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1.
Phys Rev Lett ; 129(20): 201801, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36461983

RESUMO

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

2.
Hum Reprod ; 36(9): 2549-2557, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34164665

RESUMO

STUDY QUESTION: Is there is an association between smoking and pregnancy complications in pregnant women with polycystic ovarian syndrome (PCOS)? SUMMARY ANSWER: There is an increased risk of developing gestational diabetes mellitus (GDM) among women with PCOS who smoke. WHAT IS KNOWN ALREADY: Smokers are at increased risk of developing Type 2 Diabetes Mellitus (DM). Given the common pathophysiology and shared risk factors between type 2 DM and GDM, we sought to assess whether an association between smoking and the development of GDM exists. STUDY DESIGN, SIZE, DURATION: This is a retrospective population-based study utilizing data from the HCUP-NIS over 11 years from 2004 to 2014. Pregnant women with PCOS who did smoke were compared to pregnant women with PCOS who did not smoke. A second comparison was made between pregnant smokers with and without PCOS. Of the 443 590 women who smoked during pregnancy and the 14 882 women with PCOS, 631 women were both smokers and diagnosed with PCOS. PARTICIPANTS/MATERIALS, SETTING, METHODS: The Healthcare Cost and Utilization Project-Nationwide Inpatient Sample (HCUP-NIS) is the largest inpatient sample database in the USA and is composed of hospital inpatient stays submitted by hospitals throughout the entire country. Each year, the database provides information relating to 7 million inpatient stays, including patient characteristics, diagnosis and procedures. The data are representative of ∼20% of admissions to US hospitals across 48 states and the District of Columbia. MAIN RESULTS AND THE ROLE OF CHANCE: There were no differences in the risks of preterm delivery (aOR1.2; CI 0.8-1.9), placental abruption (aOR1.1; CI 0.4-3.2), pregnancy induced hypertension (aOR1.0; CI 0.7-1.5), rate of operative vaginal delivery (aOR1.5; CI 0.9-2.5) and rates of cesarean section (C/S) (aOR1.0; CI 0.7-1.3) between smoking and non-smoking women with PCOS. A significant association between smoking and GDM was observed in women with PCOS (aOR1.5; CI1.01-2.1). LIMITATIONS, REASONS FOR CAUTION: The limitations of our study are its retrospective nature and the fact that it relies on an administrative database. Data regarding smoking and PCOS diagnosis could be skewed due to patients' underreporting, lack of documentation and documentation differences. WIDER IMPLICATIONS OF THE FINDINGS: The public health implications of confirming smoking as a risk for GDM among women with PCOS are many. This can lead to earlier screening in pregnancy of smokers for GDM. Earlier initiation of interventions could decrease fetal complications and possibly have an impact on the life and long-term health of the offspring. Future studies are needed in order to assess whether smoking cessation during pregnancy decreases the risk of GDM in that gestation. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used. The authors report no competing interests. TRIAL REGISTRATION NUMBER: N/A.


Assuntos
Diabetes Mellitus Tipo 2 , Síndrome do Ovário Policístico , Cesárea , Feminino , Humanos , Placenta , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/epidemiologia , Gravidez , Estudos Retrospectivos , Fumar/efeitos adversos
3.
BMC Cancer ; 21(1): 1100, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645411

