Monitoring the incidence and causes of disease potentially transmitted by food in Australia: Annual report of the OzFoodNet network, 2016.

ABSTRACT: In 2016, a total of 44,455 notifications of enteric diseases potentially related to food were received by state and territory health departments in Australia. Consistent with previous years, campylobacteriosis (n = 24,171) and salmonellosis (n = 18,060) were the most frequently-notified infections. Notable increases in incidence were observed for shiga toxin-producing Escherichia coli (n = 343; 166% increase), shigellosis (n = 1,408; 93% increase), campylobacteriosis (33% increase) and salmonellosis (30% increase) when compared with the historical five-year mean. The extent to which the introduction of culture-independent testing as a method of diagnosis has contributed to these increases remains unclear. In total, 188 gastrointestinal outbreaks, including 177 foodborne outbreaks, were reported in 2016. The 11 non-foodborne outbreaks were due to environmental or probable environmental transmission (nine outbreaks) and animal-to-person or probable animal-to-person transmission (two outbreaks). No outbreaks of waterborne or probable waterborne transmission were reported in 2016. Foodborne outbreaks affected 3,639 people, resulting in at least 348 hospital admissions and four deaths. Eggs continue to be a source of Salmonella Typhimurium infection across the country: 35 egg-related outbreaks, affecting approximately 510 people, were reported across six jurisdictions in 2016. Three large multi-jurisdictional Salmonella outbreaks associated with mung bean sprouts (n = 419 cases); bagged salad products (n = 311 cases); and rockmelons (n = 144 cases) were investigated in 2016. These outbreaks highlight the risks associated with fresh raw produce and the ongoing need for producers, retailers and consumers to implement strategies to reduce potential Salmonella contamination.

The implications of high bed occupancy rates on readmission rates in England: A longitudinal study.

Hospital bed occupancy rates in the English National Health Service have risen to levels considered clinically unsafe. This study assesses the association of increased bed occupancy with changes in the percentage of overnight patients discharged from hospital on a given day, and their subsequent 30-day readmission rate. Longitudinal panel data methods are used to analyse secondary care records (n = 4,193,590) for 136 non-specialist Trusts between April 2014 and February 2016. The average bed occupancy rate across the study period was 90.4%. A 1% increase in bed occupancy was associated with a 0.49% rise in the discharge rate, and a 0.011% increase in the 30-day readmission rate for discharged patients. These associations became more pronounced once bed occupancy exceeded 95%. When bed occupancy rates were high, hospitals discharged a greater proportion of their patients. Those were mostly younger and less clinically complex, suggesting that hospitals are successfully prioritising early discharge amongst least vulnerable patients. However, while increased bed occupancy was not associated with a substantial increase in overall 30-day readmission rates, the relationship was more pronounced in older and sicker patients, indicating possible links with short-fallings in discharge processes.

Quantification of placental change in mouse models of preeclampsia using magnetic resonance microscopy.

Abnormal development of the placenta is postulated to be central to the aetiology of preeclampsia. This study investigates changes in placental histopathology in mouse models of preeclampsia compared to the morphology using magnetic resonance microscopy (MRM) (11.7 T) of intact ex vivo tissue followed by 3D analysis of the image data. Here, C57BL/6JArc pregnant mice were subject to either normal pregnancy (n=3), or to one of two experimental models of preeclampsia; TNF-α infusion  (n=3) or reduced uterine perfusion pressure(RUPP) (n=3). Placental tissue was collected at gestational day (gd) 17, fixed in formalin and incubated with Magnavist™ contrast agent, and high resolution images (50 µm × 50 µm × 50 µm voxels) obtained by magnetic resonance imaging at 11.74 T. Visual segmentation into placental subregions and three dimensional (3D) reconstruction followed by volume analysis was performed with Amira™ 3D analysis software. The significance of differences between treatment groups in total and regional volumes was assessed. In a single placenta the volumes measure by standard histology were compared. Three placentas from each animal were imaged, segmented into anatomical regions and 3D reconstructions generated. Total placental volume, labyrinth and decidual volume were not significantly different between groups. The junctional zone volume was found to be significantly larger in the RUPP animals (18.5±1.5 mm3) compared to TNF-α infused animals (15.8±1.5) or control animals (15.0±0.7, P<0.01). However, the decidual/junctional zone volume was smaller in the TNF-a compared to control animals (P<0.05). Placental structural change in experimental models of preeclampsia is able to be visualized and quantified using MRM and 3-D analysis. These techniques could prove to be a powerful tool in examining changes in placental morphology.

