Non-human primate neuroimaging is a rapidly growing area of research that promises to transform and scale translational and cross-species comparative neuroscience. Unfortunately, the technological ...and methodological advances of the past two decades have outpaced the accrual of data, which is particularly challenging given the relatively few centers that have the necessary facilities and capabilities. The PRIMatE Data Exchange (PRIME-DE) addresses this challenge by aggregating independently acquired non-human primate magnetic resonance imaging (MRI) datasets and openly sharing them via the International Neuroimaging Data-sharing Initiative (INDI). Here, we present the rationale, design, and procedures for the PRIME-DE consortium, as well as the initial release, consisting of 25 independent data collections aggregated across 22 sites (total = 217 non-human primates). We also outline the unique pitfalls and challenges that should be considered in the analysis of non-human primate MRI datasets, including providing automated quality assessment of the contributed datasets.
•Openly shared, large non-human primate neuroimaging data resource•Multiple imaging modalities contributed from investigators around the world•Quality assessments of the dataset•Discussed pitfalls and challenges in analyzing the non-human primate MRI data
The PRIMatE Data Exchange (PRIME-DE) consortium is an open science resource for the neuroimaging community aiming to facilitate efforts to map the non-human primate connectome. It aggregates and shares anatomical, functional, and diffusion MRI datasets from laboratories throughout the world.
Prior studies have demonstrated associations between beta‐adrenergic receptor (βAR) polymorphisms and left ventricular dysfunction—an important cause of allograft nonutilization for transplantation. ...We hypothesized that βAR polymorphisms predispose donor hearts to LV dysfunction after brain death. A total of 1043 organ donors managed from 2001–2006 were initially studied. The following βAR single nucleotide polymorphisms were genotyped: β1AR 1165C/G (Arg389Gly), β1AR 145A/G (Ser49Gly), β2AR 46G/A (Gly16Arg) and β2AR 79C/G (Gln27Glu). In multivariable regression analyses, the β2AR46 SNP was significantly associated with LV systolic dysfunction, with each minor allele additively decreasing the odds for LV ejection fraction <50%. The β1AR1165 and β2AR46 SNPs were associated with higher dopamine requirement during the donor management period: donors with the GG and AA genotypes had ORs of 2.64 (95% CI 1.52–4.57) and 2.70 (1.07–2.74) respectively for requiring >10 μg/kg/min of dopamine compared to those with the CC and GG genotypes. However, no significant associations were found between βAR SNPs and cardiac dysfunction in 364 donors managed from 2007–2008, perhaps due to changes in donor management, lack of power in this validation cohort, or the absence of a true association. βAR polymorphisms may be associated with cardiac dysfunction after brain death, but these relationships require further study in independent donor cohorts.
A genetics study performed in 1,400 potential organ donors reveals possible associations between beta‐adrenergic receptor polymorphisms and cardiac function after brain death. See editorial by Salomon on page 3173.
Background: Symptoms of major depressive disorder (MDD) have been linked to regional brain function through imaging studies of symptom provocation in normal control subjects and baseline studies of ...subjects with MDD. We examined associations between change in depressive symptom factors and change in regional brain metabolism from before to after treatment of MDD.
Methods: Thirty-nine outpatients with MDD underwent
18F-fluorodeoxyglucose positron emission tomography scanning before and after treatment with either paroxetine or interpersonal psychotherapy. Associations were determined between changes in regional brain metabolism and changes in four Hamilton Depression Rating Scale factors (anxiety/somatization ANX, psychomotor retardation PR, cognitive disturbance COGN, and sleep disturbance) and two corresponding Profile of Mood States subscales (tension TENS and fatigue FATIG).
Results: Improvement in ANX, PR, TENS, and FATIG factors was associated with decreasing ventral frontal lobe metabolism. Improvement in ANX and TENS was also associated with decreasing ventral anterior cingulate gyrus (AC) and anterior insula activity, whereas improvement in PR was associated with increasing dorsal AC activity. COGN improvement was associated with increasing dorsolateral prefrontal cortex metabolism.