RESUMO

BACKGROUND: Swallowing therapy is commonly provided as a treatment to lessen the risk or severity of dysphagia secondary to radiotherapy (RT) for head and neck cancer (HNC); however, best practice is not yet established. This trial will compare the effectiveness of prophylactic (high and low intensity) versus reactive interventions for swallowing in patients with HNC undergoing RT. METHODS: This multi-site, international randomized clinical trial (RCT) will include 952 adult patients receiving radiotherapy for HNC and who are at high risk for post-RT dysphagia. Participants will be randomized to receive one of three interventions for swallowing during RT: RE-ACTIVE, started promptly if/when dysphagia is identified; PRO-ACTIVE EAT, low intensity prophylactic intervention started before RT commences; or, PRO-ACTIVE EAT+EXERCISE, high intensity prophylactic intervention also started before RT commences. We hypothesize that the PRO-ACTIVE therapies are more effective than late RE-ACTIVE therapy; and, that the more intensive PRO-ACTIVE (EAT + EXERCISE) is superior to the low intensive PRO-ACTIVE (EAT). The primary endpoint of effectiveness is duration of feeding tube dependency one year post radiation therapy, selected as a pragmatic outcome valued equally by diverse stakeholders (e.g., patients, caregivers and clinicians). Secondary outcomes will include objective measures of swallow physiology and function, pneumonia and weight loss, along with various patient-reported swallowing-related outcomes, such as quality of life, symptom burden, and self-efficacy. DISCUSSION: Dysphagia is a common and potentially life-threatening chronic toxicity of radiotherapy, and a priority issue for HNC survivors. Yet, the optimal timing and intensity of swallowing therapy provided by a speech-language pathologist is not known. With no clearly preferred strategy, current practice is fraught with substantial variation. The pragmatic PRO-ACTIVE trial aims to specifically address the decisional dilemma of when swallowing therapy should begin (i.e., before or after a swallowing problem develops). The critical impact of this dilemma is heightened by the growing number of young HNC patients in healthcare systems that need to allocate resources most effectively. The results of the PRO-ACTIVE trial will address the global uncertainty regarding best practice for dysphagia management in HNC patients receiving radiotherapy. TRIAL REGISTRATION: The protocol is registered with the US Patient Centered Outcomes Research Institute, and the PRO-ACTIVE trial was prospectively registered at ClinicalTrials.gov , under the identifier NCT03455608 ; First posted: Mar 6, 2018; Last verified: Jun 17, 2021. Protocol Version: 1.3 (January 27, 2020).


Assuntos
Transtornos de Deglutição/prevenção & controle , Deglutição , Neoplasias de Cabeça e Pescoço/radioterapia , Lesões por Radiação/complicações , Adulto , Tomada de Decisões , Deglutição/fisiologia , Deglutição/efeitos da radiação , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/terapia , Nutrição Enteral/instrumentação , Humanos , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Pneumonite por Radiação , Autoeficácia , Método Simples-Cego , Fatores de Tempo , Redução de Peso
4.
J Ment Health ; 30(2): 179-193, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32310728

RESUMO

BACKGROUND: Our planet is currently experiencing the largest wave of urban growth in history, with 55% of the world's population (4.2 billion people) currently living in urban areas, a figure set to rise to 70% by 2050. Primary care is the first point of treatment for most mental health disorders. Since the urban environment and health are intrinsically linked, it is useful to examine the effectiveness of Nature-Based Solutions in addressing mental health. AIMS: The aim of this scoping review was to examine "How urban green spaces can improve mental health and wellbeing among patients attending general practice and primary care?" METHODS: The scoping review framework comprised a five-stage process developed by Arksey and O'Malley. RESULTS: Twenty-five studies were included in the review, mostly cross-sectional studies. A wide range of mental health outcomes were identified. Out of the 25 included studies, 23 showed positive associations between mental health and green space characteristics. CONCLUSION: Our findings suggest that while green spaces are associated with positive mental health outcomes, most studies were cross-sectional in nature and provided limited evidence for association. Furthermore, the population samples used in most of the studies were taken from national survey data and were not specifically primary care patients. Further studies that assess primary care patients specifically are warranted.


Assuntos
Transtornos Mentais , Saúde Mental/estatística & dados numéricos , Parques Recreativos , População Urbana , Estudos Transversais , Humanos , Transtornos Mentais/epidemiologia , Atenção Primária à Saúde
5.
Phys Rev Lett ; 125(13): 131802, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-33034464

RESUMO

We report the final measurement of the neutrino oscillation parameters Δm_{32}^{2} and sin^{2}θ_{23} using all data from the MINOS and MINOS+ experiments. These data were collected using a total exposure of 23.76×10^{20} protons on target producing ν_{µ} and ν[over ¯]_{µ} beams and 60.75 kt yr exposure to atmospheric neutrinos. The measurement of the disappearance of ν_{µ} and the appearance of ν_{e} events between the Near and Far detectors yields |Δm_{32}^{2}|=2.40_{-0.09}^{+0.08}(2.45_{-0.08}^{+0.07})×10^{-3} eV^{2} and sin^{2}θ_{23}=0.43_{-0.04}^{+0.20}(0.42_{-0.03}^{+0.07}) at 68% C.L. for normal (inverted) hierarchy.

