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BACKGROUND: Renal impairment post-percutaneous coronary intervention (post-PCI) is a well-described adverse effect following the administration of contrast media. Within a large cohort of registry patients, we aimed to explore the incidence, predictors and clinical outcomes of renal impairment post-PCI. METHODS: The Victorian Cardiac Outcomes Registry is an Australian state-based clinical quality registry focusing on collecting data from all PCI capable centres. Data from 36 970 consecutive PCI cases performed between 2014 and 2018 were analysed. Patients were separated into three groups based on post-procedure creatinine levels (new renal impairment (NRI), defined as an absolute rise in serum creatinine>44.2 µmol/L or>25% of baseline creatinine; new renal impairment requiring dialysis (NDR), defined as worsening renal failure that necessitated a new requirement for renal dialysis; no NRI). Multivariate logistic regression analysis was performed to investigate the impact of NRI and NDR on clinical outcomes. RESULTS: 3.1% (n=1134) of patients developed NRI, with an additional 0.6% (n=225) requiring dialysis. 96.3% (n=35 611) of patients did not develop NRI. Those who developed renal impairment were more comorbid, with higher rates of diabetes (22% vs 38% vs 38%, p<0.001), peripheral vascular disease (3.4% vs 8.2% vs 11%, p<0.001), chronic kidney disease (19% vs 49.7% vs 54.2%) and severe left ventricular dysfunction (5% vs 22% vs 40%, p<0.001). Multivariable analysis found that when compared with the no NRI group, those in the combined NRI/NDR group were at a greater risk of 30-day mortality (OR 4.77; 95% CI 3.89 to 5.86, p<0.001) and 30-day major adverse cardiac events (OR 3.72; 95% CI 3.15 to 4.39, p<0.001). CONCLUSIONS: NRI post-PCI remains a common occurrence, especially among comorbid patients, and is associated with a significantly increased morbidity and mortality risk.

Iron is critical for life. Nature capitalizes on the physical attributes of iron biominerals for functional, structural, and sensory applications. Iron biomineralization is well exemplified by the magnetite-bearing radula of chitons, the hardest known biomineral of any animal. Although magnetism is an integral property of iron biominerals, limited information exists on the magnetic state, structure, and orientation of these nanoscale materials during mineralization. The advent of quantum-based magnetic microscopy provides a new avenue to probe these biological systems directly, providing detailed magnetic information of the iron oxide structures. Here two complementary quantum magnetic microscopy methods are applied, based on nitrogen-vacancy centers in diamond, to spatially map the mineral phases ferrihydrite and magnetite in the developing teeth of the chiton Acanthopleura hirtosa. The images reveal previously undiscovered long-range magnetic order, established at the onset of magnetite mineralization. This is in contrast to electron microscopy studies that show no strong common crystallographic orientation. The implications of these results are important, not just for the insights gained in biomineralization of the target organism, but also for the study of a broad range of iron minerals in the physical and biological sciences.

Coronary artery disease (CAD) screening and diagnosis are core cardiac specialty services. From symptoms, autopsy correlations supported reductions in coronary blood flow and dynamic epicardial and microcirculatory coronaries artery disease as etiologies. While angina remains a clinical diagnosis, most cases require correlation with a diagnostic modality. At the onset of the evidence building process much research, now factored into guidelines were conducted among population and demographics that were homogenous and often prior to newer technologies being available. Today we see a more diverse multi-ethnic population whose characteristics and risks may not consistently match the populations from which guideline evidence is derived. While it would seem very unlikely that for the majority, scientific arguments against guidelines would differ, however from a translational perspective, there will be populations who differ and importantly there are cost-efficacy questions, e.g., the most suitable first-line tests or what parameters equate to an adequate test. This article reviews non-invasive diagnosis of CAD within the context of multi-ethnic patient populations.

Most cancer-related deaths are a result of metastasis, and thus the importance of this process as a target of therapy cannot be understated. By asking 'how can we effectively treat cancer?', we do not capture the complexity of a disease encompassing >200 different cancer types - many consisting of multiple subtypes - with considerable intratumoural heterogeneity, which can result in variable responses to a specific therapy. Moreover, we have much less information on the pathophysiological characteristics of metastases than is available for the primary tumour. Most disseminated tumour cells that arrive in distant tissues, surrounded by unfamiliar cells and a foreign microenvironment, are likely to die; however, those that survive can generate metastatic tumours with a markedly different biology from that of the primary tumour. To treat metastasis effectively, we must inhibit fundamental metastatic processes and develop specific preclinical and clinical strategies that do not rely on primary tumour responses. To address this crucial issue, Cancer Research UK and Cancer Therapeutics CRC Australia formed a Metastasis Working Group with representatives from not-for-profit, academic, government, industry and regulatory bodies in order to develop recommendations on how to tackle the challenges associated with treating (micro)metastatic disease. Herein, we describe the challenges identified as well as the proposed approaches for discovering and developing anticancer agents designed specifically to prevent or delay the metastatic outgrowth of cancer.

