Nonlinear characterisation of power ultrasonic devices used in bone surgery

Ultrasonic cutting has existed in surgery since the 1950s. However, it was not until the end of the 20th century that advances in ultrasonic tool design, transduction and control allowed commercially viable ultrasonic cutting devices to enter the market. Ultrasonic surgical devices, like those in other power ultrasonic applications such as drilling and welding, require devices to be driven at high power to ensure sufficient output motion is produced to fulfil the application it is designed to perform. With the advent of novel surgical techniques surgeons require tuned ultrasonic tools which can reduce invasiveness while giving access to increasingly difficult to reach surgical sites. To fulfil the requirements of novel surgical procedures new tuned tools need to be designed. Meanwhile, it is well documented that power ultrasonic devices, whilst driven at high power, are inherently nonlinear and, if no attempt is made to understand and subsequently control these behaviours, it is likely that these devices will suffer from poor performance or even failure. The behaviour of the commercial ultrasonic transducer used in bone surgery (Piezosurgery® Device) is dynamically characterised through finite element and experimental methods whilst operating in conjunction with a variety of tuned inserts. Finite element analysis was used to predict modal parameters as well as stress levels within the tuned devices whilst operating at elevated amplitudes of vibration, while experimental modal analysis validated predicted resonant frequencies and mode shapes between 0-80kHz. To investigate the behaviour of tuned devices at elevated vibrational amplitudes near resonance, responses were measured whilst the device was excited via the burst sine sweep method. In an attempt to provide an understanding of the effects that geometry, material selection and wavelength of tuned assemblies have on the behaviour of an ultrasonic device, tuned inserts consisting of a simple rod horn design were characterised alongside more complex cutting inserts which are used in maxillofacial and craniofacial surgery. From these results the aim will be to develop guidelines for design of tuned inserts. Meanwhile, Langevin transducers, commonly known as sandwich or stack transducers, in their most basic form generally consist of four parts; a front mass, a back mass, a piezoceramic stack and a stud or bolt holding the parts together under a compressive pre-load. It is traditionally proposed that the piezoceramic stack is positioned at or close to the vibrational nodal point of the longitudinal mode, however, this also corresponds with the position of highest dynamic stress. It is also well documented that piezoceramic materials possess a low linear stress threshold, therefore this research, in part, investigates whether locating the piezoceramic stack away from a position of intrinsic high stress will affect the behaviour of the device. Through experimental characterisation it has been observed that the tuned devices under investigation exhibited; resonant frequency shifts, jump amplitudes, hysteretic behaviour as well as autoparametric vibration. The source of these behaviours have been found to stem from device geometry, but also from heating within the piezoceramic elements as well as joints with different joining torques

Macroalgal Monitoring in the Great Bay Estuary: 2018 Annual Report

Since 2013, the abundance and taxa of intertidal macroalgae have been assessed at fixed locations throughout the Great Bay Estuary in New Hampshire. Algal abundance may be influenced by environmental conditions such as nutrient levels, water temperature, light and invasive species. Therefore, abundance of different algal groups can provide insights into the overall health of the estuary and signal ecological change. In 2018, intertidal abundance data for percentage cover and biomass were collected, as planned, from five of the eight sites. For the first time, subtidal sampling arrays were also incorporated at all four sites in Great Bay proper to monitor macroalgae at lower elevations and to collect data on eelgrass communities coexisting with the algae

Seaweed Monitoring in the Great Bay Estuary: 2019 Annual Report

As global warming increases temperature and nitrogen inputs change—either due to greater inputs associated with growing populations in the Great Bay or with nitrogen reductions at wastewater treatment plants—it is important to understand how these changes are impacting the estuary. To that end, the abundance and taxa of intertidal seaweeds have been assessed at fixed locations throughout the estuary since 2013. Seaweed abundance may be influenced by environmental conditions such as nutrient levels, water temperature, light availability, and invasive species. Therefore, seaweed communities can provide insights into the overall health of the estuary and signal ecological change. In 2019, abundance data (percent cover and biomass) were collected from five of the eight intertidal sampling locations and four subtidal locations. Two more sampling arrays were established at each subtidal site, making three replicates per site. Data from 2013-2019 show appreciable cover and biomass of nuisance seaweeds (reds and greens), including several introduced species. Green seaweeds decreased in cover at the two intertidal sites that are sampled annually (Depot Road and Adams Point), and cover of red seaweed decreased at one site (Depot Road). However, there were no decreases at the other six sites, and results from 2019 still show high levels of nuisance seaweed at the lowest intertidal elevations. In subtidal areas, percent cover assessments by snorkel appeared successful based on strong correlations between cover and biomass. Percent cover of seagrass measured by snorkel was very similar to independent measurements from underwater photos. The abundance of seaweed in association with eelgrass beds was ecologically significant and may have impacted eelgrass density and productivity. Further monitoring of seaweed and eelgrass is required to determine potential impacts to the estuary from emerging threats of increased nutrients from impervious surfaces and rising water temperatures due to global warming, as well as reduced nutrient threats from improvements to wastewater treatment plants and stormwater management. For example, the 2019 eelgrass survey showed an increase in area of eelgrass beds within Great and Little Bays which co-occurred with declines in nuisance seaweed at two of our stations in Great Bay

