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1.
Philos Trans A Math Phys Eng Sci ; 382(2271): 20230071, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38522458

RESUMO

We look at what astronomy from the Moon might be like over the next few decades. The Moon offers the possibility of installing large telescopes or interferometers with instruments larger than those on orbiting telescopes. We first present examples of ambitious science cases, in particular ideas that cannot be implemented from Earth. After a general review of observational approaches, from photometry to high contrast and high angular resolution imaging, we propose as a first step a 1-metre-class precursor and explore what science can be done with it. We add a proposal to use the Earth-Moon system to test the quantum physics theory. This article is part of a discussion meeting issue 'Astronomy from the Moon: the next decades (part 2)'.

2.
Int J Mol Sci ; 25(8)2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38674146

RESUMO

Even though some studies have shown possible clinical relationship between molecular subtypes and tumor infiltrating natural killer (NK) cells around tumors, there are few studies showing the clinical relevance of peripheral NK cell activity at diagnosis in female patients with invasive breast cancer. A total of 396 female invasive breast cancer patients who received curative surgical treatment from March 2017 to July 2021 were retrospectively analyzed. NK cell activation-induced interferon-gamma (IFN-γ) secretion measured by enzyme-linked immunosorbent assay was used to measure the activity of peripheral NK cells. Statistical analyses were performed to determine clinical relationships with major clinicopathologic parameters. Quadripartite NK cell activity measured by induced interferon-gamma showed significant relevance with staging and body mass index, and some of the inflammatory serological markers, namely N/L (neutrophil/lymphocyte), P/N (platelet/neutrophil), and P/L (platelet/lymphocyte), showed significantly different NK activity in each interval by univariate analysis. A binary subgroup analysis, setting the IFN-γ secretion cut-off at 100 pg/mL, showed that stage III was significantly increased and axillary lymph node metastasis positivity was increased in the group of IFN-γ < 100 pg/mL, and IFN-γ secretion decreased with an increasing N stage, increased BMI (body mass index), and decreased production of IFN-γ. Following this, the same binary analysis, but with the IFN-γ secretion cut-off at 250 pg/mL, also showed that secretion in stage III was increased in those concentrations with <250 pg/mL, axillary lymph node positivity appeared to be correlated, and BMI ≥ 30 increased in prevalence. Additional ANOVA post hoc tests (Bonferroni) were performed on some serological markers that tended to be somewhat inconsistent. By subgroup analysis with Bonferroni adjustment between the IFN-γ secretion and TNM stage, no significant difference in IFN-γ secretion could be identified at stages I, II, and IV, but at stage III, the IFN-γ secretion < 100 pg/mL was significantly higher than 250 ≤ IFN-γ secretion < 500 pg/mL or IFN-γ secretion ≥ 500 pg/mL. According to this study, stage III was significantly associated with the lowest IFN-γ secretion. Compared to a higher level of IFN-γ secretion, a lower level of IFN-γ secretion seemed to be associated with increased body mass index. Unlike when IFN-γ secretion was analyzed in quartiles, as the IFN-γ secretion fell below 100 pg/mL, the correlation between axillary lymph node positivity and increased N stage, increased BMI, and increased N/L and P/L, which are suggested poor prognostic factors, became more pronounced. We think a peripheral IFN-γ secretion test might be convenient and useful tool for pretreatment risk assessment and selecting probable candidates for further treatment such as immunotherapy in some curable but high-risk invasive breast cancer patients, compared to other costly assaying of tissue NK cell activity at diagnosis.


Assuntos
Neoplasias da Mama , Interferon gama , Células Matadoras Naturais , Estadiamento de Neoplasias , Humanos , Feminino , Interferon gama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/imunologia , Pessoa de Meia-Idade , Células Matadoras Naturais/metabolismo , Células Matadoras Naturais/imunologia , Idoso , Adulto , Estudos Retrospectivos , Índice de Massa Corporal , Metástase Linfática
3.
Sensors (Basel) ; 23(13)2023 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-37447888

RESUMO

Internet of Things (IoT) architectures generally focus on providing consistent performance and reliable communications. The convergence of IoT, edge, fog, and cloud aims to improve the quality of service of applications, which does not typically emphasize energy efficiency. Considering energy in IoT architectures would reduce the energy impact from billions of IoT devices. The research presented in this paper proposes an optimization framework that considers energy consumption of nodes when selecting a node for processing an IoT request in edge-fog-cloud layered architecture. The IoT use cases considered in this paper include smart grid, autonomous vehicles, and eHealth. The proposed framework is evaluated using CPLEX simulations. The results provide insights into mechanisms that can be used to select nodes energy-efficiently whilst meeting the application requirements and other network constraints in multi-layered IoT architectures.


