Understanding the mechanism by which Gd(III) coiled coils achieve magnetic resonance relaxivity - a study into the water coordination chemistry.

A class of Gd(III) coiled coils achieve high MRI relaxivity, in part due to their slow rotational correlation time. However, extending their length is unable to further enhance performance, as the mechanism by which relaxivity is achieved is dominated by the presence of three inner sphere waters in rapid exchange, through an associative mechanism.

Left ventricular dysfunction and intra-ventricular dyssynchrony in idiopathic pulmonary arterial hypertension.

BACKGROUND: Left ventricular (LV) filling pressures are normal in idiopathic pulmonary arterial hypertension (IPAH). However, direct and indirect interactions between the RV and LV can affect LV performance. We explored LV strain and LV intra-ventricular dyssynchrony in IPAH using feature tracking CMR (CMR-FT). METHODS: Seventy IPAH patients and 40 healthy volunteers were included. Patients underwent CMR and right heart catheterisation. The 4-chamber cine was used to calculate LV longitudinal strain (EllLV). LV circumferential (EccLV) and radial strain (ErrLV) were derived from a short axis cine. LV longitudinal, circumferential and radial intra-ventricular dyssynchrony indices were calculated. RESULTS: There were no differences between the IPAH and healthy volunteer group in LV ejection fraction (66.1% vs 64.2% p = 0.6672). EccLV (-29.1 vs -32.1 p = 0.0323) and EllLV (-16.6 vs -23.7 p < 0.0001) were lower in IPAH. In patients with more severe disease, there was greater impairment of ErrLV compared to mild disease (50.9 vs 87.5 P < 0.0001). LV synchrony was impaired in all directions in IPAH. ErrLV was associated with RV ejection fraction (r = 0.66), RV end-systolic volume index (r = -0.59), pulmonary vascular resistance (PVR)(r = 0.51) and stroke volume index (SVI)(r = 0.44). In a multivariate model with age, SVI and PVR, ErrLV (HR 0.970 p = 002) and radial dyssynchrony (HR 3.759 p < 0.0001) independently predicted survival. CONCLUSION: In IPAH, LV is dyssynchronous with impaired function. Measures of LV strain and intraventricular synchrony were associated with known markers of disease severity. These LV variables which are likely to be related to ventricular interaction, may add incremental value to known prognostic variables in IPAH.

Non-fatal opioid overdose, naloxone access, and naloxone training among people who recently used opioids or received opioid agonist treatment in Australia: The ETHOS Engage study.

BACKGROUND: Overdose is a major cause of morbidity and mortality among people who use opioids. Naloxone can reverse opioid overdoses and can be distributed and administered with minimal training. People with experience of overdose are a key population to target for overdose prevention strategies. This study aims to understand if factors associated with recent non-fatal opioid overdose are the same as factors associated with naloxone access and naloxone training in people who recently used opioids or received opioid agonist treatment (OAT). METHODS: ETHOS Engage is an observational study of people who inject drugs in Australia. Logistic regression models were used to estimate odds ratios for non-fatal opioid overdose, naloxone access and naloxone training. RESULTS: Between May 2018-September 2019, 1280 participants who recently used opioids or received OAT were enrolled (62% aged >40 years; 35% female, 80% receiving OAT, 62% injected drugs in the preceding month). Recent opioid overdose (preceding 12 months) was reported by 7% of participants, lifetime naloxone access by 17%, and lifetime naloxone training by 14%. Compared to people receiving OAT with no additional opioid use, recent opioid, benzodiazepine (preceding six months), and hazardous alcohol use was associated with recent opioid overdose (aOR 3.91; 95%CI: 1.68-9.10) and lifetime naloxone access (aOR 2.12; 95%CI 1.29-3.48). Among 91 people who reported recent overdose, 65% had never received take-home naloxone or naloxone training. CONCLUSIONS: Among people recently using opioids or receiving OAT, benzodiazepine and hazardous alcohol use is associated with non-fatal opioid overdose. Not all factors associated with non-fatal overdose correspond to factors associated with naloxone access. Naloxone access and training is low across all groups. Additional interventions are needed to scale up naloxone provision.

