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BACKGROUND: With the approval of disease-modifying treatments (DMTs) for early Alzheimer's disease (AD), there is an increased need for efficient and non-invasive detection methods for cerebral amyloid-ß (Aß) pathology. Current methods, including positron emission tomography (PET) and cerebrospinal fluid (CSF) analysis, are costly and invasive methods that may limit access to new treatments. Plasma tau phosphorylated at threonine-217 (P-tau217) presents a promising alternative, yet optimal cutoffs for treatment eligibility with DMTs like aducanumab require further investigation. This study evaluates the efficacy of one- and two-cutoff strategies for determining DMT eligibility at the Butler Hospital Memory & Aging Program (MAP). METHODS: In this retrospective, cross-sectional diagnostic cohort study, we first developed P-tau217 cutoffs using site-specific and BioFINDER-2 training data, which were then tested in potential DMT candidates from Butler MAP (total n = 150). ROC analysis was used to calculate the area under the curve (AUC) and accuracy of P-tau217 interpretation strategies, using Aß-PET/CSF testing as the standard of truth. RESULTS: Potential DMT candidates at Butler MAP (n = 50), primarily diagnosed with mild cognitive impairment (n = 29 [58%]) or mild dementia (21 [42%]), were predominantly Aß-positive (38 [76%]), and half (25 [50%]) were subsequently treated with aducanumab. Elevated P-tau217 predicted cerebral Aß positivity in potential DMT candidates (AUC = 0.97 [0.92-1]), with diagnostic accuracy ranging from 0.88 (0.76-0.95, p = 0.028) to 0.96 (0.86-1, p < .001). When using site-specific cutoffs, a subset of DMT candidates (10%) exhibited borderline P-tau217 (between 0.273 and 0.399 pg/mL) that would have potentially required confirmatory testing. CONCLUSIONS: This study, which included participants treated with aducanumab, confirms the utility of one- and two-cutoff strategies for interpreting plasma P-tau217 in assessing DMT eligibility. Using P-tau217 could potentially replace more invasive diagnostic methods, and all aducanumab-treated participants would have been deemed eligible based on P-tau217. However, false positives remain a concern, particularly when applying externally derived cutoffs that exhibited lower specificity which could have led to inappropriate treatment of Aß-negative participants. Future research should focus on prospective validation of P-tau217 cutoffs to enhance their generalizability and inform standardized treatment decision-making across diverse populations.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Proteínas tau , Humanos , Doença de Alzheimer/sangue , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/diagnóstico por imagem , Proteínas tau/sangue , Proteínas tau/líquido cefalorraquidiano , Feminino , Masculino , Idoso , Estudos Retrospectivos , Estudos Transversais , Peptídeos beta-Amiloides/sangue , Biomarcadores/sangue , Anticorpos Monoclonais Humanizados/uso terapêutico , Fosforilação , Imunoterapia/métodos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Estudos de Coortes , Tomografia por Emissão de Pósitrons/métodosRESUMO
Background: Older adults with heart failure are at elevated risk of Alzheimer's disease and related dementias (AD/ADRD). Research suggests that insomnia and depressive episodes contribute somewhat dissociable impacts on risk for AD/ADRD in this patient population, although the temporal ordering of effects is unknown. Objective: This study examined time to dementia diagnosis among patients with comorbid insomnia and/or depressive episodes in an epidemiological sample. Methods: Secondary data analyses were conducted using a cohort study of 203,819 Veterans with a primary admission diagnosis of heart failure in 129 VA Medical Centers. Results: Patients with diagnoses of both insomnia and depressive episodes had the shortest time to a dementia diagnosis at both 1-year (Hazard ratioâ=â1.43, 95% CI [1.36, 1.51]) and 3-year follow-up time points (Hazard ratioâ=â1.40, 95% CI [1.34, 1.47]) versus patients with one or neither comorbidity. Conclusions: Individuals with both comorbidities had the shortest time to dementia onset. Screening for these comorbidities may help to identify patients at elevated risk of dementia who could benefit from enhanced monitoring or early intervention strategies for more rapid detection and management of dementia symptoms.
