On the origin of the A1g_{1g} and B1g_{1g} electronic Raman scattering peaks in the superconducting state of YBa2_{2}Cu3_{3}O7−δ_{7-\delta}

The electronic Raman scattering has been investigated in optimally oxygen doped YBa$_{2}$Cu$_{3}$O$_{7-\delta}$ single crystals as well as in crystals with non-magnetic, Zn, and magnetic, Ni, impurities. We found that the intensity of the A$_{1g}$ peak is impurity independent and their energy to $T_{c}$ ratio is almost constant ($2\Delta/k_{B}T_{c}\sim5$). Moreover, the signal at the B$_{1g}$ channel is completely smeared out when non-magnetic Zn impurities are present. These results are qualitatively interpreted in terms of the Zeyher and Greco's theory that relates the electronic Raman scattering in the A$_{1g}$ and B$_{1g}$ channels to \textit{d}-CDW and superconducting order parameters fluctuations, respectively.Comment: Submited to Phys. Rev. Let

Comparison of Resting PD/PA with Fractional Flow Reserve Using a Monorail Pressure Catheter

Background: The RXi™ system (ACIST Medical Systems, MN, USA) is a new Fractional Flow Reserve (FFR) technology utilising an ultrathinmonorail microcatheter (Navvus®; ACIST Medical Systems) with an optical pressure sensor located close to the distal catheter tip. FFR measurement using monorail microcatheter is comparable to the conventional pressure wires. However, the predictive value of resting distal coronary artery pressure/aortic pressure (Pd/Pa) on hyperemic FFR value in the real world practice is unknown. Objective: To explore the diagnostic accuracy of resting Pd/Pa in relation to hyperemic FFR using the monorail pressure catheter. Methods: Resting Pd/Pa and FFR were measured using monorail pressure catheter in 67 consecutive patients with intermediate coronary artery lesions (30% to 80% diameter stenoses) between 01-03-2016 to 17-01-2017. Of 121 studied lesions, 29 (23.97%) were excluded because of no hyperemic FFR due to postive resting Pd/Pa (n=17), severe or non-critical stenosis (n=11) and suboptimal acquisition (n=1), leaving 92 lesions for final analysis. Hyperemic FFR was induced with intracoronary adenosine. The selection of coronary wire and the dose of intracoronary nitroglycerine were at the operators’ discretions. Results: Bland-Altman plots showed a moderate degree of scatter between Pd/Pa and FFR value. On average, Pd/Pa exceeded FFR by 0.066 (-0.09 to +0.22). Receiver-operating characteristic curves of the resting Pd/Pa with FFR≤0.80 as the reference variable showed an area under the curve of 0.78 (95% confidence intervals 0.680 to 0.881, pb0.001), with a diagnostic accuracy of 79.3% when the resting Pd/Pa was ≤0.86. Certain cutoff values of Pd/Pa can reliably predict whether hyperemic FFR was positive or negative (FFR cutoff≤0.80). Resting Pd/Pa value of N0.96 had a negative predictive value (NPV) of 100% and sensitivity of 100%; the resting Pd/Pa value of ≤0.82 had a positive predictive value (PPV) of 100% and specificity of 98.3%. These were consistent regardless of coronary vessel, location of lesion or degree of diameter stenosis. Conclusions: Certain range of resting Pd/Pa measured by monorail pressure catheter had excellent NPV and sensitivity or excellent PPV and specificity to predict hyperemic FFR. Clinical outcome studies are required to determine whether the results might obviate the need for hyperemia in selected patients

Thirty-Day Clinical Outcome of Primary Percutaneous Intervention Versus Fibrinolysis Followed by Coronary Angiography in ST-Segment Elevation Myocardial Infarction

Background: Primary percutaneous coronary intervention (PCI)is the preferred reperfusion strategy in patients with ST-segment elevation myocardial infarction (STEMI). However, timely PCI cannot be offered to many patients. Objective: The purpose of this study was to compare the 30-day clinical outcome of primary PCI strategy and fibrinolysis followed by coronary angiography strategy in STEMI patients. Methods: This was a prospective, observational, single center study. All patients admitted for STEMI from 1 January 2016 to 30 November 2016 were screened for the study. Patients were divided into 2 reperfusion strategies: primary PCI or fibrinolysis followed by coronary angiography. Primary outcome was composite of all-cause mortality at 30 days. Results: A total of 178 patients were identified: 33 (18.5%) underwent primary PCI and 145 (81.5%) underwent fibrinolysis first. The median door-to-balloon time in the primary PCI group was 161.0 minutes (IQR 84.5). The median time from fibrinolysis-to-arrival at catheterization lab was 1738 minutes (IQR 901). The median total ischaemic time was 369 min (IQR 524) and 210 (IQR 247) for the primary PCI and fibrinolysis first group respectively (p=0.002). Kaplan-Meier survival analysis for 30-day all-cause mortality was 24.2% vs 9.7% respectively in primary PCI and fibrinolysis group p=0.018). Multivariate Linear Regression showed that Killip Class and LVEF were independent predictors of 30-day all-cause mortality. Reperfusion strategy was not associated with 30-day all-cause mortality (p=0.216). Conclusions: The clinical outcome of primary PCI strategy in STEMI is not better than fibrinolysis followed by coronary angiography strategy when timely PCI cannot be performed