Incidence and risk factors of chronic thromboembolic pulmonary hypertension following venous thromboembolism, a population-based cohort study in England.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of unresolved organised pulmonary emboli/thrombi obstructing the major pulmonary arteries. The aim of this study was to estimate the incidence and risk factors of CTEPH in a cohort with first venous thromboembolism (VTE). This was a population-based cohort study of patients with first VTE and no active cancer in England between 2001 and 2012. CTEPH was assessed using a rigorous case-ascertainment algorithm. Risk factors for CTEPH were studied using a nested case-control approach by matching CTEPH cases to VTE patients without CTEPH. Adjusted odds ratios (OR) of comorbidities were estimated from conditional logistic regression. During 81,413 person-years of follow-up among 23,329 patients with first VTE (mean follow-up 3.5 years; maximum 11.0 years) 283 patients were diagnosed with CTEPH (incidence rate 3.5 per 1000 person-years); cumulative incidence was 1.3% and 3.3% at 2 and 10 years after pulmonary embolism, and 0.3% and 1.3% following deep vein thrombosis (DVT), respectively. Risk factors for CTEPH included age over 70, OR 2.04 (95% CI 1.23 to 3.38), female gender, 1.44 (1.06 to 1.94), pulmonary embolism at first VTE, 3.11 (2.23 to 4.35), subsequent pulmonary embolism and DVT, 3.17 (2.02 to 4.96) and 2.46 (1.34 to 4.51) respectively, chronic obstructive pulmonary disease 3.17 (2.13 to 4.73), heart failure 2.52 (1.76 to 3.63) and atrial fibrillation, 2.42 (1.71 to 3.42). CTEPH develops most commonly after pulmonary embolism and less frequently after DVT. Awareness of risk factors may increase referrals to specialised centres for confirmation of CTEPH and initiation of specific treatment.

Highly nonlinear yttrium-aluminosilicate optical fiber with a high intrinsic stimulated Brillouin scattering threshold.

Highly nonlinear (high-NA small-mode-area) optical fibers also possessing an intrinsically high stimulated Brillouin scattering threshold are described. More specifically, silica clad, yttrium-aluminosilicate core fibers are shown to exhibit an intrinsically low Brillouin gain coefficient between 0.125 and 0.139×10-11 m/W and a Brillouin gain linewidth of up to 500 MHz. Losses on the order of 0.7 dB/m were measured, resulting from impurities in the precursor materials. Nonlinear refractive index values are determined to be similar to that of silica, but significant measurement uncertainty is attributed to the need to estimate dispersion curves since their direct measurement could not be made. The interest for highly nonlinear optical fibers with a low intrinsic Brillouin gain coefficient is expected to continue, especially with the growing developments of narrow-linewidth high-energy laser systems.

A multi-centre cohort study evaluating the role of inflammatory markers in patient's presenting with acute ureteric colic (MIMIC).

BACKGROUND: Spontaneous Stone Passage (SSP) rates in acute ureteric colic range from 47 to 75%. There is conflicting evidence on the role of raised inflammatory markers in acute ureteric colic. The use of an easily applicable biomarker that could predict SSP or need for intervention would improve the management of obstructing ureteric stones. Thus, there is a need to determine in an appropriately powered study, in patients who are initially managed conservatively, which factors at the time of acute admission can predict subsequent patient outcome such as SSP and the need for intervention. Particularly, establishing whether levels of white cell count (WBC) at presentation are associated with likelihood of SSP or intervention may guide clinicians on the management of these patients' stones. DESIGN: Multi-center cohort study disseminated via the UK British Urology Researchers in Surgical Training (BURST) and Australian Young Urology Researchers Organisation (YURO). PRIMARY RESEARCH QUESTION: What is the association between WBC and SSP in patients discharged from emergency department after initial conservative management? PATIENT POPULATION: Patients who have presented with acute renal colic with CT KUB evidence of a solitary ureteric stone. A minimum sample size of 720 patients across 15 centres will be needed. HYPOTHESIS: A raised WBC is associated with decreased odds of spontaneous stone passage. PRIMARY OUTCOME: The occurrence of SSP within six months of presentation with acute ureteric colic (YES/NO). SSP was defined as absence of need for intervention to assist stone passage. STATISTICAL ANALYSIS PLAN: A multivariable logistic regression model will be constructed, where the outcome of interest is SSP using data from patients who do not undergo intervention at presentation. A random effect will be used to account for clustering of patients within hospitals/institutions. The model will include adjustments for gender, age as control variables.

De Novo Designed Imaging Agents Based on Lanthanide Peptides Complexes.

Herein are discussed a selection of lanthanide peptide/protein complexes in view of their potential applications as imaging agents, both in terms of luminescence detection and magnetic resonance imaging. Though this chapter covers a range of different peptides and protein, if focuses specifically on the opportunities afforded by the de novo design of coiled coils, miniature protein scaffolds, and the development on lanthanide-binding sites into these architectures. The requirements for lanthanide coordination and the challenges that need to be addressed when preparing lanthanide peptides with a view to their potential adoption as clinical imaging applications, will be highlighted.

Tunable continuous wave emission via phase-matched second harmonic generation in a ZnSe microcylindrical resonator.

