Negative Delta Research Articles

Genotype-phenotype relationship in Iranian patients with cystic fibrosis.

Cystic fibrosis (CF), the most common hereditary, life-threatening disease, is caused by a mutation in the CFTR gene. Because different mutations can affect clinical manifestations of patients, this study was conducted to investigate the possible genotype-phenotype relationship in a group of Iranian patients with CF. This case-series study was conducted in 30 patients with CF who were referred to a tertiary pediatric hospital in Tehran. In this study, the DNA of the patients was evaluated for delta F508 mutation, whereas some parameters such as the age at diagnosis, the sweat chloride level, and clinical manifestations related to pancreatic insufficiency and pulmonary involvement were also assessed. Among all the studied patients, 16.6% had a delta F508 mutation, either homozygote or heterozygote. The mean age at diagnosis was lower in patients with the delta F508 mutation, but the sweat chloride level tended to be higher in these patients. All the patients with the delta F508 mutation had exocrine pancreatic insufficiency, which tended to be higher than 84% in those without this mutation. In addition, all of these patients had pulmonary involvement, which tended to be higher than 64% in those with negative delta F508 mutation. According to the results of this study, the frequency of delta F508 mutations in Iranian patients appears to be much lower than what is seen in American and the European patients. In those with the delta F508 mutation, pulmonary involvement and pancreatic insufficiency are more common; the sweat chloride level tended to be higher, but the age at diagnosis was lower, all of which resemble a more severe form of disease.

Blood collection on filter paper for HIV antibodies detection: experience of SampaCentro Project

Introduction: Blood samples collected on filter paper (dried blood spot [DBS]) is an immunoassay that has been used for antibodies screening. Objective: To evaluate the strategy of DBS blood collection for detection of HIV antibodies, evaluation of Q-Preven HIV 1 + 2 - DBS kit lot, and to analyze the stability of DBS samples. Methods: Blood collection on DBS was performed according to World Health Organization (WHO) recommendations. The evaluation of the kit lot for HIV antibodies detection was performed using delta (d) values from the results of 774 DBS samples from volunteers men who have sex with men (MSM) recruited in the central region of Sao Paulo city, Brazil. Results: DBS blood collection was performed without complications. The positive (5.26) and negative (5.23) delta values allowed to clearly differentiate HIV antibodies reactive and non-reactive samples. We observed good performance of the kit lot and samples were stable on DBS form. Conclusion: Blood collection on DBS is feasible for the study of MSM population and is suitable for laboratory routine. The overall performance of Q Preven HIV-1 + 2 - DBS kit was satisfactory, having reached the quality levels required for the development of this study.

Choice of Management in a Rare Case of Symptomatic Wolff-Parkinson-White (WPW) Syndrome Type B

Introduction: Wolff-Parkinson-White (WPW) syndrome type B is a congenital condition involving abnormal electrical conduction between the atria and the ventricles that provide an accessory pathway (AP) for a re-entrant tachycardia circuit. Background: This case report illustrates a 28-year-old male who presented with multiple episodes of rapid, regular palpitations associated with dizziness and nausea. These episodes of palpitations often resolve spontaneously. Physical examination revealed normal first and second heart sounds with no audible murmurs. Other systemic examinations were unremarkable. A 12 lead electrocardiogram showed an atrioventricular re-entrant tachycardia (AVRT) of 210 beats per minute. Intravenous amiodarone was given to which he responded. Post pharmacological cardioversion, the repeated ECG showed shortened PR interval and broad QRS complexes associated with negative delta waves in lead V1, T-wave inversion in inferior leads and precordial leads of V5-V6 which represented a Type B pattern. He was then referred to the electrophysiology unit at the National Heart Institute for radiofrequency ablation (RFA) and Holter monitoring. Conclusion: Wolff-Parkinson-White (WPW) Type B should be considered as a differential diagnosis for a young individual who presents with frequent palpitations. RFA is well known as a permanent solution to the prevention of tachyarrhythmia.

