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1.
Phys Rev Lett ; 132(23): 233002, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38905657

RESUMEN

We experimentally study the influence of the binding energy on nondipole effects in K-shell single-photon ionization of atoms at high photon energies. We find that for each ionization event, as expected by momentum conservation, the photon momentum is transferred almost fully to the recoiling ion. The momentum distribution of the electrons becomes asymmetrically deformed along the photon propagation direction with a mean value of 8/(5c)(E_{γ}-I_{P}) confirming an almost 100 year old prediction by Sommerfeld and Schur [Ann. Phys. (N.Y.) 396, 409 (1930)10.1002/andp.19303960402]. The emission direction of the photoions results from competition between the forward-directed photon momentum and the backward-directed recoil imparted by the photoelectron. Which of the two counteracting effects prevails depends on the binding energy of the emitted electron. As an example, we show that at 20 keV photon energy, Ne^{+} and Ar^{+} photoions are pushed backward towards the radiation source, while Kr^{+} photoions are emitted forward along the light propagation direction.

2.
Phys Rev Lett ; 129(20): 201801, 2022 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-36461983

RESUMEN

This Letter presents the results from the MiniBooNE experiment within a full "3+1" scenario where one sterile neutrino is introduced to the three-active-neutrino picture. In addition to electron-neutrino appearance at short baselines, this scenario also allows for disappearance of the muon-neutrino and electron-neutrino fluxes in the Booster Neutrino Beam, which is shared by the MicroBooNE experiment. We present the 3+1 fit to the MiniBooNE electron-(anti)neutrino and muon-(anti)neutrino data alone and in combination with MicroBooNE electron-neutrino data. The best-fit parameters of the combined fit with the exclusive charged-current quasielastic analysis (inclusive analysis) are Δm^{2}=0.209 eV^{2}(0.033 eV^{2}), |U_{e4}|^{2}=0.016(0.500), |U_{µ4}|^{2}=0.500(0.500), and sin^{2}(2θ_{µe})=0.0316(1.0). Comparing the no-oscillation scenario to the 3+1 model, the data prefer the 3+1 model with a Δχ^{2}/d.o.f.=24.7/3(17.3/3), a 4.3σ(3.4σ) preference assuming the asymptotic approximation given by Wilks's theorem.

3.
J Chem Phys ; 157(15): 154309, 2022 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-36272776

RESUMEN

The fragmentation dynamics of two isomers of C3H6, cyclopropane and propene, induced by 4 keV/u Ar8+ are investigated employing a reaction microscope. Four two-body and two three-body dissociation channels of C3H6 2+ dications are identified for each isomer, among which the channels involving CC bond breaking are found to be much more favored than H3 + and H2 + formation channels. The observation of the CH3 + or H3 + formation channels from cyclopropane are direct evidence of the proton migration within the carbon skeleton before dissociation. Obvious isomer effects are revealed by comparing the relative branching ratios of different channels of the two isomers. Moreover, it was shown that a sequential dissociation mechanism with H elimination prior to CC bond cleavage may be dominant for the two three-body dissociation channels for both isomers.

