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1.
Phys Rev Lett ; 132(6): 062702, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38394565

RESUMO

The cross section of the ^{13}C(α,n)^{16}O reaction is needed for nuclear astrophysics and applications to a precision of 10% or better, yet inconsistencies among 50 years of experimental studies currently lead to an uncertainty of ≈15%. Using a state-of-the-art neutron detection array, we have performed a high resolution differential cross section study covering a broad energy range. These measurements result in a dramatic improvement in the extrapolation of the cross section to stellar energies potentially reducing the uncertainty to ≈5% and resolving long standing discrepancies in higher energy data.

2.
Rev Med Chil ; 148(7): 1011-1017, 2020 Jul.
Artigo em Espanhol | MEDLINE | ID: mdl-33399686

RESUMO

For more than a century the training of medical professionals has been organized according to the Flexnerian model, which comprises three cycles: basic, clinical and clerkship. On the other hand, the accelerated development of biomedical sciences modified the competences of the first cycle. Additionally, new skills required for medical practice, such as teamwork and innovation as a tool to solve health problems, challenged in recent years the classic paradigm of medical education. Therefore, the medical schools have developed multiple strategies to deal with it, such as curricular integration using competency-based education models, incorporating basic and clinical sciences in parallel during the curriculum, ensuring a relevant and applicable scientific knowledge throughout the training process. Although in Chile the Flexner prototype is still followed, the basic sciences are taught as single or integrated courses or using a systems approach. In this article we report a diagnosis about the local integration of fundamental sciences in medical training. We also compare our schools with those of Canada, Europe and Latin America. Recommendations aimed at modernizing medical school curricula are made.


Assuntos
Educação Médica , Faculdades de Medicina , Ciência , Chile , Currículo , Educação Médica/organização & administração , Humanos , Ciência/educação
3.
Phys Rev Lett ; 121(4): 042501, 2018 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-30095940

RESUMO

Full calculations of six-nucleon reactions with a three-body final state have been elusive and a long-standing issue. We present neutron spectra from the T(t,2n)α (TT) reaction measured in inertial confinement fusion experiments at the OMEGA laser facility at ion temperatures from 4 to 18 keV, corresponding to center-of-mass energies (E_{c.m.}) from 16 to 50 keV. A clear difference in the shape of the TT-neutron spectrum is observed between the two E_{c.m.}, with the ^{5}He ground state resonant peak at 8.6 MeV being significantly stronger at the higher than at the lower energy. The data provide the first conclusive evidence of a variant TT-neutron spectrum in this E_{c.m.} range. In contrast to earlier available data, this indicates a reaction mechanism that must involve resonances and/or higher angular momenta than L=0. This finding provides an important experimental constraint on theoretical efforts that explore this and complementary six-nucleon systems, such as the solar ^{3}He(^{3}He,2p)α reaction.

4.
Phys Rev Lett ; 119(22): 222701, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29286782

RESUMO

Few-body nuclear physics often relies upon phenomenological models, with new efforts at the ab initio theory reported recently; both need high-quality benchmark data, particularly at low center-of-mass energies. We use high-energy-density plasmas to measure the proton spectra from ^{3}He+T and ^{3}He+^{3}He fusion. The data disagree with R-matrix predictions constrained by neutron spectra from T+T fusion. We present a new analysis of the ^{3}He+^{3}He proton spectrum; these benchmarked spectral shapes should be used for interpreting low-resolution data, such as solar fusion cross-section measurements.

