Liberal Threshold Research Articles

Cerebellar integrity and contributions to cognition in C9orf72-mediated frontotemporal dementia

BackgroundThe GGGGCC hexanucleotide repeat expansion in the non-coding region of the chromosome 9 open reading frame 72 gene (C9orf72) is the most common genetic cause of familial frontotemporal dementia (FTD). This study aims to clarify the patterns of cerebellar atrophy in FTD patients with and without a C9orf72 repeat expansion compared with healthy controls and determine whether associations between cerebellar atrophy and cognition differ between patient groups. MethodsThirty C9orf72 repeat expansion-positive FTD patients, 30 C9orf72 repeat expansion-negative FTD patients, and 30 age-, sex-, and education-matched healthy controls underwent brain MRI and cognitive assessments. Patient groups were matched for clinical diagnosis, disease duration, general cognition, and disease severity. ResultsCompared with controls, the C9orf72 positive group showed cerebellar changes bilaterally involving the lobules V, VI, Crus I, Crus II, VIIb, VIIIa, left VIIIb, and right lobules I–IV. All these changes were localised within the regions affected in the C9orf72 negative group. No significant differences were found between patient groups. Correlation analyses with a liberal threshold found the cerebellar integrity to be associated with attention, language, and executive function in the C9orf72 positive group. In the C9orf72 negative group, these associations included attention, working memory, language, episodic memory, and executive function. ConclusionsThis study clarifies the impact of C9orf72 repeat expansion on cerebellar integrity in FTD. The findings reveal overlapping patterns of cerebellar atrophy in C9orf72 positive and negative groups. The associations with cognitive functions suggest that the type of pathology linked with cerebellar atrophy is another relevant variable to consider in future studies.

Same action, different meaning: neural substrates of action semantic meaning.

Voluntary actions are shaped by desired goals and internal intentions. Multiple factors, including the planning of subsequent actions and the expectation of sensory outcome, were shown to modulate kinetics and neural activity patterns associated with similar goal-directed actions. Notably, in many real-world tasks, actions can also vary across the semantic meaning they convey, although little is known about how semantic meaning modulates associated neurobehavioral measures. Here, we examined how behavioral and functional magnetic resonance imaging measures are modulated when subjects execute similar actions (button presses) for two different semantic meanings-to answer "yes" or "no" to a binary question. Our findings reveal that, when subjects answer using their right hand, the two semantic meanings are differentiated based on voxel patterns in the frontoparietal cortex and lateral-occipital complex bilaterally. When using their left hand, similar regions were found, albeit only with a more liberal threshold. Although subjects were faster to answer "yes" versus "no" when using their right hand, the neural differences cannot be explained by these kinetic differences. To the best of our knowledge, this is the first evidence showing that semantic meaning is embedded in the neural representation of actions, independent of alternative modulating factors such as kinetic and sensory features.

Increasing spatial coverage in rough terrain and vegetated areas using InSAR optimized pixel selection: application to Tohoku, Japan

ABSTRACT One of the major limitations of using Interferometric Synthetic Aperture Radar (InSAR) in time series analysis is the low-phase coherence associated with rough terrain and vegetated areas, which results in limited spatial coverage in such regions. Permanent scatterers technique was introduced to overcome this limitation using time-series analysis. However, identifying major scatterers within a pixel requires the single-looked pixels oversampling which can be a demanding process especially with large interferometric stacks and vast study areas. Therefore, using multilooked temporal coherent pixels was proposed to increase processing efficiency and coverage by utilizing distributed targets, but this technique may exclude pixels with reliable phase returns because of their temporal varying neighboring pixels. In this paper, we propose a technique to identify multilooked temporal stable pixels with reliable phase returns independent of their neighboring pixels. We conduct a simulation analysis to relate the spatial coherence of a pixel with its expected temporal correlation in the time series analysis module. We found that a liberal temporal correlation threshold of 0.53 in multilooked pixels stack is equivalent to a spatial coherence threshold of 0.2 when using number of looks of 9, which is considered acceptable in temporal coherent pixels, in terms of phase standard deviation. Applying these findings to study the 2011 Tohoku earthquake in the northeastern part of Japan resulted in increasing the number of usable pixels and spatial coverage index by nearly 50.4% and 36.8%, respectively, compared to the temporal coherent pixels. Furthermore, we propose an approach to integrate GPS observations with InSAR time series analysis, which resulted in deformation maps of the megathrust 2011 Tohoku earthquake with mean RMSE of 11.4 mm and a correlation of 98% in comparison to GPS observations.