6.
Ann Oncol ; 30(4): 597-603, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30891595

RESUMO

BACKGROUND: Noninvasive genotyping using plasma cell-free DNA (cfDNA) has the potential to obviate the need for some invasive biopsies in cancer patients while also elucidating disease heterogeneity. We sought to develop an ultra-deep plasma next-generation sequencing (NGS) assay for patients with non-small-cell lung cancers (NSCLC) that could detect targetable oncogenic drivers and resistance mutations in patients where tissue biopsy failed to identify an actionable alteration. PATIENTS AND METHODS: Plasma was prospectively collected from patients with advanced, progressive NSCLC. We carried out ultra-deep NGS using cfDNA extracted from plasma and matched white blood cells using a hybrid capture panel covering 37 lung cancer-related genes sequenced to 50 000× raw target coverage filtering somatic mutations attributable to clonal hematopoiesis. Clinical sensitivity and specificity for plasma detection of known oncogenic drivers were calculated and compared with tissue genotyping results. Orthogonal ddPCR validation was carried out in a subset of cases. RESULTS: In 127 assessable patients, plasma NGS detected driver mutations with variant allele fractions ranging from 0.14% to 52%. Plasma ddPCR for EGFR or KRAS mutations revealed findings nearly identical to those of plasma NGS in 21 of 22 patients, with high concordance of variant allele fraction (r = 0.98). Blinded to tissue genotype, plasma NGS sensitivity for de novo plasma detection of known oncogenic drivers was 75% (68/91). Specificity of plasma NGS in those who were driver-negative by tissue NGS was 100% (19/19). In 17 patients with tumor tissue deemed insufficient for genotyping, plasma NGS identified four KRAS mutations. In 23 EGFR mutant cases with acquired resistance to targeted therapy, plasma NGS detected potential resistance mechanisms, including EGFR T790M and C797S mutations and ERBB2 amplification. CONCLUSIONS: Ultra-deep plasma NGS with clonal hematopoiesis filtering resulted in de novo detection of targetable oncogenic drivers and resistance mechanisms in patients with NSCLC, including when tissue biopsy was inadequate for genotyping.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , DNA Tumoral Circulante/genética , Técnicas de Genotipagem/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias Pulmonares/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/antagonistas & inibidores , Carcinogênese/genética , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/isolamento & purificação , Análise Mutacional de DNA , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Humanos , Biópsia Líquida , Pulmão/patologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Estudos Prospectivos , Sensibilidade e Especificidade , Adulto Jovem
7.
Phys Rev Lett ; 123(4): 042502, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31491269

RESUMO

We report the first measurement of the neutron cross section on argon in the energy range of 100-800 MeV. The measurement was obtained with a 4.3-h exposure of the Mini-CAPTAIN detector to the WNR/LANSCE beam at LANL. The total cross section is measured from the attenuation coefficient of the neutron flux as it traverses the liquid argon volume. A set of 2631 candidate interactions is divided in bins of the neutron kinetic energy calculated from time-of-flight measurements. These interactions are reconstructed with custom-made algorithms specifically designed for the data in a time projection chamber the size of the Mini-CAPTAIN detector. The energy averaged cross section is 0.91±0.10(stat)±0.09(syst) b. A comparison of the measured cross section is made to the GEANT4 and FLUKA event generator packages, where the energy averaged cross sections in this range are 0.60 and 0.68 b, respectively.

