Circadian Rhythm Disturbances in Patients with Alzheimer's Disease: A Review

Circadian Rhythm Disturbances (CRDs) affect as many as a quarter of Alzheimer's disease (AD) patients during some stage of their illness. Alterations in the suprachiasmatic nucleus and melatonin secretion are the major factors linked with the cause of CRDs. As a result, the normal physiology of sleep, the biological clock, and core body temperature are affected. This paper systematically discusses some of the causative factors, typical symptoms, and treatment options for CRDs in patients with AD. This paper also emphasizes the implementation of behavioral and environmental therapies before embarking on medications to treat CRDs. Pharmacotherapeutic options are summarized to provide symptomatic benefits for the patient and relieve stress on their families and professional care providers. As of today, there are few studies relative to CRDs in AD. Large randomized trials are warranted to evaluate the effects of treatments such as bright light therapy and engaging activities in the reduction of CRDs in AD patients

Understanding Achievement in Numeracy Among Primary School Children in Ethiopia: Evidence from RISE Ethiopia Study

Ethiopia has succeeded in rapidly expanding access to primary education over the past two decades. However, learning outcomes remain low among primary school children and particularly among girls and children from disadvantaged backgrounds. Starting with a systematic review of quantitative studies on the determinants of learning outcomes among primary school children in Ethiopia, this study then examined key determinants of students’ numeracy achievement over the 2018-19 school year. The study focused on Grade 4 children (N= 3,353) who are part of an on-going longitudinal study. The two questions that guided this study are: what are the key determinants of numeracy achievement at Grade 4 in primary schools in Ethiopia, and how does our current empirical study contribute to understanding achievement differences in numeracy among primary school children in Ethiopia? We employed descriptive and inferential statistics to examine factors that determine differences in numeracy scores at the start and end of the school year, as well as determinants of numeracy scores at the end of the school year conditional on achievement at the start of the school year. We examined differences across gender, region, and rural-urban localities. We also used ordinary least squares and school ‘fixed effects’ approaches to estimate the key child, household and school characteristics that determine numeracy scores in Grade 4. The findings revealed that boys significantly outperformed girls in numeracy both at the start and end of the 2018/19 school year, but the progress in numeracy scores over the school year by boys was similar to that of girl

A Simulation Based Performance Evaluation of Optical Ethernet Switch

With the advent of several new Cloud Radio Access Network (C-RAN) technologies, todays networking environment is dramatically altered and is experiencing a rapid transformation. One of the most important is Ethernet based C-RAN, in support of which many products such as optical Ethernet switches have recently appeared on the market. This paper presents the performance analysis of such switches with respect to Packet Loss Ratio (PLR), Latency and Packet Delay Variation (PDV). We employed the Simula based on Discrete Event Modelling on Simula (DEMOS), a context class for discrete event simulation to simulate a cut-through optical Ethernet switch under two types of traffics: High priority (HP) traffic and Low priority (LP) traffic. In this way, the paper evaluates the optical Ethernet switch performance quantitatively. The results obtained from the simulator showed that the high quality of service was reflected on HP traffic and the low quality of service in LP traffic. Hence, HP traffic can be used for transporting Radio over Ethernet (RoE) traffic while LP traffic can used for transporting time insensitive application. It is also found that HP traffic experiences a PDV equals to the duration of maximum sized LP traffic in Optical Ethernet switch.Comment: arXiv admin note: text overlap with arXiv:1911.0761

Improving starting time in operating rooms of a tertiary hospital in Rwanda: a quality improvement project