5.
Inorg Chem ; 56(5): 2712-2721, 2017 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-28186742

RESUMO

The substitution of lithium for copper in Cu2ZnSnS4 (CZTS) has been experimentally and theoretically investigated. Formally, the (Cu1-xLix)ZnSnS4 system exhibits two well-defined solid solutions. Indeed, single crystal structural analyses demonstrate that the low (x < 0.4) and high (x > 0.6) lithium-content compounds adopt the kesterite structure and the wurtz-kesterite structure, respectively. For x between 0.4 and 0.6, the two aforementioned structure types coexist. Moreover, 119Sn NMR analyses carried out on a (Cu0.7Li0.3)2ZnSnS4 sample clearly indicate that lithium replaces copper preferentially on two of the three available 2-fold crystallographic sites commonly occupied by Cu and Zn in disordered kesterite. Furthermore, the observed individual lines in the NMR spectrum suggest that the propensity of Cu and Zn atoms to be randomly distributed over the 2c and 2d crystallographic sites is lowered when lithium is partially substituted for copper. Additionally, the first-principles calculations provide insights into the arrangement of Li atoms as a function of the Cu/Zn disorder and its effect on the structural (lattice parameters) and optical properties of CZTS (band gap evolution). Those calculations agree with the experimental observations and account for the evolutions of the unit cell parameters as well as for the increase of band gap when the Li-content increases. The calculation of the formation enthalpy of point defect unambiguously indicates that Li modifies the Cu/Zn disorder in a manner similar to the change of Cu/Zn disorder induced by Ag alloying. Overall, it was found that Li alloying is a versatile way of tuning the optoelectronic properties of CZTS making it a good candidate as wide band gap materials for the top cells of tandem solar cells.

6.
Phys Rev Lett ; 117(3): 035002, 2016 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-27472118

RESUMO

Light nuclei were created during big-bang nucleosynthesis (BBN). Standard BBN theory, using rates inferred from accelerator-beam data, cannot explain high levels of ^{6}Li in low-metallicity stars. Using high-energy-density plasmas we measure the T(^{3}He,γ)^{6}Li reaction rate, a candidate for anomalously high ^{6}Li production; we find that the rate is too low to explain the observations, and different than values used in common BBN models. This is the first data directly relevant to BBN, and also the first use of laboratory plasmas, at comparable conditions to astrophysical systems, to address a problem in nuclear astrophysics.

8.
Gen Comp Endocrinol ; 226: 50-5, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26723188

RESUMO

An understanding of stress physiology is important for species management because high levels of stress can hamper reproduction and affect an individual's ability to cope with threats to their survival, such as disease and human-wildlife conflict. A commonly used indicator of stress, faecal concentrations of cortisol metabolites (FCM), can be used to assess the impact of social, biological and environmental factors. Measurements of FCM are particularly valuable for endangered species that are logistically challenging to study and where non-invasive techniques are preferred. As the second most endangered canid in Africa, the African wild dog (Lycaon pictus) has been the focus of considerable conservation research, yet there is still little understanding of factors associated with stress, in either captive or free-ranging populations. The present study therefore aimed to determine whether stress levels differ between captive and free-ranging populations, and to detect social, biological and environmental factors that are stressful in these populations. Faecal samples were collected from 20 captive and 62 free-ranging animals. Within free-ranging populations, the sexes differed significantly, but there was no effect of social status, age or breeding period for either sex. Captive females had higher FCM concentrations than free-ranging females. In captive populations, FCM concentrations differed among zoos and with reproductive status in females, but were not related to age class or group-housing structure. In conclusion, FCM is a useful indicator of stress and should be considered an integrative aspect of management, for both in situ and ex situ African wild dog populations.


Assuntos
Canidae/fisiologia , Fezes/química , Glucocorticoides/análise , Reprodução/fisiologia , Estresse Fisiológico/fisiologia , Animais , Animais Selvagens/metabolismo , Cruzamento , Espécies em Perigo de Extinção , Feminino , Hidrocortisona/metabolismo , Masculino
9.
Mol Phylogenet Evol ; 93: 363-79, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26282950

RESUMO

Recent investigations on the evolutionary history of the common midwife toad (Alytes obstetricans) revealed high levels of geographically structured genetic diversity but also a situation where delineation of major historical lineages and resolution of their relationships are much more complex than previously thought. We studied sequence variation in one mitochondrial and four nuclear genes throughout the entire distribution range of all recognized A. obstetricans subspecies to infer the evolutionary processes that shaped current patterns of genetic diversity and population subdivision. We found six divergent, geographically structured mtDNA haplogroups diagnosing population lineages, and varying levels of admixture in nuclear markers. Given the timeframe inferred for the splits between major lineages, the climatic and environmental changes that occurred during the Pleistocene seem to have shaped the diversification history of A. obstetricans. Survival of populations in allopatric refugia through the Ice Ages supports the generality of the "refugia-within-refugia" scenario for the Iberian Peninsula. However, lineages corresponding to subspecies A. o. almogavarii, A. o. pertinax, A. o. obstetricans, and A. o. boscai responded differently to Pleistocene climatic oscillations after diverging from a common ancestor. Alytes o. obstetricans expanded northward from a northern Iberian refugium through the western Pyrenees, leaving a signal of contrasting patterns of genetic diversity, with a single mtDNA haplotype north of the Pyrenees from SW France to Germany. Both A. o. pertinax and A. o. boscai are widespread and genetically diverse in Iberia, the latter comprising two divergent lineages with a long independent history. Finally, A. o. almogavarii is mostly restricted to the north-eastern corner of Iberia north of the Ebro river, with additional populations in a small region in south-eastern France. This taxon exhibits unparalleled levels of genetic diversity and little haplotype sharing with other lineages, suggesting a process of incipient speciation.


