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Background: The need for advanced home healthcare (HHC) is expected to increase, with registered nurses (RNs) as key figures. Given the difficulties recruiting and retaining RNs in the HHC sector, understanding their work satisfaction is imperative. Aim: This study aimed to explore RNs’ experiences of work satisfaction in the municipal HHC. Methods: Individual interviews were conducted with RNs (n = 8) in four municipalities in Norway. The data were evaluated using qualitative content analysis. Results: Work satisfaction in HHC was organised into one theme ‘alone and together’ under four categories—the patient, the co-worker, the registered nurse, and the organisation—and 15 subcategories, including patient diversity, supportive co-workers and professional environment, appropriate workload and responsibilities, and provision of preconditions for self-management. Conclusions: Patients, co-workers, and organisations were identified as crucial areas affecting RNs’ work satisfaction in the municipal HHC. Awareness of these areas is essential to promote RNs’ work satisfaction. Patients’ diversity adds positively to RNs’ work satisfaction. Notably, RNs working alone can affect their work satisfaction not only negatively but also positively.

Background: The need for advanced home healthcare (HHC) is expected to increase, with registered nurses (RNs) as key figures. Given the difficulties recruiting and retaining RNs in the HHC sector, understanding their work satisfaction is imperative. Aim: This study aimed to explore RNs’ experiences of work satisfaction in the municipal HHC. Methods: Individual interviews were conducted with RNs (n = 8) in four municipalities in Norway. The data were evaluated using qualitative content analysis. Results: Work satisfaction in HHC was organised into one theme ‘alone and together’ under four categories—the patient, the co-worker, the registered nurse, and the organisation—and 15 subcategories, including patient diversity, supportive co-workers and professional environment, appropriate workload and responsibilities, and provision of preconditions for self-management. Conclusions: Patients, co-workers, and organisations were identified as crucial areas affecting RNs’ work satisfaction in the municipal HHC. Awareness of these areas is essential to promote RNs’ work satisfaction. Patients’ diversity adds positively to RNs’ work satisfaction. Notably, RNs working alone can affect their work satisfaction not only negatively but also positively.

Examinationsdatum: 2024-05-24

Background: The need for advanced home healthcare (HHC) is expected to increase, with registered nurses (RNs) as key figures. Given the difficulties recruiting and retaining RNs in the HHC sector, understanding their work satisfaction is imperative. Aim: This study aimed to explore RNs’ experiences of work satisfaction in the municipal HHC. Methods: Individual interviews were conducted with RNs (n = 8) in four municipalities in Norway. The data were evaluated using qualitative content analysis. Results: Work satisfaction in HHC was organised into one theme ‘alone and together’ under four categories—the patient, the co-worker, the registered nurse, and the organisation—and 15 subcategories, including patient diversity, supportive co-workers and professional environment, appropriate workload and responsibilities, and provision of preconditions for self-management. Conclusions: Patients, co-workers, and organisations were identified as crucial areas affecting RNs’ work satisfaction in the municipal HHC. Awareness of these areas is essential to promote RNs’ work satisfaction. Patients’ diversity adds positively to RNs’ work satisfaction. Notably, RNs working alone can affect their work satisfaction not only negatively but also positively.

Examinationsdatum: 2024-05-24

Background: The need for advanced home healthcare (HHC) is expected to increase, with registered nurses (RNs) as key figures. Given the difficulties recruiting and retaining RNs in the HHC sector, understanding their work satisfaction is imperative. Aim: This study aimed to explore RNs’ experiences of work satisfaction in the municipal HHC. Methods: Individual interviews were conducted with RNs (n = 8) in four municipalities in Norway. The data were evaluated using qualitative content analysis. Results: Work satisfaction in HHC was organised into one theme ‘alone and together’ under four categories—the patient, the co-worker, the registered nurse, and the organisation—and 15 subcategories, including patient diversity, supportive co-workers and professional environment, appropriate workload and responsibilities, and provision of preconditions for self-management. Conclusions: Patients, co-workers, and organisations were identified as crucial areas affecting RNs’ work satisfaction in the municipal HHC. Awareness of these areas is essential to promote RNs’ work satisfaction. Patients’ diversity adds positively to RNs’ work satisfaction. Notably, RNs working alone can affect their work satisfaction not only negatively but also positively.

Background: The need for advanced home healthcare (HHC) is expected to increase, with registered nurses (RNs) as key figures. Given the difficulties recruiting and retaining RNs in the HHC sector, understanding their work satisfaction is imperative. Aim: This study aimed to explore RNs’ experiences of work satisfaction in the municipal HHC. Methods: Individual interviews were conducted with RNs (n = 8) in four municipalities in Norway. The data were evaluated using qualitative content analysis. Results: Work satisfaction in HHC was organised into one theme ‘alone and together’ under four categories—the patient, the co-worker, the registered nurse, and the organisation—and 15 subcategories, including patient diversity, supportive co-workers and professional environment, appropriate workload and responsibilities, and provision of preconditions for self-management. Conclusions: Patients, co-workers, and organisations were identified as crucial areas affecting RNs’ work satisfaction in the municipal HHC. Awareness of these areas is essential to promote RNs’ work satisfaction. Patients’ diversity adds positively to RNs’ work satisfaction. Notably, RNs working alone can affect their work satisfaction not only negatively but also positively.

In recent years, machine learning has become crucial in remote sensing analysis, particularly in the domain of Land-use/Land-cover (LULC). The synergy of machine learning and satellite imagery analysis has demonstrated significant productivity in this field, as evidenced by several studies. A notable challenge within this area is the semantic segmentation mapping of land usage over extensive territories, where the accessibility of accurate land-use data and the reliability of ground truth land-use labels pose significant difficulties. For example, providing a detailed and accurate pixel-wise labeled dataset of the Flanders region, a first-level administrative division of Belgium, can be particularly insightful. Yet there is a notable lack of regulated, formalized datasets and workflows for such studies in many regions globally. This paper introduces a comprehensive approach to addressing these gaps. We present a densely labeled ground truth map of Flanders paired with Sentinel-2 satellite imagery. Our methodology includes a formalized dataset division and sampling method, utilizing the topographic map layout 'Kaartbladversnijdingen,' and a detailed semantic segmentation model training pipeline. Preliminary benchmarking results are also provided to demonstrate the efficacy of our approach.

T-cell lymphoblastic lymphoma (T-LBL) is a rare and aggressive lymphatic cancer, often diagnosed at a young age. Patients are treated with intensive chemotherapy, potentially followed by a hematopoietic stem cell transplantation. Although prognosis of T-LBL has improved with intensified treatment protocols, they are associated with side effects and 10–20% of patients still die from relapsed or refractory disease. Given this, the search toward less toxic anti-lymphoma therapies is ongoing. Here, we targeted the recently described DNA hypermethylated profile in T-LBL with the DNA hypomethylating agent decitabine. We evaluated the anti-lymphoma properties and downstream effects of decitabine, using patient derived xenograft (PDX) models. Decitabine treatment resulted in prolonged lymphoma-free survival in all T-LBL PDX models, which was associated with downregulation of the oncogenic MYC pathway. However, some PDX models showed more benefit of decitabine treatment compared to others. In more sensitive models, differentially methylated CpG regions resulted in more differentially expressed genes in open chromatin regions. This resulted in stronger downregulation of cell cycle genes and upregulation of immune response activating transcripts. Finally, we suggest a gene signature for high decitabine sensitivity in T-LBL. Altogether, we here delivered pre-clinical proof of the potential use of decitabine as a new therapeutic agent in T-LBL.

