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Relative intensity noise (RIN) can be used to characterize pulse-to-pulse energy variations of ultrafast lasers, and is a very important performance parameter when considering the suitability of a laser for an application. However, owing to a wide range of measurement and analysis techniques, comparison of RIN values is non-trivial. Here, we clearly layout a definition of RIN as a percentage value for ultrafast laser systems. Furthermore, we analytically describe how the RIN can be measured in the time and frequency domains, and reveal the conditions under which these two widely employed approaches are equivalent. Finally, we experimentally measure the RIN of an ultrafast supercontinuum laser to be 6.57% in the time domain and 6.98% in the frequency domain at 850 nm, and 17.06% in the time domain and 17.08% in the frequency domain at 1000 nm, thus demonstrating the expected strong agreement when the measurements and signal processing are performed appropriately.
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UV supercontinuum laser sources based on resonant dispersive wave (RDW) generation in gas-filled hollow-core (HC) fibers offer an attractive architecture for numerous applications. However, the narrow UV spectral peak inherent to RDW generation limits the suitability for applications that require broad spectral coverage within the UV region such as spectroscopic scatterometry. In this Letter, we demonstrate how the UV spectrum can be shaped by modulating the peak power of the pump pulses driving the RDW generation, thereby creating a broadened and flattened UV spectrum. Using an argon-filled anti-resonant HC fiber, we generate a UV spectrum with a center wavelength of 323.6 nm with an FWHM of 51.7 nm, corresponding to a relative bandwidth of 16.1%.
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BACKGROUND: In Parkinson's disease, mild cognitive impairment and dementia are associated with α-synuclein deposition and spread. However, coexistent Alzheimer's disease and cerebrovascular disease are common at autopsy, and may affect cognition. Our objective was to map cognitive impairment in Parkinson's disease to these different causes using clinical assessment. METHODS: Neuropsychological testing was performed in a cross-sectional sample of cognitively impaired patients with Parkinson's disease. The pattern of deficits in varying cognitive domains was mapped to the presentations that typify different diseases. Data were analysed by an expert multidisciplinary panel, referencing diagnostic criteria, to reach a consensus diagnosis for the cognitive dysfunction. RESULTS: There were 45 participants with Parkinson's disease and cognitive impairment, 73.3% male, mean age 69.1 years (SD 8.3). Twenty-seven (60.0%) had mild cognitive impairment, and 18 had dementia (40.0%). Cognitive impairment was primarily attributable to Lewy body disease alone in 19 of 45 patients (42.2%), to Lewy body disease plus Alzheimer's in 14 of 45 (31.1%), to Lewy body plus cerebrovascular disease in 6 of 45 (13.3%), and to Lewy body plus Alzheimer's and cerebrovascular disease in 1 of 45 (2.2%). The cognitive decline was not primarily Lewy-related in 5 of 45 patients (11.1%); in 4 of 45 (8.9%), it was primarily attributable to Alzheimer's disease, and 1 of 45 (2.2%) had behavioural-variant frontotemporal dementia. CONCLUSION: Neuropsychological testing identifies distinct patterns of cognitive impairment in Parkinson's disease that provide clear pointers to comorbid disease processes, the most common being Alzheimer's disease. This approach may prove useful in clinical practice and has implications for clinical trials that target α-synuclein.
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Disfunção Cognitiva/complicações , Disfunção Cognitiva/psicologia , Testes Neuropsicológicos , Doença de Parkinson/complicações , Doença de Parkinson/psicologia , Idoso , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/psicologia , Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/diagnóstico , Transtornos Cerebrovasculares/psicologia , Disfunção Cognitiva/diagnóstico , Estudos Transversais , Feminino , Humanos , Doença por Corpos de Lewy/complicações , Doença por Corpos de Lewy/diagnóstico , Doença por Corpos de Lewy/psicologia , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnósticoRESUMO
OBJECTIVES: The Montreal Cognitive Assessment (MoCA) is a common tool for screening mild cognitive impairment (MCI) and dementia. Studies in multiple clinical groups provide evidence for various factor structures mapping to different cognitive domains. We tested the factor structure of the MoCA in a large cohort of early Parkinson disease (PD). MATERIALS AND METHODS: Complete MoCA data were available from an observational cohort study for 1738 patients with recent-onset PD (64.6% male, mean age 67.6, SD 9.2). Confirmatory factor analysis (CFA) was applied to test previously defined two-factor, six-factor, and three-factor models in the full sample and in a subgroup with possible cognitive impairment (MoCA < 26). Secondary analysis used exploratory factor analysis (EFA; principal factors with oblique rotation). RESULTS: The mean MoCA score was 25.3 (SD 3.4, range 10-30). Fit statistics in the six-factor model (χ2 /df 17.77, root mean square error of approximation [RMSEA] 0.10, comparative fit index [CFI] 0.74, Tucker-Lewis index [TLI] 0.69, standardised root mean square residual [SRMR] 0.07) indicated poorer fit than did previous studies. Findings were similar in the two-factor and three-factor models. EFA suggested an alternative six-factor solution (short-term recall, visuospatial-executive, attention/working memory, verbal-executive, orientation, and expressive language), although CFA did not support the validity of the new model. CONCLUSIONS: The factor structure of the MoCA in early PD was not consistent with that of previous research. This may reflect higher cognitive performance and differing demographics in our sample. The results do not support a clear, clinically relevant factor structure in an early PD group, suggesting that the MoCA should be followed with detailed assessment to obtain domain-specific cognitive profiles.
