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1.
Nature ; 623(7987): 502-508, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37968524

RESUMEN

The capability to reach ultracold atomic temperatures in compact instruments has recently been extended into space1,2. Ultracold temperatures amplify quantum effects, whereas free fall allows further cooling and longer interactions time with gravity-the final force without a quantum description. On Earth, these devices have produced macroscopic quantum phenomena such as Bose-Einstein condensates (BECs), superfluidity, and strongly interacting quantum gases3. Terrestrial quantum sensors interfering the superposition of two ultracold atomic isotopes have tested the universality of free fall (UFF), a core tenet of Einstein's classical gravitational theory, at the 10-12 level4. In space, cooling the elements needed to explore the rich physics of strong interactions or perform quantum tests of the UFF has remained elusive. Here, using upgraded hardware of the multiuser Cold Atom Lab (CAL) instrument aboard the International Space Station (ISS), we report, to our knowledge, the first simultaneous production of a dual-species BEC in space (formed from 87Rb and 41K), observation of interspecies interactions, as well as the production of 39K ultracold gases. Operating a single laser at a 'magic wavelength' at which Rabi rates of simultaneously applied Bragg pulses are equal, we have further achieved the first spaceborne demonstration of simultaneous atom interferometry with two atomic species (87Rb and 41K). These results are an important step towards quantum tests of UFF in space and will allow scientists to investigate aspects of few-body physics, quantum chemistry and fundamental physics in new regimes without the perturbing asymmetry of gravity.

2.
Nature ; 562(7727): 391-395, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30333576

RESUMEN

Owing to the low-gravity conditions in space, space-borne laboratories enable experiments with extended free-fall times. Because Bose-Einstein condensates have an extremely low expansion energy, space-borne atom interferometers based on Bose-Einstein condensation have the potential to have much greater sensitivity to inertial forces than do similar ground-based interferometers. On 23 January 2017, as part of the sounding-rocket mission MAIUS-1, we created Bose-Einstein condensates in space and conducted 110 experiments central to matter-wave interferometry, including laser cooling and trapping of atoms in the presence of the large accelerations experienced during launch. Here we report on experiments conducted during the six minutes of in-space flight in which we studied the phase transition from a thermal ensemble to a Bose-Einstein condensate and the collective dynamics of the resulting condensate. Our results provide insights into conducting cold-atom experiments in space, such as precision interferometry, and pave the way to miniaturizing cold-atom and photon-based quantum information concepts for satellite-based implementation. In addition, space-borne Bose-Einstein condensation opens up the possibility of quantum gas experiments in low-gravity conditions1,2.

3.
Am J Epidemiol ; 192(12): 2063-2074, 2023 11 10.
Artículo en Inglés | MEDLINE | ID: mdl-37552955

RESUMEN

The Aspirin in Reducing Events in the Elderly (ASPREE) Trial recruited 19,114 participants across Australia and the United States during 2010-2014. Participants were randomized to receive either 100 mg of aspirin daily or matching placebo, with disability-free survival as the primary outcome. During a median 4.7 years of follow-up, 37% of participants in the aspirin group permanently ceased taking their study medication and 10% commenced open-label aspirin use. In the placebo group, 35% and 11% ceased using study medication and commenced open-label aspirin use, respectively. In order to estimate compliance-adjusted effects of aspirin, we applied rank-preserving structural failure time models. The results for disability-free survival and most secondary endpoints were similar in intention-to-treat and compliance-adjusted analyses. For major hemorrhage, cancer mortality, and all-cause mortality, compliance-adjusted effects of aspirin indicated greater risks than were seen in intention-to-treat analyses. These findings were robust in a range of sensitivity analyses. In accordance with the original trial analyses, compliance-adjusted results showed an absence of benefit with aspirin for primary prevention in older people, along with an elevated risk of clinically significant bleeding.


