Association of fetal growth restriction and stillbirth in twin compared with singleton pregnancies.

OBJECTIVE: Twin pregnancies are at an increased risk of stillbirth compared to singletons. Fetal growth restriction (FGR) is a leading cause of perinatal mortality and morbidity, in both singleton and multiple pregnancies. Whether the contribution of FGR to stillbirth in twin pregnancies differs from that in singletons is yet to be determined. The main aim of this study was to determine the association between FGR and stillbirth in twin compared to singleton pregnancies. The secondary objectives include an assessment of the contribution of FGR to stillbirths, stratified by gestational age at delivery. Furthermore, we aimed to compare the association between FGR and stillbirth in twin pregnancies using the twin-specific versus singleton birthweight charts, stratified by chorionicity. METHODS: This was a cross-sectional study including pregnancies receiving obstetric care and birth at St George's Hospital, London. The exclusion criteria included triplet and higher order pregnancies, those resulting in miscarriage or livebirths at or prior to 23+6 weeks, or had a termination of pregnancy, or with missing data on the gestational age at birth. FGR and small for gestational age (SGA) were defined as birthweight <5th and <10th centile, respectively. While standard logistic regression was used for singleton pregnancies, the association of FGR and SGA designation with stillbirth in twin pregnancies was investigated with mixed-effects logistic regression models. For twin pregnancies, intercepts were allowed to vary for twin pairs to account for inter-twin dependency. Analyses were stratified by gestational age at delivery and chorionicity. RESULTS: The study included 95,342 singleton and 3,576 twin pregnancies. There were 494 (0.52%) stillbirths in singleton and 41 (1.15%) stillbirths in twin pregnancies (17 dichorionic and 24 monochorionic). FGR and SGA were significantly associated with stillbirth in singleton pregnancies, across all gestational ages at delivery (before 32 weeks- SGA: OR 2.36; 95% CI 1.78-3.13, p<0.001 and FGR: OR 2.67; 95% CI 2.02- 3.55, p<0.001; between 32-36 weeks- SGA: OR 2.70; 95% CI 1.71-4.31, p<0.001 and FGR: OR 2.82; 95% CI 1.78- 4.47, p<0.001; above 36 weeks- SGA: OR 3.85; 95% CI 2.83 - 5.21, p<0.001 and FGR: OR 4.43; 95% CI 3.16 - 6.12, p<0.001) A greater proportion of fetuses from twin pregnancies were diagnosed as SGA and FGR when singleton compared to the twin-specific chart was used (48.43% vs. 9.12%, and 36.73% vs. 6.23%, respectively). When stratified by gestational age at delivery, both SGA and FGR determined by the twin-specific charts were associated with significantly increased odds of having a stillbirth for those delivered before 32 weeks (SGA: OR 3.87; 95% CI 1.56-9.50, p=0.003 and FGR: OR 5.26; 95% CI 2.11-13.01, p<0.001), those delivered between 32-36 weeks (SGA: OR 6.67; 95% CI 2.11-20.41, p=0.001 and FGR: OR 9.54; 95% CI 3.01-29.40, p<0.001) and those delivered beyond 36 weeks (SGA: OR 12.68 95% CI 2.47-58,15, p=0.001 and FGR: OR 23.84; 95% CI 4.62-110.25, p<0.001), whereas the association of stillbirth with either SGA or FGR was inconsistent when analysed using singleton charts (before 32 weeks- SGA: p=0.014 and FGR: p=0.005; between 32-36 weeks- SGA: p=0.036 and FGR: p=0.008; above 36 weeks- SGA: p=0.080 and FGR: p=0.063). For dichorionic twins delivered before 32 weeks, the odds of an SGA or FGR fetus having a stillbirth was increased when analysed using twin-specific charts. In contrast, monochorionic twins delivered before 32 weeks showed lower and non-significant associations with stillbirth for both SGA and FGR cases using either twin-specific or singleton charts. In dichorionic twin pregnancies delivered between 32-36 weeks, the OR for stillbirth of SGA using twin birthweight chart was 6.70 (95% CI 0.80-56.46, p=0.059), and using singleton chart was 0.92 (95% CI 0.11-7.71, p=0.934) and statistically non-significant. Similarly, the OR for stillbirth of FGR using twin birthweight chart and singleton chart was 9.59 (95% CI 1.14-81.06, p=0.025), and 1.40 (95% CI 0.17-11.76, p=0.735), respectively. On the other hand, in monochorionic twin pregnancies delivered between 32-36 weeks, the OR for stillbirth of SGA and FGR using twin birthweight chart was 9.37 (95% CI 2.20- 37.72, p=0.001), and 13.55 (95% CI 3.12 - 55.94 p < 0.001) respectively. CONCLUSIONS: Our study demonstrates a significant association between SGA, particularly for FGR, with increased odds of stillbirths in singleton pregnancies across all gestational ages. For twin pregnancies, when twin-specific charts were used, SGA and in particular FGR were associated with a significantly increased risk of stillbirth, across all gestational ages at delivery. This article is protected by copyright. All rights reserved.