Assuntos
Conservação de Recursos Energéticos , Internet das Coisas , Veículos Autônomos , Comunicação , Sistemas Computacionais
4.
Int J Mol Sci ; 23(5)2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-35269680

RESUMO

The anticancer effects of ruxolitinib and calcitriol against breast cancer were reported previously. However, the effect of ruxolitinib and calcitriol combination treatment on various molecular subtypes of breast cancer remains unexplored. In this study, we used MCF-7, SKBR3, and MDA-MB-468 cells to investigate the effect of ruxolitinib and calcitriol combination treatment on cell proliferation, apoptosis, cell cycle, and cell signaling markers, in vitro and in vivo. Our results revealed the synergistic anticancer effect of ruxolitinib and calcitriol combination treatment in SKBR3 and MDA-MB-468 cells, but not in MCF-7 cells in vitro, via cell proliferation inhibition, apoptosis induction, cell cycle arrest, and the alteration of cell signaling protein expression, including cell cycle-related (cyclin D1, CDK1, CDK4, p21, and p27), apoptosis-related (c-caspase and c-PARP), and cell proliferation-related (c-Myc, p-p53, and p-JAK2) proteins. Furthermore, in the MDA-MB-468 xenograft mouse model, we demonstrated the synergistic antitumor effect of ruxolitinib and calcitriol combination treatment, including the alteration of c-PARP, cyclin D1, and c-Myc expression, without significant drug toxicity. The combination exhibited a synergistic effect in HER2-enriched and triple-negative breast cancer subtypes. In conclusion, our results suggest different effects of the combination treatment of ruxolitinib and calcitriol depending on the molecular subtype of breast cancer.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Animais , Apoptose , Neoplasias da Mama/metabolismo , Calcitriol/farmacologia , Calcitriol/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células , Ciclina D1 , Feminino , Humanos , Camundongos , Nitrilas , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Pirazóis , Pirimidinas , Neoplasias de Mama Triplo Negativas/patologia
5.
Philos Trans A Math Phys Eng Sci ; 379(2188): 20200187, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33222650

RESUMO

We address three major questions in astronomy, namely the detection of biosignatures on habitable exoplanets, the geophysics of exoplanets and cosmology. To achieve this goal, two requirements are needed: (i) a very large aperture to detect spectro-polarimetric and spatial features of faint objects such as exoplanets, (ii) continuous monitoring to characterize the temporal behaviour of exoplanets such as rotation period, meteorology and seasons. An Earth-based telescope is not suited for continuous monitoring and the atmosphere limits the ultimate angular resolution and spectro-polarimetrical domain. Moreover, a space telescope in orbit is limited in aperture, to perhaps 15 m over many decades. This is why we propose an OWL-class lunar telescope with a 50-100 m aperture for visible and IR astronomy, based on ESO's Overwhelmingly Large Telescope concept, unachievable on Earth for technical issues such as wind stress that are not relevant for a lunar platform. It will be installed near the south pole of the Moon to allow continuous target monitoring. The low gravity of the Moon will facilitate its building and manoeuvring, compared to Earth-based telescopes. We introduce a new original idea: such a large lunar telescope will allow Intensity Interferometric measurements when coupled with large Earth-based telescopes, leading to picosecond angular resolution. Rather than going into all details, our objective is essentially to inject new ideas and give a kind of roadmap. In particular, the choice of a final location will have to find a compromise between the cool temperature of craters at the Moon South Pole and the visibility of Earth for some science objectives. This article is part of a discussion meeting issue 'Astronomy from the Moon: the next decades'.

