin-A (PLIN1). This initiates a signaling cascade that leads to the activation of lipases, such as adipose triglyceride lipase (ATGL) and monoglyceride lipase (MGL) or α/β hydrolase-domain 6 (ABHD6), allowing triglycerides to be hydrolyzed sequentially into fatty acids (FA) and glycerol , which is co-stored with NE, is released from sympathetic nerve terminals and inhibits lipolysis by binding to its receptor NPYR1 . NPY recvia afferent sensory feedback in order to maintain thermoregulation.Lipolysis increases the availability of free fatty acids which in turn activate local WAT afferents that mediate acute induction of thermogenesis in distant BAT depots . This davagus efferent axis regulates fat mass gain , the ventromedial hypothalamus (VMH), the dorsomedial hypothalamus (DMH), the lateral hypothalamus (LH) and the paraventricular nucleus of the hypothalamus (PVH) . These nThe most well-defined neurocircuit in the context of integrative physiology is the melanocortin system, which consists of the functionally antagonistic anorexigenic proopiomelanocortin (POMC)-expressing neurons and the orexigenic agouti-related peptide (AgRP)-expressing neurons in the arcuate nucleus (ARC) of the mediobasal hypothalamus . POMC neImportantly, both AgRP and POMC neurons express receptors for leptin, insulin and other energy-state communicating hormones and are therefore subject to feedback regulation .PVH) dynamically regulates the sympathetic innervation downstream of leptin-sensitive AGRP and POMC neurons in the ARC  in white adipocytes enhances sympathetic activity  mRNA . Pharmacvia the circulation, but also through sensory innervation of adipose depots. Sensory nerve endings allow for the detection of local leptin levels directly in the adipose tissue depot  . ATMs frvia the production and secretion of acetylcholine, which acts on adipocytes via acetylcholine receptors, stimulating the PKA pathway and subsequently inducing thermogenic gene expression  has been shown to decrease food intake in mice and inhibit adipocyte development . NPFF isin vivo and in vitro studies have shown anti-inflammatory effects mediated by melanocortin agonists acting on macrophages  expressed in adipose tissue resident immune cells . Severalrophages . For exarophages . Activatrophages . Howeverrophages . These lrophages .via neurotransmitter release.It is clear that ATMs impact the innervation of adipose tissue in numerous ways and vice versa the adipose tissue innervation directly impacts ATM functions via the neuroregulatory receptor RET, which ultimately leads to an increased cytokine secretion , thereby regulating adipocyte function and energy expenditure  were recently shown to be indirectly regulated by the SNS . Activatenditure . Mice wienditure . Notablyenditure .via the IL-17F effector cytokine (The neurotransmitter acetylcholine (ACh) is an important contributor to immune cell function [for review see  and Cox] and B ccytokine . TGFβ1 pcytokine . CollectUnderstanding the complex signaling networks that integrate energy availability signals from adipose tissue in the CNS to generate physiological outputs is crucial for understanding the pathophysiology of obesity and metabolic diseases such as type 2 diabetes. The findings discussed in this review clearly highlight the importance of the melanocortin system in the CNS-adipose crosstalk. However, specific neuronal populations in the mediobasal hypothalamus modify the activity of melanocortin neurons. Defining the exact molecular nature of these regulatory neurons has proven challenging. Owing to their structural and functional diversity, our current understanding of the neurocircuits involved in the control of adipose tissue is still limited. Recent technical advances in neuroscience have led to the possibility of identifying and characterizing the neurocircuits involved in the control of adipose tissue homeostasis. Identifying druggable targets on these specific neuronal populations is a prerequisite for developing novel interventions and therapeutic approaches for obesity and associated metabolic diseases.


Cognitive reserve (CR) refers to adaptability allowing for better cognitive outcomes given the degree of brain changes or other risk factors for cognitive decline. Despite significant research efforts, our knowledge of cognitive reserve proxies remains limited. Studies predominantly use a single sociodemographic variable  as a proxy measure when CR can manifest in multiple domains. Studies also tend to rely on older samples, whereas adversity factors of cognitive performance may have differing onset ages, suggesting different risk or protective mechanisms at different ages. We examine two cohort datasets spanning from early adolescence  up to the cusp of mid-adulthood  to evaluate the role of CR proxies across over 100 variables. Defined as a moderator between a cognitive outcome and structural brain measure, these variables cover behavioral, environmental, physical and mental health, and psychological trait domains. Using cross-validated regularized regression, we identified dozens of factors acting as CR proxies . We then use a within-family design to examine the moderation effect over and above genetic and environmental covariates. For example, adolescents who read more tend to show better cognitive performance given their gray matter volume . This study aims to identify factors that could be targeted with scalable prevention and intervention efforts earlier in life to maximize cognitive functioning.


