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1.
Mol Cell ; 78(5): 824-834.e15, 2020 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-32325029

RESUMO

Studying posttranslational modifications classically relies on experimental strategies that oversimplify the complex biosynthetic machineries of living cells. Protein glycosylation contributes to essential biological processes, but correlating glycan structure, underlying protein, and disease-relevant biosynthetic regulation is currently elusive. Here, we engineer living cells to tag glycans with editable chemical functionalities while providing information on biosynthesis, physiological context, and glycan fine structure. We introduce a non-natural substrate biosynthetic pathway and use engineered glycosyltransferases to incorporate chemically tagged sugars into the cell surface glycome of the living cell. We apply the strategy to a particularly redundant yet disease-relevant human glycosyltransferase family, the polypeptide N-acetylgalactosaminyl transferases. This approach bestows a gain-of-chemical-functionality modification on cells, where the products of individual glycosyltransferases can be selectively characterized or manipulated to understand glycan contribution to major physiological processes.


Assuntos
Glicosiltransferases/metabolismo , Polissacarídeos/metabolismo , Engenharia de Proteínas/métodos , Vias Biossintéticas , Membrana Celular/metabolismo , Glicosilação , Glicosiltransferases/química , Glicosiltransferases/fisiologia , Células HEK293 , Células Hep G2 , Humanos , Células K562 , N-Acetilgalactosaminiltransferases/química , N-Acetilgalactosaminiltransferases/metabolismo , N-Acetilgalactosaminiltransferases/fisiologia , Polissacarídeos/química , Proteínas/metabolismo , Polipeptídeo N-Acetilgalactosaminiltransferase
2.
EMBO J ; 41(16): e110410, 2022 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-35698800

RESUMO

Although amyloid fibres are highly stable protein aggregates, a specific combination of human Hsp70 system chaperones can disassemble them, including fibres formed of α-synuclein, huntingtin, or Tau. Disaggregation requires the ATPase activity of the constitutively expressed Hsp70 family member, Hsc70, together with the J domain protein DNAJB1 and the nucleotide exchange factor Apg2. Clustering of Hsc70 on the fibrils appears to be necessary for disassembly. Here we use atomic force microscopy to show that segments of in vitro assembled α-synuclein fibrils are first coated with chaperones and then undergo bursts of rapid, unidirectional disassembly. Cryo-electron tomography and total internal reflection fluorescence microscopy reveal fibrils with regions of densely bound chaperones, preferentially at one end of the fibre. Sub-stoichiometric amounts of Apg2 relative to Hsc70 dramatically increase recruitment of Hsc70 to the fibres, creating localised active zones that then undergo rapid disassembly at a rate of ~ 4 subunits per second. The observed unidirectional bursts of Hsc70 loading and unravelling may be explained by differences between the two ends of the polar fibre structure.


Assuntos
Proteínas de Choque Térmico HSP70 , alfa-Sinucleína , Amiloide/metabolismo , Proteínas Amiloidogênicas/metabolismo , Proteínas de Choque Térmico HSC70/metabolismo , Proteínas de Choque Térmico HSP40/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Chaperonas Moleculares/metabolismo , Agregados Proteicos , Ligação Proteica , alfa-Sinucleína/metabolismo
3.
Acc Chem Res ; 57(1): 59-69, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38103045

