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1.
Nat Immunol ; 15(1): 98-108, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24292363

RESUMO

Dendritic cells (DCs) that orchestrate mucosal immunity have been studied in mice. Here we characterized human gut DC populations and defined their relationship to previously studied human and mouse DCs. CD103(+)Sirpα(-) DCs were related to human blood CD141(+) DCs and to mouse intestinal CD103(+)CD11b(-) DCs and expressed markers of cross-presenting DCs. CD103(+)Sirpα(+) DCs aligned with human blood CD1c(+) DCs and mouse intestinal CD103(+)CD11b(+) DCs and supported the induction of regulatory T cells. Both CD103(+) DC subsets induced the TH17 subset of helper T cells, while CD103(-)Sirpα(+) DCs induced the TH1 subset of helper T cells. Comparative analysis of transcriptomes revealed conserved transcriptional programs among CD103(+) DC subsets and identified a selective role for the transcriptional repressors Bcl-6 and Blimp-1 in the specification of CD103(+)CD11b(-) DCs and intestinal CD103(+)CD11b(+) DCs, respectively. Our results highlight evolutionarily conserved and divergent programming of intestinal DCs.


Assuntos
Diferenciação Celular/imunologia , Células Dendríticas/imunologia , Mucosa Intestinal/imunologia , Transcriptoma/imunologia , Animais , Antígenos CD/imunologia , Antígenos CD/metabolismo , Antígenos CD1/imunologia , Antígenos CD1/metabolismo , Antígeno CD11b/imunologia , Antígeno CD11b/metabolismo , Diferenciação Celular/genética , Células Cultivadas , Análise por Conglomerados , Apresentação Cruzada/genética , Apresentação Cruzada/imunologia , Células Dendríticas/metabolismo , Citometria de Fluxo , Glicoproteínas/imunologia , Glicoproteínas/metabolismo , Humanos , Cadeias alfa de Integrinas/imunologia , Cadeias alfa de Integrinas/metabolismo , Integrinas/genética , Integrinas/imunologia , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Microscopia Confocal , Análise de Sequência com Séries de Oligonucleotídeos , Receptores de Quimiocinas/genética , Receptores de Quimiocinas/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Transcriptoma/genética
2.
Nature ; 587(7835): 588-593, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33239800

RESUMO

The quantum spin properties of nitrogen-vacancy defects in diamond enable diverse applications in quantum computing and communications1. However, fluorescent nanodiamonds also have attractive properties for in vitro biosensing, including brightness2, low cost3 and selective manipulation of their emission4. Nanoparticle-based biosensors are essential for the early detection of disease, but they often lack the required sensitivity. Here we investigate fluorescent nanodiamonds as an ultrasensitive label for in vitro diagnostics, using a microwave field to modulate emission intensity5 and frequency-domain analysis6 to separate the signal from background autofluorescence7, which typically limits sensitivity. Focusing on the widely used, low-cost lateral flow format as an exemplar, we achieve a detection limit of 8.2 × 10-19 molar for a biotin-avidin model, 105 times more sensitive than that obtained using gold nanoparticles. Single-copy detection of HIV-1 RNA can be achieved with the addition of a 10-minute isothermal amplification step, and is further demonstrated using a clinical plasma sample with an extraction step. This ultrasensitive quantum diagnostics platform is applicable to numerous diagnostic test formats and diseases, and has the potential to transform early diagnosis of disease for the benefit of patients and populations.


Assuntos
Técnicas Biossensoriais/métodos , Diagnóstico Precoce , Infecções por HIV/diagnóstico , Infecções por HIV/virologia , HIV-1/genética , Nanodiamantes/química , RNA Viral/sangue , Avidina/química , Técnicas Biossensoriais/instrumentação , Biotina/química , Fluorescência , Ouro/química , HIV-1/isolamento & purificação , Humanos , Limite de Detecção , Nanopartículas Metálicas/química , Microfluídica/instrumentação , Microfluídica/métodos , Micro-Ondas , Técnicas de Amplificação de Ácido Nucleico , Papel , Plasma/virologia , Teoria Quântica , Sensibilidade e Especificidade , Imagem Individual de Molécula , Temperatura
3.
Phys Rev Lett ; 132(13): 130602, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38613262

