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Summary: Background: The inflammatory response in patients with traumatic brain injury (TBI) offers opportunities for stratification and intervention. Previous unselected approaches to immunomodulation in patients with TBI have not improved patient outcomes. Methods: Serum and plasma samples from two prospective, multi-centre observational studies of patients with TBI were used to discover (Collaborative European NeuroTrauma Effectiveness Research [CENTER-TBI], Europe) and validate (Transforming Research and Clinical Knowledge in Traumatic Brain Injury [TRACK-TBI] Pilot, USA) individual variations in the immune response using a multiplex panel of 30 inflammatory mediators. Mediators that were associated with unfavourable outcomes (Glasgow outcome score-extended [GOS-E] ≤ 4) were used for hierarchical clustering to identify patients with similar signatures. Findings: Two clusters were identified in both the discovery and validation cohorts, termed early-inflammatory and pauci-inflammatory. The early-inflammatory phenotype had higher concentrations of interleukin-6 (IL-6), IL-15, and monocyte chemoattractant protein 1 (MCP1). Patients with the early-inflammatory phenotype were older and more likely to have an unfavourable GOS-E at 6 months. There were no differences in the baseline injury severity scores between patients in each phenotype. A combined IL-15 and MCP1 signature identified patients with the early-inflammatory phenotype in both cohorts. Inflammatory processes mediated outcomes in older patients with moderate-severe TBI. Interpretation: Our findings offer a precision medicine approach for future clinical trials of immunomodulation in patients with TBI, by using inflammatory signatures to stratify patients. Funding: CENTER-TBI study was supported by the European Union 7th Framework Programme. TRACK-TBI is supported by the National Institute of Neurological Disorders and Stroke.

Summary: Background: Traumatic brain injury is conventionally categorised as mild, moderate, or severe on the Glasgow Coma Scale (GCS). Recently developed biomarkers can provide more objective and nuanced measures of the extent of brain injury. Methods: Exposure–response relationships were investigated in 2479 patients aged ≥16 enrolled in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study. Neurofilament protein-light (NFL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and glial fibrillary acidic protein (GFAP) were assayed from serum sampled in the first 24 h; concentrations were divided into quintiles within GCS severity groups. Relationships with the Glasgow Outcome Scale-Extended were examined using modified Poisson regression including age, sex, major extracranial injury, time to sample, and log biomarker concentration as covariates. Findings: Within severity groups there were associations between biomarkers and outcomes after adjustment for covariates: GCS 13–15 and negative CT imaging (relative risks [RRs] from 1.28 to 3.72), GCS 13–15 and positive CT (1.21–2.81), GCS 9–12 (1.16–2.02), GCS 3–8 (1.09–1.94). RRs were associated with clinically important differences in expectations of prognosis. In patients with GCS 3 (RRs 1.51–1.80) percentages of unfavourable outcome were 37–51% in the lowest quintiles of biomarker levels and reached 90–94% in the highest quintiles. Similarly, for GCS 15 (RRs 1.83–3.79), the percentages were 2–4% and 19–28% in the lowest and highest biomarker quintiles, respectively. Interpretation: Conventional TBI severity classification is inadequate and underestimates heterogeneity of brain injury and associated outcomes. The adoption of circulating biomarkers can add to clinical assessment of injury severity. Funding: European Union 7th Framework program (EC grant 602150), Hannelore Kohl Stiftung, One Mind, Integra LifeSciences, Neuro-Trauma Sciences, NIHR Rosetrees Trust.

Abstract Introduction The study aimed to evaluate comparability in terms of efficacy, safety and immunogenicity of Sun’s ranibizumab biosimilar with reference ranibizumab in patients with neovascular age-related macular degeneration (nAMD). Methods This prospective, randomised, double-blind, two-group, parallel-arm, multicentre, phase 3 comparative study included patients with nAMD ≥ 50 years, randomised (in a 2:1 ratio) in a double-blind manner to receive 0.5 mg (0.05 mL) intravitreal injection of either Sun’s ranibizumab or reference ranibizumab in the study eye every 4 weeks until week 16 (total of four doses). Results Primary endpoint results demonstrated equivalence in the proportion of patients who lost fewer than 15 letters from baseline best-corrected visual acuity (BCVA) to the end of week 16 (99% of patients in Sun’s ranibizumab and 100% in reference ranibizumab; p > 0.9999), with the proportional difference (90% confidence interval) at −1% (−2.51, +0.61) lying within a pre-specified equivalence margin. Visual acuity improved by 15 or more letters in 43% of Sun’s ranibizumab group and 37% of the reference ranibizumab group (p = 0.4267). The mean increase in BCVA was 15.7 letters in Sun’s ranibizumab group and 14.6 letters in the reference ranibizumab group (p

