Resonant ultrasonic bone penetrating needles

Bone biopsy is an invasive clinical procedure where a bone sample is recovered for analysis during the diagnosis of a medical condition. The procedure is performed while the patient is under either local or general anaesthesia as the patient can experience significant discomfort and possibly large haematoma due to the large axial and rotational forces applied through the needle to penetrate bone. It is well documented that power ultrasonic surgical devices offer advantages of low cutting force, high accuracy and preservation of soft tissues. This thesis details a study of the design, analysis and evaluation of a class of novel power ultrasonic needles for bone penetration, particularly biopsy. Micrometric vibrations generated at the distal tip of a full-wavelength resonant ultrasonic device are used to penetrate the bone. Both ultrasonic longitudinal (L) and longitudinal-torsional (L-T) coupled vibration have proven successful in several applications including ultrasonic surgical devices. Interest in ultrasonic bone cutting has grown since it was first introduced commercially as Piezosurgery in the 1990s. More recent studies have focused on precision cutting of bone, reducing the risk of damage to surrounding delicate tissues in comparison with manual and other powered instruments. Finite element analysis (FEA) is used to design full wavelength ultrasonic needle devices, where the geometry of the device is systematically modified to deter modal coupling by monitoring the frequency spacing between the longitudinal mode of interest and the neighbouring parasitic modes. FEA is further exploited to predict the achievable torsional displacement in a composite mode device tuned to vibrate in a longitudinal-torsional motion through degeneration of the longitudinal motion. While the L-mode device requires the operator to apply a slow backward and forward rotation and a small forward force, to maintain a forward motion and avoid imprinting, a L-T motion at the tip device could avoid this, simplifying the procedure, increasing precision and resulting in a cylindrical, less damaged hole surface. The dynamic behaviours predicted by FEA are validated through experimental modal analysis (EMA) demonstrating the effectiveness of FEA for the design of these devices. EMA is performed by exciting the ultrasonic needle device with a low power random excitation over a predetermined frequency range and measuring the vibration response using a 3D laser Doppler vibrometer (LDV) across a grid of points on the surface of the device. Harmonic analysis was used to investigate the behaviour of the devices at high excitation levels to capture the inherent nonlinearity of the tuned device. The response is captured using bi-directional frequency sweeps across the tuned mode of interest at increasing excitation levels. Ultrasonic surgical instruments typically require to be driven at high excitation levels to generate sufficient vibration amplitude to cut or aspirate tissue or seal vessels. The nonlinearities of the instrument and load presented by the target tissue result in resonance frequency shift, variation in the electric impedance and instability in the vibrational response which can negatively affect the efficacy of the instrument. A resonance tracking system was developed to monitor the voltage and current and adjust the frequency in real time to compensate for the frequency shift. Additional functionality was incorporated to allow modifications to the excitation signal shape and to enable power modulation techniques to be tested in a study of their effects on the rate of progression of the device in its target tissue. Prototype ultrasonic needle devices were evaluated in penetration tests conducted in bone mimic materials and animal bones. The devices recovered trabecular bone from the metaphysis of an ovine femur, and the biopsy samples were architecturally comparable to samples extracted using a trephine biopsy needle. The resonant needle device extracted a cortical bone sample from the central diaphysis, which is the strongest part of the bone, and the biopsy was of superior quality to the sample recovered by a trephine bone biopsy needle. The biopsy sample extracted by the resonant needle was architecturally uniform and cylindrical with an absence of chipping on the surface, suggesting that the biopsy was extracted with precision and control. To penetrate with the L mode device, the operator had to apply a slow backward and forward rotation and the small forward force, to maintain a forward motion. The rotation had to avoid imprinting of the needle tip in the bone, which otherwise resulted in the device stalling. However the L-T mode device, realised by incorporating helical cuts along the axial length, could penetrate the same animal bone sample only requiring the small forward force, hence simplifying the procedure for the operator. The L-T device also provided increased precision, resulting in a cylindrical, less damaged hole surface. Finally, a case study related to skull-based surgery is presented. The petrous apex is a pyramidal shaped structure at the anterior superior portion of the temporal bone and can be the location of tumours, cysts and lesions requiring diagnostic investigation. The petrous apex is challenging to access due to its medial location in the skull base and closeness to important neurovascular structures. An extended surgical approach removes the subject but is associated with morbidity and hence a minimally invasive procedure to access this site to retrieve a biopsy provides a valuable test case for the ultrasonic needle. Guided by the expertise and experience of an ear, nose and throat surgeon, the ultrasonic needle devices were modified and demonstrated in lab-based studies as a new technology for this bone penetration procedure

