Abstract
Diverse and inclusive marine research is paramount to addressing ocean sustainability challenges in the 21st century, as envisioned by the UN Decade of Ocean Science for Sustainable ...Development. Despite increasing efforts to diversify ocean science, women continue to face barriers at various stages of their career, which inhibits their progression to leadership within academic institutions. In this perspective, we draw on the collective experiences of thirty-four global women leaders, bolstered by a narrative review, to identify practical strategies and actions that will help empower early career women researchers to become the leaders of tomorrow. We propose five strategies: (i) create a more inclusive culture, (ii) ensure early and equitable career development opportunities for women ECRs, (iii) ensure equitable access to funding for women ECRs, (iv) offer mentoring opportunities and, (v) create flexible, family-friendly environments. Transformational, meaningful, and lasting change will only be achieved through commitment and collaborative action across various scales and by multiple stakeholders.
Multiple sclerosis (MS) is a heterogeneous disease. In order to understand the partial responsiveness to IFNbeta in Relapsing Remitting MS (RRMS) we studied the pharmacological effects of IFNbeta ...therapy.
Large scale gene expression profiling was performed on peripheral blood of 16 RRMS patients at baseline and one month after the start of IFNbeta therapy. Differential gene expression was analyzed by Significance Analysis of Microarrays. Subsequent expression analyses on specific genes were performed after three and six months of treatment. Peripheral blood mononuclear cells (PBMC) were isolated and stimulated in vitro with IFNbeta. Genes of interest were measured and validated by quantitative realtime PCR. An independent group of 30 RRMS patients was used for validation.
Pharmacogenomics revealed a marked variation in the pharmacological response to IFNbeta between patients. A total of 126 genes were upregulated in a subset of patients whereas in other patients these genes were downregulated or unchanged after one month of IFNbeta therapy. Most interestingly, we observed that the extent of the pharmacological response correlates negatively with the baseline expression of a specific set of 15 IFN response genes (R = -0.7208; p = 0.0016). The negative correlation was maintained after three (R = -0.7363; p = 0.0027) and six (R = -0.8154; p = 0.0004) months of treatment, as determined by gene expression levels of the most significant correlating gene. Similar results were obtained in an independent group of patients (n = 30; R = -0.4719; p = 0.0085). Moreover, the ex vivo results could be confirmed by in vitro stimulation of purified PBMCs at baseline with IFNbeta indicating that differential responsiveness to IFNbeta is an intrinsic feature of peripheral blood cells at baseline.
These data imply that the expression levels of IFN response genes in the peripheral blood of MS patients prior to treatment could serve a role as biomarker for the differential clinical response to IFNbeta.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Previously, we demonstrated that cognitive behavior therapy for ultra-high risk (called CBTuhr) halved the incidence of psychosis over an 18-month period. Follow-up data from the same study are used ...to evaluate the longer-term effects at 4 years post-baseline.
The Dutch Early Detection and Intervention Evaluation study was a randomized controlled trial of 196 UHR patients comparing CBTuhr with treatment-as-usual (TAU) for comorbid disorders with TAU only. Of the original 196 patients, 113 consented to a 4-year follow-up (57.7%; CBTuhr = 56 vs TAU = 57). Over the study period, psychosis incidence, remission from UHR status, and the effects of transition to psychosis were evaluated.
The number of participants in the CBTuhr group making the transition to psychosis increased from 10 at 18-month follow-up to 12 at 4-year follow-up whereas it did not change in the TAU group (n = 22); this still represents a clinically important (incidence rate ratio IRR = 12/22 = 0.55) and significant effect (F(1,5) = 8.09, P = .03), favoring CBTuhr. The odds ratio of CBTuhr compared to TAU was 0.44 (95% CI: 0.24-0.82) and the number needed to treat was 8. Moreover, significantly more patients remitted from their UHR status in the CBTuhr group (76.3%) compared with the TAU group (58.7%) t(120) = 2.08, P = .04. Importantly, transition to psychosis was associated with more severe psychopathology and social functioning at 4-year follow-up.
CBTuhr to prevent a first episode of psychosis in persons at UHR of developing psychosis is still effective at 4-year follow-up. Our data also show that individuals meeting the formal criteria of a psychotic disorder have worse functional and social outcomes compared with non-transitioned cases.
The trial is registered at Current Controlled Trials as trial number ISRCTN21353122 (http://controlled-trials.com/ISRCTN21353122/gaag).