Abstract Recorded earthquake‐induced changes in hydrogeological systems date back over 2,000 years. As a part of our ongoing hydrogeochemical monitoring effort to study such changes, we collected 406 groundwater samples twice a week between February 2021 and July 2023 from two bore wells in the Kopili fault zone of Northeast India. We analyzed stable isotope ratios (δ2H, δ18O) and dissolved element concentrations to obtain a 2.5‐year hydrogeochemical time series and responses to multiple regional earthquakes (Mw ≥ 3) within the monitored period. We find significant but transient anomalies in both the chemical and isotopic composition of groundwater at one of the observation wells (OW1) after the 2021 Assam Mw 6.4 earthquake, followed by prolonged alterations in the hydrochemistry at both wells. We do not identify any precursory changes. Using multivariate statistical techniques and analyzing compositional changes before and after the mainshock, we infer that the hydrochemical anomalies at OW1, representing an immediate response to the mainshock, can be attributed to the potential breach of a hydrological barrier. This, in turn, allowed the infiltration of new water into the OW1 aquifer, potentially sourced from the nearby Brahmaputra River. Subsequently, during the post‐anomaly period, the earthquake‐induced fracturing and the associated changes in permeability sustained a prolonged period of mixing between surface water and groundwater, resulting in newly formed hydrochemistry at both wells. Our findings highlight the dynamic nature of aquifer properties during earthquakes. Long‐term continuous evaluation of such changes may provide new insights into feedback between tectonics and fluid flow in the crust.

Abstract Background Diabetic striatopathy, also known as hyperglycemic hemichorea-hemiballismus, is a rare movement disorder associated with nonketotic hyperglycemia in patients with poorly controlled diabetes mellitus. The pathophysiology is not fully elucidated but may involve hyperviscosity, ischemia, and alterations in basal ganglia neurotransmitters. Case presentation We present a case of a 64-year-old Asian female patient with longstanding poorly controlled type 2 diabetes mellitus who developed abrupt-onset right-sided hemichorea-hemiballismus. Laboratory results showed hyperglycemia without ketoacidosis. Neuroimaging revealed left putaminal hyperdensity on computed tomography and T1 hyperintensity on magnetic resonance imaging. With insulin therapy and tetrabenazine, her movements improved but persisted at 1-month follow-up. Discussion This case illustrates the typical features of diabetic striatopathy, including acute choreiform movements contralateral to neuroimaging abnormalities in the setting of nonketotic hyperglycemia. While neuroleptics may provide symptomatic relief, prompt glycemic control is critical given the risk of recurrence despite imaging normalization. Conclusion Diabetic striatopathy should be recognized as a rare disorder that can occur with poorly controlled diabetes. Further study of its pathophysiological mechanisms is needed to better guide management. Maintaining tight glycemic control is essential to prevent recurrence of this debilitating movement disorder.

Mobile smart contracts (MSCs) are essential to facilitate quick, safe, and decentralized transactions on mobile blockchain networks. Scalable blockchain solutions facilitate the establishment of a mobile blockchain ecosystem characterized by enhanced resilience and adaptability. This encourages an increase in the number of users and, thus, spreads the adoption of blockchain technology in the mobile domain. With the inception of blockchain technology, a wide range of applications use smart contracts due to their high customizability. However, problems with scalability and resource-intensive consensus procedures prevent their general use. Therefore, this work seeks to identify and analyze these constraints by conducting a systematic survey using Kitchenham’s guidelines for available scalable blockchains and consensus methods. Out of a preliminary pool of 2,073 publications, our study, which consists of 25 selected studies, identifies 12 consensus mechanisms and 13 scalable blockchain systems. Our investigation shows that, despite the wide range of techniques, no blockchain solution provides the scalability and lightweight operating requirements to implement smart contracts on mobile devices. This realization draws attention to a significant gap in academic and industry-driven blockchain research that may have implications for creating MSCs. Our findings encourage academics to explore scalable and energy-efficient blockchain technology, targeting creating more approachable smart contracts designed with mobile devices in mind.