Shortening NMR experimental times.

Conventionally, arrayed nuclear magnetic resonance experiments, such as diffusion and relaxation, are performed with the same number of scans (NS) at each iteration despite the signal-to-noise ratio being more than sufficient for many of the iterations. Here, we propose a simple yet effective approach that significantly shortens experimental times by varying NS through the arrayed experiments while keeping the signal-to-noise ratio essentially the same and retaining experimental accuracy.

Jump-and-return sandwiches: A new family of binomial-like selective inversion sequences with improved performance.

A new family of binomial-like inversion sequences, named jump-and-return sandwiches (JRS), has been developed by inserting a binomial-like sequence into a standard jump-and-return sequence, discovered through use of a stochastic Genetic Algorithm optimisation. Compared to currently used binomial-like inversion sequences (e.g., 3-9-19 and W5), the new sequences afford wider inversion bands and narrower non-inversion bands with an equal number of pulses. As an example, two jump-and-return sandwich 10-pulse sequences achieved 95% inversion at offsets corresponding to 9.4% and 10.3% of the non-inversion band spacing, compared to 14.7% for the binomial-like W5 inversion sequence, i.e., they afforded non-inversion bands about two thirds the width of the W5 non-inversion band.

The protective effect of apolipoprotein in models of trophoblast invasion and preeclampsia.

Preeclampsia is a hypertensive disorder of pregnancy. It is associated with abnormal placentation via poor placental invasion of the uterine vasculature by trophoblast cells, leading to poor placental perfusion, oxidative stress, and inflammation, all of which are implicated in its pathogenesis. A dyslipidemia characterized by low plasma levels of high-density lipoproteins (HDL) and elevated triglycerides has been described in preeclampsia. Apolipoprotein A-I (apoA-I), a constituent of HDL is an anti-inflammatory agent. This study investigated whether apoA-I protects against hypertension and adverse placental changes in a proinflammatory cytokine (TNF-α)-induced model of preeclampsia. Further, this study investigated whether apoA-I protects against the inhibitory effect of TNF-α in a human in vitro model of trophoblast invasion. Administration of apoA-I to pregnant mice before infusion with TNF-α resulted in a significant reduction in the cytokine-induced increase in systolic blood pressure. MRI measurement of T2 relaxation, a parameter that is tissue specific and sensitive to physiological changes within tissues, showed a reversal of TNF-α-induced placental changes. Preincubation of endothelial cells with apoA-I protected against the TNF-α-induced inhibition of HTR-8/SVneo (trophoblast) cell integration into endothelial (UtMVEC) networks. These data suggest that a healthy lipid profile may affect pregnancy outcomes by priming endothelial cells in preparation for trophoblast invasion.

Physical characterization using diffusion NMR spectroscopy.

NMR diffusion measurements (or dNMR) provide a powerful tool for analysis of solution organization and microgeometry of the environment by probing random molecular motion. Being a very versatile method, dNMR can be applied to a large variety of samples and systems. Here, a brief introduction into dNMR and a summary of recent advances in the field are presented. The research topics include restricted diffusion, anisotropic diffusion, polymer dynamics, solution structuring and dNMR method development. The dNMR studied systems include plants, cells (cell models), liquid crystals, polymer solutions, ionic liquids, supercooled solutions, untreated water, amino acid solutions and more. It is demonstrated how a variety of dNMR methods can be applied to a system to extract the data on particular structures present among, formed by or surrounding the diffusing particles. It is also demonstrated how dNMR methods can be developed to allow probing larger geometries, low sample concentrations and faster processes. Copyright © 2016 John Wiley & Sons, Ltd.

Strategy to improve the quality of care in England.

