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1.
Nature ; 620(7975): 813-823, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37558877

RESUMO

Twenty-five years since foundational publications on valuing ecosystem services for human well-being1,2, addressing the global biodiversity crisis3 still implies confronting barriers to incorporating nature's diverse values into decision-making. These barriers include powerful interests supported by current norms and legal rules such as property rights, which determine whose values and which values of nature are acted on. A better understanding of how and why nature is (under)valued is more urgent than ever4. Notwithstanding agreements to incorporate nature's values into actions, including the Kunming-Montreal Global Biodiversity Framework (GBF)5 and the UN Sustainable Development Goals6, predominant environmental and development policies still prioritize a subset of values, particularly those linked to markets, and ignore other ways people relate to and benefit from nature7. Arguably, a 'values crisis' underpins the intertwined crises of biodiversity loss and climate change8, pandemic emergence9 and socio-environmental injustices10. On the basis of more than 50,000 scientific publications, policy documents and Indigenous and local knowledge sources, the Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES) assessed knowledge on nature's diverse values and valuation methods to gain insights into their role in policymaking and fuller integration into decisions7,11. Applying this evidence, combinations of values-centred approaches are proposed to improve valuation and address barriers to uptake, ultimately leveraging transformative changes towards more just (that is, fair treatment of people and nature, including inter- and intragenerational equity) and sustainable futures.


Assuntos
Ecossistema , Justiça Ambiental , Política Ambiental , Objetivos , Desenvolvimento Sustentável , Humanos , Biodiversidade , Desenvolvimento Sustentável/economia , Política Ambiental/economia , Mudança Climática
2.
Prehosp Emerg Care ; 28(2): 405-412, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-36857200

RESUMO

OBJECTIVE: Early recognition of traumatic brain injury (TBI) is important to facilitate time-sensitive care. Electroencephalography (EEG) can identify TBI, but feasibility of EEG has not been evaluated in prehospital settings. We tested the feasibility of obtaining single-channel EEG during air medical transport after trauma. We measured association between quantitative EEG features, early blood biomarkers, and abnormalities on head computerized tomography (CT). METHODS: We performed a pilot prospective, observational study enrolling consecutive patients transported by critical care air ambulance from the scene of trauma to a Level I trauma center. During transport, prehospital clinicians placed a sensor on the patient's forehead to record EEG. We reviewed EEG waveforms and selected 90 seconds of recording for quantitative analysis. EEG data processing included fast Fourier transform to summarize component frequency power in the delta (0-4 Hz), theta (4-8 Hz), and alpha (8-13 Hz) ranges. We collected blood samples on day 1 and day 3 post-injury and measured plasma levels of two brain injury biomarkers (ubiquitin C-terminal hydrolase L1 [UCH-L1] and glial fibrillary acidic protein [GFAP]). We compared predictors between individuals with and without CT-positive TBI findings. RESULTS: Forty subjects were enrolled, with EEG recordings successfully obtained in 34 (85%). Reasons for failure included uncharged battery (n = 5) and user error (n = 1). Data were lost in three cases. Of 31 subjects with data, interpretable EEG signal was recorded in 26 (84%). Mean age was 48 (SD 16) years, 79% were male, and 50% suffered motor vehicle crashes. Eight subjects (24%) had CT-positive TBI. Subjects with and without CT-positive TBI had similar median delta power, alpha power, and theta power. UCH-L1 and GFAP plasma levels did not differ across groups. Delta power inversely correlated with UCH-L1 day 1 plasma concentration (r = -0.60, p = 0.03). CONCLUSIONS: Prehospital EEG acquisition is feasible during air transport after trauma.