Assuntos
Anuros/genética , Proteínas de Anfíbios/genética , Animais , DNA Mitocondrial/genética , França , Especiação Genética , Variação Genética , Haplótipos , Marrocos , Tipagem de Sequências Multilocus , NADH Desidrogenase/genética , Filogenia , Filogeografia , Portugal , Refúgio de Vida Selvagem , Espanha
10.
J Helminthol ; 89(4): 487-95, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25007150

RESUMO

Ethiopian wolves, Canis simensis, are an endangered carnivore endemic to the Ethiopian highlands. Although previous studies have focused on aspects of Ethiopian wolf biology, including diet, territoriality, reproduction and infectious diseases such as rabies, little is known of their helminth parasites. In the current study, faecal samples were collected from 94 wild Ethiopian wolves in the Bale Mountains of southern Ethiopia, between August 2008 and February 2010, and were screened for the presence of helminth eggs using a semi-quantitative volumetric dilution method with microscopy. We found that 66 of the 94 faecal samples (70.2%) contained eggs from at least one group of helminths, including Capillaria, Toxocara, Trichuris, ancylostomatids, Hymenolepis and taeniids. Eggs of Capillaria sp. were found most commonly, followed by Trichuris sp., ancylostomatid species and Toxocara species. Three samples contained Hymenolepis sp. eggs, which were likely artefacts from ingested prey species. Four samples contained taeniid eggs, one of which was copro-polymerase chain reaction (copro-PCR) and sequence positive for Echinococcus granulosus, suggesting a spillover from a domestic parasite cycle into this wildlife species. Associations between presence/absence of Capillaria, Toxocara and Trichuris eggs were found; and egg burdens of Toxocara and ancylostomatids were found to be associated with geographical location and sampling season.


Assuntos
Infecções por Cestoides/veterinária , Espécies em Perigo de Extinção , Infecções por Nematoides/veterinária , Lobos , Animais , Infecções por Cestoides/epidemiologia , Infecções por Cestoides/parasitologia , Ecossistema , Etiópia/epidemiologia , Fezes/parasitologia , Hymenolepis/isolamento & purificação , Nematoides/classificação , Nematoides/isolamento & purificação , Infecções por Nematoides/epidemiologia , Infecções por Nematoides/parasitologia , Contagem de Ovos de Parasitas , Taenia/isolamento & purificação
11.
Cell Tissue Res ; 355(2): 471-80, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24362491

RESUMO

Ovarian fragments were exposed to 0.5 M sucrose and 1 M ethylene glycol (freezing solution; FS) with or without selenium or Trolox. Histological and ultrastructural analyses showed that the percentages of normal follicles in control tissue and in tissue after exposure to FS + 50 µM Trolox were similar. Trolox prevented endoplasmic reticulum (ER)-related vacuolization, which is commonly observed in oocytes and stromal tissue after exposure to FS. From the evaluated stress markers, superoxide dismutase 1 (SOD1) was up-regulated in ovarian tissue exposed to FS + 10 ng/ml selenium. Ovarian fragments were subsequently frozen-thawed in the presence of FS with or without 50 µM Trolox, followed by in vitro culture (IVC). Antioxidant capacity in ovarian fragments decreased after freeze-thawing in Trolox-free FS compared with FS + 50 µM Trolox. Although freezing itself minimized the percentage of viable follicles in each solution, Trolox supplementation resulted in higher rates of viable follicles (67 %), even after IVC (61 %). Furthermore, stress markers SOD1 and ERp29 were up-regulated in ovarian tissue frozen-thawed in Trolox-free medium. Relative mRNA expression of growth factors markers was evaluated after freeze-thawing followed by IVC. BMP4, BMP5, CTGF, GDF9 and KL were down-regulated independently of the presence of Trolox in FS but down-regulation was less pronounced in the presence of Trolox. Thus, medium supplementation with 50 µM Trolox prevents ER stress and, consequently, protects ovarian tissue from ER-derived cytoplasmic vacuolization. ERp29 but not ERp60, appears to be a key marker linking stress caused by freezing-thawing and cell vacuolization.