The Five Year Forward View describes 'closing the care and quality gap' as one of three strategic challenges facing the English NHS by 2020. The need for a coherent national strategy for achieving high-quality, affordable care has rarely been more pressing, but how effectively do existing national decisions and interventions support clinicians delivering care on the front line? And, in a complex and dynamic environment with multiple players, how should the health service move forward to develop a balanced strategy for quality that accommodates longer term goals as well as more immediate political priorities? Research by a team at the Health Foundation has assessed how the array of organisations, initiatives and approaches to quality stack up as an emergent strategy. Four concepts were used to provide a yardstick for quality-related policies and activities to help identify potential imbalances, gaps and duplication. The findings of this work, together with suggested steps to rectify the issues identified, are described here.

Gd-DTPA-Dopamine-Bisphytanyl Amphiphile: Synthesis, Characterisation and Relaxation Parameters of the Nanoassemblies and Their Potential as MRI Contrast Agents.

Here, a new amphiphilic magnetic resonance imaging (MRI) contrast agent, a Gd(III)-chelated diethylenetriaminepentaacetic acid conjugated to two branched alkyl chains via a dopamine spacer, Gd-DTPA-dopamine-bisphytanyl (Gd-DTPA-Dop-Phy), which is readily capable of self-assembling into liposomal nanoassemblies upon dispersion in an aqueous solution, is reported. In vitro relaxivities of the dispersions were found to be much higher than Magnevist, a commercially available contrast agent, at 0.47 T but comparable at 9.40 T. Analysis of variable temperature (17)O NMR transverse relaxation measurements revealed the water exchange of the nanoassemblies to be faster than that previously reported for paramagnetic liposomes. Molecular reorientation dynamics were probed by (1)H NMRD profiles using a classical inner and outer sphere relaxation model and a Lipari-Szabo "model-free" approach. High payloads of Gd(III) ions in the liposomal nanoassemblies made solely from the Gd-DTPA-Dop-Phy amphiphiles, in combination with slow molecular reorientation and fast water exchange makes this novel amphiphile a suitable candidate to be investigated as an advanced MRI contrast agent.

Analysis of the liver lipidome reveals insights into the protective effect of exercise on high-fat diet-induced hepatosteatosis in mice.

The accumulation of lipid at ectopic sites, including the skeletal muscle and liver, is a common consequence of obesity and is associated with tissue-specific and whole body insulin resistance. Exercise is well known to improve insulin resistance by mechanisms not completely understood. We performed lipidomic profiling via mass spectrometry in liver and skeletal muscle samples from exercise-trained mice to decipher the lipid changes associated with exercise-induced improvements in whole body glucose metabolism. Obesity and insulin resistance were induced in C57BL/6J mice by high-fat feeding for 4 wk. Mice then underwent an exercise training program (treadmill running) 5 days/wk (Ex) for 4 wk or remained sedentary (Sed). Compared with Sed, Ex displayed improved (P < 0.01) whole body metabolism as measured via an oral glucose tolerance test. Deleterious lipid species such as diacylglycerol (P < 0.05) and cholesterol esters (P < 0.01) that accumulate with high-fat feeding were decreased in the liver of trained mice. Furthermore, the ratio of phosphatidylcholine (PC) to phosphatidylethanolamine (PE) (the PC/PE ratio), which is associated with membrane integrity and linked to hepatic disease progression, was increased by training (P < 0.05). These findings occurred without corresponding changes in the skeletal muscle lipidome. A concomitant decrease (P < 0.05) was observed for the fatty acid transporters CD36 and FATP4 in the liver, suggesting that exercise stimulates a coordinated reduction in fatty acid entry into hepatocytes. Given the important role of the liver in the regulation of whole body glucose homeostasis, hepatic lipid regression may be a key component by which exercise can improve metabolism.

Evaluation of Gd-DTPA-monophytanyl and phytantriol nanoassemblies as potential MRI contrast agents.

