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Surgical pulmonary valve replacement is commonly required to palliate patients with CHD affecting the right ventricular outflow tract; however, concerns remain about mid- and long-term durability. Post-operative short-term anticoagulation has been hypothesised to improve valve durability.
Methods:
This is a single-centre, retrospective study of paediatric patients who underwent surgical pulmonary valve replacement and received a direct oral anticoagulant in addition to aspirin post heart valve insertion. The primary objective was a composite safety score consisting of clinically relevant non-major bleeding, major bleeding, bleeding-related readmission, and medication discontinuation.
Results:
The study analysed 34 patients with a median age 14 years (Interquartile range (IQR): 11, 15) and weight 45 kg (IQR: 35, 55). Ten patients met the composite endpoint (10/34, 29%), with 4 patients experiencing major bleeding (4/34, 12%), 6 experiencing clinically relevant non-major bleeding (6/34, 18%), and 3 patients being readmitted within 90 days of surgical pulmonary valve replacement for bleeding (3/29, 8.8%) resulting in 10 patients discontinuing medication early (10/34, 29%). Lower weight was identified as a significant risk factor for adverse event development (p = 0.04).
Conclusion:
We observed a higher overall bleeding rate, driven predominately by clinically relevant non-major bleeding events, than other studies using short-term anticoagulation after surgical pulmonary valve replacement. Additional studies should be aimed at evaluating the dosing and safety of direct oral anticoagulants in children in the post-operative period.
Kant’s 1784 lectures on Achenwall is commonly known as the Feyerabend lectures because the manuscript was attributed to Gottfried Feyerabend. These lectures range over the topics eventually treated in Kant’s Metaphysics of Morals (1798), which include both right and ethics. From these lectures we learn how Kant thought about the concepts of end in itself, self-sufficient end and human dignity just prior to writing the Groundwork (1785). Kant accepts much of what he finds in Achenwall, but also advances criticisms of the concept of obligation found in Achenwall and also in Baumgarten. He also rejects Achenwall’s attempt to justify coercion of duties of right simply through the distinction, common in the tradition since Pufundorf, between perfect and imperfect duties. The present discussion concludes that in the 1780s Kant’s position on the relation of right to ethics was still unclear. He appears to base right on the ethical value of humanity as end in itself, but also worries that grounding right on an ethical principle cannot explain why duties of right may be coerced.
A minority of earthquake-exposed individuals develop post-traumatic stress disorder (PTSD), often alongside comorbid depression and anxiety symptoms. No systematic review has examined psychological interventions for adults with substantial earthquake-related PTSD symptoms.
Aims
To synthesise studies evaluating psychological interventions for adult earthquake-related PTSD and conduct meta-analyses estimating overall effect sizes.
Method
The review was pre-registered with PROSPERO (CRD42023441020). PsycINFO, MEDLINE, EMBASE, CINAHL and Scopus were searched for studies (last search conducted July 2024). Randomised controlled trials (RCTs), non-randomised and non-controlled studies evaluating psychological interventions for adults with substantial earthquake-related PTSD symptoms were eligible. Outcomes were PTSD, depression and anxiety symptoms. Narrative syntheses and meta-analyses summarised study findings. The Mixed Methods Appraisal Tool guided quality assessments.
Results
Sixteen studies were identified (eight RCTs, four non-randomised and four non-controlled studies), representing 1315 participants receiving psychological intervention. Interventions included cognitive behavioural therapy (CBT), specific CBT variants, eye movement desensitisation and reprocessing, interpersonal psychotherapy and an internet-based intervention focusing on social cognitive theory. Studies generally reported statistically and clinically significant improvements associated with psychological interventions. Among studies included in meta-analyses, overall effect size was 2.11 (95% CI = 0.92, 3.31) for PTSD symptoms and 1.01 (95% CI = 0.50, 1.52) for depression symptoms.
Conclusions
Psychological interventions are associated with good outcomes among adults with earthquake-related PTSD. The most evidence currently exists for CBT-based interventions, which are recommended as first-line treatments. Efficient intervention options, including single-session and group-based treatments, also show promise and are recommended for addressing widespread treatment need.
Diversifying the simplified landscape of corn and soybeans in the Midwest is an emerging priority in both the public and private sectors to reap a suite of climate, social, agronomic, and economic benefits. However, little research has documented the perspectives of farmers, the primary stakeholders in diversification efforts. This preliminary report uses newly collected survey data (n = 725) from farmers in the states of Illinois, Indiana, and Iowa to provide descriptive statistics and tests to understand what farmers in the region think about agricultural diversification, including their perspectives on its benefits, barriers, and opportunities. For the purposes of the study, we define diversification as extended rotations, perennials, horticulture, grazed livestock, and agroforestry practices. We find that a majority or plurality of farmers in the sample believe that diversified systems are superior to non-diversified systems at achieving a range of environmental, agronomic, and economic goals, although many farmers are still forming opinions. Farmers believe that primarily economic barriers stand in the way of diversification, including the lack of affordable land, low short-term returns on investment, and lack of labor. Farmers identified key opportunities to increase diversification through developing processing capacity for local meat and specialty crops, increasing demand for diversified products, and providing more information on returns on investment of diversified systems. Different interventions, however, may be needed to support farmers who are already diversified compared to non-diversified farmers. Building on these initial results, future studies using these data will develop more detailed analyses and recommendations for policymakers, the private sector, and agricultural organizations to support diversification.