CDH1 Gene Mutation Hereditary Diffuse Gastric Cancer Outcomes: Analysis of a Large Cohort, Systematic Review of Endoscopic Surveillance, and Secondary Cancer Risk Postulation

Hereditary diffuse gastric cancer (HDGC) is a rare signet-ring cell adenocarcinoma (SRCC) linked to CDH1 (E-cadherin) inactivating germline mutations, and increasingly other gene mutations. Female CDH1 mutation carriers have additional risk of lobular breast cancer. Risk management includes prophylactic total gastrectomy (PTG). The utility of endoscopic surveillance is unclear, as early disease lacks macroscopic lesions. The current systematic biopsy protocols have unknown efficacy, and other secondary cancer risks are postulated. We conducted a retrospective study of consecutive asymptomatic HDGC patients undergoing PTG, detailing endoscopic, pathologic, and outcome results. A systematic review compared endoscopic biopsy foci detection via random sampling versus Cambridge Protocol against PTG findings. A population-level secondary-cancer-risk postulation among sporadic gastric SRCC patients was completed using the Surveillance, Epidemiology, and End Results database. Of 97 patients, 67 underwent PTG, with 25% having foci detection on random endoscopic biopsy despite 75% having foci on final pathology. There was no improvement in the endoscopic detection rate by Cambridge Protocol. The postulated hazard ratio among sporadic gastric SRCC patients for a secondary colorectal SRCC was three-fold higher, relative to conventional adenocarcinoma patients. Overall, HDGC patients should not rely on endoscopic surveillance to delay PTG, and may have secondary SRCC risks. A definitive determination of actual risk requires collaborative patient outcome data bankin

PRECISE - pregabalin in addition to usual care for sciatica: Study protocol for a randomised controlled trial

Background: Sciatica is a type of neuropathic pain that is characterised by pain radiating into the leg. It is often accompanied by low back pain and neurological deficits in the lower limb. While this condition may cause significant suffering for the individual, the lack of evidence supporting effective treatments for sciatica makes clinical management difficult. Our objectives are to determine the efficacy of pregabalin on reducing leg pain intensity and its cost-effectiveness in patients with sciatica.Methods/Design: PRECISE is a prospectively registered, double-blind, randomised placebo-controlled trial of pregabalin compared to placebo, in addition to usual care. Inclusion criteria include moderate to severe leg pain below the knee with evidence of nerve root/spinal nerve involvement. Participants will be randomised to receive either pregabalin with usual care (n = 102) or placebo with usual care (n = 102) for 8 weeks. The medicine dosage will be titrated up to the participant's optimal dose, to a maximum 600 mg per day. Follow up consultations will monitor individual progress, tolerability and adverse events. Usual care, if deemed appropriate by the study doctor, may include a referral for physical or manual therapy and/or prescription of analgesic medication. Participants, doctors and researchers collecting participant data will be blinded to treatment allocation. Participants will be assessed at baseline and at weeks 2, 4, 8, 12, 26 and 52. The primary outcome will determine the efficacy of pregabalin in reducing leg pain intensity. Secondary outcomes will include back pain intensity, disability and quality of life. Data analysis will be blinded and by intention-to-treat. A parallel economic evaluation will be conducted from health sector and societal perspectives.Discussion: This study will establish the efficacy of pregabalin in reducing leg pain intensity in patients with sciatica and provide important information regarding the effect of pregabalin treatment on disability and quality of life. The impact of this research may allow the future development of a cost-effective conservative treatment strategy for patients with sciatica.Trial registration: ClinicalTrial.gov, ACTRN 12613000530729