4.
Zhonghua Yi Xue Za Zhi ; 102(11): 795-800, 2022 Mar 22.
Artículo en Zh | MEDLINE | ID: mdl-35325959

RESUMEN

Objective: To evaluate the efficacy and safety of selective genicular artery embolization for the treatment of the knee pain secondary to osteoarthritis. Methods: From October 2020 to July 2021, 17 patients (23 knees) aged (68±7) years with moderate to severe knee pain secondary to knee osteoarthritis were prospectively included in the General Hospital of Ningxia Medical University. There were 6 males and 11 females included in this research. Patients were assessed with knee pain, stiffness, and function with the Visual Analogue Scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at baseline, using the Kellgren-Lawrence (K-L) grading to evaluate the severity of KOA, and using the Magnetic Resonance Knee Osteoarthritis Score (MOAKS) to evaluate the MR imaging characteristics of the affected knee. Selective genicular artery embolization (GAE) was performed in all patients. The patients were followed up for 6 months after the procedure. Patients were assessed with the VAS score and WOMAC scale at 1 d, 1 week and 1, 3 and 6 months after the procedure to evaluate the clinical outcomes, including the improvement of knee joint pain, stiffness and function, as well as the occurrence of adverse reactions. Results: Three to seven genicular artery branches were superselected and embolized in 23 knees, and 4 to 7 genicular artery branches were embolized in 7 patients with K-L grade 4. The clinical improvement was 95.6% (22/23) at 1 month, 86.9% (20/23) at 3 months, and 91.3% (21/23) at 6 months. Twenty-three knees completed the 6-month follow-up, and the VAS score, WOMAC pain score, and total WOMAC score at 1, 3, and 6 months after surgery were (2.5±1.3), (3.4±2.4), and (19.7±9.8) points, (3.0±1.8), (4.5±3.4), and (22.3±11.3) points, (2.8±1.5), (4.1±3.0), and (20.5±11.0) points, which were lower than the (6.6±0.9), (11.4±2.6) and (47.0±12.0) points at baseline (all P<0.001). During the follow-up period, 7 patients had adverse reactions: 3 cases had skin ecchymosis in the femoral artery puncture area, 4 cases had knee joint stiffness and pain within 1 day after operation, which were relieved spontaneously in 1 week, 6 patients had joint clicking during extension and flexion activities after operation, of which 3 cases subsided spontaneously within 3 months after operation. None of the patients had major procedure-related adverse events. Conclusion: GAE has a high clinical improvement rate and a low incidence of adverse reactions in the treatment of the pain secondary to knee osteoarthritis, which provides a new treatment option for patients who fail to respond to conservative treatment.


Asunto(s)
Articulación de la Rodilla , Osteoartritis de la Rodilla , Anciano , Arterias , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/terapia , Dolor/etiología , Resultado del Tratamiento
5.
Phys Rev Lett ; 126(5): 053202, 2021 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-33605768

RESUMEN

Strong-field ionization of atoms by circularly polarized femtosecond laser pulses produces a donut-shaped electron momentum distribution. Within the dipole approximation this distribution is symmetric with respect to the polarization plane. The magnetic component of the light field is known to shift this distribution forward. Here, we show that this magnetic nondipole effect is not the only nondipole effect in strong-field ionization. We find that an electric nondipole effect arises that is due to the position dependence of the electric field and which can be understood in analogy to the Doppler effect. This electric nondipole effect manifests as an increase of the radius of the donut-shaped photoelectron momentum distribution for forward-directed momenta and as a decrease of this radius for backwards-directed electrons. We present experimental data showing this fingerprint of the electric nondipole effect and compare our findings with a classical model and quantum calculations.

6.
Eur J Neurol ; 28(2): 430-437, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32969141

RESUMEN

BACKGROUND AND PURPOSE: The pharmacologic effects of pioglitazone on the incidence of Parkinson disease (PD) are not clear. No study has examined the interaction between pioglitazone and statin treatment on prevention of PD. This study analyzed the associations between pioglitazone, statins, and the incidence of PD in patients with diabetes mellitus (DM) in Taiwan. METHODS: We used the National Health Insurance database from 1996 to 2013. DM and PD were diagnosed according to the International Classification of Diseases, Ninth Revision, Clinical Modification codes. We used the propensity score-matching method to match the study groups. Cox regression analyses were employed to calculate the relative risk of the incidence of PD. RESULTS: There were 48 828 patients matched and categorized equally into the pioglitazone group and the non-pioglitazone group. The number of PD patients in the pioglitazone group and the non-pioglitazone group was 275 (1.1%) and 417 (1.7%), respectively. The pioglitazone group had a lower incidence of PD, with an adjusted hazard ratio (aHR) of 0.66 [95% confidence interval (CI): 0.57-0.78], and this benefit was dose-dependent. Of note, as compared with either pioglitazone or statin treatment, our results first showed that the combination of pioglitazone and statins further lowered the risk of PD, with an aHR of 0.78 (95% CI: 0.64-0.94; P = 0.010). CONCLUSIONS: Our study results suggested that pioglitazone could be a promising agent for reducing the incidence of PD in patients with DM, and works synergistically with statins.