Conclusions: Brain regions that show significant relationships with symptom provocation in normal control subjects have similar relationships with MDD symptoms as they improve with treatment.
The role of antibody‐mediated rejection (AMR) in pancreas transplantation is poorly understood. Here, we report on a patient who developed AMR of his pancreas allograft after receiving a simultaneous ...pancreas‐kidney transplant. Pre‐operative enhanced cytotoxicity and flow cytometry T‐cell crossmatches were negative; B‐cell crossmatches were not performed as per institutional protocol. The patient's post‐operative course was significant for elevated serum amylase levels and development of hyperglycemia approximately 1 month after transplantation. A pancreatic biopsy at this time showed no cellular infiltrate but strong immunofluorescent staining for C4d in the interacinar capillaries. Analysis of the patient's serum identified donor‐specific HLA‐DR alloantibodies. He received intravenous immunoglobulin (IVIg), rituximab and plasmapheresis, and his pancreatic function normalized. We conclude that clinically significant AMR can develop in a pancreas allograft and recommend that pancreatic biopsies be assessed for C4d deposition if the patient has risk factors for AMR and/or the pathologic evidence for cell‐mediated rejection is underwhelming.
HLA-DP antigens are beta-alpha heterodimers encoded by polymorphic HLA-DPB1 and -DPA1 alleles, respectively, in strong linkage disequilibrium (LD) with each other. Non-permissive unrelated donor ...(UD)-recipient HLA-DPB1 mismatches across three different T-cell epitope (TCE) groups are associated with increased mortality after hematopoietic SCT (HCT), but the role of HLA-DPA1 is unclear. We studied 1281 onco-hematologic patients after 10/10 HLA-matched UD-HCT facilitated by the National Marrow Donor Program. Non-permissive mismatches defined solely by HLA-DPB1 TCE groups were associated with significantly higher risks of TRM compared to permissive mismatches (hazard ratio (HR) 1.30, confidence interval (CI) 1.06-1.53; P=0.009) or allele matches. Moreover, non-permissive HLA-DPB1 TCE group mismatches in the graft versus host (GvH) direction significantly decreased the risk of relapse compared to permissive mismatches (HR 0.55, CI 0.37-0.80; P=0.002) or allele matches. Splitting each group into HLA-DPA1*02:01 positive or negative, in frequent LD with HLA-DPB1 alleles from two of the three TCE groups, or into HLA-DPA1 matched or mismatched, did not significantly alter the observed risk associations. Our findings suggest that the effects of clinically non-permissive HLA-DPB1 TCE group mismatches are independent of HLA-DPA1, and that selection of donors with non-permissive DPB1 TCE mismatches in GvH direction might provide some protection from disease recurrence.
Background: The frequent comorbidity of major depressive disorder (MDD) and obsessive-compulsive disorder (OCD) suggests a fundamental relationship between them. We sought to determine whether MDD ...and OCD have unique cerebral metabolic patterns that remain the same when they coexist as when they occur independently.
Methods:
18F-fluorodeoxyglucose positron emission tomography (PET) brain scans were obtained on 27 subjects with OCD alone, 27 with MDD alone, 17 with concurrent OCD+MDD, and 17 normal control subjects, all in the untreated state. Regional cerebral glucose metabolism was compared between groups.
Results: Left hippocampal metabolism was significantly lower in subjects with MDD alone and in subjects with concurrent OCD+MDD than in control subjects or subjects with OCD alone. Hippocampal metabolism was negatively correlated with depression severity across all subjects. Thalamic metabolism was significantly elevated in OCD alone and in MDD alone. Subjects with concurrent OCD+MDD had significantly lower metabolism in thalamus, caudate, and hippocampus than subjects with OCD alone.