Cartilage diseases affect a large population worldwide and are associated with a significant burden to patients and society. Osteoarthritis (OA) is the most common chronic joint disorder and the fastest growing cause of disability. Cartilage focal defects, predisposing to early OA and degeneration impair the function of many joints, including the articular joint, intervertebral disc and temporomandibular joint. Presently, no effective therapy is available, except for palliative care primarily used to delay invasive and often suboptimal surgical interventions. Regenerative medicine therapies directed at the early stage of osteoarthritis, and tissue engineering approaches to reconstruct cartilage defects provide great potential for cartilage and joint repair in the future. This current research topic represents a collected series of articles in this field. Highlights are summarized below.Liu et al. provided a timely review describing the factors that affect cartilage homeostasis and function, and the emerging regenerative approaches that are informing the future treatment options. Tissue engineering approaches combining cell and biomaterial strategies to reconstruct the complex and functional cartilage tissue are still under active research. Two review articles in the current topic have described the use of 3D printing technology in cartilage tissue reconstruction in general  and for irregularly shaped cartilage in particular . Electrospun gelatin/polycaprolactone (GT/PCL) nanofiber membranes at optimum GT/PCL ratio were used to support in vivo cartilage regeneration from autologous chondrocytes in a swine model . Also xenogeneic acellular cartilage matrix (ACM) materials encapsulated with autologous chondrocytes showed capacity to promote cell proliferation and cartilage formation in goat, with only a minor immune-inflammatory response . This provides scientific evidence for future clinical application of ACM in cartilage tissue engineering. Next to biomaterials, appropriate cell sources are important for cartilage repair. Combined physioxia and fibronectin adherence have shown to select and propagate a meniscus progenitor population that can potentially be used to treat meniscal tears or defects . Additional stimuli can further enhance the cartilage repair potential of cells. For example, a magnetic field applied to magnetic nanoparticles-loaded cells decreased cellular senescence and enhanced chondrogenic capability of adipose-derived mesenchymal stem cells . Senescence can also be targeted using a senolytic peptide, fork head box O transcription factor 4-D-Retro-Inverso (FOXO4-DRI), which removed the senescent cells among chondrocytes .Bi et al. have established an model combining transection of the anterior and posterior cruciate ligaments, and the meniscus, and a cartilage defect in rhesus macaques, which closely resembled the pathophysiological processes of spontaneous knee OA in humans.Last but not least, appropriate animal models for OA are still lacking and play a pivotal role in the development of regenerative therapies.


Whole-exome and targeted sequencing are widely utilized both in translational cancer genomics and in the setting of precision medicine. The benchmarking of computational methods and tools that are in continuous development is fundamental for the correct interpretation of somatic genomic profiling results. To this aim we developed synggen, a tool for the fast generation of large-scale realistic and heterogeneous cancer whole-exome and targeted sequencing synthetic datasets, which enables the incorporation of phased germline single nucleotide polymorphisms and complex allele-specific somatic genomic events. Synggen performances and effectiveness in generating synthetic cancer data are shown across different scenarios and considering different platforms with distinct characteristics.https://bitbucket.org/CibioBCG/synggen/.synggen is freely available at Bioinformatics online. The interrogation of next-generation sequencing (NGS), principally whole-exome (WES) and targeted sequencing (TS), is rapidly becoming a preferred approach for the exploration of large tissue and liquid biopsy-based cohorts, especially in the context of precision medicine. In this setting, a precise benchmarking of the large collection of computational tools that are continuously developed is fundamental for the correct interpretation of somatic genomic profiling results. Although many simulators of synthetic cancer genomes and NGS data have been developed in the last years  combine these reference models and a set of user-specified germline and somatic genomic profiles to create synthetic sequencing files (FASTQ format).Synggen is a tool written in C programming language to generate synthetic NGS files, in the form of WES or TS experiments, representing heterogeneous cancer genomes and matched controls. The tool provides two execution modes which allow to (i) exploit a set of control (non-cancer) NGS sequencing files (BAM format) to generate three Read Depth Model (RDM), which measures the average intra-sample depth of coverage variability by calculating the probability, across all input files, of observing sequencing reads at any captured genomic region and position; only reads aligning at the lowest genomic coordinate are considered when paired-end data is used; (ii) a Quality Model (QM), which measures the distribution of base qualities across sequencing read positions; (iii) Position-Based Error (PBE), which measures for each captured genomic position [not representing a common single nucleotide polymorphism (SNP)] the probability of observing platform-specific systematic errors supported by high quality reads and bases  and point mutations (PMs). Phased SNPs are used to realistically represent the genetic background of specific individuals and to generate both cancer and matched control samples. Somatic CNAs are defined as allele-specific copy numbers  and are incorporated across all affected WES/TS captured regions to modulate the RDM distribution and to adjust SNP allelic fractions. Of note, both overlapping and nested somatic copy number alterations can be represented  samples (BAM files) available from The Cancer Genome Atlas dataset, focusing on patients having high (>80%) tumor content WES (Sure Select All Exome v3) cancer tissue samples. Generation of synthetic NGS cancer data was instead tested for increasing number of sequencing reads produced. A cancer sample was generated with tumor content at 80% and incorporating patient-specific germline SNPs and patient-specific somatic CNAs and PMs (details in the To demonstrate the effectiveness of synggen in generating benchmarking datasets, we simulated two liquid biopsy cfDNA scenarios considering data produced in We developed synggen to perform fast and scalable generation of cancer and matched control WES and TS synthetic data without the need for intermediate FASTA files generation and exploiting multi-threaded computation. Synggen allows to emulate platform-specific NGS data characteristics and allows to incorporate germline-phased SNPs and complex somatic allele-specific copy number alterations and point mutations. In addition, it allows to create clonal and sub-clonal events across different tumor content scenarios enabling the generation of large-scale complex benchmarking datasets. Synggen is easy to use and is provided with a collection of additional scripts to simplify further its usability.Conflict of Interest: none declared.btac792_Supplementary_DataClick here for additional data file.


