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Amyotrophic lateral sclerosis is a devastating neurodegenerative disease, characterized by loss of central and peripheral motor neurons. Although the disease is clinically and genetically heterogeneous, axonal hyperexcitability is a commonly observed feature that has been suggested to reflect an early pathophysiological step linked to the neurodegenerative cascade. Therefore, it is important to clarify the mechanisms causing axonal hyperexcitability and how these relate to the clinical characteristics of patients. Measures derived directly from a nerve excitability recording are frequently used as study end points, although their biophysical basis is difficult to deduce. Mathematical models can aid in the interpretation but are reliable only when applied to group-averaged recordings. Consequently, model estimates of membrane properties cannot be compared with clinical characteristics or treatment effects in individual patients, posing a considerable limitation in heterogeneous diseases, such as amyotrophic lateral sclerosis. To address these challenges, we revisited nerve excitability using a new pattern analysis-based approach (principal component analysis). We evaluated disease-specific patterns of excitability changes and established their biophysical origins. Based on the observed patterns, we developed new compound measures of excitability that facilitate the implementation of this approach in clinical settings. We found that excitability changes in amyotrophic lateral sclerosis patients (n = 161, median disease duration = 11 months) were characterized by four unique patterns compared with controls (n = 50, age and sex matched). These four patterns were best explained by changes in resting membrane potential (modulated by Na+/K+ currents), slow potassium and sodium currents (modulated by their gating kinetics) and refractory properties of the nerve. Consequently, we were able to show that altered gating of slow potassium channels was associated with, and predictive of, the rate of progression of the disease on the amyotrophic lateral sclerosis functional rating scale. Based on these findings, we designed four composite measures that capture these properties to facilitate implementation outside this study. Our findings demonstrate that changes in nerve excitability in patients with amyotrophic lateral sclerosis are dominated by four distinct patterns, each with a distinct biophysical origin. Based on this new approach, we provide evidence that altered slow potassium-channel function might play a role in the rate of disease progression. The magnitudes of these patterns, quantified using a similar approach or our new composite measures, have potential as efficient measures to study membrane properties directly in amyotrophic lateral sclerosis patients, and thus aid prognostic stratification and trial design. [ABSTRACT FROM AUTHOR]

Background: Low-density lipoprotein cholesterol (LDL-C) and type 2 diabetes (T2DM) are both independent risk factors for aortic stenosis (AS). In AS patients, whether LDL-C or T2DM is associated with fast AS progression (FASP) and their interaction is unknown. This study aims to test the hypothesis that there is a heightened risk of FASP when elevated LDL-C coexists with T2DM. Methods: The Real-world Data of Cardiometabolic Protections (RED-CARPET) study enrolled participants with mild (peak aortic velocity = 2–3 m/s), moderate (3–4 m/s) and severe (≥4 m/s) AS between January 2015 and December 2020 at a single center. Participants were further stratified by baseline LDL-C joint T2DM, follow-up echocardiography was performed after 6 months, and the primary outcome was FASP, defined as the annual change in aortic peak velocity (≥0.3 m/s/year). Results: Among the 170 participants included, 45.3% had mild AS, 41.2% had moderate AS, and 13.5% had severe AS. The mean age was 66.84 ± 12.64 years, and 64.1% were women. During the followup period of 2.60 ± 1.43 years, 35 (20.6%) cases of FASP were identified. Using non-T2DM with LDL-C <2.15 mmol/L as reference, FASP risk was 1.30 [odds ratio (OR), 95% CI (0.99–7.78, p = 0.167)] for non-T2DM with LDL-C 2.15–3.14 mmol/L, 1.60 [OR, 95% CI (1.17–3.29, p = 0.040)] for non-T2DM with LDL-C ≥3.14 mmol/L, 2.21 [OR, 95% CI (0.49–4.32, p = 0.527)] for T2DM with LDL-C <2.15 mmol/L, 2.67 [OR, 95% CI (1.65–7.10, p = 0.004)] for T2DM with LDL-C 2.15–3.14 mmol/L, and 3.20 [OR, 95% CI (1.07–5.34, p = 0.022)] for T2DM with LDL-C ≥3.14 mmol/L. Conclusions: LDL-C joint T2DM was associated with FASP. This investigation suggests that fast progression of AS may develop if LDL-C is poorly managed in T2DM. Additional research is needed to validate this finding and explore the possible biological mechanism to improve the cardiometabolic management of T2DM and seek possible prevention for AS progression for this population. [ABSTRACT FROM AUTHOR]

Introduction: Although there have been many researches on the etiology and risk factors with the onset of hemifacial spasm, researches on the risk factors related to progression rate are limited. This study aims to analyze the risk factors related to the progression rate of hemifacial spasm. Methods: The study enrolled 142 patients who underwent microvascular decompression for hemifacial spasm. Based on the duration and severity of symptoms, patients were classified into rapid progression group and slow progression group. To analyze risk factors, univariate and multivariate logistic regression analyses were conducted. Of 142 patients with hemifacial spasm, 90(63.3%) were classified as rapid progression group, 52(36.7%) were classified as slow progression group. Results: In the univariate analysis, there were significant statistical differences between the two groups in terms of age of onset (P = 0.021), facial nerve angle (P < 0.01), hypertension (P = 0.01), presence of APOE +4 expression (P < 0.01) and different degrees of brainstem compression in the Root Entry Zone (P < 0.01). In the multivariable analyses, there were significant statistical differences between the two groups in terms of age of symptom onset (P < 0.01 OR = 6.591), APOE +4 (P < 0.01 OR = 5.691), brainstem compression (P = 0.006 OR = 5.620), and facial nerve angle (P < 0.01 OR = 5.758). Furthermore, we found no significant correlation between the severity of facial spasms and the progression rate of the disease (t = 2.47, P = 0.12 > 0.05). Conclusion: According to our study, patients with facial nerve angle ≤ 96.5°, severer compression of the brainstem by offending vessels, an onset age > 45 years and positive expression of APOE ε4, may experience faster progression of hemifacial spasm. [ABSTRACT FROM AUTHOR]