Transfusion thresholds for guiding red blood cell transfusion.

Transfusion thresholds for guiding red blood cell transfusion.

Characterizing flortaucipir tau‐PET deposition patterns across the Alzheimer’s disease spectrum: A comparison between regional and whole‐brain approaches

AbstractBackgroundThe pattern of tau‐PET deposition might not always follow the classical post‐mortem Braak stages (Vogel et al, 2020). Yet, most current studies use a temporal meta‐ROI to calculate tau‐PET abnormality. We assessed inter‐individual patterns of tau binding across the spectrum of late‐onset Alzheimer’s disease (AD). We computed a score representing the spatial extent uptake of tau‐PET and compared it to a classical temporal meta‐ROI.MethodWe selected 766 ADNI participants along the AD spectrum (controls [CN], early mild cognitive impairment [eMCI], late MCI [lMCI] and AD patients) who underwent flortaucipir tau‐PET and had an available beta‐amyloid (Aβ)status (Table 1). We fitted 2‐distribution Gaussian mixture‐models to calculate thresholds of liberal and conservative tau retention (50% and 90% probability to be in the high SUVR distribution, respectively) in the classical Braak stages and all 70 FreeSurfer brain regions. Using this categorization, we defined positivity in the different Braak stages (Figure 1A‐C) and individual regions (Figure 1B‐D). We calculated a fine‐grained measure of spatial extent by summing the number of regions showing tau abnormality (Figure 1D and 2A). We also computed a temporal meta‐ROI SUVR (Figure 2B, Jack et al, 2018 regions).ResultIn Aβ‐positive participants 14% CN, 44% eMCI and 78% lMCI‐AD had elevated SUVRs in Braak stage 1 using the conservative threshold (Figure 1C, yellow). Participants who progressed to subsequent Braak stage(s), defined with conservative thresholds, were positive on all previous stages using a liberal or conservative threshold (Figure 1C yellow and green, 99% of the sample). Only the spatial extent of tau deposition was associated with worse cognition in CN individuals (Figure 3). In AD patients, both greater spatial extent of tau deposition and higher temporal meta‐ROI SUVR were associated with lower cognition, with the spatial extent index showing stronger associations (Figure 3). In AD, further widespread spatial extent and temporal binding was associated with younger age (Figure 4).ConclusionIn a typical amnestic cohort of late‐onset AD,the pattern of tau deposition follows the traditional Braak stages. Using a spatial extent index provides stronger results than a temporal‐meta ROI index in detecting associations with cognition.

Brain structural changes in subjective cognitive decline: A whole brain surface‐based analysis in the FACEHBI cohort

AbstractBackgroundSubjective cognitive decline (SCD) has been associated with increased risk of subsequent mild cognitive impairment (MCI) and dementia. Evidence from magnetic resonance imaging studies shows that neurodegenerative changes are already present years before dementia and thus, examining brain changes in SCD may contribute to identify potential biomarkers at an early stage of Alzheimer’s disease.Method198 individuals with SCD from the FACEHBI cohort were included (124 females; mean age 65.76 years). All subjects underwent magnetic resonance imaging and 18F‐Florbetaben positron emission tomography scan at baseline and were clinically follow‐up. Whole‐brain cortical surface‐based morphometry analysis were conducted using Freesurfer. Changes in cortical morphology (cortical thickness and surface area) were examined in relation to age, gender, brain amyloid beta deposition, ApoE‐e4 status (52 carrier/ 146 non carrier) and progression to MCI or dementia at the 4‐year follow‐up. Age, sex and years of education were included as covariates in all analyses.ResultAt p=0.05 corrected, higher age was associated with widespread cortical thickness reduction and reduced surface area in bilateral parahippocampal, left cuneus and middle frontal and in the right superior frontal cortex. Males had reduced cortical thickness in the right lingual and reduced surface area in the right superior temporal cortex. Higher amyloid beta deposition was related to higher surface area in the left inferior parietal cortex and no significant results were found in relation to ApoE‐e4 status. At the 4‐year follow‐up, 33 subjects had progressed to MCI and 118 remained cognitively unimpaired, but there were no significant differences in baseline cortical thickness or surface area between them. With a liberal threshold of p<0.0001 uncorrected, we found a cluster of reduced cortical thickness in the right isthmus cingulate in those who converted to MCI four years later.ConclusionBrain morphological changes in SCD are mainly characterized by cortical thickness reduction in relation to age and increased left inferior parietal surface area in relation to higher brain amyloid burden. Baseline reduced cortical thickness in the right isthmus cingulate is the only region associated with subsequent clinical progression to MCI and thus, it might be a useful predictive biomarker of cognitive decline in SCD individuals.

