Basal rot of narcissus : understanding pathogenicity in fusarium oxysporum f. sp. narcissi

Fusarium oxysporum is a globally distributed soilborne fungal pathogen causing root rots, bulb rots, crown rots and vascular wilts on a range of horticultural plants. Pathogenic F. oxysporum isolates are highly host specific and are classified as formae speciales. Narcissus is an important ornamental crop and both the quality and yield of flowers and bulbs can be severely affected by a basal rot caused by F. oxysporum f. sp. narcissi (FON); 154 Fusarium isolates were obtained from different locations and Narcissus cultivars in the United Kingdom, representing a valuable resource. A subset of 30 F. oxysporum isolates were all found to be pathogenic and were therefore identified as FON. Molecular characterisation of isolates through sequencing of three housekeeping genes, suggested a monophyletic origin with little divergence. PCR detection of 14 Secreted in Xylem (SIX) genes, previously shown to be associated with pathogenicity in other F. oxysporum f. spp., revealed different complements of SIX7, SIX9, SIX10, SIX12 and SIX13 within FON isolates which may suggest a race structure. SIX gene sequences were unique to FON and SIX10 was present in all isolates, allowing for molecular identification of FON for the first time. The genome of a highly pathogenic isolate was sequenced and lineage specific (LS) regions identified which harboured putative effectors including the SIX genes. Real-time RT-PCR, showed that SIX genes and selected putative effectors were expressed in planta with many significantly upregulated during infection. This is the first study to characterise molecular variation in FON and provide an analysis of the FON genome. Identification of expressed genes potentially associated with virulence provides the basis for future functional studies and new targets for molecular diagnostics

Concurrent infection with the filarial helminth Litomosoides sigmodontis attenuates or worsens Influenza A virus pathogenesis in a stage-dependent manner

Filarial helminths infect approximately 120 million people worldwide initiating a type 2 immune response in the host. Influenza A viruses stimulate a virulent type 1 pro-inflammatory immune response that in some individuals can cause uncontrolled immunopathology and fatality. Although coinfection with filariasis and influenza is a common occurrence, the impact of filarial infection on respiratory viral infection is unknown. The aim of this study was to determine the impact of pre-existing filarial infection on concurrent infection with influenza A virus. A murine model of co-infection was established using the filarial helminth Litomosoides sigmodontis and the H1N1 (A/WSN/33) influenza A virus (IAV). Co-infection was performed at 3 different stages of L. sigmodontis infection (larval, juvenile adult, and patency), and the impact of co-infection was determined by IAV induced weight loss and clinical signs, quantification of viral titres, and helminth counts. Significant alterations of IAV pathogenesis, dependent upon stage of infection, was observed on co-infection with L. sigmodontis. Larval stage L. sigmodontis infection alleviated clinical signs of IAV co-infection, whilst more established juvenile adult infection also significantly delayed weight loss. Viral titres remained unaltered at either infection stage. In contrast, patent L. sigmdodontis infection led to a reversal of age-related resistance to IAV infection, significantly increasing weight loss and clinical signs of infection as well as increasing IAV titre. These data demonstrate that the progression of influenza infection can be ameliorated or worsened by pre-existing filarial infection, with the outcome dependent upon the stage of filarial infection

Extending cognitive-behavioural theory and therapy to medically unexplained symptoms and long term conditions:a hybrid transdiagnostic/problem specific approach

Medically Unexplained Symptoms (MUS) are not only common and distressing, but also are typically poorly managed in general medical settings. Those suffering from these problems tend to incur significantly higher health costs than the general population. There are many effective treatments for different MUS; these are almost entirely based on Cognitive-behavioural approaches. However, the wide range of treatment protocols tend to be “syndrome specific”. As such, they do not generalise well in terms of training and application, making them expensive and difficult to disseminate, suggesting the desirability of developing a transdiagnostic approach. The general basis of such a CBT grounded transdiagnostic approach is considered, and the particular need to incorporate cognitive elements of both anxiety/health anxiety (threat) and depression (loss) is highlighted. Key empirically grounded and evidence based processes (both specific and general) previously identified as underpinning the maintenance of MUS are delineated. The way in which these can be combined in a transdiagnostic model which accounts for most MUS presentations is presented and linked to a formulation driven transdiagnostic treatment strategy, which is described. However, the need to take more syndrome-specific issues into account in treatment is identified, suggesting that the optimum treatment may be a hybrid transdiagnostic/specific approach with formulation, shared understanding, belief change strategies and behavioural experiments at its heart. The generalisation of such approaches to psychological problems occurring in the context of “Long Term Conditions” is identified as a further important development which is now within reach

Newcomer families' experiences with programs and services to support early childhood development in Canada: A scoping review