Appropriate Localisation of Epicardial Accessory Pathway of WPW Sydrome-Initial Step to Success

Subepicardial posteroseptal accessory pathways, which consist of accessory pathway (AP) required ablation from within the subepicardial venous system, including the middle cardiac vein and other coronary veins [1]. As the electrocardiogram (ECG) algorithm accurately localizes accessory pathways prior to ablation, it may help the physician advice the patient regarding the likelihood of success and complications of the procedure. The ECG algorithm may aid selection of patients in whom coronary sinus angiography should be perfomied in order to delineate its anatomy, thus allowing mapping in the coronary veins and anomalous structures of the coronary sinus. A negative delta wave in lead II identifies the subepicardial posteroseptal accessory pathway as per Arudas criteria [2]. We report a Electrocardiogram manifest of classic subepicardial pathway arising from middle cardiaac vein. We report a 50years old lady presented with history of recurrent palpitations of 2 years duration.No past history of any cardiac disease. Baseline ECG (Figure 1) showed evidence of pre- excitation with positive delta wave in leads I, AVL, V1-V6 with negative delta wave in leads II, III, AVF. A distinctive ECG clue for the presence of an epicardial AP was a steeply negative delta wave in lead II.Electrophysiological studies confirmed subepicardial pathway arising from middle cardiac vein and successful ablation of the pathway done.Since we localized the pathway as epicardial pathway on ECG by applying Arudas criteria, coronary venous sinus angiography done and ablated by left sided approach by transseptalpuncture, stressing importance of ECG localization.

Chaotic Dynamics in Kicked Ratchets

A one-dimensional deterministic continuous dynamical system is studied and shown to exhibit chaotic behavior and complex trans- port properties. Our model is an overdamped rocking ratchet with finite dissipation that is periodically kicked with a delta function driving force, without finite inertia terms or temporal or spatial stochastic forces. This is perhaps the simplest model reported in the literature for a ratchet that exhibits a complex chaotic behavior. We present both numerical and analytical results that predict many key features of the system, such as current reversals, as well as the presence of chaotic behavior and bifurcation. In particular, we show that alternate positive and negative delta functions as the unbiased driving force on a ratchet potential produces both synchronized and chaotic regions.

Design criteria for tetradentate phenanthroline-derived heterocyclic ligands to separate Am(III) from Eu(III)

To design novel phenanthroline-derived soft ligands for selectively separating minor actinides from lanthanides, four tetradentate phenanthroline-derived heterocyclic ligands (BTPhen, BPyPhen, BPzPhen, and BBizPhen) were constructed and their complexation behaviors with Am(III) and Eu(III) were systematically investigated by density functional theory (DFT) coupled with relativistic small-core pseudopotential. In all the 1:1-type species, the metal ion is in the center of the cavity and coordinates with two nitrogen atoms (N1 and N1') of the phenanthroline skeleton and the other two nitrogen atoms (N2 and N2') of the auxiliary groups. The bond lengths of Am-N are comparable to or even shorter than those of Eu-N bonds because the ionic radii of Am(III) are larger than those of Eu(III). Additionally, the negative Delta Delta G (Am/Eu) value for the reaction of [M(H2O)(4)(NO3)(3)] + L -> ML(NO3)(3) + 4H(2)O indicates that the complexation reaction of Am(III) is more energetically favorable than that of Eu(III); this can be considered as an important design criterion to screen phenanthroline-derived ligands for MA(III) extraction. According to this criterion, the selectivity of tetradentate phenanthroline-derived ligands for separating Am(III) over Eu(III) follows the order of BTPhen > BBizPhen > BPyPhen > BPzPhen.

Dynamics of Bankrupt Stocks

We model and study the behavior of bankrupt stocks. We are interested in the dynamics of stocks and options, and in particular the cost of establishing positions with negative delta. This extends a model of Avellaneda and Lipkin which was used to model hard-to-borrow stocks. This model is a two-dimensional integrate-and-fire model which captures the self-reinforcing aspect of short squeezes and subsequent “crashes” when price support at some point vanishes. The only source of randomness in our model is the timing of these crashes. We understand the asymptotic behavior of this model and the risk-neutral measure.

