Large-Scale Agile Transformation: A Case Study of Transforming Business, Development and Operations

Today, product development organizations are adopting agile methods in units outside the software development unit, such as in sales, market, legal, operations working with the customer. This broader adoption of agile methods has been labeled large-scale agile transformation and is considered a particular type of organizational change, originating in the software development units. So far, there is little research-based advice on conducting such transformations. Aiming to contribute towards providing relevant research advice on large-scale agile transformation, we apply a research-based framework for evaluating organizational agility on a product development program in a maritime service provider organization. We found that doing a large-scale agile transformation involves many significant challenges, such as having a shared understanding of the problem, getting access to users, and getting commitment to change that needs to be done. In order to overcome such challenges, we discuss the need for a holistic and integrated approach to agile transformation involving all the units linked to software development.publishedVersio

Fecal Calprotectin Excretion in Preterm Infants during the Neonatal Period

Fecal calprotectin has been proposed as a non-invasive marker of intestinal inflammation in inflammatory bowel disease in adults and children. Fecal calprotectin levels have been reported to be much higher in both healthy full-term and preterm infants than in children and adults.To determine the time course of fecal calprotectin (f-calprotectin) excretion in preterm infants from birth until hospital discharge and to identify factors influencing f-calprotectin levels in the first weeks of life, including bacterial establishment in the gut.F-calprotectin was determined using an ELISA assay in 147 samples obtained prospectively from 47 preterm infants (gestational age, and birth-weight interquartiles 27–29 weeks, and 880–1320 g, respectively) at birth, and at 2-week intervals until hospital discharge. (p = 0.047).During the first weeks of life, the high f-calprotectin values observed in preterm infants could be linked to the gut bacterial establishment

Safety and efficacy of tenecteplase in patients with wake-up stroke assessed by non-contrast CT (TWIST): a multicentre, open-label, randomised controlled trial

Background: Current evidence supports the use of intravenous thrombolysis with alteplase in patients with wake-up stroke selected with MRI or perfusion imaging and is recommended in clinical guidelines. However, access to advanced imaging techniques is often scarce. We aimed to determine whether thrombolytic treatment with intravenous tenecteplase given within 4·5 h of awakening improves functional outcome in patients with ischaemic wake-up stroke selected using non-contrast CT. Methods: TWIST was an investigator-initiated, multicentre, open-label, randomised controlled trial with blinded endpoint assessment, conducted at 77 hospitals in ten countries. We included patients aged 18 years or older with acute ischaemic stroke symptoms upon awakening, limb weakness, a National Institutes of Health Stroke Scale (NIHSS) score of 3 or higher or aphasia, a non-contrast CT examination of the head, and the ability to receive tenecteplase within 4·5 h of awakening. Patients were randomly assigned (1:1) to either a single intravenous bolus of tenecteplase 0·25 mg per kg of bodyweight (maximum 25 mg) or control (no thrombolysis) using a central, web-based, computer-generated randomisation schedule. Trained research personnel, who conducted telephone interviews at 90 days (follow-up), were masked to treatment allocation. Clinical assessments were performed on day 1 (at baseline) and day 7 of hospital admission (or at discharge, whichever occurred first). The primary outcome was functional outcome assessed by the modified Rankin Scale (mRS) at 90 days and analysed using ordinal logistic regression in the intention-to-treat population. This trial is registered with EudraCT (2014–000096–80), ClinicalTrials.gov (NCT03181360), and ISRCTN (10601890). Findings: From June 12, 2017, to Sept 30, 2021, 578 of the required 600 patients were enrolled (288 randomly assigned to the tenecteplase group and 290 to the control group [intention-to-treat population]). The median age of participants was 73·7 years (IQR 65·9–81·1). 332 (57%) of 578 participants were male and 246 (43%) were female. Treatment with tenecteplase was not associated with better functional outcome, according to mRS score at 90 days (adjusted OR 1·18, 95% CI 0·88–1·58; p=0·27). Mortality at 90 days did not significantly differ between treatment groups (28 [10%] patients in the tenecteplase group and 23 [8%] in the control group; adjusted HR 1·29, 95% CI 0·74–2·26; p=0·37). Symptomatic intracranial haemorrhage occurred in six (2%) patients in the tenecteplase group versus three (1%) in the control group (adjusted OR 2·17, 95% CI 0·53–8·87; p=0·28), whereas any intracranial haemorrhage occurred in 33 (11%) versus 30 (10%) patients (adjusted OR 1·14, 0·67–1·94; p=0·64). Interpretation: In patients with wake-up stroke selected with non-contrast CT, treatment with tenecteplase was not associated with better functional outcome at 90 days. The number of symptomatic haemorrhages and any intracranial haemorrhages in both treatment groups was similar to findings from previous trials of wake-up stroke patients selected using advanced imaging. Current evidence does not support treatment with tenecteplase in patients selected with non-contrast CT. Funding: Norwegian Clinical Research Therapy in the Specialist Health Services Programme, the Swiss Heart Foundation, the British Heart Foundation, and the Norwegian National Association for Public Health

