bluuebunny/crossref_metadata_2025_split huggingface dataset:
A whole blood based resuscitation strategy in civilian medical services: Experience from a Norwegian hospital in the period 2017–2020
Authors: Hagen Kristin Gjerde , Strandenes Geir , Kristoffersen Einar Klæboe , Braathen Hanne , Sivertsen Joar , Bjerkvig Christopher Kalhagen , Sommerfelt‐Pettersen Nina , Aasheim Irmelin Beathe , Lunde Turid Helen Felli , Hervig Tor , Apelseth Torunn Oveland 
Published: July 2021

AbstractBackgroundCivilian and military guidelines recommend early balanced transfusion to patients with life‐threatening bleeding. Low titer group O whole blood was introduced as the primary blood product for resuscitation of massive hemorrhage at Haukeland University Hospital, Bergen, Norway, in December 2017. In this report, we describe the whole blood program and present results from the first years of routine use.Study design and methodsPatients who received whole blood from December 2017 to April 2020 were included in our quality registry for massive transfusions. Post‐transfusion blood samples were collected to analyze isohemagglutinin (anti‐A/‐B) and hemolysis markers. Administration of other blood products, transfusion reactions, and patient survival (days 1 and 30) were recorded. User experiences were surveyed for both clinical and laboratory staff.ResultsTwo hundred and five patients (64% male and 36% female) received 836 units in 226 transfusion episodes. Patients received a mean of 3.7 units (range 1–35) in each transfusion episode. The main indications for transfusion were trauma (26%), gastrointestinal (22%), cardiothoracic/vascular (18%), surgical (18%), obstetric (11%), and medical (5%) bleeding. There was no difference in survival between patients with blood type O when compared with non‐group O. Haptoglobin level was lower in the transfusion episodes for non‐O group patients, however no clinical hemolysis was reported. No patients had conclusive transfusion‐associated adverse events. Both clinical and laboratory staff preferred whole blood to component therapy for massive transfusion.DiscussionThe experience from Haukeland University Hospital indicates that whole blood is feasible, safe, and effective for in‐hospital treatment of bleeding.
Evaluation of KP‐1199: a novel acetaminophen analog for hemostatic function and antinociceptive effects
Authors: Reddoch‐Cardenas Kristin M. , Cheppudira Bopaiah P. , Garza Thomas , Hopkins Chad D. , Bunker Kevin D. , Slee Deborah H. , Cap Andrew P. , Bynum James A. , Christy Robert J. 
Published: July 2021

AbstractBackgroundAcetaminophen (APAP) is a widely self‐prescribed analgesic for mild to moderate pain, but overdose or repeat doses can lead to liver injury and death. Kalyra Pharmaceuticals has developed a novel APAP analog, KP‐1199, currently in Phase 1 clinical studies, which lacks hepatotoxicity. In this study, the authors evaluated the antinociceptive effect of KP‐1199 on thermal injury‐induced nociceptive behaviors as well as hemostatic parameters using human blood samples.MethodsFull‐thickness thermal injury was induced in anesthetized adult male Sprague–Dawley rats. On day 7 post‐injury, KP‐1199 (30 and 60 mg/kg) or APAP (60 mg/kg) was administered orally. Antinociception of KP‐1199 and APAP were assessed at multiple time points using Hargreaves' test. In separate experiments, human whole blood was collected and treated with either KP‐1199, APAP, or Vehicle (citrate buffer) at 1× (214 μg/ml) and 10× (2140 μg/ml) concentrations. The treated blood samples were assessed for: clotting function, thrombin generation, and platelet activation.ResultsAPAP did not produce antinociceptive activity. KP‐1199 treatment significantly increased the nociceptive threshold, and the antinociceptive activity persisted up to 3 h post‐treatment. In human samples, 10× APAP caused significantly prolonged clotting times and increased platelet activation, whereas KP‐1199 had caused no negative effects on either parameter tested.ConclusionThese results suggest that KP‐1199 possesses antinociceptive activity in a rat model of thermal injury. Since KP‐1199 does not induce platelet activation or inhibit coagulation, it presents an attractive alternative to APAP for analgesia, especially for battlefield or surgical scenarios where blood loss and blood clotting are of concern.
Platelet aggregation in whole blood is not impaired by a platelet‐sparing leukoreduction filter and instead depends upon the presence of leukocytes
Authors: Rice Joseph , Bill Jerome R. , Razatos Anna , Marschner Susanne 
Published: July 2021

