Multisite intervention studies have become increasingly common in infection control, for example, looking for a change in hospital infection rates after a regional policy change. The design of these studies can take various forms, from pre–post observational studies to randomized trials, in which sites are randomly assigned to the intervention or in which the intervention is sequentially introduced to different sites over time. Data collected under these settings are clustered by hospital and/or ward, consist of repeated measurements and, in some cases, exhibit temporal and/or seasonal patterns. Failure to account for these features in data analysis could well result in biased estimates of intervention effectiveness and impact on the generalizability of model results.

Background: Hereditary transthyretin-mediated (hATTR) amyloidosis is a multi-systemic, heterogenous, life-threatening disease. Patisiran resulted in significant improvement in neuropathy and QoL at 18-months compared to placebo, and was generally well-tolerated in the Phase 3 APOLLO study. Methods: Multi-center, OLE study to evaluate the efficacy and safety of long-term patisiran dosing for ≤ 5 years in hATTR amyloidosis patients with polyneuropathy who have completed the APOLLO study (NCT02510261). Endpoints include safety, tolerability and long-term efficacy of patisiran. Measures of clinical benefit are the same endpoints used in APOLLO including changes in mNIS+7 composite neuropathy impairment score and QoL (Norfolk QoL-DN) Results: As of December 2017, 184 of 186 (99%) patients who completed APOLLO and 25 patients from the Ph 2 OLE study enrolled in the Global OLE study. Baseline data for 211(APOLLO/placebo, n=49; APOLLO/patisiran, n=137 and patisiran Ph 2 OLE, n=25) patients included: median age 61 years (26-84); 74% males; 46% V30M. Interim safety data and 12-month efficacy results will be presented. Conclusions: The global OLE study includes a diverse population of hATTR amyloidosis patients. Interim data will include the long-term safety and maintenance of effect in patients continuing on patisiran, as well as the impact of treatment with patisiran on patients previously treated with placebo.

Decreases in cognitive function related to increases in oxidative stress and inflammation occur with ageing. Acknowledging the free radical-quenching activity and anti-inflammatory action of the carotenoid lycopene, the aim of the present review was to assess if there is evidence for a protective relationship between lycopene and maintained cognitive function or between lycopene and development or progression of dementia. A systematic literature search identified five cross-sectional and five longitudinal studies examining these outcomes in relation to circulating or dietary lycopene. Among four studies evaluating relationships between lycopene and maintained cognition, three reported significant positive relationships. Neither of the two studies reporting on relationship between lycopene and development of dementia reported significant results. Of four studies investigating circulating lycopene and pre-existing dementia, only one reported significant associations between lower circulating lycopene and higher rates of Alzheimer's disease mortality. Acknowledging heterogeneity among studies, there is insufficient evidence and a paucity of data to draw firm conclusions or tease apart direct effects of lycopene. Nevertheless, as low circulating lycopene is a predictor of all-cause mortality, further investigation into its relationship with cognitive longevity and dementia-related mortality is warranted.

A power MOSFET-based push–pull configuration nanosecond-pulse generator has been designed, constructed, and characterized to permeabilize cells for biological and medical applications. The generator can deliver pulses with durations ranging from 80 ns up to 1 µs and pulse amplitudes up to 1.4 kV. The unit has been tested for in vitro experiments on a medulloblastoma cell line. Following the exposure of cells to 100, 200, and 300 ns electric field pulses, permeabilization tests were carried out, and viability tests were conducted to verify the performance of the generator. The maximum temperature rise of the biological load was also calculated based on Joule heating energy conservation and experimental validation. Our results indicate that the developed device has good capabilities to achieve well-controlled electro-manipulation in vitro.

