bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac resynchronization therapy non-responder to responder conversion rate in the more response to cardiac resynchronization therapy with MultiPoint Pacing (MORE-CRT MPP) study: results from Phase I
Authors: Leclercq Christophe , Burri Haran , Curnis Antonio , Delnoy Peter Paul , Rinaldi Christopher A , Sperzel Johannes , Lee Kwangdeok , Calò Leonardo , Vicentini Alfredo , Concha Joaquin Fernandez , Thibault Bernard 
Published: February 2019

Abstract

Aims
To assess the impact of MultiPoint™ Pacing (MPP)—programmed according to the physician’s discretion—in non-responders to standard biventricular pacing after 6 months.

Methods and results
The study enrolled 1921 patients receiving a quadripolar cardiac resynchronization therapy (CRT) system capable of MPP™ therapy. A core laboratory assessed echocardiography at baseline and 6 months and defined volumetric non-response to biventricular pacing as &lt;15% reduction in left ventricular end-systolic volume (LVESV). Clinical sites randomized patients classified as non-responders in a 1:1 ratio to receive MPP (236 patients) or continued biventricular pacing (231 patients) for an additional 6 months and evaluated rate of conversion to echocardiographic response. Baseline characteristics of both groups were comparable. No difference was observed in non-responder to responder conversion rate between MPP and biventricular pacing (31.8% and 33.8%, P = 0.72). In the MPP arm, 68 (29%) patients received MPP programmed with a wide LV electrode anatomical separation (≥30 mm) and shortest LV1–LV2 and LV2–RV timing delays (MPP-AS); 168 (71%) patients received MPP programmed with other settings (MPP-Other). MPP-AS elicited a significantly higher non-responder conversion rate compared to MPP-Other (45.6% vs. 26.2%, P = 0.006) and a trend in a higher conversion rate compared to biventricular pacing (45.6% vs. 33.8%, P = 0.10).

Conclusions
After 6 months, investigator-discretionary MPP programming did not significantly increase echocardiographic response compared to biventricular pacing in CRT non-responders.
Short- and long-term outcomes of alcohol septal ablation for hypertrophic obstructive cardiomyopathy in patients with mild left ventricular hypertrophy: a propensity score matching analysis
Authors: Veselka Josef , Faber Lothar , Liebregts Max , Cooper Robert , Januska Jaroslav , Kashtanov Maksim , Dabrowski Maciej , Hansen Peter Riis , Seggewiss Hubert , Hansvenclova Eva , Bundgaard Henning , ten Berg Jurriën , Stables Rodney Hilton , Jensen Morten Kvistholm 
Published: February 2019

Abstract

Aims
Based on European guidelines, alcohol septal ablation (ASA) for hypertrophic obstructive cardiomyopathy (HOCM) is indicated only in patients with interventricular septum (IVS) thickness &gt;16 mm. The aim of this study was to evaluate the short- and long-term outcomes in ASA patients with mild hypertrophy (IVS ≤ 16 mm).

Methods and results
We retrospectively evaluated 1505 consecutive ASA patients and used propensity score to match 172 pairs (344 patients) in groups IVS ≤ 16 mm or IVS &gt; 16 mm. There was no occurrence of post-ASA ventriculoseptal defect in the whole cohort (n = 1505). Matched patients had 30-day mortality rate 0% in IVS ≤ 16 mm group and 0.6% in IVS &gt; 16 mm group (P = 1). Patients in IVS ≤ 16 mm group had more ASA-attributable early complications (16% vs. 9%; P = 0.049), which was driven by higher need for pacemaker implantation (13% vs. 8%; P = 0.22). The mean follow-up was 5.4 ± 4.3 years and the annual all-cause mortality rate was 1.8 and 3.2 deaths per 100-patient-years in IVS ≤ 16 group and IVS &gt; 16 group, respectively (log-rank test P = 0.04). There were no differences in symptom relief and left ventricular (LV) gradient reduction. Patients with IVS ≤ 16 mm had less repeated septal reduction procedures (log-rank test P = 0.03).