Whispering gallery mode microresonators made from crystalline materials are of great interest for studies of low threshold nonlinear phenomena. Compared to amorphous materials, crystalline structures often exhibit desirable properties such as high indices of refraction, high nonlinearities, and large windows of transparency, making them ideal for use in frequency comb generation, microlasing and all-optical processing. In particular, crystalline materials can also possess a non-centrosymmetric structure which gives rise to the second order nonlinearity, necessary for three photon processes such as frequency doubling and parametric down-conversion. Here we report a novel route to fabricating crystalline zinc selenide microcylindrical resonators from our semiconductor fibre platform and demonstrate their use for tunable, low power continuous wave second harmonic generation. Visible red light is observed when pumped with a telecommunications band source by a process that is phase-matched between different higher order radial modes, possible due to the good spatial overlap between the pump and signal in the small volume resonator. By exploiting the geometrical flexibility offered by the fibre platform together with the ultra-wide 500-22000 nm transmission window of the ZnSe material, we expect these resonators to find use in applications ranging from spectroscopy to quantum information systems.

Kerr nonlinear switching in a hybrid silica-silicon microspherical resonator.

A hybrid silicon-core, silica-clad microspherical resonator has been fabricated from the semiconductor core fiber platform. Linear and nonlinear characterization of the resonator properties have shown it to exhibit advantageous properties associated with both materials, with the low loss cladding supporting high quality (Q) factor whispering gallery modes which can be tuned through the nonlinear response of the crystalline core. By exploiting the large wavelength shift associated with the Kerr nonlinearity, we have demonstrated all-optical modulation of a weak probe on the timescale of the femtosecond pump pulse. This novel geometry offers a route to ultra-low loss, high-Q silica-based resonators with enhanced functionality.

A Randomised Controlled Trial to Delay or Prevent Type 2 Diabetes after Gestational Diabetes: Walking for Exercise and Nutrition to Prevent Diabetes for You.

Aims. To develop a program to support behaviour changes for women with a history of Gestational Diabetes Mellitus (GDM) and a Body Mass Index (BMI) > 25 kg/m(2) to delay or prevent Type 2 Diabetes Mellitus. Methods. Women diagnosed with GDM in the previous 6 to 24 months and BMI > 25 kg/m(2) were randomized to an intervention (I) (n = 16) or a control (C) (n = 15) group. The intervention was a pedometer program combined with nutrition coaching, with the primary outcome increased weight loss in the intervention group. Secondary outcomes included decreased waist and hip measurements, improved insulin sensitivity and body composition, increased physical activity, and improved self-efficacy in eating behaviours. Results. Median (IQR) results were as follows: weight: I -2.5 (2.3) kg versus C +0.2 (1.6) kg (P = 0.009), waist: I -3.6 (4.5) cm versus C -0.1 (3.6) cm (P = 0.07), and hip: I -5.0 (3.3) cm versus C -0.2 (2.6) cm (P = 0.002). There was clinical improvement in physical activity and eating behaviours and no significant changes in glucose metabolism or body composition. Conclusion. A pedometer program and nutrition coaching proved effective in supporting weight loss, waist circumference, physical activity, and eating behaviours in women with previous GDM.

A prospective cross-sectional study of laparoscopic subtotal Lind fundoplication for gastro-oesophageal reflux disease--a durable and effective anti-reflux procedure.

INTRODUCTION: Laparoscopic partial fundoplication for gastro-oesophageal reflux disease (GORD) is reported to have fewer side effects when compared to Nissen fundoplication, but doubts remain over its long term durability in controlling reflux. The aim of this study was to assess outcome of symptoms for all patients presenting with GORD undergoing routine laparoscopic subtotal Lind fundoplication. MATERIALS & METHODS: All patients undergoing laparoscopic fundoplication between August, 1999 and November, 2007 performed by a single surgeon were included in the study. The anti-reflux procedure studied was laparoscopic Lind (300°) fundoplication with crural repair in all cases. Patients completed pre and post-operative questionnaires containing validated scoring systems for heartburn, gas bloat, dysphagia and overall patient satisfaction. RESULTS: Over the 100-month period, 320 consecutive patients underwent laparoscopic subtotal Lind fundoplication. Of these, 256 (80%) replied to the questionnaire at a mean of 31 months (range 3-96 months) following surgery. 91.4% of respondents had an improvement in heartburn symptom score with a significant reduction in score from 7.74 preoperatively to 1.25 postoperatively (p<0.001). There was also a significant reduction of mean modified Visick score for reflux control (heartburn and regurgitation) from 3.49 preoperatively to 1.48 after surgery (p<0.001). In total, 22 patients developed recurrent reflux symptoms with half of these reporting their recurrence within two years following surgery. Because of this all were tested with post-operative pH testing, yet only one had a 24-h pH time outside the normal range. Overall patient satisfaction was high with a visual analogue score of 9 and 88% of the patients claimed they would have the operation again. CONCLUSION: Laparoscopic Lind fundoplication demonstrates excellent reflux control when performed routinely for all patients presenting with GORD. This technique is both durable and efficacious in controlling reflux symptoms.

