The impact of unilateral pulmonary artery stenosis on right ventricular to pulmonary arterial coupling in patients with transposition of the great arteries.

BACKGROUND: Unilateral pulmonary artery (PA) stenosis is common in the transposition of the great arteries (TGA) after arterial switch operation (ASO) but the effects on the right ventricle (RV) remain unclear. AIMS: To assess the effects of unilateral PA stenosis on RV afterload and function in pediatric patients with TGA-ASO. METHODS: In this retrospective study, eight TGA patients with unilateral PA stenosis underwent heart catheterization and cardiac magnetic resonance (CMR) imaging. RV pressures, RV afterload (arterial elastance [Ea]), PA compliance, RV contractility (end-systolic elastance [Ees]), RV-to-PA (RV-PA) coupling (Ees/Ea), and RV diastolic stiffness (end-diastolic elastance [Eed]) were analyzed and compared to normal values from the literature. RESULTS: In all TGA patients (mean age 12 ± 3 years), RV afterload (Ea) and RV pressures were increased whereas PA compliance was reduced. RV contractility (Ees) was decreased resulting in RV-PA uncoupling. RV diastolic stiffness (Eed) was increased. CMR-derived RV volumes, mass, and ejection fraction were preserved. CONCLUSION: Unilateral PA stenosis results in an increased RV afterload in TGA patients after ASO. RV remodeling and function remain within normal limits when analyzed by CMR but RV pressure-volume loop analysis shows impaired RV diastolic stiffness and RV contractility leading to RV-PA uncoupling.

Releasing incompatible males drives strong suppression across populations of wild and Wolbachia-carrying Aedes aegypti in Australia.

Releasing sterile or incompatible male insects is a proven method of population management in agricultural systems with the potential to revolutionize mosquito control. Through a collaborative venture with the "Debug" Verily Life Sciences team, we assessed the incompatible insect technique (IIT) with the mosquito vector Aedes aegypti in northern Australia in a replicated treatment control field trial. Backcrossing a US strain of Ae. aegypti carrying Wolbachia wAlbB from Aedes albopictus with a local strain, we generated a wAlbB2-F4 strain incompatible with both the wild-type (no Wolbachia) and wMel-Wolbachia Ae. aegypti now extant in North Queensland. The wAlbB2-F4 strain was manually mass reared with males separated from females using Verily sex-sorting technologies to obtain no detectable female contamination in the field. With community consent, we delivered a total of three million IIT males into three isolated landscapes of over 200 houses each, releasing ∼50 males per house three times a week over 20 wk. Detecting initial overflooding ratios of between 5:1 and 10:1, strong population declines well beyond 80% were detected across all treatment landscapes when compared to controls. Monitoring through the following season to observe the ongoing effect saw one treatment landscape devoid of adult Ae. aegypti early in the season. A second landscape showed reduced adults, and the third recovered fully. These encouraging results in suppressing both wild-type and wMel-Ae. aegypti confirms the utility of bidirectional incompatibility in the field setting, show the IIT to be robust, and indicate that the removal of this arbovirus vector from human-occupied landscapes may be achievable.

The effects of percutaneous branch pulmonary artery interventions on exercise capacity, lung perfusion, and right ventricular function in biventricular CHD: a systematic review.

BACKGROUND: Branch pulmonary artery stenosis is common after surgical repair in patients with biventricular CHD and often requires reinterventions. However, (long-term) effects of percutaneous branch pulmonary artery interventions on exercise capacity, right ventricular function, and lung perfusion remain unclear. This review describes the (long-term) effects of percutaneous branch pulmonary artery interventions on exercise capacity, right ventricular function, and lung perfusion following PRISMA guidelines. METHODS: We performed a systematic search in PubMed, Embase, and Cochrane including studies about right ventricular function, exercise capacity, and lung perfusion after percutaneous branch pulmonary artery interventions. Study selection, data extraction, and quality assessment were performed by two researchers independently. RESULTS: In total, 7 eligible studies with low (n = 2) and moderate (n = 5) risk of bias with in total 330 patients reported on right ventricular function (n = 1), exercise capacity (n = 2), and lung perfusion (n = 7). Exercise capacity and lung perfusion seem to improve after a percutaneous intervention for branch pulmonary artery stenosis. No conclusions about right ventricular function or remodelling, differences between balloon and stent angioplasty or specific CHD populations could be made. CONCLUSION: Although pulmonary artery interventions are frequently performed in biventricular CHD, data on relevant outcome parameters such as exercise capacity, lung perfusion, and right ventricular function are largely lacking. An increase in exercise capacity and improvement of lung perfusion to the affected lung has been described in case of mild to more severe pulmonary artery stenosis during relatively short follow-up. However, there is need for future studies to evaluate the effect of pulmonary artery interventions in various CHD populations.