Assuntos
Resgate Aéreo , Lesões Encefálicas Traumáticas , Serviços Médicos de Emergência , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Prospectivos , Ubiquitina Tiolesterase , Lesões Encefálicas Traumáticas/diagnóstico , Estudos de Coortes , Biomarcadores , Estudos Observacionais como Assunto
3.
Am J Emerg Med ; 75: 197.e1-197.e3, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37945412

RESUMO

We describe a case of a young male who presented to the emergency department with unilateral eye pain, blurred vision, conjunctival injection, and ocular pH of 9, one day after direct ocular exposure to palytoxin (PTX) from coral in a home saltwater fish tank. Although uncommon, ocular PTX toxicity is a potentially vision-threatening condition that requires prompt recognition. This case report documents the successful management of presumed ocular PTX exposure and suggests additional workup and treatment considerations for future patients.


Assuntos
Antozoários , Venenos de Cnidários , Animais , Humanos , Masculino , Venenos de Cnidários/toxicidade , Acrilamidas/toxicidade , Face
4.
Artigo em Inglês | MEDLINE | ID: mdl-38758056

RESUMO

OBJECTIVE: Identification of biomarkers of cognitive recovery after traumatic brain injury (TBI) will inform care and improve outcomes. This study assessed the utility of neurofilament (NF-L and pNF-H), a marker of neuronal injury, informing cognitive performance following moderate-to-severe TBI (msTBI). SETTING: Level 1 trauma center and outpatient via postdischarge follow-up. PARTICIPANTS: N = 94. Inclusion criteria: Glasgow Coma Scale score less than 13 or 13-15 with clinical evidence of moderate-to-severe injury traumatic brain injury on clinical imaging. Exclusion criteria: neurodegenerative condition, brain death within 3 days after injury. DESIGN: Prospective observational study. Blood samples were collected at several time points post-injury. Cognitive testing was completed at 6 months post-injury. MAIN MEASURES: Serum NF-L (Human Neurology 4-Plex B) pNF-H (SR-X) as measured by SIMOA Quanterix assay. Divided into 3 categorical time points at days post-injury (DPI): 0-15 DPI, 16-90 DPI, and >90 DPI. Cognitive composite comprised executive functioning measures derived from 3 standardized neuropsychological tests (eg, Delis-Kaplan Executive Function System: Verbal Fluency, California Verbal Learning Test, Second Edition, Wechsler Adult Intelligence Scale, Third Edition). RESULTS: pNF-H at 16-90 DPI was associated with cognitive outcomes including a cognitive-executive composite score at 6 months (ß = -.430, t34 = -3.190, P = .003). CONCLUSIONS: Results suggest that "subacute" elevation of serum pNF-H levels may be associated with protracted/poor cognitive recovery from msTBI and may be a target for intervention. Interpretation is limited by small sample size and including only those who were able to complete cognitive testing.

5.
Br J Psychiatry ; 223(6): 533-541, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38108319

RESUMO

BACKGROUND: Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed. AIMS: To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au. METHOD: This phase 3, double-blind, randomised, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand. Participants received twice-weekly subcutaneous racemic ketamine or midazolam for 4 weeks. Initially, the trial tested fixed-dose ketamine 0.5 mg/kg versus midazolam 0.025 mg/kg (cohort 1). Dosing was revised, after a Data Safety Monitoring Board recommendation, to flexible-dose ketamine 0.5-0.9 mg/kg or midazolam 0.025-0.045 mg/kg, with response-guided dosing increments (cohort 2). The primary outcome was remission (Montgomery-Åsberg Rating Scale for Depression score ≤10) at the end of week 4. RESULTS: The final analysis (those who received at least one treatment) comprised 68 in cohort 1 (fixed-dose), 106 in cohort 2 (flexible-dose). Ketamine was more efficacious than midazolam in cohort 2 (remission rate 19.6% v. 2.0%; OR = 12.1, 95% CI 2.1-69.2, P = 0.005), but not different in cohort 1 (remission rate 6.3% v. 8.8%; OR = 1.3, 95% CI 0.2-8.2, P = 0.76). Ketamine was well tolerated. Acute adverse effects (psychotomimetic, blood pressure increases) resolved within 2 h. CONCLUSIONS: Adequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period. The subcutaneous route is practical and feasible.