AbstractBackgroundRecent studies characterizing in vitro hemostatic properties of whole blood (WB) leukoreduced (LR) with a platelet‐sparing filter have described subtle, if any, changes to viscoelastic clotting; however, reductions in platelet (PLT) content and impedance aggregometry (IA) responses have been noted. The effects of filtration of WB (i.e., filter‐contact effects, reduction in platelet and leukocyte count) have not been rigorously investigated as to their individual impacts on platelet IA responses.Study Design and MethodsWB units from healthy donors were collected and characterized to assess the effects of platelet‐sparing leukoreduction (LR) upon the in vitro hemostatic measures of platelet IA and thromboelastometry. Further characterization of platelet IA responses was carried out in WB samples to delineate the effects of platelet count and leukocyte presence/absence upon the response.ResultsWB filtration reduced the platelet count and IA responses but had no impact on viscoelastic clotting measures in fresh WB. Experiments revealed that IA responses have a linear correlation with platelet count in both apheresis platelets and WB and that passage of platelets through the WB‐LR filter has no impact upon the strength of this response. Further experiments in LR WB showed that addition of autologous leukocytes back to the platelets fully restored the platelet aggregation response to pre‐filtration levels.ConclusionWB filtration results in platelet count reduction and leukocyte removal; however, platelet IA is not degraded by passage through the filter. Apparent declines in platelet IA responses can be fully attributed to the reduction in platelet count and the removal of leukocytes.
A Retrospective Account of Seminal Research by H. M. Zbib
Authors: Hirth J. P. 
Published: July 2021

Abstract
Throughout his career, Zbib was innovative, originating models in seminal papers that anticipated areas of subsequent increased interest. These include strain-gradient plasticity, discrete dislocation dynamics, multiscale modeling, arrays of Somigliana ring dislocations and nanoscale plasticity. We comment here on these aspects of his work. Many of the papers in this volume represent applications of these ideas.
Impact of the Unit Cell Choice on the Efficiency of Dispersion Curve Calculations Using Generalized Bloch Mode Synthesis
Authors: Cool Vanessa , Van Belle Lucas , Claeys Claus , Deckers Elke , Desmet Wim 
Published: July 2021

Abstract
Recently, the potential of metamaterials and phononic crystals to cope with conflicting requirements for obtaining lightweight structures with desirable noise and vibration properties has been demonstrated. These, often periodic, structures are commonly studied based on their representative unit cell (UC) of which the vibro-acoustic performance is examined by means of their wave propagation, visualized by dispersion curves. Typically, the UC is discretized using a finite element technique to capture the possibly complex geometry. This leads to a high computation cost for the dispersion curve calculation which can be strongly reduced by applying modal-based model order reduction techniques such as the (generalized) Bloch mode synthesis (GBMS). In this paper, the choice of the UC is shown to have an impact on the dispersion curve calculation time. Moreover, the efficiency of GBMS strongly depends on the UC choice. The highest reduction in computation time is accomplished when the number of boundary degrees-of-freedom is limited.
Poststretch Isometric Contractions of the Hamstrings: Just a Brief Stretch to Achieve Supramaximal Isometric Force
Authors: Chapman Neil , William Whitting John , Broadbent Suzanne , Crowley-McHattan Zachary , Meir Rudi 
Published: July 2021