RESUMO

ConspectusPreparing and manipulating pure magnetic states in molecular systems are the key initial requirements for harnessing the power of synthetic chemistry to drive practical quantum sensing and computing technologies. One route for achieving the requisite higher spin states in organic systems exploits the phenomenon of singlet fission, which produces pairs of triplet excited states from initially photoexcited singlets in molecular assemblies with multiple chromophores. The resulting spin states are characterized by total spin (quintet, triplet, or singlet) and its projection onto a specified molecular or magnetic field axis. These excited states are typically highly polarized but exhibit an impure spin population pattern. Herein, we report the prediction and experimental verification of molecular design rules that drive the population of a single pure magnetic state and describe the progress toward its experimental realization.A vital feature of this work is the close partnership among theory, chemical synthesis, and spectroscopy. We begin by presenting our theoretical framework for understanding spin manifold interconversion in singlet fission systems. This theory makes specific testable predictions about the intermolecular structure and orientation relative to an external magnetic field that should lead to pure magnetic state preparation and provides a powerful tool for interpreting magnetic spectra. We then test these predictions through detailed magnetic spectroscopy experiments on a series of new molecular architectures that meet one or more of the identified structural criteria. Many of these architectures rely on the synthesis of molecules with features unique to this effort: rigid bridges between chromophores in dimers, heteroacenes with tailored singlet/triplet-pair energy level matching, or side-group engineering to produce specific crystal structures. The spin evolution of these systems is revealed through our application and development of several magnetic resonance methods, each of which has different sensitivities and relevance in environments relevant to quantum applications.Our theoretical predictions prove to be remarkably consistent with our experimental results, though experimentally meeting all the structural prescriptions demanded by theory for true pure-state preparation remains a challenge. Our magnetic spectra agree with our model of triplet-pair behavior, including funneling of the population to the ms = 0 magnetic sublevel of the quintet under specified conditions in dimers and crystals, showing that this phenomenon is subject to control through molecular design. Moreover, our demonstration of novel and/or highly sensitive detection mechanisms of spin states in singlet fission systems, including photoluminescence (PL), photoinduced absorption (PA), and magnetoconductance (MC), points the way toward both a deeper understanding of how these systems evolve and technologically feasible routes toward experiments at the single-molecule quantum limit that are desirable for computational applications.

4.
Proc Natl Acad Sci U S A ; 119(29): e2201879119, 2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35858318

RESUMO

The photo-driven process of singlet fission generates coupled triplet pairs (TT) with fundamentally intriguing and potentially useful properties. The quintet 5TT0 sublevel is particularly interesting for quantum information because it is highly entangled, is addressable with microwave pulses, and could be detected using optical techniques. Previous theoretical work on a model Hamiltonian and nonadiabatic transition theory, called the JDE model, has determined that this sublevel can be selectively populated if certain conditions are met. Among the most challenging, the molecules within the dimer undergoing singlet fission must have their principal magnetic axes parallel to one another and to an applied Zeeman field. Here, we present time-resolved electron paramagnetic resonance (TR-EPR) spectroscopy of a single crystal sample of a tetracenethiophene compound featuring arrays of dimers aligned in this manner, which were mounted so that the orientation of the field relative to the molecular axes could be controlled. The observed spin sublevel populations in the paired TT and unpaired (T+T) triplets are consistent with predictions from the JDE model, including preferential 5TT0 formation at z ‖ B0, with one caveat-two 5TT spin sublevels have little to no population. This may be due to crossings between the 5TT and 3TT manifolds in the field range investigated by TR-EPR, consistent with the intertriplet exchange energy determined by monitoring photoluminescence at varying magnetic fields.

5.
J Am Chem Soc ; 146(11): 7763-7770, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38456418

RESUMO

Blends comprising organic semiconductors and inorganic quantum dots (QDs) are relevant for many optoelectronic applications and devices. However, the individual components in organic-QD blends have a strong tendency to aggregate and phase-separate during film processing, compromising both their structural and electronic properties. Here, we demonstrate a QD surface engineering approach using electronically active, highly soluble semiconductor ligands that are matched to the organic semiconductor host material to achieve well-dispersed inorganic-organic blend films, as characterized by X-ray and neutron scattering, and electron microscopies. This approach preserves the electronic properties of the organic and QD phases and also creates an optimized interface between them. We exemplify this in two emerging applications, singlet-fission-based photon multiplication (SF-PM) and triplet-triplet annihilation-based photon upconversion (TTA-UC). Steady-state and time-resolved optical spectroscopy shows that triplet excitons can be transferred with near unity efficiently across the organic-inorganic interface, while the organic films maintain efficient SF (190% yield) in the organic phase. By changing the relative energy between organic and inorganic components, yellow upconverted emission is observed upon 790 nm NIR excitation. Overall, we provide a highly versatile approach to overcome longstanding challenges in the blending of organic semiconductors with QDs that have relevance for many optical and optoelectronic applications.

