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Isopenicillin N synthase (IPNS) catalyzes formation of the β-lactam and thiazolidine rings of isopenicillin N from its linear tripeptide l-δ-(α-aminoadipoyl)-l-cysteinyl-d-valine (ACV) substrate in an iron- and dioxygen (O

Complementary XFEL methods reveal O2 reaction intermediates and global protein dynamics during Isopenicillin N synthase catalysis., Isopenicillin N synthase (IPNS) catalyzes the unique reaction of l-δ-(α-aminoadipoyl)-l-cysteinyl-d-valine (ACV) with dioxygen giving isopenicillin N (IPN), the precursor of all natural penicillins and cephalosporins. X-ray free-electron laser studies including time-resolved crystallography and emission spectroscopy reveal how reaction of IPNS:Fe(II):ACV with dioxygen to yield an Fe(III) superoxide causes differences in active site volume and unexpected conformational changes that propagate to structurally remote regions. Combined with solution studies, the results reveal the importance of protein dynamics in regulating intermediate conformations during conversion of ACV to IPN. The results have implications for catalysis by multiple IPNS-related oxygenases, including those involved in the human hypoxic response, and highlight the power of serial femtosecond crystallography to provide insight into long-range enzyme dynamics during reactions presently impossible for nonprotein catalysts.

Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.

Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent. Publisher PDF

© 2020 The Author(s) Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.

Introduction This study explored caregivers' perceptions of how children with sensory processing disorders participate in community outings, strategies to support successful outings and if multi-sensory environments mitigate participation barriers. Methods Seven mothers and two grandmothers of children with sensory challenges participated in focus groups. Following focus groups, participants took part in a workshop on sensory processing disorders and behaviour management strategies and experienced a multi-sensory environment. To ensure trustworthiness, researchers individually coded data, corroborated to develop categories, then recoded until reaching consensus. Three participants reviewed conclusions that the researchers derived from audit trails and focus groups to verify credibility. Results When asked about their child's participation challenges, participants identified sensory processing difficulties, environmental triggers, specific locations visited and how caregivers managed participation challenges. Participants relied on preparation, planning and consistency. Participants had varying exposure to multi-sensory environments and some were uncertain how they supported participation. Conclusion Participants reported positive outcomes resulting from proactive planning to manage behaviour, anticipating environmental triggers and challenges posed by locations they visited, and that their child's challenges and their own abilities to meet them evolved over time. They speculated multi-sensory environments could support participation when they were well-designed.

Background and Purpose: This process improvement project was conducted to improve the emergency department (ED) door to needle time (DTN) for intravenous (IV) alteplase times for stroke patients arriving both by local emergency medical services (EMS) and by private owned vehicles (POV). Ultimate goal was to meet American Heart Association (AHA) and American Stroke Association (ASA) Get With the Guidelines (GWTG) Target Stroke Honor Roll Elite Plus. Methods: A two-year nurse led multidisciplinary collaborative process improvement (PI) plan was designed to include local EMS, emergency department (ED) and radiology personnel. The patient workflow was streamlined allowing EMS Stroke Alert patients, as well as patients arriving in the ED in POV, with stroke symptoms, to go straight to the radiology department for immediate computed tomography (CT) scans. The PI plan was based on Six Sigma methodology and included a 90-day pilot data analysis led by Registered Nurse (RN) Directors, Neurologists, ED Physicians, Medical Imaging, Quality Improvement, and RN Stroke Coordinator. As part of the project design a recognition award was given to team mates with the best patient outcomes. The “Golden Lobe” award was awarded to EMS and ED team members for their significant improvement in stroke patient outcomes. Results: January 2016 to July 2018, a total of 79 were included. Average DTN times for EMS patients decreased 5.4 minutes, from 40.7 to 35.3. Average DTN times for POV patients decreased 17.8 minutes, from 51.8 to 34. Additional improvements were noted on transferring large vessel occlusion, drip and ship cases 81 minutes faster, from 196 to 115. Complication rates associated with IV alteplase decreased by 2.9% and stroke mimic rate reduced by 6.1%. Conclusion: In conclusion, nurse led multi-disciplinary collaborative PI project was successful in reducing DTN time for patients exhibiting stroke symptoms regardless if they arrived EMS or POV. Not only did the ED team improve DTN time, they also decreased IV alteplase complication rates, stroke mimic rates and stroke interventional transfer times.