Catheter ablation of an epicardial accessory pathway via the middle cardiac vein

Radiofrequency catheter ablation (RFA) of Wolff-ParkinsonWhite syndrome can be challenging and is associated with failure in up to 5% of cases. The main causes for initial failure were difficulties in catheter manipulation, inadequate accessory pathway (AP) mapping primarily due to epicardial or parahisian localization, and multiple pathways or insertions. Epicardial APs are most commonly found in the posteroseptal (PS) and left posterior regions. This kind of epicardial AP results from a connection between an extension of the coronary sinus (CS) myocardial coat along the middle cardiac vein (MCV), posterior coronary vein (PCV), or the neck of a CS anomaly and left ventricular epicardium. Therefore, they can be successfully ablated only from inside the CS or its branches, if endocardial ablation fails. A 19-year-old female with recurrent supraventricular tachycardia was referred for an electrophysiologic study (EPS). The ECG demonstrated ventricular preexcitation indicating PS-AP (Figure A). After induction of the orthodromic atrioventricular reciprocating tachycardia (AVRT), it quickly degenerated to ventricular tachycardia requiring electrical cardioversion. Ventricular pacing revealed the earliest atrial activation of the CS ostium. However, right and left PS endocardial RFA attempts failed to ablate the AP. CS venography revealed the presence of a mildly fusiform MCV (Figure B), and RFA in this area (Figure C and Video 1*) achieved successful ablation of ventriculoatrial conduction. Because of the close proximity of the CS ostium and posterolateral branch of the right coronary artery, caution should be exercised during RFA into the CS. A distinctive ECG clue for the presence of an epicardial AP in the PS area was a steeply negative delta wave in lead II. 223

Analysis of household ignitable liquids and their post-combustion weathered residues using compound-specific gas chromatography-combustion-isotope ratio mass spectrometry

The continuing rise in home and vehicular arson cases involving the use of ignitable liquids continues to be an area of concern for criminal and civil investigators. In this study, the compound-specific δ13C values of various components of four flammable household chemicals were measured using a single quadrupole mass spectrometer and an isotope ratio mass spectrometer as simultaneous detectors for a gas chromatograph. Whereas compound-specific carbon isotope ratios were able to discriminate between different sources of neat (pre-combustion) ignitable liquids, analyses of the post-combustion residues were problematic. Weathering caused by combustion resulted in a significant increase in the 13C content of specific peaks relative to the neat liquids (i.e. less negative delta values) such that the isotopic comparison of pre- and post-combustion residues resulted in fractionation ranging from 0 to +10‰. Because of the current lack of understanding of isotopic fractionation during combustion, and because of problems encountered with co-elution in the more complex samples, compound-specific IRMS does not appear to be suitable for fire debris analysis. The comparison of non-combusted or non-weathered ignitable liquids is much more reliable, especially for relatively simple mixtures, and is best suited for exclusionary purposes until such time as a comprehensive database of samples is developed. Without a measure of the population variance, one cannot presently predict the false positive identification rate for the comparison of two ignitable liquids; i.e. the probability that two random ignitable liquid samples have indistinguishable isotope ratios.

The change in differing leukocyte populations during vaccination to bovine respiratory disease and their correlations with lung scores, health records, and average daily gain1,2,3

Bovine respiratory disease (BRD) is the most economically important disease in U.S. feedlots. Infection can result in morbidity, mortality, and reduced average daily gain. Cheap and reliable genetic methods of prediction and protection from BRD would be highly advantageous to the industry. The immune response may correlate with BRD incidence. Cattle (n = 2,182) were vaccinated against common viral and bacterial pathogens of BRD. Two blood samples were collected, one during booster vaccination and one 21d later, enabling 3 phenotypes for each trait [prebooster (pre), postbooster (post), and delta (post minus pre)]. From the blood samples innate and adaptive responses [counts of white blood cells (WBC), neutrophils, lymphocytes, monocytes, eosinophils, and basophils] were measured. In addition, feedlot ADG and binary traits [health records (HR; 0 = healthy, 1 = ill) and lung scores (LS; collected at harvest; 0 = no lesions, 1 = lesions)] were also recorded. Traits ADG, HR, and LS have all been significantly correlated with infection to BRD. In this investigation we aimed to find correlations between the immune response and ADG, HR, and LS to find an easily measurable trait that would be a good predictor of BRD resistance after vaccination. The results showed an average positive delta for the innate immune response (eosinophils, basophils, neutrophils), whereas the adaptive immune response had an average negative delta (lymphocytes). Overall, we discovered that the immune responses had moderately high heritabilities (h(2); lowest: delta monocytes, 0.21 ± 0.05; greatest: pre lymphocytes: 0.5 ± 0.05), with lymphocytes having the greatest h(2) throughout the study (h(2) ≥ 0.41). All genetic correlations were calculated using bivariate REML models. Although LS did not significantly correlate with any of the immune phenotypes, both ADG (post lymphocytes, -0.24 ± 0.12) and HR (pre eosinophils, -0.67 ± 0.29; delta WBC, -0.5 ± 0.24, and delta lymphocytes, -0.67 ± 0.21) did. All the significant genetic correlations with HR were negative; resistance to BRD appears to be a function of greater delta lymphocytes and WBC. The increase in eosinophils may potentially link its role in decreasing lymphocytes. These results may enable producers to predict if revaccination, quarantine, and breeding of animals is required to reduce the incidence of BRD postvaccination. In addition, immunological phenotypes maybe used to aid genomic selection indices to select animals with greater rates of protection after BRD vaccination.