Assuntos
Transtorno Depressivo Resistente a Tratamento , Ketamina , Humanos , Ketamina/efeitos adversos , Depressão , Midazolam/efeitos adversos , Austrália , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico
6.
Am J Emerg Med ; 72: 221.e1-221.e3, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37648591

RESUMO

Allergic reactions to Crotalidae polyvalent immune Fab and Crotalidae immune F(ab')2 are uncommon but potentially life-threatening. It is unknown whether cross-reactivity reactions exist between these two antivenoms. We report a case of a patient who suffered anaphylaxis from Crotalidae polyvalent immune Fab but subsequently was safely administered Crotalidae immune F(ab')2 after a presumed Agkistrodon contortix (copperhead) envenomation. This single case supports the safety of Crotalidae immune F(ab')2 administration in patients with a history of anaphylaxis to Crotalidae polyvalent immune Fab treatment.


Assuntos
Agkistrodon , Anafilaxia , Humanos , Animais , Cavalos , Anafilaxia/induzido quimicamente , Anafilaxia/tratamento farmacológico , Antivenenos/efeitos adversos , Fragmentos Fab das Imunoglobulinas/efeitos adversos , Pacientes
7.
Brain Inj ; 37(4): 356-371, 2023 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-36628484

RESUMO

OBJECTIVE: This scoping review aimed to summarize the existing knowledge base on the pharmacological management of neuropsychiatric symptoms in geriatric TBI and identify gaps in the literature to guide future research. METHODS: Seven electronic databases and nine gray literature databases were systematically searched for articles that examined pharmacological management of neuropsychiatric symptoms in adults aged 65 years and over with TBI. The search was guided by four main concepts and selected based on inclusion criteria. Unpublished studies and abstract-only articles were excluded. RESULTS: Eight studies met full inclusion criteria. Patterns of psychotropic medication prescription and prescribing principles for geriatric TBI were elucidated. There were no clear or consistent prescribing guidance. Therefore, prescribing recommendations could not be addressed. Current management is inferred from research primarily done in younger adults, or extrapolated from the literature and practice of treating other psychiatric and neurological disorders. CONCLUSION: There are significant gaps in knowledge and no evidence-based guidelines for the treatment of neuropsychiatric symptoms in geriatric TBI. TBI among older adults is distinct from those of younger adults and thereby demands a unique approach to treatment and research. The authors' proposed guideline is an important first step in facilitating guideline development and future research.


Assuntos
Lesões Encefálicas Traumáticas , Transtornos Mentais , Idoso , Humanos , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/diagnóstico , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/etiologia
8.
Nano Lett ; 22(4): 1703-1709, 2022 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-35112873

RESUMO

Dynamically reconfigurable metasurfaces promise compact and lightweight spatial light modulation for many applications, including LiDAR, AR/VR, and LiFi systems. Here, we design and computationally investigate high-quality-factor silicon-on-lithium niobate metasurfaces with electrically driven, independent control of its constituent nanobars for full phase tunability with high tuning efficiency. Free-space light couples to guided modes within each nanobar via periodic perturbations, generating quality factors exceeding 30,000 while maintaining a bar spacing of <λ/1.5. We achieve nearly 2π phase variation with an applied bias not exceeding ±25 V, maintaining a reflection efficiency above 91%. Using full-field simulations, we demonstrate a high-angle (51°) switchable beamsplitter with a diffracted efficiency of 93% and an angle-tunable beamsteerer, spanning 18-31°, with up to 86% efficiency, all using the same metasurface device. Our platform provides a foundation for highly efficient wavefront-shaping devices with a wide dynamic tuning range capable of generating nearly any transfer function.