Asunto(s)
Aspirina , Hemorragia , Humanos , Estados Unidos/epidemiología , Anciano , Anciano de 80 o más Años , Aspirina/uso terapéutico , Hemorragia/inducido químicamente , Australia/epidemiología , Método Doble Ciego
4.
Acta Neurochir (Wien) ; 165(7): 1881-1889, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37178247

RESUMEN

BACKGROUND: Since its approval by the US Food and Drug Administration (FDA) in 2018, the flow disruptor Woven EndoBridge (WEB) device has become increasingly popular for the endovascular treatment of unruptured and ruptured cerebral aneurysms. However, the occlusion rates seem rather low and the retreatment rates rather high compared to other treatment methods. For initially ruptured aneurysms, a retreatment rate of 13 % has been reported. A variety of retreatment strategies has been proposed; however, there is a paucity of data concerning microsurgical clipping of WEB-pretreated aneurysms, especially previously ruptured ones. Thus, we present a single-center series of five ruptured aneurysms treated with the WEB device and retreated with microsurgical clipping. METHODS: A retrospective study including all patients presenting with a ruptured aneurysm undergoing WEB treatment at our institution between 2019 and 2021 was performed. Subsequently, all patients with an aneurysm remnant or recurrence of the target aneurysm retreated with microsurgical clipping were identified. RESULTS: Overall, five patients with a ruptured aneurysm treated with WEB and retreated with microsurgical clipping were included. Besides one basilar apex aneurysm, all aneurysms were located at the anterior communicating artery (AComA) complex. All aneurysms were wide-necked with a mean dome-to-neck ratio of 1.5. Clipping was feasible and safe in all aneurysms, and complete occlusion was achieved in 4 of 5 aneurysms. CONCLUSIONS: Microsurgical clipping for initially ruptured WEB-treated aneurysms is a feasible, safe, and effective treatment method in well-selected patients.


Asunto(s)
Aneurisma Roto , Embolización Terapéutica , Procedimientos Endovasculares , Aneurisma Intracraneal , Humanos , Estudios Retrospectivos , Procedimientos Endovasculares/métodos , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/cirugía , Resultado del Tratamiento , Aneurisma Roto/diagnóstico por imagen , Aneurisma Roto/cirugía , Embolización Terapéutica/métodos , Retratamiento
5.
Osteoporos Int ; 32(10): 1961-1971, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33721032

RESUMEN

This study demonstrates a substantial and persistent anti-osteoporosis treatment gap in men and women ≥50 years old who sustained major osteoporotic fracture(s) between 2005 and 2014 in Denmark. This was not substantially reduced by including hospital-administered anti-osteoporosis treatments. Strengthened post-fracture organization of care and secondary fracture prevention is highly needed. INTRODUCTION: The purpose of this study was to evaluate the Danish anti-osteoporosis treatment gap from 2005 to 2014 in patients sustaining a major osteoporotic fracture (MOF), and to assess the impact of including hospital-administered anti-osteoporosis medications (AOM) on the treatment gap among these patients. METHODS: In this retrospective, registry-based study, we included men and women aged 50 years or older and living in Denmark, who sustained at least one MOF between 2005 and 2014. We applied a repeated cross-sectional design to generate cohorts of patients sustaining a first MOF, hip, vertebral, humerus, or forearm fracture, respectively, within each calendar year. We evaluated the treatment gap as the proportion of patients within each cohort not receiving treatment with AOM within 1 year of the fracture. Hospital-administered AOM was identified by SKS code. RESULTS: The treatment gap among MOF patients decreased from 85% in 2005 to 79% in 2014. The gap was smaller among hip and vertebral fracture patients as compared to humerus and forearm fracture patients, and it was smaller in women than in men. The use of hospital-administered AOM was relatively uncommon, with a maximum of 0.9% of MOF patients initiating hospital-administered AOM (in 2012). We observed substantial variations in this proportion between fracture types and gender. Hospital-administered AOM was most commonly used among vertebral fracture patients. CONCLUSION: A significant treatment gap among patients sustaining a major osteoporotic fracture was present throughout our analysis, and including hospital-administered AOM did not significantly improve the treatment gap assessment. Improved secondary fracture prevention is urgently needed.