Effects of low-volume walking programme and vitamin E supplementation on oxidative damage and health-related variables in healthy older adults

BackgroundBoth exercise and vitamin E supplementation have been shown to reduce oxidative stress and cardiovascular disease risk in older adults, and when combined there is evidence suggesting that they act synergistically. The currently recommended amount of exercise for older adults is 150 min/week of moderate-intensity exercise; however, the minimum amount of exercise necessary to achieve health benefits is not known. The purpose of this study was to investigate the effects of 12 weeks of participation in a low-volume walking exercise programme (i.e. 90 min/week) combined with daily vitamin E supplementation on thiobarbituric acid reactive substances (TBARS) and oxidised low-density lipoprotein (LDL) concentrations in older adults.MethodsThe participants were recruited from the following four groups separately: 1) control (CG, n = 14), 2) vitamin E supplementation (SG, n = 10), 3) walking (WG, n = 7), or 4) walking + supplementation (WSG, n = 7). In the CG, participants were advised to maintain their normal lifestyle during the study. Participants in both the SG and WSG received 450 IU (300 mg) /day of α-tocopherol for 12 weeks. The exercise programme for the WG and WSG consisted of two 30–60 minute sessions weekly for 12 weeks (average walking time was 44.5 ± 1.6 min/session). Blood samples were collected at baseline and at 12 weeks.ResultsDelta plasma oxidised LDL concentrations did not differ among four groups (One-factor ANOVA, P = 0.116). However, negative delta plasma TBARS, a marker of oxidative damage, concentrations were observed in the WG, WSG and SG relative to the CG at the end of the study period (One-factor ANOVA, P = 0.001; post hoc tests; CG compared with WG, WSG and SG, P = 0.005; P = 0.021; P = 0.024, respectively).ConclusionThese findings suggest that a low-volume of physical activity and/or vitamin E supplementation may be an effective intervention strategy for reducing TBARS concentrations of older adults.Trial registrationUMIN000008304

Distribution characteristics and sources of sedimentary organic matter in the pearl river estuary and adjacent coastal waters, southern China

Geochemical descriptors (carbon, nitrogen contents, and their isotopes) of sedimentary organic matter (OM) were investigated in the Pearl River estuary (PRE) and adjacent coastal waters. The comprehensive geochemical data of surface and deep sediments were provided, and the sources of sedimentary OM were discussed in this area mainly impacted by human activities. Surface (1-10 cm) and deep (190-200 cm) sedimentary total organic carbon (TOC) were 1.2% and 0.6%, and total nitrogen (TN) contents were 0.09% and 0.05%, with delta C-13 of -24.3 parts per thousand and -24.5 parts per thousand, on the average, respectively. Higher TOC and TN contents combining with relatively negative delta C-13 values in surface sediments suggested the increasing OM inputs from rivers in recent years. Terrestrial organic carbon (OC) contents were 0.70% and 0.36%, and marine OC contents were 0.50% and 0.28% on the average, respectively, in surface and deep sediment. Surface terrestrial and marine OC were lower in river outfalls due to the high current energy, and deep terrestrial and marine OC showed the increasing trend away from the coast. Lower delta N-13 was mainly attributed to the influence of river sewage discharge in this study.

