scholarly journals Longitudinal Study to Assess the Quantitative Use of Fundus Autofluorescence for Monitoring Disease Progression in Choroideremia

2021 ◽  
Vol 10 (2) ◽  
pp. 232
Author(s):  
Adam M Dubis ◽  
Wei S Lim ◽  
Jasleen K Jolly ◽  
Maria Toms ◽  
Robert E MacLaren ◽  
...  
Keyword(s):  
Disease Progression ◽  
Exponential Decay ◽  
Half Life ◽  
Fundus Autofluorescence ◽  
Area Measurement ◽  
Timely Manner ◽  
Measurement Variability ◽  
Slow Progression ◽  
Exponential Decay Model

Background: Characterisation of preserved autofluorescence (PAF) area in choroideremia (CHM) and its validity for monitoring disease progression in clinical trials is of importance. Methods: Eighty patients with molecularly confirmed CHM were recruited. PAF area was measured manually by 2 graders and half-life was calculated based on exponential decay model. Results: Mean age at baseline and follow-up examination was 38.1 (range, 10–69) and 40.7 (range, 11–70) years. Mean follow-up interval was 29 months (range, 6–104). The median LogMAR visual acuity was 0.10 (OD) and 0.18 (OS). Interobserver repeatability for PAF area was −0.99 to 1.03 mm2 (−6.46 to 6.49% of area). There was a statistically significant relationship between age and rate of PAF area loss (r2 = 0.28, p = 0.012). The half-life for PAF area was 13.7 years (range, 1.7–216.0 years). The correlation between half-life and age was stronger than between half-life and log transformed baseline PAF area, although neither was statistically significant. Conclusions: The intra- and inter-observer PAF area measurement variability provides a baseline change, which must be overcome in a clinical trial if this metric were to be used. Treatments must slow progression to alter the exponential decay in a timely manner accounting for naturally slow progression patterns.

Tree windthrow and forest soil turnover

1989 ◽  
Vol 19 (3) ◽  
pp. 386-389 ◽  
Author(s):  
D. A. Norton
Keyword(s):  
Forest Soil ◽  
Exponential Decay ◽  
Half Life ◽  
Soil Development ◽  
Turnover Time ◽  
Important Influence ◽  
Plant Distribution ◽  
Canopy Trees ◽  
Decay Model ◽  
Exponential Decay Model

Soil turnover as a result of tree windthrow has an important influence on soil development and plant distribution in forests. Estimates of the time needed for soil turnover in a given area are often made, but unless these take into account the potential for reestablishment of canopy trees onto sites previously affected by windthrow, they are likely to substantially underestimate turnover time. Soil turnover is not a regular, uniform process, but rather results in a mosaic of soils with different turnover histories. Because soil turnover follows an exponential decay model, some area of soil will never be turned over. As it is therefore not possible to define the time when all the soil in an area has been turned over, it is proposed that soil turnover half-life (the time at which half the soil has been turned over) be used as a measure of soil turnover.

Choriocapillaris flow impairment could predict the enlargement of geographic atrophy lesion

2020 ◽  
Vol 105 (1) ◽  
pp. 97-102 ◽  
Author(s):  
Riccardo Sacconi ◽  
Eleonora Corbelli ◽  
Enrico Borrelli ◽  
Luigi Capone ◽  
Adriano Carnevali ◽  
...  
Keyword(s):  
Fundus Autofluorescence ◽  
Control Area ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Slow Progression ◽  
Minimum Angle ◽  
Perfusion Density ◽  
Prospective Longitudinal

AimTo analyse the choriocapillaris (CC) flow status in the area that subsequently showed geographic atrophy (GA) expansion secondary to age-related macular degeneration (AMD) during 1-year follow-up, matching optical coherence tomography angiography (OCT-A) and fundus autofluorescence (FAF).MethodsIn this prospective longitudinal observational study, 30 eyes of 20 consecutive patients with GA secondary to AMD (mean age 75.5±7.4 years) were included. All patients underwent OCT-A and FAF at baseline and 1-year follow-up. Main outcome measures included analysis of perfusion density (PD) in the ‘area surrounding GA margin’ (between the GA border and 500 µm distance) in comparison with the ‘control area’ (area outside the 500 µm line), and of the ‘expansion area’ (area that subsequently developed GA expansion during 1-year follow-up).ResultsDuring the 1-year follow-up, visual acuity significantly decreased from 0.34±0.38 Logarithm of the Minimum Angle of Resolution (LogMAR) to 0.39±0.40 LogMAR (p<0.001), and mean GA area increased from 6.82±5.47 mm2 to 8.76±6.28 mm2 (p<0.001). CC PD of the area surrounding the GA margin revealed a significant flow impairment compared with control area (PD 0.679±0.076 and 0.734±0.057, respectively (p<0.001)). Furthermore, the PD of the expansion area showed a greater CC flow impairment in comparison to the remaining area surrounding GA margin (p<0.001).ConclusionsWe reported a greater CC impairment in the area that subsequently developed GA expansion, suggesting that the CC flow impairment could predict the enlargement of GA lesion. The CC impairment could be considered as a new a risk factor for GA progression and a biomarker to be measured to determine efficacy of new interventions aiming to slow progression of GA.