Purpose: To determine the cut-off points of minimum linear diameter (MLD) and base diameter (BD) at which the progression rate of idiopathic full-thickness macular holes (MHs) decreases before vitrectomy. Study design: A retrospective study. Methods: We investigated the differences in MLD and BD between baseline and operation days in patients with stages 2, 3, and 4 MHs using optical coherence tomography (OCT). Each difference in OCT parameters was divided by the time interval to calculate the MH progression rates and the cut-off points of MLD and BD. Results: Overall, 269 patients (282 eyes) were included. It took an average of 36.02 ± 24.69 (7–197) days from baseline to operation. MLD and BD progressed faster in stages 2 and 3 without posterior vitreous detachment (PVD) than in stage 4 with PVD (MLD: p < 0.001 and p = 0.007; BD: p < 0.001 and p = 0.019, respectively). Simple linear regression showed the relationship between baseline MLD and BD, and the progression rate; the progression rate decreased as baseline MLD (p = 0.004) and BD increased (p < 0.001). For baseline MLD and BD, the cut-off points where the progression rate decreased were 306.0 and 470.0 μm, respectively. Conclusion: The group without PVD progressed faster than the group with PVD. Moreover, the progression rates were faster in MHs with MLD < 306.0 μm and BD < 470.0 μm. In these patients, vitrectomy without delay is expected to improve the visual prognosis. [ABSTRACT FROM AUTHOR]

Abstract Background Scoliosis is widely prevalent among osteogenesis imperfecta (OI) patients, and is progressive with age. However, factors affecting scoliosis in OI are not well known. Methods We retrospectively retrieved longitudinal radiographic and clinical records of consecutive OI patients seeking treatments at our hospital from 2014 to 2022, graded their pre-operative spinal conditions into four outcome groups, estimated their progression rates, and descriptively and inferentially analyzed the genetic and non-genetic factors that may affect the outcomes and progression rates. Results In all, 290 OI patients met the inclusion criteria, where 221 had genetic records. Of these 221, about 2/3 had mutations in COL1A1 or COL1A2, followed by mutations in WNT1 (9.0%), IFITM5 (9.0%) and other OI risk genes. With an average age of 12.0 years (interquartile range [IQR] 6.9–16.1), 70.7% of the cohort had scoliosis (Cobb angle > 10°), including 106 (36.5%) mild (10°–25°), 40 (13.8%) moderate (25°–50°), and 59 (20.3%) severe (> 50°) scoliosis patients. Patients with either COL1A1 and COL1A2 were strongly biased toward having mild or no scoliosis, whereas patients with mutations in IFITM5, WNT1 and other recessive genes were more evenly distributed among the four outcome grades. Lower-limb discrepancy, bone mineral density (BMD) and age of first drug used were all significantly correlated with severity outcomes. Using multivariate logistic regression, we estimated that each year older adds an odds ratio of 1.13 (95% confidence interval [CI] 1.07–1.2) in progression into advanced stages of scoliosis. We estimated a cohort-wide progression rate of 2.7 degrees per year (95% CI 2.4–3.0). Early-onset patients experienced fast progressions during both infantile and adolescent stages. Twenty-five of the 59 (42.8%) patients with severe scoliosis underwent spinal surgeries, enjoying an average Cobb angle reduction of 33° (IQR 23–40) postoperatively. Conclusion The severity and progression of scoliosis in osteogenesis imperfecta were affected by genetic factors including genotypes and mutation types, and non-genetic factors including age and BMD. As compared with COL1A1, mutations in COL1A2 were less damaging while those on IFITM5 and other recessive genes conferred damaging effects. Progression rates were the fastest in the adolescent adult age-group.

Background: Scoliosis is widely prevalent among osteogenesis imperfecta (OI) patients, and is progressive with age. However, factors affecting scoliosis in OI are not well known. Methods: We retrospectively retrieved longitudinal radiographic and clinical records of consecutive OI patients seeking treatments at our hospital from 2014 to 2022, graded their pre-operative spinal conditions into four outcome groups, estimated their progression rates, and descriptively and inferentially analyzed the genetic and non-genetic factors that may affect the outcomes and progression rates. Results: In all, 290 OI patients met the inclusion criteria, where 221 had genetic records. Of these 221, about 2/3 had mutations in COL1A1 or COL1A2, followed by mutations in WNT1 (9.0%), IFITM5 (9.0%) and other OI risk genes. With an average age of 12.0 years (interquartile range [IQR] 6.9–16.1), 70.7% of the cohort had scoliosis (Cobb angle > 10°), including 106 (36.5%) mild (10°–25°), 40 (13.8%) moderate (25°–50°), and 59 (20.3%) severe (> 50°) scoliosis patients. Patients with either COL1A1 and COL1A2 were strongly biased toward having mild or no scoliosis, whereas patients with mutations in IFITM5, WNT1 and other recessive genes were more evenly distributed among the four outcome grades. Lower-limb discrepancy, bone mineral density (BMD) and age of first drug used were all significantly correlated with severity outcomes. Using multivariate logistic regression, we estimated that each year older adds an odds ratio of 1.13 (95% confidence interval [CI] 1.07–1.2) in progression into advanced stages of scoliosis. We estimated a cohort-wide progression rate of 2.7 degrees per year (95% CI 2.4–3.0). Early-onset patients experienced fast progressions during both infantile and adolescent stages. Twenty-five of the 59 (42.8%) patients with severe scoliosis underwent spinal surgeries, enjoying an average Cobb angle reduction of 33° (IQR 23–40) postoperatively. Conclusion: The severity and progression of scoliosis in osteogenesis imperfecta were affected by genetic factors including genotypes and mutation types, and non-genetic factors including age and BMD. As compared with COL1A1, mutations in COL1A2 were less damaging while those on IFITM5 and other recessive genes conferred damaging effects. Progression rates were the fastest in the adolescent adult age-group. [ABSTRACT FROM AUTHOR]

Appropriate prediction models can assist healthcare systems in delaying or reversing osteoarthritis (OA) progression. We aimed to identify a reliable algorithm for predicting the progression rate and fate of OA based on patient‐specific information. From May 2003 to 2019, 83,280 knees were collected. Age, sex, body mass index, bone mineral density, physical demands for occupation, comorbidities, and initial Kellgren–Lawrence (K‐L) grade were used as variables for the prediction models. The prediction targets were divided into dichotomous groups for even distribution. We compared the performances of logistic regression (LR), random forest (RF), and extreme gradient boost (XGB) algorithms. Each algorithm had the best precision when the model used all variables. XGB showed the best results in accuracy, recall, F1 score, specificity, and error rates (progression rate/fate of OA: 0.710/0.877, 0.542/0.637, 0.637/0.758, 0.859/0.981, and 0.290/0.123, respectively). The feature importance of RF and XGB had the same order up to the top six for each prediction target. Age and initial K‐L grade had the highest feature importance in RF and XGB for the progression rate and fate of OA, respectively. The XGB and RF machine learning algorithms showed better performance than conventional LR in predicting the progression rate and fate of OA. The best performance was obtained when all variables were combined using the XGB algorithm. For each algorithm, the initial K‐L grade and physical demand for occupation were the greatest contributors with superior feature importance compared with the others. [ABSTRACT FROM AUTHOR]