6.
J Phys Chem A ; 128(20): 3982-3992, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38717589

RESUMO

Tetraceno[2,3-b]thiophene is regarded as a strong candidate for singlet fission-based solar cell applications due to its mixed characteristics of tetracene and pentacene that balance exothermicity and triplet energy. An electronically weakly coupled tetraceno[2,3-b]thiophene dimer (Et2Si(TIPSTT)2) with a single silicon atom bridge has been synthesized, providing a new platform to investigate the singlet fission mechanism involving the two acene chromophores. We study the excited state dynamics of Et2Si(TIPSTT)2 by monitoring the evolution of multiexciton coupled triplet states, 1TT to 5TT to 3TT to T1 + S0, upon photoexcitation with transient absorption, temperature-dependent transient absorption, and transient/pulsed electron paramagnetic resonance spectroscopies. We find that the photoexcited singlet lifetime is 107 ps, with 90% evolving to form the TT state, and the complicated evolution between the multiexciton states is unraveled, which can be an important reference for future efforts toward tetraceno[2,3-b]thiophene-based singlet fission solar cells.

7.
Eur J Appl Physiol ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38940932

RESUMO

PURPOSE: To assess the effect of a remote handgrip contraction during wide-pulse high-frequency (WPHF) neuromuscular electrical stimulation (NMES) on the magnitude of extra torque, progressive increase in torque during stimulation, and estimates of the persistent inward current (PIC) contribution to motoneuron firing in the plantar flexors. METHODS: Ten participants performed triangular shaped contractions to 20% of maximal plantar flexion torque before and after WPHF NMES with and without a handgrip contraction, and control conditions. Extra torque, the relative difference between the initial and final torque during stimulation, and sustained electromyographic (EMG) activity were assessed. High-density EMG was recorded during triangular shaped contractions to calculate ∆F, an estimate of PIC contribution to motoneuron firing, and its variation before vs after the intervention referred to as ∆F change score. RESULTS: While extra torque was not significantly increased with remote contraction (WPHF + remote) vs WPHF (+ 37 ± 63%, p = 0.112), sustained EMG activity was higher in this condition than WPHF (+ 3.9 ± 4.3% MVC EMG, p = 0.017). Moreover, ∆F was greater (+ 0.35 ± 0.30 Hz) with WPHF + remote than control (+ 0.03 ± 0.1 Hz, p = 0.028). A positive correlation was found between ∆F change score and extra torque in the WPHF + remote (r = 0.862, p = 0.006). DISCUSSION: The findings suggest that the addition of remote muscle contraction to WPHF NMES enhances the central contribution to torque production, which may be related to an increased PIC contribution to motoneuron firing. Gaining a better understanding of these mechanisms should enable NMES intervention optimization in clinical and rehabilitation settings, improving neuromuscular function in clinical populations.

8.
Issues Ment Health Nurs ; 45(1): 37-54, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37988631

RESUMO

The safety of service users and staff is paramount in cultivating a therapeutic environment within inpatient mental health units. The Safewards model, originating in the United Kingdom, aims to reduce conflict and containment rates through 10 interventions. This study used participatory action research to explore the perspective of tangata whai ora and staff regarding the adaptation of the Safewards model to the unique New Zealand context. Such adaptation is critical due to significant health outcome disparities between Maori and non-Maori populations and the disproportionate representation of Maori within mental health services. In adhering to the principles of Te Tiriti o Waitangi, cultural adaptation becomes an imperative obligation. The study utilised qualitative content analysis and thematic analysis, drawing data from focus groups of staff (n = 15) and tangata whai ora (n = 3). This study describes a New Zealand Safewards model, which must include Te Ao Maori, align with current practices, adapt Safewards interventions and gain acceptance. Organisational change management is pivotal in the integration of this model into nursing practice. The outcomes of this study hold the potential to contribute to the formulation and implementation of a New Zealand Safewards model, while also bearing relevance for the international adaptation of Safewards to culturally diverse countries and healthcare systems.