Asunto(s)
Diabetes Mellitus , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Enfermedad de Parkinson , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/epidemiología , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Incidencia , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/epidemiología , Pioglitazona/uso terapéutico , Estudios Retrospectivos , Factores de Riesgo , Taiwán/epidemiología
7.
Beijing Da Xue Xue Bao Yi Xue Ban ; 53(3): 566-572, 2021 Jun 18.
Artículo en Zh | MEDLINE | ID: mdl-34145862

RESUMEN

OBJECTIVE: To develop machine learning models for predicting intensive care unit (ICU) readmission using ensemble learning algorithms. METHODS: A publicly accessible American ICU database, medical information mart for intensive care (MIMIC)-Ⅲ as the data source was used, and the patients were selected by the inclusion and exclusion criteria. A set of variables that had the predictive ability of outcome including demographics, vital signs, laboratory tests, and comorbidities of patients were extracted from the dataset. We built the ICU readmission prediction models based on ensemble learning methods including random forest, adaptive boosting (AdaBoost), and gradient boosting decision tree (GBDT), and compared the prediction performance of the machine learning models with a conventional Logistic regression model. Five-fold cross validation was used to train and validate the prediction models. Average sensitivity, positive prediction value, negative prediction value, false positive rate, false negative rate, area under the receiver operating characteristic curve (AUROC) and Brier score were used as performance measures. After constructing the prediction models, top 10 predictive variables based on importance ranking were identified by the model with the best discrimination. RESULTS: Among these ICU readmission prediction models, GBDT (AUROC=0.858) had better performance than random forest (AUROC=0.827), and was slightly superior to AdaBoost (AUROC=0.851) in terms of AUROC. Compared with Logistic regression (AUROC=0.810), the discrimination of the three ensemble learning models was much better. The feature importance provided by GBDT showed that the top ranking variables included vital signs and laboratory tests. The patients with ICU readmission had higher mean arterial pressure, systolic blood pressure, diastolic blood pressure, and heart rate than the patients without ICU readmission. Meanwhile, the patients readmitted to ICU experienced lower urine output and higher serum creatinine. Overall, the patients having repeated admissions during their hospitalization showed worse heart function and renal function compared with the patients without ICU readmission. CONCLUSION: The ensemble learning based ICU readmission prediction models had better performance than Logistic regression model. Such ensemble learning models have the potential to aid ICU physicians in identifying those patients with high risk of ICU readmission and thus help improve overall clinical outcomes.


Asunto(s)
Enfermedad Crítica , Readmisión del Paciente , Humanos , Unidades de Cuidados Intensivos , Aprendizaje Automático , Curva ROC
8.
Beijing Da Xue Xue Bao Yi Xue Ban ; 53(6): 1163-1170, 2021 Dec 18.
Artículo en Zh | MEDLINE | ID: mdl-34916699

RESUMEN

OBJECTIVE: To construct length of intensive care unit (ICU) stay (LOS-ICU) prediction models for ICU patients, based on three machine learning models support vector machine (SVM), classification and regression tree (CART), and random forest (RF), and to compare the prediction perfor-mance of the three machine learning models with the customized simplified acute physiology score Ⅱ(SAPS-Ⅱ) model. METHODS: We used medical information mart for intensive care (MIMIC)-Ⅲ database for model development and validation. The primary outcome was prolonged LOS-ICU(pLOS-ICU), defined as longer than the third quartile of patients' LOS-ICU in the studied dataset. The recursive feature elimination method was used to do feature selection for three machine learning models. We utilized 5-fold cross validation to evaluate model prediction performance. The Brier value, area under the receiver operation characteristic curve (AUROC), and estimated calibration index (ECI) were used as perfor-mance measures. Performances of the four models were compared, and performance differences between the models were assessed using two-sided t test. The model with the best prediction performance was employed to generate variable importance ranking, and the identified top five important predictors were pre-sented. RESULTS: The final cohort in our study consisted of 40 200 eligible ICU patients, of whom 23.7% were with pLOS-ICU. The proportion of the male patients was 57.6%, and the age of all the ICU patients was (61.9±16.5) years.Results showed that the three machine learning models outperformed the customized SAPS-Ⅱ model in terms of all the performance measures with statistical significance (P < 0.01). Among the three machine learning models, the RF model achieved the best overall performance (Brier value, 0.145), discrimination (AUROC, 0.770) and calibration (ECI, 7.259). The calibration curve showed that the RF model slightly overestimated the risk of pLOS-ICU in high-risk ICU patients, but underestimated the risk of pLOS-ICU in low-risk ICU patients. Top five important predictors for pLOS-ICU identified by the RF model included age, heart rate, systolic blood pressure, body tempe-rature, and ratio of arterial oxygen tension to the fraction of inspired oxygen(PaO2/FiO2). CONCLUSION: The RF algorithm-based pLOS-ICU prediction model had a best prediction performance in this study. It lays a foundation for future application of the RF-based pLOS-ICU prediction model in ICU clinical practice.