T-cell lymphoblastic lymphoma (T-LBL) is a rare and aggressive lymphatic cancer, often diagnosed at a young age. Patients are treated with intensive chemotherapy, potentially followed by a hematopoietic stem cell transplantation. Although prognosis of T-LBL has improved with intensified treatment protocols, they are associated with side effects and 10–20% of patients still die from relapsed or refractory disease. Given this, the search toward less toxic anti-lymphoma therapies is ongoing. Here, we targeted the recently described DNA hypermethylated profile in T-LBL with the DNA hypomethylating agent decitabine. We evaluated the anti-lymphoma properties and downstream effects of decitabine, using patient derived xenograft (PDX) models. Decitabine treatment resulted in prolonged lymphoma-free survival in all T-LBL PDX models, which was associated with downregulation of the oncogenic MYC pathway. However, some PDX models showed more benefit of decitabine treatment compared to others. In more sensitive models, differentially methylated CpG regions resulted in more differentially expressed genes in open chromatin regions. This resulted in stronger downregulation of cell cycle genes and upregulation of immune response activating transcripts. Finally, we suggest a gene signature for high decitabine sensitivity in T-LBL. Altogether, we here delivered pre-clinical proof of the potential use of decitabine as a new therapeutic agent in T-LBL.

T-cell lymphoblastic lymphoma (T-LBL) is a rare and aggressive lymphatic cancer, often diagnosed at a young age. Patients are treated with intensive chemotherapy, potentially followed by a hematopoietic stem cell transplantation. Although prognosis of T-LBL has improved with intensified treatment protocols, they are associated with side effects and 10–20% of patients still die from relapsed or refractory disease. Given this, the search toward less toxic anti-lymphoma therapies is ongoing. Here, we targeted the recently described DNA hypermethylated profile in T-LBL with the DNA hypomethylating agent decitabine. We evaluated the anti-lymphoma properties and downstream effects of decitabine, using patient derived xenograft (PDX) models. Decitabine treatment resulted in prolonged lymphoma-free survival in all T-LBL PDX models, which was associated with downregulation of the oncogenic MYC pathway. However, some PDX models showed more benefit of decitabine treatment compared to others. In more sensitive models, differentially methylated CpG regions resulted in more differentially expressed genes in open chromatin regions. This resulted in stronger downregulation of cell cycle genes and upregulation of immune response activating transcripts. Finally, we suggest a gene signature for high decitabine sensitivity in T-LBL. Altogether, we here delivered pre-clinical proof of the potential use of decitabine as a new therapeutic agent in T-LBL.

The concept of cumulative impacts is widespread in policy documents, regulations and ecological studies, but quantification methods are still evolving. Infrastructure development usually takes place in landscapes with preexisting anthropogenic features. Typically, their impact is determined by computing the distance to the nearest feature only, thus ignoring the potential cumulative impacts of multiple features. We propose the cumulative ZOI approach to assess whether and to what extent anthropogenic features lead to cumulative impacts. The approach estimates both effect size and zone of influence (ZOI) of anthropogenic features and allows for estimation of cumulative effects of multiple features distributed in the landscape. First, we use simulations and an empirical study to understand under which circumstances cumulative impacts arise. Second, we demonstrate the approach by estimating the cumulative impacts of tourist infrastructure in Norway on the habitat of wild reindeer (Rangifer t. tarandus), a near-threatened species highly sensitive to anthropogenic disturbance. In the simulations, we showed that analyses based on the nearest feature and our cumulative approach are indistinguishable in two extreme cases: when features are few and scattered and their ZOI is small, and when features are clustered and their ZOI is large. The empirical analyses revealed cumulative impacts of private cabins and tourist resorts on reindeer, extending up to 10 and 20 km, with different decaying functions. Although the impact of an isolated private cabin was negligible, the cumulative impact of ‘cabin villages’ could be much larger than that of a single large tourist resort. Focusing on the nearest feature only underestimates the impact of ‘cabin villages’ on reindeer. The suggested approach allows us to quantify the magnitude and spatial extent of cumulative impacts of point, linear, and polygon features in a computationally efficient and flexible way and is implemented in the on

The concept of cumulative impacts is widespread in policy documents, regulations and ecological studies, but quantification methods are still evolving. Infrastructure development usually takes place in landscapes with preexisting anthropogenic features. Typically, their impact is determined by computing the distance to the nearest feature only, thus ignoring the potential cumulative impacts of multiple features. We propose the cumulative ZOI approach to assess whether and to what extent anthropogenic features lead to cumulative impacts. The approach estimates both effect size and zone of influence (ZOI) of anthropogenic features and allows for estimation of cumulative effects of multiple features distributed in the landscape. First, we use simulations and an empirical study to understand under which circumstances cumulative impacts arise. Second, we demonstrate the approach by estimating the cumulative impacts of tourist infrastructure in Norway on the habitat of wild reindeer (Rangifer t. tarandus), a near-threatened species highly sensitive to anthropogenic disturbance. In the simulations, we showed that analyses based on the nearest feature and our cumulative approach are indistinguishable in two extreme cases: when features are few and scattered and their ZOI is small, and when features are clustered and their ZOI is large. The empirical analyses revealed cumulative impacts of private cabins and tourist resorts on reindeer, extending up to 10 and 20 km, with different decaying functions. Although the impact of an isolated private cabin was negligible, the cumulative impact of ‘cabin villages’ could be much larger than that of a single large tourist resort. Focusing on the nearest feature only underestimates the impact of ‘cabin villages’ on reindeer. The suggested approach allows us to quantify the magnitude and spatial extent of cumulative impacts of point, linear, and polygon features in a computationally efficient and flexible way and is implemented in the on

T-cell lymphoblastic lymphoma (T-LBL) is a rare and aggressive lymphatic cancer, often diagnosed at a young age. Patients are treated with intensive chemotherapy, potentially followed by a hematopoietic stem cell transplantation. Although prognosis of T-LBL has improved with intensified treatment protocols, they are associated with side effects and 10–20% of patients still die from relapsed or refractory disease. Given this, the search toward less toxic anti-lymphoma therapies is ongoing. Here, we targeted the recently described DNA hypermethylated profile in T-LBL with the DNA hypomethylating agent decitabine. We evaluated the anti-lymphoma properties and downstream effects of decitabine, using patient derived xenograft (PDX) models. Decitabine treatment resulted in prolonged lymphoma-free survival in all T-LBL PDX models, which was associated with downregulation of the oncogenic MYC pathway. However, some PDX models showed more benefit of decitabine treatment compared to others. In more sensitive models, differentially methylated CpG regions resulted in more differentially expressed genes in open chromatin regions. This resulted in stronger downregulation of cell cycle genes and upregulation of immune response activating transcripts. Finally, we suggest a gene signature for high decitabine sensitivity in T-LBL. Altogether, we here delivered pre-clinical proof of the potential use of decitabine as a new therapeutic agent in T-LBL.