Non-pharmacological interventions for preventing delirium in hospitalised non-ICU patients.

Non-pharmacological interventions for preventing delirium in hospitalised non-ICU patients.

Non-pharmacological interventions for preventing delirium in hospitalised non-ICU patients.

Non-pharmacological interventions for preventing delirium in hospitalised non-ICU patients.

EBNEO Commentary: Red blood cell transfusion thresholds in extremely low birthweight infants.

Franz AR, Engel C, Bassler D, Rüdiger M, Thome UH, Maier RF, Krägeloh-Mann I, Kron M, Essers J, Bührer C, Rellensmann G, Rossi R, Bittrich HJ, Roll C, Höhn T, Ehrhardt H, Avenarius S, Körner HT, Stein A, Buxmann H, Vochem M, Poets CF; ETTNO Investigators. Effects of Liberal vs Restrictive Transfusion Thresholds on Survival and Neurocognitive Outcomes in Extremely Low-Birth-Weight Infants: The ETTNO Randomized Clinical Trial. JAMA. 2020 Aug 11;324(6):560–570. PMID: 32780138. Erin Grace. Neonatal Fellow. Department of Neonatal Medicine, Women's and Children's Hospital, North Adelaide, South Australia. SAHMRI Women and Kids, South Australian Health and Medical Institute, North Adelaide, South Australia. Robinson Research Institute and the Adelaide Medical School, the University of Adelaide, Adelaide, South Australia. Cathie Hilditch. Paediatric Registrar. SAHMRI Women and Kids, South Australian Health and Medical Institute, North Adelaide, South Australia. Robinson Research Institute and the Adelaide Medical School, the University of Adelaide, Adelaide, South Australia. Amy Keir. Consultant Neonatologist. Department of Neonatal Medicine, Women's and Children's Hospital, North Adelaide, South Australia. Healthy Mothers, Babies and Children Theme, South Australian Health and Medical Institute, North Adelaide, South Australia. Robinson Research Institute and the Adelaide Medical School, the University of Adelaide, Adelaide, South Australia. In this European multicentre randomised controlled trial, the Effects of Transfusion Thresholds on Neurocognitive Outcome of Extremely Low birth Weight Infants (ETTNO), 1013 preterm infants with a birthweight less than 1000 grams were included. The study was undertaken across 2011–2014 with longer term follow-up beyond this period.1 At 24 months’ corrected age, rates of the primary outcome of death or neurodevelopmental impairment were similar in the liberal and restrictive threshold groups (44.4% and 42.9%; odds ratio, 1.05). The rates of mortality, cognitive impairment and complications including bronchopulmonary dysplasia and necrotising enterocolitis were similar between groups. To examine the study more closely, randomisation occurred with the first 72 hours of age with the majority of infants randomised at 2.5 days of age. Twenty-five per cent of infants in each group received at least one red blood cell transfusion prior to randomisation. Deferred/delayed cord clamping (DCC) for 30–45 seconds was implemented at each study site with 308/492 (63%) in the liberal group and 319/519 (61%) in the restrictive group receiving DCC. The mean difference in mean haematocrits ranged from 1.5 to 3.4% from the week of randomisation to week 11. Whether this difference is clinically meaningful is worth considering. The authors note that the separation in these haematocrit values, and consequently the potential oxygen-carrying capacity achieved, may be too small to cause a difference in study outcomes.1 The lowest mean haematocrit in the restrictive group was in week 9 at 31.7% (SD 4.6). A comprehensive list of further study limitations is well laid out by the authors. These included potential limited generalisability due to the infants being primarily from a white German population group, the changes in clinical practices that may have occurred since 2011–2014, and the proportion of infants who received a red blood cell transfusion not justified by the study protocol. Risk of bias (ROB) in the study, assessed using the Cochrane ROB tool,2 was deemed low risk overall. The potential for post randomisation confounding exists, with 14% of infants receiving a transfusion not justified by the protocol and 7% did not receive a transfusion when dictated by the protocol. Analysis of the per-protocol population was consistent with the primary analysis findings. Other postrandomisation confounding risks were deemed low as there was minimal loss to follow up with similar numbers between groups. The results of the recently published Transfusion of Prematures (TOP) trial are consistent with this trial. Combining the results will hopefully enable a much anticipated individual patient data meta-analysis.1 Anaemia of prematurity is a term used broadly across the highly variable and complex course of prematurity in relation to red blood cell transfusion practice. It is possible that a difference approach to transfusion in the first days of age requires a transfusion trigger based on optimisation of oxygen kinetics, rather than a threshold per se.4 At this point, however, lower red cell transfusion thresholds compared to more liberal thresholds seem an appropriate clinical approach, especially for those preterm infants 48–72 hours of age or older. https://ebneo.org/transfusion-thresholds-low-birthweight-infants The authors have no conflicts of interest to declare.