Assuntos
Eletricidade , Silício , Nióbio , Óxidos
9.
Nonlinear Dyn ; 111(10): 9649-9679, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37025428

RESUMO

This paper proposes a data-driven approximate Bayesian computation framework for parameter estimation and uncertainty quantification of epidemic models, which incorporates two novelties: (i) the identification of the initial conditions by using plausible dynamic states that are compatible with observational data; (ii) learning of an informative prior distribution for the model parameters via the cross-entropy method. The new methodology's effectiveness is illustrated with the aid of actual data from the COVID-19 epidemic in Rio de Janeiro city in Brazil, employing an ordinary differential equation-based model with a generalized SEIR mechanistic structure that includes time-dependent transmission rate, asymptomatics, and hospitalizations. A minimization problem with two cost terms (number of hospitalizations and deaths) is formulated, and twelve parameters are identified. The calibrated model provides a consistent description of the available data, able to extrapolate forecasts over a few weeks, making the proposed methodology very appealing for real-time epidemic modeling.

10.
RNA ; 26(12): 1976-1999, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32989044

RESUMO

Coronavirus EndoU inhibits dsRNA-activated antiviral responses; however, the physiologic RNA substrates of EndoU are unknown. In this study, we used mouse hepatitis virus (MHV)-infected bone marrow-derived macrophage (BMM) and cyclic phosphate cDNA sequencing to identify the RNA targets of EndoU. EndoU targeted viral RNA, cleaving the 3' side of pyrimidines with a strong preference for U ↓ A and C ↓ A sequences (endoY ↓ A). EndoU-dependent cleavage was detected in every region of MHV RNA, from the 5' NTR to the 3' NTR, including transcriptional regulatory sequences (TRS). Cleavage at two CA dinucleotides immediately adjacent to the MHV poly(A) tail suggests a mechanism to suppress negative-strand RNA synthesis and the accumulation of viral dsRNA. MHV with EndoU (EndoUmut) or 2'-5' phosphodiesterase (PDEmut) mutations provoked the activation of RNase L in BMM, with corresponding cleavage of RNAs by RNase L. The physiologic targets of EndoU are viral RNA templates required for negative-strand RNA synthesis and dsRNA accumulation. Coronavirus EndoU cleaves U ↓ A and C ↓ A sequences (endoY ↓ A) within viral (+) strand RNA to evade dsRNA-activated host responses.


Assuntos
Vírus da Hepatite Murina/enzimologia , RNA/química , Endorribonucleases Específicas de Uridilato/metabolismo , Proteínas não Estruturais Virais/metabolismo , Animais , Células Cultivadas , Macrófagos/virologia , Camundongos , Camundongos Endogâmicos C57BL , Mutação , Motivos de Nucleotídeos , Ligação Proteica , RNA/metabolismo , Endorribonucleases Específicas de Uridilato/genética , Proteínas não Estruturais Virais/genética
11.
Catheter Cardiovasc Interv ; 100(7): 1316-1322, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36403283

RESUMO

OBJECTIVES: To assess the correlation between the aortic valve annular plane (AVAP) obtained by preprocedural computed tomography (CT) with on-table three-dimensional rotational angiography (3DRA), in patients undergoing transcatheter aortic valve replacement (TAVR). BACKGROUND: Accurate assessment of the AVAP is critical during TAVR procedures to enable optimal positioning and minimize complications. Most commonly, preprocedural CT has been used to determine the AVAP. However, this can differ from the actual AVAP obtained during the TAVR procedure. METHODS: Consecutive TAVR patients at a single center undergoing both preprocedural CT and 3DRA were included in the study. The AVAP assessment by CT was performed using 3mensio software (Pie Medical Imaging). 3DRA assessment was performed using DynaCT (Siemens). RESULTS: A total of 100 patients were included in the analysis. A difference of ≥5° and ≥10° in both the LAO/RAO and cranial/caudal components of the AVAP projection angle as assessed by CT and 3DRA was recorded in 39% and 10% of patients, respectively. The concordance correlation coefficient for the LAO/RAO and cranial/caudal implantation angles was 0.519 (95% CI: 0.377-0.661) and 0.558 (95% CI: 0.432-0.684), respectively. CONCLUSION: Correlation between preprocedural CT and on-table 3DRA in the prediction of the actual AVAP at the time of TAVR implantation is moderate.