The concept of cumulative impacts is widespread in policy documents, regulations and ecological studies, but quantification methods are still evolving. Infrastructure development usually takes place in landscapes with preexisting anthropogenic features. Typically, their impact is determined by computing the distance to the nearest feature only, thus ignoring the potential cumulative impacts of multiple features. We propose the cumulative ZOI approach to assess whether and to what extent anthropogenic features lead to cumulative impacts. The approach estimates both effect size and zone of influence (ZOI) of anthropogenic features and allows for estimation of cumulative effects of multiple features distributed in the landscape. First, we use simulations and an empirical study to understand under which circumstances cumulative impacts arise. Second, we demonstrate the approach by estimating the cumulative impacts of tourist infrastructure in Norway on the habitat of wild reindeer (Rangifer t. tarandus), a near-threatened species highly sensitive to anthropogenic disturbance. In the simulations, we showed that analyses based on the nearest feature and our cumulative approach are indistinguishable in two extreme cases: when features are few and scattered and their ZOI is small, and when features are clustered and their ZOI is large. The empirical analyses revealed cumulative impacts of private cabins and tourist resorts on reindeer, extending up to 10 and 20 km, with different decaying functions. Although the impact of an isolated private cabin was negligible, the cumulative impact of ‘cabin villages’ could be much larger than that of a single large tourist resort. Focusing on the nearest feature only underestimates the impact of ‘cabin villages’ on reindeer. The suggested approach allows us to quantify the magnitude and spatial extent of cumulative impacts of point, linear, and polygon features in a computationally efficient and flexible way and is implemented in the on

T-cell lymphoblastic lymphoma (T-LBL) is a rare and aggressive lymphatic cancer, often diagnosed at a young age. Patients are treated with intensive chemotherapy, potentially followed by a hematopoietic stem cell transplantation. Although prognosis of T-LBL has improved with intensified treatment protocols, they are associated with side effects and 10–20% of patients still die from relapsed or refractory disease. Given this, the search toward less toxic anti-lymphoma therapies is ongoing. Here, we targeted the recently described DNA hypermethylated profile in T-LBL with the DNA hypomethylating agent decitabine. We evaluated the anti-lymphoma properties and downstream effects of decitabine, using patient derived xenograft (PDX) models. Decitabine treatment resulted in prolonged lymphoma-free survival in all T-LBL PDX models, which was associated with downregulation of the oncogenic MYC pathway. However, some PDX models showed more benefit of decitabine treatment compared to others. In more sensitive models, differentially methylated CpG regions resulted in more differentially expressed genes in open chromatin regions. This resulted in stronger downregulation of cell cycle genes and upregulation of immune response activating transcripts. Finally, we suggest a gene signature for high decitabine sensitivity in T-LBL. Altogether, we here delivered pre-clinical proof of the potential use of decitabine as a new therapeutic agent in T-LBL.

Beneficial interactions between plant roots and rhizosphere microorganisms are pivotal for plant fitness. Nevertheless, the molecular mechanisms controlling the feedback between root architecture and microbial community structure remain elusive in maize. Here, we demonstrate that transcriptomic gradients along the longitudinal root axis associate with specific shifts in rhizosphere microbial diversity. Moreover, we have established that root-derived flavones predominantly promote the enrichment of bacteria of the taxa Oxalobacteraceae in the rhizosphere, which in turn promote maize growth and nitrogen acquisition. Genetic experiments demonstrate that LRT1-mediated lateral root development coordinates the interactions of the root system with flavone-dependent Oxalobacteraceae under nitrogen deprivation. In summary, these experiments reveal the genetic basis of the reciprocal interactions between root architecture and the composition and diversity of specific microbial taxa in the rhizosphere resulting in improved plant performance. These findings may open new avenues towards the breeding of high-yielding and nutrient-efficient crops by exploiting their interaction with beneficial soil microorganisms. The link between rhizosphere microbial community, root architecture and performance in nitrogen-poor soils is comprehensively investigated in maize, and the role of exuded flavone to promote specific beneficial bacterial taxa is characterized.

Aim: Intraosseous (IO)-access plays an alternative route during resuscitation. Our study in preterm and term stillborns was performed to find alternative IO puncture sites beside the recommended proximal tibia. Methods: The cadavers used were legal donations. 20 stillborns (mean: 29.2weeks, IQR 27.1 +/- 39.6) were investigated. Spectral-CT were analysed to calculate the diameter and circumferences of: i) proximal humerus ii) distal femur iii) proximal tibia iv) diaphyseal tibial. Contrast medium was applied under video documentation to investigate the drainage into the vascular system. Results: In term newborns, diameter of the cortex of the proximal humeral head is 12.1 +/- 1.8 mm, distal end of the femur 11.9 +/- 3.4 mm and the proximal tibial bone 12.0 +/- 2.4 mm with cross-sectional diameter of 113.5 +/- 19.7 mm(2), 120.6 +/- 28.2 mm(2) and 111.6 +/- 29.5 mm(2), respectively. Regarding the preterm groups, there is a strong age-related growth in diameter and cross-sectional size. The diaphyseal area is the smallest in all measured bones with an age-dependent increase and is about half of that of metaphyseal diameters (proximal and distal) and about one third of that of metaphyseal cross sectional areas. The proximal femoral head region has the largest diameter of all measured bones with an egg-shaped formation with an extensive joint capsula. All investigated metaphyseal areas lack a clearly enclosed bone marrow cavity. Infusion of contrast medium into the distal femoral end and the proximal humerus head demonstrate the drainage of contrast medium into the central venous system within seconds. Conclusion: Proximal humeral head and distal femoral end might be alternative IO areas which may lead to further IO puncture sites in neonates.

Salmon lice cause economic losses in salmonid aquaculture. The use of cleaner fish has become an important tool to fight lice. Lumpfish and several species of wrasses are used. There are extensive fisheries for wrasses, and aquaculture of ballan wrasse and lumpfish. Fisheries and use have evolved fast, but the development of a regulatory framework has lagged behind. Challenges linked to poor welfare, diseases and changes in the genetic structure have raised questions on the sustainability of the current practice, and The Norwegian Food Safety Authorities stated that if the welfare is not improved and the effect of cleaner fish better documented, the use can be reduced or terminated. This will have implications for the Swedish and potential future Danish fishery. This report presents the state-of-knowledge on biology, fisheries and how management have dealt with the fisheries and use.