Conclusion
Selected patients with HOCM and mild hypertrophy (IVS ≤ 16 mm) had more early post-ASA complications driven by need for pacemaker implantation, but their long-term survival is better than in patients with IVS &gt;16 mm. While relief of symptoms and LV obstruction reduction is similar in both groups, a need for repeat septal reduction is higher in patients with IVS &gt; 16 mm.
Temporal variations in the triggering of myocardial infarction by air temperature in Augsburg, Germany, 1987–2014
Authors: Chen Kai , Breitner Susanne , Wolf Kathrin , Hampel Regina , Meisinger Christa , Heier Margit , von Scheidt Wolfgang , Kuch Bernhard , Peters Annette , Schneider Alexandra ,   for the KORA Study Group, Peters A , Schulz H , Schwettmann L , Leidl R , Heier M , Strauch K 
Published: February 2019

Abstract

Aims
The association between air temperature and mortality has been shown to vary over time, but evidence of temporal changes in the risk of myocardial infarction (MI) is lacking. We aimed to estimate the temporal variations in the association between short-term exposures to air temperature and MI in the area of Augsburg, Germany.

Methods and results
Over a 28-years period from 1987 to 2014, a total of 27 310 cases of MI and coronary deaths were recorded. Daily meteorological parameters were measured in the study area. A time-stratified case-crossover analysis with a distributed lag non-linear model was used to estimate the risk of MI associated with air temperature. Subgroup analyses were performed to identify subpopulations with changing susceptibility to air temperature. Results showed a non-significant decline in cold-related MI risks. Heat-related MI relative risk significantly increased from 0.93 [95% confidence interval (CI): 0.78–1.12] in 1987–2000 to 1.14 (95% CI: 1.00–1.29) in 2001–14. The same trend was also observed for recurrent and non-ST-segment elevation MI events. This increasing population susceptibility to heat was more evident in patients with diabetes mellitus and hyperlipidaemia. Future studies using multicentre MI registries at different climatic, demographic, and socioeconomic settings are warranted to confirm our findings.

Conclusion
We found evidence of rising population susceptibility to heat-related MI risk from 1987 to 2014, suggesting that exposure to heat should be considered as an environmental trigger of MI, especially under a warming climate.
Spotlight on S-ICD™ therapy: 10 years of clinical experience and innovation
Authors: Bögeholz Nils , Willy Kevin , Niehues Philipp , Rath Benjamin , Dechering Dirk G , Frommeyer Gerrit , Kochhäuser Simon , Löher Andreas , Köbe Julia , Reinke Florian , Eckardt Lars 
Published: February 2019

Abstract
Subcutaneous ICD (S-ICD™) therapy has been established in initial clinical trials and current international guideline recommendations for patients without demand for pacing, cardiac resynchronization, or antitachycardia pacing. The promising experience in ‘ideal’ S-ICD™ candidates increasingly encourages physicians to provide the benefits of S-ICD™ therapy to patients in clinical constellations beyond ‘classical’ indications of S-ICD™ therapy, which has led to a broadening of S-ICD™ indications in many centres. However, the decision for S-ICD™ implantation is still not covered by controlled randomized trials but rather relies on patient series or observational studies. Thus, this review intends to give a contemporary update on available empirical evidence data and technical advancements of S-ICD™ technology and sheds a spotlight on S-ICD™ therapy in recently discovered fields of indication beyond ideal preconditions. We discuss the eligibility for S-ICD™ therapy in Brugada syndrome as an example for an adverse and dynamic electrocardiographic pattern that challenges the S-ICD™ sensing and detection algorithms. Besides, the S-ICD™ performance and defibrillation efficacy in conditions of adverse structural remodelling as exemplified for hypertrophic cardiomyopathy is discussed. In addition, we review recent data on potential device interactions between S-ICD™ systems and other implantable cardio-active systems (e.g. pacemakers) including specific recommendations, how these could be prevented. Finally, we evaluate limitations of S-ICD™ therapy in adverse patient constitutions, like distinct obesity, and present contemporary strategies to assure proper S-ICD™ performance in these patients. Overall, the S-ICD™ performance is promising even for many patients, who may not be ‘classical’ candidates for this technology.
Recombinant multicopy plasmids in yeast – interactions with the endogenous 2 μm
Authors: Hohnholz Ruben , Achstetter Tilman 
Published: February 2019

