Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 174
Filtrar
1.
Behav Brain Res ; : 115062, 2024 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-38768689

RESUMEN

To conserve sequential behavior in relation to the topographic challenges of space, it is proposed that humans and nonhuman animals can organize behavior using different scaling principles. To deal with increases in linear distance, isochrony suggest that there is a corresponding increase in speed, whereas to deal with changes in curvature, speed is adjusted according to a power function. The present study investigates whether these principles provide a framework for describing the organization of mouse behavior in a variety of standard experimental tasks. The structure of movement was examined in ambulation during open field exploration; manipulation in a string-pulling task, in which a string is advanced hand over hand to retrieve food; and rung-walking, in which the limbs successively step from rung to rung on a horizontal ladder. Both principles were found to be conserved in the organization of mouse behavior across scales of movement. These principles provide novel measures of the temporal and geometric features of movement in the mouse and insights into how the temporal and geometric features of movement are conserved within different species.

2.
Rev Sci Instrum ; 94(5)2023 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-37227193

RESUMEN

Recently, great progress has been made in the field of ultrasensitive microwave detectors, reaching even the threshold for utilization in circuit quantum electrodynamics. However, cryogenic sensors lack the compatibility with broad-band metrologically traceable power absorption measurements at ultralow powers, which restricts their range of applications. Here, we demonstrate such measurements using an ultralow-noise nanobolometer, which we extend by an additional direct-current (dc) heater input. The tracing of the absorbed power relies on comparing the response of the bolometer between radio frequency and dc-heating powers traced to the Josephson voltage and quantum Hall resistance. To illustrate this technique, we demonstrate two different methods of dc-substitution to calibrate the power that is delivered to the base temperature stage of a dilution refrigerator using our in situ power sensor. As an example, we demonstrate the ability to accurately measure the attenuation of a coaxial input line between the frequencies of 50 MHz and 7 GHz with an uncertainty down to 0.1 dB at a typical input power of -114 dBm.

3.
Rev Sci Instrum ; 94(5)2023 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-37249411

RESUMEN

We report calibrated microwave transmission and reflection measurements of a qubit sample holder at millikelvin temperatures. The methodology we present extends our previous work on one-port cryogenic short-open-load (SOL) calibration to a two-port SOLT measurement by implementing an unknown thru (T) standard. We report the resulting calibrated transmission and reflection at millikelvin temperatures through a printed circuit board that is installed into the sample holder. Finally, we consider a cascade of components at the end of a qubit drive line that includes (1) a cryogenic attenuator, (2) a coaxial cable, and (3) a qubit sample holder. Using experimentally determined parameters for return losses for all three components, we calculate the negligible state-preparation error in the frequency band of 5-7 GHz due to control pulse distortions arising from reflection at the coaxial launches. Taken together, our results highlight the utility of calibrated cryogenic scattering parameter measurements for the validation of qubit packaging and the wiring in its immediate vicinity.

4.
Anim Cogn ; 26(3): 861-883, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36494587

RESUMEN

The nature of the representation guiding spatial navigation has been investigated extensively; however, most of this work has used behavioral tasks that involved learning the location of food reward or an escape platform. In contrast, relatively few studies have focused on the spatial representation of a home base, a ubiquitous feature of open-field behavior, and its ability to be encoded relative to environmental cues. The current set of experiments investigated acquisition and retention of the location of home base establishment. In general, proximal cues anchored the position of the home base during acquisition sessions across all four experiments. Although mice established a home base during retention sessions, previous experience did not influence its position during retention sessions. These observations demonstrate that stimulus control of home base position depends on access to proximal cues. Further work is needed to determine the extent that home base establishment may provide a framework to encode goal-directed spatial behaviors.


Asunto(s)
Señales (Psicología) , Navegación Espacial , Ratones , Animales , Conducta Exploratoria
5.
Behav Processes ; 201: 104713, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35901935

RESUMEN

Age-related changes in spatial and temporal processing have been documented across a range of species. Rodent studies typically investigate differences in performance between adult and senescent animals; however, progressive loss of neurons in the hippocampus and cortex has been observed to occur as early as after adolescence. Therefore, the current study evaluated the effects of age in three- and ten-month-old female rats on the organization of movement in open field and food protection behaviors, two tasks that have previously dissociated hippocampal and cortical pathology. Age-related differences were observed in general measures of locomotion, spatial orientation, and attentional processing. The results of the current study are consistent with age-related changes in the processing of spatial information and motivation that occur earlier in life than previously anticipated. These observations establish a foundation for future studies evaluating interventions that influence these age-related differences in performance.