Sea cage fish farming is typically open to the environment, with disease transmission possible between farmed and wild hosts. In salmonid aquaculture, salmon louse Lepeophtheirus salmonis infestations cause production losses, reduce welfare for farmed fish and increase infestation rates for wild fish populations. The high density of hosts in farms likely also shifts the coevolutionary arms race between host and parasite, with ecological and evolutionary consequences for the salmon louse. Using farm-reported salmon and louse abundances and publicly reported estimates of wild salmonid host abundances and the salmon lice they carry, we estimated (1) the relative abundance of farmed and wild salmonid hosts and (2) the relative importance of each for the abundance of salmon lice for the coastal zone of Norway from 1998 to 2017. Farmed hosts increased in importance over time with the expansion of the industry. From 2013 to 2017, farmed salmonids outnumbered wild salmonids by 267-281:1. By 2017, farmed salmonids accounted for 99.6% of available hosts and produced 99.1% of adult female salmon lice and 97.6% of mated (ovigerous) adult female salmon lice in Norwegian coastal waters. The persistent dominance of farmed hosts has clear implications: (1) management decisions that aim to limit lice abundance can be guided by lice data from farms alone, as lice on wild salmonids make a trivial contribution to the national lice population; and (2) strategies to prevent or treat lice infestations are vulnerable to the evolution of resistance, as the pool of wild hosts is inconsequential and will not act as a refuge large enough to stem the evolution of resistance. As the Norwegian salmon industry expands and salmon lice infestations continue, farmed salmon will drive the ecology and evolution of salmon lice.

To discover microorganisms that naturally possess chemical weapons against the phytopathogen Fusarium oxysporum, the biological and chemical diversity of plant leaf endophytes was investigated. Endophytes were isolated from the palm tree Astrocaryum sciophyllum collected in pristine forests of French Guiana. Several Xylariaceae inhibited the growth of F. oxysporum and were further explored. Antifungal specialized metabolites were isolated from the Xylariaceae BSNB-0294 strain in confrontation with the phytopathogen and led to the identification of undescribed compounds, i.e., two depsipeptides named xylariaceins, two metabolites containing a 3-imidazolinone moiety, and four new compounds including a nitro-phenylpropanamide and three phenylalanine analogues named xylariains A-D. In parallel, the chemical investigation of the phytopathogen during the coculture led to the identification of an unknown compound, which we named focicin. The production of focicin was exacerbated during the competition. Matrix-assisted laser desorption/ionization coupled to time-of-flight mass spectometry (MALDI-TOF MS) imaging of the competition between BSNB-0294 (endophytic strain) and F. oxysporum f.sp. ciceris (phytopathogen) highlighted time-dependent chemical interactions between the two microorganisms.

Resistance to parasites is believed to have a widespread influence on demographic and adaptive processes. In systems where parasites impose a fitness cost on their host, heterozygotes may be selected because they are more resistant to parasites than homozygotes. Our objective was to assess the relationships between genomewide individual heterozygosity and abomasal nematode burdens in female Svalbard reindeer (Rangifer tarandus platyrhynchus) after the effects of host age, locality, season, and year had been accounted for. Samples were obtained from 306 female reindeer that were culled and genotyped at nine microsatellite loci. Reindeer in our study populations are mainly parasitized by the gastrointestinal nematodes Ostertagia gruehneri and Marshallagia marshalli. The infection intensity of each parasite differed between subpopulations, and among host age classes, seasons and years. We found no significant relationships between abomasal worm burdens, or lumen and mucosa larvae, of either O. gruehneri or M. marshalli and individual heterozygosity (or mean d(2)) alone or in interactions with host age, locality, and year. Although we analysed one of the largest data set available to date on gastrointestinal nematodes of a wild ruminant, we used a typical data set of nine genetic neutral markers that may have had low power to detect heterozygosity-fitness correlations. We conclude that the proportion of the variance in parasite resistance explained by individual heterozygosity for neutral genetic markers is low in Svalbard reindeer and in vertebrates in general, and we suggest that the candidate-gene approach might be more fruitful for further research on gene-fitness correlations.

To discover microorganisms that naturally possess chemical weapons against the phytopathogen Fusarium oxysporum, the biological and chemical diversity of plant leaf endophytes was investigated. Endophytes were isolated from the palm tree Astrocaryum sciophyllum collected in pristine forests of French Guiana. Several Xylariaceae inhibited the growth of F. oxysporum and were further explored. Antifungal specialized metabolites were isolated from the Xylariaceae BSNB-0294 strain in confrontation with the phytopathogen and led to the identification of undescribed compounds, i.e., two depsipeptides named xylariaceins, two metabolites containing a 3-imidazolinone moiety, and four new compounds including a nitro-phenylpropanamide and three phenylalanine analogues named xylariains A-D. In parallel, the chemical investigation of the phytopathogen during the coculture led to the identification of an unknown compound, which we named focicin. The production of focicin was exacerbated during the competition. Matrix-assisted laser desorption/ionization coupled to time-of-flight mass spectometry (MALDI-TOF MS) imaging of the competition between BSNB-0294 (endophytic strain) and F. oxysporum f.sp. ciceris (phytopathogen) highlighted time-dependent chemical interactions between the two microorganisms.

Aim: Intraosseous (IO)-access plays an alternative route during resuscitation. Our study in preterm and term stillborns was performed to find alternative IO puncture sites beside the recommended proximal tibia. Methods: The cadavers used were legal donations. 20 stillborns (mean: 29.2weeks, IQR 27.1 +/- 39.6) were investigated. Spectral-CT were analysed to calculate the diameter and circumferences of: i) proximal humerus ii) distal femur iii) proximal tibia iv) diaphyseal tibial. Contrast medium was applied under video documentation to investigate the drainage into the vascular system. Results: In term newborns, diameter of the cortex of the proximal humeral head is 12.1 +/- 1.8 mm, distal end of the femur 11.9 +/- 3.4 mm and the proximal tibial bone 12.0 +/- 2.4 mm with cross-sectional diameter of 113.5 +/- 19.7 mm(2), 120.6 +/- 28.2 mm(2) and 111.6 +/- 29.5 mm(2), respectively. Regarding the preterm groups, there is a strong age-related growth in diameter and cross-sectional size. The diaphyseal area is the smallest in all measured bones with an age-dependent increase and is about half of that of metaphyseal diameters (proximal and distal) and about one third of that of metaphyseal cross sectional areas. The proximal femoral head region has the largest diameter of all measured bones with an egg-shaped formation with an extensive joint capsula. All investigated metaphyseal areas lack a clearly enclosed bone marrow cavity. Infusion of contrast medium into the distal femoral end and the proximal humerus head demonstrate the drainage of contrast medium into the central venous system within seconds. Conclusion: Proximal humeral head and distal femoral end might be alternative IO areas which may lead to further IO puncture sites in neonates.

Beneficial interactions between plant roots and rhizosphere microorganisms are pivotal for plant fitness. Nevertheless, the molecular mechanisms controlling the feedback between root architecture and microbial community structure remain elusive in maize. Here, we demonstrate that transcriptomic gradients along the longitudinal root axis associate with specific shifts in rhizosphere microbial diversity. Moreover, we have established that root-derived flavones predominantly promote the enrichment of bacteria of the taxa Oxalobacteraceae in the rhizosphere, which in turn promote maize growth and nitrogen acquisition. Genetic experiments demonstrate that LRT1-mediated lateral root development coordinates the interactions of the root system with flavone-dependent Oxalobacteraceae under nitrogen deprivation. In summary, these experiments reveal the genetic basis of the reciprocal interactions between root architecture and the composition and diversity of specific microbial taxa in the rhizosphere resulting in improved plant performance. These findings may open new avenues towards the breeding of high-yielding and nutrient-efficient crops by exploiting their interaction with beneficial soil microorganisms. The link between rhizosphere microbial community, root architecture and performance in nitrogen-poor soils is comprehensively investigated in maize, and the role of exuded flavone to promote specific beneficial bacterial taxa is characterized.