Sparse and conflicting data exist regarding the normal partogram of grand-multiparous (GMP, defined as parity of 6+) parturients. Customized partograms may potentially lower cesarean delivery rates for protraction disorders in this population. In this study, we aim to construct a normal labor curve of GMP women and compare it to the multiparous (MP, defined as parity of 2–5) partogram. We conducted a multicenter retrospective cohort analysis of deliveries between the years 2003 and 2019. Eligible parturients were the trials of labor of singletons ≥37 + 0 weeks in cephalic presentation with ≥2 documented cervical examinations during labor. Exclusion criteria were elective cesarean delivery without a trial of labor, preterm labor, major fetal anomalies, and fetal demise. GMP comprised the study group while the MP counterparts were the control group. A total of 78,292 deliveries met the inclusion criteria, comprising 10,532 GMP and 67,760 MP parturients. Our data revealed that during the first stage of labor, cervical dilation progressed at similar rates in MPs and GMPs, while head descent was a few minutes faster in GMPs compared to MPs, regardless of epidural anesthesia. The second stage of labor was faster in GMPs compared to MPs; the 95th percentile of the second stage duration of GMPs (48 min duration) was 43 min less than that of MPs (91 min duration). These findings remained similar among deliveries with and without epidural analgesia or labor induction. We conclude that GMPs' and MPs' cervical dilation progression in the active phase of labor was similar, and the second stage of labor was shorter in GMPs, regardless of epidural use. Thus, GMPs' uterus function during labor corresponds, and possibly surpasses, that of MPs. These findings indicate that health providers can use the standard partogram of the active phase of labor when caring for GMP parturients. [ABSTRACT FROM AUTHOR]

Purpose: While the postoperative closure rate of idiopathic macular holes (IMH) is quite high, its success rate and visual prognosis differ depending on macular hole (MH) characteristics. This study investigated the IMH progression rate before vitrectomy. Methods: This retrospective study compared optical coherence tomography (OCT) taken at baseline and on operation day for patients with stage 2, 3 and 4 IMH to determine the changes in minimum linear diameter (MLD), base diameter (BD), height and MH index (MHI). The IMH progression rate was calculated by dividing each difference in OCT parameters by the time interval. Results: A total of 224 eyes of 216 patients were included. The average time interval from baseline to operation was 35.59 ± 23.43 (7–137) days. Final visual acuity was related to preoperative MLD, BD, best‐corrected visual acuity and time interval between baseline and operation (p = 0.005, p = 0.003, p <0.001 and p = 0.005 respectively). Between baseline and operation, the average MLD and BD increased significantly (all p <0.001). The average progression rates of MLD and BD assessed by simple regression analysis were 0.698 μm/day (R2 = 0.066, p <0.001) and 1.368 μm/day (R2 = 0.097, p <0.001) respectively. When patients were classified according to the MH stage, the progression rates of MLD and BD in those with stage 2 MH were significantly faster than those with stage 3 or 4 MH. Conclusion: The relatively smaller MHs in stage 2 progress faster than those in stages 3 and 4. Therefore, it would ultimately be beneficial to perform vitrectomy without delay in patients with stage 2 MH. [ABSTRACT FROM AUTHOR]

Backward erosion piping (BEP) is a form of internal erosion which can lead to failure of levees and dams. Most research focused on the critical head difference at which piping failure occurs. Two aspects have received less attention, namely (1) the temporal evolution of piping and (2) the local hydraulic conditions in the pipe and at the pipe tip. We present small-scale experiments with local pressure measurements in the pipe during equilibrium and pipe progression for different sands and degrees of hydraulic loading. The experiments confirm a positive relation between progression rate and grain size as well as the degree of hydraulic overloading. Furthermore, the analysis of local hydraulic conditions shows that the rate of BEP progression can be better explained by the bed shear stress and sediment transport in the pipe than by the seepage velocity at the pipe tip. The experiments show how different processes contribute to the piping process and these insights provide a first empirical basis for modeling pipe development using coupled seepage-sediment transport equations. [ABSTRACT FROM AUTHOR]

Little is known regarding the optimal timing of dysphagia assessment and PEG indication in amyotrophic lateral sclerosis (ALS). The study aims to investigate the progression of dysphagia in a cohort of ALS patients and to analyse whether there are variables linked to a faster progression of dysphagia and faster indication of PEG placement. A retrospective cohort study in 108 individuals with ALS. Fiberoptic endoscopic evaluation of swallowing was performed 6 monthly until PEG indication or death. Dysphagia severity and PEG indication were assessed using Penetration Aspiration Scale. Progression Index (PI) analysed the risk of disease progression (fast/slow) in relation to dysphagia onset and PEG indication. Patients were grouped based on ALS onset and PI. Person-time incidence rates were computed considering dysphagia onset and PEG indication from ALS symptoms during the entire observation period and have been reported as monthly and 6-month rates. Cox regression survival analysis assessed dysphagia and PEG risk factors depending on onset. Person-time incidence rates of dysphagia progression and PEG risk were increased based on type of ALS onset and PI. Patients with a fast progressing disease and with bulbar onset (BO) show statistically significant increased risk of dysphagia (BO 178.10% hazard ratio (HR) = 2.781 P < 0.01; fast 181.10% HR 2.811 P < 0.01). Regarding PEG risk, fast patients and patients with BO had a statistically significant increased risk (fast 147.40% HR 2.474 P < 0.01, BO 165.40% HR 2.654 P < 0.01). Fast PI predicts the likelihood of faster progression of dysphagia and PEG indication and should be included in multidisciplinary assessments and considered in the design of future guidelines regarding dysphagia management in ALS patients. Level of Evidence Level IV. [ABSTRACT FROM AUTHOR]