6.
Sensors (Basel) ; 20(19)2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33023036

RESUMO

Continuous delivery has gained increased popularity in industry as a development approach to develop, test, and deploy enhancements to software components in short development cycles. In order for continuous delivery to be effectively adopted, the services that a component depends upon must be readily available to software engineers in order to systematically apply quality assurance techniques. However, this may not always be possible as (i) these requisite services may have limited access and (ii) defects that are introduced in a component under development may cause ripple effects in real deployment environments. Service virtualisation (SV) has been introduced as an approach to address these challenges, but existing approaches to SV still fall short of delivering the required accuracy and/or ease-of-use to virtualise services for adoption in continuous delivery. In this work, we propose a novel machine learning based approach to predict numeric fields in virtualised responses, extending existing research that has provided a way to produce values for categorical fields. The SV approach introduced here uses machine learning techniques to derive values of numeric fields that are based on a variable number of pertinent historic messages. Our empirical evaluation demonstrates that the Cognitive SV approach can produce responses with the appropriate fields and accurately predict values of numeric fields across three data sets, some of them based on stateful protocols.

7.
Ann Surg Oncol ; 26(9): 2952-2958, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31264119

RESUMO

BACKGROUND: Multifocal papillary thyroid microcarcinoma (PTMC) has been associated with poor outcomes; however, we often encounter pathologically confirmed unilateral multifocal PTMC after surgery. To date, no consensus on the proper surgical extent for patients with this form of PTMC has been reported. OBJECTIVE: The aim of this study was to analyze the effect of the type of surgical treatment on disease recurrence in patients with unilateral multifocal PTMC. METHODS: We retrospectively analyzed data from 255 patients with unilateral, multifocal, node-negative PTMC between March 1999 and December 2012. We evaluated two groups of patients: those who underwent unilateral lobectomy (Group I, n = 127) and those who underwent total thyroidectomy (Group II, n = 128). During the follow-up period, which lasted a median of 94.8 months, we assessed locoregional recurrence (LRR). RESULTS: There was no statistically significant difference between the two groups with regard to LRR at follow-up (3.15% for Group I vs. 0.78% for Group II; p = 0.244). The association between the type of surgical treatment and LRR remained nonsignificant after adjusting for potential confounders such as age, tumor size, microscopic extrathyroidal extension, and lymphovascular invasion (p = 0.115). During follow-up, the incidence of transient hypocalcemia (0% vs. 8.6%; p = 0.001) and vocal fold paralysis (1.6% vs. 9.4%; p = 0.011) was higher in Group II than in Group I. CONCLUSIONS: Even though randomized controlled trials are the only option to obtain a definitive answer to this question, unilateral lobectomy may be a safe operative option for selected patients with unilateral, multifocal, node-negative PTMC.


Assuntos
Carcinoma Papilar/cirurgia , Recidiva Local de Neoplasia/diagnóstico , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/classificação , Tireoidectomia/mortalidade , Adulto , Idoso , Carcinoma Papilar/patologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Prognóstico , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Neoplasias da Glândula Tireoide/patologia
8.
Nature ; 461(7264): 621-6, 2009 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-19759536

RESUMO

Many anti-infectives inhibit the synthesis of bacterial proteins, but none selectively inhibits their degradation. Most anti-infectives kill replicating pathogens, but few preferentially kill pathogens that have been forced into a non-replicating state by conditions in the host. To explore these alternative approaches we sought selective inhibitors of the proteasome of Mycobacterium tuberculosis. Given that the proteasome structure is extensively conserved, it is not surprising that inhibitors of all chemical classes tested have blocked both eukaryotic and prokaryotic proteasomes, and no inhibitor has proved substantially more potent on proteasomes of pathogens than of their hosts. Here we show that certain oxathiazol-2-one compounds kill non-replicating M. tuberculosis and act as selective suicide-substrate inhibitors of the M. tuberculosis proteasome by cyclocarbonylating its active site threonine. Major conformational changes protect the inhibitor-enzyme intermediate from hydrolysis, allowing formation of an oxazolidin-2-one and preventing regeneration of active protease. Residues outside the active site whose hydrogen bonds stabilize the critical loop before and after it moves are extensively non-conserved. This may account for the ability of oxathiazol-2-one compounds to inhibit the mycobacterial proteasome potently and irreversibly while largely sparing the human homologue.