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Disfunção Cognitiva/diagnóstico , Testes de Estado Mental e Demência , Doença de Parkinson/psicologia , Idoso , Estudos de Coortes , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Dementia is a common, debilitating feature of late Parkinson's disease (PD). PD dementia (PDD) is associated with α-synuclein propagation, but coexistent Alzheimer's disease (AD) pathology may coexist. Other pathologies (cerebrovascular, transactive response DNA-binding protein 43 (TDP-43)) may also influence cognition. We aimed to describe the neuropathology underlying dementia in PD. METHODS: Systematic review of autopsy studies published in English involving PD cases with dementia. Comparison groups included PD without dementia, AD, dementia with Lewy bodies (DLB) and healthy controls. RESULTS: 44 reports involving 2002 cases, 57.2% with dementia, met inclusion criteria. While limbic and neocortical α-synuclein pathology had the strongest association with dementia, between a fifth and a third of all PD cases in the largest studies had comorbid AD. In PD cases with dementia, tau pathology was moderate or severe in around a third, and amyloid-ß pathology was moderate or severe in over half. Amyloid-ß was associated with a more rapid cognitive decline and earlier mortality, and in the striatum, distinguished PDD from DLB. Positive correlations between multiple measures of α-synuclein, tau and amyloid-ß were found. Cerebrovascular and TDP-43 pathologies did not generally contribute to dementia in PD. TDP-43 and amyloid angiopathy correlated with coexistent Alzheimer pathology. CONCLUSIONS: While significant α-synuclein pathology is the main substrate of dementia in PD, coexistent pathologies are common. In particular, tau and amyloid-ß pathologies independently contribute to the development and pattern of cognitive decline in PD. Their presence should be assessed in future clinical trials where dementia is a key outcome measure. TRIAL REGISTRATION NUMBER: CRD42018088691.
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Doença de Alzheimer/epidemiologia , Doença de Alzheimer/patologia , Autopsia , Encéfalo/patologia , Demência/epidemiologia , Demência/patologia , Doença de Parkinson/epidemiologia , Doença de Parkinson/patologia , Autopsia/estatística & dados numéricos , Comorbidade , HumanosRESUMO
Autism Spectrum Disorder (ASD) is associated with complex distress and challenging behaviours that have a negative impact on the everyday life of those with ASD, as well as their parents and carers. These challenging behaviours include negative emotional behaviours, motor behaviours, and changes in routines. Even though challenging behaviours occur in most subjects with ASD, the cause of these largely remains unknown. It has been implicated that these challenging behaviours are associated with a change in the health of those with ASD. More research needs to be conducted that can establish a direct association. Towards this goal, the present study aimed to explore whether health status had an impact on the distressing behaviour in the subjects diagnosed with ASD. We analysed the response from the parents/carers in a Macedonian population of those with ASD, to determine which challenging behaviours were most likely to be observed during a change in health. Based on a scoring system, the manifestation of challenging behaviour was evaluated and compared with the changes in health. Changes in appetite or dietary preferences, irritability and low mood, and loss of previously acquired skills had the greatest association with a change in health. These findings provide early insight into types of challenging behaviours that are directly associated with a change in health. Our results demonstrate a relationship between health status and challenging behaviour in the subject with autism, suggesting that caregivers may need to consider this when choosing strategies for managing challenging behaviour.
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Agenesis of the Corpus Callosum (ACC) can result in multiple neurological deficits including social and behavioural issues. However, the underlying aetiology, clinical co-morbidity and the contributing risk factors remain elusive, resulting in inaccurate prognosis and delayed therapy. The main objective of this study was to comprehensively describe the epidemiology and clinical co-morbidity associated with patients diagnosed with ACC. The secondary objective was to identify the factors that contribute towards increased risk for ACC. For this, we analysed 22 years (1998-2020) of clinical data across the whole of Wales, UK collected through the Congenital Anomaly Register & Information Service (CARIS) and Public Health Wales (PHW). Our results demonstrate that complete ACC (84.1%) was the prevalent subtype, in comparison to partial ACC. Further, ventriculomegaly/hydrocephalus (26.37%) and ventricular septal defect (21.92%) were identified to be the most prevalent neural malformation (NM) and congenital heart disorder (CHD) in our cohort. Although 12.7% of subjects with ACC had both an NM and CHD, we found no significant association between them (χ2 (1, n = 220) = 3.84, p = 0.33). We found socioeconomic deprivation and increased maternal age contributed towards an increased risk for ACC. To the best of our knowledge, this study for the first time defines the clinical phenotypes and the factors that contribute to ACC within the Welsh population. These findings will be of value to both patients and healthcare professionals, who may take preventative or remedial measures.