Summary: Background: Limited evidence existed on the comparative effectiveness of decompressive craniectomy (DC) versus craniotomy for evacuation of traumatic acute subdural hematoma (ASDH) until the recently published randomised clinical trial RESCUE-ASDH. In this study, that ran concurrently, we aimed to determine current practice patterns and compare outcomes of primary DC versus craniotomy. Methods: We conducted an analysis of centre treatment preference within the prospective, multicentre, observational Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (known as CENTER-TBI) and NeuroTraumatology Quality Registry (known as Net-QuRe) studies, which enrolled patients throughout Europe and Israel (2014–2020). We included patients with an ASDH who underwent acute neurosurgical evacuation. Patients with severe pre-existing neurological disorders were excluded. In an instrumental variable analysis, we compared outcomes between centres according to treatment preference, measured by the case-mix adjusted proportion DC per centre. The primary outcome was functional outcome rated by the 6-months Glasgow Outcome Scale Extended, estimated with ordinal regression as a common odds ratio (OR), adjusted for prespecified confounders. Variation in centre preference was quantified with the median odds ratio (MOR). CENTER-TBI is registered with ClinicalTrials.gov, number NCT02210221, and the Resource Identification Portal (Research Resource Identifier SCR_015582). Findings: Between December 19, 2014 and December 17, 2017, 4559 patients with traumatic brain injury were enrolled in CENTER-TBI of whom 336 (7%) underwent acute surgery for ASDH evacuation; 91 (27%) underwent DC and 245 (63%) craniotomy. The proportion primary DC within total acute surgery cases ranged from 6 to 67% with an interquartile range (IQR) of 12–26% among 46 centres; the odds of receiving a DC for prognostically similar patients in one centre versus another randomly selected centre were trebled (adjusted median odds ratio 2.7, p

Optical wireless communication (OWC) has emerged as a promising solution to the radio spectrum crunch. OWC technology requires more access points (APs) compared to other wireless technologies, making it crucial to have reliable OWC APs to ensure low repair rates and optimal network availability. To address this, our paper provides methods to enhance the reliability of duplex OWC AP transceivers and calculates their reliability parameters. The transceiver design consists of several independent modules, and we calculate the failure in time (FIT) for each module using MTBF calculator software and component datasheets. Our reliability analysis includes two methods: mean time between failure (MTBF) calculations using reliability block diagrams and Markov chain modeling. The former identifies modules with a high failure rate and determines the system’s cumulative downtime or repair time, while the latter accounts for the repair rates of individual modules for availability calculations. Both methods complement each other and provide insight into fault-tolerant system designs. Furthermore, we perform a life cycle cost analysis of the proposed fault-tolerant transceiver designs to facilitate appropriate design choices for different applications.

Background For certain ocular movement abnormalities, the exact neuroanatomical localization of the causative lesion is still not defined. Oculomotor apraxia, apraxia of eye opening and closing, and motor impersistence are rarely reported in acute stroke, particularly following venous stroke. Case Report A 34-year-old man presented with headache, vomiting, focal seizures with bilateral tonic-clonic movements, and altered sensorium. Magnetic resonance imaging revealed bilateral frontal and left parietal hemorrhagic infarcts, and contrast venography revealed superior sagittal sinus thrombosis. The patient received anticoagulant treatment with antiepileptics. On re-examination on day 3, the patient had a rare combination of apraxia of eyelid closure, motor impersistence, and oculomotor apraxia. By Day 10 of admission, all oculomotor abnormalities had subsided. Conclusion To the best of our knowledge, this is the first report of the combination of oculomotor apraxia and apraxia of eyelid closure with motor impersistence in a patient with cerebral venous sinus thrombosis.

Abstract Potential lack of enough wireless frequency spectrum has guided researchers towards visible light communication (VLC), emerging as a sturdy support to Wi‐Fi. Though the IEEE 802.15.7 standard has comprehensive medium access control (MAC) and physical (PHY) layer specifications, the emerging VLC technology still faces MAC challenges. Further, throughput is one of the major concerns for the VLC personal area network (VPAN) as it directly impacts the network speed. We propose a novel Markov chain model with two clear channel assessments, which proves to be a significant milestone in improving the network throughput for a star topology VPAN. This paper extends the already available analytical models for the MAC layer to efficiently plan and predict the VPAN performance. We also extensively evaluate other network metrics, like network collision probability and end‐to‐end epoch, to demonstrate the proposed model's applicability. We verify the model's analytical results with elaborate MATLAB simulations and obtain good estimation, especially for large network sizes.