Hamstring strain injuries are common in sport. Supramaximal eccentric or high-intensity isometric contractions are favored in hamstring strain injury prevention. The effect of combining these contraction modes in such prevention programs as a poststretch isometric contraction is unknown. Poststretch isometric contractions incorporate an active stretch and result in greater final isometric force than isometric contractions at comparable joint angles. This study compared torque and muscle activation levels between maximal voluntary isometric contraction and maximal poststretch isometric contractions of the knee flexors. Participants (n = 9) completed baseline maximal voluntary isometric contraction at 150° knee flexion and maximal poststretch isometric contractions at 120° knee flexion actively stretching at 60°/s to 150° knee flexion for final isometric contraction. Torque of the knee flexors and surface electromyography root mean square (sEMGRMS) of biceps femoris long head were simultaneously recorded and compared between baseline and poststretch isometric at 150° knee flexion. Torque was 14% greater in the poststretch isometric condition compared with baseline maximal voluntary isometric contraction (42.45 [20.75] N·m, 14% [22.18%], P < .001) without increase in sEMGRMS of biceps femoris long head (−.03 mV, ±.06, P = .130, d = .93). Poststretch isometric contractions resulted in supramaximal levels of poststretch isometric torque without increased activation of biceps femoris long head.
Exploring pain interference with motor skill learning in humans: a protocol for a systematic review
Authors: Matthews David , Elgueta Cancino Edith , Falla Deborah , Khatibi Ali 
Published: July 2021

IntroductionMotor skill learning is intrinsic to living. Pain demands attention and may disrupt non-pain-related goals such as learning new motor skills. Although rehabilitation approaches have used motor skill learning for individuals in pain, there is uncertainty on the impact of pain on learning motor skills.Methods and analysisThe protocol of this systematic review has been designed and is reported in accordance with criteria set out by the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. Web of Science, Scopus, MEDLINE, Embase and CINAHL databases; key journals; and grey literature will be searched up until March 2021, using subject-specific searches. Two independent assessors will oversee searching, screening and extracting of data and assessment of risk of bias. Both behavioural and activity-dependent plasticity outcome measures of motor learning will be synthesised and presented. The quality of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.Ethics and disseminationNo patient data will be collected, and therefore, ethical approval was not required for this review. The results of this review will provide further understanding into the complex effects of pain and may guide clinicians in their use of motor learning strategies for the rehabilitation of individuals in pain. The results of this review will be published in a peer-reviewed journal and presented at scientific conferences.PROSPERO registration numberCRD42020213240.
#3122 Is subjective cognitive decline (SCD) a better marker of susceptibility to functional cognitive disorder (FCD) than to neurodegeneration?: The caerphilly prospective study
Authors: Ball Harriet A , Bayer Antony , Coulthard Elizabeth , Fish Mark , Gallacher John , Ben-Shlomo Yoav 
Published: July 2021

Objective/AimsDoes Subjective Cognitive Decline (SCD) indicate susceptibility to Functional Cognitive Disorder (FCD) more often than it indicates neurodegeneration? Prior research has focused on clinical populations where FCD is increasingly identified, but associations could differ at the community level. A clinical diagnosis of FCD requires cognitive symptoms, internal inconsistency, the absence of another explanatory disorder, and significant impairment; but we know little about its aetiology and prevalence. Cognitive internal inconsistency has not been systematically studied.Methods1,143 men were followed in the Caerphilly Prospective Study. Their subjective experience of cognitive change at average age 73 years was compared to their previous rate of objective cognitive change (using the Cambridge Cognition Examination). Logistic regression models examined potential predictors of SCD (measured in the preceding decade) including sociodemographic factors, vascular risk markers (ischaemic heart disease, vascular medications, smoking history), alcohol exposure, sleep problems, depression, anxiety trait, and objective cognition. We also looked for markers of cognitive internal inconsistency (delayed recall proportionately better than immediate recall, using the Rivermead Behavioural Memory Test). Finally, subjective and objective cognition at average age 73 were used to predict change in objective cognition nine years later.ResultsSCD was common (30%), and only weakly related to prior objective cognitive decline (sensitivity 36% [95% CI 30-42], specificity 72% [95% CI 68-75]). Longitudinal independent predictors of SCD were older age, poor sleep quality and higher trait anxiety: rate of decline in objective cognition did not independently predict subsequent SCD (adjusted OR 1.18 [95% CI 0.72 1.95]). Those with SCD (compared to those without) had mildly worse scores on immediate recall, but their delayed recall was in proportion to their immediate recall, i.e., there was no evidence of cognitive internal inconsistency. SCD did not predict future objective cognitive change (p=0.84). Important limitations include the male-only sample and the possibility of survivor bias.ConclusionsSCD is common, but is only weakly associated with prior objective cognitive decline, is not predicted by vascular risk markers (aside from age), and does not predict future objective cognitive decline. The high community prevalence of SCD is instead driven partly via sleep difficulties and anxiety. Our results suggest those with SCD may have a mild deficit in attentional processes but relatively intact memory for the items they do encode. Subjectively experiencing cognitive decline in the absence of an objective decline appears to be a highly prevalent example of poor meta-cognition, which could be a driver to later FCD.
#3097 Temporal and spectral dynamics of reward and risk processing in the amygdala revealed with stereo-EEG recordings in epilepsy
Authors: Manssuer Luis , Qiong Ding , Zhao Yijie , Yang Rocky , Zhang ChenCheng , Zhan Shikun , Sun Bomin , Voon Valerie 
Published: July 2021