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Aims To gather the views of dentists practising within North Wales on their preferences as to how they would prefer to interact with the North Wales Local Dental Committee (LDC) (NWLDC).Design Descriptive cross-sectional survey.Setting Online electronic questionnaire.Materials and methods Survey circulated via the NWLDC's current communication channels, local professional groups, the local health board and Health Education and Improvement Wales' MaxCourse email distribution.Results A total of 167 unique responses were received from across North Wales, which included 132 responses from primary care dentists, yielding a response rate of 40.6%. Respondents would prefer to interact with the NWLDC via email notifications (88%), virtual meetings (52.1%) and via the LDC website (41.9%). Furthermore, 31.1% wanted a combination of both physical and virtual attendance at an LDC meeting to be an option and 43.7% of respondents did not want to attend LDC meetings as a preferred method of engaging with the LDC. The survey indicated that holding an educational event just before the LDC meeting will not have a positive impact on subsequent participation in the LDC meeting for 91.6% of respondents. The survey revealed that 70% had never visited the NWLDC's website, with only 20.4% of people visiting it more than once a year. Also, 83.8% stated that the pandemic had made no difference on them accessing the NWLDC website. The results allowed the identification of the top five 'core elements' for an ideal LDC website and which elements should have their access restricted only to LDC members.Conclusions The survey revealed that the respondents want greater communication from the NWLDC and that this is best achieved over a variety of different communication platforms, using the NWLDC website as a primary information resource to which the other communication methods are tethered. It is recognised that only a minority will want to, or be able to, attend the quarterly LDC meetings and so it is imperative that the NWLDC's communication strategy accommodates these individuals, both proactively and passively, by effective use of digital media and to continuously monitor its effectiveness so that it can adapt its strategy to maximise engagement and information delivery. There is a need to expand the representation of the LDC committee to encompass those who have newly entered the profession or are new to the area. The NWLDC recognises the need to reach out to dentists across North Wales who many feel isolated and disenfranchised to establish a constructive, mutually beneficial relationship.
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Aims To gather the views of North Wales dentists on the current communication methods of the North Wales Local Dental Committee (LDC) (NWLDC) and how this could be optimised to improve engagement from members.Design Descriptive cross-sectional survey.Setting Online electronic questionnaire.Materials and methods Survey circulated via the NWLDC's current communication channels, local professional groups, the local health board and Health Education and Improvement Wales' Maxcourse distribution list.Results A total of 167 unique responses were received from across North Wales. In total, 79.1% were from dentists, of which most were working in the general dental services (63.6%) on a mixed practice basis (61.9%). Furthermore, 69.5% of respondents felt they received too little information from the LDC, 71.3% never attended LDC meetings and only 15.6% attended more than one meeting a year. The pandemic has had no impact for 82.6% in increasing their engagement with the LDC.Conclusions Communication between the LDC and the dental community within an area is crucial. This survey has shown that, despite the best of intentions, the current communication methods utilised by the NWLDC are not effective at maximising the inclusiveness and participation with the LDC. The survey revealed that there is a lack of clarity over the LDC's role and who is 'allowed' to attend LDC meetings. It showed that although the dental practitioners practising within North Wales want to receive information and updates from the NWLDC, the communication methods which are currently being used are not reaching the majority of them.
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Climate, deforestation, and forest fires are closely coupled in the Amazon, but models of fire that include these interactions are lacking. We trained machine learning models on temperature, rainfall, deforestation, land-use, and fire data to show that spatial and temporal patterns of fire in the Amazon are strongly modified by deforestation. We find that fire count across the Brazilian Amazon increases by 0.44 percentage points for each percentage point increase in deforestation rate. We used the model to predict that the increased deforestation rate in the Brazilian Amazon from 2013 to 2020 caused a 42% increase in fire counts in 2020. We predict that if Brazil had achieved the deforestation target under the National Policy on Climate Change, there would have been 32% fewer fire counts across the Brazilian Amazon in 2020. Using a regional chemistry-climate model and exposure-response associations, we estimate that the improved air quality due to reduced smoke emission under this scenario would have resulted in 2,300 fewer deaths due to reduced exposure to fine particulate matter. Our analysis demonstrates the air quality and public health benefits that would accrue from reducing deforestation in the Brazilian Amazon.