Oxidation Regulates the Inflammatory Properties of the Murine S100 Protein S100A8

The myeloid cell-derived calcium-binding murine protein, S100A8, is secreted to act as a chemotactic factor at picomolar concentrations, stimulating recruitment of myeloid cells to inflammatory sites, S100A8 may be exposed to oxygen metabolites, particularly hypochlorite, the major oxidant generated by activated neutrophils at inflammatory sites. Here we show that hypochlorite oxidizes the single Cys residue (Cys(41)) of S100A8. Electrospray mass spectrometry and SDS-polyacrylamide gel electrophoresis analysis indicated that low concentrations of hypochlorite (40 mu M) converted 70-80% of S100A8 to the disulfide-linked homodimer, The mass was 20,707 Da, 92 Da more than expected, indicating additional oxidation of susceptible amino acids (possibly methionine). Phorbol 12-myristate 13-acetate activation of differentiated HL-60 granulocytic cells generated an oxidative burst that was sufficient to efficiently oxidize exogenous S100A8 within 10 min, and results implicate involvement of the myeloperoxidase system. Moreover, disulfide-linked dimer was identified in lung lavage fluid of mice with endotoxin-induced pulmonary injury. S100A8 dimer was inactive in chemotaxis and failed to recruit leukocytes in vivo. Positive chemotactic activity of recombinant Ala(41)S100A8 indicated that Cys41 was not essential for function and suggested that covalent dimerization may structurally modify accessibility of the chemotactic hinge domain. Disulfide-dependent dimerization may be a physiologically significant regulatory mechanism controlling S100A8-provoked leukocyte recruitment

Sleep and lifestyle in young adult monozygotic twin pairs discordant for body mass index

Objectives: The causal nature of the sleep-obesity association is unclear. To control for potential confounding by genes and shared environment, we studied monozygotic twin pairs discordant for body mass index (BMI). First, we investigated sleep in relation to BMI. Second, we examined associations of objective and subjective sleep duration and sleep debt (objective or subjective sleep duration minus subjective sleep need) with eating behaviors and physical activity (PA). Design: Cross-sectional study. Setting: Finnish twins in everyday life circumstances. Participants: Seventy-four healthy young adult monozygotic twin pairs, of whom 36 were BMI-discordant (∆BMI ≥ 3 kg/m2). Measurements: Clinical measurements estimated BMI and body composition. Sleep, eating, and PA behaviors were measured by self-report and actigraphy. Results: Compared to co-twins with lower BMI, co-twins with higher BMI reported shorter sleep (P = .043), more snoring (P = .0093), and greater tiredness (P = .0013) and trended toward eveningness (P = .036). Actigraphy-measured sleep duration correlated highly within BMI-discordant twin pairs (r = 0.63, P = .004). Subjective sleep debt was consistently positively associated with disinhibited eating and binge eating, but not with BMI. Subjective and objective sleep debt had negative correlations with moderate-to-vigorous PA. Conclusions: Twins with higher BMI showed less favorable sleep characteristics than their co-twins with lower BMI. Subjective sleep debt is a potential target for intervention to reduce eating and PA behaviors that promote weight gain. Experimental studies could elucidate mechanisms underlying tiredness in individuals with higher BMI and investigate causal relationships between sleep debt, BMI, and lifestylePeer reviewe

Analysis of Cellular and Membrane Extracts of Human-leukocytes From Rheumatoid-arthritis Patients Using Two-dimensional Electrophoresis

Peripheral blood leukocytes from 30 patients with classic or definite rheumatoid arthritis (RA) and 18 healthy controls were separated into lymphocytes, monocytes and granulocytes and labelled with 35S-methionine. The integral membrane proteins with an amphiphilic nature were separated from hydrophilic proteins by use of the nonionic detergent Triton X-114. Both whole cells and membrane proteins were isotope labelled and separated by high resolution two-dimensional electrophoresis under denaturing conditions. Polypeptide spots were visualised by autoradiography. No consistent differences were found when leukocytes from RA patients were compared to the controls.info:eu-repo/semantics/publishe