Assuntos
Povo Maori , Serviços de Saúde Mental , Humanos , Nova Zelândia , Reino Unido
9.
Langmuir ; 39(13): 4799-4808, 2023 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-36940205

RESUMO

Controlling the dispersibility of nanocrystalline inorganic quantum dots (QDs) within organic semiconductor (OSC):QD nanocomposite films is critical for a wide range of optoelectronic devices. This work demonstrates how small changes to the OSC host molecule can have a dramatic detrimental effect on QD dispersibility within the host organic semiconductor matrix as quantified by grazing incidence X-ray scattering. It is commonplace to modify QD surface chemistry to enhance QD dispersibility within an OSC host. Here, an alternative route toward optimizing QD dispersibilities is demonstrated, which dramatically improves QD dispersibilities through blending two different OSCs to form a fully mixed OSC matrix phase.

10.
Curr Top Membr ; 91: 139-156, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37080678

RESUMO

The endothelial glycocalyx (EG) is a gel-like structure that forms a layer in between the surface of the endothelium and lumen. EG was once thought to be merely a structural support for the endothelium. However, in recent years, the importance of EG as a first line of defense and a key regulator to endothelial integrity has been illuminated. With advanced age, EG deterioration becomes more noticeable and at least partially associated with endothelial dysfunction. Hyaluronan (HA), one of the critical components of the EG, has distinct properties and roles to the maintenance of EG and endothelial function. Therefore, given the intimate relationship between the EG and endothelium during the aging process, HA may serve as a promising therapeutic target to prevent endothelial dysfunction.


Assuntos
Ácido Hialurônico , Doenças Vasculares , Humanos , Endotélio Vascular , Glicocálix
11.
Proc Natl Acad Sci U S A ; 117(34): 20696-20705, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32769209

RESUMO

Regulatory T (Treg) cells, expressing CD25 (interleukin-2 receptor α chain) and Foxp3 transcription factor, maintain immunological self-tolerance and suppress various immune responses. Here we report a feature of skin Treg cells expanded by ultraviolet B (UVB) exposure. We found that skin Treg cells possessing a healing function are expanded by UVB exposure with the expression of an endogenous opioid precursor, proenkephalin (PENK). Upon UVB exposure, skin Treg cells were expanded with a unique TCR repertoire. Also, they highly expressed a distinctive set of genes enriched in "wound healing involved in inflammatory responses" and the "neuropeptide signaling pathway," as indicated by the high expression of Penk. We found that not only was PENK expression at the protein level detected in the UVB-expanded skin Treg (UVB-skin Treg) cells, but that a PENK-derived neuropeptide, methionine enkephalin (Met-ENK), from Treg cells promoted the outgrowth of epidermal keratinocytes in an ex vivo skin explant assay. Notably, UVB-skin Treg cells also promoted wound healing in an in vivo wound closure assay. In addition, UVB-skin Treg cells produced amphiregulin (AREG), which plays a key role in Treg-mediated tissue repair. Identification of a unique function of PENK+ UVB-skin Treg cells provides a mechanism for maintaining skin homeostasis.