It can be difficult for families with young children to navigate early childhood development supports. In particular, newcomer families often encounter additional barriers and require resources, programs, and services that are tailored to their unique assets, experiences, and needs. We conducted a scoping review of the literature published between 2000 and 2019 to explore what is known about newcomer families’ experiences with programs and services to support early childhood development in Canada. We searched 12 databases, screened 2390 articles, and included 34 articles for synthesis and analysis. Three common and connected themes were identified: 1) effective intercultural understanding, responsiveness, and communication are critical to ensuring full access to meaningful programs and services; 2) some newcomer families face systemic barriers exacerbated by their immigration status, and; 3) feelings and perceptions of families and service providers, as well as social supports, networks, and relationships influence how programs and services are accessed and experienced. Our review identifies the requirement for additional, participatory research that centres the voices and perspectives of newcomer children and their families and the need to expand that research to less populated and rural areas of the country to inform meaningful and culturally relevant policies, programs, and services for newcomer families to support their children’s well-being

Hematopoietic Defects in rps29 Mutant Zebrafish Depend Upon p53 Activation

Disruption of ribosomal proteins is associated with hematopoietic phenotypes in cell culture and animal models. Mutations in ribosomal proteins are seen in patients with Diamond Black- fan anemia, a rare congenital disease characterized by red cell aplasia and distinctive cranio- facial anomalies. A zebrafish screen uncovered decreased hematopoietic stem cells in embryos with mutations in ribosomal protein rps29. Here, we determined that rps29L/L embryos also have red blood cell defects and increased apoptosis in the head. As the p53 pathway has been shown to play a role in other ribosomal protein mutants, we studied the genetic relationship of rps29 and p53. Transcriptional profiling revealed that genes upregulated in the rps29 mutant are enriched for genes upregulated by p53 after irradiation. p53 mutation near completely rescues the rps29 morphological and hematopoietic phenotypes, demonstrating that p53 medi- ates the effects of rps29 knockdown. We also identified neuronal gene orthopedia protein a (otpa) as one whose expression correlates with rps29 expression, suggesting that levels of expression of some genes are dependent on rps29 levels. Together, our studies demonstrate a role of p53 in mediating the cellular defects associated with rps29 and establish a role for rps29 and p53 in hematopoietic stem cells and red blood cell development.Stem Cell and Regenerative Biolog

Tissue Tropism in Host Transcriptional Response to Members of the Bovine Respiratory Disease Complex.

Bovine respiratory disease (BRD) is the most common infectious disease of beef and dairy cattle and is characterized by a complex infectious etiology that includes a variety of viral and bacterial pathogens. We examined the global changes in mRNA abundance in healthy lung and lung lesions and in the lymphoid tissues bronchial lymph node, retropharyngeal lymph node, nasopharyngeal lymph node and pharyngeal tonsil collected at the peak of clinical disease from beef cattle experimentally challenged with either bovine respiratory syncytial virus, infectious bovine rhinotracheitis, bovine viral diarrhea virus, Mannheimia haemolytica or Mycoplasma bovis. We identified signatures of tissue-specific transcriptional responses indicative of tropism in the coordination of host's immune tissue responses to infection by viral or bacterial infections. Furthermore, our study shows that this tissue tropism in host transcriptional response to BRD pathogens results in the activation of different networks of response genes. The differential crosstalk among genes expressed in lymphoid tissues was predicted to be orchestrated by specific immune genes that act as 'key players' within expression networks. The results of this study serve as a basis for the development of innovative therapeutic strategies and for the selection of cattle with enhanced resistance to BRD

Draft genome sequence of an onion basal rot isolate of Fusarium proliferatum

Fusarium proliferatum is a component of the onion basal rot disease complex. We present an annotated F. proliferatum draft genome sequence, totaling 45.8 Mb in size, assembled into 597 contigs, with a predicted 15,418 genes. The genome contains 58 secondary metabolite clusters and homologs of the Fusarium oxysporum effector SIX2

Comparison of treatment effect sizes from pivotal and postapproval trials of novel therapeutics approved by the FDA based on surrogate markers of disease: a meta-epidemiological study

