Capacity building to address antimicrobial resistance in remote Australia: The inaugural HOT NORTH Antimicrobial Academy.

BACKGROUND: Rates of antimicrobial resistance (AMR) for some pathogens in Australia are considerably higher in rural and remote compared to urban regions. The inaugural Hot North Antimicrobial Academy was a 9-month educational programme aimed to build workforce knowledge and capacity in antimicrobial use, audit, stewardship, surveillance and drug resistance in remote primary health care. METHODS: The Academy was advertised to Aboriginal and Torres Strait Islander, regional and remote healthcare workers. Participants were Aboriginal health practitioners, nurses, pharmacists and doctors from Queensland, Northern Territory, South Australia and Western Australia working in remote primary health care with a focus on Indigenous health. Due to COVID-19 restrictions, the Academy ran virtually from February-November 2021 using Microsoft Teams. The Academy was evaluated using surveys and yarning circles to assess impact and knowledge gain. RESULTS: Participants and faculty from across Australia attended 19 lectures and mentorship sessions. Eleven participants commenced and eight (73%) completed the Academy. The Academy raised participants awareness of AMR guidelines, governance and generating change; built confidence in advocacy; grew knowledge about drug resistant infections; and created a community of AMR champions in Indigenous health. CONCLUSION: The evaluation confirmed the Academy met the needs of participants, provided opportunities to move stewardship from tertiary hospitals into Indigenous and remote clinics and developed skills in research, audit, stewardship and advocacy for all involved. All sessions were recorded for future use, with facilitation by the National Aboriginal Community Controlled Health Organisation (NACCHO) in future years.

Generalized Electrical Substitution Methods and Detectors for Absolute Optical Power Measurements.

We have developed generalized methods for electrical substitution optical measurements, as well as cryogenic detectors which can be used to implement them. The new methods detailed here enable measurement of arbitrary periodic waveforms by an electrical substitution radiometer (ESR), which means that spectral and dynamic optical power can be absolutely calibrated directly by a primary standard detector. Cryogenic ESRs are not often used directly by researchers for optical calibrations due to their slow response times and cumbersome operation. We describe two types of ESRs with fast response times, including newly developed cryogenic bolometers with carbon nanotube absorbers, which are manufacturable by standard microfabrication techniques. These detectors have response times near 10 ms, spectral coverage from the ultraviolet to far-infrared, and are ideal for use with generalized electrical substitution. In our first tests of the generalized electrical substitution method with FTS, we have achieved uncertainty in detector response of 0.13 % (k=1) and total measurement uncertainty of 1.1 % (k=1) in the mid-infrared for spectral detector responsivity calibrations. The generalized method and fast detectors greatly expand the range of optical power calibrations which can be made using a wideband primary standard detector, which can shorten calibration chains and improve uncertainties.

Room temperature laser power standard using a microfabricated, electrical substitution bolometer.

The design and performance of a room temperature electrical substitution radiometer for use as an absolute standard for measuring continuous-wave laser power over a wide range of wavelengths, beam diameters, and powers are described. The standard achieves an accuracy of 0.46% (k = 2) for powers from 10 mW to 100 mW and 0.83% (k = 2) for powers from 1 mW to 10 mW and can accommodate laser beam diameters (1/e2) up to 11 mm and wavelengths from 300 nm to 2 µm. At low power levels, the uncertainty is dominated by sensitivity to fluctuations in the thermal environment. The core of the instrument is a planar, silicon microfabricated bolometer with vertically aligned carbon nanotube absorbers, commercial surface mount thermistors, and an integrated heater. Where possible, commercial electronics and components were used. The performance was validated by comparing it to a National Institute of Standards and Technology primary standard through a transfer standard silicon trap detector and by comparing it to the legacy "C-series" standards in operation at the U.S. Air Force Metrology and Calibration Division (AFMETCAL).

Nature of fiber-coupled detector responsivity measurements at 0.1% using a primary standard.

We demonstrate the capability to measure the absolute power responsivity of optical fiber-coupled detectors at an expanded uncertainty of 0.1%, by direct comparison with a cryogenic primary standard. To facilitate synchronous power measurements, commercial all-fiber beam-splitters direct laser diode light simultaneously to the device under test and the primary standard. We investigate the use of single-mode, polarisation maintaining, and photonic crystal fibers to access the cryogenic standard, and report a reduction in the temperature dependent effective refractive index of these fibers of 0.1%, 0.15% and 0.3% respectively in going from room temperature to 5 K. We also evaluate the polarisation dependent loss of the beam-splitters, the stability of the beam-splitter ratio between the cryogenic detector and the device under test and the temporal and modal stability of the Fabry-Pérot laser diode sources. It is shown that the stability of the optical fiber beam-splitters limits the overall performance of the measurement system to an expanded uncertainty of 0.1%.