8.
Phys Rev Lett ; 123(2): 022501, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31386522

RESUMO

We present extractions of the nucleon nonsinglet moments utilizing new precision data on the deuteron F_{2} structure function at large Bjorken-x determined via the Rosenbluth separation technique at Jefferson Lab Experimental Hall C. These new data are combined with a complementary set of data on the proton previously measured in Hall C at similar kinematics and world datasets on the proton and deuteron at lower x measured at SLAC and CERN. The new Jefferson Lab data provide coverage of the upper third of the x range, crucial for precision determination of the higher moments. In contrast to previous extractions, these moments have been corrected for nuclear effects in the deuteron using a new global fit to the deuteron and proton data. The obtained experimental moments represent an order of magnitude improvement in precision over previous extractions using high x data. Moreover, recent exciting developments in lattice QCD calculations provide a first ever comparison of these new experimental results with calculations of moments carried out at the physical pion mass, as well as a new approach that first calculates the quark distributions directly before determining moments.

9.
Br J Anaesth ; 122(3): 361-369, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30770054

RESUMO

BACKGROUND: The aim of this post hoc analysis of a large cohort study was to evaluate the association between night-time surgery and the occurrence of intraoperative adverse events (AEs) and postoperative pulmonary complications (PPCs). METHODS: LAS VEGAS (Local Assessment of Ventilatory Management During General Anesthesia for Surgery) was a prospective international 1-week study that enrolled adult patients undergoing surgical procedures with general anaesthesia and mechanical ventilation in 146 hospitals across 29 countries. Surgeries were defined as occurring during 'daytime' when induction of anaesthesia was between 8:00 AM and 7:59 PM, and as 'night-time' when induction was between 8:00 PM and 7:59 AM. RESULTS: Of 9861 included patients, 555 (5.6%) underwent surgery during night-time. The proportion of patients who developed intraoperative AEs was higher during night-time surgery in unmatched (43.6% vs 34.1%; P<0.001) and propensity-matched analyses (43.7% vs 36.8%; P=0.029). PPCs also occurred more often in patients who underwent night-time surgery (14% vs 10%; P=0.004) in an unmatched cohort analysis, although not in a propensity-matched analysis (13.8% vs 11.8%; P=0.39). In a multivariable regression model, including patient characteristics and types of surgery and anaesthesia, night-time surgery was independently associated with a higher incidence of intraoperative AEs (odds ratio: 1.44; 95% confidence interval: 1.09-1.90; P=0.01), but not with a higher incidence of PPCs (odds ratio: 1.32; 95% confidence interval: 0.89-1.90; P=0.15). CONCLUSIONS: Intraoperative adverse events and postoperative pulmonary complications occurred more often in patients undergoing night-time surgery. Imbalances in patients' clinical characteristics, types of surgery, and intraoperative management at night-time partially explained the higher incidence of postoperative pulmonary complications, but not the higher incidence of adverse events. CLINICAL TRIAL REGISTRATION: NCT01601223.


Assuntos
Plantão Médico/estatística & dados numéricos , Complicações Intraoperatórias/epidemiologia , Pneumopatias/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Operatórios , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Incidência , Internacionalidade , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
10.
JAMA ; 321(23): 2292-2305, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-31157366