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Comorbidade , Demência , Depressão , Distúrbios do Início e da Manutenção do Sono , Veteranos , Humanos , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Distúrbios do Início e da Manutenção do Sono/diagnóstico , Masculino , Feminino , Demência/epidemiologia , Demência/diagnóstico , Veteranos/psicologia , Idoso , Estudos de Coortes , Depressão/epidemiologia , Depressão/diagnóstico , Idoso de 80 Anos ou mais , Fatores de Tempo , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnósticoRESUMO
Background: With the approval of disease-modifying treatments (DMTs) for early Alzheimer's disease (AD), there is an increased need for efficient and non-invasive detection methods for cerebral amyloid-ß (Aß) pathology. Current methods, including positron emission tomography (PET) and cerebrospinal fluid (CSF) analysis, are costly and invasive methods that may limit access to new treatments. Plasma tau phosphorylated at threonine-217 (P-tau217) presents a promising alternative, yet optimal cutoffs for treatment eligibility with DMTs like aducanumab require further investigation. This study evaluates the efficacy of one- and two-cutoff strategies for determining DMT eligibility at the Butler Hospital Memory & Aging Program (MAP). Methods: In this retrospective, cross-sectional diagnostic cohort study, we first developed P-tau217 cutoffs using site-specific training data and BioFINDER-2, which were then tested in potential DMT candidates from Butler MAP (total n = 150). ROC analysis was used to calculate the area under the curve (AUC) and accuracy of P-tau217 interpretation strategies, using Aß-PET/CSF testing as the standard of truth. Results: Potential DMT candidates at Butler MAP (n = 50), primarily diagnosed with mild cognitive impairment (n = 29 [58%]) or mild dementia (21 [42%]), were predominantly Aß-positive (38 [76%]), and half (25 [50%]) were subsequently treated with aducanumab. Elevated P-tau217 predicted cerebral Aß positivity in potential DMT candidates (AUC = 0.97 [0.92-1]), with diagnostic accuracy ranging from 0.88 (0.76-0.95, p = 0.028) to 0.96 (0.86-1, p < .001). When using site-specific cutoffs, a subset of DMT candidates (10%) exhibited borderline P-tau217 (between 0.273 and 0.399 pg/mL) that would have potentially required from confirmatory testing. Conclusions: This study, which included participants treated with aducanumab, confirms the utility of one- and two-cutoff strategies for interpreting plasma P-tau217 in assessing DMT eligibility. Using P-tau217 could potentially replace more invasive diagnostic methods, and all aducanumab-treated participants would have been deemed eligible based on P-tau217. However, false positives remain a concern, particularly when applying externally derived cutoffs that exhibited lower specificity which could have led to inappropriate treatment of Aß-negative participants. Future research should focus on prospective validation of P-tau217 cutoffs to enhance their generalizability and inform standardized treatment decision-making across diverse populations.
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Contributions of brain glutamate (Glu) to conscious emotion are not well understood. Here, we evaluate the relationship of experimentally induced change in neocortical Glu (ΔGlu) and subjective states in well individuals, using combined application of pharmacological challenge, magnetic resonance spectroscopy (MRS), and comprehensive affective assessment. Drug challenge with d-amphetamine (AMP) (20 mg oral), methamphetamine (MA) (Desoxyn, 20 mg oral), and placebo (PBO) was conducted on three separate test days in a within-subjects double blind design. Proton MRS quantified neurometabolites in the right dorsal anterior cingulate cortex 140-150 min post-drug and PBO. Subjective states were assessed at half hour intervals over 5.5 h on each session, yielding 3792 responses per participant (91,008 responses overall, N = 24 participants), with self-reports reduced by principal components analysis (PCA). PCA produced a primary factor score of AMP- and MA-induced positive agency (ΔPA). MRS indicated drug-induced ΔGlu related positively to ΔPA (ΔGluMA r = +0.44, p < 0.05, N = 21), with large effects in females (ΔGluMA r = +0.52, p < 0.05; ΔGluAMP r = +0.61, p < 0.05, N = 11). Subjective states related to ΔGlu included rise in subjective stimulation, vigor, friendliness, elation, positive mood, positive affect (r's = +0.51 to +0.74, p < 0.05), and alleviation of anxiety in females (r = -0.61, p < 0.05, N = 11). These self-reports correlated with ΔGlu to the extent they loaded on ΔPA (r = 0.95 AMP, p = 5 × 10-10; r = 0.63 MA, p = 0.0015, N = 11), indicating the coherence of ΔGlu effects on emotional states. Timing data indicated Glu shaped positive emotion both concurrently and prospectively, with no relationship with pre-MRS emotion (ΔGluAMP r = +0.59 to +0.65, p's < 0.05; ΔGluMA r = +0.53, p < 0.05, N = 11). Together these findings indicate substantive, mechanistic contributions of neocortical Glu to positive agentic states in healthy individuals, which are most readily observed in women. The findings illustrate the promise of combined application of pharmacological challenge, comprehensive affective assessment, and MRS neuroimaging techniques in basic and clinical studies.
