Neurocognitive and Academic Outcomes at Age 10 Years of Extremely Preterm Newborns

Despite reductions in mortality and morbidity among children born extremely preterm, they remain at high risk of neurocognitive deficits, with up to 40% having significant cognitive deficits at school age. We assessed the rate of neurocognitive impairment in a contemporary US cohort of 873 children aged 10 years who were born <28 weeks’ gestation

Development of a Scalable Edge-Cloud Computing Based Variable Rate Irrigation Scheduling Framework

Currently, variable-rate precision irrigation (VRI) scheduling methods require large amounts of data and processing time to accurately determine crop water demands and spatially process those demands into an irrigation prescription. Unfortunately, irrigated crops continue to develop additional water stress when the previously collected data is being processed. Machine learning is a helpful tool, but handling and transmitting large datasets can be problematic; more rural areas may not have access to necessary wireless data transmission infrastructure to support cloud interaction. The introduction of “edge-cloud” processing to agricultural applications has shown to be effective at increasing data processing speed and reducing the amount of data transmission to remote processing computers or base stations. In irrigation in particular, edge-cloud computing has so far had limited implementation. Therefore, an initial logic flow concept has been developed to effectively implement this new processing technique for VRI. Utilizing edge-cloud computer nodes in the field, autonomous data collection devices such as center pivot-mounted infrared canopy thermometers, soil moisture sensors, local weather stations, and UAVs could transmit highly localized crop data to the edge-cloud computer for processing. The edge computer Following the implementation of an irrigation strategy created by the edge-cloud computer with a machine learning model, data would be transmitted to the cloud (requiring transmission of only minimal model parameters), resulting in a feedback loop for continual improvement of the global model on the cloud (federated learning). VRI prescription maps from the SETMI model were used as the training data for training the machine learning model

Longitudinal Assessment of Remnant Foveal Cone Structure in a Case Series of Early Macular Telangiectasia Type 2

PURPOSE: To determine the extent of remnant cone structure within early foveal ellipsoid zone (EZ) lesions in macular telangiectasia type 2 longitudinally using both confocal and split detector adaptive optics scanning light ophthalmoscopy (AOSLO). METHODS: Spectral domain optical coherence tomography (SDOCT), confocal and split detector AOSLO were acquired from seven patients (10 eyes) with small (early) EZ lesions on SDOCT secondary to macular telangiectasia type 2 at baseline, 6 months, and 12 months. The presence of cone structure on AOSLO in areas of EZ loss as well as cones at 1° eccentricity, and their change over time were quantified. RESULTS: By split detector AOSLO, remnant cone structure was identified within and on the borders of all foveal EZ lesions. Within the extent of these lesions, cone spacing ranged from 4.97 to 9.95 µm at baseline, 5.30 to 6.10 µm at 6 months, and 4.99 to 7.12 µm at 12 months. Four eyes with significantly smaller EZ lesions showed evidence of recovery of EZ reflectivity on SDOCT B-scans. Remnant cone structure was identified in some areas where EZ reflectivity recovered at the following time point. Eyes that showed recovery of EZ reflectivity had a continuous external limiting membrane. CONCLUSIONS: Remnant cone structure can persist within small SDOCT-defined EZ lesions, which can wax and wane in appearance over time. AOSLO can help to inform the interpretation of SDOCT imaging. TRANSLATIONAL RELEVANCE: The absence of EZ in early macular telangiectasia type 2 and other retinal conditions needs careful interpretation because it does not always indicate an absence of underlying cone structure. The integrity of the external limiting membrane may better predict the presence of remnant cone structure and recovery of EZ reflectivity

The Apolipoprotein M/S1P Axis Controls Triglyceride Metabolism and Brown Fat Activity

Summary: Apolipoprotein M (apoM) is the carrier of sphingosine-1-phosphate (S1P) in plasma high-density lipoproteins. S1P is a bioactive lipid interacting with five receptors (S1P1–5). We show that lack of apoM in mice increases the amount of brown adipose tissue (BAT), accelerates the clearance of postprandial triglycerides, and protects against diet-induced obesity (i.e., a phenotype similar to that induced by cold exposure or β3-adrenergic stimulation). Moreover, the data suggest that the phenotype of apoM-deficient mice is S1P dependent and reflects diminished S1P1 stimulation. The results reveal a link between the apoM/S1P axis and energy metabolism. : Apolipoprotein M (apoM) is the carrier of sphingosine-1-phosphate (S1P) in lipoproteins. Christoffersen et al. show that lack of apoM in mice increases the amount of brown adipose tissue, accelerates the turnover of fat, and protects against obesity. The results reveal a link between the apoM/S1P axis and energy metabolism. Keywords: apolipoproteins, sphingolipids, sphingosine-1-phosphate, lipoproteins, lipid metabolism, triglyceride, brown adipose tissue, apo

