Transparency on scientific instruments

Scientists and commercial scientific instrument makers have a shared incentive against discloseing an instrument maker's contributions to research. Stricter rules to encourage reporting of such collaboration would help to improve transparency and reproducibility

The search environment is not (always) benign: reassessing the risks of organizational search

March and Simon’s (1958: 50) assumption that search happens within a “benign environment” has become taken-for-granted in organizational studies. The implications of making this assumption are not widely theorized, investigated, or even discussed, and yet, it often appears to have been unwittingly imported into explanations of organizational learning. March and Simon acknowledged that this assumption was not realistic—our work builds on theirs by investigating the origins and consequences of a non-benign search environment. We draw on in-depth qualitative research at a Fortune 500 mining firm to show how perceptions of social risk problematize the assumption of a benign search environment. Causal links are drawn between role equivalence, performance comparisons, and rivalry for social status to explain how social risk is generated and why it can lead actors to view the intraorganizational search environment as non-benign. These perceptions help create what we describe as a “paradox of local equivalence” that leads actors to search for nonlocal solutions. Our causal logic provides a new way of understanding the phenomena of nonlocal search; complements explanations of nonlocal search founded on myopia in organizational learning; and shows how the micro-foundations of existing search models can be adapted to better explain organizational learning. In doing so, this study contributes to recent efforts to improve behavioral explanations of search and learning by bringing the notion of intraorganizational conflict back to center stage in this important area of organizational theory

Unlocking community capabilities for improving maternal and newborn health: participatory action research to improve birth preparedness, health facility access, and newborn care in rural Uganda

Background: Community capacities and resources must be harnessed to complement supply side initiatives addressing high maternal and neonatal mortality rates in Uganda. This paper reflects on gains, challenges and lessons learnt from working with communities to improve maternal and newborn health in rural Uganda. Methods: A participatory action research project was supported from 2012 to 2015 in three eastern districts. This project involved working with households, saving groups, sub county and district leaders, transporters and village health teams in diagnosing causes of maternal and neonatal mortality and morbidity, developing action plans to address these issues, taking action and learning from action in a cyclical manner. This paper draws from project experience and documentation, as well as thematic analysis of 20 interviews with community and district stakeholders and 12 focus group discussions with women who had recently delivered and men whose wives had recently delivered. Results: Women and men reported increased awareness about birth preparedness, improved newborn care practices and more male involvement in maternal and newborn health. However, additional direct communication strategies were required to reach more men beyond the minority who attended community dialogues and home visits. Saving groups and other saving modalities were strengthened, with money saved used to meet transport costs, purchase other items needed for birth and other routine household needs. However saving groups required significant support to improve income generation, management and trust among members. Linkages between savings groups and transport providers improved women’s access to health facilities at reduced cost. Although village health teams were a key resource for providing information, their efforts were constrained by low levels of education, inadequate financial compensation and transportation challenges. Ensuring that the village health teams and savings groups functioned required regular supervision, review meetings and payment for supervisors to visit. Conclusions: This participatory program, which focused on building the capacity of community stakeholders, was able to improve local awareness of maternal and newborn health practices and instigate local action to improve access to healthcare. Collaborative problem solving among diverse stakeholders, continuous support and a participatory approach that allowed flexibility were essential project characteristics that enabled overcoming of challenges faced

Age of the Association between Helicobacter pylori and Man

When modern humans left Africa ca. 60,000 years ago (60 kya), they were already infected with Helicobacter pylori, and these bacteria have subsequently diversified in parallel with their human hosts. But how long were humans infected by H. pylori prior to the out-of-Africa event? Did this co-evolution predate the emergence of modern humans, spanning the species divide? To answer these questions, we investigated the diversity of H. pylori in Africa, where both humans and H. pylori originated. Three distinct H. pylori populations are native to Africa: hpNEAfrica in Afro-Asiatic and Nilo-Saharan speakers, hpAfrica1 in Niger-Congo speakers and hpAfrica2 in South Africa. Rather than representing a sustained co-evolution over millions of years, we find that the coalescent for all H. pylori plus its closest relative H. acinonychis dates to 88–116 kya. At that time the phylogeny split into two primary super-lineages, one of which is associated with the former hunter-gatherers in southern Africa known as the San. H. acinonychis, which infects large felines, resulted from a later host jump from the San, 43–56 kya. These dating estimates, together with striking phylogenetic and quantitative human-bacterial similarities show that H. pylori is approximately as old as are anatomically modern humans. They also suggest that H. pylori may have been acquired via a single host jump from an unknown, non-human host. We also find evidence for a second Out of Africa migration in the last 52,000 years, because hpEurope is a hybrid population between hpAsia2 and hpNEAfrica, the latter of which arose in northeast Africa 36–52 kya, after the Out of Africa migrations around 60 kya