Both pain and mental illness associate with work disability. However, few studies have examined the association of concurrent pain and mental distress with sickness absence (SA). We examined separate and joint associations of chronic pain, multisite pain, and mental distress with total and long-term all-cause SA among young and midlife municipal employees.As part of the Young Helsinki Health study, baseline data were collected in 2017 from 19-39-year-old employees of the City of Helsinki, Finland. Chronic (≥3 months) pain, multisite (≥2 body sites) pain and mental distress  were reported by 3911 respondents. Register data on total (>1 day) and long-term ((>11 workdays) SA for the following year were obtained from the employer and the Social Insurance Institute of Finland with respondents’ informed consent. Negative binomial regression analyses were performed with sociodemographic, socioeconomic, and health-related factors as confounders. The interaction of gender was examined.Chronic pain, multisite pain, and mental distress were associated with total SA. Chronic multisite pain was associated with long-term SA , and chronic pain  and multisite pain  with long-term SA among those with mental distress. For women, there was a synergistic interaction of multisite pain to the association with total SA .Chronic and multisite pain associate with SA among young and midlife employees. The associations are generally stronger among women and particularly among those with concurrent mental distress. Interventional studies are needed to confirm if early symptom recognition and support could reduce sickness absence.• Chronic pain and pain at multiple body sites associate with sickness absence among young and midlife employees, particularly among women and those with concurrent mental distress.• Interventional studies are needed to confirm if sickness absence could be reduced by early recognizing pain and mental distress among employees and providing preventive and therapeutic services.


Although research has shown that food insecurity may lead to sleep problems due to mental illness, it remains unclear whether physical health also mediates this relationship in addition to poor mental health. We investigated whether frailty and depressive symptoms mediated the association of food insecurity with sleep deficiency  among community-dwelling older adults. We analyzed the baseline data of the Longitudinal Study of Ageing and Health in the Philippines, a study with national representative sample of adults aged 60 years or older . Sleep deficiency was conceptualized as self-reported sleeping less than 6 hours, complaining about trouble with falling asleep and staying asleep, and/or having non-restorative sleep. Food insecurity was defined as being hungry and not having enough food in the past three months in the household. Frailty was operationalized using modified definitions under Fried’s criteria. Depressive symptoms were assessed using the Center for Epidemiological Studies-Depression Scale. Covariates included socio-demographics , health , and lifestyles . Mediation analysis was performed using PROCESS macro. The results from bootstrapping showed that the indirect effects from food insecurity through frailty  and depressive symptoms  onto sleep deficiency were significant, but the direct effect from food insecurity to sleep deficiency was not . The results suggested that the effects of food insecurity on sleep deficiency were fully mediated through frailty and depressive symptoms among community-dwelling older Filipinos. Preventing frailty and depression may help improve sleep health among individuals being food insecure.


The incidence of Anti-NMDA receptor encephalitis is 1.5 per million population per year but it has only been described sporadically in the paediatric population. The median age of onset is 21 years old. In children, seizures, abnormal movements, insomnia, and irritability are more frequently identified than psychosis or abnormal behavior. Early detection and treatment can improve treatment outcomes.Presentation of a case of a paediatric patient with Anti-NMDA receptor encephalitis displaying homicidal behavior towards her family membersCase reportA 12 year old with no significant past psychiatric and medical history, was brought in by police to the hospital after she attempted to stab her mother with a knife. She had low grade fever, headaches and lethargy prior to presentation. Organic workup revealed serum and CSF anti-nmda receptor to be positive. She received early treatment with steroids and intravenous immunoglobulins and no longer harboured further homicidal ideations.Initial suspicion of anti-NDMA receptor encephalitis should be raised and early auto-immune workup performed in paediatric patients presenting with acute change in behavior especially in young females with no past medical or psychiatric historyNo significant relationships.


The importance of resilience factors in the positive adaptation of refugee youth is widely recognised. However, their actual mechanism of impact remains under-researched. The aim of this study was therefore to explore protective and promotive resilience mechanisms on both negative and positive mental health outcomes. Promotive resilience is seen as a direct main effect and protective resilience as a moderating effect.Cross-sectional study with 160 Syrian youth aged 13-24 years, who recently resettled in Norway. A multi-dimensional measure for resilience was used to explore the potential impact of resilience factors on pathways between potentially traumatic events from war and flight (PTE), post-migration stress, mental distress and health-related quality of life (HRQoL). Analyses included regression, moderation and moderated mediation using the PROCESS macro for SPSS.A direct main effect of resilience factors (promotive resilience mechanism) was found for HRQoL and general mental distress, but not for post-traumatic stress disorder (PTSD). No moderating effects of resilience factors (protective resilience mechanism) were found. Post-migration stressors mediated the effects of PTE, and this indirect effect was present at all levels of resilience. Relational and environmental level resilience factors and combined amounts had more impact than individual level factors.Despite high risk exposure and mental distress, resilience was also high. The direct main effect of resilience factors and less impact on PTSD, suggests universal resilience building interventions may be beneficial, compared to exclusively targeting groups with high symptom levels. These interventions should target relational and environmental resilience factors as well as individual coping techniques. Additionally, reducing current stress and symptoms could increase the efficacy of resilience factors already present.• Refugee youth may have both high levels of risk and high resilience.• Universal resilience interventions should focus on relational and environmental support, as well as individual resilience.