RESUMO

Quantum computing requires a universal set of gate operations; regarding gates as rotations, any rotation angle must be possible. However a real device may only be capable of B bits of resolution, i.e., it might support only 2^{B} possible variants of a given physical gate. Naive discretization of an algorithm's gates to the nearest available options causes coherent errors, while decomposing an impermissible gate into several allowed operations increases circuit depth. Conversely, demanding higher B can greatly complexify hardware. Here, we explore an alternative: probabilistic angle interpolation (PAI). This effectively implements any desired, continuously parametrized rotation by randomly choosing one of three discretized gate settings and postprocessing individual circuit outputs. The approach is particularly relevant for near-term applications where one would in any case average over many runs of circuit executions to estimate expected values. While PAI increases that sampling cost, we prove that (a) the approach is optimal in the sense that PAI achieves the least possible overhead and (b) the overhead is remarkably modest even with thousands of parametrized gates and only seven bits of resolution available. This is a profound relaxation of engineering requirements for first generation quantum computers where even 5-6 bits of resolution may suffice and, as we demonstrate, the approach is many orders of magnitude more efficient than prior techniques. Moreover we conclude that, even for more mature late noisy intermediate-scale quantum era hardware, no more than nine bits will be necessary.

4.
Perfusion ; 39(3): 631-634, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36715461

RESUMO

The potential for increased rates of morbidity of SARS-CoV-2 within immunocompromised populations has been of concern since the pandemic's onset. Transplant providers and patients can face particularly challenging situations, in the current settings as data continues to emerge for the prevention and treatment of the immunocompromised subpopulation. This case report details a patient 9-months post orthotopic heart transplant that developed SARS-CoV-2 infection despite two prior doses of the Pfizer-BioNtech COVID-19 vaccine, and had successful rescue from refractory hypoxemia with veno-venous extracorporeal membrane oxygenation (VV ECLS).


Assuntos
COVID-19 , Transplante de Coração , Síndrome do Desconforto Respiratório , Humanos , SARS-CoV-2 , Vacina BNT162 , Síndrome do Desconforto Respiratório/terapia
5.
J Allergy Clin Immunol ; 149(2): 767-781.e6, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34331993

RESUMO

BACKGROUND: The thymus is a glandular organ that is essential for the formation of the adaptive immune system by educating developing T cells. The thymus is most active during childhood and involutes around the time of adolescence, resulting in a severe reduction or absence of naive T-cell output. The ability to generate a patient-derived human thymus would provide an attractive research platform and enable the development of novel cell therapies. OBJECTIVES: This study sought to systematically evaluate signaling pathways to develop a refined direct differentiation protocol that generates patient-derived thymic epithelial progenitor cells from multiple induced pluripotent stem cells (iPSCs) that can further differentiate into functional patient-derived thymic epithelial cells on transplantation into athymic nude mice. METHODS: Directed differentiation of iPSC generated TEPs that were transplanted into nude mice. Between 14 and 19 weeks posttransplantation, grafts were removed and analyzed by flow cytometry, quantitative PCR, bulk RNA sequencing, and single-cell RNA sequencing for markers of thymic-cell and T-cell development. RESULTS: A direct differentiation protocol that allows the generation of patient-derived thymic epithelial progenitor cells from multiple iPSC lines is described. On transplantation into athymic nude mice, patient-derived thymic epithelial progenitor cells further differentiate into functional patient-derived thymic epithelial cells that can facilitate the development of T cells. Single-cell RNA sequencing analysis of iPSC-derived grafts shows characteristic thymic subpopulations and patient-derived thymic epithelial cell populations that are indistinguishable from TECs present in primary neonatal thymus tissue. CONCLUSIONS: These findings provide important insights and resources for researchers focusing on human thymus biology.


