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Impairments of object recognition are core features of neurodegenerative syndromes, in particular posterior cortical atrophy (PCA; the 'visual-variant Alzheimer's disease'). These impairments arise from damage to higher-level cortical visual regions and are often missed or misattributed to common ophthalmological conditions. Consequently, diagnosis can be delayed for years with considerable implications for patients. We report a new test for the rapid measurement of cortical visual loss - the Graded Incomplete Letters Test (GILT). The GILT is an optimised psychophysical variation of a test used to diagnose cortical visual impairment, which measures thresholds for recognising letters under levels of increasing visual degradation (decreasing "completeness") in a similar fashion to ophthalmic tests. The GILT was administered to UK Biobank participants (total n=2,359) and participants with neurodegenerative conditions characterised by initial cortical visual (PCA, n=18) or memory loss (typical Alzheimer's disease, n=9). UK Biobank participants, including both typical adults and those with ophthalmological conditions, were able to recognise letters under low levels of completeness. In contrast, participants with PCA consistently made errors with only modest decreases in completeness. GILT sensitivity to PCA was 83.3% for participants reaching the 80% accuracy cut-off, increasing to 88.9% using alternative cut-offs (60% or 100% accuracy). Specificity values were consistently over 94% when compared to UK Biobank participants without or with documented visual conditions, regardless of accuracy cut-off. These first-release UK Biobank and clinical verification data suggest the GILT has utility in both rapidly detecting visual perceptual losses following posterior cortical damage and differentiating perceptual losses from common eye-related conditions.
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BACKGROUND: Viscoelastometric haemostatic assays (VHA) give rapid information on coagulation status, allowing individualised resuscitation. METHODS: This paper compares outcomes from two observational studies of postpartum haemorrhage (PPH) in the same institution, before and after practice changed from fixed ratio empirical transfusion of coagulation products with laboratory coagulation testing to VHA-guided fibrinogen replacement incorporated into an enhanced PPH care bundle. In both studies, all blood samples were taken near 1000â¯mL qualitative blood loss (QBL). In Study One, QBL started once PPH was identified, and resuscitation with coagulation blood products was empirical or based on laboratory tests of coagulation. In Study Two, QBL started at delivery and VHA was used to guide fibrinogen replacement if FIBTEM A5 was <12â¯mm (Claus fibrinogen ≤2â¯g/L) or to withhold coagulation products if FIBTEM A5 was >12â¯mm. RESULTS: Improved PPH outcomes were observed in Study Two, with rates of measured blood loss ≥2500â¯mL, ≥4 units red blood cell (RBC) transfusion, fresh frozen plasma transfusion and ≥8 units of any blood product transfusion all reduced (Pâ¯<â¯0.01). Clinically significant improvements occurred in women with fibrinogen ≤2â¯g/L at study entry, where the proportion of women who received ≥4 units RBC transfusion fell from 67% in Study One to 0% in Study Two (Pâ¯=â¯0.0007). CONCLUSIONS: These results suggest that use of VHA as part of an early bundle of PPH care targeting fibrinogen ≤2â¯g/L with fibrinogen concentrate reduces PPH progression. The greatest benefit was seen when fibrinogen levels were ≤2â¯g/L at first testing.
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Fibrinogênio , Hemorragia Pós-Parto , Humanos , Feminino , Hemorragia Pós-Parto/terapia , Fibrinogênio/uso terapêutico , Estudos Prospectivos , Adulto , Gravidez , Resultado do Tratamento , Tromboelastografia/métodos , Hemostáticos/uso terapêutico , Transfusão de Sangue/métodos , Testes de Coagulação SanguíneaAssuntos
Caspase 3 , Ganciclovir , Neoplasias Ovarianas , Simplexvirus , Timidina Quinase , Humanos , Feminino , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Timidina Quinase/genética , Timidina Quinase/metabolismo , Simplexvirus/genética , Ganciclovir/farmacologia , Ganciclovir/uso terapêutico , Caspase 3/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular TumoralRESUMO
We conducted a prospective observational service evaluation across the United Kingdom on the use of total intravenous anaesthesia (TIVA) for obstetric surgery between November 2022 and June 2023. The primary aim was to describe the incidence of TIVA for obstetric surgery within participating units, with secondary aims to describe maternal and neonatal postoperative recovery indicators. Of 184 maternity units in the United Kingdom, 30 (16%) contributed data to the service evaluation. There were 104 patients who underwent caesarean delivery under TIVA and 19 patients had TIVA for other reasons. Infusions of propofol and remifentanil were used in 100% and 84% of cases, respectively. Fifty-nine out of 103 live neonates (57%) required some form of respiratory support. Of the neonates with recorded data, 73% and 17% had Apgar scores < 7 at 1 and 5 min respectively. No neonates were recorded to have Apgar scores < 7 at 10 min. Further prospective research is required to investigate the impact of obstetric TIVA on maternal and neonatal outcomes and inform best practice recommendations.