Prognostic Value of N-terminal B-type Natriuretic Peptide in Patients with Acute Myocardial Infarction: A Multicenter Study

Background: Several models have been developed to help the clinician in risk stratification for Acute Coronary Syndrome (ACS),such as the TIMI and GRACE risk scores. However, there is conflicting evidence for the prognostic value of NT-ProBNP in acute myocardial infarction (AMI). Objective: (1) To explore the association of NT-proBNP with 30-day clinical outcome in AMI patients. (2) To compare the prognostic value of NT-proBNP with TIMI and GRACE risk scores in AMI patients. Methods: We conducted a multicenter, prospective observational study recruiting patients presented with AMI between 29-October-2015 and 14-January-2017, involving 1 cardiology referral centre and 4 non-cardiology hospitals. NT-proBNP level (Alere Triage®, US)was measured within 24 hours fromthe diagnosis of AMI. Patientswere followed-up for 1 month. Results: A total of 186 patients were recruited, 143 from tertiary cardiology centre and 43 from non-cardiology hospitals. Mean age was 54.7±10.0 years, 87.6% male and 64% were STEMI. The NT-proBNP level ranged from 60 to 16700pg/ml, with a median of 714pg/ml. Using the 75th centile as the cutoff, Kaplan-Meier survival analysis for the 30-day cardiac related mortality was significantly higher for patient with NT-proBNP level of ≥1600pg/ml (6.4% vs. 0.7%, p=0.02). Cox-regression analysis showed that NT-proBNP level of ≥1600pg/ml was an independent predictor of 30-day cardiac related mortality, regardless of TIMI risk score, GRACE score, LV ejection fraction and study hospitals (HR 9.274, p=0.054, 95%CI 0.965, 89.161). Readmission for heart failure at 30-day was also higher for patient with NT-proBNP level of ≥1600pg/ml (HR 9.308, p=0.053, 95%CI 0.969, 89.492). NT-proBNP level was not associated with all-cause mortality, risk of readmission for ACS, arrhythmia and stroke (pN0.05). By adding 50 score to GRACE risk score for NT-proBNP level of ≥1600pg/ml, combination of GraceNT-proBNP scores of more than 200 appeared to be a better independent predictor for 30-day cardiac related mortality (HR:28.28, p=0.004, 95%CI 2.94, 272.1). ROC analysis showed that this new score had 75% sensitivity and 91.2% specificity in predicting 30-day cardiac related mortality (AUC 0.791, p=0.046). Conclusions: NT-proBNP is a useful point-of-care risk stratification biomarker in AMI. It can be combined to the current risk score model for better risk stratification in AMI patients

Impact of Myocardial Viability Assessed by Delayed Enhancement Cardiovascular Magnetic Resonance on Clinical Outcomes in Real World Practice

Background: Delayed enhancement cardiovascular magnetic resonance imaging (DeCMRI) has become the preferred method for viability assessment. It is well established that viable dysfunctional myocardium has the potential for functional recovery after revascularization. Objective: Our objective is to evaluate whether viability assessment by DeCMRI affects clinical outcome in daily clinical practice. Methodology:We retrospectively studied 132 consecutive patients (114 male, mean age 59 ± 10 years) with ischaemic cardiomyopathy (Mean LVEF: 29.1 ± 14%) who underwent CMRI viability testing from 1st Jan-31st Dec 2015 in our centre. Patientswere divided into 3 groups: Group A: Viable myocardium- optimal medical therapy only (38.6%); B: Viable myocardium- revascularization done (29.5%); and C: Nonviable myocardium (29.5%). Results: Mean age for groups A, B and C were 61.2, 58.3, 56.2 years respectively, p=0.048. The proportion of triple vessel disease in each of the groups were 56.1%, 54.5% and 38.5% (p=0.44); whereas left main involvement was 31.7%, 21.2% and 19.2% respectively (p=0.43). Majority of group C patients did not undergo revascularisation (90%). Group B had statistically significant EF improvement (5.5%, SD 11.9) compared to Group A (-0.6%, SD 6.7) and Group C (-1.2%, SD 9.8), p value 0.014. Mortality at 1 year was significantly higher in Group A compared to Group Band C (31.4%, 7.7% and 12.8% respectively, p=0.009). MACE rates were also increased in Group A compared to the other two groups (41.2%, 20.5% and 27.0%, p=0.09). Odds Ratio for MACE was 3.01 (95% Cl 1.22 - 7.45) for Group A vs B and 2.8 (95% Cl 1.1 - 6.9) for Group A vs C. Conclusion: Patients with viable myocardium who did not undergo revascularization (group A) had the worst prognosis, even when compared to those with non-viable myocardium; with significantly higher 1-year mortality. Although not statistically significant, there was also a trend towards higher MACE in these patients. These findings emphasize that patients with poor LV function but viable myocardium need to undergo revascularisation and that optimal medical therapy alone is not sufficient