Supramolecular self-assembling amphiphiles have been widely used in drug delivery and diagnostic imaging. In this report, we present the self-assembly of Gd (III) chelated DTPA-monophytanyl (Gd-DTPA-MP) amphiphiles incorporated within phytantriol (PT), an inverse bicontinuous cubic phase forming matrix at various compositions. The dispersed colloidal nanoassemblies were evaluated as potential MRI contrast agents at various magnetic field strengths. The homogeneous incorporation of Gd-DTPA-MP in PT was confirmed by polarized optical microscopy (POM) and synchrotron small-angle X-ray scattering (SAXS) of the bulk phases of the mixtures. The liquid crystalline nanostructures, morphology, and the size distribution of the nanoassemblies were studied by SAXS, cryogenic transmission electron microscopy (cryo-TEM), and dynamic light scattering (DLS). The dispersions with up to 2 mol % of Gd-DTPA-MP in PT retained inverse cubosomal nanoassemblies, whereas the rest of the dispersions transformed to liposomal nanoassemblies. In vitro relaxivity studies were performed on all the dispersions at 0.54, 9.40, and 11.74 T and compared to Magnevist, a commercially available contrast agent. All the dispersions showed much higher relaxivities compared to Magnevist at both low and high magnetic field strengths. Image contrast of the nanoassemblies was also found to be much better than Magnevist at the same Gd concentration at 11.74 T. Moreover, the Gd-DTPA-MP/PT dispersions showed improved relaxivities over the pure Gd-DTPA-MP dispersion at high magnetic fields. These stable colloidal nanoassemblies have high potential to be used as combined delivery matrices for diagnostics and therapeutics.

A magnetic gradient induced force in NMR restricted diffusion experiments.

We predict that the phase cancellation of a precessing magnetisation field carried by a diffusing species in a bounded geometry under certain nuclear magnetic resonance pulsed magnetic field gradient sequences results in a small force over typically micrometre length scales. Our calculations reveal that the total magnetisation energy in a pore under the influence of a pulsed gradient will be distance-dependent thus resulting in a force acting on the boundary. It is shown that this effect of the magnetisation of diffusing particles will appear as either an attractive or repulsive force depending on the geometry of the pore and magnetic properties of the material. A detailed analysis is performed for the case of a pulsed gradient spin-echo experiment on parallel planes. It is shown that the force decays exponentially in terms of the spin-spin relaxation. The proof is based on classical electrodynamics. An application of this effect to soft matter is suggested.

Magnetic resonance imaging detects placental hypoxia and acidosis in mouse models of perturbed pregnancies.

Endothelial dysfunction as a result of dysregulation of anti-angiogenic molecules secreted by the placenta leads to the maternal hypertensive response characteristic of the pregnancy complication of preeclampsia. Structural abnormalities in the placenta have been proposed to result in altered placental perfusion, placental oxidative stress, cellular damage and inflammation and the release of anti-angiogenic compounds into the maternal circulation. The exact link between these factors is unclear. Here we show, using Magnetic Resonance Imaging as a tool to examine placental changes in mouse models of perturbed pregnancies, that T 2 contrast between distinct regions of the placenta is abolished at complete loss of blood flow. Alterations in T 2 (spin-spin or transverse) relaxation times are explained as a consequence of hypoxia and acidosis within the tissue. Similar changes are observed in perturbed pregnancies, indicating that acidosis as well as hypoxia may be a feature of pregnancy complications such as preeclampsia and may play a prominent role in the signalling pathways that lead to the increased secretion of anti-angiogenic compounds.

Diffusion studies of dihydroxybenzene isomers in water-alcohol systems.

Nuclear magnetic resonance diffusion studies can be used to identify different compounds in a mixture. However, because the diffusion coefficient is primarily dependent on the effective hydrodynamic radius, it is particularly difficult to resolve compounds with similar size and structure, such as isomers, on the basis of diffusion. Differential solution interactions between species in certain solutions can afford possibilities for separation. In the present study, the self-diffusion of the three isomers of dihydroxybenzene (i.e., (1,2-) catechol, (1,3-) resorcinol, and (1,4-) hydroquinone) was studied in water, aqueous monohydric alcohols (i.e., ethanol, 1-propanol, tert-butanol), and aqueous ethylene glycol. These systems allowed the effects of isomerism and differential solvent interactions on diffusion to be examined. It was found that, while in aqueous solution these isomers had the same diffusion coefficient, in water-monohydric alcohol systems the diffusion coefficient of catechol differed from those of resorcinol and hydroquinone. The separation was found to increase at higher concentrations of monohydric alcohols. The underlying chemical reasons for these differences were investigated.