Heart Failure and Major Adverse Cardiovascular Events in Atrial Fibrillation Patients: A Retrospective Primary Care Cohort Study.

BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia that is associated with an increased risk of major adverse cardiovascular events (MACE). The main goal was to analyze the links and associations between AF and MACE. METHODS: A multicenter, observational, retrospective, community-based study of a cohort (n = 40,297) of the general population aged 65-95 years between 1 January 2015 and 31 December 2021 without a previous diagnosis of AF or MACE in the Primary Care setting. RESULTS: 2574 people (6.39%) developed a first AF event, resulting in an overall incidence of 8.9/1000 people-years [CI95% 8.6-9.2]. The incidence of MACE among those with AF was 75.1/1000 people-years [CI95% 70.8-79.5], whereas among those without AF, it was 20.6/1000 people-years [CI 95% 20.2-21.1], resulting in a rate ratio of 3.65 [CI 95% 3.43-3.88, p < 0.001]. Besides, the incidence of HF with AF was 40.1 people-years [CI 95% 37.1-43.2], while in the group without AF, it was 8.3 people-years [CI 95% 7.9-8.6, p < 0.001], with a rate ratio of 4.85 [CI 95% 4.45-55.3, p < 0.001]. Before an AF diagnosis, there is already a higher risk of chronic kidney disease, ischemic cardiopathy, and peripheral artery disease. A higher risk of poor nutritional status was detected among those with MACE (49.7% vs. 26.6%, p < 0.001). CONCLUSIONS: AF diagnosis increases the incidence of heart failure fourfold. Additional information is required to establish the connection between AF, major adverse cardiovascular events, and nutritional status.

Integrated programmable spectral filter for frequency-multiplexed neuromorphic computers.

Artificial neural networks (ANN) are a groundbreaking technology massively employed in a plethora of fields. Currently, ANNs are mostly implemented through electronic digital computers, but analog photonic implementations are very interesting mainly because of low power consumption and high bandwidth. We recently demonstrated a photonic neuromorphic computing system based on frequency multiplexing that executes ANNs algorithms as reservoir computing and Extreme Learning Machines. Neuron signals are encoded in the amplitude of the lines of a frequency comb, and neuron interconnections are realized through frequency-domain interference. Here we present an integrated programmable spectral filter designed to manipulate the optical frequency comb in our frequency multiplexing neuromorphic computing platform. The programmable filter controls the attenuation of 16 independent wavelength channels with a 20 GHz spacing. We discuss the design and the results of the chip characterization, and we preliminary demonstrate, through a numerical simulation, that the produced chip is suitable for the envisioned neuromorphic computing application.

Analysis of skull bone thickness during growth: an anatomical guide for safe pin placement in halo fixation.