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BACKGROUND AND AIM: The rising incidence of hepatocellular carcinoma (HCC) in Australia is related to increasing rates of metabolic-associated fatty liver disease (MAFLD). This study aimed to prospectively characterize the metabolic profile, lifestyle, biometric features, and response to treatment of HCC patients in an Australian population. METHOD: Multicenter prospective cohort analysis of newly diagnosed HCC patients at six multidisciplinary team meetings over a 2-year period. RESULTS: Three hundred and thirteen (313) newly diagnosed HCC patients with MAFLD (n = 77), MAFLD plus other liver disease (n = 57) (the "mixed" group), and non-MAFLD (n = 179) were included in the study. Alcohol-associated liver disease (ALD) (43%) and MAFLD (43%) were the most common underlying liver diseases. MAFLD-HCC patients were older (73 years vs 67 years vs 63 years), more likely to be female (40% vs 14% vs 20%), less likely to have cirrhosis (69% vs 88% vs 85%), showed higher ECOG, and were less likely to be identified by screening (29% vs 53% vs 45%). Metabolic syndrome was more prevalent in the MAFLD and mixed groups. The severity of underlying liver disease and HCC characteristics were the same across groups. While the MAFLD population self-reported more sedentary lifestyles, reported dietary patterns were no different across the groups. Dyslipidemia was associated with tumor size, and those taking statins had a lower recurrence rate. CONCLUSION: Equal to ALD, MAFLD is now the most common underlying liver disease seen in HCC patients in Australia. Future HCC prevention screening and treatment strategies need to take this important group of patients into consideration.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Síndrome Metabólica , Humanos , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/etiologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/etiologia , Feminino , Masculino , Estudos Prospectivos , Pessoa de Meia-Idade , Idoso , Síndrome Metabólica/epidemiologia , Austrália/epidemiologia , Estilo de Vida , Resultado do Tratamento , Fígado Gorduroso/epidemiologia , Fígado Gorduroso/terapia , Fígado Gorduroso/diagnóstico , Fígado Gorduroso/etiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/terapia , Estudos de CoortesRESUMO
The Auditory Brainstem Response (ABR) plays an important role in diagnosing and managing hearing loss, but can be challenging and time-consuming to measure. Test times are especially long when multiple ABR measurements are needed, e.g., when estimating hearing threshold at a range of frequencies. While many detection methods have been developed to reduce ABR test times, the majority were designed to detect the ABR at a single stimulus level and do not consider correlations in ABR waveforms across levels. These correlations hold valuable information, and can be exploited for more efficient hearing threshold estimation. This was achieved in the current work using a Gaussian Process (GP), i.e., a Bayesian approach for non-linear regression. The function to estimate with the GP was the ABR's amplitude across stimulus levels, from which hearing threshold was ultimately inferred. Active learning rules were also designed to automatically adjust the stimulus level and efficiently locate hearing threshold. Simulation results show test time reductions of up to â¼ 50% for the GP compared to a sequentially applied Hotelling's T2 test, which does not consider correlations across ABR waveforms. A case study was also included to briefly assess the GP approach in ABR data from an adult volunteer.