Background
Prader–Willi syndrome (PWS) and Angelman syndrome (AS) are neurodevelopmental disorders in need of innovative ‘real‐world’ outcome measures to evaluate treatment effects. Instrumented gait ...analysis (IGA) using wearable technology offers a potentially feasible solution to measure “real‐world’ neurological and motor dysfunction in these groups.
Methods
Children (50% female; 6–16 years) diagnosed with PWS (n = 9) and AS (n = 5) completed ‘real‐world’ IGA assessments using the Physilog®5 wearable. PWS participants completed a laboratory assessment and a ‘real‐world’ long walk. The AS group completed ‘real‐world’ caregiver‐assisted assessments. Mean and variability results for stride time, cadence, stance percentage (%) and stride length were extracted and compared across three different data reduction protocols.
Results
The wearables approach was found to be feasible, with all participants able to complete at least one assessment. This study also demonstrated significant agreement, using Lin's concordance correlation coefficient (CCC), between laboratory and ‘real‐world’ assessments in the PWS group for mean stride length, mean stance % and stance % CV (n = 7, CCC: 0.782–0.847, P = 0.011–0.009).
Conclusion
‘Real‐world’ gait analysis using the Physilog®5 wearable was feasible to efficiently assess neurological and motor dysfunction in children affected with PWS and AS.
Herpes simplex virus type 1 (HSV-1) has been associated with pulmonary disease, mostly in severely immunocompromised patients. After reactivation and shedding in the oropharynx, the virus may reach ...the lower respiratory tract by aspiration or by contiguous spread. HSV-1 can be detected in clinical specimens by virus culture or quantitatively by nucleic acid amplification techniques. With these techniques, HSV-1 is often detected in the respiratory secretions of critically-ill patients. However, a clear diagnosis of HSV-1 pneumonia is difficult to establish because clinical criteria, radiological features and laboratory findings all lack specificity. Lower respiratory tract HSV-1 infections have not been associated with specific risk-factors. There is also an absence of consistent data concerning the effect of antiviral treatment on the outcome of critically-ill patients. Further studies are needed to better define the pathogenic role of HSV-1 in the lower respiratory tract of these patients, to improve the diagnosis, and, especially, to assess the need for antiviral treatment in the individual patient.
The phylogenetic diversity of Bacteria and Archaea in water retrieved from a Dutch oil field and units of the associated oil-water separation site were determined using two culture-independent ...methods. Denaturing gradient gel electrophoresis of PCR-amplified 16S rRNA gene fragments was used to scan the microbial diversity in (1) the oil-water emulsion produced, (2) two different oil-water separator tanks, (3) a wash tank and (4) a water injector. Longer 16S rRNA gene fragments were amplified, cloned and sequenced to determine the diversity in more detail. One of the questions addressed was whether the detected microorganisms could serve as indicators for the environments from which they were retrieved. It was observed that the community found in the production water resembled those reported previously in oil reservoirs, indicating that these ecosystems harbor specific microbial communities. It was shown that changes, like a decrease in temperature, cause a distinctive shift in these communities. The addition of SO₃²⁻ to the wash tank as ammonium bisulphite, used in the oil industry to scavenge oxygen, resulted in a complete community change, giving rise to an unwanted sulphate-reducing community. The fact that these changes in the community can be linked to changes in their environment might indicate that these tools can be used for the monitoring of changing conditions in oil reservoirs upon, for example, water flooding.
Abstract
Background
Patient involvement in discharge planning of patients with stroke can be accomplished by providing personalized outcome information and promoting shared decision-making. The aim ...of this study was to develop a patient decision aid (PtDA) for discharge planning of hospitalized patients with stroke.
Methods
A convergent mixed methods design was used, starting with needs assessments among patients with stroke and health care professionals (HCPs). Results of these assessments were used to develop the PtDA with integrated outcome information in several co-creation sessions. Subsequently, acceptability and usability were tested to optimize the PtDA. Development was guided by the International Patient Decision Aids Standards (IPDAS) criteria.
Results
In total, 74 patients and 111 HCPs participated in this study. A three-component PtDA was developed, consisting of:
1) a printed consultation sheet to introduce the options for discharge destinations, containing information that can be specified for each individual patient;
2) an online information and deliberation tool to support patient education and clarification of patient values, containing an integrated “patients-like-me” model with outcome information about discharge destinations;
3) a summary sheet to support actual decision-making during consultation, containing the patient’s values and preferences concerning discharge planning.