Clinical Outcomes and Predictors of Improved Left Ventricular Ejection Fraction in Heart Failure with Reduced Ejection Fraction due to Non-Ischemic Cardiomyopathy

Background: Left ventricular ejection fraction (LVEF) improvement is the cornerstone of LV reverse remodelling. It prognosticates heart failure with reduced ejection fraction (HFrEF). There is limited data on the clinical factors that predict LVEF improvement among non-ischemic cardiomyopathy (NICM) patients in Malaysia. Objective: To determine the 3-year outcomes and predictors of LVEF improvement in patients with (NICM) and HFrEF. Materials & Methods: We recruited patients with NICM and HFrEF (LVEF <40%) between 2016 and 2018. NICM was defined as HF with 1) normal coronary arteries or 2) any coronary artery stenosis not involving the proximal left anterior descending artery (LAD) and without transmural fibrosis in the LAD territory from cardiac magnetic resonance (CMR) imaging to account for the impaired LVEF. Clinical and imaging parameters were assessed using logistic regression statistics to determine the predictors of LVEF improvement. LVEF improvement is defined as a recovery of EF to > 40% with at least a 10-point increment from baseline. The clinical outcomes at three year were 1) change in NYHA class and 2) composite of all-cause mortality, unscheduled clinic or emergency department visits, readmission and/or ventricular arrhythmia. Results: 43 patients were recruited. The mean duration of follow-up and echocardiographic assessment interval were 46 and 23 months, respectively. The cohort had a mean age of 46±13 years, and were mostly male (72%). More patients had NYHA 1 at the end of the study (37% vs 86%). 11 patients (25%) recorded composite outcomes. 62.8% had LVEF improvement. Patients with LVEF improvement had a lower incidence of late gadolinium enhancement (51.7% vs 85.7%, odds 5.6 ,p=0.045) and midwall fibrosis on CMR (18.5% vs 62.5%, odds 7.3, p=0.003). LVEF improvement did not affect the functional NYHA recovery (92% vs 81%, p=0.28). Patients with less LVEF improvement had higher incidence of composite outcome (18.5% vs 37.5%, p=0.168). Other characteristics were not significantly different between the groups. Conclusion: Patients with NICM and LVEF improvement had lower composite outcome. Absence of late gadolinium enhancement, particularly midwall fibrosis was an independant predictor of LVEF improvement. This underscores the importance of CMR tissue characterisation to refine the prognostication of NICM patients

Zinc Supplements and Bone Health: The Role of the RANKL-RANK Axis as a Therapeutic Target

Background: To this day, empirical data suggests that zinc has important roles in matrix synthesis, bone turnover, and mineralization and its beneficial effects on bone could be mediated through different mechanisms. The influence of zinc on bone turnover could be facilitated via regulating RANKL/RANK/OPG pathway in bone tissue. Therefore, the aim of the study was to conduct a review to investigate the possible effect of the zinc mediated bone remodeling via RANKL/RANK/OPG pathway. Methods: A comprehensive systematic search was performed in MEDLINE/PubMed, Cochrane Library, SCOPUS, and Google Scholar to explore the studies investigating the effect of zinc as a bone remodeling factor via RANKL/RANK/OPG pathway regulation. Subsequently, the details of the pathway and the impact of zinc supplements on RANKL/RANK/OPG pathway regulation were discussed. Results: The pathway could play an important role in bone remodeling and any imbalance between RANKL/RANK/OPG components could lead to extreme bone resorption. Although the outcomes of some studies are equivocal, it is evident that zinc possesses protective properties against bone loss by regulating the RANKL/RANK/OPG pathway. There are several experiments where zinc supplementation resulted in upregulation of OPG expression or decreases RANKL level. However, the results of some studies oppose this. Conclusion: It is likely that sufficient zinc intake will elicit positive effects on bone health by RANKL/RANK/OPG regulation. Although the outcomes of a few studies are equivocal, it seems that zinc can exert the protective properties against bone loss by suppressing osteoclastogenesis via downregulation of RANKL/RANK. Additionally, there are several experiments where zinc supplementation resulted in upregulation of OPG expression. However, the results of limited studies oppose this. Therefore, aside from the positive role zinc possesses in preserving bone mass, further effects of zinc in RANKL/RANK/OPG system requires further animal/human studies. © 2019 Elsevier Gmb