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Potenciais Evocados Auditivos do Tronco Encefálico , Perda Auditiva , Adulto , Humanos , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Teorema de Bayes , Limiar Auditivo/fisiologia , Audição/fisiologia , Perda Auditiva/diagnóstico , Estimulação Acústica/métodosRESUMO
BACKGROUND: To define a method for identifying neonatal intensive care unit (NICU) admissions using administrative claims data. METHODS: This was a retrospective cohort study using claims from Optum's de-identified Clinformatics® Data Mart Database (CDM) from 2016 -2020. We developed a definition to identify NICU admissions using a list of codes from the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM), Current Procedural Terminology (CPT), and revenue codes frequently associated with NICU admissions. We compared agreement between codes using Kappa statistics and calculated positive predictive values (PPV) and 95% confidence intervals (CI). RESULTS: On average, revenue codes (3.3%) alone identified more NICU hospitalizations compared to CPT codes alone (1.5%), whereas the use of CPT and revenue (8.9%) and CPT or revenue codes (13.7%) captured the most NICU hospitalizations, which aligns with rates of preterm birth. Gestational age alone (4.2%) and birthweight codes alone (2.0%) identified the least number of potential NICU hospitalizations. Setting CPT codes as the standard and revenue codes as the "test,", revenue codes resulted in identifying 86% of NICU admissions (sensitivity) and 97% of non-NICU admissions (specificity). CONCLUSIONS: Using administrative data, we developed a robust definition for identifying neonatal admissions. The identified definition of NICU codes is easily adaptable, repeatable, and flexible for use in other datasets.
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Terapia Intensiva Neonatal , Nascimento Prematuro , Feminino , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Estudos Retrospectivos , HospitalizaçãoRESUMO
A network of specialist laboratories support the International Monitoring System (IMS) of the Comprehensive Nuclear-Test-Ban Treaty (CTBT) with re-measurements of radionuclide samples, including xenon gas. The measurement of four xenon fission product radionuclides (133Xe, 135Xe, 131mXe and 133mXe) can be used to detect an underground nuclear explosion. Laboratories use a range of techniques to measure the radionuclides, including beta-gamma (ß-γ) coincidence spectrometry. These highly-sensitive measurements are capable of detecting concentrations of down to 500 atoms of 133Xe in a few cm3 of xenon. In some detector systems, detection of the metastable isomers (131mXe and 133mXe) can be more challenging due to interferences between the signatures of different radionuclides. Recent work has shown that using high-purity Germanium (HPGe) high-resolution gamma detectors, these interferences can be reduced, lowering the dependence of the detection limits on radionuclide sample isotopic composition. One downside of these detectors is the reduction in detection efficiency, which impacts the overall detection sensitivity; so assessing different detector systems is a priority for radionuclide laboratories. This work presents a coincidence detector system comprising of a plastic scintillator gas cell and a large-crystal high-purity germanium detector. The energy resolution, coincidence detection efficiency, MDA and interference factors are determined from measurements of synthetic radioxenon gas samples.
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PURPOSE: To describe trends and explore factors associated with quality of life (QoL) and psychological morbidity and assess breast cancer (BC) health service use over a 12-month period for patients joining the supported self-management (SSM)/patient-initiated follow-up (PIFU) pathway. METHODS: Participants completed questionnaires at baseline, 3, 6, 9 and 12 months that measured QoL (FACT-B, EQ 5D-5L), self-efficacy (GSE), psychological morbidity (GHQ-12), roles and responsibilities (PRRS) and service use (cost diary). RESULTS: 99/110 patients completed all timepoints; 32% (35/110) had received chemotherapy. The chemotherapy group had poorer QoL; FACT-B total score mean differences were 8.53 (95% CI: 3.42 to 13.64), 5.38 (95% CI: 0.17 to 10.58) and 8.00 (95% CI: 2.76 to 13.24) at 6, 9 and 12 months, respectively. The odds of psychological morbidity (GHQ12 >4) were 5.5-fold greater for those treated with chemotherapy. Financial and caring burdens (PRRS) were worse for this group (mean difference in change at 9 months 3.25 (95% CI: 0.42 to 6.07)). GSE and GHQ-12 scores impacted FACT-B total scores, indicating QoL decline for those with high baseline psychological morbidity. Chemotherapy patients or those with high psychological morbidity or were unable to carry out normal activities had the highest service costs. Over the 12 months, 68.2% participants phoned/emailed breast care nurses, and 53.3% visited a hospital breast clinician. CONCLUSION: The data suggest that chemotherapy patients and/or those with heightened psychological morbidity might benefit from closer monitoring and/or supportive interventions whilst on the SSM/PIFU pathway. Reduced access due to COVID-19 could have affected service use.
