Comparison of disease severity in glaucoma patients identified by screening in the 1990s and in routine clinical care in the 2010s in Sweden.

BACKGROUND AND PURPOSE: In a previous study comparing the amount of visual field damage at presentation in patients having open-angle glaucoma (OAG) identified through screening and in patients diagnosed in routine clinical practice in the 1990s, the damage was considerably worse in the clinically diagnosed patients. In the present study we compare visual field damage at presentation in the same 402 screened patients with that seen in 281 newly detected previously untreated patients clinically diagnosed in the 2010s. METHODS: The perimetric visual field index mean deviation (MD) was compared in the two groups of patients. RESULTS: In the clinical patients diagnosed with bilateral visual field damage the median MD was -5.1 dB in the better eye and -13.0 dB in the worse eye. In the screened patients the median MD in the better eye was -6.5 dB and -11.5 dB in the worse eye. The differences between the clinical and screened patients were non-significant, p = 0.28 and p = 0.67 respectively. More clinical patients had severe visual field loss, defined as MD less than -20 dB, in the worse eye than in the screened patients, 18.5% versus 12.7% respectively, p = 0.037. CONCLUSION: The visual field damage at presentation in clinically diagnosed OAG patients has improved in the past 20 years, but the proportion of patients with severe visual field loss in at least one eye, almost 20%, is still unacceptably high considering that severe visual field damage at presentation is the most important risk factor for later development of glaucoma blindness.

Higher beta-hydroxybutyrate ketone levels associated with a slower kidney function decline in ADPKD.

BACKGROUND AND HYPOTHESIS: Dysregulated energy metabolism is a recently discovered key feature of Autosomal Dominant Polycystic Kidney Disease (ADPKD). Cystic cells depend on glucose and are poorly able to use other energy sources such as ketone bodies. Raising ketone body concentration reduced disease progression in animal models of polycystic kidney diseases. Therefore, we hypothesized that higher endogenous plasma beta-hydroxybutyrate concentrations are associated with reduced disease progression in patients with ADPKD. METHODS: We analyzed data from 670 patients with ADPKD participating in the DIPAK cohort, a multi-center prospective observational cohort study. Beta-hydroxybutyrate was measured at baseline using nuclear magnetic resonance spectroscopy. Participants were excluded if they had type 2 diabetes, were using disease-modifying drugs (e.g. tolvaptan, somatostatin analogs), were not fasting, or had missing beta-hydroxybutyrate levels, leaving 521 participants for the analyses. Linear regression analyses were used to study cross-sectional associations and linear mixed-effect modeling for longitudinal associations. RESULTS: Of the participants, 61% were female, with an age of 47.3 ± 11.8 years, a height-adjusted total kidney volume (htTKV) of 834 (IQR 495-1327) ml/m, and an estimated glomerular filtration rate (eGFR) of 63.3 ± 28.9 mL/min/1.73m2. The median concentration of beta-hydroxybutyrate was 94 (IQR 68-147) µmol/L. Cross-sectionally, beta-hydroxybutyrate was neither associated with eGFR nor with htTKV. Longitudinally, beta-hydroxybutyrate was positively associated with eGFR slope (B = 0.35 ml/min/1.73m2 (95% CI 0.09 to 0.61), p = 0.007), but not with kidney growth. After adjustment for potential confounders, every doubling in beta-hydroxybutyrate concentration was associated with an improvement in the annual rate of eGFR by 0.33 ml/min/1.73m2 (95% CI 0.09 to 0.57, p = 0.008). CONCLUSION: These observational analyses support the hypothesis that interventions that raise beta-hydroxybutyrate concentration could reduce the rate of kidney function decline in patients with ADPKD.

CIMT 2023: report on the 20th Annual Meeting of the Association for Cancer Immunotherapy.

The Association for Cancer Immunotherapy (CIMT) celebrated the 20th anniversary of the CIMT Annual Meeting. CIMT2023 was held 3-5 May 2023 in Mainz, Germany. 1051 academic and clinical professionals from over 30 countries attended the meeting and discussed the latest advances in cancer immunology and immunotherapy research. This report summarizes the highlights of CIMT2023.

Combined petrosal approach: a systematic review and meta-analysis of surgical complications.

