A synthetic biochemistry platform for cell free production of monoterpenes from glucose.

Cell-free systems designed to perform complex chemical conversions of biomass to biofuels or commodity chemicals are emerging as promising alternatives to the metabolic engineering of living cells. Here we design a system comprises 27 enzymes for the conversion of glucose into monoterpenes that generates both NAD(P)H and ATP in a modified glucose breakdown module and utilizes both cofactors for building terpenes. Different monoterpenes are produced in our system by changing the terpene synthase enzyme. The system is stable for the production of limonene, pinene and sabinene, and can operate continuously for at least 5 days from a single addition of glucose. We obtain conversion yields >95% and titres >15 g l-1. The titres are an order of magnitude over cellular toxicity limits and thus difficult to achieve using cell-based systems. Overall, these results highlight the potential of synthetic biochemistry approaches for producing bio-based chemicals

Risk factors for chest infection in acute stroke: a prospective cohort study

<p><b>Background and Purpose:</b> Pneumonia is a major cause of morbidity and mortality after stroke. We aimed to determine key characteristics that would allow prediction of those patients who are at highest risk for poststroke pneumonia.</p> <p><b>Methods:</b> We studied a series of consecutive patients with acute stroke who were admitted to hospital. Detailed evaluation included the modified National Institutes of Health Stroke Scale; the Abbreviated Mental Test; and measures of swallow, respiratory, and oral health status. Pneumonia was diagnosed by set criteria. Patients were followed up at 3 months after stroke.</p> <p><b>Results:</b> We studied 412 patients, 391 (94.9%) with ischemic stroke and 21 (5.1%) with hemorrhagic stroke; 78 (18.9%) met the study criteria for pneumonia. Subjects who developed pneumonia were older (mean±SD age, 75.9±11.4 vs 64.9±13.9 years), had higher modified National Institutes of Health Stroke Scale scores, a history of chronic obstructive pulmonary disease, lower Abbreviated Mental Test scores, and a higher oral cavity score, and a greater proportion tested positive for bacterial cultures from oral swabs. In binary logistic-regression analysis, independent predictors (P<0.05) of pneumonia were age >65 years, dysarthria or no speech due to aphasia, a modified Rankin Scale score ≥4, an Abbreviated Mental Test score <8, and failure on the water swallow test. The presence of 2 or more of these risk factors carried 90.9% sensitivity and 75.6% specificity for the development of pneumonia.</p> <p><b>Conclusions:</b> Pneumonia after stroke is associated with older age, dysarthria/no speech due to aphasia, severity of poststroke disability, cognitive impairment, and an abnormal water swallow test result. Simple assessment of these variables could be used to identify patients at high risk of developing pneumonia after stroke.</p&gt

Conservation and biology of the rediscovered nationally endangered Canterbury knobbled weevil, Hadramphus tuberculatus

Three areas near Burkes Pass Scenic Reserve were surveyed for the presence of Hadramphus tuberculatus, a recently rediscovered endangered weevil. The reserve itself was resurveyed to expand on a 2005/2006 survey. Non-lethal pitfall traps and mark and recapture methods were used. Six H. tuberculatus were caught in pitfall traps over 800 trap nights. Day and night searching of Aciphylla aurea was conducted. Four specimens were observed on Aciphylla flowers between 9 am and 1.30 pm within the reserve. No specimens were found outside of the reserve by either method. Other possible locations where H. tuberculatus may be found were identified and some visited. At most locations Aciphylla had already finished flowering, no H. tuberculatus were found. Presence of H. tuberculatus at other sites would be best determined by searching of Aciphylla flowers during the morning from late October onwards

Applying the trigger review method after a brief educational intervention: potential for teaching and improving safety in GP specialty training?

<p>Background: The Trigger Review Method (TRM) is a structured approach to screening clinical records for undetected patient safety incidents (PSIs) and identifying learning and improvement opportunities. In Scotland, TRM participation can inform GP appraisal and has been included as a core component of the national primary care patient safety programme that was launched in March 2013. However, the clinical workforce needs up-skilled and the potential of TRM in GP training has yet to be tested. Current TRM training utilizes a workplace face-to-face session by a GP expert, which is not feasible. A less costly, more sustainable educational intervention is necessary to build capability at scale. We aimed to determine the feasibility and impact of TRM and a related training intervention in GP training.</p> Methods We recruited 25 west of Scotland GP trainees to attend a 2-hour TRM workshop. Trainees then applied TRM to 25 clinical records and returned findings within 4-weeks. A follow-up feedback workshop was held. <p>Results: 21/25 trainees (84%) completed the task. 520 records yielded 80 undetected PSIs (15.4%). 36/80 were judged potentially preventable (45%) with 35/80 classified as causing moderate to severe harm (44%). Trainees described a range of potential learning and improvement plans. Training was positively received and appeared to be successful given these findings. TRM was valued as a safety improvement tool by most participants.</p> <p>Conclusion: This small study provides further evidence of TRM utility and how to teach it pragmatically. TRM is of potential value in GP patient safety curriculum delivery and preparing trainees for future safety improvement expectations.</p&gt