Salmon lice cause economic losses in salmonid aquaculture. The use of cleaner fish has become an important tool to fight lice. Lumpfish and several species of wrasses are used. There are extensive fisheries for wrasses, and aquaculture of ballan wrasse and lumpfish. Fisheries and use have evolved fast, but the development of a regulatory framework has lagged behind. Challenges linked to poor welfare, diseases and changes in the genetic structure have raised questions on the sustainability of the current practice, and The Norwegian Food Safety Authorities stated that if the welfare is not improved and the effect of cleaner fish better documented, the use can be reduced or terminated. This will have implications for the Swedish and potential future Danish fishery. This report presents the state-of-knowledge on biology, fisheries and how management have dealt with the fisheries and use.

Hanauma Bay is a 101-acre bay created by the partial collapse of a volcanic cone and once supported a vibrant coral reef system. It is the most popular swimming area in the Hawaiian Islands and has been reported to have averaged between 2.8 and 3.5 million visitors a year between the 1980s and the 2010s, with visitors averaging between 3000-4000 a day and peaking around 10,000-13,000 per day. Concentrations of oxybenzone and other common UV filters were measured in subsurface water samples and in sands from the beach-shower areas in Hanauma Bay. Results demonstrate that beach showers also can be a source of sunscreen environmental contamination. Hydrodynamic modeling indicates that oxybenzone contamination within Hanauma Bay's waters could be retained between 14 and 50 h from a single release event period. Focusing on only oxybenzone, two different Hazard and Risk Assessment analyses were conducted to determine the danger of oxybenzone to Hanauma Bay's coral reef system. Results indicate that oxybenzone contamination poses a significant threat to the wildlife of Hanauma Bay. To recover Hanauma Bay's natural resources to a healthy condition and to satisfactorily conserve its coral reef and sea grass habitats, effective tourism management policies need to be implemented that mitigate the threat of sunscreen pollution.

Cancer cells display DNA hypermethylation at specific CpG islands in comparison to their normal healthy counterparts, but the mechanism that drives this so-called CpG island methylator phenotype (CIMP) remains poorly understood. Here, we show that CpG island methylation in human T-cell acute lymphoblastic leukemia (T-ALL) mainly occurs at promoters of Polycomb Repressor Complex 2 (PRC2) target genes that are not expressed in normal or malignant T-cells and which display a reciprocal association with H3K27me3 binding. In addition, we revealed that this aberrant methylation profile reflects the epigenetic history of T-ALL and is established already in pre-leukemic, self-renewing thymocytes that precede T-ALL development. Finally, we unexpectedly uncover that this age-related CpG island hypermethylation signature in T-ALL is completely resistant to the FDA-approved hypomethylating agent Decitabine. Altogether, we here provide conceptual evidence for the involvement of a pre-leukemic phase characterized by self-renewing thymocytes in the pathogenesis of human T-ALL.

Natural products have proven to be an immeasurable source of bioactive compounds. The exceptional biodiversity encountered in Amazonia, alongside a rich entomofauna and frequent interactions with various herbivores is the crucible of a promising chemodiversity. This prompted us to search for novel botanical insecticides in French Guiana. As this French overseas department faces severe issues linked to insects, notably the strong incidence of vector-borne infectious diseases, we decided to focus our research on products able to control the mosquito Aedes aegypti. We tested 452 extracts obtained from 85 species originating from 36 botanical families and collected in contrasted environments against an Aedes aegypti laboratory strain susceptible to all insecticides, and a natural population resistant to both pyrethroid and organophosphate insecticides collected in Cayenne for the most active of them. 8 species (Maytenus oblongata Reissek, Celastraceae; Costus erythrothyrsus Loes., Costaceae; Humiria balsamifera Aubl., Humiriaceae; Sextonia rubra (Mez) van der Werff, Lauraceae; Piper hispidum Sw., Piperaceae; Laetia procera (Poepp.) Eichl., Salicaceae; Matayba arborescens (Aubl.) Radlk., Sapindaceae; and Cupania scrobitulata Rich., Sapindaceae) led to extracts exhibiting more than 50% larval mortality after 48h of exposition at 100 µg/mL against the natural population and were considered active. Selectivity and phytochemistry of these extracts were therefore investigated and discussed, and some active compounds highlighted. Multivariate analysis highlighted that solvents, plant tissues, plant family and location had a significant effect on mortality while light, available resources and vegetation type did not. Through this case study we highlighted that plant defensive chemistry mechanisms are crucial while searching for novel insecticidal products.

Undersökningens syfte är att få en fördjupad kunskap om hur fackets roll/påverkan ser ut vid en chefsrekrytering i en privat verksamhet utifrån ett arbetsgivarperspektiv samt om det finns en problematik eller nytta med fackets delaktighet i en chefsrekrytering. Då den övervägande delen av den svenska arbetsmarknaden grundar sig i förhållandet mellan arbetsgivare och fackliga organisationer är det intressant att undersöka fackets påverkan i en chefsrekrytering. Förhållandet mellan arbetsgivare och fackliga organisationer är av betydelse för att de har en central roll på den svenska arbetsmarknaden. Undersökningen belyser endast arbetsgivarens perspektiv på fackets delaktighet vid en chefsrekrytering, men vi anser även att fackliga organisationer kan finna värde i de resultat som undersökningen presenterar. Den teoretiska referensramen ligger till grund för undersökningens insamling av kvalitativ data. Det empiriska materialet har samlats in genom sex stycken kvalitativa intervjuer med anställda inom ett av Sveriges största bolag. Undersökningen har genomförts i samarbete med det berörda svenska bolaget. Resultatet visar på att fackets roll/påverkan inte är av stor betydelse i en chefsrekrytering. Undersökningen visar också att det finns en problematik och en nytta med fackets delaktighet vid en chefsrekrytering. Problematiken med fackets delaktighet i en chefsrekrytering är att deras involvering är väldigt tidskrävande. Samtidigt är nyttan att de bidrar med ett medarbetarperspektiv. Vidare har undersökningen åskådliggjort att den generella inställningen till facket skiljer sig beroende på vilken geografisk region respondenterna tillhör., The aim with the research is to deepen the understanding and knowledge of the role and impact that trade union has from an employer perspective on recruitment of managers in a private sector and if there is a problem or benefit with the trade union’s participation in the process. As the major part of the Swedish labour market’s foundation is the relation between employers and trade unions it is of interest to investigate trade unions impact on recruitment of managers. The relation between employers and trade unions is of significance since it has a central role at the Swedish labour market. The research is solely focusing on the relation from the employer perspective, but we believe that the trade union also can find the value in the findings from the research. The theoretical framework creates the foundation for the collection of qualitative data. The empirical material has been collected through six qualitative interviews with employees in one of the largest Swedish companies. The research has been conducted in cooperation with the concerned Swedish company. The result show that the role and impact of the trade union in recruitment of managers is not of significant importance. The investigation also shows that there is a problem and benefit with the trade union participation at manager recruitment processes. The problem with the unions participation at a manager recruitment is that their involvement demands a lot of time. Simultaneously the benefit of the participation is that they contribute with an employee perspective. Furthermore the research gives that the general attitude to the trade union is dependent on which geographical region that the respondents belong to.