Assuntos
Células-Tronco Pluripotentes Induzidas/citologia , Linfócitos T/fisiologia , Timo/citologia , Animais , Diferenciação Celular , Células Cultivadas , Células Epiteliais/citologia , Células Epiteliais/fisiologia , Humanos , Camundongos , Análise de Sequência de RNA , Timo/fisiologia
6.
Phys Rev Lett ; 129(11): 117701, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36154421

RESUMO

Impurity spins in crystal matrices are promising components in quantum technologies, particularly if they can maintain their spin properties when close to surfaces and material interfaces. Here, we investigate an attractive candidate for microwave-domain applications, the spins of group-VI ^{125}Te^{+} donors implanted into natural Si at depths as shallow as 20 nm. We show that surface band bending can be used to ionize such near-surface Te to spin-active Te^{+} state, and that optical illumination can be used further to control the Te donor charge state. We examine spin activation yield, spin linewidth, and relaxation (T_{1}) and coherence times (T_{2}) and show how a zero-field 3.5 GHz "clock transition" extends spin coherence times to over 1 ms, which is about an order of magnitude longer than other near-surface spin systems.

7.
J Card Surg ; 37(8): 2450-2452, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35650659

RESUMO

Acute respiratory distress syndrome (ARDS) following left ventricular assist device (LVAD) implantation is a rare complication. Venovenous (VV) extracorporeal membrane oxygenation (ECMO) is used as a treatment for severe ARDS and pneumonia. We report the successful use of VV ECMO for ARDS Klebsiella pneumonia following urgent LVAD HeartMate 3 implantation.


Assuntos
Oxigenação por Membrana Extracorpórea , Síndrome do Desconforto Respiratório , Procedimentos Cirúrgicos Torácicos , Humanos , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/terapia
8.
J Card Surg ; 37(3): 685-687, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35103350

RESUMO

Cardiac transplant remains the gold-standard treatment for end-stage heart failure more than 50 years after the procedure was first pioneered. The number of transplant operations performed annually has been limited by the global imbalance of donor organs to recipients. This imbalance helped fuel the development of left ventricular assist devices (LVADs) first as a bridge to cardiac transplant and subsequently as destination therapy. Driveline infection is one of several problems that continue to plague LVADs through several generations of improvement. We present a patient with an infected LVAD driveline exit site that progressed to mediastinitis, pericardial and pump infection. The device was explanted, and the patient supported with an axillary Impella 5.0 as a bridge until the time of transplant. An Impella 5.0 (or 5.5) can be used as an intermediate tool to be able to explant an infected LVAD, with mediastinitis, allowing the patient to clear the infection, and prepare the patient for transplant free of infection. METHODS: The patient consented to the study and case report. The patient signed an informed consent and permission for publication.


Assuntos
Transplante de Coração , Coração Auxiliar , Humanos
9.
Surg Endosc ; 35(10): 5705-5708, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-32968922

RESUMO

BACKGROUND: The American Society for Metabolic and Bariatric Surgery has released a Bariatric Surgical Risk/Benefit Calculator, an online tool with which patients and providers can input patient preoperative information and predict their 1-year weight loss. We seek to validate our institutional data with the national database and investigated patient factors that influence lack of treatment effect after bariatric surgery. MATERIALS AND METHODS: A retrospective review of all prospectively collected data of bariatric surgeries performed at Yale New Haven Hospital from 2017 to 2018 was conducted. By entering data into the MBSAQIP Calculator, the 1-year predicted Body Mass Index was calculated and compared to the actual weight loss. Statistical analysis was performed using an unpaired t-test with Welch's correction (Prism 8, GraphPad). RESULTS: The average difference between the actual and predicted weight loss at 1-year for 327 patients was 3.6 BMI points. When the actual weight loss was compared to predicted BMI at 1 year, a high correlation was found (R = 0.6, P = 0.003). We examined the outliers with a comparison of weight loss for those patients who's BMI fell within 5 points of the predicted versus those whose BMI recorded above 5. It was discovered those patients who had higher than 5 BMI points than predicted, had higher preoperative BMI (46.1 vs 43.6, P = 0.008). CONCLUSIONS: The MBSAQIP calculator is a useful tool to guide surgeons with decision-making and informed consent. Our institution's 1-year weight loss data correlated closely with that predicted. From the outliers, we found that patients who did not meet the predicted weight loss had significantly higher preoperative BMI. This may alter preoperative discussions with class 3 or over obese patients regarding expected weight loss and warrant investigations with the national database to develop modifications of the calculator.


