Number of baseline lesions has been shown to predict future attacks and disability in clinically isolated syndromes (CIS).
To investigate the role of baseline infratentorial lesions in long-term ...prognosis.
Subjects were included in a prospective cohort of patients with CIS. Patients underwent brain MRI within 3 months after CIS onset. Number and location of lesions at baseline were prospectively studied. Retrospective scan analysis was conducted to specifically look at number and location of infratentorial lesions. We analyzed the time to a second attack and to reach EDSS 3.0.
We included 246 patients with CIS followed for a median of 7.7 years. Patients with infratentorial lesions had both a higher risk of conversion (71.4% vs 29.6%; hazard ratio HR 3.3; 95% confidence interval CI 2.2-4.8; p < 0.001) and of developing disability (32.5% vs 12.4%; HR 2.4; 95% CI 1.3-4.3; p = 0.003). Presence of at least one cerebellar lesion was associated with an increased risk of conversion (HR 2.4; 95% CI 1.3-4.5; p = 0.007). Presence of at least one brainstem lesion increased both the risk of conversion (HR 2.9; 95% CI 1.7-5.0; p < 0.001) and disability (HR 2.5; 95% CI 1.1-5.4; p = 0.026). Broken down into number of lesions, the presence of infratentorial lesions increased both the risk of conversion (83% vs 61%) (HR 22.3; 95% CI 9.7-51.1; p < 0.001) and of reaching EDSS 3.0 (40% vs 19%) (HR 3.2; 95% CI 1.3-7.4; p = 0.008) only in patients with 9 or more lesions.
Presence of infratentorial lesions increases the risk for disability. Brainstem rather than cerebellar lesions may be responsible for poor prognosis.
Background:
The impact of global and tissue-specific brain atrophy on conversion to multiple sclerosis (MS) after a clinically isolated syndrome (CIS) is not fully gauged.
Objectives:
We aimed to ...determine the magnitude and clinical relevance of brain volume dynamics in the first year after a CIS.
Methods:
We assessed 176 patients with CIS within 3 months of onset, clinically and by conventional magnetic resonance imaging (MRI) scans, at baseline and 1 year after clinical onset. We determined the percentage of brain volume change (PBVC) and the brain parenchymal (BPF), grey matter (GMF) and white matter (WMF) fractions.
Results:
The mean follow-up time was 53 months (SD = 16.8): 76 patients (43%) experienced a second attack, 32 (18%) fulfilled MRI-only 2005 McDonald criteria and 68 (39%) remained as CIS. Statistically significant decreases in the volume measures tested were observed in patients with a second attack, for BPF and PBVC; in both MS groups for GMF; whereas in all groups, the WMF was unchanged. Patients with a second attack had larger PBVC decreases (− 0.65% versus + 0.059%; p < 0.001). PBVC decreases below − 0.817% independently predicted shorter times to a second attack.
Conclusions:
Global brain and grey matter volume loss occurred within the first year after a CIS; brain volume loss predicted conversion to MS.
Summary Background A multidisciplinary approach is thought to be the best way to manage the motor and non-motor symptoms of Parkinson's disease, but how such care should be delivered is unknown. To ...address this gap in knowledge, we assessed the effectiveness of an integrated multidisciplinary approach compared with usual care. Methods We recruited patients for our non-randomised controlled trial from six community hospitals in the Netherlands (two in regions where the integrated care intervention was available and four in control regions that administered usual care). Eligible patients were those with Parkinson's disease, aged 20–80 years, and without severe cognitive impairment or comorbidity. Patients in the intervention group were offered an individually tailored comprehensive assessment in an expert tertiary referral centre and subsequent referrals to a regional network of allied health professionals specialised in Parkinson's disease. Primary outcomes were activities of daily living (Academic Medical Center linear disability score ALDS) and quality of life (Parkinson's disease quality of life questionnaire PDQL) measured at 4, 6, and 8 months. Secondary outcomes included motor functioning (unified Parkinson's disease rating scale, part III UPDRS III, at 4 months), caregiver burden (belastungsfragebogen Parkinson angehörigen–kurzversion BELA-A-k at 4 and 8 months), and costs (during whole study period). Primary analysis was by intention to treat and included scores over 4, 6, and 8 months, with correction for baseline score. The trial is registered at Clinicaltrials.gov , number NCT00518791. Findings We recruited 301 patients (150 patients in the intervention group and 151 in the control group) between August, 2007, and December, 2009, of whom 285 completed follow-up (last follow-up was July, 2010). 101 (67%) patients in the intervention group visited the expert centre; 49 (33%) opted not to visit the expert centre. The average ALDS score from months 4, 6, and 8, with correction for baseline score, was greater in the intervention group than in the control group (difference 1·3 points, 95% CI −2·1 to 2·8; corresponding raw logit score difference 0·1, 95% CI 0·003 to 0·2) as was the average PDQL score (difference 3·0 points, 0·4 to 5·6). Secondary analysis with correction for baseline disease severity showed no differences between groups for ALDS (difference 0·9 points, 95% CI −0·6 to 2·4; corresponding raw logit score difference 0·1, −0·02 to 0·3) or PDQL (difference 1·7 points, −1·2 to 4·6). Secondary outcomes did not differ between groups (UPDRS III score difference 0·6 points, 95% CI −1·4 to 2·6; BELA-A-k score difference 0·8 points, −0·2 to 1·8; cost difference €742, −€489 to €1950). Interpretation This integrated care approach offered only small benefits to patients with Parkinson's disease, and these disappeared after correction for baseline disease severity. These results suggest that different approaches are needed to achieve more substantial health benefits. Funding NutsOhra Foundation, Stichting Parkinson Nederland, National Parkinson Foundation.
