Hewlett-Packard (Australia)

To be effective, chemotherapy against tuberculosis (TB) must kill the intracellular population of the pathogen, Mycobacterium tuberculosis. However, how host cell microenvironments affect antibiotic accumulation and efficacy remains unclear. Here, we use correlative light, electron, and ion microscopy to investigate how various microenvironments within human macrophages affect the activity of pyrazinamide (PZA), a key antibiotic against TB. We show that PZA accumulates heterogeneously among individual bacteria in multiple host cell environments. Crucially, PZA accumulation and efficacy is maximal within acidified phagosomes. Bedaquiline, another antibiotic commonly used in combined TB therapy, enhances PZA accumulation via a host cell-mediated mechanism. Thus, intracellular localisation and specific microenvironments affect PZA accumulation and efficacy. Our results may explain the potent in vivo efficacy of PZA, compared to its modest in vitro activity, and its critical contribution to TB combination chemotherapy.

Background: Sudden cardiac death (SCD) in the young is devastating. Contemporary incidence remains unclear with few recent nationwide studies and limited data addressing risk factors for causes. We aimed to determine incidence, trends, causes, and risk factors for SCD in the young. Methods and Results: The National Coronial Information System registry was reviewed for SCD in people aged 1 to 35 years from 2000 to 2016 in Australia. Subjects were identified by the International Classification of Diseases , Tenth Revision code relating to circulatory system diseases (I00–I99) from coronial reports. Baseline demographics, circumstances, and cause of SCD were obtained from coronial and police reports, alongside autopsy and toxicology analyses where available. During the study period, 2006 cases were identified (median age, 28±7 years; men, 75%; mean body mass index, 29±8 kg/m 2 ). Annual incidence ranged from 0.91 to 1.48 per 100 000 age-specific person-years, which was the lowest in 2013 to 2015 compared with previous 3-year intervals on Poisson regression model ( P =0.001). SCD incidence was higher in nonmetropolitan versus metropolitan areas (0.99 versus 0.53 per 100 000 person-years; P <0.001). The most common cause of SCD was coronary artery disease (40%), followed by sudden arrhythmic death syndrome (14%). Incidence of coronary artery disease–related SCD decreased from 2001–2003 to 2013–2015 ( P <0.001). Proportion of SCD related to sudden arrhythmic death syndrome increased during the study period ( P =0.02) although overall incidence was stable ( P =0.22). Residential remoteness was associated with coronary artery disease–related SCD (odds ratio, 1.44 [95% CI, 1.24–1.67]; P <0.001). For every 1-unit increase, body mass index was associated with increased likelihood of SCD from cardiomegaly (odds ratio, 1.08 [95% CI, 1.05–1.11]; P <0.001) and dilated cardiomyopathy (odds ratio, 1.04 [95% CI, 1.01–1.06]; P =0.005). Conclusions: Incidence of SCD in the young and specifically coronary artery disease–related SCD has declined in recent years. Proportion of SCD related to sudden arrhythmic death syndrome increased over the study period. Geographic remoteness and obesity are risk factors for specific causes of SCD in the young.

Wearable temperature sensors offer the potential to overcome several limitations associated with current laboratory- and field-based methods for core temperature assessment; however, their ability to provide accurate data at elevated core temperatures (Tc) has been questioned. Therefore, this investigation aimed to determine the concurrent validity of a wearable temperature sensor (CORE) compared to a reference telemetric temperature pill (BodyCAP) during a team-sport heat training camp prior to the 2020 Olympic Games. Female field hockey players (n = 19) in the Australian national squad completed 4 sessions in hot conditions where their temperature was monitored via CORE and BodyCAP. Concurrent validity of the wearable CORE device was determined with reference to the ingested BodyCAP pill. Lin's Concordance Correlation Coefficients determined there was "poor" agreement between devices during all sessions. Mean bias demonstrated that CORE underestimated Tc in all sessions (-0.06°C to -0.34°C), with wide mean 95% confidence intervals (±0.35°C to ±0.56°C). Locally estimated scatterplot smoothing regression lines illustrated a non-linearity of error, with greater underestimation of Tc by the CORE device, as Tc increased. The two devices disagreed more than ±0.3°C for 41-60% of all data samples in each session. Our findings do not support the use of the CORE device as a valid alternative to telemetric temperature pills for Tc assessment, particularly during exercise in hot conditions where elevated Tc are expected.

