Exploring the Problem-Finding and Problem-Solving Approach for Designing Organizations

An emerging problem-finding and problem-solving approach suggests that management's discovering problems to solve, opportunities to seize, and challenges to respond to, are vital to organizations. This paper explores the extent to which the problem-finding and problem-solving approach can provide a foundation for joining the capabilities, dynamic capabilities, and governance perspectives as a way to help scholars and practitioners to coherently design organizations from the perspective of design science. The problem-finding and problem-solving approach offers a unit of analysis and a set of behavioral assumptions that enable us to address open questions within the extant literature and to propose new questions in management research.

Spaceflight modulates gene expression in the whole blood of astronauts

Astronauts are exposed to a unique combination of stressors during spaceflight, which leads to alterations in their physiology and potentially increases their susceptibility to disease, including infectious diseases. To evaluate the potential impact of the spaceflight environment on the regulation of molecular pathways mediating cellular stress responses, we performed a first-of-its-kind pilot study to assess spaceflight-related gene-expression changes in the whole blood of astronauts. Using an array comprised of 234 well-characterized stress-response genes, we profiled transcriptomic changes in six astronauts (four men and two women) from blood preserved before and immediately following the spaceflight. Differentially regulated transcripts included those important for DNA repair, oxidative stress, and protein folding/degradation, including HSP90AB1, HSP27, GPX1, XRCC1, BAG-1, HHR23A, FAP48, and C-FOS. No gender-specific differences or relationship to number of missions flown was observed. This study provides a first assessment of transcriptomic changes occurring in the whole blood of astronauts in response to spaceflight

Studying Host-Pathogen Interactions In 3-D: Organotypic Models For Infectious Disease And Drug Development

Representative, reproducible and high-throughput models of human cells and tissues are critical for a meaningful evaluation of host-pathogen interactions and are an essential component of the research developmental pipeline. The most informative infection models - animals, organ explants and human trials - are not suited for extensive evaluation of pathogenesis mechanisms and screening of candidate drugs. At the other extreme, more cost effective and accessible infection models such as conventional cell culture and static co-culture may not capture physiological and three-dimensional aspects of tissue biology that are important in assessing pathogenesis, and effectiveness and cytotoxicity of therapeutics. Our lab has used innovative bioengineering technology to establish biologically meaningful 3-D models of human tissues that recapitulate many aspects of the differentiated structure and function of the parental tissue in vivo, and we have applied these models to study infectious disease. We have established a variety of different 3-D models that are currently being used in infection studies - including small intestine, colon, lung, placenta, bladder, periodontal ligament, and neuronal models. Published work from our lab has shown that our 3-D models respond to infection with bacterial and viral pathogens in ways that reflect the infection process in vivo. By virtue of their physiological relevance, 3-D cell cultures may also hold significant potential as models to provide insight into the neuropathogenesis of HIV infection. Furthermore, the experimental flexibility, reproducibility, cost-efficiency, and high throughput platform afforded by these 3-D models may have important implications for the design and development of drugs with which to effectively treat neurological complications of HIV infection

The association between long-term conditions and uptake of population-based screening for colorectal cancer: results from two English cohort studies

Introduction: Uptake of screening for colorectal cancer (CRC) can reduce mortality, and population-based screening is offered in England. To date, there is little evidence on the association between having a long-term condition (LTC) and CRC screening uptake. The objective of this study was to examine the association between having an LTC and uptake of CRC screening in England with the guaiac fecal occult blood test, with a particular focus on common mental disorders. Methods: The study was a preregistered secondary analysis of two cohorts: first, a linked data set between the regional Yorkshire Health Study (YHS) and the National Health Service National Bowel Cancer Screening Program (BCSP, years 2006–2014); second, the national English Longitudinal Study of Ageing (ELSA, years 2014–2015). Individuals eligible for BCSP screening who participated in either the YHS (7,142) or ELSA Wave 7 (4,099) were included. Study registration: ClinicalTrials.gov, number NCT02503969. Results: In both the cohorts, diabetes was associated with lower uptake (YHS odds ratio [OR] for non-uptake 1.35, 95% CI 1.03–1.78; ELSA 1.33, 1.03–1.72) and osteoarthritis was associated with increased uptake (YHS 0.75, 0.57–0.99; ELSA 0.76, 0.62–0.93). After controlling for broader determinants of health, there was no evidence of significantly different uptake for individuals with common mental disorders. Conclusion: Two large independent cohorts provided evidence that uptake of CRC screening is lower among individuals with diabetes and higher among individuals with osteoarthritis. Further work should compare barriers and facilitators to screening among individuals with either of these conditions. This study also demonstrates the benefits of data linkage for improving clinical decision-making