PRECISE - pregabalin in addition to usual care: Statistical analysis plan

Background: Sciatica is a severe, disabling condition that lacks high quality evidence for effective treatment strategies. This a priori statistical analysis plan describes the methodology of analysis for the PRECISE study. Methods/design: PRECISE is a prospectively registered, double blind, randomised placebo controlled trial of pregabalin compared to placebo, in addition to usual care in patients with sciatica. The aim of this study is to determine the efficacy and cost-effectiveness of pregabalin in reducing leg pain intensity (primary outcome). Secondary outcomes include disability (key secondary), back pain intensity, quality of life, participants' perceived global effect, work absenteeism and health utilisation. Information about medication usage and tolerability are also collected. Outcomes are collected over one year (weeks 2, 4, 8, 12, 26 and 52). Double data entry will be conducted for primary and key secondary outcomes. Other outcomes will be checked using a risk-based approach. Analyses will be consistent with the intention-to-treat principle. Statistical tests will be two-tailed with a p value <0.05 considered significant. Group allocation will remain masked until analyses and interpretation are finalised. Repeated-measure linear mixed models will assess the effect of treatment (pregabalin versus placebo) on primary and secondary outcomes at all time points. Fixed effects will include group allocation, visit as a categorical variable and the interaction between group and visit. Covariates will include baseline leg pain and symptom duration, with an interaction term between baseline leg pain and visit. Pairwise differences between groups will be tested at weeks 8 and 52. The number of serious adverse events and adverse events will be reported, and the proportion of patients per group who have at least one event will be compared using Fisher's exact test. An economic evaluation will be conducted if there is a treatment effect on the primary outcome at week 8. A subgroup analysis will assess whether presenting features of neuropathic pain at baseline modify the treatment effect of leg pain at week 8. Discussion: This statistical analysis plan provides detailed methodology for the analysis of the PRECISE study, which aims to deliver much needed evidence about effective and affordable management of sciatica. Trial registration: Australian and New Zealand Clinical Trials Registry ( ACTRN12613000530729. Registered 13 May 2013

Urban interventionism as a challenge to aesthetic order::Towards an aesthetic criminology

This article is concerned with ideas of urban order and considers the scope for playing with people’s expectations of order. In particular, drawing on criminological, philosophical and urban studies literatures, the article explores the notion of aesthetic order. The power to dictate aesthetic order is highlighted. The example of urban interventionism is used to consider those that challenge an approved aesthetic order. Here the article draws on cultural criminology and visual criminology, with illustrations coming from research in Toronto, Canada. Influenced by Alison Young’s (2014a) conceptualisation of ‘cities within the city’, the article considers how different people using the same space have different or overlapping ways of understanding aesthetic order. Of relevance to criminology, it is contended that people or things that contravene an approved aesthetic order may face banishment and criminalisation. It is concluded that respect for such difference is required. An aesthetic criminology is suggested

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Recessive mutations in SPTBN2 implicate β-III spectrin in both cognitive and motor development

β-III spectrin is present in the brain and is known to be important in the function of the cerebellum. Heterozygous mutations in SPTBN2, the gene encoding β-III spectrin, cause Spinocerebellar Ataxia Type 5 (SCA5), an adult-onset, slowly progressive, autosomal-dominant pure cerebellar ataxia. SCA5 is sometimes known as "Lincoln ataxia," because the largest known family is descended from relatives of the United States President Abraham Lincoln. Using targeted capture and next-generation sequencing, we identified a homozygous stop codon in SPTBN2 in a consanguineous family in which childhood developmental ataxia co-segregates with cognitive impairment. The cognitive impairment could result from mutations in a second gene, but further analysis using whole-genome sequencing combined with SNP array analysis did not reveal any evidence of other mutations. We also examined a mouse knockout of β-III spectrin in which ataxia and progressive degeneration of cerebellar Purkinje cells has been previously reported and found morphological abnormalities in neurons from prefrontal cortex and deficits in object recognition tasks, consistent with the human cognitive phenotype. These data provide the first evidence that β-III spectrin plays an important role in cortical brain development and cognition, in addition to its function in the cerebellum; and we conclude that cognitive impairment is an integral part of this novel recessive ataxic syndrome, Spectrin-associated Autosomal Recessive Cerebellar Ataxia type 1 (SPARCA1). In addition, the identification of SPARCA1 and normal heterozygous carriers of the stop codon in SPTBN2 provides insights into the mechanism of molecular dominance in SCA5 and demonstrates that the cell-specific repertoire of spectrin subunits underlies a novel group of disorders, the neuronal spectrinopathies, which includes SCA5, SPARCA1, and a form of West syndrome

Genomic insights into the origin of farming in the ancient Near East

We report genome-wide ancient DNA from 44 ancient Near Easterners ranging in time between ~12,000 and 1,400 BC, from Natufian hunter–gatherers to Bronze Age farmers. We show that the earliest populations of the Near East derived around half their ancestry from a ‘Basal Eurasian’ lineage that had little if any Neanderthal admixture and that separated from other non-African lineages before their separation from each other. The first farmers of the southern Levant (Israel and Jordan) and Zagros Mountains (Iran) were strongly genetically differentiated, and each descended from local hunter–gatherers. By the time of the Bronze Age, these two populations and Anatolian-related farmers had mixed with each other and with the hunter–gatherers of Europe to greatly reduce genetic differentiation. The impact of the Near Eastern farmers extended beyond the Near East: farmers related to those of Anatolia spread westward into Europe; farmers related to those of the Levant spread southward into East Africa; farmers related to those of Iran spread northward into the Eurasian steppe; and people related to both the early farmers of Iran and to the pastoralists of the Eurasian steppe spread eastward into South Asia