Despite advances in the development of systemic anticoagulants, there remain few agents approved for utilisation in patients with mechanical heart valves. Currently, recommendations for periprocedural and long-term anticoagulation in mechanical heart valves include unfractionated heparin or vitamin K antagonists, and there are some reports for off-label use of low-molecular-weight heparins. Emerging data on parenteral direct thrombin inhibitors, such as bivalirudin, have led to increased utilisation in both extracorporeal membrane oxygenation and ventricular assist devices. We present the case of a paediatric patient with rheumatic heart disease who had significant bleeding on unfractionated heparin who successfully received prolonged bivalirudin therapy in the setting of mechanical aortic and mitral heart valves.
We review some of the processes leading to dispersion and mixing in porous media, exploring the differences between the travel time distribution of fluid particles within a pore throat and between pore throats of different size within the porous layer. A recent paper of Liu et al. (2024) has combined a model of these travel time distributions with a continuous time random walk to quantify the dispersion as a function of the Peclet number. We describe some further problems relating to dispersive mixing of tracer which may be amenable to this approach, including dispersion caused by macroscopic lenses of different permeability, dispersion of tracer which partitions between the fluid and matrix and the effects of buoyancy on mixing.
Diagnosis in psychiatry faces familiar challenges. Validity and utility remain elusive, and confusion regarding the fluid and arbitrary border between mental health and illness is increasing. The mainstream strategy has been conservative and iterative, retaining current nosology until something better emerges. However, this has led to stagnation. New conceptual frameworks are urgently required to catalyze a genuine paradigm shift.
Methods
We outline candidate strategies that could pave the way for such a paradigm shift. These include the Research Domain Criteria (RDoC), the Hierarchical Taxonomy of Psychopathology (HiTOP), and Clinical Staging, which all promote a blend of dimensional and categorical approaches.
Results
These alternative still heuristic transdiagnostic models provide varying levels of clinical and research utility. RDoC was intended to provide a framework to reorient research beyond the constraints of DSM. HiTOP began as a nosology derived from statistical methods and is now pursuing clinical utility. Clinical Staging aims to both expand the scope and refine the utility of diagnosis by the inclusion of the dimension of timing. None is yet fit for purpose. Yet they are relatively complementary, and it may be possible for them to operate as an ecosystem. Time will tell whether they have the capacity singly or jointly to deliver a paradigm shift.
Conclusions
Several heuristic models have been developed that separately or synergistically build infrastructure to enable new transdiagnostic research to define the structure, development, and mechanisms of mental disorders, to guide treatment and better meet the needs of patients, policymakers, and society.
Negative symptoms are a key feature of several psychiatric disorders. Difficulty identifying common neurobiological mechanisms that cut across diagnostic boundaries might result from equifinality (i.e., multiple mechanistic pathways to the same clinical profile), both within and across disorders. This study used a data-driven approach to identify unique subgroups of participants with distinct reward processing profiles to determine which profiles predicted negative symptoms.
Methods
Participants were a transdiagnostic sample of youth from a multisite study of psychosis risk, including 110 individuals at clinical high-risk for psychosis (CHR; meeting psychosis-risk syndrome criteria), 88 help-seeking participants who failed to meet CHR criteria and/or who presented with other psychiatric diagnoses, and a reference group of 66 healthy controls. Participants completed clinical interviews and behavioral tasks assessing four reward processing constructs indexed by the RDoC Positive Valence Systems: hedonic reactivity, reinforcement learning, value representation, and effort–cost computation.
Results
k-means cluster analysis of clinical participants identified three subgroups with distinct reward processing profiles, primarily characterized by: a value representation deficit (54%), a generalized reward processing deficit (17%), and a hedonic reactivity deficit (29%). Clusters did not differ in rates of clinical group membership or psychiatric diagnoses. Elevated negative symptoms were only present in the generalized deficit cluster, which also displayed greater functional impairment and higher psychosis conversion probability scores.
Conclusions
Contrary to the equifinality hypothesis, results suggested one global reward processing deficit pathway to negative symptoms independent of diagnostic classification. Assessment of reward processing profiles may have utility for individualized clinical prediction and treatment.