ObjectiveSpine injury is highly prevalent in patients with poly-trauma, but data on the co-occurrence of spine trauma in patients with traumatic brain injury (TBI) are scarce. In this study, we used the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) database to assess the prevalence, characteristics, and outcomes of patients with TBI and a concurrent traumatic spinal injury (TSI).MethodsData from the European multi-center CENTER-TBI study were analyzed. Adult patients with TBI (≥18 years) presenting with a concomitant, isolated TSI of at least serious severity (Abbreviated Injury Scale; AIS ≥3) were included. For outcome analysis, comparison groups of TBI patients with TSI and systemic injuries (non-isolated TSI) and without TSI were created using propensity score matching. Rates of mortality, unfavorable outcomes (Glasgow Outcome Scale Extended; GOSe < 5), and full recovery (GOSe 7–8) of all patients and separately for patients with only mild TBI (mTBI) were compared between groups at 6-month follow-up.ResultsA total of 164 (4%) of the 4,254 CENTER-TBI core study patients suffered from a concomitant isolated TSI. The median age was 53 [interquartile range (IQR): 37–66] years and 71% of patients were men. mTBI was documented in 62% of cases, followed by severe TBI (26%), and spine injuries were mostly cervical (63%) or thoracic (31%). Surgical spine stabilization was performed in 19% of cases and 57% of patients were admitted to the ICU. Mortality at 6 months was 11% and only 36% of patients regained full recovery. There were no significant differences in the 6-month rates of mortality, unfavorable outcomes, or full recovery between TBI patients with and without concomitant isolated TSI. However, concomitant non-isolated TSI was associated with an unfavorable outcome and a higher mortality. In patients with mTBI, a negative association with full recovery could be observed for both concomitant isolated and non-isolated TSI.ConclusionRates of mortality, unfavorable outcomes, and full recovery in TBI patients with and without concomitant, isolated TSIs were comparable after 6 months. However, in patients with mTBI, concomitant TSI was a negative predictor for a full recovery. These findings might indicate that patients with moderate to severe TBI do not necessarily exhibit worse outcomes when having a concomitant TSI, whereas patients with mTBI might be more affected.

BackgroundPain is an unpleasant sensation that signals potential or actual bodily injury. The locations of bodily pain can be communicated and recorded by freehand drawing on 2D or 3D (manikin) surface maps. Freehand pain drawings are often part of validated pain questionnaires (eg, the Brief Pain Inventory) and use 2D templates with undemarcated body outlines. The simultaneous analysis of drawings allows the generation of pain frequency maps that are clinically useful for identifying areas of common pain in a disease. The grid-based approach (dividing a template into cells) allows easy generation of pain frequency maps, but the grid’s granularity influences data capture accuracy and end-user usability. The grid-free templates circumvent the problem related to grid creation and selection and provide an unbiased basis for drawings that most resemble paper drawings. However, the precise capture of drawn areas poses considerable challenges in producing pain frequency maps. While web-based applications and mobile-based apps for freehand digital drawings are widely available, tools for generating pain frequency maps from grid-free drawings are lacking. ObjectiveWe sought to provide an algorithm that can process any number of freehand drawings on any grid-free 2D body template to generate a pain frequency map. We envisage the use of the algorithm in clinical or research settings to facilitate fine-grain comparisons of human pain anatomy between disease diagnosis or disorders or as an outcome metric to guide monitoring or discovery of treatments. MethodsWe designed a web-based tool to capture freehand pain drawings using a grid-free 2D body template. Each drawing consisted of overlapping rectangles (Scalable Vector Graphics elements) created by scribbling in the same area of the body template. An algorithm was developed and implemented in Python to compute the overlap of rectangles and generate a pain frequency map. The utility of the algorithm was demonstrated on drawings obtained from 2 clinical data sets, one of which was a clinical drug trial (ISRCTN68734605). We also used simulated data sets of overlapping rectangles to evaluate the performance of the algorithm. ResultsThe algorithm produced nonoverlapping rectangles representing unique locations on the body template. Each rectangle carries an overlap frequency that denotes the number of participants with pain at that location. When transformed into an HTML file, the output is feasibly rendered as a pain frequency map on web browsers. The layout (vertical-horizontal) of the output rectangles can be specified based on the dimensions of the body regions. The output can also be exported to a CSV file for further analysis. ConclusionsAlthough further validation in much larger clinical data sets is required, the algorithm in its current form allows for the generation of pain frequency maps from any number of freehand drawings on any 2D body template.