Patient Blood Management

Impact Statement: Patient blood management (PBM) recommendations can help providers manage anemia and assist in transfusion-related decision-making. Introduction: Blood transfusions are often a necessary treatment for operative patients, but they are not without potential complications, including hemolytic reactions, and even death. Establishing parameters and guidelines for transfusions in patients undergoing an operation is imperative in treating them safely and effectively; patient blood management protocols provide these guidelines. Literature review: Patient blood management (PBM) is based on three pillars: treatment of underlying anemia, minimizing blood loss, and the use of transfusion thresholds. Establishing hemoglobin levels that dictate transfusion thresholds can be either restrictive (transfusing at lower thresholds) or liberal (transfusing at higher thresholds). Current literature recommends restrictive transfusion thresholds (hemoglobin less than 7 gm/dL) with consideration for individual patient status. Description of the case: A 56-year old male underwent an emergent exploratory laparotomy to locate a source of bleeding four days after having a hemicolectomy. He received one unit of packed red blood cells (PRBCs) in the intensive care unit overnight and arrived in the operating room (OR) on a phenylephrine drip. After induction, the patient required a vasopressin drip as well. The patient remained hemodynamically unstable and his hemoglobin was 9.8 g/dL, thus, the decision was made to administer one unit of PRBCs in the OR. The patient remained unstable throughout the case and a hemoglobin recheck was 9.5 g/dL, so a second unit of PRBCs was given. The transfusion threshold utilized in this case was liberal (less than 10 g/dL). Discussion and conclusions: In this case, all three pillars of PBM were taken into account. Pre-operative anemia was treated with a blood transfusion. Determining the cause and providing treatment of anemia before surgery can help decrease the need for transfusions. There was minimal intraoperative blood loss during the case, however techniques to manage this potential complication include: cell saver, hemodilution, and goal-directed fluid therapy. Finally, a liberal transfusion threshold was found appropriate as the patient was hemodynamically unstable. A lower transfusion threshold (less than 7 g/dL) is generally recommended for stable patients. Utilization of PBM can help guide transfusion decision-making and decrease the number of blood products given without increasing patient morbidity or mortality.

The Relationship Among Glucose Metabolism, Cerebral Blood Flow, and Functional Activity: a Hybrid PET/fMRI Study.

18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) estimate brain activities from different aspects, including regional glucose uptake (rGU) by 18FDG-PET, regional cerebral blood flow (rCBF) by arterial spin labeling, and dynamic changes of deoxyhemoglobin by blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI). However, the relationships between them remain incompletely understood. In the current study, twenty-four subjects (14 males, 10 females) were recruited and investigated the correlation among rGU, rCBF, and BOLD fMRI-derived metrics reflecting the neural activity, including amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC) by hybrid PET/fMRI. Correlation analyses were performed across subject and across space at both voxel level and region level, considering partial volume effects by adjusting for gray matter volume. Each pair of metrics showed significant across-space correlations. rGU against ReHo showed the highest mean correlation coefficients. rGU had higher correlations with three resting-state (RS) fMRI metrics than did ASL-rCBF. However, the across-subject correlations were not significant among functional modalities (rGU, rCBF, and RS-fMRI BOLD data) at either voxel level or region level even with a liberal threshold, except for significant across-subject correlation between RS-fMRI metrics (ALFF, ReHo, and DC). These comprehensive findings from hybrid PET/MR might provide complementary information to reveal the underlying mechanisms of the brain activity and open new perspective to interpret pathologic conditions.

Assessing the appropriateness of blood transfusion among injured patients at a Ghanaian tertiary hospital: Time for clarity on the use of a scarce resource.