Assuntos
Cebus/metabolismo , Cromanos/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Congelamento , Ovário/efeitos dos fármacos , Ovário/patologia , Vitamina E/análogos & derivados , Animais , Calreticulina/metabolismo , Crioprotetores/farmacologia , Feminino , Proteínas de Choque Térmico HSP70/metabolismo , Ovário/metabolismo , Ovário/ultraestrutura , Superóxido Dismutase/metabolismo
12.
Clin Ophthalmol ; 18: 2369-2380, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39193320

RESUMO

Purpose: The aim of the research was to evaluate the use of teleophthalmology at a university practice during the COVID-19 pandemic, specifically examining precision, effectiveness, and patient satisfaction. Patients and Methods: Telemedicine visits were offered to new and established patients requesting appointments with the Stony Brook University Department of Ophthalmology between March 30 and June 2, 2020. Records from these visits were reviewed for chief complaint, past medical and ocular history, diagnoses, treatment/management, and providers' sub-specialty. Precision was determined by comparing agreement between diagnoses of the telemedicine visit with those of the subsequent in-person visit. The decision to follow up in person was made by the physician and patient. Diagnostic precision as well as progression, improvement, or stability of patients' symptoms were determined by the physician's assessment at follow-up visits. Post-telemedicine visit satisfaction surveys were sent to all patients. Results: Telemedicine visits were offered to 783 patients, 520 (66.4%) of whom accepted. Of these 520 patients, 409 (78.7%) were established and 105 (20.2%) had in-person, follow-up visits. Overall, the diagnostic precision of the follow-up visits was 89.5%. Precision differed significantly across ophthalmologic subspecialties. Of the patients who had in-person follow-up visits, 56.8% remained stable, 32.4% improved, and 10.8% worsened. Established patients presented with more extensive ocular histories/procedures and experienced a higher percentage of worsening symptoms/disease stage compared to new patients. Oculoplastics/orbit was the most prevalent diagnostic subspecialty that worsened. Surveys were sent to all patients completing telemedicine visits, 15.0% of whom responded. Overall satisfaction was 91.9%, although only 23.0% of respondents preferred telemedicine to an in-office visit. Conclusion: Telehealth provides high levels of precision and patient satisfaction for a wide range of ophthalmologic visits, although most patients still prefer in-office examinations. Employing teleophthalmology for follow-up and emergency care may provide patients with an effective alternative during pandemic situations and beyond.


Telemedicine involves integration of modern telecommunications technology into medical practice. Over the years, it has demonstrated greater and more widespread utility for different medical specialties, including ophthalmology. As a response to the recent COVID-19 pandemic, the Stony Brook University Department of Ophthalmology provided an option of telemedicine for patients in lieu of in-person eye examinations. In this paper, Stony Brook ophthalmologists report on their experience with teleophthalmology, particularly regarding its utilization, accuracy, effectiveness, precision, and acceptability. The authors examined the records of 520 patients who had telemedicine encounters between March 30 and June 2, 2020. Precision was determined by comparing the initial and final diagnoses of all patients who had an in-person follow-up appointment following a telemedicine visit. Of 105 patients that followed up, precision was determined to be 89.5%. Precision was compared across ophthalmologic subspecialties and found to be statistically similar (p>0.05). Approximately a third of patients improved, while nearly 11% worsened. Established and oculoplastics patients were more significantly likely to worsen. Surverys were sent out to study patients to gauge their satisfaction with their telemedicine experience. Although satisfaction was nearly 92%, only 23% of patients preferred telemedicine to an in-person physician encounter. The authors conclude that teleophthalmology provides a high level of diagnostic precision and patient satisfaction; nevertheless, most patients prefer in-person physician encounters. Telemedicine may provide an effective alternative to in-person ophthalmology assessments, especially during a pandemic. There appears to be a lesser but potentially useful role for teleophthalmology in a non-pandemic setting.