Icequakes at or near the bed of a glacier have the potential to allow us to investigate the interaction of ice with the underlying till or bedrock. Understanding this interaction is important for studying basal sliding of glaciers and ice streams, a critical process in ice dynamics models used to constrain future sea-level rise projections. However, seismic observations on glaciers can be dominated by seismic energy from surface crevassing. We present a method of automatically detecting basal icequakes and discriminating them from surface crevassing, comparing this method to a commonly used spectrum-based method of detecting icequakes. We use data from Skeidararjökull, an outlet glacier of the Vatnajökull Ice Cap, South-East Iceland, to demonstrate that our method outperforms the commonly used spectrum-based method. Our method detects a higher number of basal icequakes, has a lower rate of incorrectly identifying crevassing as basal icequakes and detects an additional, spatially independent basal icequake cluster. We also show independently that the icequakes do not originate from near the glacier surface. We conclude that the method described here is more effective than currently implemented methods for detecting and discriminating basal icequakes from surface crevassing.

Introduction: Identification of latent safety threats (LSTs) in the emergency department is an important aspect of quality improvement that can lead to improved patient care. In situ simulation (ISS) takes place in the real clinical environment and multidisciplinary teams can participate in diverse high acuity scenarios to identify LSTs. The purpose of this study is to examine the influence that the profession of the participant (i.e. physician, registered nurse, or respiratory therapist) has on the identification of LSTs during ISS. Methods: Six resuscitation- based adult and pediatric simulated scenarios were developed and delivered to multidisciplinary teams in the Kingston General Hospital ED. Each ISS session consisted of a 10- minute scenario, followed by 3-minutes of individual survey completion and a 7- minute group debrief led by ISS facilitators. An objective assessor recorded LSTs identified during each debrief. Surveys were completed prior to debrief to reduce response bias. Data was collected on participant demographics and perceived LSTs classified in the following categories: medication; equipment; resources and staffing; teamwork and communication; or other. Two reviewers evaluated survey responses and debrief notes to formulate a list of unique LSTs across scenarios and professions. The overall number and type of LSTs from surveys was identified and stratified by health care provider. Results: Thirteen ISS sessions were conducted with a total of 59 participants. Thirty- four unique LSTs (8 medication, 15 equipment, 5 resource, 4 communication, and 2 miscellaneous issues) were identified from surveys and debrief notes. Overall, MDs (n = 12) reported 19 LSTss (n = 41) reported 77 LSTs, and RTs (n = 6) reported 4 LSTs based on individual survey data. The most commonly identified category of LSTs reported by MDs (36.8%) and RTs (75%) was equipment issues while RNs most commonly identified medication issues (36.4%). Participants with □5 years of experience in their profession, on average identified more LSTs in surveys than participants with >5 years experience (1.9 LSTs vs 1.5 LSTs respectively). Conclusion: Nursing staff identified the highest number of LSTs across all categories. There was fairly unanimous identification of major LSTs across professions, however each profession did identify unique perspectives on LSTs in survey responses. ISS programs with the purpose of LST identification would benefit from multidisciplinary participation.

The Commensal Real-time Australian Square Kilometre Array Pathfinder Fast Transients survey is the first extensive astronomical survey using phased array feeds. Since January 2017, it has been searching for fast radio bursts in fly’s eye mode. Here, we present a calculation of the sensitivity and total exposure of the survey that detected the first 20 of these bursts, using the pulsars B1641-45 and B0833-45 as calibrators. The beamshape, antenna-dependent system noise, and the effects of radio-frequency interference and fluctuations during commissioning are quantified. Effective survey exposures and sensitivities are calculated as a function of the source counts distribution. Statistical ‘stat’ and systematics ‘sys’ effects are treated separately. The implied fast radio burst rate is significantly lower than the 37 sky−1 day−1 calculated using nominal exposures and sensitivities for this same sample by Shannon et al. (2018). At the Euclidean (best-fit) power-law index of −1.5 (−2.2), the rate is $12.7_{-2.2}^{+3.3}$ (sys) ± 3.6 (stat) sky−1 day−1 ( $20.7_{-1.7}^{+2.1}$ (sys) ± 2.8 (stat) sky−1 day−1) above a threshold of 56.6 ± 6.6(sys) Jy ms (40.4 ± 1.2(sys) Jy ms). This strongly suggests that these calculations be performed for other FRB-hunting experiments, allowing meaningful comparisons to be made between them.