ABSTRACT
Flp-mediated site specific intramolecular recombination in Saccharomyces cerevisiae is considered responsible for amplification of the endogenous 2 μm plasmid. For YEp-type vectors, a similar mechanism can be imagined by which such plasmids achieve high copy numbers, a trait desired for many research applications and necessary for industrial production. We have cultivated yeast carrying one of six isomeric YEp-type model expression plasmids under two different conditions and back transformed the shuttle vectors into Escherichia coli. Our analysis of 586 ampR clones represents a high-resolution snapshot of plasmid forms present in the transformed yeast cells with a detection limit of structural changes of &lt;2%. Altered forms summed up to about 11%, constituting likely a lower limit. We have observed two categories of recombination events. One is Flp based, with products of intermolecular recombination with the 2 μm, likely intermediates that are prerequisites for YEp-type plasmid amplification. The other type is based on Flp-independent homologous recombination leading to oligomerization of such plasmids also in a 2μm-free [cir°] strain, i.e. in the absence of Flp. Beyond the general maintenance and its functional sequences, only the gene of interest and its expression might have an impact on the physiology of the host.
A Case for Promoting Movement Medicine: Preventing Disability in the LIFE Randomized Controlled Trial
Authors: Fanning Jason , Rejeski W Jack , Chen Shyh-Huei , Nicklas Barbara J , Walkup Michael P , Axtell Robert S , Fielding Roger A , Glynn Nancy W , King Abby C , Manini Todd M , McDermott Mary M , Newman Anne B , Pahor Marco , Tudor-Locke Catrine , Miller Michael E ,   LIFE Study Investigators
Published: February 2019

Abstract

Background
The movement profile of older adults with compromised function is unknown, as is the relationship between these profiles and the development of major mobility disability (MMD)—a critical clinical outcome. We first describe the dimensions of movement in older adults with compromised function and then examine whether these dimensions predict the onset of MMD.

Methods
Older adults at risk for MMD (N = 1,022, mean age = 78.7 years) were randomized to receive a structured physical activity intervention or health education control. We assessed MMD in 6-month intervals (average follow-up of 2.2 years until incident MMD), with activity assessed at baseline, 6-, 12- and 24-month follow-up via accelerometry.

Results
A principal components analysis of 11 accelerometer-derived metrics yielded three components representing lifestyle movement (LM), extended bouts of moderate-to-vigorous physical activity (MVPA), and stationary body posture. LM accounted for the greatest proportion of variance in movement (53%). Within health education, both baseline LM (HR = 0.74; 95% CI 0.62 to 0.88) and moderate-to-vigorous physical activity (HR = 0.69; 95% CI 0.54 to 0.87) were associated with MMD, whereas only LM was associated with MMD within physical activity (HR = 0.74; 95% CI 0.61 to 0.89). There were similar nonlinear relationships present for LM in both physical activity and health education (p < .04), whereby risk for MMD was lower among individuals with higher levels of LM.

Conclusions
Both LM and moderate-to-vigorous physical activity should be central in treatment regimens for older adults at risk for MMD.

Trial Registration
clinicaltrials.gov Identifier NCT01072500
Poor-quality antimalarials further health inequities in Uganda
Authors: Evans Daniel R , Higgins Colleen R , Laing Sarah K , Awor Phyllis , Ozawa Sachiko 
Published: February 2019

Abstract
Substandard and falsified medications are a major threat to public health, directly increasing the risk of treatment failure, antimicrobial resistance, morbidity, mortality and health expenditures. While antimalarial medicines are one of the most common to be of poor quality in low- and middle-income countries, their distributional impact has not been examined. This study assessed the health equity impact of substandard and falsified antimalarials among children under five in Uganda. Using a probabilistic agent-based model of paediatric malaria infection (Substandard and Falsified Antimalarial Research Impact, SAFARI model), we examine the present day distribution of the burden of poor-quality antimalarials by socio-economic status and urban/rural settings, and simulate supply chain, policy and patient education interventions. Patients incur US$26.1 million (7.8%) of the estimated total annual economic burden of substandard and falsified antimalarials, including $2.3 million (9.1%) in direct costs and $23.8 million (7.7%) in productivity losses due to early death. Poor-quality antimalarials annually cost $2.9 million to the government. The burden of the health and economic impact of malaria and poor-quality antimalarials predominantly rests on the poor (concentration index −0.28) and rural populations (98%). The number of deaths among the poorest wealth quintile due to substandard and falsified antimalarials was 12.7 times that of the wealthiest quintile, and the poor paid 12.1 times as much per person in out-of-pocket payments. Rural populations experienced 97.9% of the deaths due to poor-quality antimalarials, and paid 10.7 times as much annually in out-of-pocket expenses compared with urban populations. Our simulations demonstrated that interventions to improve medicine quality could have the greatest impact at reducing inequities, and improving adherence to antimalarials could have the largest economic impact. Substandard and falsified antimalarials have a significant health and economic impact, with greater burden of deaths, disability and costs on poor and rural populations, contributing to health inequities in Uganda.
‘Peace through strength’: Europe and NATO deterrence beyond the US Nuclear Posture Review
Authors: McCrisken Trevor , Downman Maxwell 
Published: February 2019