13.
Opt Lett ; 38(16): 3099-102, 2013 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-24104659

RESUMO

In general, a pair of uncorrelated Gaussian states mixed in a beam splitter (BS) produces a correlated state at the output. However, when the inputs are identical Gaussian states the output state is equal to the input, and no correlations appear, as the interference had not taken place. On the other hand, since physical phenomena do have observable effects, and the BS is there, a question arises on how to reveal the interference between the two beams. We prove theoretically and demonstrate experimentally that this is possible if at least one of the two beams is prepared in a discordant, i.e., Gaussian correlated, state with a third beam. We also apply the same technique to reveal the erasure of polarization information. Our experiment involves thermal states and the results show that Gaussian discordant states, even when they show a positive Glauber P-function, may be useful to achieve specific tasks.

14.
Eur J Neurol ; 20(6): 915-20, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23347399

RESUMO

BACKGROUND AND PURPOSE: Methcathinone abuse is a new cause of manganism. The psychostimulant is prepared from pseudoephedrine using potassium permanganate as an oxidant. We describe the clinical, biological, neuroimaging characteristics and follow-up results in a large Estonian cohort of intravenous methcathinone users. METHODS: During 2006-2012 we studied 38 methcathinone abusers with a mean age of 33 years. Subjects were rated by the Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn and Yahr (HY), and Schwab and England (SE) rating scales. Twenty-four cases were reassessed 9-70 (20 ±â€…15) months after the initial evaluation. Manganese (Mn) in plasma and hair was analysed by inductively coupled plasma-atom emission spectrometry. Magnetic resonance imaging (MRI) was performed in 11, and single-photon emission computed tomography (SPECT) with iodobenzamide (IBZM) in eight subjects. RESULTS: The average total UPDRS score was 43 ±â€…21. The most severely affected domains in UPDRS Part III were speech and postural stability, the least affected domain was resting tremor. At follow-up there was worsening of HY and SE rating scales. Subjects had a higher mean level of Mn in hair (2.9 ±â€…3.8 ppm) than controls (0.82 ±â€…1.02 ppm), P = 0.02. Plasma Mn concentrations were higher (11.5 ±â€…6.2 ppb) in active than in former users (5.6 ±â€…1.8 ppb), P = 0.006. Active methcathinone users had increased MRI T1-signal intensity in the globus pallidus, substantia nigra and periaquaductal gray matter. IBZM-SPECT showed normal symmetric tracer uptake in striatum. CONCLUSION: Methcathinone abusers develop a distinctive hypokinetic syndrome. Though the biomarkers of Mn exposure are characteristic only of recent abuse, the syndrome is not reversible.


Assuntos
Manganês/sangue , Doença de Parkinson Secundária/sangue , Doença de Parkinson Secundária/induzido quimicamente , Propiofenonas , Transtornos Relacionados ao Uso de Substâncias/sangue , Adolescente , Adulto , Biomarcadores/sangue , Biomarcadores/química , Estudos de Coortes , Estônia/epidemiologia , Feminino , Seguimentos , Cabelo/química , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson Secundária/epidemiologia , Propiofenonas/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adulto Jovem
15.
J Intellect Disabil Res ; 57(8): 703-15, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22845742

RESUMO

BACKGROUND: The quality of support provided to people with disability who show challenging behaviour could be influenced by the quality of the behaviour support plans (BSPs) on which staff rely for direction. This study investigated the content validity of the Behaviour Support Plan Quality Evaluation tool (BSP-QEII), originally developed to guide the development of BSPs for children in school settings, and evaluated its application for use in accommodation and day-support services for adults with intellectual disability. METHOD: A three-round Delphi study involving a purposive sample of experienced behaviour support practitioners (n = 30) was conducted over an 8-week period. The analyses included deductive content analysis and descriptive statistics. RESULTS: The 12 quality domains of the BSP-QEII were affirmed as valid for application in adult accommodation and day-support service settings. Two additional quality domains were suggested, relating to the provision of detailed background on the client and the need for plans to reflect contemporary service philosophy. Furthermore, the results suggest that some issues previously identified in the literature as being important for inclusion in BSPs might not currently be a priority for practitioners. These included: the importance of specifying replacement or alternative behaviours to be taught, descriptions of teaching strategies to be used, reinforcers, and the specification of objective goals against which to evaluate the success of the intervention programme. CONCLUSIONS: The BSP-QEII provides a potentially useful framework to guide and evaluate the development of BSPs in services for adults with intellectual disability. Further research is warranted to investigate why practitioners are potentially giving greater attention to some areas of intervention practice than others, even where research has demonstrated these others areas of practice could be important to achieving quality outcomes.