Natural products have proven to be an immeasurable source of bioactive compounds. The exceptional biodiversity encountered in Amazonia, alongside a rich entomofauna and frequent interactions with various herbivores is the crucible of a promising chemodiversity. This prompted us to search for novel botanical insecticides in French Guiana. As this French overseas department faces severe issues linked to insects, notably the strong incidence of vector-borne infectious diseases, we decided to focus our research on products able to control the mosquito Aedes aegypti. We tested 452 extracts obtained from 85 species originating from 36 botanical families and collected in contrasted environments against an Aedes aegypti laboratory strain susceptible to all insecticides, and a natural population resistant to both pyrethroid and organophosphate insecticides collected in Cayenne for the most active of them. 8 species (Maytenus oblongata Reissek, Celastraceae; Costus erythrothyrsus Loes., Costaceae; Humiria balsamifera Aubl., Humiriaceae; Sextonia rubra (Mez) van der Werff, Lauraceae; Piper hispidum Sw., Piperaceae; Laetia procera (Poepp.) Eichl., Salicaceae; Matayba arborescens (Aubl.) Radlk., Sapindaceae; and Cupania scrobitulata Rich., Sapindaceae) led to extracts exhibiting more than 50% larval mortality after 48h of exposition at 100 µg/mL against the natural population and were considered active. Selectivity and phytochemistry of these extracts were therefore investigated and discussed, and some active compounds highlighted. Multivariate analysis highlighted that solvents, plant tissues, plant family and location had a significant effect on mortality while light, available resources and vegetation type did not. Through this case study we highlighted that plant defensive chemistry mechanisms are crucial while searching for novel insecticidal products.

Natural products have proven to be an immeasurable source of bioactive compounds. The exceptional biodiversity encountered in Amazonia, alongside a rich entomofauna and frequent interactions with various herbivores is the crucible of a promising chemodiversity. This prompted us to search for novel botanical insecticides in French Guiana. As this French overseas department faces severe issues linked to insects, notably the strong incidence of vector-borne infectious diseases, we decided to focus our research on products able to control the mosquito Aedes aegypti. We tested 452 extracts obtained from 85 species originating from 36 botanical families and collected in contrasted environments against an Aedes aegypti laboratory strain susceptible to all insecticides, and a natural population resistant to both pyrethroid and organophosphate insecticides collected in Cayenne for the most active of them. 8 species (Maytenus oblongata Reissek, Celastraceae; Costus erythrothyrsus Loes., Costaceae; Humiria balsamifera Aubl., Humiriaceae; Sextonia rubra (Mez) van der Werff, Lauraceae; Piper hispidum Sw., Piperaceae; Laetia procera (Poepp.) Eichl., Salicaceae; Matayba arborescens (Aubl.) Radlk., Sapindaceae; and Cupania scrobitulata Rich., Sapindaceae) led to extracts exhibiting more than 50% larval mortality after 48h of exposition at 100 µg/mL against the natural population and were considered active. Selectivity and phytochemistry of these extracts were therefore investigated and discussed, and some active compounds highlighted. Multivariate analysis highlighted that solvents, plant tissues, plant family and location had a significant effect on mortality while light, available resources and vegetation type did not. Through this case study we highlighted that plant defensive chemistry mechanisms are crucial while searching for novel insecticidal products.

As popularity of algebraic effects and handlers increases, so does a demand for their efficient execution. Eff, an ML-like language with native support for handlers, has a subtyping-based effect system on which an effect-aware optimizing compiler could be built. Unfortunately, in our experience, implementing optimizations for Eff is overly error-prone because its core language is implicitly-typed, making code transformations very fragile. To remedy this, we present an explicitly-typed polymorphic core calculus for algebraic effect handlers with a subtyping-based type-and-effect system. It reifies appeals to subtyping in explicit casts with coercions that witness the subtyping proof, quickly exposing typing bugs in program transformations. Our typing-directed elaboration comes with a constraint-based inference algorithm that turns an implicitly-typed Eff-like language into our calculus. Moreover, all coercions and effect information can be erased in a straightforward way, demonstrating that coercions have no computational content. Additionally, we present a monadic translation from our calculus into a pure language without algebraic effects or handlers, using the effect information to introduce monadic constructs only where necessary., Comment: 57 pages, 29 figures

Cancer cells display DNA hypermethylation at specific CpG islands in comparison to their normal healthy counterparts, but the mechanism that drives this so-called CpG island methylator phenotype (CIMP) remains poorly understood. Here, we show that CpG island methylation in human T-cell acute lymphoblastic leukemia (T-ALL) mainly occurs at promoters of Polycomb Repressor Complex 2 (PRC2) target genes that are not expressed in normal or malignant T-cells and which display a reciprocal association with H3K27me3 binding. In addition, we revealed that this aberrant methylation profile reflects the epigenetic history of T-ALL and is established already in pre-leukemic, self-renewing thymocytes that precede T-ALL development. Finally, we unexpectedly uncover that this age-related CpG island hypermethylation signature in T-ALL is completely resistant to the FDA-approved hypomethylating agent Decitabine. Altogether, we here provide conceptual evidence for the involvement of a pre-leukemic phase characterized by self-renewing thymocytes in the pathogenesis of human T-ALL.