GAS MOTION STUDY OF Lyα EMITTERS ATz∼ 2 USING FUV AND OPTICAL SPECTRAL LINES,

We present the results of Magellan/MMIRS and Keck/NIRSPEC spectroscopy for five Lya emitters (LAEs) at z=2.2 for which high-resolution FUV spectra from Magellan/MagE are available. We detect nebular emission lines including Ha on the individual basis and low-ionization interstellar (LIS) absorption lines in a stacked FUV spectrum, and measure average offset velocities of the Lya line, Delta_v_Lya, and LIS absorption lines, Delta_v_abs, with respect to the systemic velocity defined by the nebular lines. For a sample of eight z~2-3 LAEs without AGN from our study and the literature, we obtain Delta_v_Lya = 175+/-35 km s^{-1}, which is significantly smaller than that of Lyman-break Galaxies (LBGs), Delta_v_Lya=400 km s^{-1}. The stacked FUV spectrum gives Delta_v_abs = -179 +/- 73 km s^{-1}, comparable to that of LBGs. These positive Delta_v_Lya and negative Delta_v_abs suggest that LAEs also have outflows. In contrast to LBGs, however, the LAEs' Delta_v_Lya is as small as |Delta_v_abs|, suggesting low neutral hydrogen column densities. Such a low column density with a small number of resonant scattering may cause the observed strong Lya emission of LAEs. We find an anti-correlation between Lya equivalent width (EW) and Delta_v_Lya in a compilation of LAE and LBG samples. Although its physical origin is not clear, this anti-correlation result appears to challenge the hypothesis that a strong outflow, by means of a reduced number of resonant scattering, produces a large EW. If LAEs at z>6 have similarly small Delta_v_Lya values, constraints on the reionization history derived from the Lya transmissivity may need to be revised.

Stable carbon isotopes of invertebrate remains: do they reveal past methane release from lakes?

Lakes are a source of methane, an important greenhouse gas in the atmosphere. In order to understand increasing methane emissions in the present, it is important to study the variations of methane release during past periods of climate change. However, records of methane release from lakes over time scales longer than a few years are extremely rare. In this thesis a method is explored to reconstruct past methane availability in lakes based on the stable carbon isotope composition (delta 13C) of aquatic invertebrate remains. Methane-derived 13C-depleted carbon can be an alternative carbon source to plant-derived material for invertebrates in the sediment and water column of lakes, that can lead to markedly depleted delta 13C values in invertebrate tissues. Using culturing experiments, it was demonstrated that methane-derived carbon is incorporated into chironomid head capsules. Also, it was shown that chemical pre-treatments that are commonly used for sediment processing do not have a noticeable effect on delta 13C values of chironomid remains and that a minimum of 20 microgram chitinous material is required for reproducible delta 13C measurements. In study lakes in Sweden and Siberia, delta 13C values of chitinous remains of several invertebrate taxa in surface sediments were negatively correlated with diffusive methane fluxes. Strong and significant correlations are observed between diffusive methane fluxes and delta 13C of Chironomini and Daphnia remains. Similar correlations were also observed within two Swedish lakes, in which surface sediment cores were obtained along depth transects. Delta 13C values of Chironomini and Daphnia were lower in sections of the lake basin in which the sediments had higher methane release rates. This suggests that delta 13C in remains of several invertebrates, especially Chironomini and Daphnia can be indicative of methane availability in lakes. In contrast, Orthocladiinae and Ephemeroptera, always had relatively high delta 13C values, indicating a plant-derived carbon source. In a sediment record from a Siberian thermokarst lake, delta 13C values of the remains of Chironomini and Daphnia showed relatively large negative delta 13C shifts in warm periods (AD 850-1150 and since AD 1970) compared with delta 13C values of Orthocladiinae remains and bulk sediment. Based on the observed correlations between methane fluxes and delta 13C values of Chironomini and Daphnia in surface sediment samples, this suggests that more methane-derived carbon was available in warm periods compared with colder periods. The research in this thesis demonstrates the potential to use taxon-specific stable carbon isotopes analysis of invertebrate remains for qualitative reconstructions of methane availability in lakes. This new method can lead to a better understanding of lake methane emissions in relation to climate change

Serum antibody-negative Goodpasture syndrome with delta granule pool storage deficiency and eosinophilia.

Goodpasture syndrome is a rare, life-threatening autoimmune disease characterized by a triad of rapidly progressive glomerulonephritis, a hemorrhagic pulmonary condition and the presence of anti-glomerular basement membrane (anti-GBM) antibodies. The antibodies initiate destruction of the kidney glomeruli, resulting in a focal necrotizing glomerulitis, which may progress rapidly to renal failure. Autoantibody-mediated damage of alveolar basement membranes leads to diffuse pulmonary hemorrhage, which in some cases may be severe enough to cause respiratory failure. Many clinicians use a variety of assays to detect serum anti-GBM antibodies; however, these tests may be falsely negative in up to 15% of patients with Goodpasture syndrome. Here, we report an unusual case of a 40-year-old man with clinical evidence of Goodpasture syndrome, a negative anti-GBM antibody serum result, eosinophilia and delta granule pool storage deficiency. After a 14-day hospital stay and extensive workup, as well as treatment with antibiotics, steroids and ventilator support for respiratory failure, the patient continued to deteriorate and entered multisystem organ failure. The family decided to withdraw ventilator support, and the patient expired. Immunofluorescence testing for anti-GBM autoantibodies on lung and kidney tissues during an autopsy confirmed the diagnosis of Goodpasture syndrome.