Assuntos
Terapia Comportamental/normas , Hospital Dia/normas , Deficiência Intelectual/terapia , Comportamento Problema/psicologia , Garantia da Qualidade dos Cuidados de Saúde/estatística & dados numéricos , Apoio Social , Adulto , Técnicas de Observação do Comportamento/estatística & dados numéricos , Causalidade , Técnica Delphi , Feminino , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/psicologia , Masculino , Pessoa de Meia-Idade , Psicometria/estatística & dados numéricos , Indicadores de Qualidade em Assistência à Saúde/estatística & dados numéricos , Reprodutibilidade dos Testes , Adulto Jovem
16.
J Intellect Disabil Res ; 57(8): 716-27, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22845772

RESUMO

BACKGROUND: Having an objective means of evaluating the quality of behaviour support plans (BSPs) could assist service providers and statutory authorities to monitor and improve the quality of support provided to people with intellectual disability (ID) who exhibit challenging behaviour. The Behaviour Support Plan Quality Evaluation Guide II (BSP-QEII) was developed to monitor and assess BSPs prepared by teachers to support children with disability in the school system. This study investigated the application of the BSP-QEII to the assessment of BSPs for adults with ID in community support services. METHOD: The inter-rater reliability of the BSP-QEII was assessed. The utility of the BPS-QEII was then investigated with reference to a time series study of matched pairs of BSPs, developed for the same clients over a period of approximately 3 years. Differences in plan quality measured across a number of service and systemic variables were also investigated. RESULTS: The BSP-QEII was found to have good inter-rater reliability and good utility for audit purposes. It was able to discriminate changes in plan quality over time. Differences in plan quality were also evident across different service types, where specialist staff had or had not been involved, and in some instances where a statutory format for the plan had or had not been used. There were no differences between plans developed by government and community sector agencies, nor were there any regional differences across the jurisdiction. CONCLUSIONS: The BSP-QEII could usefully be adopted as an audit tool for measuring the quality of BSPs for adults with ID. In addition to being used for research and administrative auditing, the principles underpinning the BSP-QEII could also be useful to guide policy and educational activities for staff in community based services for adults with ID.


Assuntos
Terapia Comportamental/normas , Hospital Dia/normas , Deficiência Intelectual/terapia , Auditoria Administrativa/estatística & dados numéricos , Comportamento Problema/psicologia , Garantia da Qualidade dos Cuidados de Saúde/estatística & dados numéricos , Melhoria de Qualidade/normas , Apoio Social , Adulto , Técnicas de Observação do Comportamento , Causalidade , Técnica Delphi , Feminino , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/psicologia , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Psicometria/estatística & dados numéricos , Reprodutibilidade dos Testes
17.
Microbiol Resour Announc ; 12(10): e0054223, 2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37747416

RESUMO

A whole genome sequence of a Paenibacillus sp. bacterium isolated from soil in Fort Collins, Colorado was obtained. This bacterium was of particular interest due to its antibiotic potential against Gram-positive pathogen surrogates.

18.
Phys Rev Lett ; 108(25): 253601, 2012 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-23004600

RESUMO

A quantum measurement can be described by a set of matrices, one for each possible outcome, which represents the positive operator-valued measure (POVM) of the sensor. Efficient protocols of POVM extraction for arbitrary sensors are required. We present the first experimental POVM reconstruction that takes explicit advantage of a quantum resource, i.e., nonclassical correlations with an ancillary state. A POVM of a photon-number-resolving detector is reconstructed by using strong quantum correlations of twin beams generated by parametric down-conversion. Our reconstruction method is more statistically robust than POVM reconstruction methods that use classical input states.