Assuntos
Estenose da Valva Aórtica , Próteses Valvulares Cardíacas , Substituição da Valva Aórtica Transcateter , Humanos , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Resultado do Tratamento , Substituição da Valva Aórtica Transcateter/efeitos adversos , Substituição da Valva Aórtica Transcateter/métodos , Tomografia Computadorizada por Raios X , Angiografia , Angiografia por Tomografia Computadorizada/métodos , Tomografia Computadorizada Multidetectores/métodos
12.
J Am Soc Nephrol ; 32(4): 805-820, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33597122

RESUMO

BACKGROUND: Vesicoureteral reflux (VUR) is a common, familial genitourinary disorder, and a major cause of pediatric urinary tract infection (UTI) and kidney failure. The genetic basis of VUR is not well understood. METHODS: A diagnostic analysis sought rare, pathogenic copy number variant (CNV) disorders among 1737 patients with VUR. A GWAS was performed in 1395 patients and 5366 controls, of European ancestry. RESULTS: Altogether, 3% of VUR patients harbored an undiagnosed rare CNV disorder, such as the 1q21.1, 16p11.2, 22q11.21, and triple X syndromes ((OR, 3.12; 95% CI, 2.10 to 4.54; P=6.35×10-8) The GWAS identified three study-wide significant and five suggestive loci with large effects (ORs, 1.41-6.9), containing canonical developmental genes expressed in the developing urinary tract (WDPCP, OTX1, BMP5, VANGL1, and WNT5A). In particular, 3.3% of VUR patients were homozygous for an intronic variant in WDPCP (rs13013890; OR, 3.65; 95% CI, 2.39 to 5.56; P=1.86×10-9). This locus was associated with multiple genitourinary phenotypes in the UK Biobank and eMERGE studies. Analysis of Wnt5a mutant mice confirmed the role of Wnt5a signaling in bladder and ureteric morphogenesis. CONCLUSIONS: These data demonstrate the genetic heterogeneity of VUR. Altogether, 6% of patients with VUR harbored a rare CNV or a common variant genotype conferring an OR >3. Identification of these genetic risk factors has multiple implications for clinical care and for analysis of outcomes in VUR.

13.
J Biol Chem ; 295(31): 10624-10637, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32493771

RESUMO

Picornaviral RNA-dependent RNA polymerases (RdRPs) have low replication fidelity that is essential for viral fitness and evolution. Their global fold consists of the classical "cupped right hand" structure with palm, fingers, and thumb domains, and these RdRPs also possess a unique contact between the fingers and thumb domains. This interaction restricts movements of the fingers, and RdRPs use a subtle conformational change within the palm domain to close their active sites for catalysis. We have previously shown that this core RdRP structure and mechanism provide a platform for polymerases to fine-tune replication rates and fidelity to optimize virus fitness. Here, we further elucidated the structural basis for differences in replication rates and fidelity among different viruses by generating chimeric RdRPs from poliovirus and coxsackievirus B3. We designed these chimeric polymerases by exchanging the fingers, pinky finger, or thumb domains. The results of biochemical, rapid-quench, and stopped-flow assays revealed that differences in biochemical activity map to individual modular domains of this polymerase. We found that the pinky finger subdomain is a major regulator of initiation and that the palm domain is the major determinant of catalytic rate and nucleotide discrimination. We further noted that thumb domain interactions with product RNA regulate translocation and that the palm and thumb domains coordinately control elongation complex stability. Several RdRP chimeras supported the growth of infectious poliovirus, providing insights into enterovirus species-specific protein-protein interactions required for virus replication.