Investigation on key aspects of mating biology in the mosquito Aedes koreicus.

Aedes koreicus Edwards, 1917 (Hulecoetomyia koreica) is a mosquito (Diptera: Culicidae) from Northeast Asia with a rapidly expanding presence outside its original native range. Over the years, the species has been discovered in several new countries, either spreading after first introduction or remaining localised to limited areas. Notably, recent studies have demonstrated the ability of the species to transmit zoonotic parasites and viruses both in the field and in laboratory settings. Combined with its invasive potential, the possible role of Ae. koreicus in pathogen transmission highlights the public health risks resulting from its invasion. In this study, we used a recently established population from Italy to investigate aspects of biology that influence reproductive success in Ae. koreicus: autogeny, mating behaviour, mating disruption by the sympatric invasive species Aedes albopictus Skuse, 1894, and the presence of the endosymbiont Wolbachia pipientis Hertig, 1936. Our laboratory population did not exhibit autogenic behaviour and required a bloodmeal to complete its ovarian cycle. When we exposed Ae. koreicus females to males of Ae. albopictus, we observed repeated attempts at insemination and an aggressive, disruptive mating behaviour initiated by male Ae. albopictus. Despite this, no sperm was identified in Ae. koreicus spermathecae. Wolbachia, an endosymbiotic bacterium capable of influencing mosquito reproductive behaviour, was not detected in this Ae. koreicus population and, therefore, had no effect on Ae. koreicus reproduction.

Comparison of Four-Dimensional Flow MRI, Two-Dimensional Phase-Contrast MRI and Echocardiography in Transposition of the Great Arteries.

Pulmonary artery (PA) stenosis is a common complication after the arterial switch operation (ASO) for transposition of the great arteries (TGA). Four-dimensional flow (4D flow) CMR provides the ability to quantify flow within an entire volume instead of a single plane. The aim of this study was to compare PA maximum velocities and stroke volumes between 4D flow CMR, two-dimensional phase-contrast (2D PCMR) and echocardiography. A prospective study including TGA patients after ASO was performed between December 2018 and October 2020. All patients underwent echocardiography and CMR, including 2D PCMR and 4D flow CMR. Maximum velocities and stroke volumes were measured in the main, right, and left PA (MPA, LPA, and RPA, respectively). A total of 39 patients aged 20 ± 8 years were included. Maximum velocities in the MPA, LPA, and RPA measured by 4D flow CMR were significantly higher compared to 2D PCMR (p < 0.001 for all). PA assessment by echocardiography was not possible in the majority of patients. 4D flow CMR maximum velocity measurements were consistently higher than those by 2D PCMR with a mean difference of 65 cm/s for the MPA, and 77 cm/s for both the RPA and LPA. Stroke volumes showed good agreement between 4D flow CMR and 2D PCMR. Maximum velocities in the PAs after ASO for TGA are consistently lower by 2D PCMR, while echocardiography only allows for PA assessment in a minority of cases. Stroke volumes showed good agreement between 4D flow CMR and 2D PCMR.

Oncological outcomes after piecemeal endoscopic mucosal resection of large non-pedunculated colorectal polyps with covert submucosal invasive cancer.

OBJECTIVE: Management of covert submucosal invasive cancer (SMIC) discovered after piecemeal endoscopic mucosal resection (pEMR) of large (>20 mm) non-pedunculated colorectal polyps is challenging. The residual cancer risk is largely unknown. We sought to evaluate this in a large tertiary referral cohort. DESIGN: Cases of covert SMIC following pEMR were identified and followed. Oncological outcomes after surgery were divided based on residual intramural cancer, lymph node metastases (LNM) or both. Risk factors for residual intramural cancer and LNM were analysed based on the original pEMR histological variables. Risk parameters were analysed with respect to low and high-risk variables for residual intramural cancer and LNM. RESULTS: Among 3372 cases of large non-pedunculated colorectal polyps, 143 cases of covert SMIC (4.2%) were identified. 109 underwent surgical resection. Histological analysis of pEMR histology was available in 98 of 109 (90%) cases. 62 cases (63%) had no residual malignancy. 36 cases had residual malignancy (residual intramural cancer n=24; LNM n=5; both n=7). All cases of residual intramural cancer could be identified by a R1 histological deep margin. Cases with poor differentiation (PD) and/or lymphovascular invasion (LVI) had a high risk of LNM (12/33), with a very low risk without these criteria (<1%; 0/65). Cases at low risk for LNM with R0 deep margin have a low risk of residual intramural cancer (<1%; 0/35). CONCLUSION: The majority of cases of large non-pedunculated colorectal polyps with covert SMIC following pEMR will have no residual malignancy. The risk of residual malignancy can be ascertained from three key variables: PD, LVI and R1 deep margin.