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Ácido Glutâmico , Metanfetamina , Feminino , Humanos , Encéfalo , Glutamina , Espectroscopia de Ressonância Magnética/métodos , Método Duplo-CegoRESUMO
Contributions of brain glutamate to conscious emotion are not well understood. Here we evaluate the relationship of experimentally-induced change in neocortical glutamate (ΔGlu) and subjective states in well individuals. Drug challenge with d-amphetamine (AMP; 20 mg oral), methamphetamine (MA; Desoxyn®, 20 mg oral), and placebo (PBO) was conducted on three separate test days in a within-subjects double blind design. Proton magnetic resonance spectroscopy (MRS) quantified neurometabolites in the right dorsal anterior cingulate cortex (dACC) 140-150 m post-drug and PBO. Subjective states were assessed at half hour intervals over 5.5-hours on each session, yielding 3,792 responses per participant (91,008 responses overall, N=24 participants). Self-reports were reduced by principal components analysis to a single factor score of AMP- and MA-induced Positive Agency (ΔPA) in each participant. We found drug-induced ΔGlu related positively with ΔPA (ΔGluMA r=+.44, p<.05, N=21), with large effects in females (ΔGluMA r=+.52, p<.05; ΔGluAMP r=+.61, p<.05, N=11). States related to ΔGlu in females included rise in subjective stimulation, vigor, friendliness, elation, positive mood, positive affect (r's=+.51 to +.74, p<.05), and alleviation of anxiety (r=-.61, p<.05, N=11). Self-reports correlated with DGlu to the extent they loaded on ΔPA (r=.95 AMP, p=5×10-10; r=.63 MA, p=.0015, N=11), indicating coherence of ΔGlu effects. Timing data indicated Glu shaped emotion both concurrently and prospectively, with no relationship to pre-MRS emotion (ΔGluAMP r=+.59 to +.65, p's<.05; ΔGluMA r=+.53, p<.05, N=11). Together these findings indicate substantive, mechanistic contributions of neocortical Glu to positive agentic states in healthy individuals, most readily observed in women.
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Introduction: Anger can engender action by individuals and groups. It is thus important to understand anger's behavioral phenotypes and their underlying neural substrates. Here, we introduce a construct we term agentic anger, a negatively valenced internal state that motivates action to achieve risky goals. We evaluate our neurobehavioral model via testable hypotheses in two proof-of-concept studies. Study 1 Methods: Study 1 used the Incentive Balloon Analogue Risk Task in a within-subjects, repeated measures design in 39 healthy volunteers to evaluate: (a) impact of blockade of reward on agentic anger, assessed by self-reports of negative activation (NA), (b) impact of achievement of reward on exuberance, assessed by self-reports of positive activation (PA), (c) the interrelationship of these valenced states, and (d) their relationship with personality. Study 1 Results: Task-induced NA was positively correlated with task-induced PA, risk-taking on the task and trait Social Potency (SP), a measure of trait agency and reward sensitivity on the Multidimensional Personality Questionnaire Brief-Form. Study 2 Methods: Study 2 assessed functional MRI response to stakes for risk-taking in healthy volunteers receiving 20 mg d-amphetamine in a double-blinded, placebo-controlled crossover design (N = 10 males), providing preliminary information on ventral striatal response to risky rewards during catecholamine activation. Study 2 Results: Trait SP and task-induced PA were strongly positively related to catecholamine-facilitated BOLD response in the right nucleus accumbens, a brain region where DA prediction error signal shapes action value and selection. Participants' task-induced NA was strongly positively related with trait SP and task-induced PA, replicating the findings of Study 1. Discussion: Together these results inform the phenomenology and neurobiology of agentic anger, which recruits incentive motivational circuitry and motivates personal action in response to goals that entail risk (defined as exposure to uncertainty, obstacles, potential harm, loss and/or financial, emotional, bodily, or moral peril). Neural mechanisms of agency, anger, exuberance, and risk-taking are discussed, with implications for personal and group action, decision-making, social justice, and behavior change.