Background: Low-density lipoprotein cholesterol (LDL-C) and type 2 diabetes (T2DM) are both independent risk factors for aortic stenosis (AS). In AS patients, whether LDL-C or T2DM is associated with fast AS progression (FASP) and their interaction is unknown. This study aims to test the hypothesis that there is a heightened risk of FASP when elevated LDL-C coexists with T2DM., Methods: The Real-world Data of Cardiometabolic Protections (RED-CARPET) study enrolled participants with mild (peak aortic velocity = 2-3 m/s), moderate (3-4 m/s) and severe ( ≥ 4 m/s) AS between January 2015 and December 2020 at a single center. Participants were further stratified by baseline LDL-C joint T2DM, follow-up echocardiography was performed after 6 months, and the primary outcome was FASP, defined as the annual change in aortic peak velocity ( ≥ 0.3 m/s/year)., Results: Among the 170 participants included, 45.3% had mild AS, 41.2% had moderate AS, and 13.5% had severe AS. The mean age was 66.84 ± 12.64 years, and 64.1% were women. During the follow-up period of 2.60 ± 1.43 years, 35 (20.6%) cases of FASP were identified. Using non-T2DM with LDL-C < 2.15 mmol/L as reference, FASP risk was 1.30 [odds ratio (OR), 95% CI (0.99-7.78, p = 0.167)] for non-T2DM with LDL-C 2.15-3.14 mmol/L, 1.60 [OR, 95% CI (1.17-3.29, p = 0.040)] for non-T2DM with LDL-C ≥ 3.14 mmol/L, 2.21 [OR, 95% CI (0.49-4.32, p = 0.527)] for T2DM with LDL-C < 2.15 mmol/L, 2.67 [OR, 95% CI (1.65-7.10, p = 0.004)] for T2DM with LDL-C 2.15-3.14 mmol/L, and 3.20 [OR, 95% CI (1.07-5.34, p = 0.022)] for T2DM with LDL-C ≥ 3.14 mmol/L., Conclusions: LDL-C joint T2DM was associated with FASP. This investigation suggests that fast progression of AS may develop if LDL-C is poorly managed in T2DM. Additional research is needed to validate this finding and explore the possible biological mechanism to improve the cardiometabolic management of T2DM and seek possible prevention for AS progression for this population., Clinical Trial Registration: ChiCTR2000039901 (https://www.chictr.org.cn)., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 The Author(s). Published by IMR Press.)

Amyotrophic lateral sclerosis is a devastating neurodegenerative disease, characterized by loss of central and peripheral motor neurons. Although the disease is clinically and genetically heterogeneous, axonal hyperexcitability is a commonly observed feature that has been suggested to reflect an early pathophysiological step linked to the neurodegenerative cascade. Therefore, it is important to clarify the mechanisms causing axonal hyperexcitability and how these relate to the clinical characteristics of patients. Measures derived directly from a nerve excitability recording are frequently used as study end points, although their biophysical basis is difficult to deduce. Mathematical models can aid in the interpretation but are reliable only when applied to group-averaged recordings. Consequently, model estimates of membrane properties cannot be compared with clinical characteristics or treatment effects in individual patients, posing a considerable limitation in heterogeneous diseases, such as amyotrophic lateral sclerosis. To address these challenges, we revisited nerve excitability using a new pattern analysis-based approach (principal component analysis). We evaluated disease-specific patterns of excitability changes and established their biophysical origins. Based on the observed patterns, we developed new compound measures of excitability that facilitate the implementation of this approach in clinical settings. We found that excitability changes in amyotrophic lateral sclerosis patients (n = 161, median disease duration = 11 months) were characterized by four unique patterns compared with controls (n = 50, age and sex matched). These four patterns were best explained by changes in resting membrane potential (modulated by Na+/K+ currents), slow potassium and sodium currents (modulated by their gating kinetics) and refractory properties of the nerve. Consequently, we were able to show that altered gating of slow potassium channels was associated with, and predictive of, the rate of progression of the disease on the amyotrophic lateral sclerosis functional rating scale. Based on these findings, we designed four composite measures that capture these properties to facilitate implementation outside this study. Our findings demonstrate that changes in nerve excitability in patients with amyotrophic lateral sclerosis are dominated by four distinct patterns, each with a distinct biophysical origin. Based on this new approach, we provide evidence that altered slow potassium-channel function might play a role in the rate of disease progression. The magnitudes of these patterns, quantified using a similar approach or our new composite measures, have potential as efficient measures to study membrane properties directly in amyotrophic lateral sclerosis patients, and thus aid prognostic stratification and trial design., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Sparse and conflicting data exist regarding the normal partogram of grand-multiparous (GMP, defined as parity of 6+) parturients. Customized partograms may potentially lower cesarean delivery rates for protraction disorders in this population. In this study, we aim to construct a normal labor curve of GMP women and compare it to the multiparous (MP, defined as parity of 2–5) partogram. We conducted a multicenter retrospective cohort analysis of deliveries between the years 2003 and 2019. Eligible parturients were the trials of labor of singletons ≥37 + 0 weeks in cephalic presentation with ≥2 documented cervical examinations during labor. Exclusion criteria were elective cesarean delivery without a trial of labor, preterm labor, major fetal anomalies, and fetal demise. GMP comprised the study group while the MP counterparts were the control group. A total of 78,292 deliveries met the inclusion criteria, comprising 10,532 GMP and 67,760 MP parturients. Our data revealed that during the first stage of labor, cervical dilation progressed at similar rates in MPs and GMPs, while head descent was a few minutes faster in GMPs compared to MPs, regardless of epidural anesthesia. The second stage of labor was faster in GMPs compared to MPs; the 95th percentile of the second stage duration of GMPs (48 min duration) was 43 min less than that of MPs (91 min duration). These findings remained similar among deliveries with and without epidural analgesia or labor induction. We conclude that GMPs’ and MPs’ cervical dilation progression in the active phase of labor was similar, and the second stage of labor was shorter in GMPs, regardless of epidural use. Thus, GMPs’ uterus function during labor corresponds, and possibly surpasses, that of MPs. These findings indicate that health providers can use the standard partogram of the active phase of labor when caring for GMP parturients.

Purpose: To investigate the efficacy of myopia control defined by axial elongation and safety of orthokeratology lenses (OKL) in a Scandinavian (Danish) population. Methods: Sixty Danish children aged 6–12 years with myopia ranging from 0.5 to 4.75 dioptres (D) spherical component and refractive astigmatism ≤2.5 D in both eyes were randomly assigned to either OKL or single‐vision spectacles (SVS). Study duration was 18 months. Outcome measures were axial length (AL) measured with Lenstar LS900 (Haag‐Streit, Koeniz, Switzerland) and adverse events graded with Efron Grading Scale for Contact Lens Complications. Results: Nineteen participants completed the 18‐month follow‐up in the OKL group and 28 in the SVS group. The average AL elongation in the OKL group was 0.24 mm smaller as compared to the SVS group (95% confidence interval 0.12–0.36, mixed model adjusted for baseline sex, age and AL). There were no fast progressors (>0.75 D/year) in the OKL group during the follow‐up period in contrast to 22% in the SVS group. No treatment‐requiring or vision‐threatening adverse events were observed. Conclusion: Orthokeratology lenses reduced AL elongation in myopic Scandinavian children by 59%, with no treatment‐requiring or vision‐threatening adverse events. The results align with outcomes of previous clinical trials. [ABSTRACT FROM AUTHOR]