Objectives/AimsTo examine the temporal and spectral characteristics of local field potentials recorded from the amygdala in epilepsy in the context of the anticipation and receipt of rewards and losses using an incentive learning task and a risky decision-making task.Methods16 Epilepsy patients completed two tasks. In the monetary incentive delay (MID) task, patients saw reward and loss cues which indicated whether money could be won or lost depending on whether a subsequent response was or was not quick/accurate enough, respectively. This was compared with neutral cues where responses were neither rewarded nor punished regardless of response.In the risk task, patients were presented with two face down cards with values ranging from 1 to 10. When the first card is revealed, patients have to choose whether to bet or not bet that the second card is higher. After the card is revealed, patients receive a monetary reward if it is higher and a loss if it is lower. If patients do not bet, they receive nothing.ResultsIn both tasks, patients showed larger left amygdala theta band oscillatory activity to the receipt of monetary rewards compared to no money. In contrast, there were no significant responses to monetary losses. During the decision phase of the risk task, there was increased theta activity when patients chose to bet instead of not betting and when the decision had low risk (card <= 5) compared to high risk (card above 5). There were no effects of uncertainty.ConclusionsThe combined results of these two studies embellish our understanding of the role of the amygdala in motivation and decision-making processes and lend further support for its role in reward related processes rather than its often cited fear-related functions (Baxter & Murray, 2002; Murray, 2007). Theta activation is linked to cognitive processes in frontal cortices and coupled to MTL activity (Helfrich & Knight, 2016). As left amygdala theta activation was only recruited when patients were making their bet and not just anticipating reward, the pattern of results lend support to its role in cognition-emotion interactions specific to risk and reward but not uncertainty. Indeed, the hemispheric asymmetry is highly consistent with EEG studies showing left prefrontal dominance in reward processing (Manssuer et al., 2021).
#3080 A systematic review of extra-motor symptom evaluation in clinical trials for amyotrophic lateral sclerosis
Authors: Beswick Emily , Forbes Deborah , Hassan Zachary , Wong Charis , Chandran Siddharthan , Newton Judith , Carson Alan , Abrahams Sharon , Pal Suvankar 
Published: July 2021