Abstract Purpose To study variation in, and clinical impact of high Therapy Intensity Level (TIL) treatments for elevated intracranial pressure (ICP) in patients with traumatic brain injury (TBI) across European Intensive Care Units (ICUs). Methods We studied high TIL treatments (metabolic suppression, hypothermia (

Free-space optical (FSO) communication is crucial for the next-generation 5G+ wireless networks. The FSO links suffer from atmospheric-turbulence-induced bit errors. For the increasing link's performance, low-density parity-check (LDPC) codes, complemented by the belief-propagation (BP) algorithm, are an excellent option. The bit error rate (BER) of the LDPC code is characterized by a parameter called the threshold. The threshold is the signal-to-noise ratio (SNR), after which the BER falls arbitrarily and becomes close to zero. We derive the threshold for the LDPC codes under the BP algorithm for an uncorrelated flat FSO channel. The determination of the FSO channel threshold is a tedious task as the density of the log-likelihood ratio from the FSO channel cannot be assumed as Gaussian and is available only in a numerical form. It, thus, requires testing different values of SNR as a possible threshold systematically. Therefore, we propose the divide and conquer algorithm. The threshold depends on the degree distributions, channel state information (CSI), and the turbulence level. When CSI is known, we obtain the threshold at an SNR of 8.10 dB in high turbulence for a regular (3, 6) LDPC code. This threshold steps up to 12.48 dB when the CSI is unknown at the receiver. We evaluate the threshold values for various degree distributions (regular and irregular LDPC codes) under high, moderate, and low turbulence levels for both channel models (CSI known and unknown at the receiver). We also confirm the derived threshold values with MATLAB simulations.

We use a low-density parity-check (LDPC) code to mitigate the effects of fluctuations caused by atmospheric turbulence in an uncorrelated flat free-space optical (FSO) channel. To achieve the threshold close to the FSO channel's capacity, we require an optimum degree distribution for the LDPC codes. We analytically derive the degree distributions of irregular LDPC codes in the gamma-gamma distributed FSO channel by optimizing either SNR or rate. In the SNR-optimized channel, we derive degree distributions for achieving a specific threshold (0.5 dB and 5 dB) at the highest possible rate. In contrast, in the rate-optimized channel, we target a specific rate (0.75 and 0.8) at the lowest possible threshold. For the SNR-optimized case, the maximum achievable code rate decreases from 0.56 to 0.40 at a 5 dB threshold on moving from a weak to a strong turbulence regime. In the rate-optimized case, we obtain the required code rate of 0.8 at the threshold of 11.30 dB and 19.97 dB in weak and strong turbulence regimes, respectively. We report the gap to capacity, which gives how far the LDPC code is operating from the Shannon limit, for these cases, and verify the analytical results by the simulations in MATLAB. This work emphasizes the concept of adaptive coding over the FSO channel.

For supporting the upcoming applications, wireless mobile users require high bandwidth. To serve these requirements, a wireless network that has an optical backbone with a colossal bandwidth capacity is required. The radio-over-fiber (RoF) network is a promising solution that can provide high bandwidth. To accomplish this goal, we propose a converged medium access control (MAC) protocol for the RoF network, which uses a single-gate or multi-gate polling algorithm for time and wavelength allocation to the users. We propose an analytical delay model for single and multiple wavelength architectures, considering the user identification and data transfer delay for single-gate and multi-gate polling algorithms. We verify it with the results obtained from simulations. Finally, we present the mean delay and packet loss rate of the proposed algorithm by varying the user load and traffic burstiness and prove that the proposed algorithm gives better delay performance and a lower packet loss than the state-of-the-art algorithms.

Visible light communication (VLC) is being envisioned as an enabling technology to provide the much-needed spectral relief for the ever-increasing demand for Internet connectivity and data consumption. Since VLC uses illumination sources for lighting as well as communication, it is required to provide dimming control for proper lighting and enhanced error performance for reliable data communication. In this paper, we address both these issues holistically. We formulate and study the power spectral densities of dimming-based modulation schemes, namely variable on-off keying (VOOK) and variable pulse position modulation (VPPM), and hence, derive their bandwidth requirements and spectral efficiencies. Moreover, the capacity of VLC systems is severely limited by the inter-symbol interference (ISI) occurring as a result of the multipath propagation of light signals in VLC. We propose to ameliorate the error performance of VLC systems by using channel equalization for ISI mitigation, thereby enhancing the system capacity. We develop the analytical model of a dimmable VLC system employing channel equalization and use this model to study the effect of dimming and data rate on the error performance of VOOK and VPPM schemes. We present simulation and analytical results to show that the performance of dimming-based modulation schemes is significantly improved using channel equalization.

The oncoming Internet-of-things (IoT) applications and smart machine-to-machine (M2M) communication lead to an enormous increase in network traffic. To meet the escalating demands of these time-critical applications, we need a hybrid optical-wireless network, for which the radio-over-fiber (RoF) technology is a promising candidate. These networks need to support the stringent delay requirements of the above applications for a large number of mobile users. However, the existing user registration and identification approaches for these networks are not efficient for a high user density and cannot keep the overall mean delay within the permissible limit for such applications. In this article, we present a hybrid medium access control (MAC) protocol for the RoF network, for which we propose hybrid user identification and neighbor-aware hybrid user identification algorithms for high user density. Further, the MAC protocol uses a gated polling method for data transfer. Moreover, we propose an analytical delay model for the hybrid MAC protocol, which gives overall end-to-end mean delay considering user identification and data transfer. We verify it with the results obtained from the simulations. Finally, we evaluate the mean delay and packet loss rate of the proposed algorithms by varying the network load, user density, and fiber length and benchmark the performance of the proposed algorithm with the state-of-the-art (SoA).