The volume and the data detail are increasing like social media, multimedia and internet of things produced huge data flow in structured and unstructured format. The academia, government, and industry have the great attention for data generation. The cloud computing is conjoined with the data and it provides the user ability to utilize the commodity computing for queries process through the several datasets and timely return of resultant set. The several serious challenges are produced by the amount of collected data such as transfer speed and security issues. Big Data is in its initial stage and it required to be classifies the various attributes of big data such as management and quick progression rate. The results show that the one big executer configuration performance is better as compared to the six small executer configuration. It is also observed that the more executer configuration increase the utilization of the resources and the high probability is led by the resource contention so there is negative impact on the system performance. The fewer amounts of data are produced and it performs better for other applications. The data size is not always reduced by enabling data compression. The data size is reduced up-to 72% by compression and memory serialization. [ABSTRACT FROM AUTHOR]

Introduction: Limbic-predominant age-related TAR DNA-binding protein 43 (TDP-43) encephalopathy (LATE) is a recently defined neurodegenerative disease. Currently, there is no effective way to make a prognosis of time to stage-specific future conversions at an individual level. Methods: After using the Kaplan-Meier estimation and log-rank test to confirm the heterogeneity of LATE progression, we developed a deep learning-based approach to assess the stage-specific probabilities of time to LATE conversions for different subjects. Results: Our approach could accurately estimate the disease incidence and transition to next stages: the concordance index was at least 82% and the integrated Brier score was less than 0.14. Moreover, we identified the top 10 important predictors for each disease conversion scenario to help explain the estimation results, which were clinicopathologically meaningful and most were also statistically significant. Discussion: Our study has the potential to provide individualized assessment for future time courses of LATE conversions years before their actual occurrence. [ABSTRACT FROM AUTHOR]

In our study, we aimed to assess the long‐term risk of gastric cardia adenocarcinoma (GCA) for patients with different histological cardia lesions to inform future guidelines for GCA screening in China. We conducted a population‐based prospective study among 9740 subjects who underwent upper endoscopy screening during 2005 to 2009 and followed until December 2017. Cumulative incidence and mortality rates of GCA were calculated by the baseline histological diagnoses, and the hazard ratios (HRs), overall and by age and sex, were analyzed by Cox proportional hazards models. During a median follow‐up of 10 years, we identified 123 new GCA cases (1.26%) and 31 GCA deaths (0.32%). The age‐standardized incidence and mortality rates of GCA were 128.71/100 000 and 35.69/100 000 person‐years, and cumulative incidence rate in patients with cardia high‐grade dysplasia (CHGD), cardia low‐grade dysplasia (CLGD) and atrophic carditis (AC)/cardia intestinal metaplasia (CIM) was 25%, 3.05% and 1.58%, respectively. The progression rate and cancer risk of GCA increased monotonically with each step in Correa's cascade. Individuals aged 50 to 69 years had 4.4 times higher GCA incidence than those aged 40 to 49 years. Patients with CLGD had a significantly higher 3‐year GCA incidence than the normal group, while patients with AC/CIM had a comparable GCA risk during 3‐year follow‐up but a higher risk at 5‐year intervals. Our results suggested a postponed starting age of 50 years for GCA screening, immediate treatment for patients with CHGD, a 3‐year surveillance interval for patients with CLGD, and a lengthened surveillance interval of 5 years for patients with AC/CIM. [ABSTRACT FROM AUTHOR]

Recently, various visualization techniques have been used to study spondyloarthritis (SpA); indices are also being elaborated to assess the progression of radiographic changes in the spine and sacroiliac joints. Most studies dedicated to the problem of coxitis in SpA have shown that its progression parallels with a spinal inflammatory process; however, no indices for assessing the time course of changes in the hip joints (HJs) have been developed.Objective: to develop a method for assessing the radiographic progression of coxitis in early axial SpA (axSpA).Subjects and methods. Examinations were made in 175 patients (mean age, 28±6 years) with axSpA who met the 2009 ASAS criteria and had an inflammatory back pain duration of no more than 5 years. The analysis included 62 patients who had been followed up for at least 2 years and had plain pelvic bone X-ray films at the inclusion in the cohort and at 2 years after starting the follow-up. The sum of stages of radiographic coxitis (ssrC) was used to assess HJ injury progression. During the study, a formula was developed to assess the progression rate of radiographic coxitis.Results and discussion. The median difference in ssrC (ΔssrC) was 0.78 [0; 4] at baseline and at 2 years. During the study period, 63% of the patients showed no progression of ssrC; the latter increased by 1 score in 7 (11%) patients, by 2 scores in 11 (18%), by 3 scores in 1 (2%), and by 4 scores in 4 (6%). The ssrC averaged 0.54±0.79 at baseline and increased by 0.78 up to 1.32±1.34 (p=0.06) at 2 years. At baseline, the coxitis progression rate averaged 0.45 per year (it was conventionally accepted that the patients exhibited no signs of HJ injury at onset of the disease: ssrC was zero); that was 0.54 and 0.1 per year at 1 and 2 years of follow-up, respectively.Conclusion. The proposed calculation procedure is easily feasible and applicable in real practice, does not lead to additional investigations, and is economically feasible. This procedure allows monitoring the rate of radiographic coxitis progression in patients with axSpA throughout the course of the disease.

Terpios hoshinota is a black, encrusting sponge that hosts numerous symbiotic cyanobacteria in its tissues. The sponge often overgrows live scleractinian corals, thereby causing widespread and accelerated coral loss. However, our understanding of how subtropical waters influence the seasonal change in the progression rate of the sponge is poor. To elucidate the progression dynamics over a year, we obtained monthly measurements of linear progression of T. hoshinota (mm month−1) on the branching coral Montipora digitata in the subtropical waters of Sesoko Island, Okinawa, Japan from 2019 to 2020. The progression rate of T. hoshinota varied monthly throughout the year. The progression rates were the highest in summer (July, August, and October) with a mean value of 66 mm month−1, except in September, when strong typhoons came close to Okinawa and the progression rate decreased temporarily. The progression rates were the lowest in February 2020, at 9 mm month−1. The mean annual linear progression rate was estimated to be 28 mm month−1. Therefore, the progression dynamics of T. hoshinota could be linked to their growth mechanisms in relation to the seasonal changes in subtropical waters. [ABSTRACT FROM AUTHOR]