Assuntos
Encefalinas/metabolismo , Precursores de Proteínas/metabolismo , Linfócitos T Reguladores/metabolismo , Cicatrização/fisiologia , Anfirregulina/metabolismo , Animais , Células Cultivadas , Encefalina Metionina/metabolismo , Encefalinas/efeitos da radiação , Feminino , Homeostase/fisiologia , Humanos , Tolerância Imunológica/imunologia , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Precursores de Proteínas/efeitos da radiação , Tolerância a Antígenos Próprios/imunologia , Pele/metabolismo , Raios Ultravioleta , Cicatrização/imunologia
12.
J Chem Phys ; 157(16): 164702, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36319433

RESUMO

Molecular spin systems based on photoexcited triplet pairs formed via singlet fission (SF) are attractive as carriers of quantum information because of their potentially pure and controllable spin polarization, but developing systems that offer optical routes to readout as well as initialization is challenging. Herein, we characterize the electron spin magnetic resonance change in the photoluminescence intensity for a tailored organic molecular crystal while sweeping a microwave drive up to 10 GHz in a broadband loop structure. We observe resonant transitions for both triplet and quintet spin sublevel populations showing their optical sensitivity and revealing the zero-field parameters for each. We map the evolution of these spectra in both microwave frequency and magnetic field, producing a pattern of optically detected magnetic resonance (ODMR) peaks. Fits to these data using a suitable model suggest significant spin polarization in this system with orientation selectivity. Unusual excitation intensity dependence is also observed, which inverts the sign of the ODMR signal for the triplet features, but not for the quintet. These observations demonstrate optical detection of the spin sublevel population dictated by SF and intermolecular geometry, and highlight anisotropic and multi-scale dynamics of triplet pairs.

13.
Am J Perinatol ; 39(10): 1124-1131, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-33321532

RESUMO

OBJECTIVE: Human cases of acute profound hypoxic-ischemic (HI) injury (HII), in which the insult duration timed with precision had been identified, remains rare, and there is often uncertainty of the prior state of fetal health. STUDY DESIGN: A retrospective analysis of 10 medicolegal cases of neonatal encephalopathy-cerebral palsy survivors who sustained intrapartum HI basal ganglia-thalamic (BGT) pattern injury in the absence of an obstetric sentinel event. RESULTS: Cardiotocography (CTG) admission status was reassuring in six and suspicious in four of the cases. The median time from assessment by admission CTG or auscultation to birth was 687.5 minutes (interquartile range [IQR]: 373.5-817.5 minutes), while the median time interval between first pathological CTG and delivery of the infant was 179 minutes (IQR: 137-199.25 minutes). The mode of delivery in the majority of infants (60%) was by unassisted vaginal birth; four were delivered by delayed caesarean section. The median (IQR) interval between the decision to perform a caesarean section and delivery was 169 minutes (range: 124-192.5 minutes). CONCLUSION: The study shows that if a nonreassuring fetal status develops during labor and is prolonged, a BGT pattern HI injury may result, in the absence of a perinatal sentinel event. Intrapartum BGT pattern injury and radiologically termed "acute profound HI brain injury" are not necessarily synonymous. A visualized magnetic resonance imaging (MRI) pattern should preferably solely reflect the patterns description and severity, rather than a causative mechanism of injury. KEY POINTS: · BGT HI injury pattern on MRI may develop in the absence of a perinatal sentinel event.. · BGT pattern injury may not be synonymous with "acute profound HI brain injury.". · MRI pattern and severity thereof should be described rather than a causative mechanism of injury..


Assuntos
Lesões Encefálicas , Paralisia Cerebral , Hipóxia-Isquemia Encefálica , Gânglios da Base/diagnóstico por imagem , Lesões Encefálicas/complicações , Lesões Encefálicas/etiologia , Cardiotocografia/métodos , Paralisia Cerebral/etiologia , Cesárea/efeitos adversos , Feminino , Humanos , Hipóxia-Isquemia Encefálica/complicações , Hipóxia-Isquemia Encefálica/etiologia , Lactente , Recém-Nascido , Gravidez , Estudos Retrospectivos
14.
J Environ Manage ; 316: 115235, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35569361