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Neoplasias da Mama , COVID-19 , Síndrome Respiratória e Reprodutiva Suína , Autogestão , Suínos , Animais , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Qualidade de VidaRESUMO
The objective of this study was to improve the solubility and inhibit the crystallisation during the gastric-to-intestinal transfer of Erlotinib (ERL), a small molecule kinase inhibitor (smKI) compound class, which is classified as class II drug in the Biopharmaceutical Classification System (BCS). A screening approach combining different parameters (solubility in aqueous media, inhibitory effect of drug crystallisation from supersaturated drug solutions) was applied to selected polymers for the development of solid amorphous dispersions of ERL. ERL solid amorphous dispersions formulations were then prepared with 3 different polymers (Soluplus®, HPMC-AS-L, HPMC-AS-H) at a fixed drug: polymer ratio (1:4) by two different production methods (spray drying and hot melt extrusion). The spray-dried particles and cryo-milled extrudates were characterized by thermal properties, shape and particle size, solubility and dissolution behavior in aqueous media. The influence of the manufacturing process on these solid characteristics was also identified during this study. Based on the obtained results, it is concluded that the cryo-milled extrudates of HPMC-AS-L displayed better performance (enhanced solubility, reduced ERL crystallization during the simulated gastric-to-intestinal transfer) and represents a promising amorphous solid dispersion formulation for oral administration of ERL.
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Química Farmacêutica , Polímeros , Solubilidade , Cristalização , Composição de Medicamentos/métodos , Química Farmacêutica/métodos , Cloridrato de Erlotinib , Polímeros/química , ÁguaRESUMO
OBJECTIVE: We tested the hypothesis that targeted retinal laser photocoagulation (TPRP) to peripheral retinal ischaemia reduces the overall burden of aflibercept injections when treating diabetic macular oedema (DMO) over a 24-month period. METHODS: Prospective, double-masked, multicentre, randomised controlled trial in Australia comparing aflibercept monotherapy, following a treat-and-extend protocol, or combination therapy of aflibercept and TPRP for DMO. The aflibercept monotherapy group received placebo laser. The primary outcome measure was the mean number of intravitreal aflibercept injections for each group at 24 months. Secondary outcome included: mean change in central macular thickness (CMT) and vision at trial completion, the proportion of eyes whose DMO resolved and the mean injection treatment interval. Ocular and systemic adverse events were recorded. RESULTS: We enrolled 48 eyes of 47 patients; 27 eyes were randomised to combination therapy (aflibercept and TPRP) and 21 to aflibercept monotherapy. Thirty-two eyes (67%) completed the 2-year study. The number of intravitreal treatments given were similar for combination therapy (10.5 (SD 5.8) and monotherapy (11.8 (SD5.6)) (P = 0.44). The mean visual improvement (+4.0 (-1.8, 9.8) and +7.8 (2.6, 12.9) letters, P = 0.32), mean decrease in CMT (-154 (-222,-87) µm and -152 (-218,-86) µm, P = 0.96), proportion of eyes with CMT < 300 µm (48% and 67%; P = 0.50) and safety outcomes were similar in both the combination and monotherapy treatment groups (respectively). CONCLUSIONS: Laser to areas of ischaemic peripheral retina does not reduce the burden of intravitreal aflibercept injections when treating diabetic macular oedema.