Assuntos
Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/enzimologia , Inibidores de Proteases/farmacologia , Inibidores de Proteassoma , Domínio Catalítico/efeitos dos fármacos , Humanos , Ligação de Hidrogênio , Cinética , Modelos Moleculares , Mycobacterium tuberculosis/crescimento & desenvolvimento , Oxazolidinonas/metabolismo , Oxazolidinonas/farmacologia , Inibidores de Proteases/química , Complexo de Endopeptidases do Proteassoma/química , Complexo de Endopeptidases do Proteassoma/metabolismo , Carbonilação Proteica/efeitos dos fármacos , Conformação Proteica/efeitos dos fármacos , Subunidades Proteicas , Especificidade por Substrato , Tiazóis/farmacologia , Treonina/metabolismo
9.
J Org Chem ; 79(3): 867-79, 2014 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-24437451

RESUMO

High-level electronic structure calculations, including a continuum treatment of solvent, are employed to elucidate and quantify the effects of alkyl halide structure on the barriers of SN2 and E2 reactions. In cases where such comparisons are available, the results of these calculations show close agreement with solution experimental data. Structural factors investigated include α- and ß-methylation, adjacency to unsaturated functionality (allyl, benzyl, propargyl, α to carbonyl), ring size, and α-halogenation and cyanation. While the influence of these factors on SN2 reactivity is mostly well-known, the present study attempts to provide a broad comparison of both SN2 and E2 reactivity across many cases using a single methodology, so as to quantify relative reactivity trends. Despite the fact that most organic chemistry textbooks say far more about how structure affects SN2 reactions than about how it affects E2 reactions, the latter are just as sensitive to structural variation as are the former. This sensitivity of E2 reactions to structure is often underappreciated.

10.
Oncol Lett ; 28(2): 390, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38966583

RESUMO

Continued advances in the diagnosis and treatment of breast cancer (BC) have led to an increase in the number of long-term BC survivors and an increase in the incidence of metachronous BC in the contralateral breast. Therefore, it is important to understand the factors that influence the development of metachronous BC; however, the impact of the laterality of the initial ipsilateral (I)BC as a risk factor for the development of metachronous contralateral (MC)BC has not been extensively investigated. The present study included 17,082 female patients with stage 0-3 IBC from the prospectively maintained Korean Breast Cancer Registry from 1989-2013 and divided them into two groups: Patients with MCBC (n=88) and those without MCBC (n=16,994). Risk factors that present at the initial BC diagnosis that could significantly influence the development of MCBC were screened for and risks were evaluated using the Fine-Gray subdistribution hazard model. Significant differences in baseline characteristics between MCBC and non-MCBC groups were demonstrated. Patients aged <40 years, those with histological and nuclear grade 3 tumors, and those with the triple-negative BC subtype were significantly more prevalent in the MCBC group than in the non-MCBC group. Additionally, the cumulative incidence of MCBC increased over time, with a notable increase from 0.1% in year 1 to 1.6% in year 10. Survival analysis revealed no significant differences in overall or BC-specific survival between the two groups. Key predictive factors identified for MCBC included an age of <40 years at initial diagnosis, a negative progesterone receptor status, and a Ki-67 score of >14%. Overall, the present study revealed several factors associated with MCBC and emphasized the need for long-term monitoring of BC survivors, considering these newly identified risk factors.

11.
Life (Basel) ; 14(5)2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38792629

RESUMO

INTRODUCTION: Non-infectious erythema, or Red Breast Syndrome (RBS), has been observed on the skin where acellular dermal matrix was implanted, although the exact cause is yet to be determined. PATIENTS AND METHODS: A total of 214 female patients underwent breast-conserving surgery (BCS) and volume replacement using diced acellular dermal matrix (dADM) for breast cancer between December 2017 and December 2018. After collecting and evaluating relevant clinical data, inflammation markers, along with NK cell status presented by IFN-γ secretion assay, were measured using ELISA. RESULTS: Nineteen patients (8.88%) presented with RBS after BCS and dADM use. A significant increase of platelet-to-lymphocyte ratio was noted in the non-RBS group (p = 0.02). Compared to the RBS group (p = 0.042), the WBC level of the non-RBS group showed significant decrease over time. Eosinophil counts increased significantly at follow-up but went up higher in the RBS group. Multivariate analysis showed preoperative chemotherapy significantly increased the hazard of RBS (OR 3.274, p = 0.047 and OR 17.098, p < 0.001, respectively). DISCUSSION: Though no causal relationship between RBS and immune status was proven, the results suggest an association between preoperative chemotherapy and RBS in addition to the possible role of eosinophilia in leading to eosinophilic dermatoses, which warrants further exploration and elucidation.