Background: The U.S. Food and Drug Administration (FDA) often approves new drugs based on trials that use surrogate markers for endpoints, which involve certain trade-offs and may risk making erroneous inferences about the medical product’s actual clinical effect. This study aims to compare the treatment effects among pivotal trials supporting FDA approval of novel therapeutics based on surrogate markers of disease with those observed among postapproval trials for the same indication. Methods: We searched Drugs@FDA and PubMed to identify published randomized superiority design pivotal trials for all novel drugs initially approved by the FDA between 2005 and 2012 based on surrogate markers as primary endpoints and published postapproval trials using the same surrogate markers or patient-relevant outcomes as endpoints. Summary ratio of odds ratios (RORs) and difference between standardized mean differences (dSMDs) were used to quantify the average difference in treatment effects between pivotal and matched postapproval trials. Results: Between 2005 and 2012, the FDA approved 88 novel drugs for 90 indications based on one or multiple pivotal trials using surrogate markers of disease. Of these, 27 novel drugs for 27 indications were approved based on pivotal trials using surrogate markers as primary endpoints that could be matched to at least one postapproval trial, for a total of 43 matches. For nine (75.0%) of the 12 matches using the same non-continuous surrogate markers as trial endpoints, pivotal trials had larger treatment effects than postapproval trials. On average, treatment effects were 50% higher (more beneficial) in the pivotal than the postapproval trials (ROR 1.5; 95% confidence interval CI 1.01–2.23). For 17 (54.8%) of the 31 matches using the same continuous surrogate markers as trial endpoints, pivotal trials had larger treatment effects than the postapproval trials. On average, there was no difference in treatment effects between pivotal and postapproval trials (dSMDs 0.01; 95% CI -0.15–0.16). Conclusions: Many postapproval drug trials are not directly comparable to previously published pivotal trials, particularly with respect to endpoint selection. Although treatment effects from pivotal trials supporting FDA approval of novel therapeutics based on non-continuous surrogate markers of disease are often larger than those observed among postapproval trials using surrogate markers as trial endpoints, there is no evidence of difference between pivotal and postapproval trials using continuous surrogate markers

Health-related quality of life and physical recovery after a critical illness: a multi-centre randomised controlled trial of a home-based physical rehabilitation program

Introduction: Significant physical sequelae exist for some survivors of a critical illness. There are, however, few studies that have examined specific interventions to improve their recovery, and none have tested a home-based physical rehabilitation program incorporating trainer visits to participants' homes. This study was designed to test the effect of an individualised eight-week home-based physical rehabilitation program on recovery. Methods: A multi-centre randomised controlled trial design was used. Adult intensive care patients (length of stay of at least 48 hours and mechanically ventilated for 24 hours or more) were recruited from 12 Australian hospitals between 2005 and 2008. Graded, individualised endurance and strength training intervention was prescribed over eight weeks, with three physical trainer home visits, four follow-up phone calls, and supported by a printed exercise manual. The main outcome measures were blinded assessments of physical function; SF-36 physical function (PF) scale and six-minute walk test (6MWT), and health-related quality of life (SF-36) conducted at 1, 8 and 26 weeks after hospital discharge. Results: Of the 195 participants randomised, 183, 173 and 161 completed the 1, 8 and 26 weeks assessments, respectively. Study groups were similar at Week 1 post-hospital; for the intervention and control groups respectively, mean norm-based PF scores were 27 and 29 and the 6MWT distance was 291 and 324 metres. Both groups experienced significant and clinically important improvements in PF scores and 6MWT distance at 8 weeks, which persisted at 26 weeks. Mixed model analysis showed no significant group effects (P = 0.84) or group by time interactions (P = 0.68) for PF. Similar results were found for 6MWT and the SF-36 summary scores. Conclusions: This individualised eight-week home-based physical rehabilitation program did not increase the underlying rate of recovery in this sample, with both groups of critically ill survivors improving their physical function over the 26 weeks of follow-up. Further research should explore improving effectiveness of the intervention by increasing exercise intensity and frequency, and identifying individuals who would benefit most from this intervention. Trial registration: Australia and New Zealand Clinical Trials Register ACTRN1260500016667

Stratospheric Gravity Wave Fluxes and Scales during DEEPWAVE

During the Deep Propagating Gravity Wave Experiment (DEEPWAVE) project in June and July 2014, the Gulfstream V research aircraft flew 97 legs over the Southern Alps of New Zealand and 150 legs over the Tasman Sea and Southern Ocean, mostly in the low stratosphere at 12.1-km altitude. Improved instrument calibration, redundant sensors, longer flight legs, energy flux estimation, and scale analysis revealed several new gravity wave properties. Over the sea, flight-level wave fluxes mostly fell below the detection threshold. Over terrain, disturbances had characteristic mountain wave attributes of positive vertical energy flux (EFz), negative zonal momentum flux, and upwind horizontal energy flux. In some cases, the fluxes changed rapidly within an 8-h flight, even though environmental conditions were nearly unchanged. The largest observed zonal momentum and vertical energy fluxes were MFx = −550 mPa and EFz = 22 W m−2, respectively. A wide variety of disturbance scales were found at flight level over New Zealand. The vertical wind variance at flight level was dominated by short “fluxless” waves with wavelengths in the 6–15-km range. Even shorter scales, down to 500 m, were found in wave breaking regions. The wavelength of the flux-carrying mountain waves was much longer—mostly between 60 and 150 km. In the strong cases, however, with EFz \u3e 4 W m−2, the dominant flux wavelength decreased (i.e., “downshifted”) to an intermediate wavelength between 20 and 60 km. A potential explanation for the rapid flux changes and the scale “downshifting” is that low-level flow can shift between “terrain following” and “envelope following” associated with trapped air in steep New Zealand valleys