Transpetrosal approaches are known to be associated with a significant risk of complications, including CSF leak, facial palsy, hearing impairment, venous injury, and/or temporal lobe injury. We aimed to evaluate the morbidity of the standard combined petrosal approach (CPA), defined as a combination of the posterior (retrolabyrinthine) and the anterior petrosal approach. We performed a systematic review and meta-analysis of articles reporting on clinical series of patients operated on for petroclival meningiomas through CPA. Studies that used the terminology "combined petrosal approach" without matching the aforementioned definition were excluded as well as clinical series that included less than 5 patients. A total of 8 studies were included involving 160 patients. The pooled complication rates were 3% (95% CI, 0.5-5.6) for CSF leak, 8.6% (95% CI, 4.1-13.2%) for facial palsy, 8.2% (95% CI, 3.9-12.6%) for hearing impairment, 2.8% (95% CI, 0.9-6.5%) for venous complications, and finally 4.8% (95%, 1.2-8.4%) for temporal lobe injury. Contrary to the general belief, CPA is associated with an acceptable rate of complications, especially when compared to alternative approaches to the petroclival area. In view of the major advantages like shorter trajectory, multiple angles of surgical attack, and early tumor devascularization, CPA remains an important tool in the armamentarium of the skull base surgeon.

Confined placental mosaicism: placental size and function evaluated on magnetic resonance imaging.

OBJECTIVES: Evidence regarding placental function in pregnancies complicated by confined placental mosaicism (CPM) is conflicting. We aimed to compare placental function between CPM and non-CPM pregnancies prenatally and at birth. A secondary objective was to evaluate the relationship between placental function and chromosomal subtype of CPM. METHODS: This was a retrospective study of pregnancies with CPM and control pregnancies delivered at a tertiary hospital in Denmark between 2014 and 2017. Placental volume and placental transverse relaxation time (T2*) were estimated on magnetic resonance imaging (MRI), fetal weight and uterine artery pulsatility index (UtA-PI) were estimated on ultrasound and fetoplacental ratio was assessed on MRI and at birth. These estimates of placental function were adjusted for gestational age and compared between groups using the Wilcoxon rank-sum test. Within the group of CPM pregnancies, measures of placental function were compared between those at high risk (chromosome numbers 2, 3, 7, 13 and 16) and those at low risk (chromosome numbers 5, 18 and 45X). RESULTS: A total of 90 pregnancies were included, of which 12 had CPM and 78 were controls. MRI and ultrasound examinations were performed at a median gestational age of 32.6 weeks (interquartile range, 24.7-35.3 weeks). On MRI assessment, CPM placentae were characterized by a lower placental T2* Z-score (P = 0.004), a lower fetoplacental ratio (P = 0.03) and a higher UtA-PI Z-score (P = 0.03), compared with non-CPM placentae. At birth, the fetoplacental ratio was significantly lower (P = 0.02) and placental weight Z-score was higher (P = 0.01) in CPM pregnancies compared with non-CPM pregnancies. High-risk CPM pregnancies showed a reduced placental T2* Z-score (P = 0.003), lower birth-weight Z-score (P = 0.041), earlier gestational age at delivery (P = 0.019) and higher UtA-PI Z-score (P = 0.028) compared with low-risk CPM pregnancies. Low-risk CPM pregnancies did not differ in any of these parameters from non-CPM pregnancies. CONCLUSIONS: CPM pregnancies are characterized by an enlarged and dysfunctional placenta. Placental function was highly related to the chromosomal type of CPM; placental dysfunction was seen predominantly in high-risk CPM pregnancies in which chromosomes 2, 3, 7, 13 or 16 were involved. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Placental volume, thickness and transverse relaxation time (T2*) estimated by magnetic resonance imaging in relation to small for gestational age at birth.

INTRODUCTION: Placental magnetic resonance imaging (MRI) may be a valuable tool in the prediction of small for gestational age (SGA) at birth. MRI provides reliable estimates of placental volume and thickness. In addition, placental transverse relaxation time (T2*) may be directly related to placental function. This study aimed to explore and compare the predictive performance of three placental MRI parameters - volume, thickness and T2* - in relation to SGA at birth. METHODS: A mixed cohort of 85 pregnancies was retrieved from the placental MRI database at the study hospital. MRI was performed in a 1.5 T system at gestational weeks 15-41. In normal birthweight (BW) pregnancies [BW > -22 % of expected for gestational age (GA)], the correlation between each of the MRI parameters and GA was investigated by linear regression. The prediction of SGA was investigated by logistic regression analysis adjusted for GA at MRI. RESULTS: In normal BW pregnancies, a significant linear correlation was found between GA and each of the MRI parameters. Univariate analysis demonstrated that placental volume [odds ratio (OR) 0.97, p = 0.001] and placental T2* (OR 0.79, p = 0.003), but not placental thickness (OR 0.92, p = 0.862) were significant predictors of SGA. A multi-variate model including all three MRI parameters found that placental T2* was the only independent predictor of SGA (OR 0.81, p = 0.04). CONCLUSION: Among the MRI parameters investigated in this study, placental T2* was the only independent predictor of SGA in a multi-variate model. This finding underlines the strong position of T2*-weighted placental MRI in the prediction of SGA.