Assuntos
Cirurgia Bariátrica , Obesidade Mórbida , Índice de Massa Corporal , Humanos , Obesidade , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Medição de Risco , Resultado do Tratamento , Redução de Peso
10.
Vet Ophthalmol ; 24 Suppl 1: 39-49, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32946201

RESUMO

OBJECTIVE: To assess whether preoperative gonioscopy status is associated with the development of postoperative glaucoma after phacoemulsification. PROCEDURE: Eligible dogs and eyes were selected from medical records (2007-2017), and each eye was classified as having normal or abnormal gonioscopy status. Records were examined for postoperative glaucoma, and data were collected for baseline variables including patient signalment, surgical factors, and pre, intra, and postoperative medications. RESULTS: Of 305 dogs (505 eyes) selected for review in this study, 111 dogs (163 eyes) had abnormal gonioscopy findings, and 194 dogs (342 eyes) had normal gonioscopy findings. Postoperative glaucoma occurred in 24% (39/163) of eyes with abnormal gonioscopy and in 14% (49/342) eyes with normal gonioscopy. Eyes with abnormal gonioscopy status were at higher risk of postoperative glaucoma compared to normal eyes (P = .025). There was no important confounding due to the numerous baseline variables summarised above. Regardless of gonioscopy status, the risk of glaucoma was highest during the first 2 months after surgery. CONCLUSIONS: Eyes with abnormal gonioscopy findings are at increased risk of postoperative glaucoma compared with eyes with normal gonioscopy findings. Gonioscopy is recommended as a part of presurgical assessment in all dogs prior to phacoemulsification. Further study is needed to assess whether the incidence of postoperative glaucoma can be reduced by increased monitoring or altered treatment protocols in cases that are known to have abnormal gonioscopy findings prior to cataract surgery.


Assuntos
Catarata/veterinária , Doenças do Cão/cirurgia , Glaucoma/veterinária , Gonioscopia/veterinária , Facoemulsificação/veterinária , Complicações Pós-Operatórias/veterinária , Animais , Catarata/complicações , Cães , Feminino , Glaucoma/etiologia , Masculino , Facoemulsificação/efeitos adversos , Estudos Retrospectivos , Fatores de Risco
11.
Nano Lett ; 20(10): 7123-7128, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-32946244

RESUMO

We investigate gate-induced quantum dots in silicon nanowire field-effect transistors fabricated using a foundry-compatible fully depleted silicon-on-insulator (FD-SOI) process. A series of split gates wrapped over the silicon nanowire naturally produces a 2 × n bilinear array of quantum dots along a single nanowire. We begin by studying the capacitive coupling of quantum dots within such a 2 × 2 array and then show how such couplings can be extended across two parallel silicon nanowires coupled together by shared, electrically isolated, "floating" electrodes. With one quantum dot operating as a single-electron-box sensor, the floating gate serves to enhance the charge sensitivity range, enabling it to detect charge state transitions in a separate silicon nanowire. By comparing measurements from multiple devices, we illustrate the impact of the floating gate by quantifying both the charge sensitivity decay as a function of dot-sensor separation and configuration within the dual-nanowire structure.