Asunto(s)
Orientación Espacial , Percepción Espacial , Animales , Femenino , Hipocampo/fisiología , Locomoción/fisiología , Neuronas/fisiología , Ratas , Percepción Espacial/fisiología
6.
Phys Rev Lett ; 129(2): 021801, 2022 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-35867467

RESUMEN

We report the first results of a search for leptophobic dark matter (DM) from the Coherent-CAPTAIN-Mills (CCM) liquid argon (LAr) detector. An engineering run with 120 photomultiplier tubes (PMTs) and 17.9×10^{20} protons on target (POT) was performed in fall 2019 to study the characteristics of the CCM detector. The operation of this 10-ton detector was strictly light based with a threshold of 50 keV and used coherent elastic scattering off argon nuclei to detect DM. Despite only 1.5 months of accumulated luminosity, contaminated LAr, and nonoptimized shielding, CCM's first engineering run has already achieved sensitivity to previously unexplored parameter space of light dark matter models with a baryonic vector portal. With an expected background of 115 005 events, we observe 115 005+16.5 events which is compatible with background expectations. For a benchmark mediator-to-DM mass ratio of m_{V_{B}}/m_{χ}=2.1, DM masses within the range 9 MeV≲m_{χ}≲50 MeV are excluded at 90% C. L. in the leptophobic model after applying the Feldman-Cousins test statistic. CCM's upgraded run with 200 PMTs, filtered LAr, improved shielding, and 10 times more POT will be able to exclude the remaining thermal relic density parameter space of this model, as well as probe new parameter space of other leptophobic DM models.

7.
Clin Case Rep ; 10(3): e05583, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35340637

RESUMEN

Warm autoimmune hemolytic anemia (AIHA) is a hematologic disorder with an incidence of 1-3 per 105 individuals/year. Patients with systemic lupus erythematosus (SLE) develop AIHA in 3% of adult cases and 14% of pediatric cases. We report a case of AIHA refractory to multiple lines of treatment in a patient with SLE, who eventually responded to a proteasome inhibitor-based combination. A patient with systemic lupus erythematous was diagnosed with symptomatic autoimmune hemolytic anemia. The patient was refractory to multiple lines of treatment including prednisone, intravenous immune globulin, methylprednisolone, rituximab, cyclophosphamide, mycophenolate mofetil, and splenectomy. She eventually had a beneficial response to a proteasome inhibitor-based combination with bortezomib plus mycophenolate mofetil. The treatment of refractory autoimmune hemolytic anemia can be challenging. Patients with AIHA refractory to primary or secondary treatments must resort to receiving novel therapeutic modalities including combinations targeting plasma cell, T- and B-cell proliferation.

8.
Behav Brain Res ; 416: 113577, 2022 01 07.
Artículo en Inglés | MEDLINE | ID: mdl-34506841

RESUMEN

Astronauts undertaking deep space travel will receive chronic exposure to the mixed spectrum of particles that comprise Galactic Cosmic Radiation (GCR). Exposure to the different charged particles of varied fluence and energy that characterize GCR may impact neural systems that support performance on mission critical tasks. Indeed, growing evidence derived from years of terrestrial-based simulations of the space radiation environment using rodents has indicated that a variety of exposure scenarios can result in significant and long-lasting decrements to CNS functionality. Many of the behavioral tasks used to quantify radiation effects on the CNS depend on neural systems that support maintaining spatial orientation and organization of rodent open field behavior. The current study examined the effects of acute or chronic exposure to simulated GCR on the organization of open field behavior under conditions with varied access to environmental cues in male and female C57BL/6 J mice. In general, groups exhibited similar organization of open field behavior under dark and light conditions. Two exceptions were noted: the acute exposure group exhibited significantly slower and more circuitous homeward progressions relative to the chronic group under light conditions. These results demonstrate the potential of open field behavior organization to discriminate between the effects of select GCR exposure paradigms.