Reappraisal of classical electrocardiographic criteria in detecting accessory pathways with a strict para-Hisian location

Identification of electrocardiographic (ECG) criteria for para-Hisian accessory pathways (APs) is based on a small series of patients. The presence of a negative delta wave in leads V(1) and V(2) has been suggested as an ECG marker of this AP location. To validate these ECG findings in a large series of patients with strict invasive criteria for that location. We included 105 patients (39 women, 66 men; mean age 26 ± 12 years, range 5-82 years) with an ECG pattern compatible with preexcitation through an anteroseptal or midseptal AP following established ECG criteria. A para-Hisian AP was defined when the location of its successful catheter ablation coincided with either the largest recordable His bundle electrogram or a His bundle potential of>0.1 mV. Patients without that definition were included in the control group. A para-Hisian location of the AP was found in 52 patients. AP locations of the remaining 53 patients (control group) were anteroseptal (n = 39), midseptal (n = 9), and fasciculoventricular (n = 5). A negative delta wave in leads V(1) and V(2) was observed in 13 patients with para-Hisian APs (sensitivity 25%; specificity 92%). However, the sum of initial r-wave amplitudes in those leads was<0.5 mV in 44 of the patients with para-Hisian APs and in 13 patients of the control group (sensitivity 85%; specificity 75.5%; area under receiver-operator characteristic curve 0.85). The presence of negative delta waves in leads V(1) and V(2) indicates a poor sensitivity and high specificity to detect APs with a strict definition of para-Hisian location. The sum of initial r-wave amplitudes in those ECG leads could be a useful, adjunctive marker in the noninvasive identification of these challenging APs.

Urgent need for a common metric to make precipitation manipulation experiments comparable

Urgent need for a common metric to make precipitation manipulation experiments comparable

Effects of a spin-flavour-dependent interaction on the baryon mass spectrum

The effective quark interaction in a relativistically covariant constituent quark model based on the Salpeter equation is supplemented by an extra phenomenological flavour dependent force in order to account for some discrepancies mainly in the description of excited negative parity Delta resonances. Simultaneously an improved description of some other features of the light-flavoured baryon mass spectrum and of some electromagnetic form factors is obtained.

A sword of Damocles in an asymptomatic man presenting with serendipitously detected ventricular pre-excitation

MOTS CLES Syndrome de WolfA 25-year-old man was admitted to hospital for electrophysiological studies for WolfParkinson-White syndrome, discovered during a medical clearance examination to be a professional soccer referee. This athlete had no medical history, reported no symptoms and his physical examination was normal. A 12-lead electrocardiogram revealed the presence of ventricular pre-excitation, a negative delta wave in leads I and aVL, and right bundle branch-type QRS morphology, consistent with a left lateral accessory pathway (Fig. 1), which persisted during peak exercise. Electrophysiological studies confirmed the presence of a left lateral accessory pathway and the induction of atrial fibrillation by rapid atrial pacing, immediately followed by the development of ventricular fibrillation (Fig. 2a, b), requiring the delivery of two consecutive biphasic 200J DC shocks to restore sinus rhythm (Fig. 3a). The patient

Weighted barycentric sets and singular Liouville equations on compact surfaces

Given a closed surface, we prove a general existence result for some elliptic PDE with exponential nonlinearities and negative Dirac deltas, extending a theory recently obtained for the regular case. This is done by global methods: since the associated Euler functional might be unbounded from below, we define a new model space, generalizing the so-called space of formal barycenters and characterizing (up to homotopy equivalence) its low sublevels. As a result, the analytic problem is reduced to a topological one concerning the contractibility of this model space. To this aim, we prove a new functional inequality in the spirit of Chen and Li (1991) [11] and then employ a min–max scheme based on conical construction, jointly with the blow-up analysis in Bartolucci and Montefusco (2007) [4] (after Bartolucci and Tarantello, 2002; Brezis and Merle, 1991 [5,7]). This study is motivated by abelian Chern–Simons theory in self-dual regime, or from the problem of prescribing the Gaussian curvature with conical singularities (generalizing a problem raised in Kazdan and Warner, 1974 [24]).