12.
Ann Surg ; 272(2): 220-226, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32675485

RESUMO

OBJECTIVE: To develop and evaluate a novel instrument to measure SEVERE processes using video data. BACKGROUND: Surgical video data can serve an important role in understanding the relationship between intraoperative events and postoperative outcomes. However, a standard tool to measure severity of intraoperative events is not yet available. METHODS: Items to be included in the instrument were identified through literature and video reviews. A committee of experts guided item reduction, including pilot tests and revisions, and determined weighted scores. Content validity was evaluated using a validated sensibility questionnaire. Inter-rater reliability was assessed by calculating intraclass correlation coefficient. Construct validity was evaluated on a sample of 120 patients who underwent laparoscopic Roux-en-Y gastric bypass procedure, in which comprehensive video data was obtained. RESULTS: SEVERE index measures severity of 5 event types using ordinal scales. Each intraoperative event is given a weighted score out of 10. Inter-rater reliability was excellent [0.87 (95%-confidence interval, 0.77-0.92)]. In a sample of consecutive 120 patients undergoing gastric bypass procedures, a median of 12 events [interquartile range (IQR) 9-18] occurred per patient and bleeding was the most frequent type (median 10, IQR 7-14). The median SEVERE score per case was 11.3 (IQR 8.3-16.9). In risk-adjusted multivariable regression models, history of previous abdominal surgery (P = 0.02) and body mass index (P = 0.005) were associated with SEVERE scores, demonstrating construct validity evidence. CONCLUSION: The SEVERE index may prove to be a useful instrument in identifying patients with high risk of developing postoperative complications.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/métodos , Endoscopia Gastrointestinal/métodos , Complicações Intraoperatórias/diagnóstico , Monitorização Intraoperatória/métodos , Complicações Pós-Operatórias/prevenção & controle , Gravação em Vídeo , Centros Médicos Acadêmicos , Adulto , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Perda Sanguínea Cirúrgica/prevenção & controle , Estudos de Coortes , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Endoscopia Gastrointestinal/efeitos adversos , Feminino , Humanos , Complicações Intraoperatórias/prevenção & controle , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Variações Dependentes do Observador , Ontário , Projetos Piloto , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/fisiopatologia , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Medição de Risco , Resultado do Tratamento
13.
Ann Surg ; 272(6): e316-e320, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33086321

RESUMO

OBJECTIVE: The outcomes of patients treated on the COVID-minimal pathway were evaluated during a period of surging COVID-19 hospital admissions, to determine the safety of continuing to perform urgent operations during the pandemic. SUMMARY OF BACKGROUND DATA: Crucial treatments were delayed for many patients during the COVID-19 pandemic, over concerns for hospital-acquired COVID-19 infections. To protect cancer patients whose survival depended on timely surgery, a "COVID-minimal pathway" was created. METHODS: Patients who underwent a surgical procedure on the pathway between April and May 2020 were evaluated. The "COVID-minimal surgical pathway" consisted of: (A) evolving best-practices in COVID-19 transmission-reduction, (B) screening patients and staff, (C) preoperative COVID-19 patient testing, (D) isolating pathway patients from COVID-19 patients. Patient status through 2 weeks from discharge was determined as a reflection of hospital-acquired COVID-19 infections. RESULTS: After implementation, pathway screening processes excluded 7 COVID-19-positive people from interacting with pathway (4 staff and 3 patients). Overall, 122 patients underwent 125 procedures on pathway, yielding 83 admissions (42 outpatient procedures). The median age was 64 (56-79) and 57% of patients were female. The most common surgical indications were cancer affecting the uterus, genitourinary tract, colon, lung or head and neck. The median length of admission was 3 days (1-6). Repeat COVID-19 testing performed on 27 patients (all negative), including 9 patients evaluated in an emergency room and 8 readmitted patients. In the postoperative period, no patient developed a COVID-19 infection. CONCLUSIONS: A COVID-minimal pathway comprised of physical space modifications and operational changes may allow urgent cancer treatment to safely continue during the COVID-19 pandemic, even during the surge-phase.


Assuntos
COVID-19/prevenção & controle , COVID-19/transmissão , Procedimentos Clínicos/organização & administração , Infecção Hospitalar/prevenção & controle , Tratamento de Emergência , SARS-CoV-2 , Gestão da Segurança/organização & administração , Centro Cirúrgico Hospitalar/organização & administração , Procedimentos Cirúrgicos Operatórios , Idoso , COVID-19/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
Phys Rev Lett ; 125(13): 137702, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-33034472

RESUMO

We show experimentally and describe theoretically how a conventional magnetic resonance Hahn echo sequence can lead to a self-stimulated pulse echo train when an inhomogeneously broadened spin ensemble is coupled to a resonator. Effective strong coupling between the subsystems assures that the first Hahn echo can act as a refocusing pulse on the spins, leading to self-stimulated secondary echoes. Within the framework of mean field theory, we show that this process can continue multiple times leading to a train of echoes. We introduce an analytical model that explains the shape of the first echo and numerical results that account well for the experimentally observed shape and strength of the echo train and provides insights into the collective effects involved.