Hemorrhage is an important cause of preventable injury-related death. Many low- and middle-income country (LMIC) patients do not have timely access to safe blood. We sought to determine the degree of appropriateness of blood transfusion among patients with injuries requiring surgical intervention at presentation to a tertiary hospital in Ghana. We performed a retrospective review of such patients presenting to Komfo Anokye Teaching Hospital (KATH), from January 2015 to December 2016. Patients' hemoglobin levels at presentation were determined as the first record of hemoglobin after presentation and their receipt of blood transfusion was determined by explicit documentation in the chart. We defined appropriate blood transfusion practice as patients receiving transfusion when hemoglobin was equal or below a threshold, or patients not being transfused when hemoglobin was above the threshold. We considered both restrictive (hemoglobin ≤7 g/dL) and liberal (hemoglobin ≤10 g/dL) transfusion thresholds. There were 1,408 patients who presented to KATH with injuries that met inclusion criteria. Two hundred and ninety two (292) patients were excluded because of missing hemoglobin information. Four hundred and fifty eight (458;41%) patients received blood transfusion. Transfused patients had a higher mean age (38 vs 35 years) and were less likely to be male (62% vs 71%). Transfused patients underwent more external fixation procedures (28% vs 19%), trauma amputations (5% vs 1%) and trauma laparotomies (3% vs 1%). At a restrictive transfusion threshold (hemoglobin ≤7 g/dL), 20% of patients who needed a transfusion did not receive one and 39% of patients who did not need a transfusion received one. At a liberal threshold (hemoglobin ≤10 g/dL), 33% of patients who needed a transfusion did not receive one and 30% of patients who did not need a transfusion received one. Blood transfusion practice was inappropriate in 31%-39% of all patients. Our data suggest that clearer guidelines for blood transfusion among emergency surgery patients are needed in Ghana and similar LMICs to avoid inappropriate use of blood as a scarce resource.

Topographic patterns of white matter hyperintensities are associated with multimodal neuroimaging biomarkers of Alzheimer\u2019s disease

BackgroundWhite matter hyperintensities (WMH) are frequently found in Alzheimer’s disease (AD). Commonly considered as a marker of cerebrovascular disease, regional WMH may be related to pathological hallmarks of AD, including beta-amyloid (Aβ) plaques and neurodegeneration. The aim of this study was to examine the regional distribution of WMH associated with Aβ burden, glucose hypometabolism, and gray matter volume reduction.MethodsIn a total of 155 participants (IMAP+ cohort) across the cognitive continuum from normal cognition to AD dementia, FLAIR MRI, AV45-PET, FDG-PET, and T1 MRI were acquired. WMH were automatically segmented from FLAIR images. Mean levels of neocortical Aβ deposition (AV45-PET), temporo-parietal glucose metabolism (FDG-PET), and medial-temporal gray matter volume (GMV) were extracted from processed images using established AD meta-signature templates. Associations between AD brain biomarkers and WMH, as assessed in region-of-interest and voxel-wise, were examined, adjusting for age, sex, education, and systolic blood pressure.ResultsThere were no significant associations between global Aβ burden and region-specific WMH. Voxel-wise WMH in the splenium of the corpus callosum correlated with greater Aβ deposition at a more liberal threshold. Region- and voxel-based WMH in the posterior corpus callosum, along with parietal, occipital, and frontal areas, were associated with lower temporo-parietal glucose metabolism. Similarly, lower medial-temporal GMV correlated with WMH in the posterior corpus callosum in addition to parietal, occipital, and fontal areas.ConclusionsThis study demonstrates that local white matter damage is correlated with multimodal brain biomarkers of AD. Our results highlight modality-specific topographic patterns of WMH, which converged in the posterior white matter. Overall, these cross-sectional findings corroborate associations of regional WMH with AD-typical Aß deposition and neurodegeneration.

Liberal Versus Restrictive Hemoglobin Levels as Thresholds for Blood Transfusions.

Blood transfusion is a common treatment of anemia due to chronic disease or acute blood loss. However, there continues to be uncertainty concerning the appropriate threshold for transfusion. A restrictive protocol could decrease blood administered, transmissible infections, transfusion reactions, volume overload, and utilization of a limited commodity. However, anemia may result in decreased oxygen delivery which could lead to metabolic dysfunction an increased cell death. Determining an appropriate transfusion threshold is thus an important objective. A previous Cochrane review found the use of restrictive thresholds decreased transfusions compared to liberal thresholds. No difference in secondary outcomes, including 30-day mortality, hospital length of stay, cardiac events, and myocardial infarction, was noted.

Causal Factors of Anxiety and Depression in College Students: Longitudinal Ecological Momentary Assessment and Causal Analysis Using Peter and Clark Momentary Conditional Independence.