PURPOSE: To assess skull bone thickness from birth to skeletal maturity at different sites to provide a reference for the correct selection of pin type and pin placement according to age. METHODS: 270 children and adolescents (age: 0-17 years) with a normal CT scan obtained at Emergency Department for other medical reasons were included. Skull thickness was measured on the axial plane CT scans at eight different sites of the vault: midline anterior (A) and posterior (P), right and left lateral (L), antero-lateral (AL), postero-lateral (PL). RESULTS: From birth to skeletal maturity, L thickness was increased significantly less (+ 58%) compared with AL (+ 205%), P (+ 233%), PL (+ 247%), and A (+ 269%) thickness (P < 0.01). At the end of growth, the thickest and thinnest points of the vault (absolute value) were found at the P and L measurement sites, respectively (P < 0.01). Children aged < 4 years exhibited the highest variability in AL and PL skull bone thickness, with thickness < 3 mm observed in 85% (64/75 patients) and 92% (69/75 patients) of cases, respectively. CONCLUSION: We recommend that the tip of the pin should not exceed 2-3 mm in children aged < 4, and 4 mm in children aged 4-6 years, to decrease the risk of inner table perforation. After the age of 7 years and 13 years, standard-sized pin tips (5 and 6 mm, respectively) may be safely used. Children aged < 4 years show significant variability in skull thickness, and therefore a CT scan may be required for this particular age group.

Correction to: Incidence of Incisional Hernia After Emergency Subcostal Unilateral Laparotomy: Does Augmentation Prophylaxis Play a Role?

In the original article some of the column headings in Tables 1-4 were mislabeled.

Correction to: Analysis of skull bone thickness during growth: an anatomical guide for safe pin placement in halo fixation.

Unfortunately, the author group has been incorrectly listed by the first name instead of the family name in the original publication. The complete correct author group should read as follows.

Incidence of Incisional Hernia After Emergency Subcostal Unilateral Laparotomy: Does Augmentation Prophylaxis Play a Role?

BACKGROUND: Few data are available about the frequency of incisional hernia in an emergency subcostal laparotomy. Our objective is to analyze the incidence of incisional hernia after emergency subcostal laparotomy and evaluate if prophylactic mesh could help prevent it. METHODS: This study is a monocentric retrospective analysis following STROBE guideline statements of all patients who underwent an emergency subcostal laparotomy between January 2011 and July 2017 in our University Hospital. We compared complications and incidence of incisional hernia between patients who received sutures (Group S; N = 203) and patients with prophylactic onlay mesh (Group M; N = 80). A multivariate risk factor analysis of incisional hernia was performed. An incisional hernia-estimated risk calculator equation was created. RESULTS: A total of 283 patients were analyzed. There were 80 patients in Group M and 203 in Group S. In short-term outcomes, length of surgery (213 ± 115 min vs 165 ± 73.3 min, P = 0.001) and hospital stay (16.4 ± 18.7 vs 11.6 days ± 13.4, P = 0.038) were longer in Group M. Long-term follow-up was conducted in 207 patients with a mean follow-up time of 39.3 ± 23 months. Incisional hernia was detected in 29 (19.1%) patients in Group S but in only two (3.8%) patients in Group M (P = 0.008). In the multivariate analysis, a risk factor analysis included wound infection (4.91 HR (2.12-11.4); P < 0.001), previous hernia repair (2.86 HR (1.24-6.61); P = 0.014), and shock (2.64 HR (1.01-6.93); P = 0.048). CONCLUSIONS: The incidence of incisional hernia after emergency subcostal laparotomy is high. Risk factors are wound infection, shock, and previous hernia surgery. The use of prophylactic mesh augmentation was safe and reduced the incidence of incisional hernia.

The millimeter-wave spectrum and astronomical search of succinonitrile and its vibrational excited states ☠.