Genomic loci associated with performance limiting equine overriding spinous processes (kissing spines).

Commonly known as "Kissing Spines" (KS), the pathological mechanisms underlying impingement and overriding of spinous processes (ORSPs) in horses are poorly understood. Thoroughbreds, Warmbloods, and stock-type breeds, including Paint Horses and Quarter Horses are at increased risk for developing clinical signs of KS. A total of 155 stock-type and Warmblood horses presented at collaborating veterinary clinics and hospitals were examined using a strict clinical and radiographical phenotyping scheme to grade each horse from 0 for unaffected controls to 4 for severe KS. Following genotyping with the Illumina Equine SNP70 array (Illumina, Inc.) a Genome Wide Association Study (GWAS) using 61,229 filtered individual Single Nucleotide Polymorphisms (SNPs) was performed to the KS grade phenotype. Two significantly associated SNPs (BIEC2-668062 and BIEC2-668013) on chromosome 25 defined a ~1.4 Gb candidate region containing approximately 17 coding genes (EquCab3) and 195 ENSEMBL annotated variants. Investigation of the best associated SNP (BIEC2-668062) on chr25 demonstrates a significant correlation with an increase in one KS grade, on average, per A allele in this population. A significant effect of breed group, age, height or sex was not observed in this population. These preliminary results demonstrate the potential for KS diagnosis and preventative measures for WB/ST individuals supported by increased genetic risk for more severe KS grade. We propose further research including other affected breeds and evaluating causative variants, as well as the effect of BIEC2-668062 in these populations.

Local diagnostic reference levels for skeletal surveys in suspected physical child abuse.

INTRODUCTION: The purpose was to determine if an age based, local diagnostic reference level for paediatric skeletal surveys could be established using retrospective data. METHODS: All children below two years of age referred for a primary skeletal survey as a result of suspected physical abuse during 2017 or 2018 (n = 45) were retrospectively included from a large Danish university hospital. The skeletal survey protocol included a total of 33 images. Dose Area Product (DAP) and acquisition parameters for all images were recorded from the Picture Archival and Communication System (PACS) and effective dose was estimated. The 75th percentile for DAP was considered as the diagnostic reference level (DRL). RESULTS: The 75th percentile for DAP was 314 mGy∗cm2, 520 mGy∗cm2 and 779 mGy∗cm2 for children <1 month, 1-11 months and 12 < 24 months of age respectively. However, only the age group 1-11 months had a sufficient number of children (n = 27) to establish a local DRL. Thus, for the other groups the DAP result must be interpreted with caution. Effective dose was 0.19, 0.26 and 0.18 mSv for children <1, 1-11 months and 12 < 24 months of age respectively. CONCLUSION: For children between 1 and 11 months of age, a local diagnostic reference level of 520 mGy∗cm2 was determined. This may be used as an initial benchmark for primary skeletal surveys as a result of suspected physical abuse for comparison and future discussion. IMPLICATIONS FOR PRACTICE: While the data presented reflects the results of a single department, the suggested diagnostic reference level may be used as a benchmark for other departments when auditing skeletal survey radiation dose.

Potential for Electric Vehicle Adoption to Mitigate Extreme Air Quality Events in China.