RESUMO

Importance: An intraoperative higher level of positive end-expiratory positive pressure (PEEP) with alveolar recruitment maneuvers improves respiratory function in obese patients undergoing surgery, but the effect on clinical outcomes is uncertain. Objective: To determine whether a higher level of PEEP with alveolar recruitment maneuvers decreases postoperative pulmonary complications in obese patients undergoing surgery compared with a lower level of PEEP. Design, Setting, and Participants: Randomized clinical trial of 2013 adults with body mass indices of 35 or greater and substantial risk for postoperative pulmonary complications who were undergoing noncardiac, nonneurological surgery under general anesthesia. The trial was conducted at 77 sites in 23 countries from July 2014-February 2018; final follow-up: May 2018. Interventions: Patients were randomized to the high level of PEEP group (n = 989), consisting of a PEEP level of 12 cm H2O with alveolar recruitment maneuvers (a stepwise increase of tidal volume and eventually PEEP) or to the low level of PEEP group (n = 987), consisting of a PEEP level of 4 cm H2O. All patients received volume-controlled ventilation with a tidal volume of 7 mL/kg of predicted body weight. Main Outcomes and Measures: The primary outcome was a composite of pulmonary complications within the first 5 postoperative days, including respiratory failure, acute respiratory distress syndrome, bronchospasm, new pulmonary infiltrates, pulmonary infection, aspiration pneumonitis, pleural effusion, atelectasis, cardiopulmonary edema, and pneumothorax. Among the 9 prespecified secondary outcomes, 3 were intraoperative complications, including hypoxemia (oxygen desaturation with Spo2 ≤92% for >1 minute). Results: Among 2013 adults who were randomized, 1976 (98.2%) completed the trial (mean age, 48.8 years; 1381 [69.9%] women; 1778 [90.1%] underwent abdominal operations). In the intention-to-treat analysis, the primary outcome occurred in 211 of 989 patients (21.3%) in the high level of PEEP group compared with 233 of 987 patients (23.6%) in the low level of PEEP group (difference, -2.3% [95% CI, -5.9% to 1.4%]; risk ratio, 0.93 [95% CI, 0.83 to 1.04]; P = .23). Among the 9 prespecified secondary outcomes, 6 were not significantly different between the high and low level of PEEP groups, and 3 were significantly different, including fewer patients with hypoxemia (5.0% in the high level of PEEP group vs 13.6% in the low level of PEEP group; difference, -8.6% [95% CI, -11.1% to 6.1%]; P < .001). Conclusions and Relevance: Among obese patients undergoing surgery under general anesthesia, an intraoperative mechanical ventilation strategy with a higher level of PEEP and alveolar recruitment maneuvers, compared with a strategy with a lower level of PEEP, did not reduce postoperative pulmonary complications. Trial Registration: ClinicalTrials.gov Identifier: NCT02148692.


Assuntos
Cuidados Intraoperatórios , Pneumopatias/prevenção & controle , Obesidade/complicações , Respiração com Pressão Positiva/métodos , Complicações Pós-Operatórias/prevenção & controle , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Adulto , Anestesia Geral , Índice de Massa Corporal , Feminino , Humanos , Pneumopatias/etiologia , Masculino , Pessoa de Meia-Idade , Doenças Pleurais/etiologia , Doenças Pleurais/prevenção & controle , Atelectasia Pulmonar/terapia , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/prevenção & controle , Volume de Ventilação Pulmonar , Resultado do Tratamento
11.
Phys Rev Lett ; 121(22): 221801, 2018 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-30547637

RESUMO

The MiniBooNE experiment at Fermilab reports results from an analysis of ν_{e} appearance data from 12.84×10^{20} protons on target in neutrino mode, an increase of approximately a factor of 2 over previously reported results. A ν_{e} charged-current quasielastic event excess of 381.2±85.2 events (4.5σ) is observed in the energy range 200

12.
Phys Rev Lett ; 120(14): 141802, 2018 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-29694148

RESUMO

We report the first measurement of monoenergetic muon neutrino charged current interactions. MiniBooNE has isolated 236 MeV muon neutrino events originating from charged kaon decay at rest (K^{+}→µ^{+}ν_{µ}) at the NuMI beamline absorber. These signal ν_{µ}-carbon events are distinguished from primarily pion decay in flight ν_{µ} and ν[over ¯]_{µ} backgrounds produced at the target station and decay pipe using their arrival time and reconstructed muon energy. The significance of the signal observation is at the 3.9σ level. The muon kinetic energy, neutrino-nucleus energy transfer (ω=E_{ν}-E_{µ}), and total cross section for these events are extracted. This result is the first known-energy, weak-interaction-only probe of the nucleus to yield a measurement of ω using neutrinos, a quantity thus far only accessible through electron scattering.