Type 1 diabetes is the product of a complex interplay between genetic susceptibility and exposure to environmental factors. Existing bacterial profiling studies focus on people who are most at risk at the time of diagnosis; there are limited data on the gut microbiota of people with long-standing Type 1 diabetes. This study compared the gut microbiota of patients with Type 1 diabetes and good glycaemic control and high levels of physical-fitness with that of matched controls without diabetes.Ten males with Type 1 diabetes and ten matched controls without diabetes were recruited; groups were matched for gender, age, BMI, peak oxygen uptake (VO2max ), and exercise habits. Stool samples were analysed using next-generation sequencing of the 16S rRNA gene to obtain bacterial profiles from each individual. Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) was implemented to predict the functional content of the bacterial operational taxonomic units.Faecalibacterium sp., Roseburia sp. and Bacteroides sp. were typically the most abundant members of the community in both patients with Type 1 diabetes and controls, and were present in every sample in the cohort. Each bacterial profile was relatively individual and no significant difference was reported between the bacterial profiles or the Shannon diversity indices of Type 1 diabetes compared with controls. The functional profiles were more conserved and the Type 1 diabetes group were comparable with the control group.We show that both gut microbiota and resulting functional bacterial profiles from patients with long-standing Type 1 diabetes in good glycaemic control and high physical fitness levels are comparable with those of matched people without diabetes. This article is protected by copyright. All rights reserved.

Micropolarizer arrays are occasionally used in partial Stokes, full Stokes, and Mueller matrix polarimeters. When treating modulated polarimeters as linear systems, specific assumptions are made about the Dirac delta functional forms generated in the channel space by micropolarizer arrays. These assumptions are 1) infinitely fine sampling both spatially and temporally and 2) infinite array sizes. When these assumptions are lifted and the physical channel shapes are computed, channel shapes become dependent on both the physical pixel area and shape, as well as the array size. We show that under certain circumstances the Dirac delta function approximation is not valid, and give some bounding terms to compute when the approximation is valid, i.e., which array and pixel sizes must be used for the Dirac delta function approximation to hold. Additionally, we show how the physical channel shape changes as a function of array and pixel size, for a conventional 0°, 45°, −45°, 90° superpixel micropolarizer array configuration.

AIMS: To design and conduct preliminary validation of a measure of hypoglycaemia awareness and problematic hypoglycaemia, the Hypoglycaemia Awareness Questionnaire. METHODS: Exploratory and cognitive debriefing interviews were conducted with 17 adults (nine of whom were women) with Type 1 diabetes (mean ± sd age 48±10 years). Questionnaire items were modified in consultation with diabetologists/psychologists. Psychometric validation was undertaken using data from 120 adults (53 women) with Type 1 diabetes (mean ± sd age 44±16 years; 50% with clinically diagnosed impaired awareness of hypoglycaemia), who completed the following questionnaires: the Hypoglycaemia Awareness Questionnaire, the Gold score, the Clarke questionnaire and the Problem Areas in Diabetes questionnaire. RESULTS: Iterative design resulted in 33 items eliciting answers on awareness of hypoglycaemia when awake/asleep and hypoglycaemia frequency, severity and impact (healthcare utilization). Psychometric analysis identified three subscales reflecting 'impaired awareness', 'symptom level' and 'symptom frequency'. Convergent validity was indicated by strong correlations between the impaired awareness subscale and existing measures of awareness: (Gold: rs =0.75, P<0.01; Clarke: rs =0.76, P<0.01). Divergent validity was indicated by weaker correlations with diabetes-related distress (Problem Areas in Diabetes: rs =0.25, P<0.01) and HbA1c (rs =-0.05, non-significant). The impaired awareness subscale and other items discriminated between those with impaired and intact awareness (Gold score). The impaired awareness subscale and other items contributed significantly to models explaining the occurrence of severe hypoglycaemia and hypoglycaemia when asleep. CONCLUSIONS: This preliminary validation shows the Hypoglycaemia Awareness Questionnaire has robust face and content validity; satisfactory structure; internal reliability; convergent

