Evaluation of the aquatic bryophyte Fontinalis antipyretica for laboratory and field toxicity studies

Fontinalis antipyretica is an ecologically important aquatic moss in boreal streams. Bioassays using this species provide information of effects at the base of the food chain. The present study assessed toxicological effects to F. antipyretica, firstly of the positive controls copper and 3,5- dichlorophenol (3,5-DCP) in separate laboratorial bioassays, and secondly of ecologically relevant pollutants during autumn in a catchment area dominated by agriculture in a field study. The laboratorial studies assessed effects of five concentrations of copper sulphate (CuSO4, 0- 300 μM) and 3,5-DCP (0-9 mg/L) for exposure up to 21 days. This included determination of suitable mode of actions (MoAs) including maximal PS II efficiency (Fv/Fm), pigment concentration and production of reactive oxygen species (ROS), and the adverse outcomes (AO) greenness index (GI) and growth, and toxic effects on these endpoints. Copper caused clear concentration and time-dependent responses for inhibition of GI, Fv/Fm, pigment concentration, and production of ROS. 3,5-DCP caused clear concentration and time-dependent responses for inhibition of GI, Fv/Fm, and pigment concentration, additionally to weak responses for growth. Optimal exposure time was typically 7-14 days for most endpoints; however, 21 days were needed for growth. The field study assessed effects of environmentally relevant concentrations of pollutants and stressors of the test stream Skuterudbekken, compared to a reference stream with little pollution. Moss tissue was deployed from Skut 1 (located upstream of sedimentation ponds) and Skut 2 (located downstream of sedimentation ponds and European route 18) back into their respective location and additionally to the reference stream. The study additionally included comparison of native and deployed moss in the test stream, and moss sampling for endpoint analysis was done after exposure for up to 14 days. Chemical and physical conditions of streams were monitored during the exposure study. The results indicated no clear deployment status, site or time-dependent responses caused by pollution. However, site-specific negative responses on growth, Fv/Fm, and production of ROS were observed in Skut 2, possibly caused by high water discharge combined with fragmenting of F. antipyretica due to the time of year. Overall, F. antipyerica demonstrated to be a suitable study species for bioassays, with limitations including difficulties in obtaining sterile moss cultures for laboratorial assays and short life cycle period for obtaining ideal growth conditions.Fontinalis antipyretica er en økologisk viktig akvatisk mose i boreale elver og bekker. Bioassay med bruk av denne arten gir informasjon om effekter på bunnen av næringskjeden. Dette studiet undersøkte toksikologiske effekter på F. antipyretica, først av de positive kontrollene kobber og 3,5-diklorofenol (3,5-DCP) i separate laboratoriestudier, og deretter i en feltstudie med økologisk relevante forurensende stoffer på høsten i et nedbørsfelt dominert av landbruk. Laboratorieforsøkene undersøkte effekter av fem konsentrasjoner av kobbersulfat (CuSO4, 0- 300 µM) og 3,5-DCP (0-9 mg/L) etter eksponering i opptil 21 dager. Dette inkluderte å fastslå virkemåtene (eng. Mode of Action, MoA) maksimal PS II effektivitet (Fv/Fm), pigmentkonsentrasjon og produksjon av reaktive oksygenforbindelser (ROS), samt de alvorlige effektene (eng. Adverse Outcome, AO) grønnhetsindeks (GI) og vekst. Toksiske effekter på disse endepunktene ble undersøkt. Kobbereksponering førte til klar konsentrasjons- og tidsavhengig respons for hemming av GI, Fv/Fm, pigmentkonsentrasjon og produksjon av ROS. Eksponering for 3,5-DCP førte til klar konsentrasjons- og tidsavhengig respons for hemming av GI, Fv/Fm og pigmentkonsentrasjon, samt svak negativ påvirkning på vekst. Optimal eksponeringstid var typisk 7-14 dager for de fleste endepunkt, men effekt på vekst trengte 21 dager. Feltforsøket undersøkte effekten av miljømessig relevante konsentrasjoner av forurensende stoffer og stressorer i testbekken Skuterudbekken, sammenlignet med en referansebekk med lite forurensing. Mosen ble transplantert fra Skut 1 (plassert oppstrøms for sedimentasjonsdammer) og Skut 2 (plassert nedstrøms for sedimentasjonsdammer og Europavei 18), tilbake til sine respektive bekker og i tillegg referansebekken. Forsøket inkluderte også sammenligning av transplantert og frittvoksende mose i testbekken, og endepunktsanalyser ble gjort etter eksponering i opptil 14 dager. Målinger av kjemiske og fysiske variabler i bekkene ble gjort gjennom eksponeringsstudiet. Resultatene indikerte ingen klar transplantasjonsstatus-, lokasjons- eller tidsavhenging respons på grunn av forurensing. Derimot ble lokasjonsavhenging respons observert for vekst, Fv/Fm og produksjon av ROS i Skut 2, muligens på grunn av høy vannføring kombinert med fragmentering av F. antipyretica på grunn av årstiden. Alt i alt har F. antipyretica vist seg å være en passende art for bioassay, selv om det kan være begrensinger inkluderende vanskeligheter med å oppnå en steril mosekultur for laboratorieforsøk og kort periode med ideelle vekstforhold i livssyklusen.M-MIN