Electric vehicle (EV) adoption promises potential air pollutant and greenhouse gas (GHG) reduction co-benefits. As such, China has aggressively incentivized EV adoption, however much remains unknown with regard to EVs' mitigation potential, including optimal vehicle type prioritization, power generation contingencies, effects of Clean Air regulations, and the ability of EVs to reduce acute impacts of extreme air quality events. Here, we present a suite of scenarios with a chemistry transport model that assess the potential co-benefits of EVs during an extreme winter air quality event. We find that regardless of power generation source, heavy-duty vehicle (HDV) electrification consistently improves air quality in terms of NO2 and fine particulate matter (PM2.5), potentially avoiding 562 deaths due to acute pollutant exposure during the infamous January 2013 pollution episode (~1% of total premature mortality). However, HDV electrification does not reduce GHG emissions without enhanced emission-free electricity generation. In contrast, due to differing emission profiles, light-duty vehicle (LDV) electrification in China consistently reduces GHG emissions (~2 Mt CO2), but results in fewer air quality and human health improvements (145 avoided deaths). The calculated economic impacts for human health endpoints and CO2 reductions for LDV electrification are nearly double those of HDV electrification in present-day (155M vs. 87M US$), but are within ~25% when enhanced emission-free generation is used to power them. Overall, we find only a modest benefit for EVs to ameliorate severe wintertime pollution events, and that continued emission reductions in the power generation sector will have the greatest human health and economic benefits.

The organisational response of a hospital critical care service to the COVID-19 pandemic: The Groote Schuur Hospital experience.

Background: There are limited data about the coronavirus disease-19 (COVID-19)-related organisational responses and the challenges of expanding a critical care service in a resource-limited setting. Objectives: To describe the ICU organisational response to the pandemic and the main outcomes of the intensive care service of a large state teaching hospital in South Africa. Methods: Data were extracted from administrative records and a prospective patient database with ethical approval. An ICU expansion plan was developed, and resource constraints identified. A triage tool was distributed to referring wards and hospitals. Intensive care was reserved for patients who required invasive mechanical ventilation (IMV). The total number of ICU beds was increased from 25 to 54 at peak periods, with additional non-COVID ICU capacity required during the second wave. The availability of nursing staff was the main factor limiting expansion. A ward-based high flow nasal oxygen (HFNO) service reduced the need for ICU admission of patients who failed conventional oxygen therapy. A team was established to intubate and transfer patients requiring ICU admission but was only available for the first wave. Results: We admitted 461 COVID-19 patients to the ICU over a 13-month period from 5 April 2020 to 5 May 2021 spanning two waves of admissions. The median age was 50 years and duration of ICU stay was 9 days. More than a third of the patients (35%; n=161) survived to hospital discharge. Conclusion: Pre-planning, leadership, teamwork, flexibility and good communication were essential elements for an effective response. A shortage of nurses was the main constraint on ICU expansion. HFNO may have reduced the requirement for ICU admission, but patients intubated after failing HFNO had a poor prognosis. Contributions of the study: We describe the organisational requirements to successfully expand critical care facilities and strategies to reduce the need for invasive mechanical ventilation in COVID-19 pneumonia. We also present the intensive care outcomes of these patients in a resource-constrained environment.

Designing New Metal Chalcogenide Nanoclusters through Atom-by-Atom Substitution.

Atom-by-atom substitution is a promising strategy for designing new cluster-based materials, which has been used to generate new gold- and silver-containing clusters. Here, the first study focused on atom-by-atom substitution of Fe and Ni to the core of a well-defined cobalt sulfide superatom [Co6 S8 L6 ]+ ligated with triethylphosphine (L = PEt3 ) to produce [Co5 MS8 L6 ]+ (M = Fe, Ni) is reported. Electrospray ionization mass spectrometry confirms the substitution of 1-6 Fe atoms with the single Fe-substituted cluster being the dominant species. The Fe-substituted clusters oxidize in solution to generate dicationic species. In contrast, only a single Ni-substituted cluster is observed, which remains stable as a singly charged species. Collision-induced dissociation experiments indicate the reduced stability of the [Co5 FeS8 L6 ]+ toward ligand loss in comparison with the unsubstituted and Ni-substituted counterparts. Density functional theory calculations provide insights into the effect of metal atom substitution on the stability and electronic structures of the clusters. The results indicate that Fe and Ni have a different impact on the electronic structure, optical, and magnetic properties, as well as ligand-core interaction of [Co6 S8 L6 ]. This study extends the atom-by-atom substitution strategy to the metal chalcogenide superatoms providing a direct path toward designing novel atomically precise core-tailored superatoms.