In the setting of structural heart disease, ventricular tachycardia (VT) is typically associated with a re-entrant mechanism. In patients with hemodynamically tolerated VTs, activation and entrainment mapping remain the gold standard for the identification of the critical parts of the circuit. However, this is rarely accomplished, as most VTs are not hemodynamically tolerated to permit mapping during tachycardia. Other limitations include noninducibility of arrhythmia or nonsustained VT. This has led to the development of substrate mapping techniques during sinus rhythm, eliminating the need for prolonged periods of mapping during tachycardia. Recurrence rates following VT ablation are high; therefore, new mapping techniques for substrate characterization are required. Advances in catheter technology and especially multielectrode mapping of abnormal electrograms has increased the ability to identify the mechanism of scar-related VT. Several substrate-guided approaches have been developed to overcome this, including scar homogenization and late potential mapping. Dynamic substrate changes are mainly identified within regions of myocardial scar and can be identified as local abnormal ventricular activities. Furthermore, mapping strategies incorporating ventricular extrastimulation, including from different directions and coupling intervals, have been shown to increase the accuracy of substrate mapping. The implementation of extrastimulus substrate mapping and automated annotation require less extensive ablation and would make VT ablation procedures less cumbersome and accessible to more patients. These dynamic changes may play a critical role in the tachycardia mechanism when conduction velocity slows and tissue refractory periods lengthen. Dynamic substrate changes lie mainly within regions of myocardial scar or the SBZ and can be identified as functional delay in electrograms by introducing timed extrastimuli.The fundamental hypothesis of substrate mapping for scar-mediated VT is that surrogates of the isthmus can be identified. These surrogates include electrocardiographic indications for electric discontinuity such as fractionation, split potentials, LPs, and long potentials, also evident as sites displaying activation slowing.,Myocardial scar definition is a key step of any substrate-based ablation approach.High-density, multielectrode catheters can also enhance the possibility of detailed activation mapping of even poorly tolerated VTs because a complete map is faster to obtain. Recently, it has been shown that there is higher freedom from VT recurrence in patients with a fully mappable diastolic pathway recording after an ablative procedure.The use of high-resolution mapping technologies may have a role in improving clinical outcomes.,The advantages of multipolar catheters  are (1) higher mapping density and better substrate definition; (2) higher detection of LAVAs and voltage channels; and (3) higher accuracy in identifying and delineating near-field component (LAVAs) and differentiating from far-field signals.Ripple mapping is a mapping tool that shows both voltage and propagation channels into the scar in a single dynamic display. This technology has the advantage of displaying complex or continuous fractionated local EGMs as time-dependent propagation, rather than choosing a single annotation for timing. Jamil-Copley and colleagues,,Fractionated EGMs are recorded in regions where infarct healing causes wide separation of individual myocardial fibers while distorting their orientation. These anatomic changes likely cause slow and inhomogeneous activation.In the setting of post–myocardial infarction cardiomyopathy, specific EGM signatures are expressions of distinct electrophysiological phenomena. De Bakker and colleaguesMartin and colleagues,,Pace mapping is a technique used to localize the exit site of postinfarct re-entry VT circuits.,De Chillou and colleaguesCharacterization of scar regions is important for the initiation and maintenance of VT re-entry circuits, known as conducting channels (CCs).,Isochronal crowding is defined as local deceleration of propagation in a region within scar with bunching of isochrones (>2 isochrones within 1-cm radius).As re-entrant VT requires fixed or functional localized conduction slowing, Brunckhorst and colleaguesFunctional block has also been defined as an area of the myocardium that is not electrically excitable at shorter coupling intervals but is excitable at relatively long cycle lengths.Among all identified LP in a given substrate, it is not known which zone of late activation most commonly provides the substrate for re-entry. In addition, LPs may be unrelated to any VT circuits and may represent unnecessary ablation targets. The most delayed LPs are not necessarily most functionally specific for re-entry.The insight that decrement precedes unidirectional block was first described in atrial tissue sections in studies undertaken by Lammers and colleagues.,Jackson and colleaguesAcosta and colleaguesFunctionally guided substrate modification approaches that consider both activation and voltage patterns guided by extrastimuli (sense protocol) have been described as alternatives to extensive ablation required to homogenize scar , Video 1Porta-Sánchez and colleagues,EGM annotation methods based on the maximal negative derivative of the extracellular potential or maximal voltage may be inaccurate in nonuniform anisotropic tissue. Detected EGMs are strictly dependent on electrode orientation, respective to wavefront propagation, which rapidly changes directions resulting in a changeable recording according to the vector line of assessment. As a result, catheters may not identify low-voltage EGMs propagating orthogonal to their orientation, potentially missing critical arrhythmic substrate.,Arenal and colleaguesIn the study by Martin and colleagues,Brunckhorst and colleagues reported that changing the activation sequence  produced a >50% change in EGM amplitude at 28% of sites and a >100% change at 10% of sites, but only 8% of sites had an EGM amplitude classified as abnormal (≤1.5 mV) with one activation sequence and normal (>1.5 mV) with the other activation sequence. Electrically unexcitable scar (6% of sites) was associated with lower EGM amplitude but could not be reliably identified based on EGM amplitude alone for either activation sequence.,SURVIVE-VT (Substrate Ablation versus Antiarrhythmic Drug Therapy for Symptomatic Ventricular Tachycardia) has shown that a substrate-based catheter ablation procedure was associated with a significantly lower rate of implantable cardioverter-defibrillator shocks, cardiovascular death, and hospitalization for worsening heart failure.It remains to be seen whether functional substrate mapping may further improve patient outcomes in an early ablation strategy, but as a technique, it would be optimally placed to be used as a first-line safe strategy for substrate guided VT ablation.Additionally advances in mapping technology continue to play a key role in improving resolution of functional signals. Multipolar electrode catheters with 1-mm electrodes and variable interspacing have been introduced to overcome limitations in mapping in a unidirectional manner. The Advisor HD Grid Mapping Catheter (Catheter Sensor Enabled) is a multipolar catheter with electrodes equally interspaced along each spline and arranged in a grid configuration. The catheter simultaneously records EGMs along and across different orthogonal vectors when point acquisition is set in the bidirectional WAVE configuration. As well as enabling an increase in the near-field-to-far-field signal ratio, it can provide omnipolar EGMs that are independent of the incident wavefront and the fixed interelectrode spacing along and across splines, allowing calculation of conduction velocities.Current substrate modification procedures employing extensive substrate modification covering the entirety of the abnormal substrate are associated with long procedural times and may be unfeasible in unstable patients with limited cardiac reserve and large substrates.