Introduction: There are no many data on association between progression rate of Guillain-Barré syndrome (GBS) and disease outcome. Aim: The aim of our study was to analyze short-term outcome of GBS in relation to the rate of disease progression. Methods: Our retrospective study included patients diagnosed with GBS in seven tertiary healthcare centers from 2009 to 2014. According to the rate of disease progression from onset of symptoms to the nadir, patients were divided in three groups: rapid-onset GBS (nadir reached in maximum 48 h), gradual-onset (nadir reached in three to 14 days), and slow-onset (nadir in 15 to 28 days). GBS disability scale (GDS) was used to assess functional disability at nadir and on discharge. Results: Among 380 patients included in the study, 24 (6.3%) patients had rapid-onset, 274 (72.1%) gradual-onset, and 82 (21.6%) slow-onset GBS. Time from the onset of the disease to the hospital admission was much shorter in faster-onset forms (3.0 ± 4.1 days in rapid-onset vs. 6.8 ± 9.5 days in gradual-onset and 21.0 ± 9.6 days in slow-onset GBS, p < 0.01). Preceding events were less commonly identified in slow-onset forms. Patients with rapid-onset GBS were more likely to have axonal variants (p < 0.05). All three groups of patients were treated in a similar way, and there were no differences in GDS score at nadir (p > 0.05) and on discharge (p > 0.05) and no differences in the duration of hospital stay. Conclusion: Faster progression of GBS does not imply a poorer short-term functional outcome of the disease. [ABSTRACT FROM AUTHOR]

Introduction: Although there have been many researches on the etiology and risk factors with the onset of hemifacial spasm, researches on the risk factors related to progression rate are limited. This study aims to analyze the risk factors related to the progression rate of hemifacial spasm., Methods: The study enrolled 142 patients who underwent microvascular decompression for hemifacial spasm. Based on the duration and severity of symptoms, patients were classified into rapid progression group and slow progression group. To analyze risk factors, univariate and multivariate logistic regression analyses were conducted. Of 142 patients with hemifacial spasm, 90(63.3%) were classified as rapid progression group, 52(36.7%) were classified as slow progression group., Results: In the univariate analysis, there were significant statistical differences between the two groups in terms of age of onset ( P = 0.021), facial nerve angle ( P < 0.01), hypertension ( P = 0.01), presence of APOE ε4 expression ( P < 0.01) and different degrees of brainstem compression in the Root Entry Zone ( P < 0.01). In the multivariable analyses, there were significant statistical differences between the two groups in terms of age of symptom onset ( P < 0.01 OR = 6.591), APOE ε4 ( P < 0.01 OR = 5.691), brainstem compression ( P = 0.006 OR = 5.620), and facial nerve angle ( P < 0.01 OR = 5.758). Furthermore, we found no significant correlation between the severity of facial spasms and the progression rate of the disease ( t = 2.47, P = 0.12>0.05)., Conclusion: According to our study, patients with facial nerve angle ≤ 96.5°, severer compression of the brainstem by offending vessels, an onset age > 45 years and positive expression of APOE ε4, may experience faster progression of hemifacial spasm., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xu, Gu, Yuan, Jiang, Xie, Shi and Zhan.)

Background: Studies provide inconclusive results on the question whether loss of mental wellbeing is actually associated with decline in physical function in amyotrophic lateral sclerosis (ALS). The purpose of this study was to determine predictors of mental wellbeing in ALS. Methods: In total, n = 330 ALS patients were interviewed on parameters of mental wellbeing to evaluate the patients' capacity of psychosocial adaptation. These parameters were global and subjective quality of life (QoL), and depressiveness. A subsample of n = 82 ALS patients were interviewed again within approximately a year (mean 14.34 ± 5.53 months). Results: Both global and subjective QoL were stable, whereas depressiveness increased within the course of 1 year after diagnosis. Physical function decline was associated with mental wellbeing. Progression of physical disabilities and symptom duration were significant predictors of wellbeing in the sense that fast progression and short time since symptom onset (both indicating short time to adapt) were associated with low wellbeing. Conclusions: There is evidence for subsamples in ALS with regard to mental wellbeing, which are mainly determined by clinical parameters. Those subjects being reported in the literature to present with high mental wellbeing are often long survivors. High progression rate and low physical function when attending the clinic for the first time should be red flags and need special attention in clinical counseling. [ABSTRACT FROM AUTHOR]

Objective: Amyotrophic lateral sclerosis (ALS) is still incurable. Although different therapies can affect the health and survival of patients. Our aim is to evaluate the effect of umbilical mesenchymal stem cells administrated intrathecally to patients with amyotrophic lateral sclerosis on disability development and survival. Methods: This case-control study involved 67 patients treated with Wharton's jelly mesenchymal stem cells (WJ-MSC). The treated patients were paired with 67 reference patients from the PRO-ACT database which contains patient records from 23 ALS clinical studies (phase 2/3). Patients in the treatment and reference groups were fully matched in terms of race, sex, onset of symptoms (bulbar/spinal), FT9 disease stage at the beginning of therapy and concomitant amyotrophic lateral sclerosis medications. Progression rates prior to treatment varied within a range of ± 0.5 points. All patients received three intrathecal injections of Wharton's jelly-derived mesenchymal stem cells every two months at a dose of 30 × 106 cells. Patients were assessed using the ALSFRS-R scale. Survival times were followed-up until March 2020. Results: Median survival time increased two-fold in all groups. In terms of progression, three response types measured in ALSFRS-R were observed: decreased progression rate (n = 21, 31.3%), no change in progression rate (n = 33, 49.3%) and increased progression rate (n = 13, 19.4%). Risk-benefit ratios were favorable in all groups. No serious adverse drug reactions were observed. Interpretation: Wharton's jelly-derived mesenchymal stem cells therapy is safe and effective in some ALS patients, regardless of the clinical features and demographic factors excluding sex. The female sex and a good therapeutic response to the first administration are significant predictors of efficacy following further administrations. [ABSTRACT FROM AUTHOR]