Asunto(s)
Radiación Cósmica/efectos adversos , Señales (Psicología) , Conducta Exploratoria/fisiología , Orientación Espacial/fisiología , Exposición a la Radiación/efectos adversos , Animales , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Vuelo Espacial
9.
Int J Infect Dis ; 103: 268-277, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33221520

RESUMEN

BACKGROUND: Following an initial reduction in human campylobacteriosis in New Zealand after the implementation of poultry food chain-focused interventions during 2006-2008, further decline has been relatively small. We report a year-long study of notified campylobacteriosis cases, incorporating a case control study combined with a source attribution study. The purpose was to generate up-to-date evidence on the relative contributions of different sources of campylobacteriosis in New Zealand. METHODS: The study approach included: • A case-control study of notified cases (aged six months or more) sampled in a major urban centre (Auckland, every second case) and a mixed urban/rural area (Manawatu/Whanganui, every case), between 12 March 2018 and 11 March 2019. • Source attribution of human campylobacteriosis cases sampled from these two regions over the study period by modelling of multilocus sequence typing data of Campylobacter jejuni and C. coli isolates from faecal samples of notified human cases and relevant sources (poultry, cattle, sheep). RESULTS: Most cases (84%) were infected with strains attributed to a poultry source, while 14% were attributed to a cattle source. Approximately 90% of urban campylobacteriosis cases were attributed to poultry sources, compared to almost 75% of rural cases. Poultry consumption per se was not identified as a significant risk factor. However specific risk factors related to poultry meat preparation and consumption did result in statistically significantly elevated odds ratios. CONCLUSIONS: The overall findings combining source attribution and analysis of specific risk factors indicate that poultry meat remains a dominant pathway for exposure and infection.


Asunto(s)
Infecciones por Campylobacter/epidemiología , Campylobacter jejuni/aislamiento & purificación , Carne/microbiología , Aves de Corral/microbiología , Anciano , Animales , Técnicas de Tipificación Bacteriana , Infecciones por Campylobacter/microbiología , Estudios de Casos y Controles , Bovinos , Heces/microbiología , Femenino , Inocuidad de los Alimentos , Humanos , Lactante , Masculino , Tipificación de Secuencias Multilocus , Nueva Zelanda/epidemiología , Factores de Riesgo , Población Rural , Ovinos , Población Urbana
10.
Nature ; 586(7827): 47-51, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32999484

RESUMEN

Radiation sensors based on the heating effect of absorbed radiation are typically simple to operate and flexible in terms of input frequency, so they are widely used in gas detection1, security2, terahertz imaging3, astrophysical observations4 and medical applications5. Several important applications are currently emerging from quantum technology and especially from electrical circuits that behave quantum mechanically, that is, circuit quantum electrodynamics6. This field has given rise to single-photon microwave detectors7-9 and a quantum computer that is superior to classical supercomputers for certain tasks10. Thermal sensors hold potential for enhancing such devices because they do not add quantum noise and they are smaller, simpler and consume about six orders of magnitude less power than the frequently used travelling-wave parametric amplifiers11. However, despite great progress in the speed12 and noise levels13 of thermal sensors, no bolometer has previously met the threshold for circuit quantum electrodynamics, which lies at a time constant of a few hundred nanoseconds and a simultaneous energy resolution of the order of 10h gigahertz (where h is the Planck constant). Here we experimentally demonstrate a bolometer that operates at this threshold, with a noise-equivalent power of 30 zeptowatts per square-root hertz, comparable to the lowest value reported so far13, at a thermal time constant two orders of magnitude shorter, at 500 nanoseconds. Both of these values are measured directly on the same device, giving an accurate estimation of 30h gigahertz for the calorimetric energy resolution. These improvements stem from the use of a graphene monolayer with extremely low specific heat14 as the active material. The minimum observed time constant of 200 nanoseconds is well below the dephasing times of roughly 100 microseconds reported for superconducting qubits15 and matches the timescales of currently used readout schemes16,17, thus enabling circuit quantum electrodynamics applications for bolometers.