Assuntos
Enterovirus Humano B , Poliovirus , RNA Viral , RNA Polimerase Dependente de RNA , Proteínas Virais , Enterovirus Humano B/enzimologia , Enterovirus Humano B/genética , Células HeLa , Humanos , Poliovirus/enzimologia , Poliovirus/genética , Domínios Proteicos , RNA Viral/química , RNA Viral/genética , RNA Viral/metabolismo , RNA Polimerase Dependente de RNA/química , RNA Polimerase Dependente de RNA/genética , RNA Polimerase Dependente de RNA/metabolismo , Proteínas Virais/química , Proteínas Virais/genética , Proteínas Virais/metabolismo
14.
J Virol ; 94(16)2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32522851

RESUMO

Picornaviruses have both asexual and sexual RNA replication mechanisms. Asexual RNA replication mechanisms involve one parental template, whereas sexual RNA replication mechanisms involve two or more parental templates. Because sexual RNA replication mechanisms counteract ribavirin-induced error catastrophe, we selected for ribavirin-resistant poliovirus to identify polymerase residues that facilitate sexual RNA replication mechanisms. We used serial passage in ribavirin, beginning with a variety of ribavirin-sensitive and ribavirin-resistant parental viruses. Ribavirin-sensitive virus contained an L420A polymerase mutation, while ribavirin-resistant virus contained a G64S polymerase mutation. A G64 codon mutation (G64Fix) was used to inhibit emergence of G64S-mediated ribavirin resistance. Revertants (L420) or pseudorevertants (L420V and L420I) were selected from all independent lineages of L420A, G64Fix L420A, and G64S L420A parental viruses. Ribavirin resistance G64S mutations were selected in two independent lineages, and novel ribavirin resistance mutations were selected in the polymerase in other lineages (M299I, M323I, M392V, and T353I). The structural orientation of M392, immediately adjacent to L420 and the polymerase primer grip region, led us to engineer additional polymerase mutations into poliovirus (M392A, M392L, M392V, K375R, and R376K). L420A revertants and pseudorevertants (L420V and L420I) restored efficient viral RNA recombination, confirming that ribavirin-induced error catastrophe coincides with defects in sexual RNA replication mechanisms. Viruses containing M392 mutations (M392A, M392L, and M392V) and primer grip mutations (K375R and R376K) exhibited divergent RNA recombination, ribavirin sensitivity, and biochemical phenotypes, consistent with changes in the fidelity of RNA synthesis. We conclude that an extended primer grip of the polymerase, including L420, M392, K375, and R376, contributes to the fidelity of RNA synthesis and to efficient sexual RNA replication mechanisms.IMPORTANCE Picornaviruses have both asexual and sexual RNA replication mechanisms. Sexual RNA replication shapes picornavirus species groups, contributes to the emergence of vaccine-derived polioviruses, and counteracts error catastrophe. Can viruses distinguish between homologous and nonhomologous partners during sexual RNA replication? We implicate an extended primer grip of the viral polymerase in sexual RNA replication mechanisms. By sensing RNA sequence complementarity near the active site, the extended primer grip of the polymerase has the potential to distinguish between homologous and nonhomologous RNA templates during sexual RNA replication.


Assuntos
Picornaviridae/genética , RNA Polimerase Dependente de RNA/genética , Replicação Viral/efeitos dos fármacos , Substituição de Aminoácidos/genética , Antivirais/farmacologia , RNA Polimerases Dirigidas por DNA/genética , RNA Polimerases Dirigidas por DNA/metabolismo , Farmacorresistência Viral/efeitos dos fármacos , Células HeLa , Humanos , Mutação/efeitos dos fármacos , Picornaviridae/metabolismo , Picornaviridae/patogenicidade , Infecções por Picornaviridae/genética , Infecções por Picornaviridae/metabolismo , Poliovirus/genética , RNA/genética , RNA Viral/genética , RNA Polimerase Dependente de RNA/metabolismo , Ribavirina/farmacologia , Replicação Viral/genética
15.
Phys Rev Lett ; 126(12): 123201, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33834794