BackgroundAcross college campuses, the prevalence of clinically relevant depression or anxiety is affecting more than 27% of the college population at some point between entry to college and graduation. Stress and self-esteem have both been hypothesized to contribute to depression and anxiety levels. Although contemporaneous relationships between these variables have been well-defined, the causal relationship between these mental health factors is not well understood, as frequent sampling can be invasive, and many of the current causal techniques are not well suited to investigate correlated variables.ObjectiveThis study aims to characterize the causal and contemporaneous networks between these critical mental health factors in a cohort of first-year college students and then determine if observed results replicate in a second, distinct cohort.MethodsEcological momentary assessments of depression, anxiety, stress, and self-esteem were obtained weekly from two cohorts of first-year college students for 40 weeks (1 academic year). We used the Peter and Clark Momentary Conditional Independence algorithm to identify the contemporaneous (t) and causal (t-1) network structures between these mental health metrics.ResultsAll reported results are significant at P<.001 unless otherwise stated. Depression was causally influenced by self-esteem (t-1 rp, cohort 1 [C1]=–0.082, cohort 2 [C2]=–0.095) and itself (t-1 rp, C1=0.388, C2=0.382) in both cohorts. Anxiety was causally influenced by stress (t-1 rp, C1=0.095, C2=0.104), self-esteem (t-1 rp, C1=–0.067, C2=–0.064, P=.002), and itself (t-1 rp, of C1=0.293, C2=0.339) in both cohorts. A causal link between anxiety and depression was observed in the first cohort (t-1 rp, C1=0.109) and only observed in the second cohort with a more liberal threshold (t-1 rp, C2=0.044, P=.03). Self-esteem was only causally influenced by itself (t-1 rp, C1=0.389, C2=0.393). Stress was only causally influenced by itself (t-1 rp, C1=0.248, C2=0.273). Anxiety had positive contemporaneous links to depression (t rp, C1=0.462, C2=0.444) and stress (t rp, C1=0.354, C2=0.358). Self-esteem had negative contemporaneous links to each of the other three mental health metrics, with the strongest negative relationship being stress (t rp, C1=–0.334, C2=–0.340), followed by depression (t rp, C1=–0.302, C2=–0.274) and anxiety (t rp, C1=–0.256, C2=–0.208). Depression had positive contemporaneous links to anxiety (previously mentioned) and stress (t rp, C1=0.250, C2=0.231).ConclusionsThis paper is an initial attempt to describe the contemporaneous and causal relationships among these four mental health metrics in college students. We replicated previous research identifying concurrent relationships between these variables and extended them by identifying causal links among these metrics. These results provide support for the vulnerability model of depression and anxiety. Understanding how causal factors impact the evolution of these mental states over time may provide key information for targeted treatment or, perhaps more importantly, preventative interventions for individuals at risk for depression and anxiety.

Functional connectomes linking child-parent relationships with psychological problems in adolescence

The child-parent relationship is a significant factor in an adolescent’s well-being and functional outcomes. Epidemiological evidence indicates that relationships with the father and mother are differentially associated with specific psychobehavioral problems that manifest differentially between boys and girls. Neuroimaging is expected to bridge the gap in understanding such a complicated mapping between the child-parent relationships and adolescents’ problems. However, possible differences in the effects of child-father and child-mother relationships on sexual dimorphism in children’s brains and psychobehavioral problems have not been examined yet. This study used a dataset of 10- to 13-year-old children (N ​= ​93) to reveal the triad of associations among child-parent relationship, brain, and psychobehavioral problems by separately estimating the respective effects of child-father and child-mother relationships on boys and girls. We first fitted general linear models to identify the effects of paternal and maternal relationships in largely different sets of children’s resting-state functional connectivity, which we term paternal and maternal functional brain connectomes (FBCs). We then performed connectome-based predictive modeling (CPM) to predict children’s externalizing and internalizing problems from these parental FBCs. The models significantly predicted a range of girls’ internalizing problems, whereas the prediction of boys’ aggression was also significant using a more liberal uncorrected threshold. A series of control analyses confirmed that CPMs using FBCs associated with peer relationship or family socioeconomic status failed to make significant predictions of psychobehavioral problems. Lastly, a causal discovery method identified causal paths from daughter-mother relationship to maternal FBC, and then to daughter’s internalizing problems. These observations indicate sex-dependent mechanisms linking child-parent relationship, brain, and psychobehavioral problems in the development of early adolescence.

Changes to hepatic tissue oxygenation, abdominal perfusion and its association with enteral feeding with liberal transfusion threshold in anaemic preterm infants: A prospective cohort study.