Background: Delay in the first surgery start time at operating room (OR) could inevitably decrease utilization, lose very expensive OR resources, reduce satisfaction of patients and staff and potentially affect quality of patient care.Objectives: This study utilized the Strategic Problem Solving (SPS) quality improvement approach to increase the percentage of first surgeries started on time at a tertiary hospital in Rwanda.Methods: A pre- and post-intervention study was conducted between March 2016 and March 2017. The intervention included developing a policy on staff arrival time, training sessions on the policy and regular supervision of OR managers to ensure staff were arriving on time.Results: Chi square tests were performed to analyze the pre- and post-intervention results. The percentage of first surgeries started on time significantly increased from 3% pre-intervention to 25% postintervention (P<0.001), average duration of delay decreased by 55 minutes (P<0.001) and the percentages of nurses, anesthetists and surgeon arrived on time also significantly increased (P<0.001).Conclusion: The SPS approach can be useful in addressing the starting time of first surgery at OR. Support from the senior management team and buy-in from staff are essential. This project cannot eliminate confounding factors and the results cannot be generalizable to other settings. Longer term evaluation on sustainability is needed.Keywords: Delay first surgery, operating room efficiency, quality improvement, strategic problem solvin

Spatiotemporal variability of soil moisture over Ethiopia and its teleconnections with remote and local drivers

Soil moisture is one of the essential climate variables with a potential impact on local climate variability. Despite the importance of soil moisture, studies on soil moisture characteristics in Ethiopia are less documented. In this study, the spatiotemporal variability of Ethiopian soil moisture (SM) has been characterized, and its local and remote influential driving factors are investigated. An empirical orthogonal function (EOF) and KMeans clustering algorithm have been employed to classify the large domain into homogeneous zones. Complex maximum covariance analysis (CMCA) is applied to evaluate the covariability between SM and selected local and remote variables such as rainfall (RF), evapotranspiration (ET), and sea surface temperature (SST). Inter-comparison among SM datasets highlight that the FLDAS dataset better depicts the country’s SM spatial and temporal distribution (i.e., a correlation coefficient r=0.95 , rmsd=0.04m3m−3 with observations). Results also indicate that regions located in northeastern Ethiopia are drier irrespective of the season (JJAS, MAM, and OND) considered. In contrast, the western part of the country consistently depicted a wetter condition in all seasons. During summer (JJAS), the soil moisture variability is characterized by a strong east–west spatial contrast. The highest and lowest soil moisture values were observed across the country’s central western and eastern parts, respectively. Furthermore, analyses indicate that interannual variability of SM is dictated substantially by RF, though the impact on some regions is weaker. It is also found that ET likely drives the SM in the eastern part of Ethiopia due to a higher atmospheric moisture demand that ultimately invokes changes in surface humidity and rainfall. A composite analysis based on the extreme five wettest and driest SM years revealed a similar spatial distribution of wet SM with positive anomalies of RF across the country and ET over the southern regions. Remote SSTs are also found to have a significant influence on SM distribution. In particular, equatorial central Pacific and western Indian oceans SST anomalies are predominant factors for spatiotemporal SM variations over the country. Major global oceanic indices: Oceanic Nino Index (ONI), Indian Ocean Dipole (IOD), Pacific warm pool (PACWARMPOOL), and Pacific Decadal Oscillations (PDO) are found to be closely associated with the SM anomalies in various parts of the country. The associationship between these remote SST anomalies and local soil moisture is via large-scale atmospheric circulations that are linked to regional factors such as precipitation and temperature anomalies.publishedVersio

Human thymic T cell repertoire is imprinted with strong convergence to shared sequences

A highly diverse repertoire of T cell antigen receptors (TCR) is created in the thymus by recombination of gene segments and the insertion or deletion of nucleotides at the junctions. Using next-generation TCR sequencing we define here the features of recombination and selection in the human TCR alpha and TCR beta locus, and show that a strikingly high proportion of the repertoire is shared by unrelated individuals. The thymic TCRa nucleotide repertoire was more diverse than TCR beta, with 4.1 x 10(6) vs. 0.81 x 10(6) unique clonotypes, and contained nonproductive clonotypes at a higher frequency (69.2% vs. 21.2%). The convergence of distinct nucleotide clonotypes to the same amino acid sequences was higher in TCRa than in TCR beta repertoire (1.45 vs. 1.06 nucleotide sequences per amino acid sequence in thymus). The gene segment usage was biased, and generally all individuals favored the same genes in both TCR alpha and TCR beta loci. Despite the high diversity, a large fraction of the repertoire was found in more than one donor. The shared fraction was bigger in TCR alpha than TCR beta repertoire, and more common in in-frame sequences than in nonproductive sequences. Thus, both biases in rearrangement and thymic selection are likely to contribute to the generation of shared repertoire in humans.Peer reviewe