scholarly journals Half-life of Ingested Antibodies in Anopheles Stephensi Mosquito Is Less Than 10 Hours

2021 ◽  
Author(s):  
Kazutoyo Miura ◽  
Deng Bingbing ◽  
Yonas T Gebremicale ◽  
Thao P Pham ◽  
Ababacar Diouf ◽  
...  
Keyword(s):  
Exponential Decay ◽  
Mechanism Of Action ◽  
Half Life ◽  
Human Monoclonal Antibody ◽  
Critical Role ◽  
Target Antigen ◽  
Multiple Time ◽  
Human Red Blood Cells ◽  
Exponential Decay Model ◽  
Multiple Time Points

Abstract Background: A transmission-blocking vaccine (TBV) can be a useful tool to reduce malaria infection in an endemic area. For a TBV, elicited antibody (either by itself or working with complement) has a critical role in the mechanism of action, which for most known TBV targets, blockade will occur within the mosquito. However, no study has quantitively assessed the longevity of ingested antibody in Anopheles mosquito vectors. Methods: A mixture of mouse or human monoclonal antibody (mAb), human red blood cells and human serum were fed to An. stephensi mosquitoes, and their midguts were collected at multiple time points (0 to 48 hours; 12 mosquitoes at each time point) after feeds. The reactivity of antibodies against target antigen (integrity of antigen-binding region of the antibody) in each midgut was assessed by ELISA. For one mouse mAb, integrity of antibody constant region was also determined by western blot (WB) with a mouse-specific secondary antibody.Results: First, the half-life of mouse anti-Pfs25 mAb, 4B7, was determined both by ELISA and WB in three independent assays. When the ELISA and WB signals were plotted against time after feed, both data reasonably fit one-phase exponential decay models (R2 B 0.70), and the half-lives were estimated as 8.6 hours by ELISA and 4.7 hours by WB. To determine whether the longevity was affected by target antigens or species of antibody, two human anti-Pfs25 mAbs (AB1245 and AB2544), one human anti-Pfs48/45 mAb (TB31F), and one mouse anti-Pfs230 mAb (15A4-1B12) were examined by ELISA in two or three independent assays. The ELISA results of each additional mAb also reasonably fit to a one-phase exponential decay model (R2 a 0.78), and the half-lives of those mAbs were similar to that of 4B7 (7.2 to 9.3 hours), except AB1245 which showed a half-life of 4.6 hours. Conclusions: Depending on the methods of detection and mAbs used, the longevity of ingested antibody varied around 2-fold, but all estimated half-lives were < 10 hours. These data suggest a TBV with antibody dependent mechanism of action(s) is more likely to succeed when targeting earlier stages of parasites (or parasite interaction) in mosquitoes.

scholarly journals Fundus Autofluorescence

2017 ◽  
pp. 46-56
Keyword(s):  
Differential Diagnosis ◽  
Disease Progression ◽  
Fundus Autofluorescence ◽  
Predictive Markers ◽  
Retinal Diseases ◽  
Novel Therapies ◽  
Autofluorescence Imaging ◽  
Genotype Correlation ◽  
Pathophysiologic Mechanisms

Fundus autofluorescence imaging has been shown to be useful with regard to the understanding of pathophysiologic mechanisms, diagnostics, phenotype-genotype correlation, identification of predictive markers for disease progression, and monitoring of novel therapies in retinal diseases. Fundus autofluorescence imaging can be used in the diagnosis and follow-up of many diseases. This review summarizes fundus autofluorescence imaging of retinal diseases supported by photographs of clinical cases in which differential diagnosis plays an important role.