Risk factors for cutaneous squamous cell carcinoma (cSCC) metastasis have been investigated only in relatively small data sets.
To analyze and replicate risk factors for metastatic cSCC.
From English ...and Dutch nationwide cancer registry cohorts, metastatic cases were selected and 1:1 matched to controls. The variables were extracted from pathology reports from the National Disease Registration Service in England. In the Netherlands, histopathologic slides from the Dutch Pathology Registry were revised by a dermatopathologist. Model building was performed in the English data set using backward conditional logistic regression, whereas replication was performed using the Dutch data set.
In addition to diameter and thickness, the following variables were significant risk factors for metastatic cSCC in the English data set (n = 1774): poor differentiation (odds ratio OR, 4.56; 95% CI, 2.99-6.94), invasion in (OR, 1.69; 95% CI, 1.05-2.71)/beyond (OR, 4.43; 95% CI, 1.98-9.90) subcutaneous fat, male sex (OR, 2.59; 95% CI, 1.70-3.96), perineural/lymphovascular invasion (OR, 2.12; 95% CI, 1.21-3.71), and facial localization (OR, 1.57; 95% CI, 1.02-2.41). Diameter and thickness showed significant nonlinear relationships with metastasis. Similar ORs were observed in the Dutch data set (n = 434 cSCCs).
Retrospective use of pathology reports in the English data set.
cSCC staging systems can be improved by including differentiation, clinical characteristics such as sex and tumor location, and nonlinear relationships for diameter and thickness.
AbstrakKabupaten Ogan Komering Ilir (OKI) merupakan salah satu kabupaten di provinsi Sumatera Selatan yang memiliki kebudayaan yang kuat. Masyarakat OKI menjunjung tinggi adat istiadat dalam ...kehidupan sehari-hari, di antaranya seperti Midang dan Mulah, yang merupakan tradisi pernikahan masyarakat OKI. Selain itu, kabupaten OKI juga memiliki potensi wisata tinggi, di antaranya Taman Segitiga Emas dan danau Teluk Gelam. Namun, kabupaten OKI belum memiliki penjenamaan visual yang dapat mengenalkan potensi wisata yang terdapat di dalamnya, sehingga menjadikan kabupaten OKI kurang dikenal masyarakat secara luas sebagai tujuan wisata di provinsi Sumatera Selatan. Tujuan dari penelitian ini adalah untuk mengenalkan potensi wisata yang terdapat di kabupaten OKI melalui penjenamaan visual. Penelitian ini menggunakan metode perancangan design thinking oleh Tim Brown yang memiliki lima tahapan dalam melakukan perancangan desain yaitu empathize, define, ideate, protoype dan test. Proses pengumpulan data menggunakan metode kualitatif dengan melakukan observasi, wawancara, kajian literasi, dan dokumentasi. Hasil sintesis menjadi solusi pemecahan masalah dalam bentuk penjenamaan visual untuk merespon permasalahan komunikasi visual yang terjadi di kabupaten OKI. Konsep visual brand pada penelitian menjadi nilai kebaruan dari hasil perancangan, sehingga dapat menjadi media promosi yang mampu mengenalkan potensi wisata dan budaya di kabupaten OKI. Kata kunci: kabupaten Ogan Komering Ilir, media promosi, penjenamaan visual, wisata AbstractOgan Komering Ilir (OKI) district is one of the districts in South Sumatra province that has a strong culture. The community of OKI highly upholds traditional customs in their daily lives, including practices such as Midang and Mulah, which are wedding traditions of the OKI community. In addition, OKI district also has high tourism potential, including the Golden Triangle Park and Teluk Gelam lake. However, OKI district does not yet have a visual branding that can introduce the tourism potential contained in it, thus making OKI district less widely known to the public as a tourist destination in South Sumatra province. The purpose of this research is to introduce the tourism potential contained in OKI district through visual branding. This research employs the design thinking methodology developed by Tim Brown, consisting of five stages in the design process: empathize, define, ideate, prototype, and test. The data collection process utilizes qualitative methods, including observation, interviews, literary reviews, and documentation. The results of the synthesis become a problem-solving solution in the form of visual branding to respond to visual communication problems that occur in OKI district. The visual brand concept in the research becomes the novelty value of the design results, so that it can be a promotional media that is able to introduce the tourism and cultural potential in OKI district. Keywords: Ogan Komering Ilir district, promotional media, tourism, visual branding
•We compare four numerical codes for DNS of turbulent Rayleigh–Bénard convection.•The accuracy was assessed in terms of the Nusselt number.•Higher-order methods are generally more accurate at a given ...spatial resolution.•Dedicated codes are found to be more computationally efficient than general codes.