15.
Anesth Analg ; 131(2): 411-448, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32467512

RESUMO

This consensus statement presents a comprehensive and evidence-based set of guidelines for the care of postoperative nausea and vomiting (PONV) in both adult and pediatric populations. The guidelines are established by an international panel of experts under the auspices of the American Society of Enhanced Recovery and Society for Ambulatory Anesthesia based on a comprehensive search and review of literature up to September 2019. The guidelines provide recommendation on identifying high-risk patients, managing baseline PONV risks, choices for prophylaxis, and rescue treatment of PONV as well as recommendations for the institutional implementation of a PONV protocol. In addition, the current guidelines focus on the evidence for newer drugs (eg, second-generation 5-hydroxytryptamine 3 [5-HT3] receptor antagonists, neurokinin 1 (NK1) receptor antagonists, and dopamine antagonists), discussion regarding the use of general multimodal PONV prophylaxis, and PONV management as part of enhanced recovery pathways. This set of guidelines have been endorsed by 23 professional societies and organizations from different disciplines (Appendix 1).Guidelines currently available include the 3 iterations of the consensus guideline we previously published, which was last updated 6 years ago; a guideline published by American Society of Health System Pharmacists in 1999; a brief discussion on PONV management as part of a comprehensive postoperative care guidelines; focused guidelines published by the Society of Obstetricians and Gynecologists of Canada, the Association of Paediatric Anaesthetists of Great Britain & Ireland and the Association of Perianesthesia Nursing; and several guidelines published in other languages.The current guideline was developed to provide perioperative practitioners with a comprehensive and up-to-date, evidence-based guidance on the risk stratification, prevention, and treatment of PONV in both adults and children. The guideline also provides guidance on the management of PONV within enhanced recovery pathways.The previous consensus guideline was published 6 years ago with a literature search updated to October 2011. Several guidelines, which have been published since, are either limited to a specific populations or do not address all aspects of PONV management. The current guideline was developed based on a systematic review of the literature published up through September 2019. This includes recent studies of newer pharmacological agents such as the second-generation 5-hydroxytryptamine 3 (5-HT3) receptor antagonists, a dopamine antagonist, neurokinin 1 (NK1) receptor antagonists as well as several novel combination therapies. In addition, it also contains an evidence-based discussion on the management of PONV in enhanced recovery pathways. We have also discussed the implementation of a general multimodal PONV prophylaxis in all at-risk surgical patients based on the consensus of the expert panel.


Assuntos
Consenso , Gerenciamento Clínico , Náusea e Vômito Pós-Operatórios/terapia , Guias de Prática Clínica como Assunto/normas , Acetaminofen/administração & dosagem , Administração Intravenosa , Analgésicos não Narcóticos/administração & dosagem , Antieméticos/administração & dosagem , Humanos , Náusea e Vômito Pós-Operatórios/diagnóstico
16.
World Dev ; 136: 105132, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32836692

RESUMO

In the context of the major potential impacts of COVID-19 on agriculture and agricultural trade in developing countries, this Viewpoint discusses the advantages of adopting a conceptual framework previously used to discuss the impact of the HIV/AIDS pandemic on agriculture and rural livelihoods. The framework is made up of two pairs of linked concepts: 1) Susceptibility or the chance of an individual becoming infected; 2) Resistance or the ability of an individual to avoid infection; 3) Vulnerability or the likelihood of significant impacts occurring at individual, household or community level; and 4) Resilience: the active responses that enable people to avoid the worst impacts of an epidemic at different levels or to recover faster to a level accepted as normal. This framework allows the clear formulation of key questions for COVID-19: factors in the labor process itself that make people more or less susceptible; broader socio-economic and biophysical determinants of susceptibility; factors that make farm households, food enterprises and value chains more vulnerable to the impacts of the pandemic; and aspects of COVID-19 responses by governments and the private sector that might increase vulnerability. Brief examples of susceptibility of value chain operations and of their vulnerability to COVID-19 lockdown measures are given. A focus on resistance and resilience encourages investigation of local-level responses by communities and NGOs, which with appropriate monitoring and learning could be scaled up.