12.
J Pharm Sci ; 110(10): 3457-3463, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34126114

RESUMO

A new polymorphic form (Form C) of enantiopure Baclofen was isolated and characterized. Crystal structures of R-Baclofen Form A and Form C were resolved from powder diffraction data, and cell parameters by profile matching for Form B. The relative stability of these three forms is proposed based on structural data, thermal analyses and solvent-mediated conversions. The experiments highlight the stability order A < C < B at 25 °C (A is the most stable form), whereas above 180 °C it would likely be: C < A < B (C being the stable modification). Moreover, a new heterosolvate of the molecule is observed in N,N-DMF/water mixture. This heterosolvate offers a new pathway to isolate pure R-Baclofen Form B provided the lactam impurity does not exceed 3%. Upon mechanical stress Form B tends to evolve to Form C.


Assuntos
Baclofeno , Varredura Diferencial de Calorimetria , Cristalização , Difração de Pó , Difração de Raios X
13.
Sci Rep ; 10(1): 4149, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-32139743

RESUMO

Following recent tsunamis, most studies have focused on the onshore deposits, while the offshore backwash deposits, crucial for a better understanding of the hydrodynamic processes during such events and offering an opportunity for sedimentary archives of past tsunamis, have mostly been omitted. Here, we present a unique sedimentary record of the backwash from two historical tsunamis sampled in a sheltered bay in American Samoa, namely the 2009 South Pacific Tsunami and the 1960 Great Chilean Earthquake Tsunami. Although not always concomitant with a marked grain size change, backwash deposits are identified by terrestrial geochemical and mineralogical signatures, associated with basal soft sediment micro-deformations. These micro-deformations, including asymmetric flame structures, are described for the first time in historic shallow marine backwash deposits and lead us to propose an improved depositional mechanism for tsunami backflow based on hyperpycnal currents. Moreover, this study brings a potential new criterion to the proxy toolkit for identifying tsunami backwash deposits, namely the basal soft sediment micro-deformations. We suggest that further studies focus on these micro-deformations in order to test the representability of this criterion for tsunami backwash deposits. Sheltered shallow marine environments in areas repeatedly impacted by tsunamis have a higher potential for the reconstruction of paleo-tsunami catalogs and should be preferentially investigated for coastal risk assessment.

14.
J Breast Cancer ; 23(3): 259-267, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32595988

RESUMO

PURPOSE: Neoadjuvant chemotherapy (NAC) involving trastuzumab markedly increases pathologic complete response (pCR) rates in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer. Despite increasing pCR rates, long-term survival gains are controversial owing to distinctive biologic behavior mediated by the presence of hormonal receptors (HRs) that may interact with HER2 receptors. We, therefore, investigated the differences in relative survival gain provided by neoadjuvant trastuzumab-based chemotherapy on HR positive (HR+) status of patients. METHODS: We retrospectively analyzed women with stage II or III HER2+ breast cancer who underwent NAC followed by a breast cancer surgery between 2008 and 2013. The survival benefits of adding trastuzumab to NAC were analyzed by classifying patients into HR+ and HR negative (HR-) groups. RESULTS: Of 666 patients included in the study, 374 (52.1%) were HR+ and 319 (47.9%) were HR-. In the HR+ group, trastuzumab treatment led to higher pCR rates and significantly better breast cancer specific survival (BCSS) and overall survival (OS) than no trastuzumab treatment. However, among patients with HR- breast cancer, trastuzumab treatment showed no statistically significant difference between BCSS and OS following multivariate analysis. CONCLUSION: We found that the addition of trastuzumab to NAC improved relative survival benefit in HER2+/HR+ patients than in HER2+/HR- patients, even though the pCR rate increases were lower. Although pCR has been regarded as a surrogate marker for estimating long-term survival benefits after NAC, it alone may not translate into real long-term oncologic outcomes in particular cancer subtypes after trastuzumab-based NAC. Further longer-term evaluation of the objective survival benefit after NAC driven by a dual HER2 block according to HR status is warranted.