Computational codes for direct numerical simulations of Rayleigh–Bénard (RB) convection are compared in terms of computational cost and quality of the solution. As a benchmark case, RB convection at Ra=108 and Pr=1 in a periodic domain, in cubic and cylindrical containers is considered. A dedicated second-order finite-difference code (AFID/RBflow) and a specialized fourth-order finite-volume code (Goldfish) are compared with a general purpose finite-volume approach (OpenFOAM) and a general purpose spectral-element code (Nek5000). Reassuringly, all codes provide predictions of the average heat transfer that converge to the same values. The computational costs, however, are found to differ considerably. The specialized codes AFID/RBflow and Goldfish are found to excel in efficiency, outperforming the general purpose flow solvers Nek5000 and OpenFOAM by an order of magnitude with an error on the Nusselt number Nu below 5%. However, we find that Nu alone is not sufficient to assess the quality of the numerical results: in fact, instantaneous snapshots of the temperature field from a near wall region obtained for deliberately under-resolved simulations using Nek5000 clearly indicate inadequate flow resolution even when Nu is converged. Overall, dedicated special purpose codes for RB convection are found to be more efficient than general purpose codes.
The Neolithic transition has been widely debated particularly regarding the extent to which this revolution implied a demographic expansion from the Near East. We attempted to shed some light on this ...process in northeastern Iberia by combining ancient DNA (aDNA) data from Early Neolithic settlers and published DNA data from Middle Neolithic and modern samples from the same region. We successfully extracted and amplified mitochondrial DNA from 13 human specimens, found at three archaeological sites dated back to the Cardial culture in the Early Neolithic (Can Sadurní and Chaves) and to the Late Early Neolithic (Sant Pau del Camp). We found that haplogroups with a low frequency in modern populations—N* and X1—are found at higher frequencies in our Early Neolithic population (∼31%). Genetic differentiation between Early and Middle Neolithic populations was significant (FST∼0.13, P < 10−5), suggesting that genetic drift played an important role at this time. To improve our understanding of the Neolithic demographic processes, we used a Bayesian coalescence‐based simulation approach to identify the most likely of three demographic scenarios that might explain the genetic data. The three scenarios were chosen to reflect archaeological knowledge and previous genetic studies using similar inferential approaches. We found that models that ignore population structure, as previously used in aDNA studies, are unlikely to explain the data. Our results are compatible with a pioneer colonization of northeastern Iberia at the Early Neolithic characterized by the arrival of small genetically distinctive groups, showing cultural and genetic connections with the Near East.
Objective
This study seeks to contribute to the current understanding of dietary variation in the late Prehistory of the northeastern Iberian Peninsula by examining buccal dental microwear patterns ...alongside archeological data from the same populations.
Materials and Methods
Teeth from 84 adult individuals from eight distinct samples spanning the Middle‐Late Neolithic to the Middle Bronze Age (Cova de l'Avi, Cova de Can Sadurní, Cova de la Guineu, Cova Foradada, Cova del Trader, Roc de les Orenetes, Cova del Gegant, Cova dels Galls Carboners) were analyzed using optical microscopy to examine buccal dental microwear patterns.
Results
The analysis did not reveal clear chronological contrasts in the dietary habits of these samples. Nevertheless, significant differences emerged among the samples, leading to their classification into two distinct sets based on the abrasiveness of the diet informed by the microwear patterns. These findings offer similarities and differences among samples in the Iberian Peninsula, shedding light on the diverse lifestyles of these individuals.
Discussion
Integrating our new results with other available proxies points to a multifaceted specialization in dietary patterns among these samples, influenced by factors such as habitat, resource selection, and available technology. By contextualizing the results within the broader context of the Iberian Peninsula, this research discerns shared characteristics and distinctive adaptations in the dietary practices and subsistence strategies of these groups. Ultimately, this study contributes to a deeper understanding of the intricate interplay between culture and environment in shaping human diets throughout late Prehistory.
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