Observed psychopathology in offspring of parents with major depressive disorder, bipolar disorder and schizophrenia.

BACKGROUND: Children of parents with mood and psychotic disorders are at elevated risk for a range of behavioral and emotional problems. However, as the usual reporter of psychopathology in children is the parent, reports of early problems in children of parents with mood and psychotic disorders may be biased by the parents' own experience of mental illness and their mental state. METHODS: Independent observers rated psychopathology using the Test Observation Form in 378 children and youth between the ages of 4 and 24 (mean = 11.01, s.d. = 4.40) who had a parent with major depressive disorder, bipolar disorder, schizophrenia, or no history of mood and psychotic disorders. RESULTS: Observed attentional problems were elevated in offspring of parents with major depressive disorder, bipolar disorder and schizophrenia (effect sizes ranging between 0.31 and 0.56). Oppositional behavior and language/thought problems showed variable degrees of elevation (effect sizes 0.17 to 0.57) across the three high-risk groups, with the greatest difficulties observed in offspring of parents with bipolar disorder. Observed anxiety was increased in offspring of parents with major depressive disorder and bipolar disorder (effect sizes 0.19 and 0.25 respectively) but not in offspring of parents with schizophrenia. CONCLUSIONS: Our results suggest that externalizing problems and cognitive and language difficulties may represent a general manifestation of familial risk for mood and psychotic disorders, while anxiety may be a specific marker of liability for mood disorders. Observer assessment may improve early identification of risk and selection of youth who may benefit from targeted prevention.

Understanding the association between pressure ulcers and sitting in adults what does it mean for me and my carers? Seating guidelines for people, carers and health & social care professionals.

The aim of the publication was to develop a practical guide for people, carers and health and social care professionals on how the research and evidence base on pressure ulcer prevention and management can be applied to those who remain seated for extended periods of time. This publication was developed at the request of the Tissue Viability Society in order to revise the original seating guidelines from 2008 as evidence and subsequent care has moved forward in relation to this area. Since 2008, the costs for the prevention and management of pressure ulcers have increased significantly and there is limited published advice from health and social care organisations on seating and preventing pressure ulcers. These guidelines have been written for: Who live or work in primary, secondary, and tertiary settings.

In-line and cascaded DWDM transmission using a 15dB net-gain polarization-insensitive fiber optical parametric amplifier.

We demonstrate and characterize polarization-division multiplexed (PDM) DWDM data transmission for the first time in a range of systems incorporating a net-gain polarization-insensitive fiber optical parametric amplifier (PI-FOPA) for loss compensation. The PI-FOPA comprises a modified diversity-loop architecture to achieve 15dB net-gain, and up to 2.3THz (~18nm) bandwidth. Three representative systems are characterized using a 100Gb/s PDM-QPSK signal in conjunction with emulated DWDM neighbouring channels: (a) a 4x75km in-line fiber transmission system incorporating multiple EDFAs and a single PI-FOPA (b) N cascaded PI-FOPA amplification stages in an unlevelled Nx25km recirculating loop arrangement, with no EDFAs used within the loop signal path, and (c) M cascaded PI-FOPA amplification stages as part of an Mx75.6km gain-flattened recirculating loop system with the FOPA compensating for the transmission fiber loss, and EDFA compensation for loop switching and levelling loss. For the 4x75km in-line system (a), we transmit 45x50GHz-spaced signals ('equivalent' data-rate of 4.5Tb/s) with average OSNR penalty of 1.3dB over the band at 10-3 BER. For the unlevelled 'FOPA-only' 25.2km cascaded system (b), we report a maximum of eight recirculations for all 10x100GHz-spaced signals, and five recirculations for 20x50GHz-spaced signals. For the 75.6km levelled system

20 dB net-gain polarization-insensitive fiber optical parametric amplifier with >2 THz bandwidth.

A black-box polarization insensitive fiber optical parametric amplifier (PI-FOPA) is characterized for the first time using a commercial 127 Gb/s polarization-division multiplexed PDM-QPSK transponder within a multiplex of twenty-two equivalent DWDM signals across a 2.3 THz bandwidth portion of the C-band. The PI-FOPA employs a recently demonstrated diversity loop arrangement comprising two lengths of highly nonlinear fiber (HNLF) with the parametric pump being removed after the first HNLF in both directions about the loop. This arrangement is named the Half-Pass Loop FOPA or HPL-FOPA. In total, a record equivalent 2.3 Tb/s of data is amplified within the HPL-FOPA for three different pump power regimes producing net-gains of 10 dB, 15 dB and 20 dB (averaged over all signals). For the latter two regimes, the gain bandwidth is observed to extend considerably beyond the C-band, illustrating the potential for this design to amplify signals over bandwidths commensurate with the EDFA and beyond. Under the 15 dB gain condition, the average OSNR penalty to achieve 10-3 bit error rate for all twenty three signals was found to be 0.5 ± 0.3 dB. Worst case penalty was 0.8 ± 0.3 dB, verifying the use of the architecture for polarization insensitive operation. The growth of four-wave mixing signal-signal crosstalk is additionally characterized and found to be gain independent for a fixed output power per signal. A simple effective length model is developed which predicts this behavior and suggests a new configuration for significantly reduced crosstalk.