Mutual trust is a prerequisite for nurses’ sense of safety and work satisfaction – Mobile Integrated Care Model: A qualitative interview study

An increasing number of older persons have complex health care needs. This, along with the organizational principle of remaining at home, emphasizes the need to develop collaborations among organizations caring for older persons. A health care model developed in Sweden, the Mobile Integrated Care Model aims to promote work in teams across organizations. The aim of the study was to describe nurses’ experiences in working and providing health care in the Mobile Integrated Care Model in the home with home health care physicians. Semi-structured interviews were conducted with 18 nurses and analyzed through qualitative content analysis. The method was compliant with the COREQ checklist. A mutually trusting collaboration with physicians, which formed person-centered care, created work satisfaction for the nurses. Working within the Mobile Integrated Care Model was negatively impacted by being employed by different organizations, lack of time to provide health care, and physicians’ person-centered work abilities

The role of the home health care physician in mobile integrated care: a qualitative phenomenograpic study

Background: An increasing older population, along with the organizational principle of remaining at home, has moved health care from institutions into the older person’s home, where several health care providers facilitate care. The Mobile Integrated Care Model strives to provide cost-efficient, coherent, person-centered health care in the home. In the integrated care team, where the home health care physician is the medical authority, several health care professions work across organizational borders. Therefore, the aim of this study was to describe Home Health Care Physicians perceptions of working and providing health care in the Mobile Integrated Care Model, as well as perceptions of participating in and forming health care. Methods: A phenomenographic qualitative study design, with semi-structured interviews using an interview guide. Results: Working within Mobile Integrated Care Model was a different way of working as a physician. The physicians’ role was to support the patient by making safe medical decisions. Physicians described themselves as a piece in the team puzzle, where the professional knowledge of others was crucial to give quality health care. Being in the patients’ homes was expressed as adding a unique dimension in the provision of health care, and the physicians learned more about the patients by meeting them in their homes than at an institution. This aided the physicians in respecting patient autonomy in medical decision making, even though the physicians sometimes disregarded patient autonomy in favor of their own medical experience. There was a divided view on next of kin participation among the home health care physicians, ranging from always including to total absence of involving next of kin in decision making. Conclusions: The home health care physicians described the Mobile Integrated Care Model as the best way to work, but there was still a need for additional resources and structure when working in different organizations. The need for full-time employment, additional time or hours, more equipment, access to each other’s medical records, and additional collaboration with other health care providers were expressed, which could contribute to increased work satisfaction and facilitate further development of person-centered care in the Mobile Integrated Care Model

Team Autonomy in Large-Scale Agile

Large-scale software development is increasingly making use of agile practices. In large-scale projects, a team needs to align with other teams and the rest of the organization. This has been shown to threaten team autonomy, which, in turn, reduces responsiveness and flexibility. Hence, agile teams face challenges in adapting to larger-scale development. We conduct a multiple case study of three large-scale projects to investigate barriers to team autonomy in large-scale agile. Two barriers are identified: overall direction and external dependencies. We found that goals are often set by management without involving the teams, that they are often equal to deliverables and deadlines, and that team members often do not know what the goals are. Consequently, teams struggle with setting and communicating goals as well as establishing a shared direction. Organizational dependencies lead to teams having to deal with additional tasks, resulting in specific members shielding the teams from external nois

Global gene expression analyses of hematopoietic stem cell-like cell lines with inducible Lhx2 expression

BACKGROUND: Expression of the LIM-homeobox gene Lhx2 in murine hematopoietic cells allows for the generation of hematopoietic stem cell (HSC)-like cell lines. To address the molecular basis of Lhx2 function, we generated HSC-like cell lines where Lhx2 expression is regulated by a tet-on system and hence dependent on the presence of doxycyclin (dox). These cell lines efficiently down-regulate Lhx2 expression upon dox withdrawal leading to a rapid differentiation into various myeloid cell types. RESULTS: Global gene expression of these cell lines cultured in dox was compared to different time points after dox withdrawal using microarray technology. We identified 267 differentially expressed genes. The majority of the genes overlapping with HSC-specific databases were those down-regulated after turning off Lhx2 expression and a majority of the genes overlapping with those defined as late progenitor-specific genes were the up-regulated genes, suggesting that these cell lines represent a relevant model system for normal HSCs also at the level of global gene expression. Moreover, in situ hybridisations of several genes down-regulated after dox withdrawal showed overlapping expression patterns with Lhx2 in various tissues during embryonic development. CONCLUSION: Global gene expression analysis of HSC-like cell lines with inducible Lhx2 expression has identified genes putatively linked to self-renewal / differentiation of HSCs, and function of Lhx2 in organ development and stem / progenitor cells of non-hematopoietic origin