Asunto(s)
Aprendizaje Automático , Proyectos de Investigación , Anciano , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad
9.
Radiologia ; 63(6): 495-504, 2021.
Artículo en Español | MEDLINE | ID: mdl-35368367

RESUMEN

Objective: Initial COVID-19 reports described a variety of clinical presentations, but lower respiratory abnormalities are most common and chest CT findings differ between adult and pediatric patients. We aim to summarize early CT findings to inform healthcare providers on the frequency of COVID-19 manifestations specific to adult or pediatric patients, and to determine if the sensitivity of CT justifies its use in these populations. Methods: PubMed was searched for the presence of the words "CT, imaging, COVID-19" in the title or abstract, and 17 large-scale PubMed and/or Scopus studies and case reports published between January 1, 2020 and April 15, 2020 were selected for data synthesis. Results: Initial CT scans identified ground-glass opacities and bilateral abnormalities as more frequent in adults (74%, n = 698, and 89%, n = 378, respectively) than children (60%, n = 25, and 37%, n = 46). At 14+ days, CT scans evidenced varied degrees of improvement in adults but no resolution until at least 26 days after the onset of flu-like symptoms. In pediatric patients, a third (n = 9) showed additional small nodular GGOs limited to a single lobe 3-5 days after an initial CT scan. Conclusión: Early adult CT findings suggest the limited use of CT as a supplemental tool in diagnosing COVID-19 in symptomatic adult patients, with a particular focus on identifying right and left lower lobe abnormalities, GGOs, and interlobular septal thickening. Early pediatric CT findings suggest against the use of CT if RT-PCR is available given its significantly lower sensitivity in this population and radiation exposure.

10.
Ann Oncol ; 31(5): 626-633, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32205017

RESUMEN

BACKGROUND: This phase Ib study evaluated the safety, tolerability, pharmacokinetics, and preliminary efficacy of the oral AKT inhibitor ipatasertib and chemotherapy or hormonal therapy in patients with advanced or metastatic solid tumors to determine combined dose-limiting toxicities (DLTs), maximum tolerated dose, and recommended phase II doses and schedules. PATIENTS AND METHODS: The clinical study comprised four combination treatment arms: arm A (with docetaxel), arm B [with mFOLFOX6 (modified leucovorin, 5-fluorouracil, and oxaliplatin)], arm C (with paclitaxel), and arm D (with enzalutamide). Primary endpoints were safety and tolerability; secondary endpoints were pharmacokinetics, clinical activity per Response Evaluation Criteria in Solid Tumors v1.1, and prostate-specific antigen levels. RESULTS: In total, 122 patients were enrolled. Common adverse events were diarrhea, nausea, vomiting, decreased appetite, and fatigue. The safety profiles of the combination regimens were consistent with those of the background regimens, except for diarrhea, hyperglycemia, and rash, which were previously observed with ipatasertib treatment. The only combination DLT across all treatment arms was one event of grade 3 dehydration (ipatasertib 600 mg and paclitaxel). Recommended phase II doses for ipatasertib were 600 mg (and mFOLFOX6) and 400 mg (and paclitaxel), respectively. The maximum assessed dose of ipatasertib 600 mg combined with docetaxel or enzalutamide was well tolerated. Coadministration with enzalutamide (a cytochrome P450 3A inducer) resulted in approximately 50% lower ipatasertib exposure. CONCLUSIONS: Ipatasertib in combination with chemotherapy or hormonal therapy was well tolerated with a safety profile consistent with that of ATP-competitive AKT inhibitors. CLINICAL TRIAL NUMBER: NCT01362374.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Humanos , Masculino , Dosis Máxima Tolerada , Neoplasias/tratamiento farmacológico , Piperazinas , Pirimidinas/uso terapéutico
11.
Nat Mater ; 18(7): 691-696, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30962556

