Forskningsintegritet og åpen vitenskap: Kunnskaper, normer og holdninger blant ph.dkandidater i Norge (RIOS-PhD): Status våren 2021

Presentation at the online meeting Seminar for bibliotekenes nettverk for ph.d.-støtte, 26.04.21 - 27.04.21, arranged by Universitetet i Sørøst-Norge. https://www.phdontrack.net/nettverk/seminar/2021/program_final.pdf. </a

Gas-phase Fragmentation of Deprotonated p-Hydroxyphenacyl Derivatives

Electrospray ionization of methanolic solutions of p-hydroxyphenacyl derivatives HO-C6H4-C(O)-CH2-X (X = leaving group) provides abundant signals for the deprotonated species which are assigned to the corresponding phenolate anions −O-C6H4-C(O)-CH2-X. Upon collisional activation in the gas phase, these anions inter alia undergo loss of a neutral “C8H6O2” species concomitant with formation of the corresponding anions X−. The energies required for the loss of neutral roughly correlate with the gas phase acidities of the conjugate acids (HX). Extensive theoretical studies performed for X = CF3COO in order to reveal the energetically most favorable pathway for the formation of neutral “C8H6O2” suggest three different routes of similar energy demands, involving a spirocyclopropanone, epoxide formation, and a diradical, respectively

Total colonic aganglionosis : multicentre study of surgical treatment and patient-reported outcomes up to adulthood

Background: Surgery for total colonic aganglionosis (TCA) is designed to preserve continence and achieve satisfactory quality of life. This study evaluated a comprehensive group of clinical and social outcomes. Methods: An international multicentre study from eight Nordic hospitals involving examination of case records and a patient-reported questionnaire survey of all patients born with TCA between 1987 and 2006 was undertaken. Results: Of a total of 116 patients, five (4 center dot 3 per cent) had died and 102 were traced. Over a median follow-up of 12 (range 0 center dot 3-33) years, bowel continuity was established in 75 (73 center dot 5 per cent) at a median age of 11 (0 center dot 5-156) months. Mucosectomy with a short muscular cuff and straight ileoanal anastomosis (SIAA) (29 patients) or with aJpouch (JIAA) (26) were the most common reconstructions (55 of 72, 76 per cent). Major early postoperative complications requiring surgical intervention were observed in four (6 per cent) of the 72 patients. In 57 children aged over 4 years, long-term functional bowel symptoms after reconstruction included difficulties in holding back defaecation in 22 (39 per cent), more than one faecal accident per week in nine (16 per cent), increased frequency of defaecation in 51 (89 per cent), and social restrictions due to bowel symptoms in 35 (61 per cent). Enterocolitis occurred in 35 (47 per cent) of 72 patients. Supplementary enteral and/or parenteral nutrition was required by 51 (55 per cent) of 93 patients at any time during follow-up. Of 56 responders aged 2-20 years, true low BMI for age was found in 20 (36 per cent) and 13 (23 per cent) were short for age. Conclusion: Reconstruction for TCA was associated with persistent bowel symptoms, and enterocolitis remained common. Multidisciplinary follow-up, including continuity of care in adulthood, might improve care standards in patients with TCA.Peer reviewe

Ensemble prediction for nowcasting with a convection-permitting model—I: description of the system and the impact of radar-derived surface precipitation rates

A key strategy to improve the skill of quantitative predictions of precipitation, as well as hazardous weather such as severe thunderstorms and flash floods is to exploit the use of observations of convective activity (e.g. from radar). In this paper, a convection-permitting ensemble prediction system (EPS) aimed at addressing the problems of forecasting localized weather events with relatively short predictability time scale and based on a 1.5 km grid-length version of the Met Office Unified Model is presented. Particular attention is given to the impact of using predicted observations of radar-derived precipitation intensity in the ensemble transform Kalman filter (ETKF) used within the EPS. Our initial results based on the use of a 24-member ensemble of forecasts for two summer case studies show that the convective-scale EPS produces fairly reliable forecasts of temperature, horizontal winds and relative humidity at 1 h lead time, as evident from the inspection of rank histograms. On the other hand, the rank histograms seem also to show that the EPS generates too much spread for forecasts of (i) surface pressure and (ii) surface precipitation intensity. These may indicate that for (i) the value of surface pressure observation error standard deviation used to generate surface pressure rank histograms is too large and for (ii) may be the result of non-Gaussian precipitation observation errors. However, further investigations are needed to better understand these findings. Finally, the inclusion of predicted observations of precipitation from radar in the 24-member EPS considered in this paper does not seem to improve the 1-h lead time forecast skill

Simulations of the 2004 North American Monsoon: NAMAP2

The second phase of the North American Monsoon Experiment (NAME) Model Assessment Project (NAMAP2) was carried out to provide a coordinated set of simulations from global and regional models of the 2004 warm season across the North American monsoon domain. This project follows an earlier assessment, called NAMAP, that preceded the 2004 field season of the North American Monsoon Experiment. Six global and four regional models are all forced with prescribed, time-varying ocean surface temperatures. Metrics for model simulation of warm season precipitation processes developed in NAMAP are examined that pertain to the seasonal progression and diurnal cycle of precipitation, monsoon onset, surface turbulent fluxes, and simulation of the low-level jet circulation over the Gulf of California. Assessment of the metrics is shown to be limited by continuing uncertainties in spatially averaged observations, demonstrating that modeling and observational analysis capabilities need to be developed concurrently. Simulations of the core subregion (CORE) of monsoonal precipitation in global models have improved since NAMAP, despite the lack of a proper low-level jet circulation in these simulations. Some regional models run at higher resolution still exhibit the tendency observed in NAMAP to overestimate precipitation in the CORE subregion; this is shown to involve both convective and resolved components of the total precipitation. The variability of precipitation in the Arizona/New Mexico (AZNM) subregion is simulated much better by the regional models compared with the global models, illustrating the importance of transient circulation anomalies (prescribed as lateral boundary conditions) for simulating precipitation in the northern part of the monsoon domain. This suggests that seasonal predictability derivable from lower boundary conditions may be limited in the AZNM subregion.open131