Clastic sedimentary systems and their characteristics are assumed not to have been modified by carbonate bioclastic grains until the Phanerozoic. Here, we show that the presence of carbonate bioclasts produced by disintegrated biomineralizing metazoans modified fine-grained siliciclastic facies in the Late Ediacaran Tamengo Formation, Brazil, ca. 555–542 Ma. The analysis of both polished sections and thin sections shows that sand-sized carbonate bioclasts (< 2 mm) derived from the Ediacaran metazoan Corumbella created diverse sedimentary features later found in the Phanerozoic record, such as bioclastic-rich horizontal and low-angle cross-laminations, erosive pods and lenses, bioclastic syneresis cracks, ripples preserved by bioclastic caps, microbial lamination eroded and filled with bioclasts, and entrapped bioclasts within microbial mats. These sedimentary features would have hardly been recorded in fine siliciclastic facies without the sand-sized bioclasts. Based on these features, together with other sedimentary evidence, Corumbella depositional settings in the Tamengo Fm. are reinterpreted as mid-ramp, subtidal settings. The multi-component organization of the skeleton of Corumbella favoured disarticulation to yield a sand-sized bioclast, so in turn creating a new complexity to shallow marine clastic settings typical of Phanerozoic marine depositional systems.
Stigma of mental health conditions hinders recovery and well-being. The Honest, Open, Proud (HOP) program shows promise in reducing stigma but there is uncertainty about the feasibility of a randomized trial to evaluate a peer-delivered, individual adaptation of HOP for psychosis (Let's Talk).
Methods
A multi-site, Prospective Randomized Open Blinded Evaluation (PROBE) design, feasibility randomised controlled trial (RCT) comparing the peer-delivered intervention (Let's Talk) to treatment as usual (TAU). Follow-up was 2.5 and 6 months. Randomization was via a web-based system, with permuted blocks of random size. Up to 10 sessions of the intervention over 10 weeks were offered. The primary outcome was feasibility data (recruitment, retention, intervention attendance). Primary outcomes were analyzed by intention to treat. Safety outcomes were reported by as treated status. The study was prospectively registered: https://doi.org/10.1186/ISRCTN17197043.
Results
149 patients were referred to the study and 70 were recruited. 35 were randomly assigned to intervention + TAU and 35 to TAU. Recruitment was 93% of the target sample size. Retention rate was high (81% at 2.5 months primary endpoint), and intervention attendance rate was high (83%). 21% of 33 patients in Let's talk + TAU had an adverse event and 16% of 37 patients in TAU. One serious adverse event (pre-randomization) was partially related and expected.
Conclusions
This is the first trial to show that it is feasible and safe to conduct a RCT of HOP adapted for people with psychosis and individual delivery. An adequately powered trial is required to provide robust evidence.
History of prior mental disorder, particularly post-traumatic stress disorder (PTSD), increases risk for PTSD following subsequent trauma exposure. However, limited research has examined differences associated with specific prior mental disorders among people with PTSD.
Aims
The current study examined whether different prior mental disorders were associated with meaningful differences among individuals presenting to a specialist service for severe earthquake-related distress following the Canterbury earthquakes (N = 177).
Method
Two sets of comparisons were made: between participants with no history of prior disorder and participants with history of any prior disorder; and between participants with history of prior PTSD and those with history of other prior disorders. Comparisons were made in relation to sociodemographic factors, earthquake exposure, peri-traumatic distress, life events and current psychological functioning.
Results
Participants with any prior mental disorder had more current disorders than those with no prior disorder. Among participants with history of any prior disorder, those with prior PTSD reported more life events in the past 5 years than those with other prior disorders.
Conclusions
Findings suggest a history of any prior mental disorder contributes to increased clinical complexity, but not increased PTSD severity, among people with PTSD seeking treatment. Although post-disaster screening efforts should include those with prior mental disorders, it should also be recognised that those with no prior disorders are also at risk of developing equally severe PTSD.
Electronic health records and patient portals are increasingly utilized to enhance research recruitment efficiency, yet response patterns across patient groups remain unclear. We examined 10 studies at Emory Healthcare that used these tools to identify and recruit 24,000 patients over 1 year. Response rates were lower among males and Black individuals, though study interest was higher among respondents. Interest was also greater among those with frequent healthcare interactions and lower comorbidity. In a large academic health system, portal-based recruitment offered a streamlined approach to research recruitment and patient engagement, with minor variations across patient characteristics warranting continued study.