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Twisted bilayer graphene provides an ideal solid-state model to explore correlated material properties and opportunities for a variety of optoelectronic applications, but reliable, fast characterization of the twist angle remains a challenge. Here we introduce spectroscopic ellipsometric contrast microscopy (SECM) as a tool for mapping twist angle disorder in optically resonant twisted bilayer graphene. We optimize the ellipsometric angles to enhance the image contrast based on measured and calculated reflection coefficients of incident light. The optical resonances associated with van Hove singularities correlate well to Raman and angle-resolved photoelectron emission spectroscopy, confirming the accuracy of SECM. The results highlight the advantages of SECM, which proves to be a fast, nondestructive method for characterization of twisted bilayer graphene over large areas, unlocking process, material, and device screening and cross-correlative measurement potential for bilayer and multilayer materials.
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Understanding the growth mechanisms of III-nitride nanowires is of great importance to realise their full potential. We present a systematic study of silane-assisted GaN nanowire growth on c-sapphire substrates by investigating the surface evolution of the sapphire substrates during the high temperature annealing, nitridation and nucleation steps, and the growth of GaN nanowires. The nucleation step - which transforms the AlN layer formed during the nitridation step to AlGaN - is critical for subsequent silane-assisted GaN nanowire growth. Both Ga-polar and N-polar GaN nanowires were grown with N-polar nanowires growing much faster than the Ga-polar nanowires. On the top surface of the N-polar GaN nanowires protuberance structures were found, which relates to the presence of Ga-polar domains within the nanowires. Detailed morphology studies revealed ring-like features concentric with the protuberance structures, indicating energetically favourable nucleation sites at inversion domain boundaries. Cathodoluminescence studies showed quenching of emission intensity at the protuberance structures, but the impact is limited to the protuberance structure area only and does not extend to the surrounding areas. Hence it should minimally affect the performance of devices whose functions are based on radial heterostructures, suggesting that radial heterostructures remain a promising device structure.
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OBJECTIVE: We hypothesized that keratouveitis still occurs despite current widespread use of Canine adenovirus (CAV)-2 vaccinations and assessed the utility of CAV-1 and CAV-2 titers in elucidation of its etiopathogenesis. ANIMALS STUDIED: Nine dogs with unexplained keratouveitis (14 eyes) and nine control dogs. PROCEDURES: The Animal Health Trust clinical database was searched between 2008 and 2018 to identify cases of keratouveitis. Inclusion criteria included known vaccination status, interval from vaccination to development of clinical signs and availability of CAV titers. Cases were excluded if they were older than 1 year of age, or other causative ocular pathology for corneal edema was identified. Nine age-matched dogs without corneal edema but with CAV titers were included as controls. RESULTS: Mean CAV-1 and CAV-2 titers were not statistically different between dogs with keratouveitis and controls (p = .16 and p = .76, respectively). Three cases had CAV-1 titers >5000 and two of these cases had rising convalescence titers (greater than an 11-fold increase) suggesting infection with wild-type CAV-1. The six other cases did not appear to be associated with CAV infection or vaccination. CONCLUSION: Keratouveitis continues to occur despite the advent of CAV-2 vaccinations. While this study found no evidence to indicate CAV-2 vaccination causes keratouveitis, the data indicates that in a proportion of cases, contemporaneous wild-type CAV-1 infection is a possible cause.
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Infecções por Adenoviridae , Adenovirus Caninos , Edema da Córnea , Doenças do Cão , Ceratite , Cães , Animais , Doenças do Cão/diagnóstico , Edema da Córnea/veterinária , Vacinação/veterinária , Ceratite/veterinária , Infecções por Adenoviridae/complicações , Infecções por Adenoviridae/diagnóstico , Infecções por Adenoviridae/veterináriaRESUMO
We present a high-throughput method for identifying and characterizing individual nanowires and for automatically designing electrode patterns with high alignment accuracy. Central to our method is an optimized machine-readable, lithographically processable, and multi-scale fiducial marker systemâdubbed LithoTagâwhich provides nanostructure position determination at the nanometer scale. A grid of uniquely defined LithoTag markers patterned across a substrate enables image alignment and mapping in 100% of a set of >9000 scanning electron microscopy (SEM) images (>7 gigapixels). Combining this automated SEM imaging with a computer vision algorithm yields location and property data for individual nanowires. Starting with a random arrangement of individual InAs nanowires with diameters of 30 ± 5 nm on a single chip, we automatically design and fabricate >200 single-nanowire devices. For >75% of devices, the positioning accuracy of the fabricated electrodes is within 2 pixels of the original microscopy image resolution. The presented LithoTag method enables automation of nanodevice processing and is agnostic to microscopy modality and nanostructure type. Such high-throughput experimental methodology coupled with data-extensive science can help overcome the characterization bottleneck and improve the yield of nanodevice fabrication, driving the development and applications of nanostructured materials.