This article investigates the impact of the London PM gold price fixing on two exchange‐traded gold instruments: the GC gold futures contract and the GLD exchange‐traded fund. We find significantly elevated levels of trade volume and price volatility immediately following the fixing's start, well before the conclusion of the fixing and the publication of its results. Similarly, we find statistically significant return advantages in the 4 minutes following the start of the fixing for informed traders. We find no significant impacts or returns following the publication of the fixing results. Trades in the opening minutes of the fixing are significantly predictive of the price direction of the fixings, in some cases exceeding 90%. Combined, these findings support the following conclusions: that the London PM gold price fixing does have material impact on the exchange traded gold instruments, information from the fixing is leaking into markets prior the fixing results being published, and there exist economic returns for trading on these information leaks. © 2013 Wiley Periodicals, Inc. Jrl Fut Mark 34:1003–1039, 2014

The energy transfer in a large deep lake, from the largest wind‐excited basin‐scale waves down to solitary‐type waves, was investigated through a combination of inviscid nonlinear modal analysis and numerical simulations on the basis of weakly nonhydrostatic equations for internal gravitational waves. Data from four thermistor chains deployed in Lake Constance in 2003 revealed a Kelvin wave as the dominant primary basin‐scale wave that transferred its energy, through nonlinear energy cascade, to waves with smaller spatial scales. The simulation results showed that the Kelvin wave excited higher azimuthal Kelvin wave modes whose phases were locked to the parent Kelvin wave to build a steepened wave front associated with the tail of solitary‐type waves and large flow velocity in the wake of the steepened wave front. It is shown that it is the nonlinear and nonhydrostatic inviscid evolution of basin‐scale waves that shifts the flow conditions from a basinwide coherent linear flow to a flow dominated by strong currents in localized regions where damping and mixing mechanisms may act efficiently.

Outsourcing has recently spurred broad discussions due to the relatively high failure rate of outsourced activities. To analyze how organizations can increase their success rate of outsourcing activities, the authors take a two-prong approach to the outsourcing decision and execution process, covering the "why" and "how to" outsource. To determine the optimal setup, the authors introduce six outsourcing dimensions, which trigger the decision process and the subsequent procurement and execution processes. Strategic and operational considerations as well as risk implications are further elaborated.

Pine needle blight, caused by Dothistroma septosporum (Dorog.) M. Morelet, is one of the most serious foliar diseases of Pinus spp. in Australia and New Zealand. In 16 Pinus radiata (D.Don.) progeny trials in northeastern Victoria, Australia, Dothistroma-caused defoliation varied widely among trials and assessment years, ranging from 5% to 65%. The estimated narrow sense heritability ranged from nonsignificant to as high as 0.69 with a median of 0.36. Spatial autocorrelation of residuals accounted for a significant proportion of residual variance, and that increased heritability estimates. Genetic correlation between defoliation scores at an early age and growth at a later age was negative with a median value of –0.39. Phenotypic correlation between defoliation and survival was low and negative with a median value of –0.11. Economic analyses indicated that at sites with a high risk of infection, the effect of reducing defoliation on profitability was comparable with that of increasing growth at sites free from infection. The genetic parameters and economic impacts of Dothistroma were used to derive selection indices and include resistance to defoliation into the current breeding objective for radiata pine.

BACKGROUND: A drive to improve functional outcomes for patients undergoing total knee arthroplasty (TKA) has led to alternative alignment being used. Functional alignment (FA) uses intraoperative soft tissue tension to determine the optimal position of the prosthesis within the patient's soft tissue envelope. Angular limits for bone resections are followed to prevent long-term prosthesis failure. This study will use the aid of robotic assistance to plan and implement the final prosthesis position. This method has yet to be compared to the traditional mechanically aligned (MA) knee in a randomised trial. METHODS: A blinded randomised control trial with 100 patients will be undertaken via Perth Hip and Knee Clinic. Fifty patients will undergo a MA TKA and fifty will undergo a FA TKA. Both alignment techniques will be balanced via computer-assisted navigation to assess prosthetic gaps, being achieved via the initial bony resection and further soft tissue releases as required to achieve satisfactory balance. The primary outcome will be the Forgotten Joint Score (FJS) 2 years after surgery, with secondary outcomes being other patient-reported outcome measures, clinical functional assessment, radiographic position and complications. Other data that will be collected will be patient demography (sex, age, level of activity) and medical information (grade of knee injury, any other relevant medical information). The linear statistical model will be fitted to the response (FJS), including all the other variables as covariates. DISCUSSION: Many surgeons are utilising alternative alignment techniques with a goal of achieving better functional outcomes for their patients. Currently, MA TKA remains the gold standard with good outcomes and excellent longevity. There is no published RCTs comparing FA to MA yet and only two registered studies are planned or currently in progress. This study utilises a FA technique which differs from the two studies. This study will help determine if FA TKA has superior functional results for patients. TRIAL REGISTRATION: This trial has been registered with the Australian New Zealand Clinical Trials Registry (ANZCTR) http://www.anzctr.org.au : U1111-1257-2291, registered 25th Jan 2021. It is also listed on www.clinicaltrials.gov : NCT04748510.