We develop a simple model which describes the repeated injection and extraction of hydrogen in a permeable water-saturated rock which has the form of an anticline. We demonstrate that the flow is controlled by the dimensionless ratio of the square of the buoyancy speed to the product of the two-dimensional volume injection rate and the injection–extraction frequency, and we explore the cases in which this ratio is large and small. Over the first few cycles, the volume of hydrogen in the system gradually builds up since during the extraction phase, some of the water eventually reaches the extraction well, and in our model the system ceases to extract fluid for the remainder of this extraction phase. After many cycles, there is sufficient hydrogen in the system that a quasi-equilibrium state develops in which the mass of fluid injected matches the mass extracted over the course of a cycle. We show that in this equilibrium, the ratio between the mass of gas remaining in the aquifer at the end of the extraction phase, known as the cushion gas, to the mass of gas injected, known as the working gas, decreases if either the flow rate or frequency of the cycles decrease or the buoyancy speed increases, leading to more efficient storage.
We explore the interaction of natural convection and mechanical ventilation in a room where fresh air is supplied at low level and stale air is extracted at high level. Turbulent buoyant plumes rising from heat sources interact with this upward airflow and establish a steady-state stratification with a warm upper layer above a layer of the cold supply air. Adapting the volume balance model used in natural ventilation (Linden et al., J. Fluid Mech., vol. 212, 1990, pp. 309–335) leads to the prediction that the upper layer will vent from the room when the ventilation volume flux exceeds the volume flux in the plumes at the ceiling. However, our new laboratory experiments establish that there is still a stable two-layer stratification beyond this point of critical ventilation. Motivated by our observations, we propose that the kinetic energy flux supplied by the plume leads to turbulent mixing in the upper layer. We propose a new model of this mixing which is consistent with our experiments in both the over- and under-ventilated regimes. This has important implications for air recirculation in buildings with large ventilation flows, particularly hospital operating theatres and clean rooms.
Carbapenem-resistant Enterobacterales (CRE) are an urgent threat to healthcare, but the epidemiology of these antimicrobial-resistant organisms may be evolving in some settings since the COVID-19 pandemic. An updated analysis of hospital-acquired CRE (HA-CRE) incidence in community hospitals is needed.
Methods:
We retrospectively analyzed data on HA-CRE cases and antimicrobial utilization (AU) from two community hospital networks, the Duke Infection Control Outreach Network (DICON) and the Duke Antimicrobial Stewardship Outreach Network (DASON) from January 2013 to June 2023. The zero-inflated negative binomial regression model was used owing to excess zeros.
Results:
126 HA-CRE cases from 36 hospitals were included in the longitudinal analysis. The pooled incidence of HA CRE was 0.69 per 100,000 patient days (95% confidence interval [95% CI], 0.57–0.82 HA-CRE rate significantly decreased over time before COVID-19 (rate ratio [RR], 0.94 [95% CI, 0.89–0.99]; p = 0.02), but there was a significant slope change indicating a trend increase in HA-CRE after COVID-19 (RR, 1.32 [95% CI, 1.06–1.66]; p = 0.01). In 21 hospitals participating in both DICON and DASON from January 2018 to June 2023, there was a correlation between HA-CRE rates and AU for CRE treatment (Spearman’s coefficient = 0.176; p < 0.01). Anti-CRE AU did not change over time, and there was no level or slope change after COVID.
Conclusions:
The incidence of HA-CRE decreased before COVID-19 in a network of community hospitals in the southeastern United States, but this trend was disrupted by the COVID-19 pandemic.
A demonstration of a fully onboard method for generating background oriented schlieren (BOS) data on a jet exhaust is presented. Readily available commercial camera equipment is used to capture in-flight imagery of a miniature jet engine exhaust mounted on a custom-built model aircraft. The setup for image acquisition and processing algorithms are described. A new process for registration of images to reduce the degrading effects of vibration and flexure of the airframe are developed and presented along with the underpinning BOS algorithm. Results show that jet flows can be visualised using this technique using a contained system on a single aircraft and demonstrate how a simple technique, such as BOS, can be democratised to such an extent that the cost of conducting in-flight jet measurements can be reduced to the budget of any model aircraft flyer.
Marsupials give birth to immunologically naïve young after a relatively short gestation period compared with eutherians. Consequently, the joey relies significantly on maternal protection, which is the focus of the present review. The milk and the pouch environment are essential contributors to maternal protection for the healthy development of joeys. In this review, we discuss bioactive components found in the marsupial pouch and milk that form cornerstones of maternal protection. These bioactive components include immune cells, immunoglobulins, the S100 family of calcium-binding proteins, lysozymes, whey proteins, antimicrobial peptides and other immune proteins. Furthermore, we investigated the possibility of the presence of plurifunctional components in milk and pouches that are potentially bioactive. These compounds include caseins, vitamins and minerals, oligosaccharides, lipids and microRNAs. Where applicable, this review addresses variability in bioactive components during different phases of lactation, designed to fulfil the immunological needs of the growing pouch young. Yet, there are numerous additional research opportunities to pursue, including uncovering novel bioactive components and investigating their modes of action, dynamics, stability and ability to penetrate the gut epithelium to facilitate systemic effects.