The GaLactic and Extragalactic All-sky Murchison Widefield Array survey is a radio continuum survey at 72–231 MHz of the whole sky south of declination +30º, carried out with the Murchison Widefield Array. In this paper, we derive source counts from the GaLactic and Extragalactic All-sky Murchison data at 200, 154, 118, and 88 MHz, to a flux density limit of 50, 80, 120, and 290 mJy respectively, correcting for ionospheric smearing, incompleteness and source blending. These counts are more accurate than other counts in the literature at similar frequencies as a result of the large area of sky covered and this survey’s sensitivity to extended emission missed by other surveys. At S154 MHz > 0.5 Jy, there is no evidence of flattening in the average spectral index (α ≈ −0.8 where S ∝ vα) towards the lower frequencies. We demonstrate that the Square Kilometre Array Design Study model by Wilman et al. significantly underpredicts the observed 154-MHz GaLactic and Extragalactic All-sky Murchison counts, particularly at the bright end. Using deeper Low-Frequency Array counts and the Square Kilometre Array Design Study model, we find that sidelobe confusion dominates the thermal noise and classical confusion at v ≳ 100 MHz due to both the limited CLEANing depth and the undeconvolved sources outside the field-of-view. We show that we can approach the theoretical noise limit using a more efficient and automated CLEAN algorithm.

The low-frequency polarisation properties of radio sources are poorly studied, particularly in statistical samples. However, the new generation of low-frequency telescopes, such as the Murchison Widefield Array (the precursor for the low-frequency component of the Square Kilometre Array) offers an opportunity to probe the physics of radio sources at very low radio frequencies. In this paper, we present a catalogue of linearly polarised sources detected at 216 MHz, using data from the Galactic and Extragalactic All-sky Murchison Widefield Array survey. Our catalogue covers the Declination range –17° to –37° and 24 h in Right Ascension, at a resolution of around 3 arcminutes. We detect 81 sources (including both a known pulsar and a new pulsar candidate) with linearly polarised flux densities in excess of 18 mJy across a survey area of approximately 6 400 deg2, corresponding to a surface density of 1 source per 79 deg2. The level of Faraday rotation measured for our sources is broadly consistent with those recovered at higher frequencies, with typically more than an order of magnitude improvement in the uncertainty compared to higher-frequency measurements. However, our catalogue is likely incomplete at low Faraday rotation measures, due to our practice of excluding sources in the region where instrumental leakage appears. The majority of sources exhibit significant depolarisation compared to higher frequencies; however, a small sub-sample repolarise at 216 MHz. We also discuss the polarisation properties of four nearby, large-angular-scale radio galaxies, with a particular focus on the giant radio galaxy ESO 422–G028, in order to explain the striking differences in polarised morphology between 216 MHz and 1.4 GHz.

Streamwise velocity profiles and their wall-normal derivatives were used to investigate the properties of turbulent channel flow in the low polymer drag reduction $(DR)$ regime ( $DR=6.5\,\%$ to $26\,\%$ ), as realized via polymer injection at the channel surface. Streamwise velocity data were obtained over a friction Reynolds number ranging from $650$ to $1800$ using the single-velocity-component version of molecular tagging velocimetry (1c-MTV). This adaptation of the MTV technique has the ability to accurately capture instantaneous profiles at very high spatial resolution ( ${\gtrsim}850$ data points per wall-normal profile), and thus generate well-resolved derivative information as well. Owing to this ability, the present study is able to build upon and extend the recent numerical simulation analysis of White et al. (J. Fluid Mech., vol. 834, 2018, pp. 409–433) that examined the mean dynamical structure of polymer drag-reduced channel flow at friction Reynolds numbers up to $1000$ . Consistently, the present mean velocity profiles indicate that the extent of the logarithmic region diminishes with increasing polymer concentration, while statistically significant increases in the logarithmic profile slope begin to occur for drag reductions less than $15\,\%$ . Profiles of the r.m.s. streamwise velocity indicate that the maximum moves farther from the wall and increases in magnitude with reductions in drag. Similarly, with increasing drag reduction, the profile of the combined Reynolds and polymer shear stress exhibits a decrease in its maximum value that also moves farther from the wall. Correlations are presented that estimate the location and value of the maximum r.m.s. streamwise velocity and combined Reynolds and polymer shear stress. Over the range of $DR$ investigated, these effects consistently exhibit approximately linear trends as a function of $DR$ . The present measurements allow reconstruction of the mean momentum balance (MMB) for channel flow, which provides further insights regarding the physics described in the study by White et al. In particular, the present findings support a physical scenario in which the self-similar properties on the inertial domain identified from the leading-order structure of the MMB begin to detectably and continuously vary for drag reductions less than $10\,\%$ .