Stress-induced grey matter loss determined by MRI is primarily due to loss of dendrites and their synapses.

Stress, unaccompanied by signs of post-traumatic stress disorder, is known to decrease grey matter volume (GMV) in the anterior cingulate cortex (ACC) and hippocampus but not the amygdala in humans. We sought to determine if this was the case in stressed mice using high-resolution magnetic resonance imaging (MRI) and to identify the cellular constituents of the grey matter that quantitatively give rise to such changes. Stressed mice showed grey matter losses of 10 and 15 % in the ACC and hippocampus, respectively but not in the amygdala or the retrosplenial granular area (RSG). Concurrently, no changes in the number or volumes of the somas of neurons, astrocytes or oligodendrocytes were detected. A loss of synaptic spine density of up to 60 % occurred on different-order dendrites in the ACC and hippocampus (CA1) but not in the amygdala or RSG. The loss of spines was accompanied by decreases in cumulative dendritic length of neurons of over 40 % in the ACC and hippocampus (CA1) giving rise to decreases in volume of dendrites of 2.6 mm(3) for the former and 0.6 mm(3) for the latter, with no change in the amygdala or RSG. These values are similar to the MRI-determined loss of GMV following stress of 3.0 and 0.8 mm(3) in ACC and hippocampus, respectively, with no changes in the amygdala or RSG. This quantitative study is the first to relate GMV changes in the cortex measured with MRI to volume changes in cellular constituents of the grey matter.

The ω-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation trial--rationale and design.

Postoperative atrial fibrillation/flutter (PoAF) commonly complicates cardiac surgery, occurring in 25% to 60% of patients. Postoperative atrial fibrillation/flutter is associated with significant morbidity, higher long-term mortality, and increased health care costs. Novel preventive therapies are clearly needed. In experiments and short-term trials, seafood-derived long-chain ω-3 polyunsaturated fatty acids (PUFAs) influence several risk factors that might reduce risk of PoAF. A few small and generally underpowered trials have evaluated effects of ω-3-PUFAs supplementation on PoAF with mixed results. The OPERA trial is an appropriately powered, investigator-initiated, randomized, double-blind, placebo-controlled, multinational trial to determine whether perioperative oral ω-3-PUFAs reduces occurrence of PoAF in patients undergoing cardiac surgery. Additional aims include evaluation of resource use, biologic pathways and mechanisms, postoperative cognitive decline, and safety. Broad inclusion criteria encompass a "real-world" population of outpatients and inpatients scheduled for cardiac surgery. Treatment comprises a total preoperative loading dose of 8 to 10 g of ω-3-PUFAs or placebo divided over 2 to 5 days, followed by 2 g/d until hospital discharge or postoperative day 10, whichever comes first. Based on anticipated 30% event rate in controls, total enrollment of 1,516 patients (758 per treatment arm) will provide 90% power to detect 25% reduction in PoAF. The OPERA trial will provide invaluable evidence to inform biologic pathways; proof of concept that ω-3-PUFAs influence cardiac arrhythmias; and potential regulatory standards and clinical use of this simple, inexpensive, and low-risk intervention to prevent PoAF.

Modeling diffusion in restricted systems using the heat kernel expansion.

The averaged return-to-origin probability of finding a diffusing particle within a volume or in the neighborhood of the surface of a bounded region can be separated into a volume and a surface integral of the corresponding probability densities. However with the usual treatments (e.g., the commonly encountered diffusion propagator approach) there is no clear method to separate the integration of the diffusion propagators in each domain. Here we propose a general procedure based on applying the heat kernel expansion in restricted diffusion problems for the Green's function of the diffusion equation on an arbitrary region with an arbitrary boundary condition. We apply this method to the treatment of surface reaction rate in a sphere subject to the reflecting boundary condition. We determine that the rate of diffusion of a particle from the interior to the surface of the sphere changes by the square root of time plus some extra correction terms. Further, we are able to relate the diffusion propagator to the invariant properties of the region. Also in this approach we investigate how the heat kernel expansion can be applied to the problem of determining the return-to-origin probability, where we obtain a more precise result for the expansion of this probability in the case of a sphere. The advantage of this method lies in its generality and applicability to any geometrical boundary configuration and any kind of boundary condition.