Editors' introduction to special theme issue [of International Journal of Pedagogies and Learning]: Meanings emerging in practice (Part 3)

This issue publishes the third and final set of refereed papers from the first wave proceedings of the 3rd International Conference on Pedagogies and Learning, held at the Springfield Campus of the University of Southern Queensland in Australia on 27 and 28 September 2007. This third conference in the series focused on “Meanings Emerging in Practice” as a lens for examining and evaluating multiple enactments of pedagogies and learning

Faecal haemoglobin concentration in adenoma, before and after polypectomy, approaches the ideal tumour marker

BACKGROUND: Polypectomy may be performed at colonoscopy and then subsequent surveillance undertaken. It is thought that faecal haemoglobin concentration (f-Hb), estimated by quantitative faecal immunochemical tests (FIT), might be a useful tumour marker. METHODS: Consecutive patients enrolled in colonoscopy surveillance were approached at two hospitals. A specimen for FIT was provided before colonoscopy and, ideally after 3 weeks, a second FIT sample from those who had polypectomy. A single FIT system (OC-Sensor io, Eiken Chemical Co., Ltd) was used to generate f-Hb. RESULTS: 1103 Patients were invited; 643 returned a FIT device (uptake: 58.3%). Four patients had known inflammatory bowel disease (IBD) and were excluded, leaving 639 (57.9%) with an age range of 25–90 years (median 64 years), 54.6% male. Of 593 patients who had a f-Hb result and completed colonoscopy, advanced neoplasia was found in 41 (6.9%); four colorectal cancer (CRC): 0.7% and 37 advanced adenoma (AA): 6.3%, and a further 127 (21.4%) had non-advanced adenoma (NAA). The median f-Hb was significantly greater in AA as compared to NAA; 6.0 versus 1.0 μg Hb/g faeces, p < 0.0001.134/164 (81.7%) of invited patients returned a second FIT device: 28 were patients with AA in whom median pre-polypectomy f-Hb was 19.2, falling to 3.5 μg Hb/g faeces post-polypectomy, p = 0.01, and 106 with NAA had median pre-polypectomy f-Hb 0.8 compared to 1.0 μg Hb/g faeces post-polypectomy, p = 0.96. CONCLUSIONS: Quantitative FIT could provide a good tumour marker in post-polypectomy surveillance, reduce colonoscopy requirements and minimise potential risk to patients

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

The contribution of X-linked coding variation to severe developmental disorders

Abstract: Over 130 X-linked genes have been robustly associated with developmental disorders, and X-linked causes have been hypothesised to underlie the higher developmental disorder rates in males. Here, we evaluate the burden of X-linked coding variation in 11,044 developmental disorder patients, and find a similar rate of X-linked causes in males and females (6.0% and 6.9%, respectively), indicating that such variants do not account for the 1.4-fold male bias. We develop an improved strategy to detect X-linked developmental disorders and identify 23 significant genes, all of which were previously known, consistent with our inference that the vast majority of the X-linked burden is in known developmental disorder-associated genes. Importantly, we estimate that, in male probands, only 13% of inherited rare missense variants in known developmental disorder-associated genes are likely to be pathogenic. Our results demonstrate that statistical analysis of large datasets can refine our understanding of modes of inheritance for individual X-linked disorders

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Online pedagogical practices in the Faculty of Education at the University of Southern Queensland

This report is a product of ongoing discussions in the Faculty of Education, USQ, related to the role of networked computing and communications technologies in higher education. The report is informed by reflection on several years of experience using technology to enhance the provision of education, information collected as part of a recent evaluation of online courses and current notions of best practices in online learning and teaching. Section 1 of the report discusses the theoretical foundations of online learning and teaching and identifies the characteristics of sustainable, quality, online learning. Among the key ideas is the need to consider the relationships among various systems associated with online learning within an organisational context, the active and social nature of learning online, and continuity with good educational practice in other contexts. A series of vignettes presented in Section 2 provide illustrations of best practices within courses and other projects managed by the Faculty. Out of this background and experience, five propositions emerge as the basis for developing and extending online education in the Faculty of Education and in the wider university community, along with a number of recommendations for future online practices at USQ