The currently used methods for evaluating the progression of structural damages in early axial spondyloarthritis (axSpA) are little suitable to real practice since they require specially trained radiologists and increase a patient's exposure to radiation due to the need for radiography of three regions of the axial skeleton. In addition, the first radiological bone changes in the sacroiliac joints (SIJ) appear only many years after the onset of the disease, the overlying spine areas are involved in the pathological process. Objective: to develop a method for evaluating the radiographic progression of sacroiliitis (SI) in early axSpA for real clinical practice. Subjects and methods. The investigation enrolled patients from the early spondyloarthritis cohort (ESAC) formed at the V.A. Nasonova Research Institute of Rheumatology. The current ESAC comprised 164 patients; the analysis included 68 patients who had been followed up for at least 2 years and had plain pelvic bone films at the inclusion in the cohort and at 2-year follow-up. To evaluate disease progression, the investigators used the sum of radiographic SI stages in the left and right SIJs (the summary stage of radiographic SI (ssrSI), which was calculated at baseline and at 2-year follow-up. A formula for determining the rate of radiographic progression was derived. Results and discussion. At baseline and at 2-year follow-up, the median ssrSI difference (ΔssrSI) in 68 patients was 0 [0; 1.0]. During the study period, almost 60% of the patients had no progression of ssrSI, i.e. ΔssrSI was 0 in these patients, 1 and 2 scores in 12 (18%) and 13 (19%) patients, respectively, and there were singly cases, in which this figure was equal to 3, 4 and 7. The mean value of ssrSI was 3.5±1.6 at baseline and increased by 0.8, reaching 4.3±1.5 at 2 years (p = 0.006). Before included into the investigation, the patients had a progression rate of 1.75 during 1 year, which decreased to 0.4 per year in the active follow-up period. At the time of inclusion in the study, 40 (58.8%) of the 68 patients had ankylosing spondylitis (AS), and at 2 years their number increased to 51 (75.0%); i.e. 11 (39%) patients were observed to have progression of non-radiographic axSpA to AS. Conclusion. The proposed procedure to calculate ssrSI is easily feasible in real practice; it fails to lead to additional radiation exposure, is economically feasible, and allows one to monitor the rate of progression of axSpA in the early stage of the disease.

Abstract Background Spinocerebellar ataxia type 2 (SCA2) affects several neurological structures, giving rise to multiple symptoms. However, only the natural history of ataxia is well known, as measured during the study duration. We aimed to describe the progression rate of ataxia, by the Scale for the Assessment and Rating of Ataxia (SARA), as well as the progression rate of the overall neurological picture, by the Neurological Examination Score for Spinocerebellar Ataxias (NESSCA), and not only during the study duration but also in a disease duration model. Comparisons between these models might allow us to explore whether progression is linear during the disease duration in SCA2; and to look for potential modifiers. Results Eighty–eight evaluations were prospectively done on 49 symptomatic subjects; on average (SD), study duration and disease duration models covered 13 (2.16) months and 14 (6.66) years of individuals’ life, respectively. SARA progressed 1.75 (CI 95%: 0.92–2.57) versus 0.79 (95% CI 0.45 to 1.14) points/year in the study duration and disease duration models. NESSCA progressed 1.45 (CI 95%: 0.74–2.16) versus 0.41 (95% CI 0.24 to 0.59) points/year in the same models. In order to explain these discrepancies, the progression rates of the study duration model were plotted against disease duration. Then an acceleration was detected after 10 years of disease duration: SARA scores progressed 0.35 before and 2.45 points/year after this deadline (p = 0.013). Age at onset, mutation severity, and presence of amyotrophy, parkinsonism, dystonic manifestations and cognitive decline at baseline did not influence the rate of disease progression. Conclusions NESSCA and SARA progression rates were not constant during disease duration in SCA2: early phases of disease were associated with slower progressions. Modelling of future clinical trials on SCA2 should take this phenomenon into account, since disease duration might impact on inclusion criteria, sample size, and study duration. Our database is available online and accessible to future studies aimed to compare the present data with other cohorts.

Copyright of Journal of China Medical University is the property of Journal of China Medical University Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The progression rate for clinical manifestations in hemifacial spasm (HFS) varies; however, little is known about the factors contributing to this. The purpose of this study was to identify independent factors affecting the rate of symptom progression and to evaluate clinical outcomes according to progression rates. The study enrolled 1335 patients who underwent microvascular decompression for HFS between July 2004 and January 2015. We assessed detailed history, clinical manifestations, and outcomes. Based on the duration and severity of symptoms, patients were classified into rapidly progressive and slowly progressive groups. We identified predisposing factors affecting the differences between the 2 groups and evaluated the clinical outcome in each group. Of 1335 patients with HFS, 825 (61.8%) were classified as rapidly progressive, and 510 (38.2%) were classified as slowly progressive. In univariable and multivariable analyses, younger age at surgery, older age at symptom onset, and absence of intraoperative facial nerve indentation were significant predisposing factors for rapid progression. The rapidly progressive group had worse outcomes than the slowly progressive group following microvascular decompression. In this study, patients with rapidly progressive HFS had worse clinical outcomes. Therefore, patients with rapidly progressive symptoms should be warned in advance that the prognosis may be worse after microvascular decompression. This study is also useful to understand the differences in symptom progression rates in HFS in order to inform patients about symptom progression. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the influence of baseline geographic atrophy (GA) size on the rate of GA progression by using both distance and area measurements. Methods: Thirty-five eyes from 24 patients with GA due to age-related macular degeneration were obtained from anonymized datasets available at the Doheny Image Reading Center. Baseline and month 12 fundus autofluorescence (FAF) images were used for this analysis. Borders of GA lesions were semiautomatically segmented by certified reading center graders to create masks of the GA lesion. The masks from the two visits were registered and overlaid to allow the differences in area as well as the differences in the position of GA border between the visits to be computed. Distance measurements were performed using a Euclidean distance map. Sectoral (clock hour)/directional GA progression rates with respect to the foveal center were also calculated. Results: GA progressed 1.6 ± 0.9 mm2 in area and 92.9 ± 64.9 μm in distance over the 12 months. Smaller GA lesions were associated with more rapid progression when measured using distance (P = 0.0004, R = − 0.554). In contrast, there was no significant correlation in this cohort between baseline GA area and the progression measured in area (P = 0.406). In the sectoral/directional GA progression analysis, progression speed differed among clockwise directions, when progression was evaluated by using area measurements. However, this difference was not found, when evaluated by using distance measurements. Conclusions: Use of linear distance-based measurements enables evaluation of GA progression which is not confounded by baseline lesion size. [ABSTRACT FROM AUTHOR]

