Association between red cell transfusions and necrotizing enterocolitis

OBJECTIVE: Several case reports and retrospective studies have reported a temporal association between red blood cell (RBC) transfusions and necrotizing enterocolitis (NEC). In this article, we review the clinical evidence and biological plausibility of the association between RBC transfusions and NEC. METHODS: A literature search was performed using the databases PubMed, EMBASE, and Scopus, and the electronic archive of abstracts presented at the annual meetings of the Pediatric Academic Societies. RESULTS: Among all cases of NEC, 25 -40% patients were noted to have received an RBC transfusion within a 48 hour period prior to onset of NEC. Compared to infants who developed NEC unrelated to transfusion, neonates with transfusion-associated NEC were born at an earlier gestation, had lower birth weights, and had a delayed onset at 3-5 weeks of postnatal age. CONCLUSIONS: Based on current clinical evidence, transfusion-associated NEC appears to be a plausible clinical entity. However, there is a need for cautious interpretation of data because all the studies that have been conducted until date are retrospective, and therefore, susceptible to bias. A large, prospective, multi-center trial is needed to evaluate the association between RBC transfusion and NEC

Intra-rater reliability of leg blood flow during dynamic exercise using Doppler ultrasound

Abstract Developing an exercise model that resembles a traditional form of aerobic exercise and facilitates a complete simultaneous assessment of multiple parameters within the oxygen cascade is critically for understanding exercise intolerances in diseased populations. Measurement of muscle blood flow is a crucial component of such a model and previous studies have used invasive procedures to determine blood flow kinetics; however, this may not be appropriate in certain populations. Furthermore, current models utilizing Doppler ultrasound use isolated limb exercise and while these studies have provided useful data, the exercise model does not mimic the whole‐body physiological response to continuous dynamic exercise. Therefore, we aimed to measure common femoral artery blood flow using Doppler ultrasound during continuous dynamic stepping exercise performed at three independent workloads to assess the within day and between‐day reliability for such an exercise modality. We report a within‐session coefficient of variation of 5.8% from three combined workloads and a between‐day coefficient of variation of 12.7%. These values demonstrate acceptable measurement accuracy and support our intention of utilizing this noninvasive exercise model for an integrative assessment of the whole‐body physiological response to exercise in a range of populations

Hidden Markov Model and Cyber Deception for the Prevention of Adversarial Lateral Movement

Advanced persistent threats (APTs) have emerged as multi-stage attacks that have targeted nation-states and their associated entities, including private and corporate sectors. Cyber deception has emerged as a defense approach to secure our cyber infrastructure from APTs. Practical deployment of cyber deception relies on defenders\u27 ability to place decoy nodes along the APT path optimally. This paper presents a cyber deception approach focused on predicting the most likely sequence of attack paths and deploying decoy nodes along the predicted path. Our proposed approach combines reactive (graph analysis) and proactive (cyber deception technology) defense to thwart the adversaries\u27 lateral movement. The proposed approach is realized through two phases. The first phase predicts the most likely attack path based on Intrusion Detection System (IDS) alerts and network trace, and the second phase is determining optimal deployment of decoy nodes along the predicted path. We employ transition probabilities in a Hidden Markov Model to predict the path. In the second phase, we utilize the predicted attack path to deploy decoy nodes. However, it is likely that the attacker will not follow that predicted path to move laterally. To address this challenge, we employ a Partially Observable Monte-Carlo Planning (POMCP) framework. POMCP helps the defender assess several defense actions to block the attacker when it deviates from the predicted path. The evaluation results show that our approach can predict the most likely attack paths and thwarts the adversarial lateral movement

Control of blood pressure in the cold: Differentiation of skin and skeletal muscle vascular resistance