Low Fluid Shear Culture of Staphylococcus Aureus Represses hfq Expression and Induces an Attachment-Independent Biofilm Phenotype

Background: The opportunistic pathogen, Staphylococcus aureus, experiences fluctuations in fluid shear during infection and colonization of a human host. Colonization frequently occurs at mucus membrane sites such as in the gastrointestinal tract where the bacterium may experience low levels of fluid shear. The response of S. aureus to low fluid shear remains unclear. Methods: S. aureus was cultured to stationary phase using Rotating-Wall Vessel (RWV) bioreactors which produce a physiologically relevant low fluid shear environment. The bacterial aggregates that developed in the RWV were evaluated by electron microscopy as well as for antibiotic resistance and other virulence-associated stressors. Genetic expression profiles for the low-shear cultured S. aureus were determined by microarray analysis and quantitative real-time PCR. Results: Planktonic S. aureus cultures in the low-shear environment formed aggregates completely encased in high amounts of extracellular polymeric substances. In addition, these aggregates demonstrated increased antibiotic resistance indicating attachment-independent biofilm formation. Carotenoid production in the low-shear cultured S. aureus was significantly decreased, and these cultures displayed an increased susceptibility to oxidative stress and killing by whole blood. The hfq gene, associated with low-shear growth in Gram negative organisms, was also found to be down-regulated in S. aureus. Conclusions: Collectively, this data suggests that S. aureus decreases virulence characteristics in favor of a biofilm-dwelling colonization phenotype in response to a low fluid shear environment. Furthermore, the identification of an Hfq response to low-shear culture in S. aureus, in addition to the previously reported responses in Gram negative organisms, strongly suggests an evolutionarily conserved response to mechanical stimuli among structurally diverse prokaryotes

Potholes and molehills: bias in the diagnostic performance of diffusion-tensor imaging in concussion

PURPOSE: To investigate the extent of bias in a clinical study involving pothole analysis of diffusion-tensor imaging (DTI) data used to quantify white matter lesion load in diseases with a heterogeneous spatial distribution of pathologic findings, such as mild traumatic brain injury (TBI), and create a mathematical model of the bias. MATERIALS AND METHODS: Use of the same reference population to define normal findings and make comparisons with a patient group introduces bias, which potentially inflates reported diagnostic performance. In this institutional review board-approved prospective observational cohort study, DTI data were obtained in 20 patients admitted to the emergency department with mild TBI and in 16 control subjects. Potholes and molehills were defined as clusters of voxels with fractional anisotropy values more than 2 standard deviations below and above the mean of the corresponding voxels in the reference population, respectively. The number and volume of potholes and molehills in the two groups were compared by using a Mann-Whitney U test. RESULTS: Standard analysis showed significantly more potholes in mild TBI than in the control group (102.5 +/- 34.3 vs 50.6 +/- 28.9, P \u3c .001). Repeat analysis by using leave-one-out cross-validation decreased the apparent difference in potholes between groups (mild TBI group, 102.5 +/- 34.3; control group, 93.4 +/- 27.2; P = .369). It was demonstrated that even with 100 subjects, this bias can decrease the voxelwise false-positive rate by more than 30% in the control group. CONCLUSION: The pothole approach to neuroimaging data may introduce bias, which can be minimized by independent training and test groups or cross-validation methods. This bias is sufficient to call into question the previously reported diagnostic performance of DTI for mild TBI

Patient experience of CT colonography and colonoscopy after fecal occult blood test in a national screening programme