The free-space optical (FSO) communication represents a promising futuristic technology due to several benefits, which has attracted significant attention recently for various applications. FSO communication is susceptible to fading due to atmospheric turbulence. FSO channel, being a slow fading channel, inherently does not allow the efficient use of error-correcting codes (ECCs). ECCs have shown to have good performance in a fast fading channel. A way to convert the slow fading channel into a fast fading channel is by using techniques like diversity. Diversity makes the bits pass through many channels simultaneously, and thus the fast fading channel effect is observed at the receiver. In this paper, we first derive the capacity and bit error rate performance of the low-density parity-check (LDPC) codes in a fast fading channel. We then study the performance of LDPC codes in receiver diversity systems. Finally, we see the impact of using LDPC coded multiple-input multiple-output (MIMO) systems in the FSO channel. We use regular (3,6) LDPC code and irregular LDPC codes of rate 0.5, where the desired degree distribution is optimized for the channel condition.

Super passive optical network (Super-PON) is a next-generation Ethernet PON (NG-EPON) candidate that is envisaged to provide high data rate and low latency. For NG-EPON, there are two types of algorithms that manages bandwidth and wavelength scheduling, namely offline and online. The latter method is more scalable and efficient than the former method. Several online algorithms exist that propose schemes to manage wavelength and bandwidth scheduling. However, these algorithms lack in efficient wavelength utilization and switching. In this work, we propose a novel online bin-packing based dynamic bandwidth and wavelength allocation (DBWA) algorithm for Super-PON, namely updated best fit bin-packing (UBF-BP). This algorithm limits the wavelength switching per cycle, and uses the modified version of best fit bin-packing (BF-BP) technique for optimal wavelength allocation. Simulation results show that the proposed DBWA algorithm has a low complexity and overcomes the inefficiencies of wavelength utilization and switching. This results in lower network delay and higher channel utilization than the state-of-the-art DBWA. Furthermore, to verify the correctness of the proposed algorithm, we propose an analytical model and validate these simulation results with the analytical results.

Optical wireless communication (OWC), the IEEE 802.15.7 standard (revised 2018) is developed in normative reference to low-rate wireless personal area networks IEEE 802.15.4 standard. One significant difference between the two standards is the highly directional transmitters in the OWC networks. This difference opens up the possibility of adding full-duplex communication to wireless networks. Our work proposes adding full-duplex functionality in the contention-free period (CFP) of the OWC media access control (MAC) layer. We justify the significance of our proposal by implementing IEEE 802.15.7 resource allocation scheme for both our proposed full-duplex optical MAC (FD-OMAC) and the IEEE 802.15.7 MAC. Our simulation results demonstrate that the proposed work improves the spectral efficiency in the CFP without compromising delays. We also discuss the minor changes required in the IEEE 802.15.7 MAC for implementing FD-OMAC. We further extend the FD-OMAC to a multiple access point network and evaluate its performance in comparison with IEEE 802.15.7 MAC.

Filgotinib is a selective JAK1 (Janus kinase) inhibitor, showed efficacy in patients suffering from moderate-to-severe rheumatoid arthritis. In this paper, we present the data on the development and validation of a sensitive, selective and high-throughput LC-MS/MS (liquid chromatography with tandem mass spectrometry) method for the quantitation of filgotinib from rat dried blood spot (DBS) cards. To the DBS disc cards, 0.2 % formic acid enriched with internal standard (IS) was added and sonicated. Thereafter the extraction of filgotinib and the IS (tofacitinib) was accomplished using ethyl acetate as an extraction solvent. The resolution of filgotinib and the IS was achieved on a Gemini C18 column with an isocratic mobile phase, which is a mixture of 0.2 % formic acid:acetonitrile (20:80, v/v) at a flow-rate of 0.9 mL/min. The total run time was 2.90 min and the retention time of filgotinib and the IS was ~1.31 and 0.89 min, respectively. Filgotinib and the IS were analyzed using positive ion scan mode and parent-daughter mass to charge ion (m/z) transition of 426.3®291.3 and m/z 313.2®149.2, respectively, for quantitation. The calibration range was 1.37-1937 ng/mL. No matrix effect and carry over were observed. All the validation parameters met the acceptance criteria. The validated method has been applied to a pharmacokinetic study in rats. A good correlation between DBS and plasma concentrations for filgotinib was observed.