Growth mixture modeling with a sample of 749 Mexican heritage families identified parallel trajectories of adolescents’ and their mothers’ heritage cultural values and parallel trajectories of adolescents’ and their fathers’ heritage cultural values from Grades 5 to 10. Parallel trajectory profiles were then used to test cultural gap-distress theory that predicts increased parent–adolescent conflict and adolescent psychopathology over time when adolescents become less aligned with Mexican heritage values compared to their parents. Six similar parallel profiles were identified for the mother–youth and father–youth dyads, but only one of the six was consistent with the hypothesized problem gap pattern in which adolescents’ values were declining over time to become more discrepant from their parents. When compared to families in the other trajectory groups as a whole, mothers in the mother–adolescent problem gap trajectory group reported higher levels of mother–adolescent conflict in the 10th grade that accounted for subsequent increases in internalizing and externalizing symptoms assessed in 12th grade. Although the findings provided some support for cultural gap-distress predictions, they were not replicated with adolescent report of conflict nor with the father–adolescent trajectory group analyses. Exploratory pairwise comparisons between all six mother–adolescent trajectory groups revealed additional differences that qualified and extended these findings.

Recent studies reveal that at large friction Reynolds number $\unicode[STIX]{x1D6FF}^{+}$ the inertially dominated region of the turbulent boundary layer is composed of large-scale zones of nearly uniform momentum segregated by narrow fissures of concentrated vorticity. Experiments show that, when scaled by the boundary-layer thickness, the fissure thickness is $\mathit{O}(1/\sqrt{\unicode[STIX]{x1D6FF}^{+}})$ , while the dimensional jump in streamwise velocity across each fissure scales in proportion to the friction velocity $u_{\unicode[STIX]{x1D70F}}$ . A simple model that exploits these essential elements of the turbulent boundary-layer structure at large $\unicode[STIX]{x1D6FF}^{+}$ is developed. First, a master wall-normal profile of streamwise velocity is constructed by placing a discrete number of fissures across the boundary layer. The number of fissures and their wall-normal locations follow scalings informed by analysis of the mean momentum equation. The fissures are then randomly displaced in the wall-normal direction, exchanging momentum as they move, to create an instantaneous velocity profile. This process is repeated to generate ensembles of streamwise velocity profiles from which statistical moments are computed. The modelled statistical profiles are shown to agree remarkably well with those acquired from direct numerical simulations of turbulent channel flow at large $\unicode[STIX]{x1D6FF}^{+}$ . In particular, the model robustly reproduces the empirically observed sub-Gaussian behaviour for the skewness and kurtosis profiles over a large range of input parameters.

The proportion of adults aged 60 years and over is expected to increase over the coming decades. This ageing of the population represents an important health issue, given that marked reductions to cerebral macro- and microstructural integrity are apparent with increasing age. Reduced cerebral structural integrity in older adults appears to predict poorer cognitive performance, even in the absence of clinical disorders such as dementia. As such, it is becoming increasingly important to identify those factors predicting cerebral structural integrity, especially factors that are modifiable. One such factor is nutritional intake. While the literature is limited, data from available cross-sectional studies indicate that increased intake of nutrients such as B vitamins (for example, B6, B12 and folate), choline, n-3 fatty acids and vitamin D, or increased adherence to prudent whole diets (for example, the Mediterranean diet) predicts greater cerebral structural integrity in older adults. There is even greater scarcity of randomised clinical trials investigating the effects of nutritional supplementation on cerebral structure, though it appears that supplementation with B vitamins (B6, B12 and folic acid) or n-3 fatty acids (DHA or EPA) may be beneficial. The current review presents an overview of available research examining the relationship between key nutrients or adherence to select diets and cerebral structural integrity in dementia-free older adults.