RESUMO

Volcanic sites can be considered strategic areas for conservation and protection policies, but such policies may involve considerable costs However, not only are volcanic sites often integral to the tourism industry and, hence, of potential significant benefit to local economies in general; entrance fee income from tourists can also contribute to management and conservation costs in particular. Nevertheless, seasonal variations in tourism demand, resulting in over-and under-tourism situations, may impact on both the level of income generated as well as on the sustainability of sites Therefore, based on a case study of Mt Etna in Italy, this study considers establishing appropriate entry fee levels for volcano areas. First, a logit model is applied to the relevant socio-demographic and site-specific variables. The entrance fees are estimated on visitors' willingness to pay and demand elasticity. Applying contingent valuation method (CVM), two groups of tourists (high and low season visitors) are identified and surveyed, with each group demonstrating different willingness to pay and elasticity levels. Rather than applying a single fee, different entrance fees for the two groups are found to generate a higher level of revenue for the park's economic equilibrium. In addition, the different entrance fees offer the potential to mitigate the peak effects of over-tourism and support demand during under-tourism, with clear sustainability consequences. The results, which confirm four hypotheses set about Mt. Etna, could facilitate decision-makers in determining a feasible balance between management costs, tourism demand characteristics and protection commitments.


Assuntos
Renda , Turismo , Custos e Análise de Custo , Itália
15.
J Am Chem Soc ; 143(34): 13749-13758, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34397219

RESUMO

The excited-state dynamics of 6,13-bis(triisopropylsilylethynyl)pentacene is investigated to determine the role of excimer and aggregate formation in singlet fission in high-concentration solutions. Photoluminescence spectra were measured by excitation with the evanescent wave in total internal reflection, in order to avoid reabsorption effects. The spectra over nearly two magnitudes of concentration were nearly identical, with no evidence for excimer emission. Time-correlated single-photon counting measurements confirm that the fluorescence lifetime shortens with concentration. The observed rate constant grows at high concentrations, and this effect is modeled in terms of the hard-sphere radial distribution function. NMR measurements confirm that aggregation takes place with a binding constant of between 0.14 and 0.43 M-1. Transient absorption measurements are consistent with a diffusive encounter mechanism for singlet fission, with hints of more rapid singlet fission in aggregates at the highest concentration measured. These data show that excimers do not play the role of an emissive intermediate in exothermic singlet fission in solution and that, while aggregation occurs at higher concentrations, the mechanism of singlet fission remains dominated by diffusive encounters.

16.
Int J Equity Health ; 20(1): 63, 2021 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-33622337

RESUMO

BACKGROUND: Despite substantial reductions in perinatal deaths (stillbirths and early neonatal deaths), India's perinatal mortality rates remain high, both nationally and in individual states. Rates are highest among disadvantaged socio-economic groups. To address this, India's National Health Mission has trained community health workers called Accredited Social Health Activists (ASHAs) to counsel and support women by visiting them at home before and after childbirth. We conducted a qualitative study to explore the roles of ASHAs' home visits in improving equity in perinatal health between socio-economic position groups in rural Uttar Pradesh (UP), India. METHODS: We conducted social mapping in four villages of two districts in UP, followed by three focus group discussions in each village (12 in total) with ASHAs and women who had recently given birth belonging to 'higher' and 'lower' socio-economic position groups (n = 134 participants). We analysed the data in NVivo and Dedoose using a thematic framework approach. RESULTS: Home visits enabled ASHAs to build trusting relationships with women, offer information about health services, schemes and preventive care, and provide practical support for accessing maternity care. This helped many women and families prepare for birth and motivated them to deliver in health facilities. In particular, ASHAs encouraged women who were poorer, less educated or from lower caste groups to give birth in public Community Health Centres (CHCs). However, women who gave birth at CHCs often experienced insufficient emergency obstetric care, mistreatment from staff, indirect costs, lack of medicines, and referrals to higher-level facilities when complications occurred. Referrals often led to delays and higher fees that placed the greatest burden on families who were considered of lower socio-economic position or living in remote areas, and increased their risk of experiencing perinatal loss. CONCLUSIONS: The study found that ASHAs built relationships, counselled and supported many pregnant women of lower socio-economic positions. Ongoing inequities in health facility births and perinatal mortality were perpetuated by overlapping contextual issues beyond the ASHAs' purview. Supporting ASHAs' integration with community organisations and health system strategies more broadly is needed to address these issues and optimise pathways between equity in intervention coverage, processes and perinatal health outcomes.