Abstract
With its 2018 Nuclear Posture Review, the Trump administration expanded the scope of US nuclear deterrence, re-emphasizing the importance of non-strategic nuclear weapons, perceptively lowering the threshold for nuclear use and casting doubt on the future of arms control. The authors argue that these changes are consistent with the administration's wider ‘peace through strength’ approach that draws on traditional Republican thinking on security policy. While designed to demonstrate credibility and resolve to both allies and adversaries, however, this assertive approach to security policy and specifically nuclear policy as a necessary precursor to renewed engagement in strategic negotiations may have unintended consequences. This article focuses on European reactions to the strategy and argues that the Trump administration's nuclear posture challenges common European understandings in three principal areas. First, changes to US declaratory policy contest European assumptions on the role of nuclear weapons in defending NATO. Second, US modernization plans and their implications for intra-alliance relations risk accentuating controversial debates about the US commitment to Europe. Third, the apparent US rejection of arms control widens the scope for discord with European leaders. If European leaders assert a clear and credible alternative vision advocating nuclear restraint, risk reduction and arms control they could rebuild trust and confidence between the United States, NATO and Russia, demonstrating real strength and ultimately leading to more genuine opportunities for peace and sustainable European security.
Dead heat: copepod carcass occurrence along the Japanese coasts and implications for a warming ocean
Authors: Tang K W , Ivory J A , Shimode S , Nishibe Y , Takahashi K 
Published: February 2019

AbstractUnderstanding global warming effects on marine zooplankton is key to proper management of marine resources and fisheries. This is particularly urgent for Japan where the coastal water temperature has been increasing faster than the global average over the past decade. Conventional sampling and monitoring programmes, by ignoring the in situ vital status of the zooplankton, produce incomplete information about the state of the ecosystem. We showed that marine copepod carcasses were ubiquitous along a latitudinal gradient of 34–39°N of the Japanese coasts. On average, 4.4–18.1% of the individuals of the main copepod genera (Acartia, Paracalanus, Oithona, and Pseudocalanus) were carcasses, equivalent to 19–250 µg C m−3. Higher fractions of dead copepods tended to occur at higher water temperatures, implicating temperature-dependent non-predation mortality. Carcass occurrence may represent a loss of copepod production for the traditional predation-based food chain. On average, 49.5% of the carcass carbon would be remineralized in the water column via bacteria respiration, with the remainder potentially exported to the seafloor. Continuous warming in the Japanese coasts is expected to accelerate non-predation copepod mortality, with unknown consequences for the local marine food web.
Collocation methods for integro-differential algebraic equations with index 1
Authors: Liang Hui , Brunner Hermann 
Published: February 2019

Abstract
The notion of the tractability index based on the $\nu $-smoothing property of a Volterra integral operator is introduced for general systems of linear integro-differential algebraic equations (IDAEs). It is used to decouple the given IDAE system of index $1$ into the inherent system of regular Volterra integro-differential equations (VIDEs) and a system of second-kind Volterra integral equations (VIEs). This decoupling of the given general IDAE forms the basis for the convergence analysis of the two classes of piecewise polynomial collocation methods for solving the given index-$1$ IDAE system. The first one employs the same continuous piecewise polynomial space $S_m^{(0)}$ for both the VIDE part and the second-kind VIE part of the decoupled system. In the second one the VIDE part is discretized in $S_m^{(0)}$, but the second-kind VIE part employs the space of discontinuous piecewise polynomials $S_{m - 1}^{(- 1)}$. The optimal orders of convergence of these collocation methods are derived. For the first method, the collocation solution converges uniformly to the exact solution if and only if the collocation parameters satisfy a certain condition. This condition is no longer necessary for the second method; the collocation solution now converges to the exact solution for any choice of the collocation parameters. Numerical examples illustrate the theoretical results.
Nonuniqueness of Conformal Metrics With Constant Q-curvature
Authors: Bettiol Renato G , Piccione Paolo , Sire Yannick 
Published: February 2019