Agave . Today Agave cultivation, primarily for beverage production, provides an economic engine for rural communities throughout Mexico. Among known dryland-farming methods, the use of rock piles and cattle-grazed areas stand out as promising approaches for Agave cultivation. Identifying new cultivation areas to apply these approaches in Arizona, USA and Sonora, Mexico warrants a geographic assessment of areas outside the known ranges of rock piles and grasslands. The objective of this study was to predict areas for dryland-farming of Agave and develop models to identify potential areas for Agave cultivation. We used maximum entropy (MaxEnt) ecological-niche-modeling algorithms to predict suitable areas for Agave dryland farming. The model was parameterized using occurrence records of Hohokam rock piles in Arizona and grassland fields cultivated with Agave in Sonora. Ten environmental-predictor variables were used in the model, downloaded from the WorldClim 2 climate database. The model identified potential locations for using rock piles as dryland-farming methods from south-central Arizona to northwestern Sonora. The Agave-grassland model indicated that regions from central to southern Sonora have the highest potential for cultivation of Agave, particularly for the species Agave angustifolia. Results suggest that there are many suitable areas where rock piles can be used to cultivate Agave in the Sonoran Desert, particularly in the border of southeastern Arizona and northwest Sonora. Likewise, cattle-grazing grasslands provide a viable environment for cultivating Agave in southern Sonora, where the expanding bacanora-beverage industry continues to grow and where different Agave products  can potentially strengthen local economies.For centuries, humans occupying arid regions of North America have maintained an intricate relationship with  Agave genus and indigenous groups and rural communities in arid regions has been crucial to creating sustainable agroecosystems in arid regions in Mexico and North America .The area highlighted in grey was the study area used to create suitability models for (TIF)Click here for additional data file.S2 Fighttps://gadm.org/index.html].The shapefiles and data used to construct the map were obtained from GADM [(TIF)Click here for additional data file.S3 FigPublished under a CC BY license, with permission from Michael T. Searcy, original copyright 2022.(TIF)Click here for additional data file.S4 FigHighlights in red indicate the variables selected for the study.(TIF)Click here for additional data file.


Accumulating evidence suggests asymmetrical responses of cerebral blood flowduring large transient changes in mean arterial pressure. Specifically, theaugmentation in cerebral blood flow is attenuated when mean arterial pressureacutely increases, compared with declines in cerebral blood flow when meanarterial pressure acutely decreases. However, common analytical tools toquantify dynamic cerebral autoregulation assume autoregulatory responses to besymmetric, which does not seem to be the case. Herein, we provide the rationalesupporting the notion we need to consider the directional sensitivity of largeand transient mean arterial pressure changes when characterizing dynamiccerebral autoregulation. Cerebral autoregulation (CA) has commonly been described as the ability of the cerebralvasculature to react to steady-state (static CA) or transient (dynamic CA: dCA) arterialblood pressure (ABP) changes. The roles of these physiological responses are to maintaincerebral perfusion to meet the brain’s demand and minimize blood flow variations.Therefore, the extent of the vessels’ vasomotion (i.e. vasoconstriction or vasodilation)will be proportional to the ABP magnitude change, whether ABP increases or ABPdecreases. The hypothesis behind the presence of directional sensitivity of the cerebralpressure-flow relationship resides in the role brain blood vessels play against ABPtransient surges to protect the microcirculation from overperfusion. Therefore, it isthought dCA would be more efficient when ABP acutely increases in comparison with acuteABP decreases. Using an autoregulatory gain calculation between middle cerebral artery meanblood velocity (MCAv) and MAP, Tzeng et al. demonstrated a smaller gain when MAP acutelyincreased compared with MAP decreases. We demonstrated a directional sensitivity of the cerebral pressure-flowrelationship by examining changes in MCAv in response to transient increases anddecreases in MAP induced by repeated squat-stands .24 Initially, these changes werecalculated from a seated baseline, an approach that has been criticized. This calculation was further refined byusing the largest concurrent MAP oscillations without an independent resting baseline,and by adjusting for time intervals. In addition to demonstrating a directional sensitivity in the MCA4 and in the posterior cerebral artery using this novel calculation, we suggested the hysteresis-like pattern isfrequency-dependent .4 Abetter autoregulatory capacity was also demonstrated during the squatting phase(transient increase in MAP) of repeated squat-stands using the autoregulatory index.There is growing evidence of cerebral pressure-flow relationship directional sensitivityduring large transient mean arterial pressure (MAP) oscillations. In healthyindividuals, the first observation of a directional sensitivity was reported whencomparing acute increases and decreases in ABP with drugs infusions. The activation of cerebral SNA in response to an acute elevation in MAP wouldserve to protect the brain microcirculation from overperfusion and to reduce the risk ofhemorrhagic stroke. Another potential mechanism underlying this hysteresis-like patterncould be a differing intrinsic myogenic activity when ABP increases, compared with ABPdecreases. However, previous work suggests intrinsic myogenic activity influences dCAduring oscillations below 0.07 Hz and calcium-channel blockade impairs dCA in humans during oscillatory lower bodynegative pressure at frequencies between 0.03 and 0.08 Hz.Differences in cerebral sympathetic nervous activity (SNA) in response to transient MAPincreases, compared with MAP decreases, could potentially explain this directionalsensitivity of the cerebral pressure-flow relationship. Indeed, data in sleeping lambsindicate SNA recorded in the superior cervical ganglia is activated during acute ABPincreases but not acute ABP decreases.9. Interestingly, Katsogridakis et al. usedthigh-cuffs inflation and deflation to induce large transient MAP changes. This method has been shown to have extremely large variations in dCA metrics,even when tests are performed just minutes apart. Nonetheless, whether specific methodsto induce significant MAP changes are partly responsible for the directional sensitivityof the pressure-flow relationship remains to be elucidated. Further research will thusbe necessary to ensure this phenomenon is not method-dependent.Of note, there are studies reporting the absence of asymmetry in the cerebralpressure-flow relationship Nonetheless, further studies are needed, as we still do not know whether thishysteresis-like pattern remains present in other physiological and pathological states.In addition, all studies focusing on the directional sensitivity of dCA to date includedmeasures of cerebral blood velocity and MAP. The monitoring of volumetric cerebral bloodflow and cerebral perfusion pressure  in future studies is encouraged to provide more meaningful results not only inregards to the directional sensitivity of the cerebral pressure-flow relationship, butalso for all the other metrics quantifying dCA.Directional sensitivity could be highly relevant to consider while studying CBFregulation in diverse populations. Since there are many physiological contexts  and clinical/pathological states involving acute and large changes in MAP, the direction of MAP has the potential ofbeing an important variable to consider when examining dCA. We have recently reportedthat directional sensitivity of the cerebral pressure-flow relationship is present insedentary and endurance-trained participants, but absent in resistance-trained individuals.It becomes clear there is asymmetrical sensitivity of the cerebral pressure-flowrelationship during large transient MAP changes. We now need to better understand itsunderlying mechanisms and refine the current analytical tools to assess dCA, in order toeventually optimize the management of ABP in clinical populations. Replication ofstudies in various centers using different models of forced ABP oscillations (e.g.oscillatory lower body negative pressure) will also be crucial. The presence ofasymmetrical sensitivity has important implications on quantification of dCA usingstandard analysis on forced ABP oscillations. For example, transfer function analysis, acommon analytical tool to quantify dCA, assumes autoregulatory responses to be linearand symmetric, which is not the case. From now on, we consider we cannot solely useanalytical methods that do not consider the direction of large transient MAP changeswhen characterizing dCA. It will remain crucial the scientific and medical community isaware of this important characteristic of the cerebrovasculature until a global changeis undertaken by our community to take MAP direction into account in the assessment ofdCA and acute manipulation of ABP within the clinical setting.