This paper describes a method of utilising genetic algorithms to train fixed architecture feedforward and recurrent neural networks. The technique described uses the genetic algorithm to evolve changes to the weights and biases of the network rather than the weights and biases themselves. Results achieved by this technique indicate that for many problems it compares very favourably with the more common gradient descent techniques for training neural networks, and in some cases is superior. The technique is useful for those problem which are known to be difficult for the gradient descent techniques.

PURPOSE: To investigate the clinical effectiveness of endoscopic iliopsoas tendon release (IPR) at the lesser trochanter (LT) in patients with iliopsoas impingement (IPI) after total hip arthroplasty (THA). METHODS: Between November 2017 and March 2021, a consecutive series of 36 patients were treated with endoscopic IPR for diagnosed IPI. Patients included had acetabular cup position confirmed by functional imaging (OPS, Corin, Pymble, NSW), typical clinical symptoms of IPI, and a positive response to diagnostic injection. Clinical assessment included validated patient-reported outcome measures (PROMs) along with hip flexion strength and active range of motion at different time marks up to 2-year follow-up, as well as surgical complications. RESULTS: Overall, 36 consecutive patients (11 males) with a mean age of 62 ± 12 years were included. All patients had failed nonoperative management. Dynamic computed tomography assessment was available in 89% of the patients, edge loading was reported in 10%, and variable cup overhang was reported in 50%. Clinically, PROMs were significantly improved at every time mark when compared with preoperative values (P < .001), showing the biggest improvement within the first 4 weeks after surgery. At the 6-month follow-up, peak isometric hip flexion strength on the operated side was 20% lower than the contralateral side (P < .001). Failure rate of the procedure was 2.8% (1 case). Linear regression showed no association between cup overhang and clinical outcomes. CONCLUSIONS: Endoscopic IPR at the LT is a safe and reproducible technique associated with significant and immediate improvement in pain, functional outcomes, and high patient satisfaction. With minimal short-term weakness, no complications, and only a single revision, even in cases with cup malposition and/or edge loading, we believe that endoscopic IPR can be considered as one of the first-line operative options in patients with symptomatic IPI, irrespective of component position. LEVEL OF EVIDENCE: Level IV, case series.

Research into pollinators in managed landscapes has recently combined approaches of pollination ecology and landscape ecology, because key stressors are likely to interact across wide areas. While laboratory and field experiments are valuable for furthering understanding, studies are required to investigate the interacting drivers of pollinator health and diversity across a broader range of landscapes and a wider array of taxa. Here, we use a network of 96 study landscapes in six topographically diverse regions of Britain, to test the combined importance of honeybee density, insecticide loadings, floral resource availability and habitat diversity to pollinator communities. We also explore the interactions between these drivers and the cover and proximity of semi-natural habitat. We found that among our four drivers, only honeybee density was positively related to wild pollinator abundance and diversity, and the positive association between abundance and floral resources depended on insecticide loadings and habitat diversity. By contrast, our exploratory models including habitat composition metrics revealed a complex suite of interactive effects. These results demonstrate that improving pollinator community composition and health is unlikely to be achieved with general resource enhancements only. Rather, local land-use context should be considered in fine-tuning pollinator management and conservation. This article is part of the theme issue 'Natural processes influencing pollinator health: from chemistry to landscapes'.