Asunto(s)
Fracturas de Cadera , Fracturas Osteoporóticas , Estudios Transversales , Dinamarca/epidemiología , Femenino , Fracturas de Cadera/epidemiología , Fracturas de Cadera/prevención & control , Hospitales , Humanos , Masculino , Persona de Mediana Edad , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/prevención & control , Prescripciones , Estudios Retrospectivos
6.
Phys Rev Lett ; 127(10): 100401, 2021 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-34533345

RESUMEN

In contrast to light, matter-wave optics of quantum gases deals with interactions even in free space and for ensembles comprising millions of atoms. We exploit these interactions in a quantum degenerate gas as an adjustable lens for coherent atom optics. By combining an interaction-driven quadrupole-mode excitation of a Bose-Einstein condensate (BEC) with a magnetic lens, we form a time-domain matter-wave lens system. The focus is tuned by the strength of the lensing potential and the oscillatory phase of the quadrupole mode. By placing the focus at infinity, we lower the total internal kinetic energy of a BEC comprising 101(37) thousand atoms in three dimensions to 3/2 k_{B}·38_{-7}^{+6} pK. Our method paves the way for free-fall experiments lasting ten or more seconds as envisioned for tests of fundamental physics and high-precision BEC interferometry, as well as opens up a new kinetic energy regime.

7.
Nature ; 582(7811): 186-187, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32528088
8.
Osteoporos Int ; 31(8): 1535-1544, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32185437

RESUMEN

This paper demonstrates a large post-fracture anti-osteoporosis treatment gap in the period 2005 to 2015. The gap was stable in Denmark at around 88-90%, increased in Catalonia from 80 to 88%, and started to increase in the UK towards the end of our study. Improved post-fracture care is needed. INTRODUCTION: Patients experiencing a fragility fracture are at high risk of subsequent fractures, particularly within the first 2 years after the fracture. Previous studies have demonstrated that only a small proportion of fracture patients initiate therapy with an anti-osteoporotic medication (AOM), despite the proven fracture risk reduction of such therapies. The aim of this paper is to evaluate the changes in this post-fracture treatment gap across three different countries from 2005 to 2015. METHODS: This analysis, which is part of a multinational cohort study, included men and women, aged 50 years or older, sustaining a first incident fragility fracture. Using routinely collected patient data from three administrative health databases covering Catalonia, Denmark, and the United Kingdom, we estimated the treatment gap as the proportion of patients not treated with AOM within 1 year of their first incident fracture. RESULTS: A total of 648,369 fracture patients were included. Mean age 70.2-78.9 years; 22.2-31.7% were men. In Denmark, the treatment gap was stable at approximately 88-90% throughout the 2005 to 2015 time period. In Catalonia, the treatment gap increased from 80 to 88%. In the UK, an initially decreasing treatment gap-though never smaller than 63%-was replaced by an increasing gap towards the end of our study. The gap was more pronounced in men than in women. CONCLUSION: Despite repeated calls for improved secondary fracture prevention, an unacceptably large treatment gap remains, with time trends indicating that the problem may be getting worse in recent years.


Asunto(s)
Conservadores de la Densidad Ósea , Fracturas Osteoporóticas , Anciano , Conservadores de la Densidad Ósea/uso terapéutico , Estudios de Cohortes , Dinamarca/epidemiología , Europa (Continente)/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/prevención & control , España/epidemiología , Reino Unido/epidemiología
9.
Cancer Cell Int ; 20: 390, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32817744

RESUMEN

BACKGROUND: The introduction of combined conventional cytostatics and pathway-specific inhibitors has opened new treatment options for several cancer types including hematologic neoplasia such as leukaemias. As the detailed understanding of the combination-induced molecular effects is often lacking, the identification of combination-induced molecular mechanisms bears significant value for the further development of interventional approaches. METHODS: Combined application of conventional cytostatic agents (cytarabine and dexamethasone) with the PI3K-inhibitor Idelalisib was analysed on cell-biologic parameters in two acute pro-B lymphoblastic leukaemia (B-ALL) cell lines. In particular, for comparative characterisation of the molecular signatures induced by the combined and mono application, whole transcriptome sequencing was performed. Emphasis was placed on pathways and genes exclusively regulated by drug combinations. RESULTS: Idelalisib + cytostatics combinations changed pathway activation for, e.g., "Retinoblastoma in cancer", "TGF-b signalling", "Cell cycle" and "DNA-damage response" to a greater extent than the two cytostatics alone. Analyses of the top-20 regulated genes revealed that both combinations induce characteristic gene expression changes. CONCLUSION: A specific set of genes was exclusively deregulated by the drug combinations, matching the combination-specific anti-proliferative cell-biologic effects. The addition of Idelalisib suggests minor synergistic effects which are rather to be classified as additive.