RESUMEN

Heterostructures of atomically thin van der Waals bonded monolayers have opened a unique platform to engineer Coulomb correlations, shaping excitonic1-3, Mott insulating4 or superconducting phases5,6. In transition metal dichalcogenide heterostructures7, electrons and holes residing in different monolayers can bind into spatially indirect excitons1,3,8-11 with a strong potential for optoelectronics11,12, valleytronics1,3,13, Bose condensation14, superfluidity14,15 and moiré-induced nanodot lattices16. Yet these ideas require a microscopic understanding of the formation, dissociation and thermalization dynamics of correlations including ultrafast phase transitions. Here we introduce a direct ultrafast access to Coulomb correlations between monolayers, where phase-locked mid-infrared pulses allow us to measure the binding energy of interlayer excitons in WSe2/WS2 hetero-bilayers by revealing a novel 1s-2p resonance, explained by a fully quantum mechanical model. Furthermore, we trace, with subcycle time resolution, the transformation of an exciton gas photogenerated in the WSe2 layer directly into interlayer excitons. Depending on the stacking angle, intra- and interlayer species coexist on picosecond scales and the 1s-2p resonance becomes renormalized. Our work provides a direct measurement of the binding energy of interlayer excitons and opens the possibility to trace and control correlations in novel artificial materials.

12.
Eur J Neurol ; 27(11): 2389-2391, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32860282

RESUMEN

A 36-year-old woman who presented with upper limb distal weakness since the age of 15 years, with gradual progression to the lower limbs, is reported. Hereditary motor neuropathy was initially suspected based on distal weakness and hyporeflexia; however, whole exome sequencing accidentally revealed a compound heterozygous variant in the GNE gene, and ultrasound revealed increased homogeneous echogenicity in the involved muscles, which is characteristic of myopathic changes. Muscle magnetic resonance imaging revealed fatty infiltration in all limb muscles, sparing the triceps brachii, vastus lateralis and vastus medialis. Muscle biopsy revealed intracytoplasmic rimmed vacuole, supporting the diagnosis of GNE myopathy.


Asunto(s)
Miopatías Distales , Adolescente , Adulto , Miopatías Distales/diagnóstico , Miopatías Distales/genética , Femenino , Humanos , Imagen por Resonancia Magnética , Complejos Multienzimáticos , Músculo Esquelético
13.
Phys Rev Lett ; 123(23): 233602, 2019 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-31868475

RESUMEN

Virtual photons can mediate interaction between atoms, resulting in an energy shift known as a collective Lamb shift. Observing the collective Lamb shift is challenging, since it can be obscured by radiative decay and direct atom-atom interactions. Here, we place two superconducting qubits in a transmission line terminated by a mirror, which suppresses decay. We measure a collective Lamb shift reaching 0.8% of the qubit transition frequency and twice the transition linewidth. We also show that the qubits can interact via the transmission line even if one of them does not decay into it.

14.
Photochem Photobiol Sci ; 18(10): 2442-2448, 2019 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-31384873

RESUMEN

In recent years, several drugs have become relatively easy to obtain with the rapid development of the economy and improvement in people's living standards. However, pathogenic bacteria have evolved strains that are resistant to certain drugs, such as antibiotics. Peptides are generally considered to be safe, have high tolerance to drugs, and are easy to manufacture. However, peptides are easily decomposed in complex biological environments. To solve this problem, many studies have modified peptides on the surface of nanomaterials to increase their functionality, biocompatibility, and stability. Meanwhile, nanomaterials have exhibited good absorption of near-infrared (NIR) light. When the NIR laser is focused on nanomaterials, photons are absorbed and the energy of the photons is converted into heat. Low-toxicity NRC03 peptide-conjugated dopamine/nano-reduced-graphene oxide (NRC03-DA/nRGO) nanomaterials are synthesized in this study for antibacterial testing using photothermal technology. The strains used in this study were Gram-positive Staphylococcus aureus (S. aureus). Our results indicated that the synthesized NRC03-DA/nRGO exhibits good absorption of NIR light and high photothermal conversion efficiency. Moreover, the synthesized NRC03-DA/nRGO inhibits the growth and survival of S. aureus. When the NRC03 peptide is modified on the surface of DA/nRGO, its biological stability is improved and the photothermal effect generated by NIR light produces additive effects, thereby indicating potential antibacterial applications.