19.
Front Immunol ; 13: 850226, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35464424

RESUMO

Glioblastoma is the most common and aggressive form of primary brain cancer, with no improvements in the 5-year survival rate of 4.6% over the past three decades. T-cell-based immunotherapies such as immune-checkpoint inhibitors and chimeric antigen receptor T-cell therapy have prolonged the survival of patients with other cancers and have undergone early-phase clinical evaluation in glioblastoma patients. However, a major challenge for T-cell-based immunotherapy of glioblastoma and other solid cancers is T-cell infiltration into tumours. This process is mediated by chemokine-chemokine receptor and integrin-adhesion molecule interactions, yet the specific nature of the molecules that may facilitate T-cell homing into glioblastoma are unknown. Here, we have characterised chemokine receptor and integrin expression profiles of endogenous glioblastoma-infiltrating T cells, and the chemokine expression profile of glioblastoma-associated cells, by single-cell RNA-sequencing. Subsequently, chemokine receptors and integrins were validated at the protein level to reveal enrichment of receptors CCR2, CCR5, CXCR3, CXCR4, CXCR6, CD49a, and CD49d in glioblastoma-infiltrating T-cell populations relative to T cells in matched patient peripheral blood. Complementary chemokine ligand expression was then validated in glioblastoma biopsies and glioblastoma-derived primary cell cultures. Together, enriched expression of homing receptor-ligand pairs identified in this study implicate a potential role in mediating T-cell infiltration into glioblastoma. Importantly, our data characterising the migratory receptors on endogenous tumour-infiltrating T cells could be exploited to enhance the tumour-homing properties of future T-cell immunotherapies for glioblastoma.


Assuntos
Glioblastoma , Quimiocinas/metabolismo , Glioblastoma/metabolismo , Glioblastoma/terapia , Humanos , Integrinas/metabolismo , Ligantes , Subpopulações de Linfócitos T
20.
J Immunother Cancer ; 10(9)2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36167468

RESUMO

BACKGROUND: Aggressive primary brain tumors such as glioblastoma are uniquely challenging to treat. The intracranial location poses barriers to therapy, and the potential for severe toxicity. Effective treatments for primary brain tumors are limited, and 5-year survival rates remain poor. Immune checkpoint inhibitor therapy has transformed treatment of some other cancers but has yet to significantly benefit patients with glioblastoma. Early phase trials of chimeric antigen receptor (CAR) T-cell therapy in patients with glioblastoma have demonstrated that this approach is safe and feasible, but with limited evidence of its effectiveness. The choices of appropriate target antigens for CAR-T-cell therapy also remain limited. METHODS: We profiled an extensive biobank of patients' biopsy tissues and patient-derived early passage glioma neural stem cell lines for GD2 expression using immunomicroscopy and flow cytometry. We then employed an approved clinical manufacturing process to make CAR- T cells from patients with peripheral blood of glioblastoma and diffuse midline glioma and characterized their phenotype and function in vitro. Finally, we tested intravenously administered CAR-T cells in an aggressive intracranial xenograft model of glioblastoma and used multicolor flow cytometry, multicolor whole-tissue immunofluorescence and next-generation RNA sequencing to uncover markers associated with effective tumor control. RESULTS: Here we show that the tumor-associated antigen GD2 is highly and consistently expressed in primary glioblastoma tissue removed at surgery. Moreover, despite patients with glioblastoma having perturbations in their immune system, highly functional GD2-specific CAR-T cells can be produced from their peripheral T cells using an approved clinical manufacturing process. Finally, after intravenous administration, GD2-CAR-T cells effectively infiltrated the brain and controlled tumor growth in an aggressive orthotopic xenograft model of glioblastoma. Tumor control was further improved using CAR-T cells manufactured with a clinical retroviral vector encoding an interleukin-15 transgene alongside the GD2-specific CAR. These CAR-T cells achieved a striking 50% complete response rate by bioluminescence imaging in established intracranial tumors. CONCLUSIONS: Targeting GD2 using a clinically deployed CAR-T-cell therapy has a sound scientific and clinical rationale as a treatment for glioblastoma and other aggressive primary brain tumors.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Receptores de Antígenos Quiméricos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Gangliosídeos/metabolismo , Glioblastoma/genética , Glioblastoma/terapia , Glioma/metabolismo , Humanos , Inibidores de Checkpoint Imunológico , Interleucina-15/metabolismo , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/metabolismo , Linfócitos T , Ensaios Antitumorais Modelo de Xenoenxerto
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