Age at symptom onset and death and disease duration in genetic frontotemporal dementia : an international retrospective cohort study

Background: Frontotemporal dementia is a heterogenous neurodegenerative disorder, with about a third of cases being genetic. Most of this genetic component is accounted for by mutations in GRN, MAPT, and C9orf72. In this study, we aimed to complement previous phenotypic studies by doing an international study of age at symptom onset, age at death, and disease duration in individuals with mutations in GRN, MAPT, and C9orf72. Methods: In this international, retrospective cohort study, we collected data on age at symptom onset, age at death, and disease duration for patients with pathogenic mutations in the GRN and MAPT genes and pathological expansions in the C9orf72 gene through the Frontotemporal Dementia Prevention Initiative and from published papers. We used mixed effects models to explore differences in age at onset, age at death, and disease duration between genetic groups and individual mutations. We also assessed correlations between the age at onset and at death of each individual and the age at onset and at death of their parents and the mean age at onset and at death of their family members. Lastly, we used mixed effects models to investigate the extent to which variability in age at onset and at death could be accounted for by family membership and the specific mutation carried. Findings: Data were available from 3403 individuals from 1492 families: 1433 with C9orf72 expansions (755 families), 1179 with GRN mutations (483 families, 130 different mutations), and 791 with MAPT mutations (254 families, 67 different mutations). Mean age at symptom onset and at death was 49\ub75 years (SD 10\ub70; onset) and 58\ub75 years (11\ub73; death) in the MAPT group, 58\ub72 years (9\ub78; onset) and 65\ub73 years (10\ub79; death) in the C9orf72 group, and 61\ub73 years (8\ub78; onset) and 68\ub78 years (9\ub77; death) in the GRN group. Mean disease duration was 6\ub74 years (SD 4\ub79) in the C9orf72 group, 7\ub71 years (3\ub79) in the GRN group, and 9\ub73 years (6\ub74) in the MAPT group. Individual age at onset and at death was significantly correlated with both parental age at onset and at death and with mean family age at onset and at death in all three groups, with a stronger correlation observed in the MAPT group (r=0\ub745 between individual and parental age at onset, r=0\ub763 between individual and mean family age at onset, r=0\ub758 between individual and parental age at death, and r=0\ub769 between individual and mean family age at death) than in either the C9orf72 group (r=0\ub732 individual and parental age at onset, r=0\ub736 individual and mean family age at onset, r=0\ub738 individual and parental age at death, and r=0\ub740 individual and mean family age at death) or the GRN group (r=0\ub722 individual and parental age at onset, r=0\ub718 individual and mean family age at onset, r=0\ub722 individual and parental age at death, and r=0\ub732 individual and mean family age at death). Modelling showed that the variability in age at onset and at death in the MAPT group was explained partly by the specific mutation (48%, 95% CI 35\u201362, for age at onset; 61%, 47\u201373, for age at death), and even more by family membership (66%, 56\u201375, for age at onset; 74%, 65\u201382, for age at death). In the GRN group, only 2% (0\u201310) of the variability of age at onset and 9% (3\u201321) of that of age of death was explained by the specific mutation, whereas 14% (9\u201322) of the variability of age at onset and 20% (12\u201330) of that of age at death was explained by family membership. In the C9orf72 group, family membership explained 17% (11\u201326) of the variability of age at onset and 19% (12\u201329) of that of age at death. Interpretation: Our study showed that age at symptom onset and at death of people with genetic frontotemporal dementia is influenced by genetic group and, particularly for MAPT mutations, by the specific mutation carried and by family membership. Although estimation of age at onset will be an important factor in future pre-symptomatic therapeutic trials for all three genetic groups, our study suggests that data from other members of the family will be particularly helpful only for individuals with MAPT mutations. Further work in identifying both genetic and environmental factors that modify phenotype in all groups will be important to improve such estimates. Funding: UK Medical Research Council, National Institute for Health Research, and Alzheimer's Society

Protection of children Disclosure of criminal background of those with access to children

Also numbered Home Office circular HO-C--47/93; Welsh Office circular WO-C--54/93 & Department for Education Circular DFE--9/93SIGLEAvailable from British Library Document Supply Centre-DSC:5290.0065(93/17) / BLDSC - British Library Document Supply CentreGBUnited Kingdo