In anaemic preterm infants who receive packed red blood cell (PRBC) transfusions, changes to mesenteric tissue oxygenation and perfusion have been reported using a restrictive haemoglobin (Hb)-based threshold. We aimed to investigate changes to hepatic tissue oxygenation and abdominal blood flow after PRBC transfusion and its association with enteral feeding using a liberal Hb threshold (as shown inTable1). [Table: see text] MATERIAL AND METHODS: We prospectively studied a cohort of preterm infants born at < 32 weeks' gestation who received at least one PRBC transfusion and monitored them immediately before (Time 1), immediately after (Time 2) and 24hours after transfusion (Time 3). Data obtained included physiological parameters, the hepatic tissue oxygenation index and pulsed Doppler ultrasound measurements in the abdominal arterial circulation. Additionally, the effects of withholding enteral feeds were investigated. We monitored 50 PRBC transfusion episodes in 40 preterm infants, in whom the mean gestational age was 26.72 weeks (±1.6weeks) and the mean birth weight was 855.25g (±190.7g). We observed significant changes to pulsed Doppler measurements in abdominal arterial circulation (coeliac artery mean peak systolic velocity Time 2 [75.08 cm/sec] versus Time 3 [71.13 cm/sec]; mean end-diastolic velocity Time 2 [15.71 cm/sec] versus Time 3 [13.76 cm/sec]; mean resistive index Time 2 0.78 versus Time 3 0.80, right renal artery mean peak systolic velocity Time 1 58.28 cm/sec versus Time 2 50.97 cm/sec, left renal artery mean peak systolic velocity Time 1 49.20 cm/sec versus Time 2 45.40 cm/sec), but not to hepatic tissue oxygenation after PRBC transfusion (Time 1 mean 53.66 [SD, 13.34]; Time 2 mean 54.93 [SD, 9.3]; Time 3 mean 55.64 [SD, 12.86]). There were no changes to hepatic tissue oxygenation or mesenteric blood flow from withholding enteral feeds during PRBC transfusion. There were no local adverse effects from hepatic tissue oxygenation monitoring. In mildly anaemic preterm infants, when allowing a liberal Hb threshold-based trigger for PRBC transfusion, changes in abdominal arterial circulation were present, but not in hepatic tissue oxygenation. Withholding enteral feeds during PRBC transfusion had no impact on hepatic tissue oxygenation or mesenteric flows.

Preservation of Gray Matter Volume in Early Stage of Bipolar Disorder: A Case for Early Intervention: Préservation du volume de matière grise au stade précoce du trouble bipolaire: un cas pour intervention précoce.

It has been proposed that different stages of the bipolar disorder might have distinct neurobiological changes. However, the evidence for this has not been consistent, as the studies in early stages of the illness are limited by small sample sizes. The purpose of this study was to investigate the gray matter volume changes in bipolar patients who recently recovered from their first episode of mania (FEM). Using a whole-brain voxel-based analysis, we compared the regional gray matter volumes of 61 bipolar patients who have recovered from their FEM in the past 3 months with 43 age- and gender-matched healthy participants. We also performed a series of subgroup analyses to determine the effects of hospitalization during the FEM, history of depressive episodes, and exposure to lithium. No statistically significant difference was found between gray matter volumes of FEM patients and healthy participants, even at a more liberal threshold (P < 0.001, uncorrected for multiple comparisons). Voxel-based subgroup analyses did not reveal significant gray matter differences except for a trend toward decreased gray matter volume in left lateral occipital cortex (P < 0.001, uncorrected) in patients with a previous history of depression. This study represents the largest structural neuroimaging investigation of FEM published to date. Early stage of bipolar disorder was not found to be associated with significant gray matter volume changes. Our findings suggest that there might be a window of opportunity for early intervention strategies to prevent or delay neuroprogression in bipolar disorder.

Translating Surgical Transfusion Evidence into Practice: A Multicenter Prospective Observational Study