scholarly journals Survival of LA-MRSA in Dust from Swine Farms

2018 ◽  
Vol 62 (2) ◽  
pp. 147-156 ◽  
Author(s):  
Louise Feld ◽  
Hans Bay ◽  
Øystein Angen ◽  
Anders Rhod Larsen ◽  
Anne Mette Madsen
Keyword(s):  
Staphylococcus Aureus ◽  
Exponential Decay ◽  
Half Life ◽  
Storage Time ◽  
Decay Constant ◽  
Airborne Dust ◽  
Swine Farms ◽  
Exponential Decay Model ◽  
Staphylococcus Equorum ◽  
Rate Of Decay

AbstractDust is suspected to be an important factor in transmission of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) between pigs and pig farmers and their families. The aim of this study was to determine the rate of decay for Staphylococcus aureus and LA-MRSA in dust from swine farms. Electrostatic dust fall collectors (EDCs) were used for passive sampling of settling airborne dust in 11 stable sections from six swine farms. Extraction, plating, identification, and enumeration of cultivable S. aureus and LA-MRSA from the EDCs were performed after storage for 0–30 days postsampling. The survival of S. aureus was measured in 196 dust samples from all farms, and data were used to estimate the decay constant λ according to a model for exponential decay: N(t) = N0 × e−λt. The number of S. aureus colonies was up to 600-fold higher than the number of LA-MRSA colonies on MRSA selective agar. The data showed a good fit to the model (λ = 0.13, r2 = 0.86) even with a large difference in initial concentrations of S. aureus between stables. The loads of S. aureus and LA-MRSA in the dust were significantly reduced by storage time, and the half-life was 5 days for both S. aureus and LA-MRSA. In dust samples with high initial concentrations, LA-MRSA and S. aureus could still be cultivated 30 days after sampling. On all farms MRSA isolates belonged to the clonal complex (CC) 398, and at one farm some isolates also belonged to CC30. A screening for other Staphylococcus species in the farm dust revealed 13 different species numerically dominated by Staphylococcus equorum. Based on the exponential decay model, S. equorum had a half-life of 4 days. In conclusion, the presence of MRSA in airborne dust from five of six farms indicates that dust might be an important vehicle for transmission of LA-MRSA. LA-MRSA and S. aureus was found to survive well in farm dust with half-lives of 5 days, and dependent on the initial concentration they could be found in farm dust for weeks. The 99.9% die-off rate was 66 days for LA-MRSA. Thus, farm dust can pose an exposure risk for humans in the farm environment, but also when transported to other environments. On the other hand, the risk will decrease by time. These results provide important knowledge to diminish spread from farm environments to other environments on, e.g., tools or clothing, and in relation to cleaning of emptied LA-MRSA-positive stables.

scholarly journals New risk model is able to identify patients with a low risk of progression in systemic sclerosis

RMD Open ◽  
2021 ◽  
Vol 7 (2) ◽  
pp. e001524
Author(s):  
Nina Marijn van Leeuwen ◽  
Marc Maurits ◽  
Sophie Liem ◽  
Jacopo Ciaffi ◽  
Nina Ajmone Marsan ◽  
...  
Keyword(s):  
Machine Learning ◽  
Systemic Sclerosis ◽  
High Risk ◽  
Disease Progression ◽  
Risk Model ◽  
Immunosuppressive Drugs ◽  
Low Risk ◽  
Expert Assessment ◽  
Risk Of Progression

ObjectivesTo develop a prediction model to guide annual assessment of systemic sclerosis (SSc) patients tailored in accordance to disease activity.MethodsA machine learning approach was used to develop a model that can identify patients without disease progression. SSc patients included in the prospective Leiden SSc cohort and fulfilling the ACR/EULAR 2013 criteria were included. Disease progression was defined as progression in ≥1 organ system, and/or start of immunosuppression or death. Using elastic-net-regularisation, and including 90 independent clinical variables (100% complete), we trained the model on 75% and validated it on 25% of the patients, optimising on negative predictive value (NPV) to minimise the likelihood of missing progression. Probability cutoffs were identified for low and high risk for disease progression by expert assessment.ResultsOf the 492 SSc patients (follow-up range: 2–10 years), disease progression during follow-up was observed in 52% (median time 4.9 years). Performance of the model in the test set showed an AUC-ROC of 0.66. Probability score cutoffs were defined: low risk for disease progression (<0.197, NPV:1.0; 29% of patients), intermediate risk (0.197–0.223, NPV:0.82; 27%) and high risk (>0.223, NPV:0.78; 44%). The relevant variables for the model were: previous use of cyclophosphamide or corticosteroids, start with immunosuppressive drugs, previous gastrointestinal progression, previous cardiovascular event, pulmonary arterial hypertension, modified Rodnan Skin Score, creatine kinase and diffusing capacity for carbon monoxide.ConclusionOur machine-learning-assisted model for progression enabled us to classify 29% of SSc patients as ‘low risk’. In this group, annual assessment programmes could be less extensive than indicated by international guidelines.