HIV-positive patients with schizophrenia spectrum disorders experience burden of double stigma. Comorbid pathology may alter structure of stigma and shall be considered in development of individual destigmatization programs.Study of psychiatric stigma features in HIV-positive and HIV-negative patients with schizophrenic disorders.ISMI , PDD  – to study stigma in 70 patients divided into three groups with respect to their diagnosis ; BPRS  – to assess psychiatric status, RSAS  – to assess anhedonia. Dispersion analysis , Spearman and Pearson correlation were used.Patients with comorbid HIV-infection showed increased level of perceived stigma, although they resisted the stigma internalization better than others did (Table 1).Patients with schizotypal disorders and patients at early stages of HIV infection experienced the most alienation and frailty to internalization of stigma .Correlation relationship between social anhedonia and perceived stigma  observed in patients with HIV infection.Comorbid HIV infection in psychiatric patients contributes to the psychiatric stigma structure. Differentiated approaches in rehabilitation of HIV-positive mental patients should be used.


Schizophrenia spectrum disorders are among the most debilitating mental disorders and evidence on its pathophysiological underpinnings is scant. The brain-derived neurotrophic factor (BDNF) appears to be involved in the pathophysiology of these complex psychiatric disorders.The present study investigates the longitudinal variation of serum BDNF levels in a 24-month observational cohort study of Sardinian psychotic patients (LABSP). This study assessed the variation in BDNF serum levels and its relationship with psychopathological and cognitive changes. Further, we also examined if genetic variations within the BDNF gene could moderate these relationships.Every six months 105 LABSP patients were assessed for their BDNF serum levels, as well as for a series of psychopathological, cognitive, and drug-related measures. Four tag single nucleotide polymorphisms (SNPs) within the BDNF gene were selected and analyzed using Polymerase Chain Reaction (PCR). Longitudinal data were analyzed using mixed-effects linear regression models (MLRM).Analysis showed significantly lower peripheral BDNF levels in psychotic patients with depressive and negative symptoms. BDNF levels were also decreased in patients scoring lower in cognitive measures such as symbol coding and semantic fluency. In addition, Val66Met polymorphism within the BDNF gene significantly moderated the relationship between the severity of negative symptoms and BDNF levels.Our findings are consistent with previous literature suggesting that peripheral BDNF levels are associated with some cognitive domains and mood disruption in major psychosis. The results also suggest the lack of association between most BDNF genetic variants, except Val66Met polymorphism, with the severity of negative symptoms.No significant relationships.