Ultra-flat wideband single-pump Raman-enhanced parametric amplification.

We experimentally optimize a single pump fiber optical parametric amplifier in terms of gain spectral bandwidth and gain variation (GV). We find that optimal performance is achieved with the pump tuned to the zero-dispersion wavelength of dispersion stable highly nonlinear fiber (HNLF). We demonstrate further improvement of parametric gain bandwidth and GV by decreasing the HNLF length. We discover that Raman and parametric gain spectra produced by the same pump may be merged together to enhance overall gain bandwidth, while keeping GV low. Consequently, we report an ultra-flat gain of 9.6 ± 0.5 dB over a range of 111 nm (12.8 THz) on one side of the pump. Additionally, we demonstrate amplification of a 60 Gbit/s QPSK signal tuned over a portion of the available bandwidth with OSNR penalty less than 1 dB for Q2 below 14 dB.

Genomic Appraisal of the Multifactorial Basis for In Vitro Acquisition of Miltefosine Resistance in Leishmania donovani.

Protozoan parasites of the Leishmania donovani complex are the causative agents of visceral leishmaniasis (VL), the most severe form of leishmaniasis, with high rates of mortality if left untreated. Leishmania parasites are transmitted to humans through the bite of infected female sandflies (Diptera: Phlebotominae), and approximately 500,000 new cases of VL are reported each year. In the absence of a safe human vaccine, chemotherapy, along with vector control, is the sole tool with which to fight the disease. Miltefosine (hexadecylphosphatidylcholine [HePC]), an antitumoral drug, is the only successful oral treatment for VL. In the current study, we describe the phenotypic traits of L. donovani clonal lines that have acquired resistance to HePC. We performed whole-genome and RNA sequencing of these resistant lines to provide an inclusive overview of the multifactorial acquisition of experimental HePC resistance, circumventing the challenge of identifying changes in membrane-bound proteins faced by proteomics. This analysis was complemented by assessment of the in vitro infectivity of HePC-resistant parasites. Our work underscores the importance of complementary "omics" to acquire the most comprehensive insight for multifaceted processes, such as HePC resistance.

Assessing Conformance with Benford's Law: Goodness-Of-Fit Tests and Simultaneous Confidence Intervals.

Benford's Law is a probability distribution for the first significant digits of numbers, for example, the first significant digits of the numbers 871 and 0.22 are 8 and 2 respectively. The law is particularly remarkable because many types of data are considered to be consistent with Benford's Law and scientists and investigators have applied it in diverse areas, for example, diagnostic tests for mathematical models in Biology, Genomics, Neuroscience, image analysis and fraud detection. In this article we present and compare statistically sound methods for assessing conformance of data with Benford's Law, including discrete versions of Cramér-von Mises (CvM) statistical tests and simultaneous confidence intervals. We demonstrate that the common use of many binomial confidence intervals leads to rejection of Benford too often for truly Benford data. Based on our investigation, we recommend that the CvM statistic Ud(2), Pearson's chi-square statistic and 100(1 - α)% Goodman's simultaneous confidence intervals be computed when assessing conformance with Benford's Law. Visual inspection of the data with simultaneous confidence intervals is useful for understanding departures from Benford and the influence of sample size.

An ultrasonographic scoring method for transabdominal monitoring of ascarid burdens in foals.

REASONS FOR PERFORMING STUDY: Parascaris spp. infections can lead to life-threatening small intestinal impactions in foals. Currently available diagnostic techniques cannot estimate the magnitude of an ascarid burden, and hence identify foals potentially at risk of developing impactions. OBJECTIVES: To describe and evaluate an ultrasonographic transabdominal scoring technique for monitoring of ascarid burdens in foals and to perform a cost-benefit analysis of the application of this technique. STUDY DESIGN: A transabdominal ultrasonographic technique was validated against ascarid worm counts from 10 foals aged 162-294 days. In a treatment trial, 15 foals were randomly allocated to 3 treatment groups: ivermectin, oxibendazole and no treatment. Blinded ultrasound examinations were performed daily for 5 consecutive days following treatment. Foals were examined ultrasonographically twice by the same investigator, and by different investigators for intra- and interobserver agreement evaluation. Cost-benefit analyses identified threshold values for the probability of ascarid impactions above which the screening method becomes cost-effective. METHODS: The ultrasound technique used 3 locations along the ventral midline. An ascarid scoring system was established that assessed the magnitude of ascarid burden ranging from 1-4. The method was validated against worm burdens of 10 worms and above with calculation of diagnostic specificity, sensitivity, and predictive values. Treatment trial data were evaluated statistically using mixed model analysis. Kappa values were generated for intra- and interobserver agreement. RESULTS: Two consecutive examinations were found to detect worm burdens >10 ascarids reliably. Ascarid scores declined in response to both anthelmintic treatments, although differences were not statistically significant. Kappa values indicated fair to moderate intra- and interobserver agreements. The majority of cost-benefit analyses indicated that ultrasound examinations are cost effective when the probability of ascarid impactions is above a range of 0.0001-0.0082 (i.e. 1 in 10,000 to 8 in 1000 foals). CONCLUSIONS: The ultrasonographic screening techniques can be a useful tool for monitoring ascarid burdens in foals.