Influence of Carbon and Microbial Community Priming on the Attenuation of Uranium in a Contaminated Floodplain Aquifer.

The capacity for subsurface sediments to sequester radionuclide contaminants, such as uranium (U), and retain them after bioremediation efforts are completed is critical to the long-term stewardship of re-mediated sites. In U bioremediation strategies, carbon amendment stimulates bioreduction of U(VI) to U(IV), immobilizing it within the sediments. Sediments enriched in natural organic matter are naturally capable of sequestering significant U, but may serve as sources to the aquifer, contributing to plume persistence. Two types of organic-rich sediments were compared to better understand U release mechanisms. Sediments that were artificially primed for U removal were retrieved from an area previously biostimulated while detrital-rich sediments were collected from a location never subject to amendment. Batch incubations demonstrated that primed sediments rapidly removed uranium from the groundwater, whereas naturally reduced sediments released a sizeable portion of U before U(VI)-reduction commenced. Column experiments confirmed that U release persisted for 65 pore volumes in naturally reduced sediments, demonstrating their sink-source behavior. Acetate addition to primed sediments shifted the microbial community from sulfate-reducing bacteria within Desulfobacteraceae to the iron-reducing Geobacteraceae and Firmicutes, associated with efficient U(VI) removal and retention, respectively. In contrast, Geobacteraceae communities in naturally reduced sediments were replaced by sequences with similarity to Pseudomonas spp. during U release, while U(VI) removal only occurred with enrichment of Firmicutes. These investigations stress the importance of characterizing zones with heterogeneous carbon pools at U-contaminated sites prior to the determination of a remedial strategy to identify areas, which may contribute to long-term sourcing of the contaminants.

Four-wave mixing and octave-spanning supercontinuum generation in a small core hydrogenated amorphous silicon fiber pumped in the mid-infrared.

An octave-spanning supercontinuum is generated in a hydrogenated amorphous silicon core fiber when pumped in the mid-infrared regime. The broadband wavelength conversion which extends from the edge of the telecommunications band into the mid-infrared (1.64-3.37 µm) is generated by four-wave mixing (FWM) and subsequent pulse break-up, facilitated by the high material nonlinear figure of merit and the anomalous dispersion of the relatively small 1.7 µm diameter core fiber. The FWM sidebands and corresponding supercontinuum can be tuned through the pump parameters, and show good agreement with the predicted phase-matching curves for the fiber.

Optical detection and modulation at 2µm-2.5µm in silicon.

Recently the 2µm wavelength region has emerged as an exciting prospect for the next generation of telecommunications. In this paper we experimentally characterise silicon based plasma dispersion effect optical modulation and defect based photodetection in the 2-2.5µm wavelength range. It is shown that the effectiveness of the plasma dispersion effect is dramatically increased in this wavelength window as compared to the traditional telecommunications wavelengths of 1.3µm and 1.55µm. Experimental results from the defect based photodetectors show that detection is achieved in the 2-2.5µm wavelength range, however the responsivity is reduced as the wavelength is increased away from 1.55µm.

Ultrafast optical control using the Kerr nonlinearity in hydrogenated amorphous silicon microcylindrical resonators.

Microresonators are ideal systems for probing nonlinear phenomena at low thresholds due to their small mode volumes and high quality (Q) factors. As such, they have found use both for fundamental studies of light-matter interactions as well as for applications in areas ranging from telecommunications to medicine. In particular, semiconductor-based resonators with large Kerr nonlinearities have great potential for high speed, low power all-optical processing. Here we present experiments to characterize the size of the Kerr induced resonance wavelength shifting in a hydrogenated amorphous silicon resonator and demonstrate its potential for ultrafast all-optical modulation and switching. Large wavelength shifts are observed for low pump powers due to the high nonlinearity of the amorphous silicon material and the strong mode confinement in the microcylindrical resonator. The threshold energy for switching is less than a picojoule, representing a significant step towards advantageous low power silicon-based photonic technologies.

Nonlinear transmission properties of hydrogenated amorphous silicon core fibers towards the mid-infrared regime.

The nonlinear transmission properties of hydrogenated amorphous silicon (a-Si:H) core fibers are characterized from the near-infrared up to the edge of the mid-infrared regime. The results show that this material exhibits linear losses on the order of a few dB/cm, or less, over the entire wavelength range, decreasing down to a value of 0.29 dB/cm at 2.7µm, and negligible nonlinear losses beyond the two-photon absorption (TPA) edge ~ 1.7µm. By measuring the dispersion of the nonlinear Kerr and TPA parameters we have found that the nonlinear figure of merit (FOM(NL)) increases dramatically over this region, with FOM(NL) > 20 around 2µm and above. This characterization demonstrates the potential for a-Si:H fibers and waveguides to find use in nonlinear applications extending beyond telecoms and into the mid-infrared regime.