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The realization of a table-top tunable deep-ultraviolet (UV) laser source with excellent noise properties would significantly benefit the scientific community, particularly within imaging and spectroscopic applications, where source noise has a crucial role. Here we provide a thorough characterization of the pulse-to-pulse relative intensity noise (RIN) of such a deep-UV source based on an argon (Ar)-filled anti-resonant hollow-core (AR HC) fiber. Suitable pump pulses are produced using a compact commercially available laser centered at 1030 nm with a pulse duration of 400 fs, followed by a nonlinear compression stage that generates pulses with 30 fs duration, 24.2 µJ energy at 100 kHz repetition rate and a RIN of < 1%. Pump pulses coupled into the AR HC fiber undergo extreme spectral broadening creating a supercontinuum, leading to efficient energy transfer to a phase-matched resonant dispersive wave (RDW) in the deep-UV spectral region. The center wavelength of the RDW could be tuned between 236 and 377 nm by adjusting the Ar pressure in a 140 mm length of fiber. Under optimal pump conditions the RIN properties were demonstrated to be exceptionally good, with a value as low as 1.9% at ~ 282 nm. The RIN is resolved spectrally for the pump pulses, the generated RDW and the broadband supercontinuum. These results constitute the first broadband RIN characterization of such a deep-UV source and provide a significant step forward towards a stable, compact and tunable laser source for applications in the deep-UV spectral region.
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Deep-UV (DUV) supercontinuum (SC) sources based on gas-filled hollow-core fibers constitute perhaps the most viable solution towards ultrafast, compact, and tunable lasers in the UV spectral region, which can even also extend into the mid-infrared (IR). Noise and spectral stability of such broadband sources are key parameters that define their true potential and suitability towards real-world applications. In order to investigate the spectral stability and noise levels in these fiber-based DUV sources, we generate an SC spectrum that extends from 180 nm (through phase-matched dispersive waves - DWs) to 4 µm by pumping an argon-filled hollow-core anti-resonant fiber at a mid-IR wavelength of 2.45 µm. We characterize the long-term stability of the source over several days and the pulse-to-pulse relative intensity noise (RIN) of the DW at 275 nm. The results indicate no sign of spectral degradation over 110 hours, but the RIN of the DW pulses at 275 nm is found to be as high as 33.3%. Numerical simulations were carried out to investigate the spectral distribution of the RIN and the results confirm the experimental measurements and that the poor noise performance is due to the high RIN of the mid-IR pump laser, which was hitherto not considered in numerical modelling of these sources. The results presented herein provide an important step towards an understanding of the noise mechanism underlying such complex light-gas nonlinear interactions and demonstrate the need for pump laser stabilization.
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BACKGROUND: The detection of prodromal Parkinson's disease (PD) is desirable to test drugs with neuroprotective potential, but will be affected by known disease variations. OBJECTIVE: To assess the prevalence of four key non-motor prodromal PD markers, and evaluate the sensitivity of case detection when non-motor screening tools for prodromal PD are implemented in an early clinical PD cohort. METHODS: Hyposmia (University of Pennsylvania smell identification test ≤15th centile or Sniffin' Sticks at or ≤10th centile corrected for age and sex), rapid-eye movement sleep behaviour disorder (RBD questionnaire >4), constipation (<1 daily spontaneous bowel motion) and depression (Leeds >6) were recorded in recent onset PD cases, and proposed non-motor screening criteria applied. RESULTS: In 1,719 PD cases, mean age 68.6 years (SD 8.1), 65.5% male, mean disease duration 1.3 years (SD 0.9), 72.2% were hyposmic, 43.3% had RBD, 22.1% depression, and 21.5% constipation. 11.6% of cases had no key non-motor features, 38.8% one, 32.1% two, 15.5% three, and 2.0% all four. Increasing numbers of non-motor features were associated with younger age (pâ=â0.019), higher motor scores (pâ<â0.001), more postural instability gait difficulty (PIGD) (pâ<â0.001), greater cognitive impairment (pâ<â0.001) and higher total non-motor burden (pâ<â0.001). Cases with hyposmia alone were younger (pâ<â0.001), had less severe cognitive (p = 0.006) and other non-motor features (pâ<â0.001). All screening criteria selected younger patients (p = 0.001, pâ<â0.001), three of four greater overall non-motor burden (p = 0.005, pâ<â0.001), and inclusion of RBD more cognitive impairment (p = 0.003, p = 0.001) and PIGD (p = 0.004, p = 0.001). CONCLUSIONS: Varying sensitivity levels, and age and phenotype selectivity, are found when different non-motor screening methods to detect prodromal PD are applied to an early clinical PD cohort.