OBJECTIVE: To investigate patient experience of CT colonography (CTC) and colonoscopy in a national screening programme. METHODS: Retrospective analysis of patient experience postal questionnaires. We included screenees from a fecal occult blood test (FOBt) based screening programme, where CTC was performed when colonoscopy was incomplete or deemed unsuitable. We analyzed questionnaire responses concerning communication of test risks, test-related discomfort and post-test pain, as well as complications. CTC and colonoscopy responses were compared using multilevel logistic regression. RESULTS: Of 67,114 subjects identified, 52,805 (79 %) responded. Understanding of test risks was lower for CTC (1712/1970 = 86.9 %) than colonoscopy (48783/50975 = 95.7 %, p < 0.0001). Overall, a slightly greater proportion of screenees found CTC unexpectedly uncomfortable (506/1970 = 25.7 %) than colonoscopy (10,705/50,975 = 21.0 %, p < 0.0001). CTC was tolerated well as a completion procedure for failed colonoscopy (unexpected discomfort; CTC = 26.3 %: colonoscopy = 57.0 %, p < 0.001). Post-procedural pain was equally common (CTC: 288/1970,14.6 %, colonoscopy: 7544/50,975,14.8 %; p = 0.55). Adverse event rates were similar in both groups (CTC: 20/2947 = 1.2 %; colonoscopy: 683/64,312 = 1.1 %), but generally less serious with CTC. CONCLUSIONS: Even though CTC was reserved for individuals either unsuitable for or unable to complete colonoscopy, we found only small differences in test-related discomfort. CTC was well tolerated as a completion procedure and was extremely safe. CTC can be delivered across a national screening programme with high patient satisfaction. KEY POINTS: • High patient satisfaction at CTC is deliverable across a national screening programme. • Patients who cannot tolerate screening colonoscopy are likely to find CTC acceptable. • CTC is extremely safe; complications are rare and almost never serious. • Patients may require more detailed information regarding the expected discomfort of CTC

A CAT with caveats: is the Consensual Assessment Technique a reliable measure of graphic design creativity?

The Consensual Assessment Technique (CAT) is considered one of the gold standards for creativity assessment, and graphic design, arguably, is the most ubiquitous domain within the creative industries. For the first time, this study tests two tasks to measure graphic design creativity, and by extension, the reliability of the CAT as a measure of graphic design creativity. Initial research suggested the level of consensus amongst judges (often referred to as inter-rater reliability) was too low to be reliable, and may be unduly influenced by a judge’s preference for technical execution. In this study, 16 professional graphic designers were randomly assigned instructions to discount technical execution from creativity ratings, or given instruction that gave no stipulation, for 60 artworks. Inter-rater reliability scores were acceptable for each task and experimental condition, but were higher for judges that received instructions to discount technical execution. These and other results are discussed, and the argument presented that, for future CAT studies in this domain, specific instructions to discount technical execution offers a more reliable measure of graphic design creativity

The representation of scientific research in the national curriculum and secondary school pupils’ perceptions of research, its function, usefulness and value to their lives

Young people’s views on what research is, how it is conducted and whether it is important, influences the decisions they make about their further studies and career choices. In this paper we report the analysis of questionnaire data with a particular focus on pupil perceptions of research in the sciences and of the scientific method. The questionnaire was a 25-item Likert Scale (1-5) distributed to seven collaborating schools. We received 2634 returns from pupils across key stages 3, 4 and 5. We also asked teachers to complete the questionnaire in order to explore how they thought their pupils would respond. We received 54 teacher responses. Statistically significant differences in the responses were identified through a chi-square test on SPSS. As what is being taught influences secondary pupil views on research we also consider how the term ‘research’ appears in the national curriculum for England and Wales and the three main English exam boards. The main theoretical construct that informs our analysis of the questionnaire data and the national curriculum is Angela Brew’s 4-tier descriptor of perceptions of research (domino, trading, layer, journey). We use this framework in order to map what, when and how research is presented to school pupils in England and Wales. We also use this framework in order to highlight and discuss certain pupil views that emerged from the questionnaire data and which indicate areas where curriculum and pedagogy intervention may be necessary: pupils seem less confident in their understanding of research as involving the identification of a research question; and, they often see research as a means to confirm one’s own opinion. They do however understand research as involving the generation of new knowledge and the collection of new data, such as interviews and questionnaires as well as laboratory work, field trips and library searches and they appear relatively confident in their statements about their ability to do research, their school experiences of research and the importance of research in their future career choice