Owing to its several advantages over other wireless schemes, visible light communication (VLC) shall be at the forefront of optical wireless communication technology. However, due to multipath reflections and spatial distribution of light-emitting diode (LED) transmitters, there is an inherent delay spread in the VLC channels. We perform a comprehensive quantitative study on the effect of several practical factors like LED semi-angle, wall reflectivity, number of reflections, number of LED panels, room size, and user locations on the channel delay parameters, namely RMS delay spread and coherence bandwidth of the channel. We present the detailed derivation of the multipath VLC channel model and incorporate the effect of inter-symbol interference in bit error rate (BER) performance of the multipath VLC system. We analyze the average BER of the system under different practical scenarios and determine the penalty in signal to noise ratio entailed by a change in the system parameters mentioned above. We conclude that it is sufficient to model up to three reflections in the VLC channel to emulate the effect of multipath propagation on the channel characterization and BER analysis of the system. The results and analyses presented herein provide critical insights into the effect of multipath reflections in indoor VLC links, particularly the BER performance and channel delay characteristics. We also provide some key recommendations for the design of practical VLC systems by outlining the data rates that can be served under different system configurations.

Introduction: Neurocognitive problems associated with posttraumatic stress disorder (PTSD) can interact with impairment resulting from traumatic brain injury (TBI). Research question: We aimed to identify neurocognitive problems associated with probable PTSD following TBI in a civilian sample. Material and methods: The study is part of the CENTER-TBI project (Collaborative European Neurotrauma Effectiveness Research) that aims to better characterize TBI. For this cross-sectional study, we included patients of all severities aged over 15, and a Glasgow Outcome Score Extended (GOSE) above 3. Participants were assessed at six months post-injury on the PTSD Checklist-5 (PCL-5), the Trail Making Test (TMT), the Rey Auditory Verbal Learning Test (RAVLT) and the Cambridge Neuropsychological Test Automated Battery (CANTAB). Primary analysis was a complete case analysis. Regression analyses were performed to investigate the association between the PCL-5 and cognition. Results: Of the 1134 participants included in the complete case analysis, 13.5% screened positive for PTSD. Probable PTSD was significantly associated with higher TMT-(B-A) (OR ​= ​1.35, 95% CI: 1.14–1.60, p ​

Statistical models for outcome prediction are central to traumatic brain injury research and critical to baseline risk adjustment. Glasgow coma score (GCS) and pupil reactivity are crucial covariates in all such models but may be measured at multiple time points between the time of injury and hospital and are subject to a variable degree of unreliability and/or missingness. Imputation of missing data may be undertaken using full multiple imputation or by simple substitution of measurements from other time points. However, it is unknown which strategy is best or which time points are more predictive. We evaluated the pseudo-R2 of logistic regression models (dichotomous survival) and proportional odds models (Glasgow Outcome Score-extended) using different imputation strategies on the The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study dataset. Substitution strategies were easy to implement, achieved low levels of missingness (<< 10%) and could outperform multiple imputation without the need for computationally costly calculations and pooling multiple final models. While model performance was sensitive to imputation strategy, this effect was small in absolute terms and clinical relevance. A strategy of using the emergency department discharge assessments and working back in time when these were missing generally performed well. Full multiple imputation had the advantage of preserving time-dependence in the models: the pre-hospital assessments were found to be relatively unreliable predictors of survival or outcome. The predictive performance of later assessments was model-dependent. In conclusion, simple substitution strategies for imputing baseline GCS and pupil response can perform well and may be a simple alternative to full multiple imputation in many cases.