scholarly journals Chronic kidney disease progression among patients with type 2 diabetes identified in US administrative claims: a population cohort study

2020 ◽  
Author(s):  
Csaba P Kovesdy ◽  
Danielle Isaman ◽  
Natalia Petruski-Ivleva ◽  
Linda Fried ◽  
Michael Blankenburg ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Cohort Study ◽  
Kidney Disease ◽  
Disease Progression ◽  
Administrative Claims ◽  
Short Period ◽  
Ckd Stage

Abstract Background Chronic kidney disease (CKD), one of the most common complications of type 2 diabetes (T2D), is associated with poor health outcomes and high healthcare expenditures. As the CKD population increases, a better understanding of the prevalence and progression of CKD is critical. However, few contemporary studies have explored the progression of CKD relative to its onset in T2D patients using established markers derived from real-world care settings. Methods This retrospective, population-based cohort study assessed CKD progression among adults with T2D and with newly recognized CKD identified from US administrative claims data between 1 January 2008 and 30 September 2018. Included were patients with T2D and laboratory evidence of CKD as indicated by the established estimated glomerular filtration rate (eGFR) and urine albumin:creatinine ratio (UACR) criteria. Disease progression was described as transitions across the eGFR- and UACR-based stages. Results A total of 65 731 and 23 035 patients with T2D contributed to the analysis of eGFR- and UACR-based CKD stage progression, respectively. CKD worsening was observed in approximately 10–17% of patients over a median follow-up of 2 years. Approximately one-third of patients experienced an increase in eGFR values or a decrease in UACR values during follow-up. Conclusions A relatively high proportion of patients were observed with disease progression over a short period of time, highlighting the need for better identification of patients at risk of rapidly progressive CKD. Future studies are needed to determine the clinical characteristics of these patients to inform earlier diagnostic and therapeutic interventions aimed at slowing disease progression.

scholarly journals Continuous HIV-1 Escape from Autologous Neutralization and Development of Cross-Reactive Antibody Responses Characterizes Slow Disease Progression of Children

Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 260
Author(s):  
Stefania Dispinseri ◽  
Mariangela Cavarelli ◽  
Monica Tolazzi ◽  
Anna Maria Plebani ◽  
Marianne Jansson ◽  
...  
Keyword(s):  
Disease Progression ◽  
Antibody Responses ◽  
Viral Escape ◽  
Target Cells ◽  
Transmitted Virus ◽  
Slow Progressors ◽  
Vaccine Antigens ◽  
Kinetics Of ◽  
Hiv 1

The antibodies with different effector functions evoked by Human Immunodeficiency Virus type 1 (HIV-1) transmitted from mother to child, and their role in the pathogenesis of infected children remain unresolved. So, too, the kinetics and breadth of these responses remain to be clearly defined, compared to those developing in adults. Here, we studied the kinetics of the autologous and heterologous neutralizing antibody (Nab) responses, in addition to antibody-dependent cellular cytotoxicity (ADCC), in HIV-1 infected children with different disease progression rates followed from close after birth and five years on. Autologous and heterologous neutralization were determined by Peripheral blood mononuclear cells (PBMC)- and TZMbl-based assays, and ADCC was assessed with the GranToxiLux assay. The reactivity to an immunodominant HIV-1 gp41 epitope, and childhood vaccine antigens, was assessed by ELISA. Newborns displayed antibodies directed towards the HIV-1 gp41 epitope. However, antibodies neutralizing the transmitted virus were undetectable. Nabs directed against the transmitted virus developed usually within 12 months of age in children with slow progression, but rarely in rapid progressors. Thereafter, autologous Nabs persisted throughout the follow-up of the slow progressors and induced a continuous emergence of escape variants. Heterologous cross-Nabs were detected within two years, but their subsequent increase in potency and breadth was mainly a trait of slow progressors. Analogously, titers of antibodies mediating ADCC to gp120 BaL pulsed target cells increased in slow progressors during follow-up. The kinetics of antibody responses to the immunodominant viral antigen and the vaccine antigens were sustained and independent of disease progression. Persistent autologous Nabs triggering viral escape and an increase in the breadth and potency of cross-Nabs are exclusive to HIV-1 infected slowly progressing children.