CONTEXT: Dinitriles with a saturated hydrocarbon skeleton and a -C≡N group at each end can have large electric dipole moments. Their formation can be related to highly reactive radicals such as CH2CN, C2N or CN. Thus, these saturated dinitriles are potential candidates to be observed in the ISM. AIMS: Our goal is the investigation of the rotational spectrum of one of the simplest dinitriles N≡C-CH2-CH2-C≡N, succinonitrile, whose actual rotational parameters are not precise enough to allow its detection in the ISM. In addition, the rotational spectra for its vibrational exicted states will be analyzed. METHODS: The rotational spectra of succinonitrile was measured in the frequency range 72-116.5 GHz using a new broadband millimeter-wave spectrometer based on radio astronomy receivers with Fast Fourier Transform backends. The identification of the vibrational excited states of succinonitrile was supported by high-level ab initio calculations on the harmonic and anharmonic force fields. RESULTS: A total of 459 rotational transitions with maximum values of J and Ka quantum numbers 70 and 14, respectively, were measured for the ground vibrational state of succinonitrile. The analysis allowed us to accurately determine the rotational, quartic and sextic centrifugal distortion constants. Up to eleven vibrational excited states, resulting from the four lowest frequency vibrational modes ν 13, ν 12, ν 24 and ν 23 were identified. In addition to the four fundamental modes, we observed overtones together with some combination states. The rotational parameters for the ground state were employed to unsuccessfully search for succinonitrile in the cold and warm molecular clouds Orion KL, Sgr B2(N), B1-b and TMC-1, using the spectral surveys captured by IRAM 30m at 3mm and the Yebes 40m at 1.3cm and 7mm.

Broad band high resolution rotational spectroscopy for Laboratory Astrophysics.

We present a new experimental setup devoted to the study of gas phase molecules and processes using broad band high spectral resolution rotational spectroscopy. A reactor chamber has been equipped with radio receivers similar to those used by radio astronomers to search for molecular emission in space. The whole Q (31.5-50 GHz) and W bands (72-116.5 GHz) are available for rotational spectroscopy observations. The receivers are equipped with 16×2.5 GHz Fast Fourier Transform spectrometers with a spectral resolution of 38.14 kHz allowing the simultaneous observation of the complete Q band and one third of the W band. The whole W band can be observed in three settings in which the Q band is always observed. Species such as CH3CN, OCS, and SO2 are detected, together with many of their isotopologues and vibrationally excited states, in very short observing times. The system permits automatic overnight observations and integration times as long as 2.4×105 seconds have been reached. The chamber is equipped with a radiofrequency source to produce cold plasmas and with four ultraviolet lamps to study photochemical processes. Plasmas of CH4, N2, CH3CN, NH3, O2, and H2, among other species, have been generated and the molecular products easily identified by their rotational spectrum, and mass spectrometry and optical spectroscopy. Finally, the rotational spectrum of the lowest energy conformer of CH3CH2NHCHO (N-Ethylformamide), a molecule previously characterized in microwave rotational spectroscopy, has been measured up to 116.5 GHz allowing the accurate determination of its rotational and distortion constants and its search in space.

Using radio astronomical receivers for molecular spectroscopic characterization in astrochemical laboratory simulations: A proof of concept.

We present a proof of concept on the coupling of radio astronomical receivers and spectrometers with chemical reactors and the performances of the resulting setup for spectroscopy and chemical simulations in laboratory astrophysics. Several experiments including cold plasma generation and UV photochemistry were performed in a 40 cm long gas cell placed in the beam path of the Aries 40 m radio telescope receivers operating in the 41-49 GHz frequency range interfaced with fast Fourier transform spectrometers providing 2 GHz bandwidth and 38 kHz resolution. The impedance matching of the cell windows has been studied using different materials. The choice of the material and its thickness was critical to obtain a sensitivity identical to that of standard radio astronomical observations. Spectroscopic signals arising from very low partial pressures of CH3OH, CH3CH2OH, HCOOH, OCS, CS, SO2 (<10-3 mbar) were detected in a few seconds. Fast data acquisition was achieved allowing for kinetic measurements in fragmentation experiments using electron impact or UV irradiation. Time evolution of chemical reactions involving OCS, O2 and CS2 was also observed demonstrating that reactive species, such as CS, can be maintained with high abundance in the gas phase during these experiments.