BACKGROUND:Prognostication is an essential tool for risk adjustment and decision making in the intensive care unit (ICU). Research into prognostication in ICU has so far been limited to data from admission or the first 24 hours. Most ICU admissions last longer than this, decisions are made throughout an admission, and some admissions are explicitly intended as time-limited prognostic trials. Despite this, temporal changes in prognostic ability during ICU admission has received little attention to date. Current predictive models, in the form of prognostic clinical tools, are typically derived from linear models and do not explicitly handle incremental information from trends. Machine learning (ML) allows predictive models to be developed which use non-linear predictors and complex interactions between variables, thus allowing incorporation of trends in measured variables over time; this has made it possible to investigate prognosis throughout an admission. METHODS AND FINDINGS:This study uses ML to assess the predictability of ICU mortality as a function of time. Logistic regression against physiological data alone outperformed APACHE-II and demonstrated several important interactions including between lactate & noradrenaline dose, between lactate & MAP, and between age & MAP consistent with the current sepsis definitions. ML models consistently outperformed logistic regression with Deep Learning giving the best results. Predictive power was maximal on the second day and was further improved by incorporating trend data. Using a limited range of physiological and demographic variables, the best machine learning model on the first day showed an area under the receiver-operator characteristic curve (AUC) of 0.883 (σ = 0.008), compared to 0.846 (σ = 0.010) for a logistic regression from the same predictors and 0.836 (σ = 0.007) for a logistic regression based on the APACHE-II score. Adding information gathered on the second day of admission improved the maximum AUC to 0.895 (σ = 0.008). Beyond the second day, predictive ability declined. CONCLUSION:This has implications for decision making in intensive care and provides a justification for time-limited trials of ICU therapy; the assessment of prognosis over more than one day may be a valuable strategy as new information on the second day helps to differentiate outcomes. New ML models based on trend data beyond the first day could greatly improve upon current risk stratification tools.

MotivationBiomedical entities, their identifiers and names, are essential in the representation of biomedical facts and knowledge. In the same way, the complete set of biomedical and chemical terms, i.e. the biomedical "term space" (the "Lexeome"), forms a key resource to achieve the full integration of the scientific literature with biomedical data resources: any identified named entity can immediately be normalized to the correct database entry. This goal does not only require that we are aware of all existing terms, but would also profit from knowing all their senses and their semantic interpretation (ambiguities, nestedness).ResultThis study compiles a resource for lexical terms of biomedical interest in a standard format (called "LexEBI"), determines the overall number of terms, their reuse in different resources and the nestedness of terms. LexEBI comprises references for protein and gene entries and their term variants and chemical entities amongst other terms. In addition, disease terms have been identified from Medline and PubmedCentral and added to LexEBI. Our analysis demonstrates that the baseforms of terms from the different semantic types show only little polysemous use. Nonetheless, the term variants of protein and gene names (PGNs) frequently contain species mentions, which should have been avoided according to protein annotation guidelines. Furthermore, the protein and gene entities as well as the chemical entities, both do comprise enzymes leading to hierarchical polysemy, and a large portion of PGNs make reference to a chemical entity. Altogether, according to our analysis based on the Medline distribution, 401,869 unique PGNs in the documents contain a reference to 25,022 chemical entities, 3,125 disease terms or 1,576 species mentions.ConclusionLexEBI delivers the complete biomedical and chemical Lexeome in a standardized representation (http://www.ebi.ac.uk/Rebholz-srv/LexEBI/). The resource provides the disease terms as open source content, and fully interlinks terms across resources.

Copy number variants (CNVs) at chromosome 16p13.11 have been associated with a range of neurodevelopmental disorders including autism, ADHD, intellectual disability and schizophrenia. Significant sex differences in prevalence, course and severity have been described for a number of these conditions but the biological and environmental factors underlying such sex-specific features remain unclear. We tested the burden and the possible sex-biased effect of CNVs at 16p13.11 in a sample of 10,397 individuals with a range of neurodevelopmental conditions, clinically referred for array comparative genomic hybridisation (aCGH); cases were compared with 11,277 controls. In order to identify candidate phenotype-associated genes, we performed an interval-based analysis and investigated the presence of ohnologs at 16p13.11; finally, we searched the DECIPHER database for previously identified 16p13.11 copy number variants. In the clinical referral series, we identified 46 cases with CNVs of variable size at 16p13.11, including 28 duplications and 18 deletions. Patients were referred for various phenotypes, including developmental delay, autism, speech delay, learning difficulties, behavioural problems, epilepsy, microcephaly and physical dysmorphisms. CNVs at 16p13.11 were also present in 17 controls. Association analysis revealed an excess of CNVs in cases compared with controls (OR = 2.59; p = 0.0005), and a sex-biased effect, with a significant enrichment of CNVs only in the male subgroup of cases (OR = 5.62; p = 0.0002), but not in females (OR = 1.19, p = 0.673). The same pattern of results was also observed in the DECIPHER sample. Interval-based analysis showed a significant enrichment of case CNVs containing interval II (OR = 2.59; p = 0.0005), located in the 0.83 Mb genomic region between 15.49-16.32 Mb, and encompassing the four ohnologs NDE1, MYH11, ABCC1 and ABCC6. Our data confirm that duplications and deletions at 16p13.11 represent incompletely penetrant pathogenic mutations that predispose to a range of neurodevelopmental disorders, and suggest a sex-limited effect on the penetrance of the pathological phenotypes at the 16p13.11 locus.