The organisational response of a hospital critical care service to the COVID-19 pandemic: The Groote Schuur Hospital experience

Background. There are limited data about the coronavirus disease-19 (COVID-19)-related organisational responses and the challenges of expanding a critical care service in a resource-limited setting.Objectives. To describe the ICU organisational response to the pandemic and the main outcomes of the intensive care service of a large state teaching hospital in South Africa.Methods. Data were extracted from administrative records and a prospective patient database with ethical approval. An ICU expansion plan was developed, and resource constraints identified. A triage tool was distributed to referring wards and hospitals. Intensive care was reserved for patients who required invasive mechanical ventilation (IMV). The total number of ICU beds was increased from 25 to 54 at peak periods, with additional non-COVID ICU capacity required during the second wave. The availability of nursing staff was the main factor limiting expansion. A ward-based high flow nasal oxygen (HFNO) service reduced the need for ICU admission of patients who failed conventional oxygen therapy. A team was established to intubate and transfer patients requiring ICU admission but was only available for the first wave. Results. We admitted 461 COVID-19 patients to the ICU over a 13-month period from 5 April 2020 to 5 May 2021 spanning two waves of admissions. The median age was 50 years and duration of ICU stay was 9 days. More than a third of the patients (35%; n=161) survived to hospital discharge. Conclusions. Pre-planning, leadership, teamwork, flexibility and good communication were essential elements for an effective response. A shortage of nurses was the main constraint on ICU expansion. HFNO may have reduced the requirement for ICU admission, but patients intubated after failing HFNO had a poor prognosis.

Public Health and Climate Benefits and Trade-Offs of U.S. Vehicle Electrification.

Vehicle electrification is a common climate change mitigation strategy, with policymakers invoking co-beneficial reductions in carbon dioxide (CO2) and air pollutant emissions. However, while previous studies of U.S. electric vehicle (EV) adoption consistently predict CO2 mitigation benefits, air quality outcomes are equivocal and depend on policies assessed and experimental parameters. We analyze climate and health co-benefits and trade-offs of six U.S. EV adoption scenarios: 25% or 75% replacement of conventional internal combustion engine vehicles, each under three different EV-charging energy generation scenarios. We transfer emissions from tailpipe to power generation plant, simulate interactions of atmospheric chemistry and meteorology using the GFDL-AM4 chemistry climate model, and assess health consequences and uncertainties using the U.S. Environmental Protection Agency Benefits Mapping Analysis Program Community Edition (BenMAP-CE). We find that 25% U.S. EV adoption, with added energy demand sourced from the present-day electric grid, annually results in a ~242 M ton reduction in CO2 emissions, 437 deaths avoided due to PM2.5 reductions (95% CI: 295, 578), and 98 deaths avoided due to lesser ozone formation (95% CI: 33, 162). Despite some regions experiencing adverse health outcomes, ~$16.8B in damages avoided are predicted. Peak CO2 reductions and health benefits occur with 75% EV adoption and increased emission-free energy sources (~$70B in damages avoided). When charging-electricity from aggressive EV adoption is combustion-only, adverse health outcomes increase substantially, highlighting the importance of low-to-zero emission power generation for greater realization of health co-benefits. Our results provide a more nuanced understanding of the transportation sector's climate change mitigation-health impact relationship.

Presence of a 34-gene signature is a favorable prognostic marker in squamous non-small cell lung carcinoma.

BACKGROUND: The tumor immune microenvironment is a heterogeneous entity. Gene expression analysis allows us to perform comprehensive immunoprofiling and may assist in dissecting the different components of the immune infiltrate. As gene expression analysis also provides information regarding tumor cells, differences in interactions between the immune system and specific tumor characteristics can also be explored. This study aims to gain further insights in the composition of the tumor immune infiltrate and to correlate these components to histology and overall survival in non-small cell lung cancer (NSCLC). METHODS: Archival tissues from 530 early stage, resected NSCLC patients with annotated tumor and patient characteristics were analyzed using the NanoString nCounter Analysis system. RESULTS: Unsupervised clustering of the samples was mainly driven by the overall level of inflammation, which was not correlated with survival in this patient set. Adenocarcinoma (AD) showed a significantly higher degree of immune infiltration compared to squamous cell carcinoma (SCC). A 34-gene signature, which did not correlate with the overall level of immune infiltration, was identified and showed an OS benefit in SCC. Strikingly, this benefit was not observed in AD. This difference in OS in SCC specifically was confirmed in two independent NSCLC cohorts. The highest correlation between expression of the 34-gene signature and specific immune cell populations was observed for NK cells, but although a plausible mechanism for NK cell intervention in tumor growth could be established in SCC over AD, this could not be translated back to immunohistochemistry, which showed that NK cell infiltration is scarce irrespective of histology. CONCLUSIONS: These findings suggest that the ability of immune cell infiltration and the interaction between tumor and immune cells may be different between AD and SCC histology and that a subgroup of SCC tumors seems more susceptible to Natural Killer cell recognition and killing, whereas this may not occur in AD tumors. A highly sensitive technique like NanoString was able to detect this subgroup based on a 34-gene signature, but further research will be needed to assist in explaining the biological rationale of such low-level expression signatures.