RESUMO

The light sources that power photonic networks are small and scalable, but they also require the incorporation of optical isolators that allow light to pass in one direction only, protecting the light source from damaging backreflections. Unfortunately, the size and complex integration of optical isolators makes small-scale and densely integrated photonic networks infeasible. Here, we overcome this limitation by designing a single device that operates both as a coherent light source and as its own optical isolator. Our design relies on high-quality-factor dielectric metasurfaces that exhibit intrinsic chirality. By carefully manipulating the geometry of the constituent silicon metaatoms, we design three-dimensionally chiral modes that act as optical spin-dependent filters. Using spin-polarized Raman scattering together with our chiral metacavity, we demonstrate Raman lasing in the forward direction, while the lasing action is suppressed by over an order of magnitude for reflected light. Our high-Q chiral metasurface design presents a new approach toward compactly isolating integrated light sources by directly tailoring the emission properties of the light source itself.

16.
Nano Lett ; 20(7): 5127-5132, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32497434

RESUMO

Metasurface lenses provide an ultrathin platform in which to focus light, but weak light-matter interactions limit their dynamic tunability. Here we design submicron-thick, ultrahigh quality factor (high-Q) metalenses that enable dynamic modulation of the focal length and intensity. Using full-field simulations, we show that quality factors exceeding 5000 can be generated by including subtle, periodic perturbations within the constituent Si nanoantennas. Such high-Q resonances enable lens modulation based on the nonlinear Kerr effect, with focal lengths varying from 4 to 6.5 µm and focal intensities decreasing by half as input intensity increases from 0.1 to 1 mW/µm2. We also show how multiple high-Q resonances can be embedded in the lens response through judicious placement of the perturbations. Our high-Q lens design, with quality factors 2 orders of magnitude higher than existing lens designs, provides a foundation for reconfigurable, multiplexed, and hyperspectral metasurface imaging platforms.

17.
J Virol ; 93(14)2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31068422

RESUMO

Template-dependent RNA replication mechanisms render picornaviruses susceptible to error catastrophe, an overwhelming accumulation of mutations incompatible with viability. Viral RNA recombination, in theory, provides a mechanism for viruses to counteract error catastrophe. We tested this theory by exploiting well-defined mutations in the poliovirus RNA-dependent RNA polymerase (RDRP), namely, a G64S mutation and an L420A mutation. Our data reveal two distinct mechanisms by which picornaviral RDRPs influence error catastrophe: fidelity of RNA synthesis and RNA recombination. A G64S mutation increased the fidelity of the viral polymerase and rendered the virus resistant to ribavirin-induced error catastrophe, but only when RNA recombination was at wild-type levels. An L420A mutation in the viral polymerase inhibited RNA recombination and exacerbated ribavirin-induced error catastrophe. Furthermore, when RNA recombination was substantially reduced by an L420A mutation, a high-fidelity G64S polymerase failed to make the virus resistant to ribavirin. These data indicate that viral RNA recombination is required for poliovirus to evade ribavirin-induced error catastrophe. The conserved nature of L420 within RDRPs suggests that RNA recombination is a common mechanism for picornaviruses to counteract and avoid error catastrophe.IMPORTANCE Positive-strand RNA viruses produce vast amounts of progeny in very short periods of time via template-dependent RNA replication mechanisms. Template-dependent RNA replication, while efficient, can be disadvantageous due to error-prone viral polymerases. The accumulation of mutations in viral RNA genomes leads to error catastrophe. In this study, we substantiate long-held theories regarding the advantages and disadvantages of asexual and sexual replication strategies among RNA viruses. In particular, we show that picornavirus RNA recombination counteracts the negative consequences of asexual template-dependent RNA replication mechanisms, namely, error catastrophe.