The present review is a historical perspective of methodology and applications using inert liquids for respiratory support and as a vehicle to deliver biological agents to the respiratory system. As such, the background of using oxygenated inert liquids (considered a drug when used in the lungs) opposed to an oxygen-nitrogen gas mixture for respiratory support is presented. The properties of these inert liquids and the mechanisms of gas exchange and lung function alterations using this technology are described. In addition, published preclinical and clinical trial results are discussed with respect to treatment modalities for respiratory diseases. Finally, this forward-looking review provides a comprehensive overview of potential methods for administration of drugs/gene products to the respiratory system and potential biomedical applications. Aerosol drugs have been delivered to the lungs for several thousand years . The useDuring the last 20 years, the combination of nanocrystal technology combined with an inert perfluorochemical vehicle has demonstrated the efficacy of large volume drug delivery to the entire lung because of the vehicle physical-chemical properties  . FurtherThe use of liquids for respiratory support is reviewed in this section, as well as the physical properties of fluid used and the rationale for using specific liquids.2; CO2) and diffusion gradients at atmospheric conditions limited the functional use of saline solution to provide adequate gas exchange  was investigated as respiratory media; however, these oils, although having high gas solubility, also demonstrated toxic effects . Perfluo2 and CO2 are specific to respiratory gas exchange and carried only as dissolved gases with solubilities ranging as much as 16 and three times greater, respectively, in PFC than in saline. Oxygen solubilities range from 35 to 70 ml gas per deciliter at 25°C . It is noteworthy that perflubron  is the only medical grade perfluorochemical approved by the FDA for emergency medical use. While many properties of PFC liquids vary, they do provide relatively low surface tension and viscosity, and are more dense than both water and soft tissue.Please refer to  at 25°C . The carVariations in specific physicochemical properties of the PFC liquids are significant to their use as respiratory media and as vehicles for the administration of biological agents. Fluids of higher vapor pressure may volatilize from the lung more rapidly than liquids having lower vapor pressure. Fluids with greater spreading coefficients (dependent on surface tension) may distribute more easily in the lung than fluids whose spreading coefficients are lower  . Fluids The initial preclinical studies in liquid spontaneous breathing and ventilation support were directed at breathing in unusual environments such as deep sea diving, zero gravity, and space travel . It was Subsequently, several separate investigational new drug applications were approved by the FDA to investigate the safety and efficacy of PFCs, mainly PFOB, as a liquid breathing media in neonates. While animal studies over the years showed significant efficacy and safety of liquid breathing, clinical studies using several techniques in humans  had mixed outcomes. The findings from non-clinical and clinical studies are summarized below.2 requirements that are characteristics of ventilator-induced lung injury . These studies supported the use of liquid ventilation as a superior source of respiratory support when compared with gas media with spontaneous breathing or conventional mechanical ventilation (CMV). Various studies also demonstrated short-term beneficial physiologic responses in lung function because of improved alveolar recruitment and significant preservation of normal histological structure of the lung . Non-clig injury .Recent studies continue to show PFOB improves oxygenation  in animaAnimal studies consistently support the safety of PFOB, as few negative effects have been reported. Studies show PFOB is not absorbed systemically and causes no long-term harm . SeveralEarly clinical studies demonstrated that infants with severe RDS, meconium aspiration, and CDH tolerated liquid PFC in their lungs and were able to effectively exchange gas and maintain cardiovascular stability .Consistent with those studies and animal studies, additional published reports indicated PFOB increased gas exchange  in adultMost importantly, the utility of PFOB was demonstrated in a multicenter study of premature infants with severe RDS refractory to other available treatments  . ThirteeMore recently, lavage with PFC has been shown to be safe for treatment of persistent and difficult-to-treat lung atelectasis . BronchoFollow-up imaging studies up to 20 years after treatment with PFOB in humans demonstrated no negative effects from this treatment . The stuIn early liquid ventilation studies, it was reported that PFOB usage in adults increased lung compliance , which iSystemic administration of therapeutics to target the lung is faced with numerous challenges secondary to potential degradation by serum and hepatic enzymes and rapid renal clearance. Compromised pulmonary blood flow in the injured lung may further limit passive diffusion of the drug from the blood into the lung parenchyma. Retention of the therapeutics in the lung is also often suboptimal. These challenges can be mitigated by local administration of therapeutics through inhalation or airway instillation . HoweverSome studies have successfully demonstrated that lungs filled with PFC liquid have the ability to deliver active and inactive agents for the diagnosis and treatment of respiratory disorders.Respiratory infections affect distally located alveoli with bacteria and viruses multiplying in the alveolar cells. Distal lung distribution of intra-tracheally delivered anti-infective agents is essential to halt disease progression. In a newborn lamb model of acid lung injury, gentamicin administration during tidal liquid ventilation using PFC resulted in significantly higher lung gentamicin levels compared with intravenous administration . This teIn an animal model of meconium aspiration syndrome, partial liquid ventilation improved regional distribution of intratracheally administered radio-labelled surfactant compared with conventional mechanical ventilation. There was more uniform distribution of surfactant between the lungs as well as between both ventral and dorsal regions of the lungs. Such uniform distribution was associated with improved systemic oxygenation . PFC wasInhalational smoke-induced acute lung injury is characterized by airway epithelial injury leading to excess leakage of plasma substrates into large airways and the formation of fibrin casts. Interventions to prevent or treat airway casts are limited. In this regard, PFC has been used for intratracheal administration of plasminogen activators (tissue plasminogen activator [tPA] and single-chain urokinase plasminogen activator [scuPA]) for management of airway clot and fibrinous cast formation associated with smoke-induced acute lung injury. Enzymatic activities of the plasminogen activator following dispersion and storage in PFC were preserved, and PFC administration alone did not impact physiologic or histological differences. In contrast, PFC-facilitated plasminogen activator delivery resulted in significantly better physiologic and histologic outcomes. PFC-facilitated delivery of plasminogen activator demonstrated improved outcomes than achieved by nebulization of plasminogen activators alone .2 during liquid ventilation potentially could be different compared with the gas-filled lung.Drug delivery during PFC PLV respiratory support has been demonstrated with other soluble gases in PFOB such as inspired nitric oxide (NO). NO administration with PLV in surfactant-depleted adult pigs resulted in a significant improvement in gas exchange and decrease in pulmonary artery pressure, most notably without deleterious effects on systemic hemodynamic conditions . In a coTwenty-two percent of all pediatric hospital admissions are due to respiratory illness. Genetic lung diseases account for increased morbidity and mortality . GeneticCRISPR-Cas9 gene editing provides an unprecedented opportunity to manipulate genes in somatic cells. Editing technologies have demonstrated clear therapeutic promise in non-human primates and early human clinical trials . New appThe postnatal lung presents important limitations to airway delivery because of the substantial mucus and surfactant barrier at the air-epithelial interface, repulsive charge interactions at the cell membrane, and unequal reagent distribution due to the heterogeneity of lung disease with some areas being overinflated and others collapsed . Further2 and CO2 solubility of PFC liquids allows effective gas exchange, even in lungs filled with fluid. PFCs also reduce surface tension, which assists lung volume recruitment at reduced inspiratory pressures by eliminating the air-liquid interface. Importantly, PFC liquids effectively penetrate collapsed regions of the lung to facilitate access to under-ventilated regions. This is particularly important in non-homogenous lung diseases such as surfactant protein diseases, in which PFC liquids could simultaneously facilitate delivery of therapies, increase gas exchange, and improve pulmonary function. Several groups have exhibited the superior effectiveness of PFC liquids as vehicles for pulmonary distribution of genetic cargo (The fluid-filled fetal lung physiology could be partially mimicked in postnatal lungs with PFC liquids because of their high spreading coefficients and intriguing properties for pulmonary distribution of biological agents. The high Oic cargo . PFC liqic cargo . Use of ic cargo . Many stic cargo . As suchic cargo . By adapThe fact that aqueous solutions are not readily soluble in PFCs is an important consideration for PFC drug delivery. Some research projects have circumvented this barrier by relying on bulk flow turbulent mixing . HoweverWhen lung parenchymal disease and/or injury are present in the lung, pulmonary ventilation and perfusion are compromised. Ventilation can be irregular and perfusion may be inhibited by ventilation-perfusion mismatch. The route of therapy administration is hindered by these abnormalities, rendering standard intravenous and aerosol/endotracheal tube delivery ineffective in delivering therapeutic agents to the affected area.Liquid ventilation with an inert respiratory gas solubility is a revolutionary mode for respiratory support, as well as delivery of drug/gene product to the respiratory system. As noted, inert perfluorochemical liquids have low viscosity and high oxygen and carbon dioxide capabilities . The phyThe use of PFC liquid in the respiratory system enhances ventilation and perfusion matching, boosting exposure of the drug/gene product to the circulation, successfully reaching required therapeutic serum drug levels . Studies