The High Resolution Infrared Spectrum of HCl.

The chloroniumyl cation, HCl+, has been recently identified in space from Herschel's spectra. A joint analysis of extensive vis-UV spectroscopy emission data together with a few high-resolution and high-accuracy millimiter-wave data provided the necessary rest frequencies to support the astronomical identification. Nevertheless, the analysis did not include any infrared (IR) vibration-rotation data. Furthermore, with the end of the Herschel mission, infrared observations from the ground may be one of the few available means to further study this ion in space. In this work, we provide a set of accurate rovibrational transition wavenumbers as well as a new and improved global fit of vis-UV, IR and millimiter-wave spectroscopy laboratory data, that will aid in future studies of this molecule.

Extending the applicability of an open-ring trap to perform experiments with a single laser-cooled ion.

A special ion trap was initially built up to perform ß-ν correlation experiments with radioactive ions. The trap geometry is also well suited to perform experiments with laser-cooled ions, serving for the development of a new type of Penning trap, in the framework of the project TRAPSENSOR at the University of Granada. The goal of this project is to use a single (40)Ca(+) ion as detector for single-ion mass spectrometry. Within this project and without any modification to the initial electrode configuration, it was possible to perform Doppler cooling on (40)Ca(+) ions, starting from large clouds and reaching single ion sensitivity. This new feature of the trap might be important also for other experiments with ions produced at radioactive ion beam facilities. In this publication, the trap and the laser system will be described, together with their performance with respect to laser cooling applied to large ion clouds down to a single ion.

Efficacy and Hemotoxicity of Stealth Doxorubicin-Loaded Magnetic Nanovectors on Breast Cancer Xenografts.

In the field of oncology, research is now focused on the development of theranostic nanosystems that combine the functions of drug delivery and imaging for diagnosis/monitoring. In this context, we designed polyethylene glycol (PEG)ylated superparamagnetic iron oxide nanoparticles (SPIONs) for the delivery of doxorubicin (DOX), an antineoplastic agent. These DOX-loaded PEGylated SPIONs, or DLPS, should be useful for the delivery of DOX in vivo, as well as for magnetic drug targeting (MDT) and magnetic resonance imaging (MRI). The aim of this study was to evaluate the potential applications of DLPS in vivo as drug carrier systems for the reduction of xenograft breast tumors induced in nude mice. Prior to the animal model experiments, the main internalization pathways for the nanovectors in MDA-MB435 breast cancer cells were determined to be based on caveolae- and clathrin-mediated endocytosis. The time- and quantity-dependence of the nanoparticle uptake by the cells altered the in vitro cytotoxicity of the DLPS. The in vitro antiproliferative effect of the DLPS was dependent not only on DOX concentration, but also on the efficacy of nanoparticle internalization. Evaluation of the effect of DLPS treatment on xenograft tumors in nude mice showed that DLPS limited tumor growth in a manner comparable to that of free DOX under normal conditions of tumor growth. The application of an external magnetic field on tumors, i.e., MDT, did not improve the efficacy of the DLPS treatment. Nevertheless, the vectorization of DOX with DLPS appears to limit the hematologic side effects usually associated with DOX treatment.

[North-South cooperation on transfusion and hematology teaching: A Benin experience]. / Coopération Nord-Sud pour le renforcement des capacités du personnel de santé en hématologie et transfusion : expérience du Bénin.

Hematologic diseases are a significant part of health disorders in Benin. As an example, anemia is the second cause of hospitalization, measuring up to 7.9% all over the country (National Plan of Sanitary Development, 2009-2018). By contrast, there is only one active hematologist in the country. Thanks to two partnerships, on one hand between the health sciences faculty in Cotonou (Benin) and the medicine one in Tours (France), and on the other hand between the Beninese Blood Transfusion National Agency and the French Blood Establishment, a first blood transfusion and hematology formation was held in Cotonou on December 2014. Among other benefits, was created an hematology-transfusion network in order to facilitate relations between Beninese hospital doctors, with the support of the two French partner institutions. The article describes this progress.