10.
Br J Dermatol ; 180(1): 157-164, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30098007

RESUMEN

BACKGROUND: The reported real-life use of prescribed topical antipsoriatic drugs is conflicting and based on heterogeneous data sources. OBJECTIVES: To describe the utilization of topical antipsoriatic drugs among patients with psoriasis in Denmark. METHODS: A drug utilization study was performed based on nationwide Danish health registry data. We identified patients who received a first-time hospital diagnosis of psoriasis and redeemed at least one topical drug prescription in the period 2005-2015 (n = 7743). Patients were followed for 3 years from the time of diagnosis. Use of topical and systemic antipsoriatic drugs was described, specified by the type of treatment. RESULTS: The total use of topical drugs was divided between corticosteroids with calcipotriol (31%), calcipotriol (6·5%), very potent corticosteroids (24%), potent corticosteroids (30%), moderate corticosteroids (7·2%) and corticosteroids with antimicrobials (1·6%). There was a 19% reduction in the overall use of topical drugs during the study period. Use increased around the time of diagnosis and the majority of patients redeemed more than two packages of topical drugs during the first year after being diagnosed. Regional differences in patients' use of topical drugs varied considerably. The distribution of use of topical drugs was uneven, with a minority of all patients (25%) using 70% of the total amount of topical treatment. There was a 70% increase in the use of methotrexate over the study period. Biologics were used by up to 6%. CONCLUSIONS: The study provides further evidence that the use of topical antipsoriatic drugs shows considerable heterogeneity over time and regional practices, and differences between patients.


Asunto(s)
Fármacos Dermatológicos/administración & dosificación , Prescripciones de Medicamentos/estadística & datos numéricos , Utilización de Medicamentos/estadística & datos numéricos , Psoriasis/tratamiento farmacológico , Administración Cutánea , Adulto , Antiinfecciosos/administración & dosificación , Calcitriol/administración & dosificación , Calcitriol/análogos & derivados , Dinamarca , Femenino , Estudios de Seguimiento , Glucocorticoides/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros/estadística & datos numéricos
11.
Bioorg Med Chem ; 27(14): 3167-3178, 2019 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-31186146

RESUMEN

Pyrazoloquinolinones (PQs) have been extensively studied as modulators of GABAA receptors with different subunit composition, exerting modulatory effects by binding at α+/ß- interfaces of GABAA receptors. PQs with a substituent in position R7 have been reported to preferentially modulate α6- subunit containing GABAA receptors which are mostly expressed in the cerebellum but were also found in the olfactory bulb, in the cochlear nucleus, in the hippocampus and in the trigeminal sensory pathway. They are considered potentially interesting in the context of sensori-motor gating deficits, depressive-like behavior, migraine and orofacial pain. Here we explored the option to modify the lead ligands' R7 position. In the compound series we observed two different patterns of allosteric modulation in recombinantly expressed α6ß3γ2 receptors, namely monophasic and biphasic positive modulation. In the latter case the additional phase occurred in the nanomolar range, while all compounds displayed robust modulation in the micromolar range. Nanomolar, near silent binding has been reported to occur at benzodiazepine binding sites, but was not investigated at the diazepam insensitive α6+/γ2- interface. To clarify the mechanism underlying the biphasic effect we tested one of the compounds in concatenated receptors. In these constructs the subunits are covalently linked, allowing to form either the α6+/γ2- interface, or the α6+/ß3- interface, to study the resulting modulation. With this approach we were able to ascribe the nanomolar modulation to the α6+/γ2- interface. While not all compounds display the nanomolar phase, the strong modulation at the α6+/ß3 interface proved to be tolerant for all tested R7 groups. This provides the future option to introduce e.g. isotope labelled or fluorescent moieties or substituents that enhance solubility and bioavailability.