Plasma-induced signatures reveal an extracellular milieu possessing an immunoregulatory bias in treatment-naive paediatric inflammatory bowel disease.

The inflammatory state associated with Crohn's disease (CD) and ulcerative colitis (UC) remains incompletely defined. To understand more clearly the extracellular milieu associated with inflammatory bowel disease (IBD), we employed a bioassay whereby plasma of treatment naive paediatric IBD patients (n = 22 CD, n = 15 UC) and unrelated healthy controls (uHC, n = 10) were used to induce transcriptional responses in a healthy leucocyte population. After culture, gene expression was measured comprehensively with microarrays and analysed. Relative to uHC, plasma of CD and UC patients induced distinct responses consisting, respectively, of 985 and 895 regulated transcripts [|log2 ratio| ≥ 0·5 (1·4-fold); false discovery rates (FDR) ≤ 0·01]. The CD:uHC and UC:uHC signatures shared a non-random, commonly regulated, intersection of 656 transcripts (χ(2)  = P < 0·001) and were highly correlative [Pearson's correlation coefficient = 0·96, 95% confidence interval (CI) = 0.96, 0.97]. Despite sharing common genetic susceptibility loci, the IBD signature correlated negatively with that driven by plasma of type 1 diabetes (T1D) patients (Pearson's correlation coefficient = -0·51). Ontological analyses revealed the presence of an immunoregulatory plasma milieu in IBD, as transcripts for cytokines/chemokines, receptors and signalling molecules consistent with immune activation were under-expressed relative to uHC and T1D plasma. Multiplex enzyme-linked immunosorbent assay (ELISA) and receptor blockade studies confirmed transforming growth factor (TGF)-ß and interleukin (IL)-10 as contributors to the IBD signature. Analysis of CD patient signatures detected a subset of transcripts associated with responsiveness to 6-mercaptopurine treatment. Through plasma-induced signature analysis, we have defined a unique, partially TGF-ß/IL-10-dependent immunoregulatory signature associated with IBD that may prove useful in predicting therapeutic responsiveness.

Suppression of WDM four-wave mixing crosstalk in fibre optic parametric amplifier using Raman-assisted pumping.

We perform an extensive numerical analysis of Raman-Assisted Fibre Optical Parametric Amplifiers (RA-FOPA) in the context of WDM QPSK signal amplification. A detailed comparison of the conventional FOPA and RA-FOPA is reported and the important advantages offered by the Raman pumping are clarified. We assess the impact of pump power ratios, channel count, and highly nonlinear fibre (HNLF) length on crosstalk levels at different amplifier gains. We show that for a fixed 200 m HNLF length, maximum crosstalk can be reduced by up to 7 dB when amplifying 10x58Gb/s QPSK signals at 20 dB net-gain using a Raman pump of 37 dBm and parametric pump of 28.5 dBm in comparison to a standard single-pump FOPA using 33.4 dBm pump power. It is shown that a significant reduction in four-wave mixing crosstalk is also obtained by reducing the highly nonlinear fibre interaction length. The trend is shown to be generally valid for different net-gain conditions and channel grid size. Crosstalk levels are additionally shown to strongly depend on the Raman/parametric pump power ratio, with a reduction in crosstalk seen for increased Raman pump power contribution.

Transfusion-associated dyspnea--shadow or substance?

New Zealand Blood Service Haemovigilance uses International Society of Blood Transfusion/International Haemovigilance Network definitions to categorize transfusion reactions (TR). Transfusion-associated dyspnoea (TAD) is a category for TR with respiratory features (TRRF) that do not fit definitive entities. TRRF, including TAD, are clinically significant. TR classified as TAD were reviewed. We found that many TAD may have been transfusion-associated circulatory overload. Better information in TR reports and refining TR diagnostic criteria may result in less misclassification of TRRF. TAD may represent mild, atypical or overlap entities, and there may be a residuum of cases with currently unexplained pathophysiology.