Influencia de las anomalías faringolaríngeas diagnosticadas mediante laringoscopia indirecta en la predicción de la dificultad de intubación / Influence of pharyngolaryngeal anomalies diagnosed through indirect laryngoscopy in the prediction of difficult intubation

Objetivo: Detectar anomalías faringolaríngeas no valoradas habitualmente en la evaluación de la vía aérea difícil mediante la realización en el preoperatorio de una laringoscopia indirecta con el laringoscopio rígido e investigar su influencia en la predicción de la dificultad de intubación traqueal (DIT). Métodos: Estudio observacional prospectivo en 300 pacientes consecutivos sometidos a intervenciones quirúrgicas programadas bajo anestesia general. Además de evaluar los predictores demográficos y clínicos comunes de la vía aérea difícil, les fue practicada en el preoperatorio una laringoscopia indirecta con el laringoscopio rígido para diagnosticar las anomalías faringolaríngeas. Después, bajo anestesia general y laringoscopia directa comprobamos en qué pacientes existía DIT. Se investigó la asociación de todas las variables anteriores con la DIT, se confeccionó un modelo de regresión logística con fines predictivos y su poder de discriminación se consiguió valorando el área bajo la curva ROC obtenida. Resultados: Se contabilizaron 46 anomalías: 31 alteraciones de la epiglotis (22 epiglotis abarquilladas, 9 epiglotis flácidas o hipertrofiadas), 6 amígdalas linguales hipertróficas, 3 tumores en la vía aérea superior y 6 alteraciones de la lengua. Se encontró DIT en 14 casos (4,66%). El modelo elaborado y sus coeficientes para confeccionarlo fueron: f(x) = 1,322 + (2,173 distancia tiromentoniana < 6,5 cm) + (1,813 epiglotis abarquillada) - (1,310* cm abertura boca). El poder global de discriminación era 0,83 (IC 95%: 0,70-0,95). Conclusiones: La laringoscopia indirecta permitió el diagnóstico de las anomalías faringolaríngeas, y de ellas la epiglotis abarquillada fue una de las variables incluidas en el modelo de regresión logística (AU)

Objective: To determine the pharyngolaryngeal anomalies not usually included in the evaluation of difficult airway, in order to investigate the influence of these anomalies in the prediction of difficult intubation. To do this, indirect laryngoscopy with a 70° rigid laryngoscope was performed on all patients during the preoperative period. Methods: This is an observational, prospective study on 300 consecutive patients who were scheduled for endotracheal intubation under general anesthesia. In addition to assessing the airway in the preoperative period by demographic and clinical predictors of difficult airway, rigid indirect laryngoscopy was performed to diagnose pharyngolaryngeal anomalies. Later, under general anesthesia and direct laryngoscopy it was checked to see if there was difficulty in intubating the larynx, and its association with all previous variables was investigated. A logistic regression model for prediction purposes was developed, and its power of discrimination was achieved by assessing the area under the curve. Results: During the examination by indirect laryngoscopy 46 anomalies were found, which were as follows: 31 abnormalities of the epiglottis (22 omega epiglottis, 9 flaccid or hypertrophic epiglottis); 6 findings of hypertrophic lingual tonsils, 3 cases of upper airway tumors, and 6 patients with tongue disorders. Intubation difficulty was found in 14 cases (4.66%). The regression model found, and its coefficients to develop it were: f(x) = 1.322 + (2.173 thyromental distance < 6.5 cm) + (1.813 omega epiglottis) - (1.310*cm opening mouth). Global power of discrimination was 0.83, with a 95% confidence interval from 0.709 to 0.952). Conclusion: Indirect laryngoscopy allowed pharyngolaryngeal anomalies to be diagnosed, including omega epiglottis, which was one of the variables included in the logistic regression model (AU)

Influence of pharyngolaryngeal anomalies diagnosed through indirect laryngoscopy in the prediction of difficult intubation.