scholarly journals IMG-18. ASSESSMENT OF SUSPECTED DISEASE PROGRESSION USING MULTIPARAMETRIC 18F-CHOLINE PET/MRI IN CHILDHOOD AND TEENAGE-YOUNG ADULT GLIOMAS

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii358-iii358
Author(s):  
Valentina Ferrazzoli ◽  
Ananth Shankar ◽  
Julia Cockle ◽  
Christine Tang ◽  
Ahmed Al-khayfawee ◽  
...  
Keyword(s):  
Disease Progression ◽  
Posterior Fossa ◽  
Cerebral Blood Volume ◽  
Posterior Fossa Tumour ◽  
Recurrent Tumour ◽  
Normal Appearing White Matter ◽  
Conventional Mri ◽  
Apparent Diffusion ◽  
Teenagers And Young Adults

Abstract OBJECTIVES Evaluation of post-treatment glioma burden remains a significant challenge in children, teenagers and young adults (TYA). The aim of this study was to evaluate the utility of ChoPET/MRI for evaluation of suspected disease progression in childhood and TYA gliomas. METHODS 27 patients (mean age 14 years, range 6–21 years) with suspected glioma disease progression were evaluated with ChoPET/MRI (n=59). Relative cerebral blood volume (rCBV), apparent diffusion coefficient (ADC) and maximum standardised uptake values (SUVmax) in enhancing (enh) and non-enhancing (ne) tumour and normal-appearing white matter (wm) were calculated (rCBVenh, rCBVne, rCBVwm, ADCenh, ADCne, ADCwm, SUVenh, SUVne, SUVwm). 2 blinded radiologists scored tumour probability (1 = unlikely; 5 = definitely). Sensitivity and specificity calculated with gold standard histopathology or clinical follow-up. RESULTS Accuracy for the detection of residual/recurrent tumour on conventional MRI was 96.3% (91.7% ≤14 years, 100% ≥15 years) and ChoPET was 73.1% (66.7% ≤14 years, 80.0% ≥15 years). Lack of agreement was observed in 9/27 patients, with ChoPET superior to MRI in 1 case of a posterior fossa tumour. Tumour component analysis demonstrated significantly higher SUVenh and SUVne than SUVwm (SUVenh: p&lt;0.001; SUVne: p=0.004, equivalent to results were observed for ADV and rCBV (ADCenh, ADCne: p&lt;0.001 vs ADCwm; rCBVenh, rCBVne: p&lt;0.001 vs rCBVwm). CONCLUSIONS MRI is more sensitive than ChoPET in the evaluation of suspected disease progression in TYA gliomas. However, quanititative ChoPET is able to detect enhancing and non-enhancing tumour and may be helpful in evaluating posterior fossa disease where MRI is equivocal.

Dissecting the Effects of Disease and Treatment on Impulsivity in Parkinson's Disease

2012 ◽  
Vol 18 (6) ◽  
pp. 942-951 ◽  
Author(s):  
Alison C. Simioni ◽  
Alain Dagher ◽  
Lesley K. Fellows
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Progression ◽  
Risk Taking ◽  
Temporal Discounting ◽  
Baseline Risk ◽  
Neural Basis ◽  
Risky Decision ◽  
Balloon Analogue Risk Task

AbstractConverging evidence, including observations in patients with Parkinson's disease (PD), suggests that dopamine plays a role in impulsivity. This multi-faceted construct includes considerations of both time and risk; determining how these more specific processes are affected by PD and dopaminergic treatment can inform neurobiological models. We examined the effects of PD and its treatment on temporal discounting and risky decision-making in a cohort of 23 mild-moderate PD patients and 20 healthy participants. Patients completed the Balloon Analogue Risk Task and a temporal discounting paradigm both on and off their usual dopamine replacement therapy. PD patients did not differ from controls in their initial risk-taking on the Balloon Analogue Risk Task, but took progressively more risks across trials when on medication. A subset of patients and controls was tested again, 1.5–3 years later, to explore the effects of disease progression. On follow-up, baseline risk-taking diminished in patients, but the tendency to take increasing risks across trials persisted. Neither disease progression nor its treatment affected the temporal discounting rate. These findings suggest a different neural basis for temporal discounting and risk-taking, and demonstrate that risk-taking can be further decomposed into initial and trial-by-trial effects, with dopamine affecting only the latter. (JINS, 2012, 18, 1–10)

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