Asunto(s)
Quinolonas/química , Receptores de GABA-A/química , Sitios de Unión , Humanos , Ligandos
12.
Rev Med Liege ; 74(1): 15-19, 2019 Jan.
Artículo en Francés | MEDLINE | ID: mdl-30680968

RESUMEN

Diabetic nephropathy is a complication of diabetes that affects 25-40 % of diabetic patients. This complication is usually associated with other microangiopathic disorders. We describe a case of a patient suffering from type 2 diabetes with proteinuria, and no signs of retinopathy. This case allows us to discuss and review different etiologies of proteinuria in diabetic patients, particularly in patients who don't suffer from retinopathy.


La néphropathie diabétique est une complication qui affecte 25 à 40 % des patients diabétiques. Cette complication est classiquement associée à d'autres atteintes microangiopathiques. Nous rapportons ici l'histoire d'un patient diabétique de type 2 présentant une protéinurie sans signes de rétinopathie. Ce cas permet de discuter des différentes étiologies d'une protéinurie chez les patients diabétiques, en particulier chez les patients sans rétinopathie.


Asunto(s)
Carcinoma de Células Escamosas/diagnóstico , Glomerulonefritis/etiología , Neoplasias Pulmonares/diagnóstico , Anciano , Diabetes Mellitus Tipo 2/complicaciones , Resultado Fatal , Glomerulonefritis/diagnóstico , Humanos , Masculino , Proteinuria/etiología
13.
Psychol Med ; 47(3): 484-494, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27776562

RESUMEN

BACKGROUND: Laboratory tasks to delineate anxiety disorder features are used to refine classification and inform our understanding of etiological mechanisms. The present study examines laboratory measures of response inhibition, specifically the inhibition of a pre-potent motor response, in clinical anxiety. Data on associations between anxiety and response inhibition remain inconsistent, perhaps because of dissociable effects of clinical anxiety and experimentally manipulated state anxiety. Few studies directly assess the independent and interacting effects of these two anxiety types (state v. disorder) on response inhibition. The current study accomplished this goal, by manipulating state anxiety in healthy and clinically anxious individuals while they complete a response inhibition task. METHOD: The study employs the threat-of-shock paradigm, one of the best-established manipulations for robustly increasing state anxiety. Participants included 82 adults (41 healthy; 41 patients with an anxiety disorder). A go/nogo task with highly frequent go trials was administered during alternating periods of safety and shock threat. Signal detection theory was used to quantify response bias and signal-detection sensitivity. RESULTS: There were independent effects of anxiety and clinical anxiety on response inhibition. In both groups, heightened anxiety facilitated response inhibition, leading to reduced nogo commission errors. Compared with the healthy group, clinical anxiety was associated with excessive response inhibition and increased go omission errors in both the safe and threat conditions. CONCLUSIONS: Response inhibition and its impact on go omission errors appear to be a promising behavioral marker of clinical anxiety. These results have implications for a dimensional view of clinical anxiety.


Asunto(s)
Trastornos de Ansiedad/fisiopatología , Miedo/fisiología , Inhibición Psicológica , Desempeño Psicomotor/fisiología , Detección de Señal Psicológica/fisiología , Adulto , Biomarcadores , Femenino , Humanos , Masculino , Adulto Joven
14.
Psychol Med ; 47(10): 1806-1815, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28290265