Undersökningens syfte är att få en fördjupad kunskap om hur fackets roll/påverkan ser ut vid en chefsrekrytering i en privat verksamhet utifrån ett arbetsgivarperspektiv samt om det finns en problematik eller nytta med fackets delaktighet i en chefsrekrytering. Då den övervägande delen av den svenska arbetsmarknaden grundar sig i förhållandet mellan arbetsgivare och fackliga organisationer är det intressant att undersöka fackets påverkan i en chefsrekrytering. Förhållandet mellan arbetsgivare och fackliga organisationer är av betydelse för att de har en central roll på den svenska arbetsmarknaden. Undersökningen belyser endast arbetsgivarens perspektiv på fackets delaktighet vid en chefsrekrytering, men vi anser även att fackliga organisationer kan finna värde i de resultat som undersökningen presenterar. Den teoretiska referensramen ligger till grund för undersökningens insamling av kvalitativ data. Det empiriska materialet har samlats in genom sex stycken kvalitativa intervjuer med anställda inom ett av Sveriges största bolag. Undersökningen har genomförts i samarbete med det berörda svenska bolaget. Resultatet visar på att fackets roll/påverkan inte är av stor betydelse i en chefsrekrytering. Undersökningen visar också att det finns en problematik och en nytta med fackets delaktighet vid en chefsrekrytering. Problematiken med fackets delaktighet i en chefsrekrytering är att deras involvering är väldigt tidskrävande. Samtidigt är nyttan att de bidrar med ett medarbetarperspektiv. Vidare har undersökningen åskådliggjort att den generella inställningen till facket skiljer sig beroende på vilken geografisk region respondenterna tillhör., The aim with the research is to deepen the understanding and knowledge of the role and impact that trade union has from an employer perspective on recruitment of managers in a private sector and if there is a problem or benefit with the trade union’s participation in the process. As the major part of the Swedish labour market’s foundation is the relation between employers and trade unions it is of interest to investigate trade unions impact on recruitment of managers. The relation between employers and trade unions is of significance since it has a central role at the Swedish labour market. The research is solely focusing on the relation from the employer perspective, but we believe that the trade union also can find the value in the findings from the research. The theoretical framework creates the foundation for the collection of qualitative data. The empirical material has been collected through six qualitative interviews with employees in one of the largest Swedish companies. The research has been conducted in cooperation with the concerned Swedish company. The result show that the role and impact of the trade union in recruitment of managers is not of significant importance. The investigation also shows that there is a problem and benefit with the trade union participation at manager recruitment processes. The problem with the unions participation at a manager recruitment is that their involvement demands a lot of time. Simultaneously the benefit of the participation is that they contribute with an employee perspective. Furthermore the research gives that the general attitude to the trade union is dependent on which geographical region that the respondents belong to.

Mankind is on the verge of a postantibiotic era. New concepts are needed in our battle to attenuate infectious diseases around the world and broad spectrum plant-inspired synergistic pharmaceutical preparations should find their place in the global fight against pathogenic microorganisms. To progress towards the discovery of potent antifungal agents against human pathologies, we embarked upon developing chemometric approach coupled with statistical design to unravel the origin of the anticandidal potential of a set of 66 essential oils (EOs). EOs were analyzed by GC-MS and tested against Candida albicans and C. parapsilosis (Minimal Inhibitory Concentration, MIC). An Orthogonal Partial Least Square (OPLS) analysis allowed us to identify six molecules presumably responsible for the anticandidal activity of the oils: (Z)-ligustilide, eugenol, eugenyl acetate, citral, thymol, and β-citronellol. These compounds were combined following a full factorial experimental design approach in order to optimize the anticandidal activity and selectivity index (SI = IC50(MRC5 cells)/MIC) through reconstituted mixtures. (Z)-Ligustilide and citral were the most active compounds, while (Z)-ligustilide and eugenol were the two main factors that most contributed to the increase of the SI. These two terpenes can, therefore, be used to construct bioinspired synergistic anticandidal mixtures.

Mankind is on the verge of a postantibiotic era. New concepts are needed in our battle to attenuate infectious diseases around the world and broad spectrum plant-inspired synergistic pharmaceutical preparations should find their place in the global fight against pathogenic microorganisms. To progress towards the discovery of potent antifungal agents against human pathologies, we embarked upon developing chemometric approach coupled with statistical design to unravel the origin of the anticandidal potential of a set of 66 essential oils (EOs). EOs were analyzed by GC-MS and tested against Candida albicans and C. parapsilosis (Minimal Inhibitory Concentration, MIC). An Orthogonal Partial Least Square (OPLS) analysis allowed us to identify six molecules presumably responsible for the anticandidal activity of the oils: (Z)-ligustilide, eugenol, eugenyl acetate, citral, thymol, and beta-citronellol. These compounds were combined following a full factorial experimental design approach in order to optimize the anticandidal activity and selectivity index (SI = IC50(MRC5 cells)/MIC) through reconstituted mixtures. (Z)-Ligustilide and citral were the most active compounds, while (Z)-ligustilide and eugenol were the two main factors that most contributed to the increase of the SI. These two terpenes can, therefore, be used to construct bioinspired synergistic anticandidal mixtures.

Mankind is on the verge of a postantibiotic era. New concepts are needed in our battle to attenuate infectious diseases around the world and broad spectrum plant-inspired synergistic pharmaceutical preparations should find their place in the global fight against pathogenic microorganisms. To progress towards the discovery of potent antifungal agents against human pathologies, we embarked upon developing chemometric approach coupled with statistical design to unravel the origin of the anticandidal potential of a set of 66 essential oils (EOs). EOs were analyzed by GC-MS and tested against Candida albicans and C. parapsilosis (Minimal Inhibitory Concentration, MIC). An Orthogonal Partial Least Square (OPLS) analysis allowed us to identify six molecules presumably responsible for the anticandidal activity of the oils: (Z)-ligustilide, eugenol, eugenyl acetate, citral, thymol, and beta-citronellol. These compounds were combined following a full factorial experimental design approach in order to optimize the anticandidal activity and selectivity index (SI = IC50(MRC5 cells)/MIC) through reconstituted mixtures. (Z)-Ligustilide and citral were the most active compounds, while (Z)-ligustilide and eugenol were the two main factors that most contributed to the increase of the SI. These two terpenes can, therefore, be used to construct bioinspired synergistic anticandidal mixtures.

IMPORTANCE Knowledge about the long-term effects of multimodal treatment in adult attention-deficit/hyperactivity disorder (ADHD) is much needed. OBJECTIVE To evaluate the long-term efficacy of multimodal treatment for adult ADHD. DESIGN, SETTING, AND PARTICIPANTS This observer-masked, 1.5-year follow-up of the Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS), a prospective, multicenter randomized clinical trial, compared cognitive behavioral group psychotherapy (GPT) with individual clinical management (CM) and methylphenidate (MPH) with placebo (2 x 2 factorial design). Recruitment started January 2007 and ended August 2010, and treatments were finalized in August 2011 with follow-up through March 2013. Overall, 433 adults with ADHD participated in the trial, and 256 (59.1%) participated in the follow-up assessment. Analysis began in November 2013 and was completed in February 2018. INTERVENTIONS After 1-year treatment with GPT or CM and MPH or placebo, no further treatment restrictions were imposed. MAIN OUTCOMES AND MEASURES The primary outcome was change in the observer-masked ADHD Index of Conners Adult ADHD Rating Scale score from baseline to follow-up. Secondary outcomes included further ADHD rating scale scores, observer-masked ratings of the Clinical Global Impression scale, and self-ratings of depression on the Beck Depression Inventory. RESULTS At follow-up, 256 of 433 randomized patients (baseline measured in 419 individuals) participated. Of the 256 patients participating in follow-up, the observer-masked ADHD Index of Conners Adult ADHD Rating Scale score was assessed for 251; the mean (SD) baseline age was 36.3 (10.1) years; 125 patients (49.8%) were men; and the sample was well-balanced with respect to prior randomization (GPT and MPH: 64 of 107; GPT and placebo: 67 of 109; CM and MPH: 70 of 110; and CM and placebo: 55 of 107). At baseline, the all-group mean ADHD Index of Conners Adult ADHD Rating Scale score was 20.6, w