In the acceptability test, all qualifying and certifying IPDAS criteria were fulfilled. The usability test showed that patients and HCPs highly appreciated the PtDA with integrated outcome information.
Conclusions
The developed PtDA was found acceptable and usable by patients and HCPs and is currently under investigation in a clinical trial to determine its effectiveness.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Synovitis in collagenase-induced osteoarthritis (CiOA) is driven by locally released S100A8/A9 proteins and enhances joint destruction. S100A8/A9 can induce reactive oxygen species (ROS) release by ...phagocytes in OA synovium via neutrophil cytosolic factor-1 (Ncf1)-regulated NOX2 activation. In the present study we investigated whether NOX2-derived ROS affect joint pathology during CiOA.
CiOA was induced in knee joints of wild type (WT) and Ncf1-deficient (Ncf1**) mice. Synovial gene expression of NOX2-subunits was measured with quantitative real-time polymerase chain reaction (qRT-PCR). Joint pathology was assessed using histology and immunohistochemistry for aggrecan neo-epitope VDIPEN. Levels of inflammatory proteins were measured with Luminex or ELISA. Phagocytes in synovium, blood, bone marrow (BM) and spleen were analyzed with flow cytometry. ROS release by phagocytes was measured with a ROS detection kit.
CiOA induction in knee joints of WT mice caused significantly increased synovial gene expression of NOX2 subunits. On day 7 of CiOA, cartilage damage and MMP activity, as measured by VDIPEN, were comparable between WT and Ncf1** mice. Synovial thickening, synovial S100A8/A9 levels and percentages of synovial macrophages, polymorphonuclear cells (PMNs), and monocytes were not different, as were levels of inflammatory mediators in serum and phagocyte percentages in blood, BM and spleen. On day 42 of CiOA, synovitis, cartilage damage, and osteophyte formation in Ncf1** mice were unaltered when compared to WT mice. ROS detection confirmed that Ncf1** PMNs lack functional NOX2, but in vitro macrophages showed ROS production, suggesting activation of compensatory mechanisms.
Absence of Ncf1-mediated ROS production does not alter joint pathology in CiOA.
Rheumatoid arthritis (RA) is a heterogeneous disease. We used cDNA microarray technology to subclassify RA patients and disclose disease pathways in rheumatoid synovium. Hierarchical clustering of ...gene expression data identified two main groups of tissues (RA-I and RA-II). A total of 121 genes were significantly higher expressed in the RA-I tissues, whereas 39 genes were overexpressed in the RA-II tissues. Among the 121 genes overexpressed in RA-I tissues, a relative majority of nine genes are located on chromosome 6p21.3. An interpretation of biological processes that take place revealed that the gene expression profile in RA-I tissues is indicative for an adaptive immune response. The RA-II group showed expression of genes suggestive for fibroblast dedifferentiation. Within the RA-I group, two subgroups could be distinguished; the RA-Ia group showed predominantly immune-related gene activity, while the RA-Ib group showed an additional higher activity of genes indicative for the classical pathway of complement activation. All tissues except the RA-Ia subgroup showed elevated expression of genes involved in tissue remodeling. These results confirm the heterogeneous nature of RA and suggest the existence of distinct pathogenic mechanisms that contribute to RA. The differences in expression profiles provide opportunities to stratify patients based on molecular criteria.
Given the heterogeneous nature of multiple sclerosis (MS), we applied DNA microarray technology to determine whether variability is reflected in peripheral blood (PB) cells. In this study, we studied ...whole-blood gene expression profiles of 29 patients with relapsing-remitting MS (RRMS) and 25 age- and sex-matched healthy controls. We used microarrays with a complexity of 43K cDNAs. The data were analyzed using sophisticated pathway-level analysis in order to provide insight into the deregulated peripheral immune response programs in MS. We found a remarkable elevated expression of a spectrum of genes known to be involved in immune defense in the PB of MS patients compared to healthy individuals. Cluster analysis revealed that the increased expression of these genes was characteristic for approximately half of the patients. In addition, the gene signature in this group of patients was comparable with a virus response program. We conclude that the transcriptional signature of the PB cells reflects the heterogeneity of MS and defines a sub-population of RRMS patients, who exhibit an activated immune defense program that resembles a virus response program, which is supportive for a link between viruses and MS.
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