Asunto(s)
Antibacterianos/farmacología , Dopamina/química , Grafito/química , Nanoestructuras/química , Péptidos/química , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/química , Materiales Biocompatibles/síntesis química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Rayos Infrarrojos
15.
Zhonghua Yi Xue Za Zhi ; 99(25): 1976-1980, 2019 Jul 02.
Artículo en Zh | MEDLINE | ID: mdl-31269604

RESUMEN

Objective: Investigate the causes of poor prognosis of mechanical thrombectomy in the time window of acute ischemic stroke (AIS) with anterior circulation. Methods: A retrospective analysis was made on the data of 78 patients with anterior circulation AIS who underwent mechanical thrombectomy in the time window from January 2017 to December 2017 in the Department of Vascular Neurosurgery of Liaocheng Brain Hospital. The modified Rankin scale (mRS) was used to evaluate the prognosis of the patients 3 months after operation. According to the prognosis,the patients were divided into the group with good prognosis (42 cases, mRS<2 points) and the group with poor prognosis (36 cases, mRS<3 points). Univariate and multivariate Logistic regression analysis was used to analyze the related factors of poor prognosis. Results: (1) Univariate analysis showed that the prognosis of patients with good combination and primary stenosis of diabetes mellitus and atherosclerosis was lower than that of patients with poor prognosis (P<0.05). The collateral circulation compensation rate and vascular recanalization rate of patients with good prognosis were higher than those of patients with poor prognosis (P<0.05). Learning significance (P<0.05). (2) Multivariate analysis showed that diabetes mellitus (P=0.035), collateral circulation compensation (P=0.011) and primary atherosclerotic stenosis (P=0.042) were independent risk factors for poor prognosis. Conclusion: Perfect preoperative evaluation and strict screening of patients, good collateral circulation compensation,individualized treatment for patients with primary atherosclerotic stenosis,and strict control of postoperative hyperglycemia can improve the clinical prognosis of endovascular therapy.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular , Humanos , Pronóstico , Estudios Retrospectivos , Trombectomía , Resultado del Tratamiento
16.
Ann Oncol ; 29(4): 917-923, 2018 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-29401246

RESUMEN

Background: Lifastuzumab vedotin (LIFA) is a humanized anti-NaPi2b monoclonal antibody conjugated to a potent antimitotic agent, monomethyl auristatin E, which inhibits cell division by blocking the polymerization of tubulin. This study is the first to compare an antibody-drug conjugate (ADC) to standard-of-care in ovarian cancer (OC) patients. Patients and methods: Platinum-resistant OC patients were randomized to receive LIFA [2.4 mg/kg, intravenously, every 3 weeks (Q3W)] or pegylated liposomal doxorubicin (PLD) (40 mg/m2, intravenously, Q4W). NaPi2b expression and serum CA-125 and HE4 levels were assessed. The primary end point was progression-free survival (PFS) in intent-to-treat (ITT) and NaPi2b-high patients. Results: Ninety-five patients were randomized (47 LIFA; 48 PLD). The stratified PFS hazard ratio was 0.78 [95% confidence interval (95% CI), 0.46-1.31; P = 0.34] with a median PFS of 5.3 versus 3.1 months (LIFA versus PLD arm, respectively) in the ITT population, and 0.71 (95% CI, 0.40-1.26; P = 0.24) with a median PFS of 5.3 months versus 3.4 months (LIFA versus PLD arm, respectively) in NaPi2b-high patients. The objective response rate was 34% (95% CI, 22% to 49%, LIFA) versus 15% (95% CI, 7% to 28%, PLD) in the ITT population (P = 0.03), and 36% (95% CI, 22% to 52%, LIFA) versus 14% (95% CI, 6% to 27%, PLD) in NaPi2b-high patients (P = 0.02). Toxicities included grade ≥3 adverse events (AEs) (46% LIFA; 51% PLD), serious AEs (30% both arms), and AEs leading to discontinuation of drug (9% LIFA; 8% PLD). Five (11%) LIFA versus 2 (4%) PLD patients had grade ≥2 neuropathy. Conclusion: LIFA Q3W was well tolerated and improved objective response rate with a modest, nonstatistically significant improvement of PFS compared with PLD in platinum-resistant OC. While the response rate for the monomethyl auristatin E-containing ADC was promising, response durations were relatively short, thereby highlighting the importance of evaluating both response rates and duration of response when evaluating ADCs in OC. Clinical trials.gov: NCT01991210.