13.
Br J Anaesth ; 121(4): 899-908, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30236252

RESUMO

BACKGROUND: There is limited information concerning the current practice of intraoperative mechanical ventilation in obese patients, and the optimal ventilator settings for these patients are debated. We investigated intraoperative ventilation parameters and their associations with the development of postoperative pulmonary complications (PPCs) in obese patients. METHODS: We performed a secondary analysis of the international multicentre Local ASsessment of VEntilatory management during General Anesthesia for Surgery' (LAS VEGAS) study, restricted to obese patients, with a predefined composite outcome of PPCs as primary end-point. RESULTS: We analysed 2012 obese patients from 135 hospitals across 29 countries in Europe, North America, North Africa, and the Middle East. Tidal volume was 8.8 [25th-75th percentiles: 7.8-9.9] ml kg-1 predicted body weight, PEEP was 4 [1-5] cm H2O, and recruitment manoeuvres were performed in 7.7% of patients. PPCs occurred in 11.7% of patients and were independently associated with age (P<0.001), body mass index ≥40 kg m-2 (P=0.033), obstructive sleep apnoea (P=0.002), duration of anaesthesia (P<0.001), peak airway pressure (P<0.001), use of rescue recruitment manoeuvres (P<0.05) and routine recruitment manoeuvres performed by bag squeezing (P=0.021). PPCs were associated with an increased length of hospital stay (P<0.001). CONCLUSIONS: Obese patients are frequently ventilated with high tidal volume and low PEEP, and seldom receive recruitment manoeuvres. PPCs increase hospital stay, and are associated with preoperative conditions, duration of anaesthesia and intraoperative ventilation settings. Randomised trials are warranted to clarify the role of different ventilatory parameters in obese patients. CLINICAL TRIAL REGISTRATION: NCT01601223.


Assuntos
Pneumopatias/etiologia , Obesidade/complicações , Obesidade/fisiopatologia , Complicações Pós-Operatórias/etiologia , Respiração Artificial , Anestesia Geral , Índice de Massa Corporal , Peso Corporal , Humanos , Estimativa de Kaplan-Meier , Tempo de Internação , Pneumopatias/epidemiologia , Respiração com Pressão Positiva , Complicações Pós-Operatórias/epidemiologia , Síndromes da Apneia do Sono/complicações , Volume de Ventilação Pulmonar
14.
J Phys Chem A ; 122(36): 7118-7130, 2018 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-30160119

RESUMO

Exposure of sulfonated poly(ether etherketone), SPEEK, in aqueous solutions to 350 nm photons induced reduction of CHCl3 to CH2Cl2 and chloride ions in the presence of HCO2H/HCO2- buffers or poly(vinyl alcohol), PVA. The kinetics of the SPEEK-sensitized photoreaction was characterized by quantum yields of halide ion formation, ϕ(Cl-), evaluated from in situ determinations of [Cl-]. Particularly efficient reductions took place when formate buffers served as H atom donors in the absence of air and with excess CHCl3. The dependence of ϕ(Cl-) on the inverse square root of the light intensity together with postirradiation formation of Cl- in the dark indicated that the CHCl3 photoreduction occurred via a chain process. EPR determinations identified the α-hydroxy radical of SPEEK and •CHCl2 as chain carriers. Most of the kinetic findings were rationalized in terms of a free radical mechanism where dimerizations of the radicals acted as termination steps. Photoreduction of CHCl3 was also detected in the presence of air albeit with lower quantum efficiencies. Observations made during postirradiation experiments indicated that a chain process was also operative under such conditions.