The Management and Supervision Tool (MaST) helps NHS mental health care professionals identify patients who are most likely to need psychiatric hospital admission or home treatment, due to severe mental illness, through a Risk of Crisis (RoC) algorithm driven by electronic health record (EHR) data analytics. We describe the derivation and validation of the MaST RoC algorithm, and its implementation to support preventative mental healthcare in the NHS.The RoC algorithm was developed and evaluated with EHR data from six UK NHS trusts using Ordered Predictor List propensity scores informed by a priori weightings from pre-existing literature, as well as real-world evidence evaluating the associations of clinical risk factors with mental health crisis using NHS EHR data. Mental health crisis was defined as admission to a psychiatric hospital or acceptance to a community crisis service within a 28-day period. Predictor variables included age, gender, accommodation status, employment status, Mental Health Act (MHA) status (under section or Community Treatment Order), and previous mental health service contacts . Data were analysed using Ordered Predictor List propensity scores. The algorithm was derived using structured EHR data from 2,620 patients in a single NHS trust and externally validated using data from 107,879 patients in five other NHS trusts. Qualitative and quantitative data on feasibility, acceptability and system efficiency impacts of MaST implementation were obtained through staff surveys and local audits.The factors associated with greatest propensity for mental health crisis included recent previous crisis, multiple previous crises, higher number of mental health service contacts in recent weeks, MHA section, accommodation status and employment status. The RoC algorithm identified 64% and 80% crises in its top quintile. Sentiment analysis of staff surveys suggested that the use of MaST improved productivity by reducing time taken to access patient information to support caseload management that was previously difficult to obtain through manual review of EHRs. The systems efficiency audit revealed a reduction in duration of crisis and inpatient admissions following MaST implementation.The MaST RoC algorithm supports the identification of people more likely to use crisis services in NHS mental health trusts, is feasible to implement, and improves systems efficiency. EHR-derived algorithms can support real-world clinical practice to improve outcomes in people receiving NHS mental healthcare.


Aedes-borne flaviviruses. Domestic dogs may be useful sentinels for West Nile virus.We tested 294 domestic pet dogs in Mexico for neutralizing antibodies for mosquito-borne flaviviruses. We found high (42.6%) exposure to West Nile virus in Reynosa (northern Mexico) and low (1.2%) exposure in Tuxtla Gutierrez (southern Mexico) but very limited exposure to  Aedes spp. and Culex spp. mosquitoes, the endemicity of human arboviral diseases is incongruent with these vector distributions . Canine exposure to WNV was widespread, and we found a higher prevalence of neutralizing antibodies to WNV in dogs from Reynosa  than in those from Tuxtla Gutierrez . The lower reported numbers of WNV cases in Mexico might be in part because of the high seroprevalence of antibodies for other flaviviruses, which have been shown to protect against severe clinical infection from WNV, thus leading to reduced testing (Culex mosquitoes in the study area. Our data suggested substantial WNV enzootic activity in Reynosa and corroborated prior observations of high use of dogs as blood meal hosts by Aedes-borne flaviviruses suggests not an absence of these viruses circulating in these communities but that dogs are likely insensitive sentinels of the viruses’ transmission in Mexico. In Chiapas, 7,972 human cases of dengue and 763 cases of Zika had been reported during 2016–2020 (Ae. aegypti in southern Texas and northern Mexico feed on dogs (,The relative lack of canine exposure to Cx. quinquefasciatus mosquitoes, a primary vector of WNV, use high numbers of dogs for blood meals. Therefore, domestic pet dogs may be useful sentinels of WNV transmission, as previously suggested in other regions (Our study suggests substantial WNV enzootic activity in Reynosa, Mexico and corroborates observations that Additional information about the usefulness of domestic dogs as sentinels for West Nile virus.