A high-quality de novo genome assembly based on nanopore sequencing of a wild-caught coconut rhinoceros beetle (Oryctes rhinoceros).

BACKGROUND: An optimal starting point for relating genome function to organismal biology is a high-quality nuclear genome assembly, and long-read sequencing is revolutionizing the production of this genomic resource in insects. Despite this, nuclear genome assemblies have been under-represented for agricultural insect pests, particularly from the order Coleoptera. Here we present a de novo genome assembly and structural annotation for the coconut rhinoceros beetle, Oryctes rhinoceros (Coleoptera: Scarabaeidae), based on Oxford Nanopore Technologies (ONT) long-read data generated from a wild-caught female, as well as the assembly process that also led to the recovery of the complete circular genome assemblies of the beetle's mitochondrial genome and that of the biocontrol agent, Oryctes rhinoceros nudivirus (OrNV). As an invasive pest of palm trees, O. rhinoceros is undergoing an expansion in its range across the Pacific Islands, requiring new approaches to management that may include strategies facilitated by genome assembly and annotation. RESULTS: High-quality DNA isolated from an adult female was used to create four ONT libraries that were sequenced using four MinION flow cells, producing a total of 27.2 Gb of high-quality long-read sequences. We employed an iterative assembly process and polishing with one lane of high-accuracy Illumina reads, obtaining a final size of the assembly of 377.36 Mb that had high contiguity (fragment N50 length = 12 Mb) and accuracy, as evidenced by the exceptionally high completeness of the benchmarked set of conserved single-copy orthologous genes (BUSCO completeness = 99.1%). These quality metrics place our assembly ahead of the published Coleopteran genomes, including that of an insect model, the red flour beetle (Tribolium castaneum). The structural annotation of the nuclear genome assembly contained a highly-accurate set of 16,371 protein-coding genes, with only 2.8% missing BUSCOs, and the expected number of non-coding RNAs. The number and structure of paralogous genes in a gene family like Sigma GST is lower than in another scarab beetle (Onthophagus taurus), but higher than in the red flour beetle (Tribolium castaneum), which suggests expansion of this GST class in Scarabaeidae. The quality of our gene models was also confirmed with the correct placement of O. rhinoceros among other members of the rhinoceros beetles (subfamily Dynastinae) in a phylogeny based on the sequences of 95 protein-coding genes in 373 beetle species from all major lineages of Coleoptera. Finally, we provide a list of 30 candidate dsRNA targets whose orthologs have been experimentally validated as highly effective targets for RNAi-based control of several beetles. CONCLUSIONS: The genomic resources produced in this study form a foundation for further functional genetic research and management programs that may inform the control and surveillance of O. rhinoceros populations, and we demonstrate the efficacy of de novo genome assembly using long-read ONT data from a single field-caught insect.

Brainstem and cerebellar volumes at magnetic resonance imaging are smaller in fetuses with congenital heart disease.

BACKGROUND: Congenital heart disease is associated with an increased risk of smaller brain volumes and structural brain damage, and impaired growth of supratentorial brain structures in utero has been linked to poor neurodevelopmental outcomes. However, little is known on brainstem and cerebellar volumes in fetuses with congenital heart disease. Moreover, it is not clear whether impaired infratentorial growth, if present, is associated with only certain types of fetal cardiac defects or with supratentorial brain growth, and whether altered biometry is already present before the third trimester. OBJECTIVE: This study aimed to investigate brainstem and cerebellar volumes in fetuses with congenital heart disease and to compare them to infratentorial brain volumes in fetuses with normal hearts. Secondarily, the study aimed to identify associations between infratentorial brain biometry and the type of cardiac defects, supratentorial brain volumes, and gestational age. STUDY DESIGN: In this retrospective case-control study, 141 magnetic resonance imaging studies of 135 fetuses with congenital heart disease and 141 magnetic resonance imaging studies of 125 controls with normal hearts at 20 to 37 gestational weeks (median, 25 weeks) were evaluated. All cases and controls had normal birthweight and no evidence of structural brain disease or genetic syndrome. Six types of congenital heart disease were included: tetralogy of Fallot (n=32); double-outlet right ventricle (n=22); transposition of the great arteries (n=27); aortic obstruction (n=24); hypoplastic left heart syndrome (n=22); and hypoplastic right heart syndrome (n=14). First, brainstem and cerebellar volumes of each fetus were segmented and compared between cases and controls. In addition, transverse cerebellar diameters, vermian areas, and supratentorial brain and cerebrospinal fluid volumes were quantified and differences assessed between cases and controls. Volumetric differences were further analyzed according to types of cardiac defects and supratentorial brain volumes. Finally, volume ratios were created for each brain structure ([volume in fetus with congenital heart disease/respective volume in control fetus] × 100) and correlated to gestational age. RESULTS: Brainstem (cases, 2.1 cm3 vs controls, 2.4 cm3; P<.001) and cerebellar (cases, 3.2 cm3 vs controls, 3.4 cm3; P<.001) volumes were smaller in fetuses with congenital heart disease than in controls, whereas transverse cerebellar diameters (P=.681) and vermian areas (P=.947) did not differ between groups. Brainstem and cerebellar volumes differed between types of cardiac defects. Overall, the volume ratio of cases to controls was 80.8% for the brainstem, 90.5% for the cerebellum, and 90.1% for the supratentorial brain. Fetuses with tetralogy of Fallot and transposition of the great arteries were most severely affected by total brain volume reduction. Gestational age had no effect on volume ratios. CONCLUSION: The volume of the infratentorial brain, which contains structures considered crucial to brain function, is significantly smaller in fetuses with congenital heart disease than in controls from midgestation onward. These findings suggest that impaired growth of both supra- and infratentorial brain structures in fetuses with congenital heart disease occurs in the second trimester. Further research is needed to elucidate associations between fetal brain volumes and neurodevelopmental outcomes in congenital heart disease.