BACKGROUND: Patients with type 1 diabetes face heightened risk of hypoglycemia after exercise. Subsequent overfeeding, as a preventative measure against hypoglycemia, negates the energy deficit after exercise. Patients are also required to reduce the insulin dose administered with postexercise foods to further combat hypoglycemia. However, the insulin dose is dictated solely by the carbohydrate content, even though postprandial glycemia is vastly influenced by glycemic index (GI). With a need to control the postexercise energy balance, appetite responses after meals differing in GI are of particular interest. OBJECTIVES: We assessed the appetite response to low-glycemic index (LGI) and high-glycemic index (HGI) postexercise meals in type 1 diabetes patients. This assessment also offered us the opportunity to evaluate the influence of GI on appetite responses independently of insulinemia, which confounds findings in individuals without diabetes. DESIGN: Ten physically active men with type 1 diabetes completed 2 trials in a randomized crossover design. After 45 min of treadmill exercise at 70% of the peak oxygen uptake, participants consumed an LGI (GI ∼37) or HGI (GI ∼92) meal with a matched macronutrient composition, negligible fiber content, and standardized insulin-dose administration. The postprandial appetite response was determined for 180 min postmeal. During this time, circulating glucose, insulin, glucagon, and glucagon-like peptide-1 (GLP-1) concentrations and subjective appetite ratings were determined. RESULTS: The HGI meal produced an ∼60% greater postprandial glucose area under the curve (AUC) than did the LGI meal (P = 0.008). Insulin, glucagon, and GLP-1 did not significantly differ between trials (P > 0.05). The fullness AUC was ∼25% greater after the HGI meal than after the LGI meal (P < 0.001), whereas hunger sensations were ∼9% lower after the HGI meal than after the LGI meal (P = 0.001). CONCLUSION: Under conditions of matched insulinemia and fib

To determine whether impaired awareness of hypoglycemia (IAH) can be improved and severe hypoglycemia (SH) prevented in type 1 diabetes, we compared an insulin pump (continuous subcutaneous insulin infusion [CSII]) with multiple daily injections (MDIs) and adjuvant real-time continuous glucose monitoring (RT) with conventional self-monitoring of blood glucose (SMBG).

OBJECTIVES: Severe hypoglycaemia affects approximately one in three people with type 1 diabetes and is the most serious side effect of insulin therapy. Our aim was to explore individualistic drivers of severe hypoglycaemia events. METHODS: In-depth semi-structured interviews were conducted with a purposive sample of 17 adults with type 1 diabetes and a history of recurrent severe hypoglycaemia, to elicit experiences of hypoglycaemia (symptoms/awareness, progression from mild to severe and strategies for prevention/treatment). Interviews were analysed using an adapted grounded theory approach. RESULTS: Three main themes emerged: hypoglycaemia-induced cognitive impairment, behavioural factors and psychological factors. Despite experiencing early hypoglycaemic symptoms, individuals often delayed intervention due to impaired/distracted attention, inaccurate risk assessment, embarrassment, worry about rebound hyperglycaemia or unavailability of preferred glucose source. Delay coupled with use of a slow-acting glucose source compromised prevention of severe hypoglycaemia. CONCLUSION: Our qualitative data highlight the multifaceted, idiosyncratic nature of severe hypoglycaemia and confirm that individuals with a history of recurrent severe hypoglycaemia may have specific thought and behaviour risk profiles. Individualised prevention plans are required, emphasising both the need to attend actively to mild hypoglycaemic symptoms and to intervene promptly with an appropriate, patient-preferred glucose source to prevent progression to severe hypoglycaemia.