Identification of genetic factors influencing metabolic dysregulation and retinal support for MacTel, a retinal disorder

Macular Telangiectasia Type 2 (MacTel) is a rare degenerative retinal disease with complex genetic architecture. We performed a genome-wide association study on 1,067 MacTel patients and 3,799 controls, which identified eight novel genome-wide significant loci (p < 5 × 10−8), and confirmed all three previously reported loci. Using MAGMA, eQTL and transcriptome-wide association analysis, we prioritised 48 genes implicated in serine-glycine biosynthesis, metabolite transport, and retinal vasculature and thickness. Mendelian randomization indicated a likely causative role of serine (FDR = 3.9 × 10−47) and glycine depletion (FDR = 0.006) as well as alanine abundance (FDR = 0.009). Polygenic risk scoring achieved an accuracy of 0.74 and was associated in UKBiobank with retinal damage (p = 0.009). This represents the largest genetic study on MacTel to date and further highlights genetically-induced systemic and tissue-specific metabolic dysregulation in MacTel patients, which impinges on retinal health

Attention bias modification: the Emperor's new suit?

A series of primarily laboratory-based studies found attention bias modification in socially anxious participants to lead to reduced anxiety. It is argued that the failure to replicate the positive results of attention bias modification in the study of Carlbring et al. may be due to reasons other than the application through the Internet. A number of controlled studies failed to replicate the positive effects of attention bias modification in clinically rather than subclinically socially anxious subjects. Given the lack of robust evidence for attention bias modification in clinically socially anxious individuals, the author is inclined to consider attention bias modification as 'the Emperor's new suit'. Results achieved with regular Internet-based treatments for social anxiety disorder based on cognitive therapy and exposure methods are much better than those achieved with attention bias modification procedures delivered 'face to face' in clinically distressed participants. Given the lack of robust evidence for attention bias modification in clinical samples, there is no need yet to investigate the implementation of attention bias modification through the Internet

A Novel Function of Apolipoprotein E: Upregulation of ATP-Binding Cassette Transporter A1 Expression

Despite the well known importance of apolipoprotein (Apo) E in cholesterol efflux, the effect of ApoE on the expression of ATP-binding cassette transporter A1 (ABCA1) has never been investigated. The objective of this study was to determine the effect of ApoE on ApoB-carrying lipoprotein-induced expression of ABCA1, a protein that mediates cholesterol efflux. Our data demonstrate that ApoB-carrying lipoproteins obtained from both wild-type and ApoE knockout mice induced ApoAI-mediated cholesterol efflux in mouse macrophages, which was associated with an enhanced ABCA1 promoter activity, and an increased ABCA1 mRNA and protein expression. In addition, these lipoproteins increased the level of phosphorylated specificity protein 1 (Sp1) and the amount of Sp1 bound to the ABCA1 promoter. However, all these inductions were significantly diminished in cells treated with ApoE-free lipoproteins, when compared to those treated with wild-type lipoproteins. Enrichment with human ApoE3 reversed the reduced inducibility of ApoE-free lipoproteins. Moreover, we observed that inhibition of Sp1 DNA-binding by mithramycin A diminished ABCA1 expression and ApoAI-mediated cholesterol efflux induced by ApoB-carrying lipoproteins, and that mutation of the Sp1-binding motif in the ABCA1 promoter region diminished ApoB-carrying lipoprotein-induced ABCA1 promoter activity. Collectively, these data suggest that ApoE associated with ApoB-carrying lipoproteins has an upregulatory role on ABCA1 expression, and that induction of Sp1 phosphorylation is a mechanism by which ApoE upregulates ABCA1 expression

Impact of alcohol use disorder severity on human immunodeficiency virus (HIV) viral suppression and CD4 count in three international cohorts of people with HIV.