The Importance of Lobbying to Advance Health and Science Policy.

Government funding and policies are critical to academic medicine. Publicfunds sustain the education, research, and patient care missions of medical schools and teaching hospitals, and regulations govern the fulfillment of those missions. Consequently, both individuals and institutions often need to engage with those who develop these policies, including through lobbying. Lobbying fulfills a constitutionally protected right to petition the government for a redress of grievances, despite perceptions that it is instead only back-room dealing and insider influence. As an important part of the system of government in the United States, lobbying is subject to complex regulations, and failure to comply can result in substantial penalties, particularly for tax-exempt entities, of which almost all medical schools and the large majority of teaching hospitals are. In this Invited Commentary, the author briefly summarizes these regulations to complement the article in this issue by Lynch and colleagues. He then argues that while regulatory compliance is essential, it is not the same as lobbying effectively. For individual academic researchers to do that involves a number of considerations, including whether to coordinate their efforts with those of their institution to leverage the expertise and resources of the institution, to maximize their chances for success with policymakers.

Understanding the role of community resilience in addressing the Ebola virus disease epidemic in Liberia: a qualitative study (community resilience in Liberia).

Background: There is an increasing recognition that community resilience plays a significant role in addressing health shocks like the Ebola virus disease (EVD) epidemic. However, the factors that constitute community resilience, and how these operate dynamically with other health system factors are less understood. Objective: This paper seeks to understand key factors that constitute community resilience and their role in responding to the EVD outbreak in Liberia. Methods: Key informant interviews were conducted between November 2017 and April 2018 with community representatives in Bomi, Margibi and Montserrado counties, and other national stakeholders involved in the EVD response in Liberia from 2014 to 2016. A national stakeholder meeting was conducted to verify and interpret information emerging from the interviews. Results: Factors that were critical for addressing the EVD epidemic in Liberia were identified as: strong leadership, tight bonds and sense of kinship at the community level; trusted communication channels; and trust among various health system stakeholders. These factors facilitated collective actions within communities and helped to direct response initiatives from other levels of the health system to the community. Foreign assistance was seen as crucial for recovery and revitalization of affected communities. However, such aid is often not targeted at addressing critical challenges in a sustainable way, especially when the assistance is highly restricted to specific activities, and those activities are determined without consultation with local actors and community groups. Conclusion: Efforts to systematically build responsible leadership and social capital at community level, including those that strengthen bonds in communities and trust across key actors in the health system, are needed to address health shocks like EVD outbreaks. Without building such capabilities in community resilience, it will be difficult to reap the expected gains from investments focusing on building physical capital and technical capabilities in health services and emergency preparedness.

Alstroemeria yellow spot virus (AYSV): a new orthotospovirus species within a growing Eurasian clade.

An orthotospovirus distinct from all other orthotospoviruses was isolated from naturally infected alstroemeria plants. Disease symptoms caused by this virus mainly consisted of yellow spots on the leaves based on which the name alstroemeria yellow spot virus (AYSV) was coined. A host range analysis was performed and a polyclonal antiserum was produced against purified AYSV ribonucleoproteins which only reacted with the homologous antigen and not with any other (established or tentative) orthotospovirus from a selection of American and Asian species. Upon thrips transmission assays the virus was successfully transmitted by a population of Thrips tabaci. The entire nucleotide sequence of the M and S RNA segments was elucidated by a conventional cloning and sequencing strategy, and contained 4797 respectively 2734 nucleotides (nt). Simultaneously, a next generation sequencing (NGS) approach (RNAseq) was employed and generated contigs covering the entire viral tripartite RNA genome. In addition to the M and S RNA nucleotide sequences, the L RNA (8865 nt) was obtained. The nucleocapsid (N) gene encoded by the S RNA of this virus consisted of 819 nucleotides with a deduced N protein of 272 amino acids and by comparative sequence alignments to other established orthotospovirus species showed highest homology (69.5% identity) to the N protein of polygonum ringspot virus. The data altogether support the proposal of AYSV as a new orthotospovirus species within a growing clade of orthotospoviruses that seem to share the Middle East basin as a region of origin.