Assuntos
Agentes Comunitários de Saúde , Equidade em Saúde , Serviços de Saúde Materna , Mortalidade Perinatal , Feminino , Humanos , Índia , Recém-Nascido , Parto , Gravidez , Pesquisa Qualitativa , População Rural
17.
J Chem Phys ; 154(17): 174705, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34241085

RESUMO

Materials design and discovery are often hampered by the slow pace and materials and human costs associated with Edisonian trial-and-error screening approaches. Recent advances in computational power, theoretical methods, and data science techniques, however, are being manifest in a convergence of these tools to enable in silico materials discovery. Here, we present the development and deployment of computational materials data and data analytic approaches for crystalline organic semiconductors. The OCELOT (Organic Crystals in Electronic and Light-Oriented Technologies) infrastructure, consisting of a Python-based OCELOT application programming interface and OCELOT database, is designed to enable rapid materials exploration. The database contains a descriptor-based schema for high-throughput calculations that have been implemented on more than 56 000 experimental crystal structures derived from 47 000 distinct molecular structures. OCELOT is open-access and accessible via a web-user interface at https://oscar.as.uky.edu.

18.
BMC Pregnancy Childbirth ; 21(1): 724, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34706676

RESUMO

BACKGROUND: Timely and skilled care is key to reducing maternal and neonatal mortality. Birth preparedness involves preparation for safe childbirth during the antenatal period to reach the appropriate health facility for ensuring safe delivery. Hence, understanding the factors associated with birth preparedness and its significance for safe delivery is essential. This paper aims to assess the levels of birth preparedness, its determinants and association with institutional deliveries in High Priority Districts of Uttar Pradesh, India. METHODS: A community-based cross-sectional survey was conducted between June-October 2018 in the rural areas of 25 high priority districts of Uttar Pradesh, India. Simple random sampling was used to select 40 blocks among 294 blocks in 25 districts and 2646 primary sampling units within the selected blocks. The survey interviewed 9458 women who had a delivery 2 months prior to the survey. Descriptive statistics were included to characterize the study population. Multivariable logistic regression analyses were performed to identify the determinants of birth preparedness and to examine the association of birth preparedness with institutional delivery. RESULTS: Among the 9458 respondents, 61.8% had birth preparedness (both facility and transportation identified) and 79.1% delivered in a health facility. Women in other caste category (aOR = 1.24, CI 1.06-1.45) and those with 10 or more years of education (aOR = 1.68, CI 1.46-1.92) were more likely to have birth preparedness. Antenatal care (ANC) service uptake related factors like early registration for ANC (aOR = 1.14, CI 1.04-1.25) and three or more front line worker contacts (aOR = 1.61, CI 1.46-1.79) were also found to be significantly associated with birth preparedness. The adjusted multivariate model showed that those who identified both facility and transport were seven times more likely to undergo delivery in a health facility (aOR = 7.00, CI 6.07-8.08). CONCLUSION: The results indicate the need for focussing on marginalized groups for improving birth preparedness. Increasing ANC registration in the first trimester of pregnancy, improving frontline worker contact, and optimum utilization of antenatal care check-ups for effective counselling on birth preparedness along with system level improvements could improve birth preparedness and consequently institutional delivery rates in Uttar Pradesh, India.