In previous work a model was developed and introduced to describe the conversion of pyrotechnic mixtures taking in consideration its particulate character and solving the heat and the mass transfer coupled with reaction kinetics [1]. In this work the model was applied to thermite mixtures with manganese(IV) oxide as oxidizer and aluminium or titanium as fuel. The modelling results of burning rate dependent of fuel‐oxidizer ratio were compared with results from experiments. For the modelling process, the educts were characterized by determining particle size and distribution and chemical reaction kinetics parameters. Other parameters were taken from literature. The modelling results are in good agreement with the experimental ones. It seems that the made physical and chemical assumptions are the main factors to describe the shape of burning rate profile in thermite combustion and the negligence are not influential. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study is to reappraise the progression of the five most common spinocerebellar ataxias (SCAs) in the Chinese population and to establish a much-needed critical comparison with that in other ethnic groups. There are very few longitudinal cohort studies of SCAs in Asian populations. An intriguing finding in an earlier study demonstrated a faster progression of SCA among Chinese than that among Caucasians.Methods: Patients with SCA1, SCA2, SCA3, SCA6 or SCA17 were consecutively assessed using the scale for the assessment and rating of ataxia (SARA) for five years. A linear mixed model was used to compare the annual progression rates measured using the SARA among patients with different SCA subtypes. Predictors of the progression rates were analyzed.Results: A total of 199 patients with SCA (10 with SCA1, 37 with SCA2, 118 with SCA3, 25 with SCA6 and 9 with SCA17) were enrolled. The mean annual increase in SARA scores was 1.23 points for SCA1, 1.52 points for SCA2, 1.60 points for SCA3, 0.99 points for SCA6 and 3.26 points for SCA17. A larger CAG repeat length (≥74) was associated with faster progression in SCA3, whereas a lower total SARA score at the first visit (<12) was associated with faster clinical progression in SCA6.Conclusion: The results of this study confirm that the annual progression rates of SCA2 and SCA3 are comparable between Han Chinese and other ethnic populations. More studies are warranted to confirm the rapid progression of SCA17 observed in our cohort. [ABSTRACT FROM AUTHOR]

Aims To evaluate the risk factors influencing the development of significant (moderate and severe) tricuspid regurgitation (TR), and its impact on all-cause mortality in large registry of referral centre. Methods and results In 1000 patients (mean age 68 ± 13 years; 50.9% male) with documented significant TR, clinical, and echocardiographic data were retrospectively analysed when the echocardiogram showed none/mild TR. Patients with congenital heart disease were excluded. The study population was divided into quartiles according to the time interval between the two echocardiograms: Group 1: ≤1.2 years, n  = 251; Group 2: 1.3–4.7 years, n  = 248, Group 3: 4.8–8.9 years, n  = 251; Group 4: ≥9.0 years, n  = 250. Baseline age [odds ratio (OR) 1.02], presence of pacemaker and defibrillator lead (OR 1.59), presence of mild (vs. none) TR (OR 8.96), reduced tricuspid annulus plane systolic excursion (OR 0.86), and tricuspid annulus dilation (OR 1.06) were independently associated with development of significant TR in a short period of time. Any valvular surgery (without concomitant tricuspid surgery) occurring between both echocardiograms was also associated with a higher risk of fast development of significant TR (OR 1.58). During a median follow-up of 2.9 years after the second echocardiogram (with significant TR), 42.1% patients died. Patients with fast development of significant TR showed worse survival than patients with slower significant TR development (log rank P  = 0.001). Fast development of significant TR was independently associated with all-cause mortality (hazard ratio per preceding year of development: 0.92, confidence interval 0.90–0.94; P  < 0.001). Conclusion By identifying patients at increased risk of developing significant TR, close echocardiographic surveillance can be indicated permitting effective therapy at an earlier stage to improve survival. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Contemporary Educational Studies / Sodobna Pedagogika is the property of Association of Slovenian Educationalists and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective To investigate the relationship between clinical features and survival time in amyotrophic lateral sclerosis (ALS) patients. Methods For this study we enrolled 101 ALS patients who visited Department of Neurology, the First Affiliated Hospital of Xi􀆳an Jiaotong University, from March 2010 to December 2015 and met the revised El Escorial Criteria. We documented the clinical features known up to the time of diagnosis, such as age of onset, BMI, body part of onset, diagnostic delay time, Ellis score, ALSFRS-r, ΔALSFRS-r, time from onset to second part involved and categories of diagnostic certainty. All the patients were regularly followed up every three months clinically or by phone. The clinical features mentioned above were analyzed for survival probability using the univariate and multivariate survival analyses. Results 1 Univariate log-rank test results: age at onset (HR 1.556, 95% CI 1.005-2.409, P=0.047), diagnostic delay time (HR 0.227, 95% CI 0.134-0.383, P <0.001), ΔALSFRS-r (HR 2.300, 95% CI 1.462-3.617, P <0.001), time from onset to second part involved (HR 0.593, 95% CI 0.377-0.934, P=0.024), and categories of diagnostic certainty (HR 1.709, 95% CI 1.065-2.743, P=0.026) were correlated to the survival time. 2 Multivariate Cox regression test results: diagnostic delay time (HR 0.948, 95% CI 0.912-0.985, P=0.006) and ΔALSFRS-r (HR 2.146, 95% CI 1.538-2.995, P <0.001) were correlated to the survival time. Conclusion Diagnostic delay time and ΔALSFRS-r are independent factors that affect the survival time in ALS. [ABSTRACT FROM AUTHOR]

Background: Spinocerebellar ataxia type 2 (SCA2) affects several neurological structures, giving rise to multiple symptoms. However, only the natural history of ataxia is well known, as measured during the study duration. We aimed to describe the progression rate of ataxia, by the Scale for the Assessment and Rating of Ataxia (SARA), as well as the progression rate of the overall neurological picture, by the Neurological Examination Score for Spinocerebellar Ataxias (NESSCA), and not only during the study duration but also in a disease duration model. Comparisons between these models might allow us to explore whether progression is linear during the disease duration in SCA2; and to look for potential modifiers.Results: Eighty-eight evaluations were prospectively done on 49 symptomatic subjects; on average (SD), study duration and disease duration models covered 13 (2.16) months and 14 (6.66) years of individuals' life, respectively. SARA progressed 1.75 (CI 95%: 0.92-2.57) versus 0.79 (95% CI 0.45 to 1.14) points/year in the study duration and disease duration models. NESSCA progressed 1.45 (CI 95%: 0.74-2.16) versus 0.41 (95% CI 0.24 to 0.59) points/year in the same models. In order to explain these discrepancies, the progression rates of the study duration model were plotted against disease duration. Then an acceleration was detected after 10 years of disease duration: SARA scores progressed 0.35 before and 2.45 points/year after this deadline (p = 0.013). Age at onset, mutation severity, and presence of amyotrophy, parkinsonism, dystonic manifestations and cognitive decline at baseline did not influence the rate of disease progression.Conclusions: NESSCA and SARA progression rates were not constant during disease duration in SCA2: early phases of disease were associated with slower progressions. Modelling of future clinical trials on SCA2 should take this phenomenon into account, since disease duration might impact on inclusion criteria, sample size, and study duration. Our database is available online and accessible to future studies aimed to compare the present data with other cohorts. [ABSTRACT FROM AUTHOR]