Alcohol use has been linked to worse human immunodeficiency virus (HIV) immunologic/virologic outcomes, yet few studies have explored the effects of alcohol use disorder (AUD). This study assessed whether AUD severity is associated with HIV viral suppression and CD4 count in the three cohorts of the Uganda Russia Boston Alcohol Network for Alcohol Research Collaboration on HIV/AIDS (URBAN ARCH) Consortium. People with HIV (PWH) in Uganda (n = 301), Russia (n = 400), and Boston (n = 251), selected in-part based on their alcohol use, were included in analyses. Logistic and linear regressions were used to assess the cross-sectional associations between AUD severity (number of DSM-5 diagnostic criteria) and (1) HIV viral suppression, and (2) CD4 count (cells/mm &lt;sup&gt;3&lt;/sup&gt; ) adjusting for covariates. Analyses were conducted separately by site. The proportion of females was 51% (Uganda), 34% (Russia), and 33% (Boston); mean age (SD) was 40.7 (9.6), 38.6 (6.3), and 52.1 (10.5), respectively. All participants in Uganda and all but 27% in Russia and 5% in Boston were on antiretroviral therapy. In Uganda, 32% met criteria for AUD, 92% in Russia, and 43% in Boston. The mean (SD) number of AUD criteria was 1.6 (2.4) in Uganda, 5.6 (3.3) in Russia, and 2.4 (3.1) in Boston. Most participants had HIV viral suppression (Uganda 92%, Russia 57%, Boston 87%); median (IQR) CD4 count was 673 (506, 866), 351 (201, 542), and 591 (387, 881), respectively. In adjusted models, there were no associations between AUD severity and HIV viral suppression: adjusted odds ratios (AOR) (95%CI) per 1 additional AUD criterion in Uganda was 1.08 (0.87, 1.33); Russia 0.98 (0.92, 1.04); and Boston 0.95 (0.84, 1.08) or CD4 count: mean difference (95%CI) per 1 additional criterion: 5.78 (-7.47, 19.03), -3.23 (-10.91, 4.44), and -8.18 (-24.72, 8.35), respectively. In three cohorts of PWH, AUD severity was not associated with HIV viral suppression or CD4 count. PWH with AUD in the current era of antiretroviral therapy can achieve virologic control

Investigating migration and mobility in the Early Roman frontier: The case of the Batavi in the Dutch Rhine delta (c. 50/30 BC–AD 40)

The study of migration is essential for understanding the earliest phases of the Roman period in the Lower Rhine delta. This paper applies an integrated and interdisciplinary approach, combining and comparing historical, archaeological and science-based evidence and methodologies, allowing a more detailed reconstruction of immigration during this period. Our study suggests that various groups migrated to our region, probably over a longer period of time, originating from different regions and arriving in a land with a (probably limited) residual population. This marked and varied immigration should be understood in the context of Roman frontier policy and the (ethnic) recruitment of Germanic groups by the Roman military.Material Culture Studie

FHIR-DHP: A standardized clinical data harmonisation pipeline for scalable AI application deployment

Background Increasing digitalisation in the medical domain gives rise to large amounts of healthcare data which has the potential to expand clinical knowledge and transform patient care if leveraged through artificial intelligence (AI). Yet, big data and AI oftentimes cannot unlock their full potential at scale, owing to non-standardised data formats, lack of technical and semantic data interoperability, and limited cooperation between stakeholders in the healthcare system. Despite the existence of standardised data formats for the medical domain, such as Fast Healthcare Interoperability Resources (FHIR), their prevalence and usability for AI remains limited.Objective We developed a data harmonisation pipeline (DHP) for clinical data sets relying on the common FHIR data standard.Methods We validated the performance and usability of our FHIR-DHP with data from the MIMIC IV database including > 40,000 patients admitted to an intensive care unit.Results We present the FHIR-DHP workflow in respect of transformation of “raw” hospital records into a harmonised, AI-friendly data representation. The pipeline consists of five key preprocessing steps: querying of data from hospital database, FHIR mapping, syntactic validation, transfer of harmonised data into the patient-model database and export of data in an AI-friendly format for further medical applications. A detailed example of FHIR-DHP execution was presented for clinical diagnoses records.Conclusions Our approach enables scalable and needs-driven data modelling of large and heterogenous clinical data sets. The FHIR-DHP is a pivotal step towards increasing cooperation, interoperability and quality of patient care in the clinical routine and for medical research