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Waveguide modes are well-known to be a valuable light-trapping resource for absorption enhancement in solar cells. However, their scarcity in the thinnest device stacks compromises the multiresonant performance required to reach the highest efficiencies in ultrathin devices. We demonstrate that enriching the modal structure on such reduced length-scales is possible by integrating transparent semiconductor/dielectric scattering structures to the device architecture as opposed to more widely studied metallic textures. This phenomenon allows transparent quasi-random structures to emerge as strong light-trapping candidates for ultrathin solar cells, given that their broad scattering profiles are well-suited to exploit the increased number of waveguide modes for multiresonant absorption enhancement. A thorough study of the design space of quasi-random textures comprising more than 1500 designs confirms the superiority of transparent structures over a metallic embodiment, identifies broad and flexible design requirements to achieve optimal performances, and demonstrates photon harvesting capabilities leading to 20% efficiency with an 80 nm GaAs absorber. Our light-trapping strategy can be applied to a wide range of material systems and device architectures, is compatible with scalable low-cost fabrication techniques, and can assist current trends to reach the highest efficiencies in ever-thinner photovoltaics.
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Photoelectrochemical (PEC) artificial leaves hold the potential to lower the costs of sustainable solar fuel production by integrating light harvesting and catalysis within one compact device. However, current deposition techniques limit their scalability1, whereas fragile and heavy bulk materials can affect their transport and deployment. Here we demonstrate the fabrication of lightweight artificial leaves by employing thin, flexible substrates and carbonaceous protection layers. Lead halide perovskite photocathodes deposited onto indium tin oxide-coated polyethylene terephthalate achieved an activity of 4,266 µmol H2 g-1 h-1 using a platinum catalyst, whereas photocathodes with a molecular Co catalyst for CO2 reduction attained a high CO:H2 selectivity of 7.2 under lower (0.1 sun) irradiation. The corresponding lightweight perovskite-BiVO4 PEC devices showed unassisted solar-to-fuel efficiencies of 0.58% (H2) and 0.053% (CO), respectively. Their potential for scalability is demonstrated by 100 cm2 stand-alone artificial leaves, which sustained a comparable performance and stability (of approximately 24 h) to their 1.7 cm2 counterparts. Bubbles formed under operation further enabled 30-100 mg cm-2 devices to float, while lightweight reactors facilitated gas collection during outdoor testing on a river. This leaf-like PEC device bridges the gulf in weight between traditional solar fuel approaches, showcasing activities per gram comparable to those of photocatalytic suspensions and plant leaves. The presented lightweight, floating systems may enable open-water applications, thus avoiding competition with land use.
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[This corrects the article DOI: 10.1371/journal.pone.0251071.].