Development of a sample preparation procedure for Sr isotope analysis of Portland cements.

The 87Sr/86Sr isotope ratio can, in principle, be used for provenancing of cement. However, while commercial cements consist of multiple components, no detailed investigation into their individual 87Sr/86Sr isotope ratios or their influence on the integral 87Sr/86Sr isotope ratio of the resulting cement was conducted previously. Therefore, the present study aimed at determining and comparing the conventional 87Sr/86Sr isotope ratios of a diverse set of Portland cements and their corresponding Portland clinkers, the major component of these cements. Two approaches to remove the additives from the cements, i.e. to measure the conventional 87Sr/86Sr isotopic fingerprint of the clinker only, were tested, namely, treatment with a potassium hydroxide/sucrose solution and sieving on a 11-µm sieve. Dissolution in concentrated hydrochloric acid/nitric acid and in diluted nitric acid was employed to determine the 87Sr/86Sr isotope ratios of the cements and the individual clinkers. The aim was to find the most appropriate sample preparation procedure for cement provenancing, and the selection was realised by comparing the 87Sr/86Sr isotope ratios of differently treated cements with those of the corresponding clinkers. None of the methods to separate the clinkers from the cements proved to be satisfactory. However, it was found that the 87Sr/86Sr isotope ratios of clinker and cement generally corresponded, meaning that the latter can be used as a proxy for the clinker 87Sr/86Sr isotope ratio. Finally, the concentrated hydrochloric acid/nitric acid dissolution method was found to be the most suitable sample preparation method for the cements; it is thus recommended for 87Sr/86Sr isotope analyses for cement provenancing.

Troubled Judging of Bronchus Compression Due to Contrast-Filled Balloon in Three-Dimensional Rotational Angiography.

Three-dimensional rotational angiography (3DRA) is a suitable technique to detect the risk of left main bronchus (LMB) compression during left pulmonary artery (LPA) stenting in partial cavopulmonary connection and total cavopulmonary connection (TCPC). We report on a case of a 4-year-old boy with hypoplastic left heart syndrome and TCPC in which 3DRA and bronchoscopy gave conflicting information on airway patency during balloon interrogation. The balloon with high contrast concentration created a severe artifact impeding visibility of the LMB. Simultaneous flexible bronchoscopy revealed an unobstructed LMB. Repeated 3DRAs with lower contrast concentration had no artifact and showed a patent airway in accordance with the bronchoscopy. Conventional LPA stenting was performed without indication for stent ovalization. The benefit of low contrast concentration in the interrogation balloon was demonstrated in a second case of an 11-year-old boy with TCPC. The margins of the LPA and LMB were clearly visible without blank-out artifact. Oval stent procedure was necessary to prevent LMB compression. When 3DRA is used for vessel-airway interrogation, the balloon contrast concentration should be low in order to avoid artifacts. When in doubt, simultaneous flexible bronchoscopy can overcome the dilemma in airway judgment.

Rapid detection of kdr mutation F1534C in Aedes aegypti using recombinase polymerase amplification and lateral flow dipsticks.

