A chemoenzymatic route to the (+)-form of the amaryllidaceae alkaloid narseronine

The enzymatically derived and enantiopure cis-1,2-dihydrocatechol 1 has been converted, over 14 one-pot operations, into the (+)-form of the alkaloid narseronine (2). The present study, which complements earlier work that established a route from metabolite 1 to enantiomer (–)-2, involves an N-bromosuccinimide/tri-n-butyltin hydride-mediated cyclisation reaction to construct the unsaturated B-ring lactone of the target compound.We thank the Australian Research Council and the Institute of Advanced Studies for generous financial support

Effect of dose rate on ion beam mixing in Nb-Si

The influence of dose rate, i.e., ion flux, on ion beam mixing in Nb‐Si bilayer samples was measured at room temperature and 325 °C. At the higher temperature, an increase in dose rate of a factor of 20 caused a decrease in the thickness of the mixed layer by a factor of 1.6 for equal total doses. At room temperature, the same change in flux had no effect on mixing. These results are consistent with radiation‐enhanced diffusion theory in the recombination‐limited regime

Understanding the Dynamic Behaviour of a Tennis Racket under Play Conditions

The 'feel' of tennis rackets is of increasing importance to manufacturers seeking product differentiation in a context where further performance enhancements are prevented by a combination of mechanical limits and regulations imposed to protect the integrity of the sport. Vibrations excited during a shot contribute greatly to the perception of 'feel'. Previous studies have been reported but none has covered the full set of mode families or the frequency range in this study. In-plane vibrations associated with the routine use of topspin shots in modern tennis have not been documented so far in the literature. To consider modal behaviour, multiple measurements during play conditions are required but this is practically impossible. This paper proposes an alternative approach and successfully relates a comprehensive modal analysis on a freely suspended racket to vibration measurements under play conditions. This is achieved through an intermediate stage comprising a necessarily more limited modal analysis on a hand-gripped racket and use of the mass modification modal analysis tool. This stage confirmed the prevailing view that hand-gripping can be considered as a mass modification distributed along the handle of the freely suspended racket but the associated mass was much lower than that of an actual hand and the hand also increased the damping ratio of frame modes significantly. Furthermore, in frame vibration measurements during forehand groundstrokes, a greater reduction in bending mode frequencies was observed, consistent with a mass-loading of around 25 % of the actual hand as a consequence of the tighter grip. In these play tests, the first two bending modes, the first torsional mode, the first eight stringbed modes, the first three hoop modes and the third in-plane bending mode were identified, with the stringbed modes being particularly prominent. © 2013 Society for Experimental Mechanics

New methods for the synthesis of certain alkaloids and terpenoids

The use of ring-fused gem-dihalocyclopropanes, Au(I)-catalyzed cyclization reactions, and chemoenzymatic techniques in the synthesis of natural products is described.We thank the Australian Research Council for generous financial support through the provision of various grants

Diagnostic accuracy of the Ottawa ankle rule to exclude fractures in acute ankle injuries in adults: a systematic review and meta-analysis