11.
Sci Rep ; 8(1): 6325, 2018 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-29679059

RESUMEN

Superconducting microwave circuits show great potential for practical quantum technological applications such as quantum information processing. However, fast and on-demand initialization of the quantum degrees of freedom in these devices remains a challenge. Here, we experimentally implement a tunable heat sink that is potentially suitable for the initialization of superconducting qubits. Our device consists of two coupled resonators. The first resonator has a high quality factor and a fixed frequency whereas the second resonator is designed to have a low quality factor and a tunable resonance frequency. We engineer the low quality factor using an on-chip resistor and the frequency tunability using a superconducting quantum interference device. When the two resonators are in resonance, the photons in the high-quality resonator can be efficiently dissipated. We show that the corresponding loaded quality factor can be tuned from above 105 down to a few thousand at 10 GHz in good quantitative agreement with our theoretical model.

12.
Sci Rep ; 6: 36349, 2016 11 25.
Artículo en Inglés | MEDLINE | ID: mdl-27886205

RESUMEN

Malignant mesothelioma (MM) is an aggressive serosal tumor associated with asbestos exposure. We previously demonstrated that mesothelial cells differentiate into cells of different mesenchymal lineages and hypothesize that osseous tissue observed in a subset of MM patients is due to local differentiation of MM cells. In this study, the capacity of human and mouse MM cells to differentiate into osteoblast-like cells was determined in vitro using a functional model of bone nodule formation and in vivo using an established model of MM. Human and murine MM cell lines cultured in osteogenic medium expressed alkaline phosphatase and formed mineralized bone-like nodules. Several human and mouse MM cell lines also expressed a number of osteoblast phenotype markers, including runt-related transcription factor 2 (RUNX2), osteopontin, osteonectin and bone sialoprotein mRNA and protein. Histological analysis of murine MM tumors identified areas of ossification within the tumor, similar to those observed in human MM biopsies. These data demonstrate the ability of MM to differentiate into another mesenchymal cell type and suggest that MM cells may contribute to the formation of the heterologous elements observed in MM tumors.


Asunto(s)
Biomarcadores/metabolismo , Neoplasias Pulmonares/metabolismo , Mesotelioma/metabolismo , Osteoblastos/citología , Osteogénesis , Adulto , Fosfatasa Alcalina/metabolismo , Animales , Diferenciación Celular , Línea Celular Tumoral , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Dexametasona/farmacología , Dexametasona/uso terapéutico , Femenino , Humanos , Sialoproteína de Unión a Integrina/genética , Sialoproteína de Unión a Integrina/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Mesotelioma/tratamiento farmacológico , Mesotelioma/genética , Mesotelioma Maligno , Ratones , Trasplante de Neoplasias , Osteoblastos/metabolismo , Osteogénesis/efectos de los fármacos , Osteonectina/metabolismo
13.
BMJ Open ; 6(10): e011811, 2016 10 21.
Artículo en Inglés | MEDLINE | ID: mdl-27797997

RESUMEN

INTRODUCTION: Medication errors are the most frequent cause of preventable harm in hospitals. Medication management in paediatric patients is particularly complex and consequently potential for harms are greater than in adults. Electronic medication management (eMM) systems are heralded as a highly effective intervention to reduce adverse drug events (ADEs), yet internationally evidence of their effectiveness in paediatric populations is limited. This study will assess the effectiveness of an eMM system to reduce medication errors, ADEs and length of stay (LOS). The study will also investigate system impact on clinical work processes. METHODS AND ANALYSIS: A stepped-wedge cluster randomised controlled trial (SWCRCT) will measure changes pre-eMM and post-eMM system implementation in prescribing and medication administration error (MAE) rates, potential and actual ADEs, and average LOS. In stage 1, 8 wards within the first paediatric hospital will be randomised to receive the eMM system 1 week apart. In stage 2, the second paediatric hospital will randomise implementation of a modified eMM and outcomes will be assessed. Prescribing errors will be identified through record reviews, and MAEs through direct observation of nurses and record reviews. Actual and potential severity will be assigned. Outcomes will be assessed at the patient-level using mixed models, taking into account correlation of admissions within wards and multiple admissions for the same patient, with adjustment for potential confounders. Interviews and direct observation of clinicians will investigate the effects of the system on workflow. Data from site 1 will be used to develop improvements in the eMM and implemented at site 2, where the SWCRCT design will be repeated (stage 2). ETHICS AND DISSEMINATION: The research has been approved by the Human Research Ethics Committee of the Sydney Children's Hospitals Network and Macquarie University. Results will be reported through academic journals and seminar and conference presentations. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ANZCTR) 370325.