Conclusions: Left hippocampal dysfunction was associated with major depressive episodes, regardless of primary diagnosis. Other cerebral metabolic abnormalities found in OCD and MDD occurring separately were not seen when the disorders coexisted. Depressive episodes occurring in OCD patients may be mediated by different basal ganglia-thalamic abnormalities than in primary MDD patients.
Widespread thrombi are found among donor lungs rejected for transplantation. The 4G/5G polymorphism in the plasminogen activator inhibitor (PAI‐1) gene impacts transcription and the 4G allele is ...associated with increased PAI‐1 levels. We hypothesized that the 4G/4G genotype would be associated with decreased lung graft utilization, potentially because of worse oxygenation in the donor. We genotyped donors managed by the California Transplant Donor Network from 2001 to 2008 for the 4G/5G polymorphism in the PAI‐1 gene. Non‐Hispanic donors from 2001 to 2005 defined the discovery cohort (n = 519), whereas donors from 2006 to 2008 defined the validation cohort (n = 369). We found, that the odds of successful lung utilization among Non‐Hispanic white donors were lower among donors with the 4G/4G genotype compared to those without this genotype in both the discovery (OR = 0.55, 95% CI = 0.3–0.9, p = 0.02) and validation (OR = 0.5, 95% CI = 0.3–0.9, p = 0.03) cohorts. This relationship was independent of age, gender, cause of death, drug use and history of smoking. Donors with the 4G/4G genotype also had a lower PaO2/FiO2 ratio (p = 0.03) and fewer donors with the 4G/4G genotype achieved the threshold PaO2/FiO2 ratio ≥ 300 (p = 0.05). These findings suggest a role for impaired fibrinolysis resulting in worse gas exchange and decreased donor utilization.
The authors demonstrate decreased lung allograft utilization among donors carrying the 4G/4G genotype of the 4G/5G promoter region polymorphism of the PAI‐1 (serpine‐1) gene.
In subjects with obsessive-compulsive disorder (OCD), lower pre-treatment metabolism in the right orbitofrontal cortex (OFC) and anterior cingulate gyrus (AC) has been associated with a better ...response to clomipramine. We sought to determine pre-treatment metabolic predictors of response to behavioral therapy (BT) vs. pharmacotherapy in subjects with OCD. To do this,
18Ffluorodeoxyglucose positron emission tomography scans of the brain were obtained in subjects with OCD before treatment with either BT or fluoxetine. A Step-Wise Variable Selection was applied to normalized pre-treatment glucose metabolic rates in the OFC, AC, and caudate by treatment response (change in Yale–Brown Obsessive-Compulsive Scale) in the larger BT group. Left OFC metabolism (normalized to the ipsilateral hemisphere) alone was selected as predicting treatment response in the BT-treated group (
F=6.07, d.f.=1,17,
P=0.025). Correlations between normalized left OFC metabolism and treatment response revealed that higher normalized metabolism in this region was associated with greater improvement in the BT-treated group (τ=0.35,
P=0.04), but worse outcome (τ=−0.57,
P=0.03) in the fluoxetine-treated group. These results suggest that subjects with differing patterns of metabolism preferentially respond to BT vs. medication.
We construct the first comprehensive radioactive background model for a dark matter search with charge-coupled devices (CCDs). We leverage the well-characterized depth and energy resolution of the ...DAMIC at SNOLAB detector and a detailed geant4-based particle-transport simulation to model both bulk and surface backgrounds from natural radioactivity down to 50 eVee . We fit to the energy and depth distributions of the observed ionization events to differentiate and constrain possible background sources, for example, bulk H 3 from silicon cosmogenic activation and surface Pb210 from radon plate-out. We observe the bulk background rate of the DAMIC at SNOLAB CCDs to be as low as 3.1±0.6 countskg-1day-1 keVee-1 , making it the most sensitive silicon dark matter detector. Finally, we discuss the properties of a statistically significant excess of events over the background model with energies below 200 eVee .
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