BACKGROUND: Ankle traumas are common presenting injuries to emergency departments in Australia and worldwide. The Ottawa Ankle Rules (OAR) are a clinical decision tool to exclude ankle fractures, thereby precluding the need for radiographic imaging in patients with acute ankle injury. Previous studies support the OAR as an accurate means of excluding ankle and midfoot fractures, but have included a paediatric population, report both the ankle and mid-foot, or are greater than 5 years old. This systematic review and meta-analysis aimed to update and assess the existing evidence of the diagnostic accuracy of the Ottawa Ankle Rule (OAR) acute ankle injuries in adults. METHODS: A systematic search and screen of was performed for relevant articles dated 1992 to 2020. Prospective and retrospective studies documenting OAR outcomes by physicians to assess ankle injuries were included. Critical appraisal of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Outcomes related to psychometric data were pooled using random effects or fixed effects modelling to calculate diagnostic performance of the OAR. Between-study heterogeneity was assessed using the Higgins I2 test, with Spearman’s correlation test for threshold effect. RESULTS: From 254 unique studies identified in the screening process, 15 were included, involving 8560 patients from 13 countries. Sensitivity, specificity, negative likelihood ratio, positive likelihood ratio and diagnostic odds ratio were 0.91 (95% CI, 0.89 to 0.92), 0.25 (95% CI, 0.24 to 0.26), 1.47 (95% CI, 1.11 to 1.93), 0.15 (95% CI, 0.72 to 0.29) and 10.95 (95% CI, 5.14 to 23.35) respectively, with high between-study heterogeneity observed (sensitivity: I2 = 94.3%, p < 0.01; specificity: I2 = 99.2%, p < 0.01). Most studies presented with low risk of bias and concern regarding applicability following assessment against QUADAS-2 criteria. CONCLUSIONS: Application of the OAR is highly sensitive and can correctly predict the likelihood of ankle fractures when present, however, lower specificity rates increase the likelihood of false positives. Overall, the use of the OAR tool is supported as a cost-effective method of reducing unnecessary radiographic referral, that should improve efficiency, lower medical costs and reduce waiting times. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12891-022-05831-7

Adequacy of clinical information in X-ray referrals for traumatic ankle injury with reference to the Ottawa Ankle Rules-a retrospective clinical audit

Study Objective To assess the adequacy of clinical information with reference to the Ottawa Ankle Rules (OAR) in X-ray referrals for adults with traumatic ankle injury in the ED of a South Australian tertiary hospital and report upon referring trends between emergency department clinicians. Methods A retrospective clinical audit of adult ankle X-ray referrals in the emergency department was conducted. Eligible referrals were screened for their adherence to the OAR, patient details, clinical history and referrer. A logistic regression was used to determine the influence of these factors on the likelihood of being referred for X-rays despite not meeting the OAR criteria. Sensitivity, specificity, positive and negative likelihood ratios and their associated confidence intervals were calculated to assess the diagnostic accuracy of the OAR for those referred. Results Out of the 262 eligible referrals, 163 were deemed to have met the criteria for the OAR. Physiotherapists showed the highest OAR compliance of 77.3% and were the most accurate in their use of the rules, with a sensitivity of 0.86. Medical officers, registrars and interns were 2.5 times more likely to still refer a patient for X-ray if they did not meet the OAR criteria, compared to physiotherapists as the baseline. Patient age, duration of injury etc. were not significantly associated with likelihood of referral (even when they did not meet OAR criteria). The overall sensitivity, specificity, positive and negative likelihood ratios of the OAR were 0.59 (95% CI [0.47–0.71]), 0.37 (95% CI [0.30–0.44]), 0.93 (95% CI [0.76–1.16]) and 1.10 (95% CI [0.82–1.48]) respectively. Conclusion The results of this audit demonstrated poor sensitivity and moderate compliance by referrers with the rule. Reasonable evidence exists for the implementation of individual and/or institutional-based change strategies to improve clinician compliance and accuracy with use of the OAR