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INTRODUCTION: Repetitive Transcranial magnetic stimulation (rTMS) is an FDA approved treatment for major depressive disorder (MDD). However, neural mechanisms contributing to rTMS effects on depressive symptoms, cognition, and behavior are unclear. Proton magnetic resonance spectroscopy (MRS), a noninvasive neuroimaging technique measuring concentrations of biochemical compounds within the brain in vivo, may provide mechanistic insights. METHODS: This systematic review summarized published MRS findings from rTMS treatment trials to address potential neurometabolic mechanisms of its antidepressant action. Using PubMed, Google Scholar, Web of Science, and JSTOR, we identified twelve empirical studies that evaluated changes in MRS metabolites in a within-subjects, pre- vs. post-rTMS treatment design in patients with MDD. RESULTS: rTMS protocols ranged from four days to eight weeks duration, were applied at high frequency to the left dorsolateral prefrontal cortex (DLPFC) in most studies, and were conducted in patients aged 13-to-70. Most studies utilized MRS point resolved spectroscopy acquisitions at 3 Tesla in the bilateral anterior cingulate cortex and DLPFC. Symptom improvements were correlated with rTMS-related increases in the concentration of glutamatergic compounds (glutamate, Glu, and glutamine, Gln), GABA, and N-acetylated compounds (NAA), with some results trend-level. CONCLUSIONS: This is the first in-depth systematic review of metabolic effects of rTMS in individuals with MDD. The extant literature suggests rTMS stimulation does not produce changes in neurometabolites independent of clinical response; increases in frontal lobe glutamatergic compounds, N-acetylated compounds and GABA following high frequency left DLPFC rTMS therapy were generally associated with clinical improvement. Glu, Gln, GABA, and NAA may mediate rTMS treatment effects on MDD symptomatology through intracellular mechanisms.
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Transtorno Depressivo Maior , Neocórtex , Depressão , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/metabolismo , Transtorno Depressivo Maior/terapia , Ácido Glutâmico/metabolismo , Glutamina/metabolismo , Humanos , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/metabolismo , Estimulação Magnética Transcraniana/métodos , Resultado do Tratamento , Ácido gama-Aminobutírico/metabolismoRESUMO
The influence of nanowire (NW) surface states increases rapidly with the reduction of diameter and hence severely degrades the optoelectronic performance of narrow-diameter NWs. Surface passivation is therefore critical, but it is challenging to achieve long-term effective passivation without significantly affecting other qualities. Here, we demonstrate that an ultrathin InP passivation layer of 2-3 nm can effectively solve these challenges. For InAsP nanowires with small diameters of 30-40 nm, the ultrathin passivation layer reduces the surface recombination velocity by at least 70% and increases the charge carrier lifetime by a factor of 3. These improvements are maintained even after storing the samples in ambient atmosphere for over 3 years. This passivation also greatly improves the performance thermal tolerance of these thin NWs and extends their operating temperature from <150 K to room temperature. This study provides a new route toward high-performance room-temperature narrow-diameter NW devices with long-term stability.
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Magnetic field-driven insulating states in graphene are associated with samples of very high quality. Here, this state is shown to exist in monolayer graphene grown by chemical vapor deposition (CVD) and wet transferred on Al2O3 without encapsulation with hexagonal boron nitride (h-BN) or other specialized fabrication techniques associated with superior devices. Two-terminal measurements are performed at low temperature using a GaAs-based multiplexer. During high-throughput testing, insulating properties are found in a 10 µm long graphene device which is 10 µm wide at one contact with an ≈440 nm wide constriction at the other. The low magnetic field mobility is ≈6000 cm2 V-1 s-1. An energy gap induced by the magnetic field opens at charge neutrality, leading to diverging resistance and current switching on the order of 104 with DC bias voltage at an approximate electric field strength of ≈0.04 V µm-1 at high magnetic field. DC source-drain bias measurements show behavior associated with tunneling through a potential barrier and a transition between direct tunneling at low bias to Fowler-Nordheim tunneling at high bias from which the tunneling region is estimated to be on the order of ≈100 nm. Transport becomes activated with temperature from which the gap size is estimated to be 2.4 to 2.8 meV at B = 10 T. Results suggest that a local electronically high quality region exists within the constriction, which dominates transport at high B, causing the device to become insulating and act as a tunnel junction. The use of wet transfer fabrication techniques of CVD material without encapsulation with h-BN and the combination with multiplexing illustrates the convenience of these scalable and reasonably simple methods to find high quality devices for fundamental physics research and with functional properties.
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AIM: Pain is a common complication of spinal cord injuries (SCI). Our objective was to quantify those who had pain on discharge from rehabilitation, and the level of interference it had on their functionality. METHOD: This study used data collected prospectively from 2018 to 2019 via the New Zealand Spinal Cord Injury Registry (NZSCIR). Questionnaires completed by patients on discharge provided the necessary data. Primary outcomes were the number of patients reporting pain, and the level of interference with their activities of daily living (ADLs), mood and sleep. Level of interference was quantified via a score from zero to 10. Scores of seven and above were considered "severe" interference. RESULTS: Seventy-six-point six percent of patients in this study group reported having pain on discharge. The median scores for interference with functionality were all three out of 10. Twenty-three-point eight percent of patients reported severe interference with sleep, 16.7% with ADLs and 16.2% with mood. CONCLUSION: The number of patients being discharged with pain from SCI rehabilitation units in New Zealand is similar to figures from other literature. Although significant functional impairments were not found overall, focus remains to optimise management for patients who do report "severe" interference.