BackgroundAmyotrophic lateral sclerosis (ALS) is increasingly recognised as a multi-system disorder, presenting with extra-motor symptoms which arise secondary to motor degeneration or are indicative of wider pathophysiology. Extra-motor symptoms such as cognitive impairment, behavioural change, neuropsychiatric symptoms, sleep disturbances, fatigue, sialorrhea, and pain are common in, and impactful upon, people with ALS.Aim/HypothesisWe aimed to systematically review historical clinical trials in ALS to identify if extra-motor features of ALS were explored as outcome measures and if so describe the tools used. We hypothesise that assessment of extra-motor symptoms has been largely neglected in trial design and that where evaluated, it has been with assessment tools which are not designed to evaluate these symptoms in people with ALS.MethodsWe reviewed clinical trials of investigative medicinal products in ALS, since the licensing of riluzole. Trial registry databases including WHO International Trials Registry, European Clinical Trials Register, clinicaltrials.gov, and PubMed were systematically searched for Phase II, III or IV trials registered, completed or published between 01/01/1994 and 16/09/2020. No language restrictions were applied. We evaluated the use of assessment tools to investigate extra-motor symptom as outcome measures.Results237 clinical trials were included in this review for use of outcome measures. These trials evaluated cognitive impairment (16 trials, 6.8%), behavioural change (38, 16%), neuropsychiatric symptoms (75, 32%), sleep disturbances (12, 5%), fatigue (18), 8%, saliva (182, 77%) and pain (55, 23%). 29 trials (12%) did not include any assessment of extra-motor symptoms. 51 versions or combinations of assessment tools were utilised in these trials. The most commonly used primary outcome measure in ALS trials, the ALS-FRS(R), is a physical functioning assessment with one sub-domain item assessing saliva. The ALS-FRS accounted for the full number of trials assessing saliva in this review. 6 instruments used were ALS-specific (designed and validated specifically for people with ALS), 14 were symptom-specific, 4 were both, and 9 were generic (evaluated the symptom within a general measure, eg QoL).ConclusionsExtra-motor symptoms have been under-evaluated in trials for people with ALS. Where evaluated, this has been primarily using assessment tools which are not specific to ALS or the extra-motor symptom, which may affect the validity of conclusions drawn regarding the impact of candidate drugs.
#3113 Evaluating the PCL-C as a measure of trauma and PTSD symptoms in patients with functional neurological symptom disorder
Authors: Yusufi Umamah 
Published: July 2021

AimsFunctional Neurological Symptom Disorder (FNSD) is common and disabling. Historically trauma was considered an essential aetiological factor, but the precise contribution of trauma to the disorder, and resulting disability, remains controversial. The PCL-C is a self-reported screening tool for PTSD symptoms based on DSM-IV criteria. A previous study in patients with FNSD demonstrated high scores on the PCL-C, with a reduction in scores following psychotherapy. However strong correlations with other psychological co-morbidities raised the possibility that the PCL-C may be capturing non-specific distress rather than indicators of previous traumatisation. The present study aimed to investigate (i) whether underlying factors measured by the PCL-C can distinguish specific trauma-memory-related symptoms from less specific emotion-regulation-related symptoms, (ii) the extent to which individual factors correlate with other psychopathology and health-related quality of life (HRQoL) measures and (iii) whether different factors change with psychotherapy, all in patients with FNSD.MethodsAn exploratory factor analysis of PCL-C responses from 473 FNSD patients pre-and post-psychotherapy was performed to generate1-4 factor models. The final factor model was determined through confirmatory factor analysis. Relationships between PCL-C factors, measures of comorbidities (depression, somatisation and anxiety) and HRQoL were assessed using regression analysis. Pre- and post-psychotherapy scores were compared.ResultsThe best model for the PCL-C comprised of two-factors: factor 1 (intrusive symptoms) explained 55.2% of the variance, whilst factor 2 (emotional dysregulation) explained 7.8% of the variance. Both factors reduced in severity after psychotherapy, but factor 2 reduced by more and correlated more strongly with a decrease in depression and anxiety than factor 1. Changes in depression, anxiety, somatic symptoms and mental HRQoL predicted 61.9% of the change in factor 2, but only 49.2% in factor 1. Improvements in mental HRQoL were strongly associated with a decrease in factor 2, but less so in factor 1.DiscussionThe factor analysis revealed the PCL-C represents two correlated but distinguishable symptom clusters in patients with FNSD: intrusive symptoms and emotional dysregulation. Both were elevated in our patient sample. The high level of intrusive symptoms suggests many patients with FNSD experience classical post-traumatic symptoms, which may indicate that subjective traumatic experiences contribute to pathogenesis and resulting disability. These symptoms showed some reduction with psychotherapy, but the greater reduction in emotional dysregulation symptoms and associated improvements in mental HRQoL suggest that psychotherapy may be more effective in reducing the burden of comorbidities and providing better coping strategies than in addressing core symptoms of the underlying disorder.