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Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Humanos , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Ranibizumab/uso terapêutico , Inibidores da Angiogênese , Estudos Prospectivos , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Retinopatia Diabética/complicações , Retinopatia Diabética/tratamento farmacológico , Proteínas Recombinantes de Fusão/uso terapêutico , Retina , Lasers , Isquemia/tratamento farmacológico , Injeções Intravítreas , Resultado do TratamentoRESUMO
OBJECTIVE: To explore a side of lesion differences in Meniere's disease (MD). DESIGN: A retrospective review (2019-2021) was conducted of patients with definite MD, as defined by 2015 Bárány Society diagnostic criteria. Testing information included pure tone audiometry, tympanometry, and extra-tympanic electrocochleography (ECochG). Normative ECochG data from healthy subjects determined the 95% cut-off value for clinical abnormality. STUDY SAMPLE: 107 patients with definite MD were included in the study and 40 healthy controls. RESULTS: The review identified 75 patients with unilateral MD and 32 patients with bilateral MD according to their clinical histories. 79% of unilateral cases were found to have MD on the L ear. 94% of bilateral MD cases had L ears more affected than R ears. Objective ECochG testing indicated a greater incidence of elevated SP/AP area curve and amplitude ratios in L ears. On binomial testing, all results indicate a highly significant bias of MD to the L side. CONCLUSIONS: Unilateral MD appears more common on the L side than the R, suggesting that the disease process underlying MD is not symmetrical. MD also appears more common in females than males. It appears that there is a physiological asymmetry in the progression/cause of MD.
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Doença de Meniere , Masculino , Feminino , Humanos , Doença de Meniere/diagnóstico , Doença de Meniere/epidemiologia , Incidência , Audiometria de Resposta Evocada/métodos , Orelha Média , Testes de Impedância AcústicaRESUMO
BACKGROUND: Mycobacterium abscessus (MABS) group are environmental organisms that can cause infection in people with cystic fibrosis (CF) and other suppurative lung diseases. There is potential for person-to-person airborne transmission of MABS among people with CF attending the same care centre. Ultraviolet light (band C, UV-C) is used for Mycobacterium tuberculosis control indoors; however, no studies have assessed UV-C for airborne MABS. AIM: To determine whether a range of UV-C doses increased the inactivation of airborne MABS, compared with no-UVC conditions. METHODS: MABS was generated by a vibrating mesh nebulizer located within a 400 L rotating drum sampler, and then exposed to an array of 265 nm UV-C light-emitting diodes (LED). A six-stage Andersen Cascade Impactor was used to collect aerosols. Standard microbiological protocols were used for enumerating MABS, and these quantified the effectiveness of UV-C doses (in triplicate). UV-C effectiveness was estimated using the difference between inactivation with and without UV-C. FINDINGS: Sixteen tests were performed, with UV-C doses ranging from 276 to 1104 µW s/cm2. Mean (±SD) UV-C effectiveness ranged from 47.1% (±13.4) to 83.6% (±3.3). UV-C led to significantly greater inactivation of MABS (all P-values ≤0.045) than natural decay at all doses assessed. Using an indoor model of the hospital environment, it was estimated that UV-C doses in the range studied here could be safely delivered in clinical settings where patients and staff are present. CONCLUSION: This study provides empirical in-vitro evidence that nebulized MABS are susceptible to UV-C inactivation.
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Mycobacterium abscessus , Mycobacterium tuberculosis , Humanos , Raios Ultravioleta , Aerossóis e Gotículas Respiratórios , Desinfecção/métodosRESUMO
The utilisation of pre-hospital early warning scores in ambulance services is widely endorsed to promptly identify patients at risk of clinical deterioration. Early warning scores enable clinicians to estimate risk based on clinical observations and vital signs, with higher scores indicating an elevated risk of adverse outcomes. Local healthcare systems establish threshold values for these scores to guide clinical decision-making, triage, and response, necessitating a careful balance between identifying critically unwell patients and managing the challenge of prioritisation. Given the limited evidence for optimal early warning scores in emergency department and pre-hospital care settings, a systematic review by Guan et al. (2022) was undertaken to assess the diagnostic accuracy of early warning scores for predicting in-hospital deterioration when applied in the emergency department or pre-hospital setting. This commentary aims to critically appraise the methods used within the review Guan et al (2022) and expand upon the findings in the context of clinical practice.