Electronic tags are widespread tools for studying aquatic animal behavior; however, tags risk behavioral manipulation and negative welfare outcomes. During an experiment to test behavioral differences of Atlantic salmon Salmo salar in different aquaculture cage types, including ones expected to elicit deeper swimming behavior, we found negative tagging effects depending on whether cages were depth-modified. In the experiment, data storage tags implanted in Atlantic salmon tracked their depth behavior and survival in unmodified sea-cages and depth-modified sea-cages that forced fish below or into a narrow seawater- or freshwater-filled snorkel tube from a 4 m net roof to the surface. All tagged individuals survived in unmodified cages; however, survival was reduced to 62% in depth-modified cages. Survivors in depth-modified cages spent considerably less time above 4 m than those in unmodified cages, and dying individuals in depth-modified cages tended to position in progressively shallower water. The maximum depth that fish in our study could attain neutral buoyancy was estimated at 22 m in seawater. We calculated that the added tag weight in water reduced this to 8 m, and subtracting the tag volume from the peritoneal cavity where the swim bladder reinflates reduced this further to 4 m. We conclude that the internal tag weight and volume affected buoyancy regulation as well as the survival and behavior of tagged fish. Future tagging studies on aquatic animals should carefully consider the buoyancy-related consequences of internal tags with excess weight in water, and the inclusion of data from dying tagged animals when estimating normal depth behaviors.

Mankind is on the verge of a postantibiotic era. New concepts are needed in our battle to attenuate infectious diseases around the world and broad spectrum plant-inspired synergistic pharmaceutical preparations should find their place in the global fight against pathogenic microorganisms. To progress towards the discovery of potent antifungal agents against human pathologies, we embarked upon developing chemometric approach coupled with statistical design to unravel the origin of the anticandidal potential of a set of 66 essential oils (EOs). EOs were analyzed by GC-MS and tested against Candida albicans and C. parapsilosis (Minimal Inhibitory Concentration, MIC). An Orthogonal Partial Least Square (OPLS) analysis allowed us to identify six molecules presumably responsible for the anticandidal activity of the oils: (Z)-ligustilide, eugenol, eugenyl acetate, citral, thymol, and beta-citronellol. These compounds were combined following a full factorial experimental design approach in order to optimize the anticandidal activity and selectivity index (SI = IC50(MRC5 cells)/MIC) through reconstituted mixtures. (Z)-Ligustilide and citral were the most active compounds, while (Z)-ligustilide and eugenol were the two main factors that most contributed to the increase of the SI. These two terpenes can, therefore, be used to construct bioinspired synergistic anticandidal mixtures.

Human-caused habitat disturbances and climate change are leading threats to biodiversity. Studying the impacts of human activities on wildlife from a behavioral perspective is a relevant starting point to understand the mechanisms underlying population and species resistance and resilience to disturbances. In this study, we assessed the effects of weather (temperature and precipitation), habitat disturbances (roads and clearcuts), and natural habitat types on the space use patterns of a threatened boreal population of woodland caribou (Rangifer tarandus caribou). An extensive data set of 288,665 relocations from 50 adult females outfitted with GPS collars over 7 years in the boreal forest of Québec, Canada was used to evaluate residency time in natural and disturbed habitats for five distinct biologically defined periods. The most parsimonious linear mixed-effects model for each period showed that individuals stayed longer in more natural habitat types. During calving and summer, residency time decreased with increasing road density, whereas residency time decreased with increasing temperature during winter and spring. We found no evidence of a synergistic effect between daily weather and human disturbances on movement behavior of caribou, but consider their respective influence as additive. We also showed large individual variation in residency time, except during the calving period. Lower individual variation in residency time during calving may be explained by strong evolutionary constraints on behavior faced by females to ensure protection and survival of their offspring. Based on our results, we suggest keeping large patches of suitable and roadless habitat for caribou to favor the spacing-out antipredator strategy exhibited by females during calving. By tracking individuals over several complete annual cycles, we showed variation in the effects of daily weather and human disturbances on residency time across biological periods. Our study highlights that the in

Mankind is on the verge of a postantibiotic era. New concepts are needed in our battle to attenuate infectious diseases around the world and broad spectrum plant-inspired synergistic pharmaceutical preparations should find their place in the global fight against pathogenic microorganisms. To progress towards the discovery of potent antifungal agents against human pathologies, we embarked upon developing chemometric approach coupled with statistical design to unravel the origin of the anticandidal potential of a set of 66 essential oils (EOs). EOs were analyzed by GC-MS and tested against Candida albicans and C. parapsilosis (Minimal Inhibitory Concentration, MIC). An Orthogonal Partial Least Square (OPLS) analysis allowed us to identify six molecules presumably responsible for the anticandidal activity of the oils: (Z)-ligustilide, eugenol, eugenyl acetate, citral, thymol, and beta-citronellol. These compounds were combined following a full factorial experimental design approach in order to optimize the anticandidal activity and selectivity index (SI = IC50(MRC5 cells)/MIC) through reconstituted mixtures. (Z)-Ligustilide and citral were the most active compounds, while (Z)-ligustilide and eugenol were the two main factors that most contributed to the increase of the SI. These two terpenes can, therefore, be used to construct bioinspired synergistic anticandidal mixtures.

IMPORTANCE Knowledge about the long-term effects of multimodal treatment in adult attention-deficit/hyperactivity disorder (ADHD) is much needed. OBJECTIVE To evaluate the long-term efficacy of multimodal treatment for adult ADHD. DESIGN, SETTING, AND PARTICIPANTS This observer-masked, 1.5-year follow-up of the Comparison of Methylphenidate and Psychotherapy in Adult ADHD Study (COMPAS), a prospective, multicenter randomized clinical trial, compared cognitive behavioral group psychotherapy (GPT) with individual clinical management (CM) and methylphenidate (MPH) with placebo (2 x 2 factorial design). Recruitment started January 2007 and ended August 2010, and treatments were finalized in August 2011 with follow-up through March 2013. Overall, 433 adults with ADHD participated in the trial, and 256 (59.1%) participated in the follow-up assessment. Analysis began in November 2013 and was completed in February 2018. INTERVENTIONS After 1-year treatment with GPT or CM and MPH or placebo, no further treatment restrictions were imposed. MAIN OUTCOMES AND MEASURES The primary outcome was change in the observer-masked ADHD Index of Conners Adult ADHD Rating Scale score from baseline to follow-up. Secondary outcomes included further ADHD rating scale scores, observer-masked ratings of the Clinical Global Impression scale, and self-ratings of depression on the Beck Depression Inventory. RESULTS At follow-up, 256 of 433 randomized patients (baseline measured in 419 individuals) participated. Of the 256 patients participating in follow-up, the observer-masked ADHD Index of Conners Adult ADHD Rating Scale score was assessed for 251; the mean (SD) baseline age was 36.3 (10.1) years; 125 patients (49.8%) were men; and the sample was well-balanced with respect to prior randomization (GPT and MPH: 64 of 107; GPT and placebo: 67 of 109; CM and MPH: 70 of 110; and CM and placebo: 55 of 107). At baseline, the all-group mean ADHD Index of Conners Adult ADHD Rating Scale score was 20.6, w