OBJECTIVE: To determine the pharyngolaryngeal anomalies not usually included in the evaluation of difficult airway, in order to investigate the influence of these anomalies in the prediction of difficult intubation. To do this, indirect laryngoscopy with a 70° rigid laryngoscope was performed on all patients during the preoperative period. METHODS: This is an observational, prospective study on 300 consecutive patients who were scheduled for endotracheal intubation under general anesthesia. In addition to assessing the airway in the preoperative period by demographic and clinical predictors of difficult airway, rigid indirect laryngoscopy was performed to diagnose pharyngolaryngeal anomalies. Later, under general anesthesia and direct laryngoscopy it was checked to see if there was difficulty in intubating the larynx, and its association with all previous variables was investigated. A logistic regression model for prediction purposes was developed, and its power of discrimination was achieved by assessing the area under the curve. RESULTS: During the examination by indirect laryngoscopy 46 anomalies were found, which were as follows: 31 abnormalities of the epiglottis (22 omega epiglottis, 9 flaccid or hypertrophic epiglottis); 6 findings of hypertrophic lingual tonsils, 3 cases of upper airway tumors, and 6 patients with tongue disorders. Intubation difficulty was found in 14 cases (4.66%). The regression model found, and its coefficients to develop it were: f(x)=1.322+(2.173 thyromental distance <6.5 cm)+(1.813 omega epiglottis)-(1.310*cm opening mouth). Global power of discrimination was 0.83, with a 95% confidence interval from 0.709 to 0.952). CONCLUSION: Indirect laryngoscopy allowed pharyngolaryngeal anomalies to be diagnosed, including omega epiglottis, which was one of the variables included in the logistic regression model.

Spectral shapes of Ar-broadened HCl lines in the fundamental band by classical molecular dynamics simulations and comparison with experiments.

Spectral shapes of isolated lines of HCl perturbed by Ar are investigated for the first time using classical molecular dynamics simulations (CMDS). Using reliable intermolecular potentials taken from the literature, these CMDS provide the time evolution of the auto-correlation function of the dipole moment, whose Fourier-Laplace transform leads to the absorption spectrum. In order to test these calculations, room temperature spectra of various lines in the fundamental band of HCl diluted in Ar are measured, in a large pressure range, with a difference-frequency laser spectrometer. Comparisons between measured and calculated spectra show that the CMDS are able to predict the large Dicke narrowing effect on the shape of HCl lines and to satisfactorily reproduce the shapes of HCl spectra at different pressures and for various rotational quantum numbers.

Targeting cancer stem cells to suppress acquired chemotherapy resistance.

Acquired resistance has curtailed cancer survival since the dawn of the chemotherapy age more than half a century ago. Although the application of stem cell (SC) concepts to cancer captured the imagination of scientists for many years, only the last decade has yielded substantial evidence that cancer SCs (CSCs) contribute to chemotherapy resistance. Recent studies suggest that the functional and molecular properties of CSCs constitute therapeutic opportunities to improve the efficacy of chemotherapy. Here we review how these properties have stimulated combination strategies that suppress acquired resistance across a spectrum of malignancies. The clinical implementation of these strategies promises to rejuvenate the effort against an enduring challenge.

Predictive value of the response to inhaled adenosine 5'-monophosphate for reducing the dose of inhaled corticosteroids in asthma.

BACKGROUND: Guidelines recommend stepping down inhaled corticosteroids (ICS) in patients with well-controlled asthma. However, no information is available on the index that should be used to predict the outcome of reducing the ICS dose. OBJECTIVE: The aim of this study was to investigate the degree of airway responsiveness to adenosine 5' monophosphate (AMP) as an index for deciding whether to reduce ICS dose. PATIENTS AND METHODS: The study population comprised 70 patients with asthma that was well controlled with ICS. Patients were treated for a 2-week baseline period with their usual dose of ICS. For the following 12 weeks, patients were treated with ICS at half their previous dose. Bronchial challenge with AMP was performed at the end of the baseline period and after 2 weeks of treatment with a reduced dose of ICS. Concentration-response curves were used to show the provocative concentration of AMP causing a 20% fall (PC20) in forced expiratory volume in 1 second (FEV1). RESULTS: A decrease in the PC20 of AMP of at least 1 doubling concentration 2 weeks after reducing the ICS dose was a significant predictor of the failure of dose reduction (P = .0011). In contrast, increased responsiveness to inhaled AMP at baseline did not predict the failure of dose reduction. CONCLUSIONS: Our results suggest that, in patients whose asthma is well controlled with ICS, measurement of the modification in the response to AMP 2 weeks after the dose of ICS was halved is a suitable method for assessing the risk of asthma exacerbation following a reduction in ICS dose.