15.
Anaesthesia ; 73 Suppl 1: 25-33, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29313906

RESUMO

Postoperative pulmonary complications are a major determinant of outcome for patients and consume huge resources within hospital, particularly in critical care. Prediction and anticipation of postoperative pulmonary complications are vital for patient selection and, in some cases, for informed patient consent. Being able to assess the likelihood of postoperative pulmonary complications also allows research into methods to reduce them by allowing allocation of patients to the appropriate arms of research trials. Some patients have pre-operative characteristics or belong to patient groups such as those with chronic obstructive pulmonary disease or obstructive sleep apnoea, where techniques and evidence-based guidance to avoid or reduce complications are becoming established. Intra-operative ventilation and the use of lung-protective ventilation may be helpful during major surgery, but studies looking at reduced tidal volumes, recruitment and levels of positive end-expiratory pressure, have this far only led to a degree of consensus in terms of tidal volume, although parameters that predispose to postoperative pulmonary complications are becoming clearer. Optimal postoperative care in terms of analgesia, positioning, physiotherapy and mobilisation is another developing area. Techniques such as continuous positive airways pressure, non-invasive ventilation and high-flow nasal humidified oxygen appear to show some benefit, but the exact roles, pressures and timings of each are currently being explored. Much remains to be researched and developed into evidence-based practice.


Assuntos
Anestesia/efeitos adversos , Transtornos Respiratórios/etiologia , Humanos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/terapia , Transtornos Respiratórios/prevenção & controle , Transtornos Respiratórios/terapia , Respiração Artificial/métodos
16.
Ann Oncol ; 28(3): 512-518, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-27993796

RESUMO

Background: Based upon preclinical synergy in murine models, we carried out a phase I trial to determine the maximum tolerated dose (MTD), toxicities, pharmacokinetics, and biomarkers of response for the combination of BKM120, a PI3K inhibitor, and olaparib, a PARP inhibitor. Patients and methods: Olaparib was administered twice daily (tablet formulation) and BKM120 daily on a 28-day cycle, both orally. A 3 + 3 dose-escalation design was employed with the primary objective of defining the combination MTD, and secondary objectives were to define toxicities, activity, and pharmacokinetic profiles. Eligibility included recurrent breast (BC) or ovarian cancer (OC); dose-expansion cohorts at the MTD were enrolled for each cancer. Results: In total, 69 of 70 patients enrolled received study treatment; one patient never received study treatment because of ineligibility. Twenty-four patients had BC; 46 patients had OC. Thirty-five patients had a germline BRCA mutation (gBRCAm). Two DLTs (grade 3 transaminitis and hyperglycemia) were observed at DL0 (BKM120 60 mg/olaparib and 100 mg b.i.d.). The MTD was determined to be BKM120 50 mg q.d. and olaparib 300 mg b.i.d. (DL8). Additional DLTs included grade 3 depression and transaminitis, occurring early in cycle 2 (DL7). Anticancer activity was observed in BC and OC and in gBRCAm and gBRCA wild-type (gBRCAwt) patients. Conclusions: BKM120 and olaparib can be co-administered, but the combination requires attenuation of the BKM120 dose. Clinical benefit was observed in both gBRCAm and gBRCAwt pts. Randomized phase II studies will be needed to further define the efficacy of PI3K/PARP-inhibitor combinations as compared with a PARP inhibitor alone.


Assuntos
Aminopiridinas/administração & dosagem , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/tratamento farmacológico , Morfolinas/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Ftalazinas/administração & dosagem , Piperazinas/administração & dosagem , Adulto , Idoso , Aminopiridinas/farmacocinética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Relação Dose-Resposta a Droga , Feminino , Mutação em Linhagem Germinativa , Humanos , Pessoa de Meia-Idade , Morfolinas/farmacocinética , Gradação de Tumores , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Inibidores de Fosfoinositídeo-3 Quinase , Ftalazinas/farmacocinética , Piperazinas/farmacocinética , Inibidores de Poli(ADP-Ribose) Polimerases/administração & dosagem , Poli(ADP-Ribose) Polimerases/genética
17.
Phys Rev Lett ; 118(22): 221803, 2017 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-28621993

RESUMO

The MiniBooNE-DM Collaboration searched for vector-boson mediated production of dark matter using the Fermilab 8-GeV Booster proton beam in a dedicated run with 1.86×10^{20} protons delivered to a steel beam dump. The MiniBooNE detector, 490 m downstream, is sensitive to dark matter via elastic scattering with nucleons in the detector mineral oil. Analysis methods developed for previous MiniBooNE scattering results were employed, and several constraining data sets were simultaneously analyzed to minimize systematic errors from neutrino flux and interaction rates. No excess of events over background was observed, leading to a 90% confidence limit on the dark matter cross section parameter, Y=ε^{2}α_{D}(m_{χ}/m_{V})^{4}≲10^{-8}, for α_{D}=0.5 and for dark matter masses of 0.01