Gene therapy for monogenic liver diseases: clinical successes, current challenges and future prospects

Over the last decade, pioneering liver-directed gene therapy trials for haemophilia B have achieved sustained clinical improvement after a single systemic injection of adeno-associated virus (AAV) derived vectors encoding the human factor IX cDNA. These trials demonstrate the potential of AAV technology to provide long-lasting clinical benefit in the treatment of monogenic liver disorders. Indeed, with more than ten ongoing or planned clinical trials for haemophilia A and B and dozens of trials planned for other inherited genetic/metabolic liver diseases, clinical translation is expanding rapidly. Gene therapy is likely to become an option for routine care of a subset of severe inherited genetic/metabolic liver diseases in the relatively near term. In this review, we aim to summarise the milestones in the development of gene therapy, present the different vector tools and their clinical applications for liver-directed gene therapy. AAV-derived vectors are emerging as the leading candidates for clinical translation of gene delivery to the liver. Therefore, we focus on clinical applications of AAV vectors in providing the most recent update on clinical outcomes of completed and ongoing gene therapy trials and comment on the current challenges that the field is facing for large-scale clinical translation. There is clearly an urgent need for more efficient therapies in many severe monogenic liver disorders, which will require careful risk-benefit analysis for each indication, especially in paediatrics

ELECtric Tibial nerve stimulation to Reduce Incontinence in Care homes: protocol for the ELECTRIC randomised trial

Background Urinary incontinence (UI) is highly prevalent in nursing and residential care homes (CH) and profoundly impacts on residents’ dignity and quality of life. Care homes predominantly use absorbent pads to contain UI rather than actively treat the condition. Transcutaneous posterior tibial nerve stimulation (TPTNS) is a non-invasive, safe, low-cost intervention with demonstrated effectiveness for reducing UI in adults. However, the effectiveness of TPTNS to treat UI in older adults living in care homes is not known. The ELECTRIC Trial aims to establish if a programme of TPTNS is a clinically effective treatment for UI in care home residents and investigate the associated costs and consequences. Methods This is a pragmatic, multicentre, placebo controlled randomised parallel group trial comparing effectiveness of TPTNS (target n=250) with sham stimulation (target n=250) in reducing volume of UI in CH residents. CH residents (men and women) with self- or staff- reported UI of more than once per week are eligible to take part, including those with cognitive impairment. Outcomes will be measured at 6, 12 and 18 weeks post randomisation using the following measures: 24-hour pad weight tests (PWT), post void residual urine (bladder scans), Patient Perception of Bladder Condition (PPBC), Minnesota Toileting Skills Questionnaire (MTSQ) and Dementia Quality of Life (DEMQOL). Economic evaluation based on a bespoke Resource Use Questionnaire will assess the costs of providing a programme of TPTNS. A concurrent process evaluation will investigate fidelity to the intervention and influencing factors and qualitative interviews will explore the experiences of TPTNS from the perspective of CH residents, family members, CH staff and managers. Discussion TPTNS is a non-invasive intervention that has demonstrated effectiveness in reducing UI in adults. The ELECTRIC Trial will involve CH staff delivering TPTNS to residents and establish whether TPTNS is more effective than sham stimulation for reducing the volume of UI in CH residents. Should TPTNS be shown to be an effective and acceptable treatment for UI in older adults in CHs, it will provide a safe, low-cost and dignified alternative to the current standard approach of containment and medication. Trial registration Clinical Trials.gov. NCT03248362. Registered on 14/08/2017. https://clinicaltrials.gov/ ISRCTN, ISRCTN 98415244. Registered on 25/04/2018. https://www.isrctn.com

Design as an isolating mechanism for capturing value from innovation: from cloaks and traps to sabotage