A novel self-tuning proportional and derivative (ST-PD) control based TCP congestion control scheme is proposed. The new scheme approaches the congestion control problem from a control-theoretical perspective and overcomes several important limitations associated with existing TCP congestion control schemes, which are heuristic based. In the proposed scheme, a PD controller is employed to keep the buffer occupancy of the bottleneck node on the connection path at an ideal operating level, and it adjusts the TCP window accordingly. The control gains of the PD controller are tuned online by a fuzzy logic controller based on the perceived bandwidth–delay product of the TCP connection. This scheme gives ST-PD TCP several advantages over current TCP implementations. These include rapid response to bandwidth variations, insensitivity to buffer sizes, and significant improvement of TCP throughput over lossy links by decoupling congestion control and error control functions of TCP.

This paper describes a study to explore the integration of group support systems (GSS) and artificial intelligence (AI) technology to provide solicitation, analytical, visualization and sense-making support for attitudes from large distributed marketing focus groups. The paper describes two experiments and the concomitant evolutionary design and development of an attitude analysis process and the MindMine comment analysis tool. The analysis process circumvents many of the problems associated with traditional data gathering via closed-ended questionnaires and potentially biased interviews by providing support for online free response evaluative comments. MindMine allows teams of raters to analyze comments from any source, including electronic meetings, discussion groups or surveys, whether they are Web-based or same-place. The analysis results are then displayed as visualizations that enable the team quickly to make sense of attitudes reflected in the comment set, which we believe provide richer information and a more detailed understanding of attitudes.

Background: Physical activity reduces cardiovascular risk, partly via direct effects on the arterial wall. We hypothesized that vascular function responses would be modality-specific, sex-dependent, and express a high degree of heritability. Methods: We recruited 90 same-sex twins (31 monozygotic, 14 dizygotic dizygotic pairs; 25.8±6.0 years) and randomized 70 (25 monozygotic, 10 dizygotic) to complete, as pairs, 3 months each of resistance and endurance training, separated by a 3-month washout. Results: Brachial artery flow-mediated (FMD%) and glyceryl-trinitrate induced dilation (GTN%) both increased following endurance (FMD%: ∆1.46%, P &lt;0.001; GTN%: ∆1.76%, P =0.004) and resistance (FMD%: ∆1.73%, P &lt;0.001; GTN%: ∆1.68%, P =0.045). About one-third of participants failed to respond to one or other mode; 10% failed to respond to both for FMD% (17% for GTN%). FMD% and GTN% increased significantly in response to both resistance and endurance in females ( P &lt;0.05), but not males. Twin analysis revealed that responses to both FMD% and GTN% with exercise training for both modalities were dependent on factors shared by monozygotic pairs and that a large contribution from genetic effects is unlikely. Conclusions: Our findings indicate that both endurance and resistance can enhance vascular function and that responses in females were more marked. Most individuals respond to one or other form of training, with few unresponsive to both; a finding that has implications for optimizing exercise-based approaches for individualized benefit. Focusing on characteristics of exercise prescription may be more important than the impact of distinct candidate genes when considering exercise as a form of vascular medicine. Registration: URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371222 ; Unique identifier: ACTRN 12616001095459.

OBJECTIVE: To establish the rate of primary compliance with medication of children discharged from the paediatric ward of a regional hospital. METHODS: All paediatric admissions to a regional hospital for a 14-week period from April to July 2000 were studied. Patient data were collected for those paediatric inpatients discharged on medication. Written prescriptions kept by the local Aboriginal Medical Service and computerized data from local pharmacies were collected and the numbers filled were compared to ward discharge prescriptions. RESULTS: There were 160 medical paediatric admissions. The median admission age was 19 months. There was no difference in patient sex, number of drugs prescribed, diagnosis of infection, mean age or the proportion of children under 2 years, between filled and unfilled prescriptions. In total, 49 prescriptions were filled from a total of 65 written (75%). This figure compares unfavourably with that of the metropolitan tertiary referral centre. CONCLUSIONS: : Primary compliance was suboptimal, with the majority of unfilled prescriptions being for antibiotics. These findings suggest that a remediable cause of treatment failure may be primary non-compliance with medication in regional settings.