17.
Mol Carcinog ; 58(3): 398-410, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30378175

RESUMO

Wnt pathway activation maintains the cancer stem cell (CSC) phenotype and promotes tumor progression, making it an attractive target for anti-cancer therapy. Wnt signaling at the tumor and tumor microenvironment (TME) front have not been investigated in depth in head and neck squamous cell carcinoma (HNSCC). In a cohort of 48 HNSCCs, increased Wnt signaling, including Wnt genes (AXIN2, LGR6, WISP1) and stem cell factors (RET, SOX5, KIT), were associated with a more advanced clinical stage. Key Wnt pathway proteins were most abundant at the cancer epithelial-stromal boundary. To investigate these observations, we generated three pairs of cancer-cancer associated fibroblast (CAF) cell lines derived from the same HNSCC patients. 3D co-culture of cancer spheres and CAFs mimicked these in vivo interactions, and using these we observed increased expression of Wnt genes (eg, WNT3A, WNT7A, WNT16) in both compartments. Of these Wnt ligands, we found Wnt3a, and less consistently Wnt16, activated Wnt signaling in both cancer cells and CAFs. Wnt activation increased CSC characteristics like sphere formation and invasiveness, which was further regulated by the presence of CAFs. Time lapse microscopy also revealed preferential Wnt activation of cancer cells. Wnt inhibitors, OMP-18R5 and OMP-54F28, significantly reduced growth of HNSCC patient-derived xenografts and suppressed Wnt activation at the tumor epithelial-stromal boundary. Taken together, our findings suggest that Wnt signaling is initiated in cancer cells which then activate CAFs, and in turn perpetuate a paracrine signaling loop. This suggests that targeting Wnt signaling in the TME is essential.


Assuntos
Carcinoma de Células Escamosas/patologia , Comunicação Celular , Neoplasias de Cabeça e Pescoço/patologia , Células-Tronco Neoplásicas/patologia , Microambiente Tumoral , Via de Sinalização Wnt , Animais , Apoptose , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Proliferação de Células , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Camundongos , Camundongos Nus , Invasividade Neoplásica , Células-Tronco Neoplásicas/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
18.
J Surg Res ; 236: 345-351, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30694776

RESUMO

BACKGROUND: Previous studies have demonstrated that ethnic minority patients experience significant metabolic improvements after bariatric surgery but less so than non-Hispanic whites. Previous research has primarily investigated differences between non-Hispanic white and black patients. Thus, there remains a need to assess differences in diabetic outcomes among other ethnic groups, including Hispanic and Asian patient populations. MATERIALS AND METHODS: A retrospective analysis including 650 patients with type II diabetes mellitus (T2DM), who underwent either laparoscopic Roux-en-Y gastric bypass or laparoscopic sleeve gastrectomy (LSG) procedures, was conducted to understand ethnic disparities in diabetic metabolic outcomes, including weight loss, serum concentrations of glucose, fasting insulin, and hemoglobin A1c (HbA1c). Data were from a single academic institution in northern California. Ethnicity data were self reported. T2DM was defined as having one or more of the following criteria: a fasting glucose concentration >125 mg/dL, HbA1c >6.5%, or taking one or more diabetic oral medications. Diabetes resolution was defined as having a fasting glucose <125 mg/dL, a HbA1c <6.5%, and discontinuation of diabetic oral medications. RESULTS: Within-group comparisons in all ethnic groups showed significant reductions in body mass index, body weight, fasting insulin, fasting glucose, and HbA1c by 6 mo, but Asian patients did not experience further improvement in body mass index or diabetic outcomes at the 12-mo visit. Black patients did not experience additional reductions in fasting insulin or glucose between the 6- and 12-mo visit and their HbA1c significantly increased. Nevertheless, the majority of patients had diabetes remission by the 12-mo postoperative visit (98%, 97%, 98%, and 92% in Non-Hispanic, Hispanic, black, and Asian, respectively). CONCLUSIONS: The results of this study demonstrate that bariatric surgery serves as an effective treatment for normalizing glucose metabolism among patients with T2DM. However, this study suggests that additional interventions that support black and Asian patients with achieving similar metabolic outcomes as non-Hispanic white and Hispanic patients warrant further consideration.