"Kiss myAsthma": Using a participatory design approach to develop a self-management app with young people with asthma.

Objective: Young people with asthma often lack engagement in self-management. Smartphone apps offer an attractive, immediate method for obtaining asthma information and self-management support. In this research we developed an evidence-based asthma app tailored to young peoples needs, created using a participatory design approach to optimize user engagement. This paper describes the participatory design process. Methods: This multi-phased research included concept generation and ideation of app design by young people with asthma, and development of asthma information by the research team. Clinical review was sought regarding safety and accuracy of app content. Participants suggestions for improvement and any problems with the app were logged throughout. Our young co-designers were invited back to test a high fidelity prototype app using a "think aloud" process and completed a usability questionnaire. Results: Twenty asthma patients aged 15-24 years contributed to the initial app design. Three respiratory specialists and two pharmacists suggested minor corrections to clinical terminology in the app which were all incorporated. Nine co-designers acted as expert reviewers of the prototype app, of whom eight completed a usability questionnaire. Median usability scores (maximum score 6) indicated high satisfaction with app content, usefulness and ease of use [median item score 5.3 (range 4.7-6.0)]. All feedback was incorporated to create an updated prototype app. Conclusions: A clinically sound asthma app has been developed which is considered highly acceptable to the young co-designers. A six-week test of the engagement, acceptability, and usefulness of the app in young people not involved in the participatory design will follow.

Conditions for addressing environmental determinants of health behavior in intersectoral policy networks: A fuzzy set Qualitative Comparative Analysis.

Improving health requires changes in the social, physical, economic and political determinants of health behavior. For the realization of policies that address these environmental determinants, intersectoral policy networks are considered necessary for the pooling of resources to implement different policy instruments. However, such network diversity may increase network complexity and therefore hamper network performance. Network complexity may be reduced by network management and the provision of financial resources. This study examined whether network diversity - amidst the other conditions - is indeed needed to address environmental determinants of health behavior. We included 25 intersectoral policy networks in Dutch municipalities aimed at reducing overweight, smoking, and alcohol/drugs abuse. For our fuzzy set Qualitative Comparative Analysis we used data from three web-based surveys among (a) project leaders regarding network diversity and size (n = 38); (b) project leaders and project partners regarding management (n = 278); and (c) implementation professionals regarding types of environmental determinants addressed (n = 137). Data on budgets were retrieved from project application forms. Contrary to their intentions, most policy networks typically addressed personal determinants. If the environment was addressed too, it was mostly the social environment. To address environmental determinants of health behavior, network diversity (>50% of the actors are non-public health) was necessary in networks that were either small (<16 actors) or had small budgets (<€183,172), when both were intensively managed. Irrespective of network diversity, environmental determinants also were addressed by small networks with large budgets, and by large networks with small budgets, when both provided network management. We conclude that network diversity is important - although not necessary - for resource pooling to address environmental determinants of health behavior, but only effective in the presence of network management. Our findings may support intersectoral policy networks in improving health behaviors by addressing a variety of environmental determinants.

Structural integration and performance of inter-sectoral public health-related policy networks: An analysis across policy phases.

BACKGROUND: Inter-sectoral policy networks may be effective in addressing environmental determinants of health with interventions. However, contradictory results are reported on relations between structural network characteristics (i.e., composition and integration) and network performance, such as addressing environmental determinants of health. This study examines these relations in different phases of the policy process. METHODS: A multiple-case study was performed on four public health-related policy networks. Using a snowball method among network actors, overall and sub-networks per policy phase were identified and the policy sector of each actor was assigned. To operationalise the outcome variable, interventions were classified by the proportion of environmental determinants they addressed. RESULTS: In the overall networks, no relation was found between structural network characteristics and network performance. In most effective cases, the policy development sub-networks were characterised by integration with less interrelations between actors (low cohesion), more equally distributed distances between the actors (low closeness centralisation), and horizontal integration in inter-sectoral cliques. The most effective case had non-public health central actors with less connections in all sub-networks. CONCLUSION: The results suggest that, to address environmental determinants of health, sub-networks should be inter-sectorally composed in the policy development rather than in the intervention development and implementation phases, and that policy development actors should have the opportunity to connect with other actors, without strong direction from a central actor.