Asunto(s)
Monitoreo de Drogas/métodos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Electrónica Médica , Hospitales Pediátricos , Tiempo de Internación , Errores de Medicación/prevención & control , Sistemas de Medicación en Hospital , Niño , Humanos , Pediatría , Preparaciones Farmacéuticas , Proyectos de Investigación
14.
BMC Infect Dis ; 16: 475, 2016 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-27600394

RESUMEN

BACKGROUND: Data containing notified cases of disease are often compromised by incomplete or partial information related to individual cases. In an effort to enhance the value of information from enteric disease notifications in New Zealand, this study explored the use of Bayesian and Multiple Imputation (MI) models to fill risk factor data gaps. As a test case, overseas travel as a risk factor for infection with campylobacteriosis has been examined. METHODS: Two methods, namely Bayesian Specification (BAS) and Multiple Imputation (MI), were compared regarding predictive performance for various levels of artificially induced missingness of overseas travel status in campylobacteriosis notification data. Predictive performance of the models was assessed through the Brier Score, the Area Under the ROC Curve and the Percent Bias of regression coefficients. Finally, the best model was selected and applied to predict missing overseas travel status of campylobacteriosis notifications. RESULTS: While no difference was observed in the predictive performance of the BAS and MI methods at a lower rate of missingness (<10 %), but the BAS approach performed better than MI at a higher rate of missingness (50 %, 65 %, 80 %). The estimated proportion (95 % Credibility Intervals) of travel related cases was greatest in highly urban District Health Boards (DHBs) in Counties Manukau, Auckland and Waitemata, at 0.37 (0.12, 0.57), 0.33 (0.13, 0.55) and 0.28 (0.10, 0.49), whereas the lowest proportion was estimated for more rural West Coast, Northland and Tairawhiti DHBs at 0.02 (0.01, 0.05), 0.03 (0.01, 0.08) and 0.04 (0.01, 0.06), respectively. The national rate of travel related campylobacteriosis cases was estimated at 0.16 (0.02, 0.48). CONCLUSION: The use of BAS offers a flexible approach to data augmentation particularly when the missing rate is very high and when the Missing At Random (MAR) assumption holds. High rates of travel associated cases in urban regions of New Zealand predicted by this approach are plausible given the high rate of travel in these regions, including destinations with higher risk of infection. The added advantage of using a Bayesian approach is that the model's prediction can be improved whenever new information becomes available.


Asunto(s)
Infecciones por Campylobacter/epidemiología , Notificación de Enfermedades , Modelos Teóricos , Viaje , Teorema de Bayes , Infecciones por Campylobacter/prevención & control , Infecciones por Campylobacter/transmisión , Humanos , Nueva Zelanda/epidemiología , Factores de Riesgo , Población Rural
15.
Phys Rev Lett ; 117(3): 030802, 2016 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-27472107

RESUMEN

We experimentally investigate and utilize electrothermal feedback in a microwave nanobolometer based on a normal-metal (Au_{x}Pd_{1-x}) nanowire with proximity-induced superconductivity. The feedback couples the temperature and the electrical degrees of freedom in the nanowire, which both absorbs the incoming microwave radiation, and transduces the temperature change into a radio-frequency electrical signal. We tune the feedback in situ and access both positive and negative feedback regimes with rich nonlinear dynamics. In particular, strong positive feedback leads to the emergence of two metastable electron temperature states in the millikelvin range. We use these states for efficient threshold detection of coherent 8.4 GHz microwave pulses containing approximately 200 photons on average, corresponding to 1.1×10^{-21} J≈7.0 meV of energy.