How firms capture value from their innovations has long interested strategy and innovation scholars. Prior work has focused on legal, economic, and social mechanisms for isolating knowledge from imitation as crucial to this process. Our contribution extends this stream of research by identifying how design choices about the way knowledge is manifested (e.g., into routines, blueprints, prototypes, or products) can inhibit a counterparty’s ability to imitate knowledge relating to a focal innovation. We derive six theoretically distinct types of knowledge manifestation that can be used for these ends, consider their impacts on the awareness, motivation, and capability of a counterparty seeking to imitate the focal knowledge, and organize them into a novel two-dimensional conceptual framework for comparison. By doing so, we add design mechanisms to the strategic toolbox of isolating mechanisms available for capturing value from innovation. This addition opens up a new channel through which organizational choice endogenously shapes appropriability regimes and introduces knowledge manifestations as an important unit of analysis for understanding innovation strategy

Delivery Model Innovation: Insights From Infrastructure Projects

This special issue seeks to bring together contributions of a nascent community of scholars studying infrastructure delivery models; what they are, how they are created, and how they change over time and across institutional fields. This area of research is crucial to advancing the field of project management and, with its links to neighboring fields such as innovation, organizational theory, and strategic management, is a fertile ground for developing new insights and knowledge. Before we introduce the articles that make up the special issue, we describe the policy environment and drivers for innovation in infrastructure delivery models, situate infrastructure delivery models within project management scholarship, and provide some conceptual scaffolding for considering the nature of innovation in delivery models. We then turn to a discussion of how each article in the special issue advances our knowledge of delivery models and project management. Drawing inspiration from the articles, we conclude by sketching out the building blocks and core conceptual components of a delivery model, and laying the foundations for a more nuanced comparison of existing, emerging, and novel delivery models over time and across institutional fields

Insulin like growth factor receptor 1 (IGF-1R) and radiotherapy resistance in laryngeal squamous cell cancer (LSCC)

Salvage surgery is the only option for radiotherapy failure LSCC, but is associated with high morbidity. There is a need to identify biomarkers of radioresistance, to inform treatment decisions

Radioresistant laryngeal cancers upregulate type 1 IGF receptor and exhibit increased cellular dependence on IGF and EGF signalling

Objectives Patients failing radiotherapy for laryngeal squamous cell carcinoma (LSCC) often require salvage total laryngectomy which has major functional consequences, highlighting a need for biomarkers of radiotherapy resistance. In other tumour types, radioresistance has been linked to epidermal growth factor receptor (EGFR) and type 1 insulin‐like growth factor receptor (IGF‐1R). Here, we evaluated IGF‐1R and EGFR as predictors and mediators of LSCC radioresistance. Design We compared IGF‐1R and EGFR immunohistochemical scores in LSCC patients achieving long‐term remission post‐radiotherapy (n=23), patients treated with primary laryngectomy (n=22) or salvage laryngectomy following radiotherapy recurrence (n=18). To model radioresistanceandnbsp;in vitro, two LSCC cell lines underwent clinically‐relevant irradiation to 55 Gy in 2.75 Gy fractions. Results IGF‐1R expression was higher in pre‐treatment biopsies of radiotherapy‐failures compared with those in long‐term remission, and was upregulated post‐radiotherapy. Patients undergoing primary laryngectomy had more advanced T/N stage and greater tumour IGF‐1R content than those achieving long‐term remission. Pre‐treatment EGFR did not associate with radiotherapy outcomes but showed a trend to upregulation post‐irradiation.andnbsp;In vitro, radiosensitivity was enhanced by inhibition of EGFR but not IGF. Repeated irradiation upregulated IGF‐1R in BICR18 and SQ20B cells and EGFR in SQ20B, and enhanced SQ20B radioresistance. Repeatedly‐irradiated SQ20B_55 cells were not radiosensitised by inhibition of IGF and/or EGFR, but IGF‐1R:EGFR co‐inhibition suppressed baseline cell survival more effectively than blockade of either pathway alone, and more effectively than in parental cells. Conclusions Radiation upregulates IGF‐1R and may enhance IGF/EGFR dependence, suggesting that IGF/EGFR blockade may have activity in LSCCs that recur post‐radiotherapy.</p