RESUMEN

BACKGROUND: Generalized anxiety disorder (GAD) and social anxiety disorder (SAD) are co-morbid and associated with similar neural disruptions during emotion regulation. In contrast, the lack of optimism examined here may be specific to GAD and could prove an important biomarker for that disorder. METHOD: Unmedicated individuals with GAD (n = 18) and age-, intelligence quotient- and gender-matched SAD (n = 18) and healthy (n = 18) comparison individuals were scanned while contemplating likelihoods of high- and low-impact negative (e.g. heart attack; heartburn) or positive (e.g. winning lottery; hug) events occurring to themselves in the future. RESULTS: As expected, healthy subjects showed significant optimistic bias (OB); they considered themselves significantly less likely to experience future negative but significantly more likely to experience future positive events relative to others (p < 0.001). This was also seen in SAD, albeit at trend level for positive events (p < 0.001 and p < 0.10, respectively). However, GAD patients showed no OB for positive events (t 17 = 0.82, n.s.) and showed significantly reduced neural modulation relative to the two other groups of regions including the medial prefrontal cortex (mPFC) and caudate to these events (p < 0.001 for all). The GAD group further differed from the other groups by showing increased neural responses to low-impact events in regions including the rostral mPFC (p < 0.05 for both). CONCLUSIONS: The neural dysfunction identified here may represent a unique feature associated with reduced optimism and increased worry about everyday events in GAD. Consistent with this possibility, patients with SAD did not show such dysfunction. Future studies should consider if this dysfunction represents a biomarker for GAD.


Asunto(s)
Trastornos de Ansiedad/fisiopatología , Ansiedad/fisiopatología , Núcleo Caudado/fisiopatología , Optimismo , Corteza Prefrontal/fisiopatología , Adulto , Ansiedad/psicología , Trastornos de Ansiedad/psicología , Núcleo Caudado/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Optimismo/psicología , Fobia Social/fisiopatología , Fobia Social/psicología , Corteza Prefrontal/diagnóstico por imagen , Adulto Joven
15.
Toxicol Pathol ; 45(3): 389-401, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-28136187

RESUMEN

This review analyzes the published data on cases of pulmonary alveolar proteinosis (PAP) in workers inhaling crystalline aluminum, indium, silicon, and titanium particles and possible sequelae, that is, inflammation and fibrosis, and compares these findings with those from animal experiments. In inhalation studies in rodents using crystalline indium and gallium compounds, pronounced PAP followed by inflammation and fibrosis down to very low concentration ranges have been reported. Crystalline aluminum, silicon, and titanium compounds also induced comparable pulmonary changes in animals, though at higher exposure levels. Laboratory animal species appear to react to the induction of PAP with varying degrees of sensitivity. The sensitivity of humans to environmental causes of PAP seems to be relatively low. Up to now, no cases of PAP, or other pulmonary diseases in humans, have been described for gallium compounds. However, a hazard potential can be assumed based on the results of animal studies. Specific particle properties, responsible for the induction of PAP and its sequelae, have not been identified. This review provides indications that, both in animal studies and in humans, PAP is not often recognized due to the absence of properly directed investigation or is concealed behind other forms of lung pathology.


Asunto(s)
Contaminantes Ocupacionales del Aire/toxicidad , Enfermedades Profesionales/inducido químicamente , Material Particulado/toxicidad , Proteinosis Alveolar Pulmonar/inducido químicamente , Fibrosis Pulmonar/inducido químicamente , Contaminantes Ocupacionales del Aire/química , Animales , Humanos , Exposición por Inhalación/efectos adversos , Exposición por Inhalación/análisis , Enfermedades Profesionales/patología , Tamaño de la Partícula , Material Particulado/química , Proteinosis Alveolar Pulmonar/patología , Fibrosis Pulmonar/patología , Especificidad de la Especie
16.
Dermatol Surg ; 43 Suppl 3: S285-S292, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33065954