Insecticide resistance monitoring is essential in assessing the efficacy of vector control measures. However, gold standard PCR-based molecular analyses for insecticide resistance detection are often hindered by time-consuming sample processing, as well as considerable infrastructure and resourcing requirements. In this study, we combined a novel one-step sample preparation reagent with a rapid isothermal molecular test that detects a knock down resistance (kdr) mutation (F1534C) that enables pyrethroid resistance in Aedes aegypti mosquitoes. We trialled the rapid F1534C pyrethroid resistance test using insecticide resistant Ae. aegypti mosquito bodies and compared results to a conventional, allele-specific quantitative PCR (AS-qPCR) coupled with melt curve genotyping in corresponding mosquito heads. From a strain of Ae. aegypti established from an insecticide resistant population in Merida, Mexico (n = 27), all the mosquito bodies (n = 27) tested positive with the rapid F1534C test regardless of whether they were homozygous or heterozygous. To assess diagnostic test specificity, we confirmed that F1534 was not detected in laboratory-reared, fully susceptible Ae. aegypti mosquito bodies (n = 28) using the rapid F1534C test or the conventional AS-qPCR melt curve analysis. All corresponding mosquito heads (n = 28) were homozygous wild-type FF1534. The rapid F1534C test thus demonstrated 100% diagnostic sensitivity (95% CI: 87.23% to 100%) and 100% diagnostic specificity (95% CI: 87.66% to 100.00%) for detection of the F1534C pyrethroid resistant single nucleotide polymorphism (SNP) in both heterozygous and homozygous Ae. aegypti. In the collection of mutant mosquitoes from Mexico, CC1534 homozygous mutants occurred at a frequency of 74.1% (n = 20) and FC heterozygous mutants at a frequency of 25.9% (n = 7). The rapid F1534C test significantly reduced the sample processing and testing time from approximately 6 h for the AS-qPCR melt curve analysis to only 25 min. These results demonstrate significant potential for our approach to resistance testing as a field-based, low-resource, rapid alternative to time-consuming and expensive laboratory-based detection.

A regional suitable conditions index to forecast the impact of climate change on dengue vectorial capacity.

BACKGROUND: The mosquitoes Aedes aegypti and Ae. albopictus are the primary vectors of dengue virus, and their geographic distributions are predicted to expand further with economic development, and in response to climate change. We aimed to estimate the impact of future climate change on dengue transmission through the development of a Suitable Conditions Index (SCI), based on climatic variables known to support vectorial capacity. We calculated the SCI based on various climate change scenarios for six countries in the Asia-Pacific region (Australia, China, Indonesia, The Philippines, Thailand and Vietnam). METHODS: Monthly raster climate data (temperature and precipitation) were collected for the period January 2005 to December 2018 along with projected climate estimates for the years 2030, 2050 and 2070 using Representative Concentration Pathway (RCP) 4·5, 6·0 and 8·5 emissions scenarios. We defined suitable temperature ranges for dengue transmission of between 17·05-34·61 °C for Ae. aegypti and 15·84-31·51 °C for Ae. albopictus and then developed a historical and predicted SCI based on weather variability to measure the expected geographic limits of dengue vectorial capacity. Historical and projected SCI values were compared through difference maps for the six countries. FINDINGS: Comparing different emission scenarios across all countries, we found that most South East Asian countries showed either a stable pattern of high suitability, or a potential decline in suitability for both vectors from 2030 to 2070, with a declining pattern particularly evident for Ae. albopictus. Temperate areas of both China and Australia showed a less stable pattern, with both moderate increases and decreases in suitability for each vector in different regions between 2030 and 2070. INTERPRETATION: The SCI will be a useful index for forecasting potential dengue risk distributions in response to climate change, and independently of the effects of human activity. When considered alongside additional correlates of infection such as human population density and socioeconomic development indicators, the SCI could be used to develop an early warning system for dengue transmission.

Critical peptic ulcer bleeding requiring massive blood transfusion: outcomes of 270 cases.