Abstract The primary aim of this investigation was to determine the individual contribution of the cutaneous and skeletal muscle circulations to the cold‐induced pressor response. To address this, we examined local vascular resistances in the cutaneous and skeletal muscle of the arm and leg. Thirty‐four healthy individuals underwent three different protocols, whereby cold air to clamp skin temperature (27°C) was passed over (1) the whole‐body, (2) the whole‐body, but with the forearm pre‐cooled to clamp cutaneous vascular resistance, and (3) the face. Cold exposure applied to the whole body or isolated to the face increased mean arterial pressure (all, P < 0.001) and total peripheral resistance (all, P < 0.047) compared to thermal neutral baseline. Whole‐body cooling increased femoral (P < 0.005) and brachial artery resistance (P < 0.003) compared to thermoneutral baseline. Moreover, when the forearm was pre‐cooled to remove the contribution of cutaneous resistance (P = 0.991), there was a further increase in lower arm vasoconstriction (P = 0.036) when whole‐body cooling was superimposed. Face cooling also caused a reflex increase in lower arm cutaneous (P = 0.009) and brachial resistance (P = 0.050), yet there was no change in femoral resistance (P = 0.815) despite a reflex increase in leg cutaneous resistance (P = 0.010). Cold stress causes an increase in blood pressure through a change in total peripheral resistance that is largely due to cutaneous vasoconstriction with face cooling, but there is additional vasoconstriction in the skeletal muscle vasculature with whole‐body cooling

Structure-guided engineering of immunotherapies targeting TRBC1 and TRBC2 in T cell malignancies

Peripheral T cell lymphomas are typically aggressive with a poor prognosis. Unlike other hematologic malignancies, the lack of target antigens to discriminate healthy from malignant cells limits the efficacy of immunotherapeutic approaches. The T cell receptor expresses one of two highly homologous chains [T cell receptor β-chain constant (TRBC) domains 1 and 2] in a mutually exclusive manner, making it a promising target. Here we demonstrate specificity redirection by rational design using structure-guided computational biology to generate a TRBC2-specific antibody (KFN), complementing the antibody previously described by our laboratory with unique TRBC1 specificity (Jovi-1) in targeting broader spectrum of T cell malignancies clonally expressing either of the two chains. This permits generation of paired reagents (chimeric antigen receptor-T cells) specific for TRBC1 and TRBC2, with preclinical evidence to support their efficacy in T cell malignancies

Effect of surgical experience and spine subspecialty on the reliability of the {AO} Spine Upper Cervical Injury Classification System

OBJECTIVE The objective of this paper was to determine the interobserver reliability and intraobserver reproducibility of the AO Spine Upper Cervical Injury Classification System based on surgeon experience (&lt; 5 years, 5–10 years, 10–20 years, and &gt; 20 years) and surgical subspecialty (orthopedic spine surgery, neurosurgery, and "other" surgery). METHODS A total of 11,601 assessments of upper cervical spine injuries were evaluated based on the AO Spine Upper Cervical Injury Classification System. Reliability and reproducibility scores were obtained twice, with a 3-week time interval. Descriptive statistics were utilized to examine the percentage of accurately classified injuries, and Pearson’s chi-square or Fisher’s exact test was used to screen for potentially relevant differences between study participants. Kappa coefficients (κ) determined the interobserver reliability and intraobserver reproducibility. RESULTS The intraobserver reproducibility was substantial for surgeon experience level (&lt; 5 years: 0.74 vs 5–10 years: 0.69 vs 10–20 years: 0.69 vs &gt; 20 years: 0.70) and surgical subspecialty (orthopedic spine: 0.71 vs neurosurgery: 0.69 vs other: 0.68). Furthermore, the interobserver reliability was substantial for all surgical experience groups on assessment 1 (&lt; 5 years: 0.67 vs 5–10 years: 0.62 vs 10–20 years: 0.61 vs &gt; 20 years: 0.62), and only surgeons with &gt; 20 years of experience did not have substantial reliability on assessment 2 (&lt; 5 years: 0.62 vs 5–10 years: 0.61 vs 10–20 years: 0.61 vs &gt; 20 years: 0.59). Orthopedic spine surgeons and neurosurgeons had substantial intraobserver reproducibility on both assessment 1 (0.64 vs 0.63) and assessment 2 (0.62 vs 0.63), while other surgeons had moderate reliability on assessment 1 (0.43) and fair reliability on assessment 2 (0.36). CONCLUSIONS The international reliability and reproducibility scores for the AO Spine Upper Cervical Injury Classification System demonstrated substantial intraobserver reproducibility and interobserver reliability regardless of surgical experience and spine subspecialty. These results support the global application of this classification system