Asunto(s)
Antibióticos Antineoplásicos/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Doxorrubicina/análogos & derivados , Inmunoconjugados/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antibióticos Antineoplásicos/efectos adversos , Anticuerpos Monoclonales Humanizados/química , Biomarcadores/metabolismo , Doxorrubicina/uso terapéutico , Resistencia a Antineoplásicos , Femenino , Humanos , Inmunoconjugados/efectos adversos , Persona de Mediana Edad , Compuestos Organoplatinos/uso terapéutico , Neoplasias Ováricas/metabolismo , Polietilenglicoles/uso terapéutico , Análisis de Supervivencia
17.
Osteoporos Int ; 29(4): 779-792, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29285627

RESUMEN

The analysis aimed to identify the treatment gaps in current fracture liaison services (FLS) and to provide recommendations for best practice establishment of future FLS across the Asia-Pacific region. The findings emphasize the unmet need for the implementation of new programs and provide recommendations for the refinement of existing ones. The study's objectives were to evaluate fracture liaison service (FLS) programs in the Asia-Pacific region and provide recommendations for establishment of future FLS programs. A systematic literature review (SLR) of Medline, PubMed, EMBASE, and Cochrane Library (2000-2017 inclusive) was performed using the following keywords: osteoporosis, fractures, liaison, and service. Inclusion criteria included the following: patients ≥ 50 years with osteoporosis-related fractures; randomized controlled trials or observational studies with control groups (prospective or retrospective), pre-post, cross-sectional and economic evaluation studies. Success of direct or indirect interventions was assessed based on patients' understanding of risk, bone mineral density assessment, calcium intake, osteoporosis treatment, re-fracture rates, adherence, and mortality, in addition to cost-effectiveness. Overall, 5663 unique citations were identified and the SLR identified 159 publications, reporting 37 studies in Asia-Pacific. These studies revealed the unmet need for public health education, adequate funding, and staff resourcing, along with greater cooperation between departments and physicians. These actions can help to overcome therapeutic inertia with sufficient follow-up to ensure adherence to recommendations and compliance with treatment. The findings also emphasize the importance of primary care physicians continuing to prescribe treatment and ensure service remains convenient. These findings highlight the limited evidence supporting FLS across the Asia-Pacific region, emphasizing the unmet need for new programs and/or refinement of existing ones to improve outcomes. With the continued increase in burden of fractures in Asia-Pacific, establishment of new FLS and assessment of existing services are warranted to determine the impact of FLS for healthcare professionals, patients, family/caregivers, and society.


Asunto(s)
Prestación Integrada de Atención de Salud/organización & administración , Evaluación de Necesidades/organización & administración , Osteoporosis/tratamiento farmacológico , Fracturas Osteoporóticas/prevención & control , Asia/epidemiología , Australasia/epidemiología , Conservadores de la Densidad Ósea/uso terapéutico , Análisis Costo-Beneficio , Prestación Integrada de Atención de Salud/economía , Costos de la Atención en Salud/estadística & datos numéricos , Humanos , Osteoporosis/diagnóstico , Osteoporosis/epidemiología , Fracturas Osteoporóticas/epidemiología , Educación del Paciente como Asunto/métodos , Evaluación de Programas y Proyectos de Salud , Recurrencia
18.
Phys Rev Lett ; 121(11): 113204, 2018 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-30265085