BACKGROUND: Critical peptic ulcer bleeding requiring massive transfusion is a gastroenterological emergency. Few data exist on management and outcomes. The Australian and New Zealand Massive Transfusion Registry collects comprehensive data on adult patients receiving massive transfusion across all bleeding contexts. AIM: To evaluate clinical factors, management (procedural interventions, transfusions) and outcomes after massive transfusion for critical peptic ulcer bleeding. METHOD: Demographics, diagnosis, procedures and mortality data were available for 5482 massive transfusion cases from 23 hospitals. International Classification of Diseases 10th Edition, Australian Modification codes were used to determine peptic ulcer bleeding and the Australian Classification of Health Intervention for interventions (i.e. endoscopic, radiological, surgical). RESULTS: Peptic ulcer bleeding accounted for 270 (4.9%) of all in-hospital massive transfusion cases; 70% were male. Median number of red blood cell (RBC) units transfused was 7 (interquartile range, 6-10). Thirty-day mortality was 19.6%. Age (75 vs 67 years; P = 0.009) and Charlson Comorbidity Index (3 vs 1; P < 0.001) were higher in those who died. Highest 24-h international normalised ratio (1.5 vs 1.4; P < 0.001) and creatinine (118 µmol/L vs 96 µmol/L; P = 0.03) and nadir platelet count (86 × 109 /L vs 118 × 109 /L; P = 0.01) were also associated with 30-day mortality. There were no differences in mortality according to number of RBC, platelets or plasma units transfused, gastroscopy (with or without intervention), interventional radiology or surgery. CONCLUSION: One in five patients with critical peptic ulcer bleeding requiring massive transfusion died by 30 days. Mortality was associated with patient characteristics rather than clinical interventions (e.g. procedures, blood product transfusion).

Is the health-awareness of leaders related to the working conditions, engagement, and exhaustion in their teams? A multi-level mediation study.

BACKGROUND: Research shows that leaders influence the health and well-being of employees, by being either a buffer or major source of employee's work stressors. Various leadership behaviors and their relation to employee outcomes have been examined. Yet, a satisfactory explanation of how leaders' behavior influences health has not been found. A new line of research investigates the construct of "health-oriented leadership", that is, the health awareness of leaders towards themselves ("self-care") and towards their employees ("staff-care"). It is hypothesized that this health-orientation has a direct effect on both leader's and employees' health, as well as an indirect effect mediated by their working conditions. METHODS: Data were derived from four company research projects, that involved employee and leader surveys on work, health, and well-being. The sample consisted of 50 teams, with 191 leaders and 604 team members. To test the relation between a leader's self-care and his/her engagement, exhaustion, as well as staff-care, multiple regression analyses and mediation analyses were conducted. The relation between a leader's staff-care, the team's job resources and demands, and the individual employee outcomes engagement and exhaustion were tested with multilevel analyses. RESULTS: Regression analysis showed that the stronger a leader's health-orientation towards him/-herself ("self-care"), the stronger was the health-orientation towards his/her employees ("staff-care"). A leader's self-care was also associated with higher work engagement and lower exhaustion and this relation was mediated by his/her job resources and demands, respectively. Multilevel analysis showed that a leader's staff-care was associated with employee work engagement and exhaustion, and that this relation was mediated by team-level job resources and demands, respectively. CONCLUSIONS: The health-orientation of leaders relates to their own as well as their teams' engagement and exhaustion, which is partly mediated by job demands and resources. Thus the construct of health-orientation may prove worthy of further exploration. For practical conclusions, this study provides support for researching not different leadership styles with very specific facets, but a general orientation towards health, which can be implemented into coaching and consulting sessions for organizations.

Prior authorization delays biologic initiation and is associated with a risk of asthma exacerbations.

Background: Biologics are effective treatments for patients with severe allergic disease. Impacts of delays in the prior authorization process on clinical outcomes has not been studied. Objective: The objective was to quantify the times for approval and filling of biologics, and whether patients were at risk of exacerbations during this time frame. Methods: The times for insurance approval and pharmacy filling of biologics (omalizumab, benralizumab, mepolizumab, dupilumab) in 80 subjects with severe asthma (n = 60) or urticaria (n = 20) from our clinic were reviewed. We compared the impact of clinical features, insurance, specialty pharmacy on fill times, and quantified exacerbations and prednisone use while awaiting biologic initiation. Results: The mean ± standard deviation (SD) time (days) from submission of a prescription to the first dose available for injection was 44.0 ± 23.2 days. This was composed of the mean ± SD time for insurance approval (21.5 ± 19.6 days) and the mean ± SD time for a specialty pharmacy to fill the medication (22.8 ± 14.1 days). There was no significant difference between the times for diagnosis (asthma versus urticaria), specific biologic, or insurance. The "buy and bill" system was faster than filling via a specialty pharmacy (mean ± SD, 7.3 ± 8.5 days versus 23.3 ± 21.3 days, respectively, p < 0.001). Clinical features of patients with fast versus slow approval times was not significantly different. The subjects with asthma were at high risk of exacerbations and need for prednisone while awaiting initiation of the biologics; 28 of 59 patients (47%) required prednisone, with an mean cumulative dose of 483.2 ± 273.7 mg per person. Conclusion: The prior authorization process for biologics was slow, and the subjects were at high risk of exacerbations during this time. The system needs to be improved to expedite approval and initiation of these medications.

Using spatial genetics to quantify mosquito dispersal for control programs.