RESUMEN

BACKGROUND: In clinical practice, different upper facial areas are commonly treated together. OBJECTIVE: To evaluate the efficacy and safety of repeated incobotulinumtoxinA injections for the treatment of upper facial lines (UFL) in a 3-month open-label extension (OLEX) period. MATERIALS AND METHODS: In the main study period (randomized, double blind, placebo controlled; n = 156), subjects with moderate-to-severe UFL (glabellar frown lines [GFL], horizontal forehead lines [HFL], and lateral periorbital lines [LPL]) on the 5-point Merz Aesthetics Scales (MAS) received 54 to 64 U incobotulinumtoxinA or placebo. In the OLEX, all subjects (n = 139) received 1 treatment with 54 to 64 U incobotulinumtoxinA. Investigator- and subject-assessed MAS scores were evaluated at rest and maximum contraction. Response was defined either as a MAS score of "none" or "mild" or a ≥1-point improvement in MAS scores. RESULTS: A clear, rapid treatment response was seen in each individual treated area and for all areas combined. At Day 30, a response of none or mild at maximum contraction (investigator's rating) was reported for 80.1%, 77.2%, and 66.9% of subjects for GFL, HFL, and LPL, respectively. IncobotulinumtoxinA was well tolerated, with no evidence of an increase in adverse events with repeat injection. CONCLUSION: IncobotulinumtoxinA is highly effective for the simultaneous treatment of UFL with a good safety profile (EudraCT Number: 2011-005887-20).

17.
Psychol Med ; 46(7): 1509-22, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26924633

RESUMEN

BACKGROUND: Major questions remain regarding the dysfunctional neural circuitry underlying the pathophysiology of bipolar disorder (BD) in both youths and adults. In both age groups, studies implicate abnormal intrinsic functional connectivity among prefrontal, limbic and striatal areas. METHOD: We collected resting-state functional magnetic resonance imaging (fMRI) data from youths and adults (ages 10-50 years) with BD (n = 39) and healthy volunteers (HV; n = 78). We identified brain regions with aberrant intrinsic functional connectivity in BD by first comparing voxel-wise mean global connectivity and then conducting correlation analyses. We used k-means clustering and multidimensional scaling to organize all detected regions into networks. RESULTS: Across the brain, we detected areas of dysconnectivity in both youths and adults with BD relative to HV. There were no significant age-group × diagnosis interactions. When organized by interregional connectivity, the areas of dysconnectivity in patients with BD comprised two networks: one of temporal and parietal areas involved in late stages of visual processing, and one of corticostriatal areas involved in attention, cognitive control and response generation. CONCLUSIONS: These data suggest that two networks show abnormal intrinsic functional connectivity in BD. Regions in these networks have been implicated previously in BD. We observed similar dysconnectivity in youths and adults with BD. These findings provide guidance for refining models of network-based dysfunction in BD.


Asunto(s)
Trastorno Bipolar/fisiopatología , Corteza Cerebral/fisiopatología , Conectoma , Cuerpo Estriado/fisiopatología , Red Nerviosa/fisiopatología , Adolescente , Adulto , Niño , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Adulto Joven
18.
Heredity (Edinb) ; 117(5): 348-357, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27436523

RESUMEN

Wild boar (Sus scrofa), one of the most widespread wildlife species, has entered a stage of continuous growth in Europe, and could even be considered a pest species. We analysed microsatellite variability in 723 wild boars from across Europe, including the northern Dinaric Balkans. Our aims were: (1) to define the population structure of wild boars in the Balkans and its relation with other European populations; (2) to estimate effective populations sizes, levels of intra- and inter-population diversity, inbreeding migration and gene flow patterns; (3) to test subpopulations for bottlenecks; (4) to interpret these results in light of current knowledge about the demographic history of wild boars in Europe; and (5) to discuss the relevance of these findings for management and conservation. Strong population structuring was observed and 14 subpopulations were revealed. High genetic diversity was found, and besides the well-known identity of the Italian populations of Sardinia and Castelporziano, we bring new insights into other potential relevant, refugial populations such as Littoral Slovenia, South Portugal, North-western Iberia and an entire cluster in the Balkans. There was evidence of gene flow going from these refugial subpopulations towards less peripheral and more admixed subpopulations. Recent population bottlenecks and expansions were detected, mostly in the peninsular refuge subpopulations. The results are consistent with the fluctuations of wild boar numbers in Europe since the beginning of the twentieth century. These results should be taken into account in future conservation and management plans for wild boar populations in Europe.