Characterization of human T cell receptor repertoire data in eight thymus samples and four related blood samples

T cell receptor (TCR) is a heterodimer consisting of TCR alpha and TCR beta chains that are generated by somatic recombination of multiple gene segments. Nascent TCR repertoire undergoes thymic selections where non-functional and potentially autoreactive receptors are removed. During the last years, the development of high-throughput sequencing technology has allowed a large scale assessment of TCR repertoire and multiple analysis tools are now also available. In our recent manuscript, Human thymic T cell repertoire is imprinted with strong convergence to shared sequences [1], we show highly overlapping thymic TCR repertoires in unrelated individuals. In the current Data in Brief article, we provide a more detailed characterization of the basic features of these thymic and related peripheral blood TCR repertoires. The thymus samples were collected from eight infants undergoing corrective cardiac surgery, two of whom were monozygous twins [2]. In parallel with the surgery, a small aliquot of peripheral blood was drawn from four of the donors. Genomic DNA was extracted from mechanically released thymocytes and circulating leukocytes. The sequencing of TCR alpha and TCR beta repertoires was performed at ImmunoSEQ platform (Adaptive Biotechnologies). The obtained repertoire data were analysed applying relevant features from immunoSEQ (R) 3.0 Analyzer (Adaptive Biotechnologies) and a freely available VDJTools software package for programming language R [3]. The current data analysis displays the basic features of the sequenced repertoires including observed TCR diversity, various descriptive TCR diversity measures, and V and J gene usage. In addition, multiple methods to calculate repertoire overlap between two individuals are applied. The raw sequence data provide a large database of reference TCRs in healthy individuals at an early developmental stage. The data can be exploited to improve existing computational models on TCR repertoire behaviour as well as in the generation of new models. (C) 2021 The Authors. Published by Elsevier Inc.Peer reviewe

Comorbidity phenotypes and risk of mortality in patients with osteoarthritis in the UK:a latent class analysis

BACKGROUND: Osteoarthritis (OA) is a common chronic condition but its association with other chronic conditions and mortality is largely unknown. This study aimed to use latent class analysis (LCA) of 30 comorbidities in patients with OA and matched controls without OA to identify clusters of comorbidities and examine the associations between the clusters, opioid use, and mortality. METHODS: A matched cohort analysis of patients derived from the IQVIA Medical Research Data (IMRD-UK) database between 2000 and 2019. 418,329 patients with newly diagnosed OA were matched to 243,170 patients without OA to identify comorbidity phenotypes. Further analysis investigated the effect of opioid use on mortality in individuals with OA and their matched controls. RESULTS: The median (interquartile range (IQR)) number of comorbidities was 2 (1–4) and 1 (0–3) in the OA and control groups respectively. LCA identified six comorbidity phenotypes in individuals with and without OA. Clusters with a high prevalence of comorbidities were characterised by hypertension, circulatory, and metabolic diseases. We identified a comorbidity cluster with the aforementioned comorbidities plus a high prevalence of chronic kidney disease, which was associated with twice the hazard of mortality in hand OA with a hazard ratio (HR) (95% CI) of 2.53 (2.05–3.13) compared to the hazard observed in hip/knee OA subtype 1.33 (1.24–1.42). The impact of opioid use in the first 12 months on hazards of mortality was significantly greater for weak opioids and strong opioids across all groups HR (95% CI) ranging from 1.11 (1.07–11.6) to 1.80 (1.69–1.92)). There was however no evidence of association between NSAID use and altered risk of mortality. CONCLUSION: This study identified six comorbidity clusters in individuals with OA and matched controls within this cohort. Opioid use and comorbidity clusters were differentially associated with the risk of mortality. The analyses may help shape the development of future interventions or health services that take into account the impact of these comorbidity clusters. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13075-022-02909-4