Assuntos
Parto Obstétrico/psicologia , Instalações de Saúde , Conhecimentos, Atitudes e Prática em Saúde , Parto/psicologia , Cuidado Pré-Natal/normas , Meios de Transporte , Adulto , Estudos Transversais , Parto Obstétrico/estatística & dados numéricos , Feminino , Humanos , Índia/epidemiologia , Gravidez , População Rural/estatística & dados numéricos , Fatores Socioeconômicos
19.
Eur Arch Otorhinolaryngol ; 278(4): 1209-1222, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32696251

RESUMO

PURPOSE: The purpose of this study is to assess the general course of acoustic, patient rated, and clinician-rated voice outcomes from pre- up to 12 months post total laryngectomy. METHODS: Patients admitted to a total laryngectomy in five participating hospitals in Australia and The Netherlands were included. Assessments took place at pre-, 3 months, 6 months, and 12 months post-surgery. Voice outcomes are evaluated with the Acoustic Voice Quality Index (AVQI), perceptual scales, and patient-reported outcome measures including VHI-10 and EQ-5D-5L. Statistical analyses include descriptive statistics, t tests (pre- to 6 months post-surgery), Linear Mixed Effect models. RESULTS: The study included 43 participants. A significant worsening of AVQI is seen from pre- to post-surgery evaluated with t test (p < 0.001). The Linear Mixed Effect model confirmed Time as a significant factor in predicting AVQI score (p ≤ 0.001), as well as perceptual rated voice quality by the clinician (p = 0.015) and patient-reported perceptual rated voice quality (p = 0.002). No statistical significance was found in VHI-10 scores over time. CONCLUSION: Successful TE-speech was achieved in most participants, some had to rely on augmentative alternative communication methods. Patient-reported outcomes indicate acceptance of the condition and sufficient coping in the long term. However, acoustic rated voice quality is abnormal at all post-surgery time-points. AVQI proved to be a useful instrument to evaluate TE-speech. There is a need for validation and determination of cut-off values for VHI-10 and AVQI for use in TE-speech.


Assuntos
Disfonia , Laringectomia , Austrália , Humanos , Países Baixos , Estudos Prospectivos , Acústica da Fala , Medida da Produção da Fala
20.
Air Med J ; 40(1): 54-59, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33455627

RESUMO

OBJECTIVE: The aeromedical transport of coronavirus patients presents risks to clinicians and aircrew. Patient positioning and physical barriers may provide additional protection during flight. This paper describes airflow testing undertaken on fixed wing and rotary wing aeromedical aircraft. METHODS: Airflow testing was undertaken on a stationary Hawker Beechcraft B200C and Leonardo Augusta Westland 139. Airflow was simulated using a Trainer 101 (MSS Professional A/S, Odense Sø, Syddanmark, Denmark) Smoke machine. Different cabin configurations were used along with variations in heating, cooling, and ventilation systems. RESULTS: For the Hawker Beechcraft B200C, smoke generated within the forward section of the cabin was observed to fill the cabin to a fluid boundary located in-line with the forward edge of the cargo door. With the curtain closed, smoke was only observed to enter the cockpit in very small quantities. For the Leonardo AW139, smoke generated within the cabin was observed to expand to fill the cabin evenly before dissipating. With the curtain closed, smoke was observed to enter the cockpit only in small quantities CONCLUSION: The use of physical barriers in fixed wing and rotary wing aeromedical aircraft provides some protection to aircrew. Optimal positioning of the patient is on the aft stretcher on the Beechcraft B200C and on a laterally orientated stretcher on the AW139. The results provide a baseline for further investigation into methods to protect aircrew during the coronavirus pandemic.


Assuntos
Resgate Aéreo , Ar Condicionado/métodos , Movimentos do Ar , COVID-19/prevenção & controle , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Ventilação/métodos , Ar Condicionado/instrumentação , COVID-19/transmissão , Humanos , Ventilação/instrumentação
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