Asunto(s)
Flujo Génico , Variación Genética , Genética de Población , Sus scrofa/genética , Animales , Peninsula Balcánica , Conservación de los Recursos Naturales , Europa (Continente) , Frecuencia de los Genes , Técnicas de Genotipaje , Endogamia , Repeticiones de Microsatélite , Modelos Genéticos , Modelos Estadísticos , Densidad de Población , Dinámica Poblacional
19.
J Vasc Interv Radiol ; 27(4): 480-6, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26922979

RESUMEN

PURPOSE: To evaluate the safety and efficacy of percutaneous irreversible electroporation (IRE) of primary and secondary liver cancer unsuitable for resection or thermal ablation. MATERIALS AND METHODS: In this prospective, single-center study, 65 malignant liver tumors (hepatocellular carcinoma, n = 33; cholangiocellular carcinoma, n = 5; colorectal cancer metastasis, n = 22; neuroendocrine cancer metastasis, n = 3; testicular cancer metastasis, n = 2) in 34 patients (27 men, 7 women; mean age, 59.4 y ± 11.2) were treated. Local recurrence-free survival (LRFS) according to the Kaplan-Meier method was evaluated after a median follow-up of 13.9 months. RESULTS: Median tumor diameter was 2.4 cm ± 1.4 (range, 0.2-7.1 cm). Of 65 tumors, 12 (18.5%) required retreatment because of incomplete ablation (n = 3) or early local recurrence (n = 9). LRFS at 3, 6, and 12 months was 87.4%, 79.8%, and 74.8%. The median time to progressive disease according to modified Response Evaluation Criteria In Solid Tumors was 15.6 months. Overall complication rate was 27.5% with six major complications and eight minor complications. Major complications included diffuse intraperitonal bleeding (n = 1), partial thrombosis of the portal vein (n = 1), and liver abscesses (n = 4). Minor complications were liver hematomas (n = 6) and clinically inapparent pneumothoraces (n = 2). CONCLUSIONS: IRE showed promising results regarding therapeutic efficacy for the percutaneous treatment of liver tumors; however, significant concerns remain regarding its safety.


Asunto(s)
Ablación por Catéter/métodos , Electroporación , Neoplasias Hepáticas/cirugía , Anciano , Ablación por Catéter/efectos adversos , Ablación por Catéter/mortalidad , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Alemania , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estudios Prospectivos , Reoperación , Factores de Riesgo , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Carga Tumoral
20.
Acta Radiol ; 57(8): 939-46, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26454065

RESUMEN

BACKGROUND: Preoperative staging of cervical lymph nodes is important to determine the extent of neck dissection in patients with oral squamous cell carcinoma (OSCC). PURPOSE: To evaluate whether a preoperative discrimination of benign and malignant cervical lymph nodes with diffusion-weighted imaging (DWI) (3T) is feasible for clinical application. MATERIAL AND METHODS: Forty-five patients with histological proven OSCC underwent preoperative 3T-MRI. DWI (b = 0, 500, and 1000 s/mm(2)) was added to the standard magnetic resonance imaging (MRI) protocol. Mean apparent diffusion coefficients (ADCmean) were measured for lymph nodes with 3 mm or more in short axis by two independent readers. Finally, these results were matched with histology. RESULTS: Mean ADC was significantly higher for malignant than for benign nodes (1.143 ± 0.188 * 10(-3) mm(2)/s vs. 0.987 ± 0.215 * 10(-3) mm(2)/s). Using an ADC value of 0.994 * 10(-3) mm(2)/s as threshold results in a sensitivity of 80%, specificity of 65%, positive predictive value of 31%, and negative predictive value of 93%. CONCLUSION: Due to a limited sensitivity and specificity DWI alone is not suitable to reliably discriminate benign from malignant cervical lymph nodes in daily clinical routine. Hence, the preoperative determination of the extent of neck dissection on the basis of ADC measurements is not meaningful.


Asunto(s)
Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/patología , Imagen de Difusión por Resonancia Magnética/métodos , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/patología , Neoplasias de la Boca/diagnóstico por imagen , Neoplasias de la Boca/patología , Anciano , Anciano de 80 o más Años , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Sensibilidad y Especificidad
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