15.
Mult Scler Relat Disord ; 43: 102146, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32498033

RESUMO

BACKGROUND: Relapsing-remitting multiple sclerosis (RRMS) is frequently diagnosed in women of reproductive age. Because the use of disease-modifying therapies (DMTs) early in the disease course is increasing, it is important to evaluate the safety of DMTs in pregnant women and their developing fetuses. Alemtuzumab, approved for the treatment of relapsing forms of MS, is administered as 2 courses of 12 mg/day on 5 consecutive days at baseline and on 3 consecutive days 12 months later. Alemtuzumab is eliminated from the body within approximately 30 days after administration; it is recommended that women of childbearing potential use effective contraception during and for 4 months after treatment. Here, we report pregnancy outcomes in alemtuzumab-treated women from the phase 2 and 3 clinical development program over 16 years. METHODS: We followed 972 women who had alemtuzumab in phase 2 (CAMMS223 [NCT00050778]) and phase 3 (CARE-MS I [NCT00530348], CARE-MS II [NCT00548405]) studies, and/or in 2 consecutive extension studies (NCT00930553; NCT02255656 [TOPAZ]). In the extension studies, patients could receive additional alemtuzumab (12 mg/day on 3 days; ≥12 months apart) as needed for disease activity. All women who received alemtuzumab in the clinical development program were included. Pregnant or lactating patients were followed up for safety. RESULTS: As of November 26, 2018, 264 pregnancies occurred in 160 alemtuzumab-treated women, with a mean age at conception of 32.6 years, and mean time from last alemtuzumab dose to conception of 35.9 months. Of the 264 pregnancies, 233 (88%) were completed, 11 (4%) were ongoing, and 20 (8%) had unknown outcomes; 16 (6%) conceptions occurred within 4 months, and 5 conceptions within 1 month of the last alemtuzumab dose. Of the 233 completed pregnancies with known outcomes, there were 155 (67%) live births with no congenital abnormalities or birth defects, 52 (22%) spontaneous abortions, 25 (11%) elective abortions, and 1 (0.4%) stillbirth. Maternal age was associated with an increased risk of spontaneous abortion in alemtuzumab-treated patients (<35 years: 15%; ≥35 years: 37%; relative risk [RR], 2.46 [95% CI: 1.53-3.95], p=0.0002). Risk of spontaneous abortion was not increased in patients becoming pregnant ≤4 months versus >4 months since alemtuzumab exposure (19% vs 23%; RR, 1.08 [95% CI: 0.41-2.85], p=0.88). Autoimmune thyroid adverse events did not increase risk for spontaneous abortion (patients with vs without thyroid adverse events, 23.7% vs 21.3%; RR, 1.11 [95% CI: 0.69-1.80], p=0.75). Annualized relapse rate was 0.10 and 0.12 in the 2 years prior to pregnancy (post alemtuzumab), and was 0.22, 0.12, and 0.12 in each of the first 3 years postpartum, respectively. CONCLUSION: Normal live births were the most common outcome in women exposed to alemtuzumab 12 mg or 24 mg in clinical studies. Spontaneous abortion rate in alemtuzumab-treated patients was comparable with rates in the general population and treatment-naive MS patients, and was not increased in women with pregnancy onset within 4 months of alemtuzumab exposure. There was a minimal increase in postpartum relapses.


Assuntos
Alemtuzumab , Antineoplásicos Imunológicos , Esclerose Múltipla Recidivante-Remitente , Resultado da Gravidez , Aborto Espontâneo , Adulto , Alemtuzumab/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Feminino , Humanos , Lactação , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Gravidez , Recidiva
16.
Sci Am ; 304(3): 20, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21438481
17.
Astrobiology ; 2(2): 153-81, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12469366