Which human factors design issues are influencing system performance in out-of-hours community palliative care? Integration of realist approaches with an established systems analysis framework to develop mid-range programme theory

Objective: To develop mid-range programme theory from perceptions and experiences of out-of-hours community palliative care, accounting for human factors design issues that might be influencing system performance for achieving desirable outcomes through quality improvement. Setting: Community providers and users of out-of-hours palliative care. Participants: 17 stakeholders participated in a workshop event. Design: In the UK, around 30% of people receiving palliative care have contact with out-of-hours services. Interactions between emotions, cognition, tasks, technology and behaviours must be considered to improve safety. After sharing experiences, participants were presented with analyses of 1072 National Reporting and Learning System incident reports. Discussion was orientated to consider priorities for change. Discussions were audio-recorded and transcribed verbatim by the study team. Event artefacts, for example, sticky notes, flip chart lists and participant notes, were retained for analysis. Two researchers independently identified context–mechanism–outcome configurations using realist approaches before studying the inter-relation of configurations to build a mid-range theory. This was critically appraised using an established human factors framework called Systems Engineering Initiative for Patient Safety (SEIPS). Results: Complex interacting configurations explain relational human-mediated outcomes where cycles of thought and behaviour are refined and replicated according to prior experiences. Five such configurations were identified: (1) prioritisation; (2) emotional labour; (3) complicated/complex systems; (4a) system inadequacies and (4b) differential attention and weighing of risks by organisations; (5) learning. Underpinning all these configurations was a sixth: (6a) trust and access to expertise; and (6b) isolation at night. By developing a mid-range programme theory, we have created a framework with international relevance for guiding quality improvement work in similar modern health systems. Conclusions: Meta-cognition, emotional intelligence, and informal learning will either overcome system limitations or overwhelm system safeguards. Integration of human-centred co-design principles and informal learning theory into quality improvement may improve results

Lack of self-averaging in neutral evolution of proteins

We simulate neutral evolution of proteins imposing conservation of the thermodynamic stability of the native state in the framework of an effective model of folding thermodynamics. This procedure generates evolutionary trajectories in sequence space which share two universal features for all of the examined proteins. First, the number of neutral mutations fluctuates broadly from one sequence to another, leading to a non-Poissonian substitution process. Second, the number of neutral mutations displays strong correlations along the trajectory, thus causing the breakdown of self-averaging of the resulting evolutionary substitution process.Comment: 4 pages, 2 figure

Cognitive Information Processing

Contains reports on seven research projects.National Institutes of Health (Grant 5 P01 GM14940-03)National Institutes of Health (Grant 5 P01 GM15006-02)Joint Services Electronics Programs (U. S. Army, U.S. Navy, and U.S. Air Force) under Contract DA 28-043-AMC-02536(E)National Institutes of Health (Grant 5 TOl GM-01555-02

Protein design in a lattice model of hydrophobic and polar amino acids

A general strategy is described for finding which amino acid sequences have native states in a desired conformation (inverse design). The approach is used to design sequences of 48 hydrophobic and polar aminoacids on three-dimensional lattice structures. Previous studies employing a sequence-space Monte-Carlo technique resulted in the successful design of one sequence in ten attempts. The present work also entails the exploration of conformations that compete significantly with the target structure for being its ground state. The design procedure is successful in all the ten cases.Comment: RevTeX, 12 pages, 1 figur

Evaluation of a new type of direct digital radiography machine

Objective. To evaluate a recently developed low-dose, largefield, direct digital X-ray scanning system for medical use.Method. Radiation dose, image quality, diagnostic capability and clinical utility of the unit were compared with those of conventional radiography.Results. Radiation doses ranged from 3% to 5% of conventional radiographic values, and a mean of 1 line-pair per millimetre could be detected. Ease of use, anatomical coverage and tolerance to patient motion were advantages. However, image quality was inferior to that of conventional radiographs, with limited fine detail visibility and penetration. Only 67 of 156 (42.9%) pathological features seen on conventional radiographs were detected, including 13 of 41 fractures (31.7%) and 11 of 18 pneumothoraces (61.1%).Conclusion. Although image quality and diagnostic performance were not ideal, potential roles in triage, foreign body detection and possibly screening were promising. Radiographic factors may have affected sensitivity. This machine demonstrated useful attributes that may, with improvement, be beneficial in the imaging of trauma and other patients