Lhx2 Is Required for Patterning and Expansion of a Distinct Progenitor Cell Population Committed to Eye Development

Progenitor cells committed to eye development become specified in the prospective forebrain and develop subsequently into the optic vesicle and the optic cup. The optic vesicle induces formation of the lens placode in surface ectoderm from which the lens develops. Numerous transcription factors are involved in this process, including the eye-field transcription factors. However, many of these transcription factors also regulate the patterning of the anterior neural plate and their specific role in eye development is difficult to discern since eye-committed progenitor cells are poorly defined. By using a specific part of the Lhx2 promoter to regulate Cre recombinase expression in transgenic mice we have been able to define a distinct progenitor cell population in the forebrain solely committed to eye development. Conditional inactivation of Lhx2 in these progenitor cells causes an arrest in eye development at the stage when the optic vesicle induces lens placode formation in the surface ectoderm. The eye-committed progenitor cell population is present in the Lhx2−/− embryonic forebrain suggesting that commitment to eye development is Lhx2-independent. However, re-expression of Lhx2 in Lhx2−/− progenitor cells only promotes development of retinal pigment epithelium cells, indicating that Lhx2 promotes the acquisition of the oligopotent fate of these progenitor cells. This approach also allowed us to identify genes that distinguish Lhx2 function in eye development from that in the forebrain. Thus, we have defined a distinct progenitor cell population in the forebrain committed to eye development and identified genes linked to Lhx2's function in the expansion and patterning of these progenitor cells

Molecular epidemiology of DFNB1 deafness in France

BACKGROUND: Mutations in the GJB2 gene have been established as a major cause of inherited non syndromic deafness in different populations. A high number of sequence variations have been described in the GJB2 gene and the associated pathogenic effects are not always clearly established. The prevalence of a number of mutations is known to be population specific, and therefore population specific testing should be a prerequisite step when molecular diagnosis is offered. Moreover, population studies are needed to determine the contribution of GJB2 variants to deafness. We present our findings from the molecular diagnostic screening of the GJB2 and GJB6 genes over a three year period, together with a population-based study of GJB2 variants. METHODS AND RESULTS: Molecular studies were performed using denaturing High Performance Liquid Chromatograghy (DHPLC) and sequencing of the GJB2 gene. Over the last 3 years we have studied 159 families presenting sensorineural hearing loss, including 84 with non syndromic, stable, bilateral deafness. Thirty families were genotyped with causative mutations. In parallel, we have performed a molecular epidemiology study on more than 3000 dried blood spots and established the frequency of the GJB2 variants in our population. Finally, we have compared the prevalence of the variants in the hearing impaired population with the general population. CONCLUSION: Although a high heterogeneity of sequence variation was observed in patients and controls, the 35delG mutation remains the most common pathogenic mutation in our population. Genetic counseling is dependent on the knowledge of the pathogenicity of the mutations and remains difficult in a number of cases. By comparing the sequence variations observed in hearing impaired patients with those sequence variants observed in general population, from the same ethnic background, we show that the M34T, V37I and R127H variants can not be responsible for profound or severe deafness

Instrumental Variable Estimation of the Causal Effect of Plasma 25-Hydroxy-Vitamin D on Colorectal Cancer Risk: A Mendelian Randomization Analysis

Vitamin D deficiency has been associated with several common diseases, including cancer and is being investigated as a possible risk factor for these conditions. We reported the striking prevalence of vitamin D deficiency in Scotland. Previous epidemiological studies have reported an association between low dietary vitamin D and colorectal cancer (CRC). Using a case-control study design, we tested the association between plasma 25-hydroxy-vitamin D (25-OHD) and CRC (2,001 cases, 2,237 controls). To determine whether plasma 25-OHD levels are causally linked to CRC risk, we applied the control function instrumental variable (IV) method of the Mendelian randomization (MR) approach using four single nucleotide polymorphisms (rs2282679, rs12785878, rs10741657, rs6013897) previously shown to be associated with plasma 25-OHD. Low plasma 25-OHD levels were associated with CRC risk in the crude model (odds ratio (OR): 0.76, 95% Confidence Interval (CI): 0.71, 0.81, p: 1.4×10−14) and after adjusting for age, sex and other confounding factors. Using an allele score that combined all four SNPs as the IV, the estimated causal effect was OR 1.16 (95% CI 0.60, 2.23), whilst it was 0.94 (95% CI 0.46, 1.91) and 0.93 (0.53, 1.63) when using an upstream (rs12785878, rs10741657) and a downstream allele score (rs2282679, rs6013897), respectively. 25-OHD levels were inversely associated with CRC risk, in agreement with recent meta-analyses. The fact that this finding was not replicated when the MR approach was employed might be due to weak instruments, giving low power to demonstrate an effect (<0.35). The prevalence and degree of vitamin D deficiency amongst individuals living in northerly latitudes is of considerable importance because of its relationship to disease. To elucidate the effect of vitamin D on CRC cancer risk, additional large studies of vitamin D and CRC risk are required and/or the application of alternative methods that are less sensitive to weak instrument restrictions