The N-terminus of IpaB provides a potential anchor to the Shigella type III secretion system tip complex protein IpaD

The type III secretion system (T3SS) is an essential virulence factor for Shigella flexneri, providing a conduit through which host-altering effectors are injected directly into a host cell to promote uptake. The type III secretion apparatus (T3SA) is comprised of a basal body, external needle, and regulatory tip complex. The nascent needle is a polymer of MxiH capped by a pentamer of invasion plasmid antigen D (IpaD). Exposure to bile salts (e.g. deoxycholate) causes a conformational change in IpaD and promotes recruitment of IpaB to the needle tip. It has been proposed that IpaB senses contact with host cell membranes, recruiting IpaC and inducing full secretion of T3SS effectors. While the steps of T3SA maturation and their external triggers have been identified, details of specific protein interactions and mechanisms have remained difficult to study due to the hydrophobic nature of the IpaB and IpaC translocator proteins. Here we explored the ability for a series of soluble N-terminal IpaB peptides to interact with IpaD. We found that DOC is required for the interaction and that a region of IpaB between residues 11–27 is required for maximum binding, which was confirmed in vivo. Furthermore, intramolecular FRET measurements indicated that movement of the IpaD distal domain away from the protein core accompanied the binding of IpaB11-226. Together these new findings provide important new insight into the interactions and potential mechanisms that define the maturation of the Shigella T3SA needle tip complex and provide a foundation for further studies probing T3SS activation

Forskningsintegritet og åpen vitenskap i ph.d.undervisningen: Praktiske spørsmål og etisk refleksjon.

Academic presentation at the Virak conference 08. - 09.06.22, Trondheim, Norway

Care planning for consumers on community treatment orders: an integrative literature review

Background Case management is the established model for care provision in mental health and is delivered within current care philosophies of person-centred and recovery-oriented care. The fact that people with a mental illness may be forced to receive care and treatment in the community poses challenges for clinicians aiming to engage in approaches that promote shared decision-making and self-determination. This review sought to gain an in-depth understanding of stakeholders’ perspectives and experiences of care planning for consumers’ on CTOs. Methods An integrative review method allowed for inclusion of a broad range of studies from diverse empirical sources. Systematic searches were conducted across six databases. Following appraisal, findings from included papers were coded into groups and presented against a framework of case management. Results Forty-eight papers were included in the review. Empirical studies came from seven countries, with the majority reporting on qualitative methods. Many similarities were reported across studies. Positive gains from CTOs were usually associated with the nature of support received, highlighting the importance of the therapeutic relationship in care planning. Key gaps in care planning included a lack of connection between CTO, treatment and consumer goals and lack of implementation of focussed interventions. Conclusions Current case management processes could be better utilised for consumers on CTOs, with exploration of how this could be achieved warranted. Workers need to be sensitive to the ‘control and care’ dynamic in the care planning relationship, with person-centred approaches requiring core and advanced practitioner and communication skills, including empathy and trust

Modified Needle-Tip PcrV Proteins Reveal Distinct Phenotypes Relevant to the Control of Type III Secretion and Intoxication by Pseudomonas aeruginosa

The type III secretion system (T3SS) is employed to deliver effector proteins to the cytosol of eukaryotic hosts by multiple species of Gram-negative bacteria, including Pseudomonas aeruginosa. Translocation of effectors is dependent on the proteins encoded by the pcrGVHpopBD operon. These proteins form a T3S translocator complex, composed of a needle-tip complex (PcrV), translocons (PopB and PopD), and chaperones (PcrG and PcrH). PcrV mediates the folding and insertion of PopB/PopD in host plasmic membranes, where assembled translocons form a translocation channel. Assembly of this complex and delivery of effectors through this machinery is tightly controlled by PcrV, yet the multifunctional aspects of this molecule have not been defined. In addition, PcrV is a protective antigen for P. aeruginosa infection as is the ortholog, LcrV, for Yersinia. We constructed PcrV derivatives containing in-frame linker insertions and site-specific mutations. The expression of these derivatives was regulated by a T3S-specific promoter in a pcrV-null mutant of PA103. Nine derivatives disrupted the regulation of effector secretion and constitutively released an effector protein into growth medium. Three of these regulatory mutants, in which the linker was inserted in the N-terminal globular domain, were competent for the translocation of a cytotoxin, ExoU, into eukaryotic host cells. We also isolated strains expressing a delayed-toxicity phenotype, which secrete translocators slowly despite the normal level of effector secretion. Most of the cytotoxic translocation-competent strains retained the protective epitope of PcrV derivatives, and Mab166 was able to protect erythrocytes during infection with these strains. The use of defined PcrV derivatives possessing distinct phenotypes may lead to a better understanding of the functional aspects of T3 needle-tip proteins and the development of therapeutic agents or vaccines targeting T3SS-mediated intoxication