While previous research has assessed the validity of the OptoGait system to the GAITRite walkway and an instrumented treadmill, no research to date has assessed this system against a traditional three-dimensional motion analysis system. Additionally, previous research has shown that the OptoGait system shows systematic bias when compared to other systems due to the configuration of the system's hardware. This study examined the agreement between the spatiotemporal gait parameters calculated from the OptoGait system and a three-dimensional motion capture (14 camera Vicon motion capture system and 2 AMTI force plates) in healthy adults. Additionally, a range of filter settings for the OptoGait were examined to determine if it was possible to eliminate any systematic bias between the OptoGait and the three-dimensional motion analysis system. Agreement between the systems was examined using 95% limits of agreement by Bland and Altman and the intraclass correlation coefficient. A repeated measure ANOVA was used to detect any systematic differences between the systems. Findings confirm the validity of the OptoGait system for the evaluation of spatiotemporal gait parameters in healthy adults. Furthermore, recommendations on filter settings which eliminate the systematic bias between the OptoGait and the three-dimensional motion analysis system are provided.

Objectives To examine the types of choices available to patients in the English NHS when being referred for acute hospital care in the light of the divergence of patient choice policy in the four countries of the UK. Methods Case studies of eight local health economies in England, Scotland, Northern Ireland and Wales (two in each country); 125 semi-structured interviews with staff in acute services providers, purchasers and general practitioners (GPs). Results GPs and providers in England both had a clear understanding of the choice of provider policy and the right of patients to choose a provider. Other referral choices potentially available to patients in all four countries were date and time of appointment, site and specialist. In practice, the availability of these choices differed between and within countries and was shaped by factors beyond choice policy, such as the number of providers in an area. There were similarities between the four countries in the way choices were offered to patients, namely lack of clarity about the options available, limited discussion of choices between referrers and patients, and tension between offering choice and managing waiting lists. Conclusions There are challenges in implementing pro-choice policy in health care systems where it has not traditionally existed. Differences between England and the other countries of the UK were limited in the way choice was offered to patients. A cultural shift is needed to ensure that patients are fully informed by GPs of the choices available to them.

Plantar pressure assessment is commonly used as a tool to assess the efficacy of insoles in reducing the risk of mechanical trauma to the plantar soft tissue during walking gait. The slow rebound (SR) Poron insole is intended to provide a custom fit to the foot and is believed to be superior in increasing the contact area and consequently reducing the contact pressure compared to a normal Poron (NP) insole. The aim of this study was to compare the effectiveness of SR or NP versus an ethylene vinyl acetate (EV) insole in increasing the contact area (CA), and in reducing the contact pressure (CP) at different regions of the foot during walking. Plantar pressure data was collected from nine healthy individuals during walking using commercially available in-shoe plantar pressure sensors. Although, the NP insole significantly increased the CA and decreased the CP on the entire foot compared to the EV, there was no significant change in CP or CA at any region of the foot in any of the tested insoles. CP showed a positive significant correlation with CA at heel, hallux and heel center in all three insoles. The expected significant negative correlation between regional CA and CP was not observed.

An evaluation of an electronic learning aid, the Texas Instruments “Speak Spell” is described. This machine is marketed as a spelling aid. Spelling performance was monitored for two groups of normal 12-year-old girls, a control group and a treatment group. The treatment group used the “Speak Spell” machine in their own homes for a period of 14 days. A significant increase in the spelling of words in the machine's lexicon was observed for the treatment group but this appeared to be only a transitory increase because spelling performance on these words began to drop to pre-machine exposure levels once the opportunity to use the machine was removed. No improvement was observed in the spelling of words not in the machine's lexicon. It is hoped that the evaluative design used, “a staggered time series design”, can be generalized to provide a relatively simple and inexpensive method of evaluating other electronic learning aids.

Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innova-tions, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.

Plantar pressure assessment is commonly used as a tool to assess the efficacy of insoles in reducing the risk of mechanical trauma to the plantar soft tissue during walking gait. The slow rebound (SR) Poron insole is intended to provide a custom fit to the foot and is believed to be\ud superior in increasing the contact area and consequently reducing the contact pressure compared to a normal Poron (NP) insole. The aim of this study was to compare the effectiveness of SR or NP versus an ethylene vinyl acetate (EV) insole in increasing the contact area (CA), and\ud in reducing the contact pressure (CP) at different regions of the foot during walking. Plantar pressure data was collected from nine healthy individuals during walking using commercially available in-shoe plantar pressure sensors. Although, the NP insole significantly increased the\ud CA and decreased the CP on the entire foot compared to the EV, there was no significant change in CP or CA at any region of the foot in any of the tested insoles. CP showed a positive significant correlation with CA at heel, hallux and heel center in all three insoles. The expected\ud significant negative correlation between regional CA and CP was not observed.