16.
Stud Health Technol Inform ; 227: 74-9, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27440292

RESUMEN

Registered nurses providing telenursing triage and advice services record information on the medication related calls they handle. However the quality and consistency of these data were rarely examined. Our aim was to examine medication related calls made to the healthdirect advice service in November 2014, to assess their basic characteristics and how the data entry format influenced information collected and data consistency. Registered nurses selected the patient question type from a range of categories, and entered the medications involved in a free text field. Medication names were manually extracted from the free text fields. We also compared the selected patient question type with the free text description of the call, in order to gauge data consistency. Results showed that nurses provided patients with advice on medication-related queries in a timely matter (the median call duration of 9 minutes). From 1835 calls, we were able to identify and classify 2156 medications into 384 generic names. However, in 204 cases (11.2% of calls) no medication name was entered. A further 308 (15.0%) of the medication names entered were not identifiable. When we compared the selected patient question with the free text description of calls, we found that these were consistent in 63.27% of cases. Telenursing and triage advice services provide a valuable resource to the public with quick and easily accessible advice. To support nurses provide quality services and record accurate information about the queries, appropriate data entry format and design would be beneficial.


Asunto(s)
Exactitud de los Datos , Preparaciones Farmacéuticas/clasificación , Teleenfermería/normas , Australia , Humanos , Enfermeras y Enfermeros , Triaje/estadística & datos numéricos
17.
Int J Nurs Stud ; 56: 9-16, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26775214

RESUMEN

BACKGROUND: High profile safety failures have demonstrated that recognising early warning signs of clinical and physiological deterioration can prevent or reduce harm resulting from serious adverse events. Early warning scoring systems are now routinely used in many places to detect and escalate deteriorating patients. Timely and accurate vital signs monitoring are critical for ensuring patient safety through providing data for early warning scoring systems, but little is known about current monitoring practices. OBJECTIVE: To establish a profile of nurses' vital signs monitoring practices, related dialogue, and adherence to health service protocol in New South Wales, Australia. METHODS: Direct observations of nurses' working practices were conducted in two wards. The observations focused on times of the day when vital signs were generally measured. Patient interactions were recorded if occurring any time during the observation periods. Participants (n=42) included nursing staff on one chronic disease medical and one acute surgical ward in a large urban teaching hospital in New South Wales. RESULTS: We observed 441 patient interactions. Measurement of vital signs occurred in 52% of interactions. The minimum five vital signs measures required by New South Wales Health policy were taken in only 6-21% of instances of vital signs monitoring. Vital signs were documented immediately on 93% of vitals-taking occasions and documented according to the policy in the patient's chart on 89% of these occasions. Nurse-patient interactions were initiated for the purpose of taking vital signs in 49% of interactions, with nurse-patient discourse observed during 88% of all interactions. Nurse-patient dialogue led to additional care being provided to patients in 12% of interactions. CONCLUSION: The selection of appropriate vital signs measured and responses to these appears to rely on nurses' clinical judgement or time availability rather than on policy-mandated frequency. The prevalence of incomplete sets of vital signs may limit identification of deteriorating patients. The findings from this study present an important baseline profile against which to evaluate the impact of introducing continuous monitoring approaches on current hospital practice.


Asunto(s)
Monitoreo Fisiológico , Relaciones Enfermero-Paciente , Personal de Enfermería en Hospital , Signos Vitales , Humanos , Nueva Gales del Sur , Investigación Cualitativa
18.
Br J Cancer ; 113(12): 1677-86, 2015 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-26645238

RESUMEN

BACKGROUND: Foxp3+ regulatory T cells (Tregs) play a vital role in preventing autoimmunity, but also suppress antitumour immune responses. Tumour infiltration by Tregs has strong prognostic significance in colorectal cancer, and accumulating evidence suggests that chemotherapy and radiotherapy efficacy has an immune-mediated component. Whether Tregs play an inhibitory role in chemoradiotherapy (CRT) response in rectal cancer remains unknown. METHODS: Foxp3+, CD3+, CD4+, CD8+ and IL-17+ cell density in post-CRT surgical samples from 128 patients with rectal cancer was assessed by immunohistochemistry. The relationship between T-cell subset densities and clinical outcome (tumour regression and survival) was evaluated. RESULTS: Stromal Foxp3+ cell density was strongly associated with tumour regression grade (P=0.0006). A low stromal Foxp3+ cell density was observed in 84% of patients who had a pathologic complete response (pCR) compared with 41% of patients who did not (OR: 7.56, P=0.0005; OR: 5.27, P=0.006 after adjustment for presurgery clinical factors). Low stromal Foxp3+ cell density was also associated with improved recurrence-free survival (HR: 0.46, P=0.03), although not independent of tumour regression grade. CONCLUSIONS: Regulatory T cells in the tumour microenvironment may inhibit response to neoadjuvant CRT and may represent a therapeutic target in rectal cancer.


