Revisiting Caspase-11 Function in Host Defense

Proinflammatory caspases play important roles in innate immunity. Much attention has focused on caspase-1, which acts to eliminate pathogens by obliterating their replicative niches as well as alerting the host to their presence. Now, emerging data have shed light on the lesser-studied proinflammatory caspase-11 in the combat between host and pathogens. Using the new tools available, researchers are further elucidating the mechanisms by which caspase-11 contributes to host defense. Here, we review the emerging understanding of caspase-11 functions and the mechanisms of activation and discuss the implications for human disease

"I Would Just Want to Know What It's Being Used for and Who's Using It": Barriers to the Adoption of SmartSurveys

Objective: Smartphones stand to transform the manner healthcare services gather patient experience information. However, there is still limited guidance on the context and circumstances which are appropriate for patients to use their smartphones to share their service experiences. The aim of this thesis is to understand the factors which act as barriers to adopting and using smartphone-based patient experience feedback (SmartSurveys). Methods: Participants were asked to envision the use of MetricWire®’s mobile application to collect patient experience data. In-depth semi-structured interviews, guided with questionnaires, were conducted with smartphone owners (n=24) in order to capture their experiences, perceptions and attitudes with using SmartSurveys. Individuals were also categorized based on their technical knowledge and motivation to protect their privacy. With consent, interviews were audio-recorded, transcribed verbatim and thematically analyzed using QSR International’s NVivo 11. Results: Interviews and questionnaires revealed that there were few concerns related to risks or usability of SmartSurveys application. However, three major themes regarding privacy emerged from the interviews. With respect to information disclosure, participants were concerned about the recipients of information, the reliability of the communication structure, and risk of losing of information agency. Conclusion: The use and adoption of SmartSurveys is highly contextual and nuanced. Participants stressed the need to disclose the purpose of data collection as well as how information is managed and by who. Healthcare providers and mHealth application developers should endeavour to inform end-users of the manner data is handled through their mobile application. Furthermore, providing the rationale for patient experience feedback will help patients comprehend how their opinions drive changes in service quality

Description, Reliability and Validation of a Novel Ground-Reaction-Force-Triggered Protocol for Simulation of Tripping Perturbations During Gait

Tripping is a common cause of falls across different age populations particularly in older adults. Concerns regarding the validity of simulated-fall research protocols reside in the current literature. The purpose of this study was to develop a novel treadmill-based tripping protocol that allowed researchers to deliver unanticipated tripping perturbations during walking with a high level of timing precision. The protocol utilized a side-by-side split-belt treadmill instrumented with force platforms. Treadmill belt acceleration profiles (two levels of perturbation severity: small perturbation vs large perturbation) were delivered unilaterally when the tripped leg bore 20% of the body weight during early stance. Peak trunk flexion angle during trip recovery was the primary variable used to represent the fall recovery response and likelihood of falls. Test-retest reliability of the fall responses was examined in a group of 10 young participants; validity was examined through differentiation of the fall responses between young and older adults (age 20.9 vs. 57.1 years, n=10 per group). We found that the perturbations were precisely delivered during the early stance phase (10-45 ms after initial contact). Moreover, this protocol elicited excellent reliability of recovery responses during both perturbation severities (ICC=0.944 and 0.911). Older adults exhibited significantly greater peak trunk flexion angle than young adults (p=0.035), indicating the current protocol was valid in differentiating individuals with different levels of fall risks. This novel protocol addressed some of the issues of previous simulated-fall protocols and may be useful as a tool for future fall research and clinical intervention

A Structured Training Course for Non-structured Design Course

In an engineering design course, teaching assistant plays a critical role to in supporting the teaching and the learning process for the participants – students and instructors.  The instructors would invite or hire a postgraduate student to be the teaching assistant.  In most cases, the postgraduate student does not has any teaching experience. This work proposed and implemented a quick start training course for the teaching assistant specifically for an engineering design course, by adopting concept-design-implementation-operation

Massive Spontaneous Haemothorax after Rivaroxaban Therapy for Acute Pulmonary Embolism

Spontaneous haemothorax complicating the treatment of pulmonary embolism is rare and potentially fatal. We describe a patient with pulmonary embolism and severe pleuritic pain who developed a life-threatening haemothorax 10 days later while on rivaroxaban therapy. This case highlights the fact that severe pleuritic pain associated with pulmonary embolism may indicate subclinical infarction of tissue near the visceral pleura with an increased risk of pleural effusion and the subsequent development of a haemothorax. It is important to recognise such danger signs warranting closer attention, especially since the increased use of direct oral anticoagulants has facilitated ambulatory care and this complication may manifest in the outpatient setting

High-resolution global climate simulations: representation of cities

Ensemble runs of high-resolution (~10 km; N1280) global climate simulations (2005–2010) with the Met Office HadGEM3 model are analysed over large urban areas in the south-east UK (London) and south-east China (Shanghai, Hangzhou, Nanjing region). With a focus on urban areas, we compare meteorological observations to study the response of modelled surface heat fluxes and screen-level temperatures to urbanisation. HadGEM3 has a simple urban slab scheme with prescribed, globally fixed bulk parameters. Misrepresenting the magnitude or the extent of urban land cover can result in land-surface model bias. As urban land-cover fractions are severely under-estimated in China, this impacts surface heat-flux partitioning and quintessential features such as the urban heat island. Combined with the neglect of anthropogenic heat emissions, this can result in misrepresentation of heat-wave intensities (or cold spells) in cities. The model performance in urban areas could be improved if bulk parameters are modelled instead of prescribed, but this necessitates the availability of local morphology data on a global level. Improving land-cover information and providing more flexible ways to account for differences between cities (e.g. anthropogenic emission; morphology) is essential for realistic future projections of city climates, especially if model output is intended for urban climate services

A Phase I Study of Dasatinib with Concurrent Chemoradiation for Stage III Non-Small Cell Lung Cancer

Objectives: Src family kinases (SFKs) are expressed in non-small cell lung cancer (NSCLC) and may be involved in tumor growth and metastases. Inhibition of SFK may also enhance radiation. The purpose of this study was to evaluate if a maximum dose of 100 mg of dasatinib could be safely administered with concurrent chemoradiation and then continued as maintenance for patients with newly diagnosed stage III NSCLC. Methods: Patients with stage III locally advanced NSCLC received paclitaxel, 50 mg/m2/week, with carboplatin area under the curve (AUC) = 2, weekly for 7 weeks, and concurrent radiotherapy, 64.8 Gy. Three dose levels of dasatinib 50, 70, and 100 mg/day were planned. Results: 11 patients with locally advanced NSCLC were entered. At the 70 mg dose level 1 patient had grade 5 pneumonitis not responsive to therapy, and one patient had reversible grade 3 pneumonitis and grade 3 pericardial effusion. Due to these toxicities the Brown University Oncology Group Data Safety Monitoring Board terminated the study. Conclusion: Dasatinib could not be safely combined with concurrent chemoradiation for stage 3 lung cancer due to pneumonitis