BACKGROUND: Hundreds of millions of people get a mosquito-borne disease every year and nearly one million die. Transmission of these infections is primarily tackled through the control of mosquito vectors. The accurate quantification of mosquito dispersal is critical for the design and optimization of vector control programs, yet the measurement of dispersal using traditional mark-release-recapture (MRR) methods is logistically challenging and often unrepresentative of an insect's true behavior. Using Aedes aegypti (a major arboviral vector) as a model and two study sites in Singapore, we show how mosquito dispersal can be characterized by the spatial analyses of genetic relatedness among individuals sampled over a short time span without interruption of their natural behaviors. RESULTS: Using simple oviposition traps, we captured adult female Ae. aegypti across high-rise apartment blocks and genotyped them using genome-wide SNP markers. We developed a methodology that produces a dispersal kernel for distance which results from one generation of successful breeding (effective dispersal), using the distance separating full siblings and 2nd- and 3rd-degree relatives (close kin). The estimated dispersal distance kernel was exponential (Laplacian), with a mean dispersal distance (and dispersal kernel spread σ) of 45.2 m (95% CI 39.7-51.3 m), and 10% probability of a dispersal > 100 m (95% CI 92-117 m). Our genetically derived estimates matched the parametrized dispersal kernels from previous MRR experiments. If few close kin are captured, a conventional genetic isolation-by-distance analysis can be used, as it can produce σ estimates congruent with the close-kin method if effective population density is accurately estimated. Genetic patch size, estimated by spatial autocorrelation analysis, reflects the spatial extent of the dispersal kernel "tail" that influences, for example, the critical radii of release zones and the speed of Wolbachia spread in mosquito replacement programs. CONCLUSIONS: We demonstrate that spatial genetics can provide a robust characterization of mosquito dispersal. With the decreasing cost of next-generation sequencing, the production of spatial genetic data is increasingly accessible. Given the challenges of conventional MRR methods, and the importance of quantified dispersal in operational vector control decisions, we recommend genetic-based dispersal characterization as the more desirable means of parameterization.

CD90+CD146+ identifies a pulmonary mesenchymal cell subtype with both immune modulatory and perivascular-like function in postnatal human lung.

Our understanding of mesenchymal cell subsets and their function in human lung affected by aging and in certain disease settings remains poorly described. We use a combination of flow cytometry, prospective cell-sorting strategies, confocal imaging, and modeling of microvessel formation using advanced microfluidic chip technology to characterize mesenchymal cell subtypes in human postnatal and adult lung. Tissue was obtained from patients undergoing elective surgery for congenital pulmonary airway malformations (CPAM) and other airway abnormalities including chronic obstructive pulmonary disease (COPD). In microscopically normal postnatal human lung, there was a fivefold higher mesenchymal compared with epithelial (EpCAM+) fraction, which diminished with age. The mesenchymal fraction composed of CD90+ and CD90+CD73+ cells was enriched in CXCL12 and platelet-derived growth factor receptor-α (PDGFRα) and located in close proximity to EpCAM+ cells in the alveolar region. Surprisingly, alveolar organoids generated from EpCAM+ cells supported by CD90+ subset were immature and displayed dysplastic features. In congenital lung lesions, cystic air spaces and dysplastic alveolar regions were marked with an underlying thick interstitium composed of CD90+ and CD90+PDGFRα+ cells. In postnatal lung, a subset of CD90+ cells coexpresses the pericyte marker CD146 and supports self-assembly of perfusable microvessels. CD90+CD146+ cells from COPD patients fail to support microvessel formation due to fibrinolysis. Targeting the plasmin-plasminogen system during microvessel self-assembly prevented fibrin gel degradation, but microvessels were narrower and excessive contraction blocked perfusion. These data provide important new information regarding the immunophenotypic identity of key mesenchymal lineages and their change in a diverse setting of congenital lung lesions and COPD.

Epinephrine stress testing during cardiac catheterization in patients with aortic coarctation.