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Two Pomeranian dogs referred for interventional correction of a left-to-right shunting patent ductus arteriosus (PDA) had inadequate femoral arterial access for any occlusion device other than micro coils. The decision was made to attempt correction of the PDA using the Amplatzer™ Vascular Plug 4 (AVP4) from a femoral venous approach. An AVP4 was successfully deployed in each dog with complete occlusion noted within 5 min. Complete occlusion was persistent at 24 h after the procedure, while both dogs were subclinical, had no residual ductal flow, and complete or near complete reverse cardiac remodeling at subsequent visits. This report demonstrates the feasibility of PDA occlusion with the AVP4 from the femoral venous approach in small dogs where femoral arterial access is inadequate for other occlusion devices.
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Doenças do Cão , Permeabilidade do Canal Arterial , Embolização Terapêutica , Cães , Animais , Permeabilidade do Canal Arterial/diagnóstico por imagem , Permeabilidade do Canal Arterial/cirurgia , Permeabilidade do Canal Arterial/veterinária , Embolização Terapêutica/veterinária , Resultado do Tratamento , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/cirurgia , Cateterismo Cardíaco/veterináriaRESUMO
Psoriasis studies increasingly employ outcomes that indicate complete disease resolution, yet remission and cure are poorly defined for psoriasis. We conducted a systematic literature review to identify definitions of psoriasis remission and cure reported in the literature. Medline, EMBASE, and The Cochrane Central Register of Controlled Trials databases were searched on July 22, 2020, for full-text studies providing definitions for psoriasis remission/cure. Definitions were analysed descriptively for endpoint, time-frame, on/off treatment, patient-reported outcomes, and disease domains. We identified 106 studies that provided 41 unique remission definitions. Most definitions included endpoints based on Psoriasis Area and Severity Index (PASI), such as PASI75 (n = 16 studies), PASI90 (n = 10), PASI100 (n = 10), and PASI of 0 (n = 3), and descriptive endpoints related to 'skin clearance' (n = 18). Few definitions specified time-frame, on/off treatment or other psoriasis-related disease domains. One small consensus-initiative defined drug-free remission for plaque psoriasis by BSA of 0 without any therapy for at least 12 months. While there is no cure for psoriasis, seven studies defined psoriasis cure using similar endpoints to those used to define remission. We identified a variety of definitions of psoriasis remission. These results will inform the development of consensus-based definitions for psoriasis remission to support efforts to improve research and clinical outcomes.
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Psoríase , Humanos , Psoríase/tratamento farmacológico , Resultado do Tratamento , Índice de Gravidade de DoençaRESUMO
This article is composed of three independent commentaries about the state of Integrated, Coordinated, Open, Networked (ICON) principles in the American Geophysical Union Biogeosciences section, and discussion on the opportunities and challenges of adopting them. Each commentary focuses on a different topic: (a) Global collaboration, technology transfer, and application (Section 2), (b) Community engagement, community science, education, and stakeholder involvement (Section 3), and (c) Field, experimental, remote sensing, and real-time data research and application (Section 4). We discuss needs and strategies for implementing ICON and outline short- and long-term goals. The inclusion of global data and international community engagement are key to tackling grand challenges in biogeosciences. Although recent technological advances and growing open-access information across the world have enabled global collaborations to some extent, several barriers, ranging from technical to organizational to cultural, have remained in advancing interoperability and tangible scientific progress in biogeosciences. Overcoming these hurdles is necessary to address pressing large-scale research questions and applications in the biogeosciences, where ICON principles are essential. Here, we list several opportunities for ICON, including coordinated experimentation and field observations across global sites, that are ripe for implementation in biogeosciences as a means to scientific advancements and social progress.