18.
Transgenic Res ; 26(4): 567-575, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28534229

RESUMO

Swine are the only livestock species that produce both the second mammalian isoform of gonadotropin-releasing hormone (GNRH2) and its receptor (GNRHR2). Previously, we reported that GNRH2 and GNRHR2 mediate LH-independent testosterone secretion from porcine testes. To further explore this ligand-receptor complex, a pig model with reduced GNRHR2 expression was developed. Small hairpin RNA sequences targeting porcine GNRHR2 were subcloned into a lentiviral-based vector, lentiviral particles were generated and microinjected into the perivitelline space of zygotes, and embryos were transferred into a recipient. One GNRHR2 knockdown (KD) female was born that subsequently produced 80 piglets from 6 litters with 46 hemizygous progeny (57% transgenic). Hemizygous GNRHR2 KD (n = 10) and littermate control (n = 7) males were monitored at 40, 100, 150, 190, 225 and 300 days of age; body weight and testis size were measured and serum was isolated and assayed for testosterone and luteinizing hormone (LH) concentrations. Body weight of GNRHR2 KD boars was not different from littermate controls (P = 0.14), but testes were smaller (P < 0.05; 331.8 vs. 374.8 cm3, respectively). Testosterone concentrations tended (P = 0.06) to be reduced in GNRHR2 KD (1.6 ng/ml) compared to littermate control (4.2 ng/ml) males, but LH levels were similar (P = 0.47). The abundance of GNRHR2 mRNA was reduced (P < 0.001) by 69% in testicular tissue from mature GNRHR2 KD (n = 5) versus littermate control (n = 4) animals. These swine represent the first genetically-engineered model to elucidate the function of GNRH2 and its receptor in mammals.


Assuntos
Animais Geneticamente Modificados/genética , Hormônio Liberador de Gonadotropina/genética , Receptores LHRH/genética , Animais , Animais Geneticamente Modificados/crescimento & desenvolvimento , Feminino , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Hormônio Liberador de Gonadotropina/biossíntese , Hemizigoto , Hormônio Luteinizante/sangue , Masculino , RNA Interferente Pequeno/genética , Receptores LHRH/biossíntese , Suínos/genética , Suínos/crescimento & desenvolvimento , Testículo/crescimento & desenvolvimento , Testículo/metabolismo , Testosterona/sangue
19.
J Phys Chem A ; 121(20): 3918-3928, 2017 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-28489378

RESUMO

Efficient reduction of CCl4 took place upon exposure to 350-nm photons of aqueous solutions containing sulfonated poly(ether etherketone) (SPEEK) as a sensitizer and either poly(vinyl alcohol) (PVA) or HCO2H/HCO2- buffer. The photoreaction formed chloride ions whose concentration increased linearly with time in solutions free of O2, whereas slower reductions occurred in the presence of air. Utilization of formate buffer as the H-atom donor yielded photoreactions at least 10 times faster than those in the presence of PVA and generated CHCl3 as another reaction product. The quantum yield of chloride ion formation, ø(Cl-), was found to be a function of both the SPEEK concentration and concentration of formate buffer. Whereas the quantum efficiency increased steadily with decreasing solution acidity, a drastic surge in the reaction rate occurred in neutral solutions. ø(Cl-) first increased rapidly to a maximum value exceeding 1 at pH 7.3 and then decreased thereafter. The dependence of r(Cl-) on (I0)1/2, where I0 is the light intensity, and the occurrence of postirradiation formation of Cl- through the reduction of CCl4 in the dark are further evidence that the photoreaction proceeded by a chain process. Several of the kinetic features were rationalized by means of a mechanism involving the α-hydroxy radicals of SPEEK and •CCl3 as chain carriers.

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