BACKGROUND: The severity of aortic coarctation (CoA) may be underestimated during cardiac catheterization. We aimed to investigate whether epinephrine stress testing improves clinical decision making and outcome in CoA. METHODS: We retrospectively evaluated CoA patients >50 kg with a peak systolic gradient (PSG) ≤20 mm Hg during cardiac catheterization who underwent epinephrine stress testing. Subsequent interventional management (stenting or balloon dilatation), complications, and medium-term clinical outcome were assessed. RESULTS: Fifty CoA patients underwent cardiac catheterization with epinephrine stress testing. Patients with a high epinephrine PSG (>20 mm Hg; n = 24) were younger and more likely to have a hypertensive response to exercise compared to patients with a low epinephrine PSG (≤20 mm Hg; n = 26). In total, 21 patients (88%) with a high epinephrine PSG underwent intervention, and 20 patients (77%) with a low epinephrine PSG were treated conservatively. After a mean follow-up of 25 ±â€¯18 months, there was a lower prevalence of hypertension in patients with a high epinephrine PSG who underwent intervention compared to patients with a low epinephrine PSG treated conservatively (19% vs. 76%; P = .001). In a multivariate model, intervention was independently associated with a 14.3-mm Hg reduction in systolic blood pressure (P = .001) and a decrease in the use of antihypertensive agents. CONCLUSIONS: In CoA patients with a low baseline PSG but high epinephrine PSG, percutaneous intervention is associated with a substantial reduction in systemic blood pressure and the use of antihypertensive medication. Accordingly, epinephrine stress testing may be a useful addition in the evaluation of CoA.

Spatial and temporal patterns of Ross River virus in south east Queensland, Australia: identification of hot spots at the rural-urban interface.

BACKGROUND: Ross River virus (RRV) is responsible for the most common vector-borne disease of humans reported in Australia. The virus circulates in enzootic cycles between multiple species of mosquitoes, wildlife reservoir hosts and humans. Public health concern about RRV is increasing due to rising incidence rates in Australian urban centres, along with increased circulation in Pacific Island countries. Australia experienced its largest recorded outbreak of 9544 cases in 2015, with the majority reported from south east Queensland (SEQ). This study examined potential links between disease patterns and transmission pathways of RRV. METHODS: The spatial and temporal distribution of notified RRV cases, and associated epidemiological features in SEQ, were analysed for the period 2001-2016. This included fine-scale analysis of disease patterns across the suburbs of the capital city of Brisbane, and those of 8 adjacent Local Government Areas, and host spot analyses to identify locations with significantly high incidence. RESULTS: The mean annual incidence rate for the region was 41/100,000 with a consistent seasonal peak in cases between February and May. The highest RRV incidence was in adults aged from 30 to 64 years (mean incidence rate: 59/100,000), and females had higher incidence rates than males (mean incidence rates: 44/100,000 and 34/100,000, respectively). Spatial patterns of disease were heterogeneous between years, and there was a wide distribution of disease across both urban and rural areas of SEQ. Overall, the highest incidence rates were reported from predominantly rural suburbs to the north of Brisbane City, with significant hot spots located in peri-urban suburbs where residential, agricultural and conserved natural land use types intersect. CONCLUSIONS: Although RRV is endemic across all of SEQ, transmission is most concentrated in areas where urban and peri-urban environments intersect. The drivers of RRV transmission across rural-urban landscapes should be prioritised for further investigation, including identification of specific vectors and hosts that mediate human spillover.

Microbial pathogen removal from domestic effluent using coral sand in Kiribati.

AIM: Infiltration experiments aimed to show the effectivity of coral sand to remove micro-organisms in septic tank wastewater treatment system, in South Tarawa, Kiribati. METHODS AND RESULTS: Laboratory experiments evaluated effective microbial removal properties of a packed bed of coral beach sand conditioned with domestic effluent. Bacterial and viral indicators Escherichia coli J6-2, Enterococci faecalis and f-RNA (MS2) bacteriophage, along with viral pathogens adenovirus, echovirus, norovirus and rotavirus, were dosed (at 106 -107  CFU, PFU or genome copies per ml concentration) with effluent to unsaturated coral sand-packed columns. For the conditions simulated, all organisms showed removal efficiencies of >4-Log Removal Values (LRVs) (i.e. >99·99% effective reduction in number). Results revealed that the conditioned coral sand had a higher affinity for attenuating viruses than the bacteria tested. MS2 phage, adenovirus, echovirus, norovirus and rotavirus were absent in leachate from the base of the sand columns. E. coli J6-2 and E. faecalis were recovered at 100 -101  CFU (colony forming units) per ml in the column effluent, following a dosage of 106  CFU per ml. Destructive sampling of the columns after experiments revealed that a high proportion of viral pathogens were retained in the top 30 mm of the sand. CONCLUSIONS: On the basis of the relative spatial distribution of trace organisms in the sand, we speculate that adsorption processes likely dominated attenuation of the viral pathogens, more so than physical straining effects. Further study is required to fully elucidate the removal mechanisms. SIGNIFICANCE AND IMPACT OF THE STUDY: To the best of our knowledge this is the first study of the effective microbial removal capacity of coral sand under unsaturated conditions. The work represents an initial exploratory step of developing some standardized design practice of on-site wastewater treatment systems in Kiribati, to offer enhanced protection of groundwater resources and reduce diarrhoeal disease.