Assuntos
Cirurgia Bariátrica , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Disparidades nos Níveis de Saúde , Obesidade Mórbida/cirurgia , Adolescente , Adulto , Idoso , Glicemia/análise , Diabetes Mellitus Tipo 2/etnologia , Diabetes Mellitus Tipo 2/etiologia , Etnicidade/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Grupos Minoritários/estatística & dados numéricos , Obesidade Mórbida/complicações , Obesidade Mórbida/metabolismo , Seleção de Pacientes , Estudos Retrospectivos , Resultado do Tratamento , Redução de Peso/etnologia , Adulto Jovem
19.
Value Health ; 22(5): 580-586, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31104738

RESUMO

OBJECTIVES: Laparoscopic metabolic surgery (MxS) can lead to remission of type 2 diabetes (T2D); however, treatment response to MxS can be heterogeneous. Here, we demonstrate an open-source predictive analytics platform that applies machine-learning techniques to a common data model; we develop and validate a predictive model of antihyperglycemic medication cessation (validated proxy for A1c control) in patients with treated T2D who underwent MxS. METHODS: We selected patients meeting the following criteria in 2 large US healthcare claims databases (Truven Health MarketScan Commercial [CCAE]; Optum Clinformatics [Optum]): underwent MxS between January 1, 2007, to October 1, 2013 (first = index); aged ≥18 years; continuous enrollment 180 days pre-index (baseline) to 730 days postindex; baseline T2D diagnosis and treatment. The outcome was no antihyperglycemic medication treatment from 365 to 730 days after MxS. A regularized logistic regression model was trained using the following candidate predictor categories measured at baseline: demographics, conditions, medications, measurements, and procedures. A 75% to 25% split of the CCAE group was used for model training and testing; the Optum group was used for external validation. RESULTS: 13 050 (CCAE) and 3477 (Optum) patients met the study inclusion criteria. Antihyperglycemic medication cessation rates were 72.9% (CCAE) and 70.8% (Optum). The model possessed good internal discriminative accuracy (area under the curve [AUC] = 0.778 [95% CI = 0.761-0.795] in CCAE test set N = 3527) and transportability (external AUC = 0.759 [95% CI = 0.741-0.777] in Optum N = 3477). CONCLUSION: The application of machine learning techniques to real-world healthcare data can yield useful predictive models to assist patient selection. In future practice, establishment of prerequisite technological infrastructure will be needed to implement such models for real-world decision support.


Assuntos
Cirurgia Bariátrica , Revisão da Utilização de Seguros/estatística & dados numéricos , Aprendizado de Máquina , Bases de Dados Factuais/estatística & dados numéricos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade
20.
Nature ; 496(7445): 334-8, 2013 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-23598342

RESUMO

Detection of nuclear spin precession is critical for a wide range of scientific techniques that have applications in diverse fields including analytical chemistry, materials science, medicine and biology. Fundamentally, it is possible because of the extreme isolation of nuclear spins from their environment. This isolation also makes single nuclear spins desirable for quantum-information processing, as shown by pioneering studies on nitrogen-vacancy centres in diamond. The nuclear spin of a (31)P donor in silicon is very promising as a quantum bit: bulk measurements indicate that it has excellent coherence times and silicon is the dominant material in the microelectronics industry. Here we demonstrate electrical detection and coherent manipulation of a single (31)P nuclear spin qubit with sufficiently high fidelities for fault-tolerant quantum computing. By integrating single-shot readout of the electron spin with on-chip electron spin resonance, we demonstrate quantum non-demolition and electrical single-shot readout of the nuclear spin with a readout fidelity higher than 99.8 percent-the highest so far reported for any solid-state qubit. The single nuclear spin is then operated as a qubit by applying coherent radio-frequency pulses. For an ionized (31)P donor, we find a nuclear spin coherence time of 60 milliseconds and a one-qubit gate control fidelity exceeding 98 percent. These results demonstrate that the dominant technology of modern electronics can be adapted to host a complete electrical measurement and control platform for nuclear-spin-based quantum-information processing.

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