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Likelihood estimates of extreme winds, including those from tropical cyclones (TCs) at certain locations are used to inform wind load standards for structural design. Here, wind speed average recurrence intervals (ARIs) determined from TC climate data dating back to the 1970s in two quantile-quantile adjusted reanalysis datasets (ERA5 and BARRA [1990]), and best-track observations for context, were compared with Standardized ARIs (AS/NZS) across seven tropical and two subtropical Australian inland coastal regions. The novelty of this work lies in determining TC-wind speed ARIs from a range of datasets that are not typically used to evaluate this metric. Inherent differences between the data used to determine the Standard ARIs (large sample size allow for larger extrapolations; GEV function) and TC data ARIs (smaller sample size and less certain data; the more asymptotic Lognormal/Weibull functions are used) led to the use of different extreme value functions. Results indicated that although these are two distinct ways of determining design wind speeds, when they are considered equivalent, there was a moderate reproduction of the ARI curves with respect to the Standard in both reanalysis datasets, suggesting that similar analyses using climate model products can provide useful information on these types of metrics with some caveats. Trends in TC wind strength affecting coastal Australia were also analyzed, indicating a potential slight downtrend in tropical West coast TC wind strength and slight uptrend for tropical East coast TC wind strength, noting considerable uncertainty given the short time period and limitations of data quality including over longer time periods. Such trends are not only limited to the relationship between TC intensity and anthropogenic warming, but also to regional changes in TC frequency and track direction. This could lead to significant trends emerging in regional Australian TC wind gust strength before several decades of warming have occurred. It is hoped that climate models can provide both longer-term and a more homogenous base for these types of evaluations and subsequent projections with respect to climate change simulations.
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Tempestades Ciclônicas , Austrália , Mudança Climática , Clima Tropical , VentoRESUMO
Obesity has been labeled as the global pandemic of the 21st century, resulting from a sedentary lifestyle and caloric excess. Nonalcoholic fatty liver disease (NAFLD), characterized by excessive hepatic steatosis, is strongly associated with obesity and metabolic syndrome and is estimated to be present in one-quarter of the world population, making it the most common cause of the chronic liver disease (CLD). NAFLD spectrum varies from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. The burden of NAFLD has been predicted to increase in the coming decades resulting in increased rates of decompensated cirrhosis, hepatocellular carcinoma (HCC), and liver-related deaths. In the current review, we describe the pathophysiology of NAFLD and NASH, risk factors associated with disease progression, related complications, and mortality. Later, we have discussed the changing epidemiology of HCC, with NAFLD emerging as the most common cause of CLD and HCC. We have also addressed the risk factors of HCC development in the NAFLD population (including demographic, metabolic, genetic, dietary, and lifestyle factors), presentation of NAFLD-associated HCC, its prognosis, and the issue of HCC development in non-cirrhotic NAFLD. Lastly, the problems related to HCC screening in the NAFLD population, the remaining challenges, and future directions, especially the need to identify the high-risk individuals, will be discussed. We will conclude the review by summarizing the clinical evidence for treating fibrosis and preventing HCC in those at risk with NAFLD-associated HCC.
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BACKGROUND AND AIMS: Little is known regarding the epidemiology and outcomes of patients with primary sclerosing cholangitis (PSC) in Australia. We, therefore, evaluated the epidemiology and clinical outcomes of PSC in a large cohort of Australian patients and compared these to the general population. METHODS: We conducted a multicentre, retrospective cohort study of PSC patients at nine tertiary liver centers across three Australian states, including two liver transplant centers. RESULTS: A total of 413 PSC patients with 3,285 person-years of follow-up were included. Three hundred and seventy-one (90%) patients had large duct PSC and 294 (71%) had associated inflammatory bowel disease. A total of 168 (41%) patients developed cirrhosis (including 34 at the time of PSC diagnosis) after a median of 15.8 (95% CI 12.4, NA) years. The composite endpoint of death or liver transplantation occurred in 49 (12%) and 78 (19%) patients, respectively, with a median transplant-free survival of 13.4 (95% CI 12.2-15) years. Compared to the general population, PSC accounted for a 240-fold increased risk of development of cholangiocarcinoma (CCA) and CCA-related death. CCA risk was increased with older age of PSC diagnosis, presence of dominant stricture and colectomy. Compared to same-aged counterparts in the general population, PSC patients who were diagnosed at an older age or with longer disease duration had reduced relative survival. CONCLUSION: In this large retrospective cohort study of PSC patients in Australia, increased age and time from diagnosis was associated with increased mortality and morbidity particularly from CCA and development of cirrhosis, necessitating need for liver transplant.