Background: Randomized controlled trials have confirmed the safety of a restrictive red-cell tranfusion threshold (8 g/dL) versus a liberal threshold in cardiac and orthopedic surgeries. We aim to examine whether these findings can be replicated with observational data and generalized to broader specialties and a lower threshold. Methods: This is a prospective observational study conducted in three region-representative hospitals in China. Inpatients aged ≥18 years undergoing surgeries from six red cell-consumptive specialties (2015–2016) were defined as the base population. Three criteria were used to derive an analytic population: no significant intraoperative bleeding (<500 mL); hemoglobin at 7–10g/dL; and stratified by specialties (CCV and nonCCV group). Propensity-score matching was used to minimize confounding effect when necessary. Findings: Of 36 607 patients, 3930 (10·7%) received transfusion. The transfusion rate significantly increased with the intraoperative bleeding and decreased with the hemoglobin (p trend <0·0001). After applying the three criteria and propensity-score matching, transfusion was unrelated with death (OR [95% CI]: CCV, 1·51 [0·25–9·23]; nonCCV, 1·41 [0·44–4·46]), composite complication (CCV, 1·36 [0·63–2·95]; nonCCV, 1·61 [0·98–2·66]), but was related with infection in nonCCV (2·15 [1·12–4·12]). Patient outcomes showed no significant differences after transfusions at hemoglobin of 7–8g/dL vs. 8–10g/dL. Interpretation: We have replicated the findings of transfusion RCTs in six specialties and a lower threshold. Tailoring both the design and analysis is crucial for using observational data to generalize RCT evidence into wide surgical transfusion practice. Funding Statement: The National Health and Family Planning Commission of China (no. 201402017). Declaration of Interests: Authors have nothing to disclose. Ethics Approval Statement: The need for written informed consent was waived by the institutional review board of Peking Union Medical College Hospital (the leading research site of MSCP; date: July 26th, 2013; no. S-574) considering that the project was a quality improvement endeavor and individual information was analyzed anonymously.

RELATIONSHIP BETWEEN CHOLINERGIC RECEPTOR BINDING AND ATTENTION IN COGNITIVE AGING USING POSITRON EMISSION TOMOGRAPHY AND THE STROOP

Introduction Cholinergic (Ach) neurotransmission has been associated with aspects of brain attention networks. Reductions in Ach are also thought to underlie cognitive symptoms in Alzheimer's Disease (AD). In a previous study using positron emission tomography (PET) imaging to measure nicotinic Ach receptor binding in vivo, our group found that Ach receptor binding was reduced in patients with AD relative to healthy controls. Reductions were observed in areas of the brain thought to mediate attention, including the anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC) and insula. The Stroop is a neuropsychological measure used in research and clinical settings to assess attention and executive function. In a different study of AD patients, we found that performance on the Stroop was associated with metabolic activity in brain networks in the right hemisphere; the Stroop COLOR-WORD condition was associated with metabolic rate in the intraparietal sulcus (IPS), ACC/mPFC, and insula. In the present study, we sought to extend these findings by examining whether Ach binding was associated with performance on the Stroop prior to the onset of dementia. Methods The study included a combined group of healthy older adults or older adults with amnestic mild cognitive impairment (MCI). All participants completed the Stroop. The Stroop included three conditions: two simpler tasks requiring participants to name colors (COLOR) and read words (WORD) and a more complex task in which participants are required to name the color of ink used for a word that names a different color from the ink color (COLOR-WORD). Cholinergic (Ach) receptor binding was quantified using PET imaging, specifically 18F-2-FA PET (2FA), a radiotracer that binds to alpha4beta2 nicotinic receptor subunits. Scanning utilized a bolus plus infusion technique and measurement of nonmetabolized 2FA from plasma to calculate distribution volume (VT/fp) in PET Ach image voxels. Ach images were pre-processed using SPM12, which included motion correction, normalization to Montreal Neurological Institute (MNI) space using a co-registered T1 MRI image, and spatial smoothing of 8?mm full width at half maximum. First, a voxel-based analysis across the entire brain was used to measure the association between voxel VT/fp and performance on the Stroop COLOR-WORD test using a liberal statistical threshold (p Results Seventy-six participants were included in the sample, comprised of 43 healthy older adults and 33 patients with amnestic MCI (age: mean=73.1 (SD=7.7), MMSE: mean=28.3 (SD=2.1), 57 males and 19 females, education: mean=15.7?years (SD=2.5)). The combined group included 19 African-Americans, 48 Caucasians, 6 Hispanics, and 3?Asian/?Pacific Islanders. Performance on the COLOR task was associated with mean VT/fp in the ACC/mPFC (r=.23 p=.04), insula (r=.28, p=.02), and IPS (r=.23 p Conclusions Across the spectrum of cognitive aging, performance on the Stroop was associated with Ach binding in key brain regions involved in attention—the IPS, ACC/mPFC, and insula. These findings suggest that Ach binding, in part, mediates attentional processing. This appears true regardless of whether the task is simple, as in the COLOR and WORD conditions, or more complex, as in the COLOR-WORD condition. Thus, changes in Ach receptor binding may be an important factor in attentional deficits resulting from cognitive aging prior to onset of AD, and Ach neurotransmission could be a potential molecular target for novel pharmaceuticals to address these symptoms. This research was funded by: This work was supported by a VA Career Development grant awarded to Brandon C. Yarns, MD, MS, and VA Merit Review grants awarded to David L. Sultzer, MD, and Rebecca J. Melrose, PhD.