Asunto(s)
Factores de Transcripción Forkhead/inmunología , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/radioterapia , Linfocitos T Reguladores/inmunología , Anciano , Quimioterapia Adyuvante , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radioterapia Adyuvante , Resultado del Tratamiento
19.
Ann Oncol ; 26(12): 2483-90, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26386124

RESUMEN

BACKGROUND: Data from murine models suggest that CD40 activation may synergize with cytotoxic chemotherapy. We aimed to determine the maximum tolerated dose (MTD) and toxicity profile and to explore immunological biomarkers of the CD40-activating antibody CP-870,893 with cisplatin and pemetrexed in patients with malignant pleural mesothelioma (MPM). PATIENTS AND METHODS: Eligible patients had confirmed MPM, ECOG performance status 0-1, and measurable disease. Patients received cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) on day 1 and CP-870,893 on day 8 of a 21-day cycle for maximum 6 cycles with up to 6 subsequent cycles single-agent CP-870,893. Immune cell subset changes were examined weekly by flow cytometry. RESULTS: Fifteen patients were treated at three dose levels. The MTD of CP-870,893 was 0.15 mg/kg, and was exceeded at 0.2 mg/kg with one grade 4 splenic infarction and one grade 3 confusion and hyponatraemia. Cytokine release syndrome (CRS) occurred in most patients (80%) following CP-870,893. Haematological toxicities were consistent with cisplatin and pemetrexed chemotherapy. Six partial responses (40%) and 9 stable disease (53%) as best response were observed. The median overall survival was 16.5 months; the median progression-free survival was 6.3 months. Three patients survived beyond 30 months. CD19+ B cells decreased over 6 cycles of chemoimmunotherapy (P < 0.001) with a concomitant increase in the proportion of CD27+ memory B cells (P < 0.001) and activated CD86+CD27+ memory B cells (P < 0.001), as an immunopharmacodynamic marker of CD40 activation. CONCLUSIONS: CP-870,893 with cisplatin and pemetrexed is safe and tolerable at 0.15 mg/kg, although most patients experience CRS. While objective response rates are similar to chemotherapy alone, three patients achieved long-term survival. AUSTRALIA NEW ZEALAND CLINICAL TRIALS REGISTRY NUMBER: ACTRN12609000294257.


Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Antígenos CD40/metabolismo , Cisplatino/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Mesotelioma/tratamiento farmacológico , Pemetrexed/administración & dosificación , Neoplasias Pleurales/tratamiento farmacológico , Adulto , Anciano , Anticuerpos Monoclonales Humanizados , Antígenos CD40/agonistas , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Masculino , Mesotelioma/diagnóstico , Mesotelioma/metabolismo , Mesotelioma Maligno , Persona de Mediana Edad , Neoplasias Pleurales/diagnóstico , Neoplasias Pleurales/metabolismo , Estudios Prospectivos
20.
Nano Lett ; 15(5): 2965-73, 2015 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-25927475

RESUMEN

Bulk 1T-TaSe2 exhibits unusually high charge density wave (CDW) transition temperatures of 600 and 473 K below which the material exists in the incommensurate (I-CDW) and the commensurate (C-CDW) charge-density-wave phases, respectively. The (13)(1/2) × (13)(1/2) C-CDW reconstruction of the lattice coincides with new Raman peaks resulting from zone-folding of phonon modes from middle regions of the original Brillouin zone back to Γ. The C-CDW transition temperatures as a function of film thickness are determined from the evolution of these new Raman peaks, and they are found to decrease from 473 to 413 K as the film thicknesses decrease from 150 to 35 nm. A comparison of the Raman data with ab initio calculations of both the normal and C-CDW phases gives a consistent picture of the zone-folding of the phonon modes following lattice reconstruction. The Raman peak at ∼154 cm(-1) originates from the zone-folded phonons in the C-CDW phase. In the I-CDW phase, the loss of translational symmetry coincides with a strong suppression and broadening of the Raman peaks. The observed change in the C-CDW transition temperature is consistent with total energy calculations of bulk and monolayer 1T-TaSe2.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...