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Atividades Cotidianas , Traumatismos da Medula Espinal , Humanos , Nova Zelândia/epidemiologia , Dor/etiologia , Traumatismos da Medula Espinal/complicações , Alta do PacienteRESUMO
Metamaterial photonic integrated circuits with arrays of hybrid graphene-superconductor coupled split-ring resonators (SRR) capable of modulating and slowing down terahertz (THz) light are introduced and proposed. The hybrid device's optical responses, such as electromagnetic-induced transparency (EIT) and group delay, can be modulated in several ways. First, it is modulated electrically by changing the conductivity and carrier concentrations in graphene. Alternatively, the optical response can be modified by acting on the device temperature sensitivity by switching Nb from a lossy normal phase to a low-loss quantum mechanical phase below the transition temperature (Tc) of Nb. Maximum modulation depths of 57.3% and 97.61% are achieved for EIT and group delay at the THz transmission window, respectively. A comparison is carried out between the Nb-graphene-Nb coupled SRR-based devices with those of Au-graphene-Au SRRs, and significant enhancements of the THz transmission, group delay, and EIT responses are observed when Nb is in the quantum mechanical phase. Such hybrid devices with their reasonably large and tunable slow light bandwidth pave the way for the realization of active optoelectronic modulators, filters, phase shifters, and slow light devices for applications in chip-scale future communication and computation systems.
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Plasmonics, as a rapidly growing research field, provides new pathways to guide and modulate highly confined light in the microwave-to-optical range of frequencies. We demonstrated a plasmonic slot waveguide, at the nanometer scale, based on the high-transition-temperature (Tc) superconductor Bi2Sr2CaCu2O8+δ (BSCCO), to facilitate the manifestation of chip-scale millimeter wave (mm-wave)-to-terahertz (THz) integrated circuitry operating at cryogenic temperatures. We investigated the effect of geometrical parameters on the modal characteristics of the BSCCO plasmonic slot waveguide between 100 and 800 GHz. In addition, we investigated the thermal sensing of the modal characteristics of the nanoscale superconducting slot waveguide and showed that, at a lower frequency, the fundamental mode of the waveguide had a larger propagation length, a lower effective refractive index, and a strongly localized modal energy. Moreover, we found that our device offered a larger SPP propagation length and higher field confinement than the gold plasmonic waveguides at broad temperature ranges below BSCCO's Tc. The proposed device can provide a new route toward realizing cryogenic low-loss photonic integrated circuitry at the nanoscale.
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PURPOSE: Three related male English Cocker Spaniels (ECS) were reported to be congenitally blind. Examination of one of these revealed complete retinal detachment. A presumptive diagnosis of retinal dysplasia (RD) was provided and pedigree analysis was suggestive of an X-linked mode of inheritance. We sought to investigate the genetic basis of RD in this family of ECS. METHODS: Following whole genome sequencing (WGS) of the one remaining male RD-affected ECS, two distinct investigative approaches were employed: a candidate gene approach and a whole genome approach. In the candidate gene approach, COL9A2, COL9A3, NHEJ1, RS1 and NDP genes were investigated based on their known associations with RD and retinal detachment in dogs and humans. In the whole genome approach, affected WGS was compared with 814 unaffected canids to identify candidate variants, which were filtered based on appropriate segregation and predicted pathogenic effects followed by subsequent investigation of gene function. Candidate variants were tested for appropriate segregation in the ECS family and association with disease was assessed using samples from a total of 180 ECS. RESULTS: The same variant in NDP (c.653_654insC, p.Met114Hisfs*16) that was predicted to result in 15 aberrant amino acids before a premature stop in norrin protein, was identified independently by both approaches and was shown to segregate appropriately within the ECS family. Association of this variant with X-linked RD was significant (P = 0.0056). CONCLUSIONS: For the first time, we report a variant associated with canine X-linked RD. NDP variants are already known to cause X-linked RD, along with other abnormalities, in human Norrie disease. Thus, the dog may serve as a useful large animal model for research.