Abstract
We establish several nonuniqueness results for the problem of finding complete conformal metrics with constant (4th-order) $Q$-curvature on compact and noncompact manifolds of dimension $\geq 5$. Infinitely many branches of metrics with constant $Q$-curvature, but without constant scalar curvature, are found to bifurcate from Berger metrics on spheres and complex projective spaces. These provide examples of nonisometric metrics with the same constant negative $Q$-curvature in a conformal class with negative Yamabe invariant, echoing the absence of a maximum principle. We also discover infinitely many complete metrics with constant $Q$-curvature conformal to $\mathbb S^m\times \mathbb R^d$, $m\geq 4$, $d\geq 1$, and $\mathbb S^m\times \mathbb H^d$, $2\leq d\leq m-3$, which give infinitely many solutions to the singular constant $Q$-curvature problem on round spheres $\mathbb S^n$ blowing up along a round subsphere $\mathbb S^k$, for all $0\leq k&lt;(n-4)/2$.
Positivity of Canonical Bases Under Comultiplication
Authors: Fan Zhaobing , Li Yiqiang 
Published: February 2019

AbstractWe show the positivity of the canonical basis for a modified quantum affine $\mathfrak{sl}_n$ under the comultiplication. Moreover, we establish the positivity of the i-canonical basis in [21] with respect to the coideal subalgebra structure.
Magnitude and Functionality of the NS1-Specific Antibody Response Elicited by a Live-Attenuated Tetravalent Dengue Vaccine Candidate
Authors: Sharma Mayuri , Glasner Dustin R , Watkins Heather , Puerta-Guardo Henry , Kassa Yoseph , Egan Michael A , Dean Hansi , Harris Eva 
Published: February 2019

Abstract

Background
Dengue virus (DENV) can cause life-threatening disease characterized by endothelial dysfunction and vascular leakage. DENV nonstructural protein 1 (NS1) induces human endothelial hyperpermeability and vascular leak in mice, and NS1 vaccination confers antibody-mediated protective immunity. We evaluated the magnitude, cross-reactivity, and functionality of NS1-specific IgG antibody responses in sera from a phase 2 clinical trial of Takeda’s live-attenuated tetravalent dengue vaccine candidate (TAK-003).

Methods
We developed an enzyme-linked immunosorbent assay to measure anti-DENV NS1 IgG in sera from DENV-naive or preimmune subjects pre- and postvaccination with TAK-003 and evaluated the functionality of this response using in vitro models of endothelial permeability.

Results
TAK-003 significantly increased DENV-2 NS1-specific IgG in naive individuals, which cross-reacted with DENV-1, -3, and -4 NS1 to varying extents. NS1-induced endothelial hyperpermeability was unaffected by prevaccination serum from naive subjects but was variably inhibited by serum from preimmune subjects. After TAK-003 vaccination, all samples from naive and preimmune vaccinees completely abrogated DENV-2 NS1-induced hyperpermeability and cross-inhibited hyperpermeability induced by DENV-1, -3, and -4 NS1. Inhibition of NS1-induced hyperpermeability correlated with NS1-specific IgG concentrations. Postvaccination sera also prevented NS1-induced degradation of endothelial glycocalyx components.

Conclusion
We provide evidence for functional NS1-specific IgG responses elicited by a candidate dengue vaccine.

Clinical Trials Registration
NCT01511250.
Generation of a common innate lymphoid cell progenitor requires interferon regulatory factor 2
Authors: Okubo Yohei , Tokumaru Shigeo , Yamamoto Yuta , Miyagawa Shin-ichi , Sanjo Hideki , Taki Shinsuke 
Published: February 2019

Abstract
Innate lymphoid cells (ILCs), composed of heterogeneous populations of lymphoid cells, contribute critically to immune surveillance at mucosal surfaces. ILC subsets develop from common lymphoid progenitors through stepwise lineage specification. However, the composition and temporal regulation of the transcription factor network governing such a process remain incompletely understood. Here, we report that deletion of the transcription factor interferon regulatory factor 2 (IRF-2), known also for its importance in the maturation of conventional NK cells, resulted in an impaired generation of ILC1, ILC2 and ILC3 subsets with lymphoid tissue inducer (LTi)-like cells hardly affected. In IRF-2-deficient mice, PD-1hi ILC precursors (ILCPs) that generate these three ILCs but not LTi-like cells were present at normal frequency, while their sub-population expressing high amounts of PLZF, another marker for ILCPs, was severely reduced. Notably, these IRF-2-deficient ILCPs contained normal quantities of PLZF-encoding Zbtb16 messages, and PLZF expression in developing invariant NKT cells within the thymus was unaffected in these mutant mice. These results point to a unique, cell-type selective role for IRF-2 in ILC development, acting at a discrete step critical for the generation of functionally competent ILCPs.