Summary The Monterey pine aphid, Essigella californica, has been associated with extensive defoliation and growth losses in radiata pine plantations in south-eastern Australia since it was first detected in 1998. HVP Plantations (HVPP) observed variation in the level of defoliation between clones in clonal seed orchards and archives, and initiated a program of assessment of progeny trials. Between 2001 and 2005, defoliation was assessed in a provenance trial, a subset of clones within a seed orchard, and 18 progeny trials (some repeatedly). Needle retention in upper crowns was scored on a scale of 1–10, rather than needle loss, because this ensured higher scores equated to the desirable state of the assessed trait. There were significant differences in the extent of retained foliage between populations, and between subpopulations within populations. The inland northern (Coastways Ranch) sub-population of Año Nuevo population had the highest level of retained foliage in the upper crown (mean score of 8.3), and the northern (Pico Creek, Haarst Ranch) sub-population of the Cambrian population had the least retained foliage (5.0). Estimates of heritability from progeny trials ranged from 0 to 0.9, and averaged about 0.5 in trials where there was a significant family (maternal) effect. Cross-site analysis using a family model resulted in an overall heritability of 0.4. Genetic correlations between assessments across two trials in 2004 and those in 2001 and 2003 were high, suggesting that defoliation due to aphids is consistent across years and can be considered to be the same trait. In addition to the observed differences between provenances and families, there were significant differences between clones, and average levels of retained foliage among clones ranged from 1.9 to 9.4. HVPP has used this information to develop an aphid-resistant breed of radiata pine which has been deployed on an increasing scale since 2005 into the most susceptible areas of its Victorian estate.

Johnstone et al. (2013) (Pacific Conservation Biology19, 122–141) make a substantial contribution to the knowledge of the forest red-tailed black cockatoo (Calyptorhynchus banksii naso) (FRTBC), presenting data on nest hollows and nest tree attributes. They discuss the threats to the current and future breeding hollows and conclude that ‘we are facing a major crisis in southern forests’. Although there are sound reasons for concern over the conservation of cockatoo species, the imminence of a crisis is not established by the data presented. We provide spatial and management context and present data relevant to discussion of threats to FRTBC hollows in south-west Western Australia. The primary strategy for providing habitat across the publicly owned forests is reservation, which formally excludes timber harvesting from more than 50% (1.3 million ha) of the forest, informally protects a further 11%, and protects habitat trees within harvested areas. Timber harvesting in these forests generally involves partial cutting, which retains trees of a wide range of size and age classes. A realistic minimum age for trees bearing hollows used by FRTBC in the jarrah (Eucalyptus marginata) forest is ~120–150 years (trees diameters of 50–60 cm), well below the 209 years highlighted by Johnstone et al. (2013). Most nest hollows occur in intermediate-sized trees. Clustering of FRTBC nest trees was not demonstrated in their data but is worthy of further investigation. Improved estimates of nest tree availability and loss would provide perspective on the threats to FRTBC, as would knowledge of population size and age structure of the FRTBC. The protection of known nest trees and control of feral competitors, where possible, would benefit FRTBC.

This paper introduces a testing strategy that is suitable for testing service-based applications. We describe an architecture that responds to changes of service operation, operation arguments and service composition changes. Our proof-of-concept test system performs runtime testing on our model atomic and composite web services using a random testing technique. A novel change identification method was developed to capture changes at the service interface. The test system is able to identify changes that occur in service operations and operational arguments in a service description of a test candidate. Our approach uses a new method to detect changes in a service inventory. Automated reconfiguration is used to support the continuous operation of the testing systems during a test candidate change.

The best evolutionary approach can be a difficult problem. In this work we have investigated two evolutionary representations to evolve non-photorealistic renderings: a variable-length classic genetic algorithm representation, and a tree-based genetic algorithm representation. These representations exhibit very different convergence behaviour, and despite considerable exploration of parameters the classic genetic algorithm was not competitive with the tree-based approach for the problem studied in this work. The aim of the work presented in this paper was to investigate whether analysis of the fitness landscapes described by the different representations can explain the difference in performance. We used several current fitness landscape measures to analyse the fitness landscapes, and found that one of the measures suggests there is a correlation between search performance and the fitness landscape.

A software system often consists of thousands of source files, which must be translated into thousands of intermediate files, which eventually must be translated into some small number of library and executable files. Collectively, these steps compose its build process. A large software system can be difficult to build. The steps can be numerous and complex. Of course, there are a variety of tools to assist us (e.g. MAKE), but their languages emphasize the specification of low-level details (e.g. compiler names and options), rather than high-level attributes (e.g. host/target platforms and required subsystems). This paper describes a new domain-specific language for specifying the composition and construction of a software system, where the emphasis is on high-level attributes. A specification is processed by a pipeline of fairly simple tools to produce a set of makefiles, which are then processed by MAKE in the usual way.