Assuntos
Poliovirus , RNA Viral , RNA Polimerase Dependente de RNA , Recombinação Genética/efeitos dos fármacos , Ribavirina/farmacologia , Proteínas Virais , Substituição de Aminoácidos , Animais , Células HeLa , Humanos , Camundongos , Mutação de Sentido Incorreto , Poliovirus/genética , Poliovirus/metabolismo , RNA/genética , RNA/metabolismo , RNA Viral/genética , RNA Viral/metabolismo , RNA Polimerase Dependente de RNA/genética , RNA Polimerase Dependente de RNA/metabolismo , Proteínas Virais/genética , Proteínas Virais/metabolismo
18.
Cardiology ; 145(9): 608-610, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32615571

RESUMO

BACKGROUND: Contrast-induced acute kidney injury (CIAKI) is a frequent and serious complication of transcatheter aortic valve replacement (TAVR). The most important procedural risk factor for CIAKI is contrast volume. OBJECTIVES: Because contrast volume is a modifiable factor that directly predicts CIAKI, we sought to identify predictors of increased contrast volume in TAVR patients. Identification of such predictors may allow both prediction and mitigation of CIAKI risk following TAVR. METHOD: We retrospectively analyzed data from consecutive patients not on hemodialysis who underwent successful TAVR at a single US center from 2013 to 2018. Using multivariable linear regression modelling, we assessed the relationships between contrast volumes and 49 patient and procedural factors hypothesized to be potential predictors. RESULTS: In 295 patients, we identified 17 factors that independently predicted contrast volume, 10 of which contributed 90% of the complete model's r2 value. Procedure year (suggesting a learning curve), aortic insufficiency, radiation dose, prior AVR, and previous pacemaker placement were statistically the most significant predictors of CIAKI. TAVR device and diabetes were notably not predictors. CONCLUSIONS: To predict and reduce contrast use in TAVR, patients at risk for increased contrast volume may be identified using the predictors elucidated in this study. For such patients, strategies for contrast reduction and renal protection may be employed.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Estenose da Valva Aórtica/cirurgia , Meios de Contraste/administração & dosagem , Meios de Contraste/efeitos adversos , Substituição da Valva Aórtica Transcateter/efeitos adversos , Próteses Valvulares Cardíacas , Humanos , Modelos Lineares , Análise Multivariada , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
19.
Bioscience ; 69(7): 566-574, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31308573

RESUMO

The circumstances under which different ecosystem service benefits can be realized differ. The benefits tend to be coproduced and to be enabled by multiple interacting social, ecological, and technological factors, which is particularly evident in cities. As many cities are undergoing rapid change, these factors need to be better understood and accounted for, especially for those most in need of benefits. We propose a framework of three systemic filters that affect the flow of ecosystem service benefits: the interactions among green, blue, and built infrastructures; the regulatory power and governance of institutions; and people's individual and shared perceptions and values. We argue that more fully connecting green and blue infrastructure to its urban systems context and highlighting dynamic interactions among the three filters are key to understanding how and why ecosystem services have variable distribution, continuing inequities in who benefits, and the long-term resilience of the flows of benefits.

20.
Nano Lett ; 18(2): 1104-1109, 2018 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-29369641

RESUMO

Metasurfaces enable almost complete control of light through ultrathin, subwavelength surfaces by locally and abruptly altering the scattered phase. To date, however, all metasurfaces obey time-reversal symmetry, meaning that forward and backward traveling waves will trace identical paths when being reflected, refracted, or diffracted. Here, we use full-field calculations to design a passive metasurface for nonreciprocal transmission of both direct and anomalously refracted near-infrared light over nanoscale optical path lengths. The metasurface consists of a 100 nm-thick, periodically patterned Si slab. Owing to the high-quality-factor resonances of the metasurface and the inherent Kerr nonlinearities of Si, this structure acts as an optical diode for free-space optical signals. This structure also exhibits nonreciprocal anomalous refraction with appropriate patterning to form a phase gradient metasurface. Compared to existing schemes for breaking time-reversal symmetry, our platform enables subwavelength nonreciprocity for arbitrary free-space optical inputs and provides a straightforward path to experimental realization. The concept is also generalizable to other metasurface functions, providing a foundation for one-way lensing and holography.

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