RESUMO

The major goals of NASA's Terrestrial Planet Finder (TPF) and the European Space Agency's Darwin missions are to detect terrestrial-sized extrasolar planets directly and to seek spectroscopic evidence of habitable conditions and life. Here we recommend wavelength ranges and spectral features for these missions. We assess known spectroscopic molecular band features of Earth, Venus, and Mars in the context of putative extrasolar analogs. The preferred wavelength ranges are 7-25 microns in the mid-IR and 0.5 to approximately 1.1 microns in the visible to near-IR. Detection of O2 or its photolytic product O3 merits highest priority. Liquid H2O is not a bioindicator, but it is considered essential to life. Substantial CO2 indicates an atmosphere and oxidation state typical of a terrestrial planet. Abundant CH4 might require a biological source, yet abundant CH4 also can arise from a crust and upper mantle more reduced than that of Earth. The range of characteristics of extrasolar rocky planets might far exceed that of the Solar System. Planetary size and mass are very important indicators of habitability and can be estimated in the mid-IR and potentially also in the visible to near-IR. Additional spectroscopic features merit study, for example, features created by other biosignature compounds in the atmosphere or on the surface and features due to Rayleigh scattering. In summary, we find that both the mid-IR and the visible to near-IR wavelength ranges offer valuable information regarding biosignatures and planetary properties; therefore both merit serious scientific consideration for TPF and Darwin.


Assuntos
Astronomia , Meio Ambiente Extraterreno , Planetas , Fenômenos Astronômicos , Planeta Terra , Marte , Oxigênio , Ozônio , Sistema Solar , Voo Espacial , Espectrofotometria Infravermelho , Vênus
18.
Astrobiology ; 10(1): 77-88, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20307184

RESUMO

After Earth's origin, our host star, the Sun, was shining 20-25% less brightly than today. Without greenhouse-like conditions to warm the atmosphere, our early planet would have been an ice ball, and life may never have evolved. But life did evolve, which indicates that greenhouse gases must have been present on early Earth to warm the planet. Evidence from the geological record indicates an abundance of the greenhouse gas CO(2). CH(4) was probably present as well; and, in this regard, methanogenic bacteria, which belong to a diverse group of anaerobic prokaryotes that ferment CO(2) plus H(2) to CH(4), may have contributed to modification of the early atmosphere. Molecular oxygen was not present, as is indicated by the study of rocks from that era, which contain iron carbonate rather than iron oxide. Multicellular organisms originated as cells within colonies that became increasingly specialized. The development of photosynthesis allowed the Sun's energy to be harvested directly by life-forms. The resultant oxygen accumulated in the atmosphere and formed the ozone layer in the upper atmosphere. Aided by the absorption of harmful UV radiation in the ozone layer, life colonized Earth's surface. Our own planet is a very good example of how life-forms modified the atmosphere over the planets' lifetime. We show that these facts have to be taken into account when we discover and characterize atmospheres of Earth-like exoplanets. If life has originated and evolved on a planet, then it should be expected that a strong co-evolution occurred between life and the atmosphere, the result of which is the planet's climate.


Assuntos
Atmosfera/química , Clima , Evolução Planetária , Sistema Solar , Oxigênio/química , Ozônio/química , Fotossíntese , Planetas , Luz Solar , Raios Ultravioleta
19.
Astrobiology ; 10(1): 89-102, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20307185

RESUMO

We discuss how to read a planet's spectrum to assess its habitability and search for the signatures of a biosphere. After a decade rich in giant exoplanet detections, observation techniques have advanced to a level where we now have the capability to find planets of less than 10 Earth masses (M(Earth)) (so-called "super Earths"), which may be habitable. How can we characterize those planets and assess whether they are habitable? This new field of exoplanet search has shown an extraordinary capacity to combine research in astrophysics, chemistry, biology, and geophysics into a new and exciting interdisciplinary approach to understanding our place in the Universe. The results of a first-generation mission will most likely generate an amazing scope of diverse planets that will set planet formation, evolution, and our planet into an overall context.


Assuntos
Planetas
20.
Astrobiology ; 10(1): 103-12, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20307186

RESUMO

We present and discuss the criteria for selecting potential target stars suitable for the search for Earth-like planets, with a special emphasis on the stellar aspects of habitability. Missions that search for terrestrial exoplanets will explore the presence and habitability of Earth-like exoplanets around several hundred nearby stars, mainly F, G, K, and M stars. The evaluation of the list of potential target systems is essential in order to develop mission concepts for a search for terrestrial exoplanets. Using the Darwin All Sky Star Catalogue (DASSC), we discuss the selection criteria, configuration-dependent subcatalogues, and the implication of stellar activity for habitability.


Assuntos
Planetas
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