RESUMEN

We demonstrate coupling between the atomic spin- and orbital-angular momentum (OAM) of the atom's center-of-mass motion in a Bose-Einstein condensate (BEC). The coupling is induced by Raman-dressing lasers with a Laguerre-Gaussian beam and creates coreless vortices in an F=1 ^{87}Rb spinor BEC. We observe correlations between spin and OAM in the dressed state and characterize the spin texture; the result is in good agreement with the theory. In the presence of the Raman field, our dressed state is stable for 0.1 s or longer, and it decays due to collision-induced relaxation. As we turn off the Raman beams, the vortex cores in the bare spin |m_{F}=1⟩ and |-1⟩ split. These spin-OAM coupled systems with the Raman-dressing approach have great potential for exploring new topological textures and quantum states.

19.
Psychol Med ; 48(8): 1325-1340, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29094675

RESUMEN

BACKGROUND: A range of endophenotypes characterise psychosis, however there has been limited work understanding if and how they are inter-related. METHODS: This multi-centre study includes 8754 participants: 2212 people with a psychotic disorder, 1487 unaffected relatives of probands, and 5055 healthy controls. We investigated cognition [digit span (N = 3127), block design (N = 5491), and the Rey Auditory Verbal Learning Test (N = 3543)], electrophysiology [P300 amplitude and latency (N = 1102)], and neuroanatomy [lateral ventricular volume (N = 1721)]. We used linear regression to assess the interrelationships between endophenotypes. RESULTS: The P300 amplitude and latency were not associated (regression coef. -0.06, 95% CI -0.12 to 0.01, p = 0.060), and P300 amplitude was positively associated with block design (coef. 0.19, 95% CI 0.10-0.28, p 0.38). All the cognitive endophenotypes were associated with each other in the expected directions (all p < 0.001). Lastly, the relationships between pairs of endophenotypes were consistent in all three participant groups, differing for some of the cognitive pairings only in the strengths of the relationships. CONCLUSIONS: The P300 amplitude and latency are independent endophenotypes; the former indexing spatial visualisation and working memory, and the latter is hypothesised to index basic processing speed. Individuals with psychotic illnesses, their unaffected relatives, and healthy controls all show similar patterns of associations between endophenotypes, endorsing the theory of a continuum of psychosis liability across the population.


Asunto(s)
Encéfalo/fisiopatología , Endofenotipos , Red Nerviosa/fisiopatología , Trastornos Psicóticos/fisiopatología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Electrofisiología , Potenciales Relacionados con Evento P300 , Femenino , Humanos , Modelos Lineales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Adulto Joven
20.
Phys Chem Chem Phys ; 20(6): 4297-4307, 2018 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-29367996

RESUMEN

In recent work, there has been considerable speculation about the atmospheric reaction of methylenimine (CH2NH), because this compound is highly reactive, soluble in water, and sticky, thus posing severe experimental challenges. In this work, we have revisited the kinetics of the OH + CH2NH reaction assisted by a single water molecule. The potential energy surfaces (PESs) for the water-assisted OH + CH2NH reaction were calculated using the CCSD(T)//BH&HLYP/aug-cc-pVTZ levels of theory. The rate coefficients for the bimolecular reaction pathways CH2NHH2O + OH and CH2NH + H2OHO were computed using canonical variational transition state theory (CVT) with small curvature tunneling correction. The reaction without water has four elementary reaction pathways, depending on how the hydroxyl radical approaches CH2NH. In all cases, the reaction begins with the formation of a single pre-reactive complex before producing abstraction and addition products. When water is added, the products of the reaction do not change, and the reaction becomes quite complex, yielding four different pre-reactive complexes and eight reaction pathways. The calculated rate coefficient for the OH + CH2NH (water-free) reaction at 300 K is 1.7 × 10-11 cm3 molecule-1 s-1 and for OH + CH2NH (water-assisted), it is 5.1 × 10-14 cm3 molecule-1 s-1. This result is similar to the isoelectronic analogous reaction OH + CH2O (water-assisted). In general, the effective rate coefficients of the water-assisted reaction are 2∼3 orders of magnitude smaller than water-free. Our results show that the water-assisted OH + CH2NH reaction cannot accelerate the reaction because the dominated water-assisted process depends parametrically on water concentration. As a result, the overall reaction rate coefficients are smaller.

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