Foot orthoses for adults with flexible pes planus: a systematic review

BACKGROUND: Foot orthoses are widely used in the management of flexible pes planus, yet the evidence to support this intervention has not been clearly defined. This systematic review aimed to critically appraise the evidence for the use of foot orthoses for flexible pes planus in adults. METHODS: Electronic databases (Medline, CINAHL, Cochrane, Web of science, SportDiscus, Embase) were systematically searched in June 2013 for randomised controlled, controlled clinical and repeated measure trials where participants had identified flexible pes planus using a validated and reliable measure of pes planus and the intervention was a rigid or semi-rigid orthoses with the comparison being a no-orthoses (shoes alone or flat non-posted insert) condition. Outcomes of interest were foot pain, rearfoot kinematics, foot kinetics and physical function. RESULTS: Of the 2,211 articles identified by the searches, 13 studies met the inclusion criteria; two were randomised controlled trials, one was a controlled trial and 10 were repeated measure studies. Across the included studies, 59 relevant outcome measures were reported with 17 calculated as statistically significant large or medium effects observed with use of foot orthoses compared to the no orthoses condition (SMD range 1.13 to -4.11). CONCLUSIONS: No high level evidence supported the use of foot orthoses for flexible pes planus. There is good to moderate level evidence that foot orthoses improve physical function (medial-lateral sway in standing (level II) and energy cost during walking (level III)). There is low level evidence (level IV) that foot orthoses improve pain, reduce rearfoot eversion, alter loading and impact forces; and reduce rearfoot inversion and eversion moments in flexible pes planus. Well-designed randomised controlled trials that include appropriate sample sizes, clinical cohorts and involve a measure of symptom change are required to determine the efficacy of foot orthoses to manage adult flexible pes planus.Helen A Banwell, Shylie Mackintosh and Dominic Thewli

Rituximab monitoring and redosing in pediatric neuromyelitis optica spectrum disorder.

Abstract OBJECTIVE: To study rituximab in pediatric neuromyelitis optica (NMO)/NMO spectrum disorders (NMOSD) and the relationship between rituximab, B cell repopulation, and relapses in order to improve rituximab monitoring and redosing. METHODS: Multicenter retrospective study of 16 children with NMO/NMOSD receiving 652 rituximab courses. According to CD19 counts, events during rituximab were categorized as "repopulation," "depletion," or "depletion failure" relapses (repopulation threshold CD19 6510 7 10(6) cells/L). RESULTS: The 16 patients (14 girls; mean age 9.6 years, range 1.8-15.3) had a mean of 6.1 events (range 1-11) during a mean follow-up of 6.1 years (range 1.6-13.6) and received a total of 76 rituximab courses (mean 4.7, range 2-9) in 42.6-year cohort treatment. Before rituximab, 62.5% had received azathioprine, mycophenolate mofetil, or cyclophosphamide. Mean time from rituximab to last documented B cell depletion and first repopulation was 4.5 and 6.8 months, respectively, with large interpatient variability. Earliest repopulations occurred with the lowest doses. Significant reduction between pre- and post-rituximab annualized relapse rate (ARR) was observed (p = 0.003). During rituximab, 6 patients were relapse-free, although 21 relapses occurred in 10 patients, including 13 "repopulation," 3 "depletion," and 4 "depletion failure" relapses. Of the 13 "repopulation" relapses, 4 had CD19 10-50 7 10(6) cells/L, 10 had inadequate monitoring ( 641 CD19 in the 4 months before relapses), and 5 had delayed redosing after repopulation detection. CONCLUSION: Rituximab is effective in relapse prevention, but B cell repopulation creates a risk of relapse. Redosing before B cell repopulation could reduce the relapse risk further. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that rituximab significantly reduces ARR in pediatric NMO/NMOSD. This study also demonstrates a relationship between B cell repopulation and relapses

Painting the ideal home: using art to express visions of technologically supported independent living for older people in North East England

This paper describes the investigation of the development of future technological products to support older people in everyday living through the agency of a community art group. Recent research has identified a number of challenges facing designers seeking to use traditional participatory design approaches to gather technology requirements data from older people. Here, a project is described that sought to get a group of older people to think creatively about their needs and desires for technological support through the medium of paint. The artistic expression technique described in this article allowed the identification of issues that had also been found by previous research that used a range of different techniques. This indicates that the approach shows promise, as it allows information to be gathered in an environment that is comfortable and familiar using methods already known by the participants and which they find enjoyable. It provides a complement (or possible alternative) to standard protocols and has the potential benefit of extracting even richer information as the primary task for participants is enjoyable in its own right and is not associated with an interrogative process. Furthermore, it is argued that some of the key risks of traditional approaches are lessened or removed by the naturalistic setting of this approach