OBJECTIVE: Impaired awareness of hypoglycemia (IAH) and defective counterregulation significantly increase severe hypoglycemia risk in type 1 diabetes (T1D). We evaluated restoration of IAH/defective counterregulation by a treatment strategy targeted at hypoglycemia avoidance in adults with T1D with IAH (Gold score ≥4) participating in the U.K.-based multicenter HypoCOMPaSS randomized controlled trial. RESEARCH DESIGN AND METHODS: Eighteen subjects with T1D and IAH (mean ± SD age 50 ± 9 years, T1D duration 35 ± 10 years, HbA1c 8.1 ± 1.0% [65 ± 10.9 mmol/mol]) underwent stepped hyperinsulinemic-hypoglycemic clamp studies before and after a 6-month intervention. The intervention comprised the HypoCOMPaSS education tool in all and randomized allocation, in a 2 × 2 factorial study design, to multiple daily insulin analog injections or continuous subcutaneous insulin infusion therapy and conventional glucose monitoring or real-time continuous glucose monitoring. Symptoms, cognitive function, and counterregulatory hormones were measured at each glucose plateau (5.0, 3.8, 3.4, 2.8, and 2.4 mmol/L), with each step lasting 40 min with subjects kept blinded to their actual glucose value throughout clamp studies. RESULTS: After intervention, glucose concentrations at which subjects first felt hypoglycemic increased (mean ± SE from 2.6 ± 0.1 to 3.1 ± 0.2 mmol/L, P = 0.02), and symptom and plasma metanephrine responses to hypoglycemia were higher (median area under curve for symptoms, 580 [interquartile range {IQR} 420-780] vs. 710 [460-1,260], P = 0.02; metanephrine, 2,412 [-3,026 to 7,279] vs. 5,180 [-771 to 11,513], P = 0.01). Glycemic threshold for deterioration of cognitive function measured by four-choice reaction time was unchanged, while the color-word Stroop test showed a degree of adaptation. CONCLUSIONS: Even in long-standing T1D, IAH and defective counterregulation may be improved by a clinical strategy

BACKGROUND: Schistosoma mansoni and Schistosoma japonicum are the most frequent causative agents of human intestinal schistosomiasis. Approximately 200 million people in the world are infected with schistosomes. Diagnosis of schistosomiasis is often difficult. High percentages of low level infections are missed in routine fecal smear analysis and current diagnostic methodologies are inadequate to monitor the progress of parasite control, especially in areas with low transmission. Improved diagnostic methods are urgently needed to evaluate the success of elimination programs. Recently, a magnetic fractionation method for isolation of parasite eggs from feces was described, which uses magnetic microspheres to form parasite egg - magnetic microsphere conjugates. This approach enables screening of larger sample volumes and thus increased diagnostic sensitivity. The mechanism of formation of the conjugates remains unexplained and may either be related to specific surface characteristics of eggs and microspheres or to their magnetic properties. METHODS/PRINCIPAL FINDINGS: Here, we investigated iron localization in parasite eggs, specifically in the eggshells. We determined the magnetic properties of the eggs, studied the motion of eggs and egg-microsphere conjugates in magnetic fields and determined species specific affinity of parasite eggs to magnetic microspheres. Our study shows that iron is predominantly localized in pores in the eggshell. Parasite eggs showed distinct paramagnetic behaviour but they did not move in a magnetic field. Magnetic microspheres spontaneously bound to parasite eggs without the presence of a magnetic field. S. japonicum eggs had a significantly higher affinity to bind microspheres than S. mansoni eggs. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the interaction of magnetic microspheres and parasite eggs is unlikely to be magnetic in origin. Instead, the filamentous surface of the eggshells may be important in facilitating the binding.

The no reflow phenomenon is reported to occur in >2% of all percutaneous coronary interventions (PCIs) and portends a poor prognosis. We analyzed data from 5,286 consecutive patients who underwent PCI from the Melbourne Interventional Group (MIG) registry from April 2004 through January 2008 who had 30-day follow-up completed. Patients without no reflow (normal reflow, n = 5,031) were compared to 255 (4.8%) with no reflow (n = 217 for transient no reflow, n = 38 for persistent no reflow). Patients with transient or persistent no reflow were more likely to present with ST-elevation myocardial infarction (MI) or cardiogenic shock (p <0.0001 for the 2 comparisons). They were also more likely to have complex lesions (American College of Cardiology/American Heart Association type B2/C), have lesions within a bypass graft, require an intra-aortic balloon pump, receive glycoprotein IIb/IIIa inhibition, and have a longer mean stent length (p <0.0001 for all comparisons). In-hospital outcomes were significantly worse in those patients with transient or persistent no reflow, with increased death, periprocedural MI, renal impairment, and major adverse cardiac events (p <0.0001 for all comparisons). Similarly, transient and persistent no reflow portended worse 30-day clinical outcomes, with a progressive increase in mortality (normal reflow 1.7% vs transient no reflow 5.5% vs persistent no reflow 13.2%, p <0.0001), MI, target vessel revascularization, and major adverse cardiac events (p <0.0001 for all comparisons) compared to patients with normal flow. In conclusion, transient or persistent no reflow complicates approximately 1 in 20 PCIs and results in stepwise increases in in-hospital and 30-day adverse outcomes.