Predictive Value of the Response to Inhaled Adenosine 5'-Monophosphate for Reducing the Dose of Inhaled Corticosteroids in Asthma

Antecedentes: En los pacientes asmáticos bien controlados, las guías recomiendan reducir las dosis de esteroides inhalados. No obstante, no existe ningún tipo de información acerca de qué determinaciones pudieran utilizarse para predecir el éxito o fracaso de esta estrategia terapéutica. Objetivo: Investigar la utilidad de la determinación de la respuesta bronquial a AMP para predecir la evolución del asma tras reducir la dosis de esteroides inhalados. Pacientes y métodos: Se estudiaron 70 pacientes asmáticos bien controlados con esteroides inhalados. Durante las primeras 2 semanas, los pacientes fueron tratados con sus dosis habituales de esteroides inhalados, para a continuación y durante las 12 semanas siguientes recibir tratamiento con la mitad de la dosis de estos fármacos indicada basalmente. Se realizaron estudios de la respuesta bronquial a AMP, tanto basalmente como al cabo de dos semanas de reducir la dosis de esteroides inhalados. Las curvas concentración-respuesta se caracterizaron mediante la concentración de agonista que inducía una caída del FEV1 del 20% (PC20). Resultados: La identificación de una reducción de la PC20 AMP de al menos una concentración doble, 2 semanas después de reducir la dosis de esteroides inhalados, podía predecir el riesgo de exacerbación del asma como consecuencia de la disminución de la dosis de la medicación controladora (P=0.0011). Por el contrario, la determinación de la respuesta basal a AMP no tenía capacidad predictiva significativa. Conclusiones: Los resultados del estudio sugieren que, en pacientes asmáticos bien controlados con esteroides inhalados, la identificación de las modificaciones de la respuesta a AMP al cabo de 2 semanas de reducir la dosis de esteroides inhalados a la mitad permite evaluar el riesgo de futuras exacerbaciones de la enfermedad (AU)

Background: Guidelines recommend stepping down inhaled corticosteroids (ICS) in patients with well-controlled asthma. However, no information is available on the index that should be used to predict the outcome of reducing the ICS dose. Objective: The aim of this study was to investigate the degree of airway responsiveness to adenosine 5’ monophosphate (AMP) as an index for deciding whether to reduce ICS dose. Patients and Methods: The study population comprised 70 patients with asthma that was well controlled with ICS. Patients were treated for a 2-week baseline period with their usual dose of ICS. For the following 12 weeks, patients were treated with ICS at half their previous dose. Bronchial challenge with AMP was performed at the end of the baseline period and after 2 weeks of treatment with a reduced dose of ICS. Concentration-response curves were used to show the provocative concentration of AMP causing a 20% fall (PC20) in forced expiratory volume in 1 second (FEV1). Results: A decrease in the PC20 of AMP of at least 1 doubling concentration 2 weeks after reducing the ICS dose was a significant predictor of the failure of dose reduction (P=.0011). In contrast, increased responsiveness to inhaled AMP at baseline did not predict the failure of dose reduction. Conclusions: Our results suggest that, in patients whose asthma is well controlled with ICS, measurement of the modification in the response to AMP 2 weeks after the dose of ICS was halved is a suitable method for assessing the risk of asthma exacerbation following a reduction in ICS dose (AU)