Author contributions: CS came up with the study idea, JS, CS, and RCA contributed to the study design. All authors performed data collection. RCA wrote the analysis plan for which JS simulated data. CS and DF performed the voice analyses, based on scripts by DAP and DF. JS cleaned the data. RCA analyzed the data, created the codebook for all variables and the supplementary website. JS drafted the Stage 1 and the Stage 2 manuscript, RCA helped with the statistical analyses and advised the results part. All authors provided critical revisions and approved the final version of the manuscript for submission. Do voices carry valid information about a speaker's personality?

Apathy has been observed in various types of neuropsychiatric illness, including degenerative, traumatic, and cerebrovascular. In this article, the authors describe the neurobiology of cerebrovascular induced apathy and its treatment.

Research on links between peoples’ personality traits and their voices has primarily focused on other peoples’ personality judgments about a target person based on a target person’s vocal characteristics, particularly voice pitch. However, it remains unclear whether individual differences in voices are linked to actual individual differences in personality traits, and thus whether vocal characteristics are indeed valid cues to personality. Here, we investigate how the personality traits of the Five Factor Model of Personality, sociosexuality, and dominance are related to measured fundamental frequency (voice pitch) and formant frequencies (formant position). For this purpose, we conducted a secondary data analysis of a large sample (2,217 participants) from eleven different, independent datasets with a Bayesian approach. Results suggest substantial negative relationships between voice pitch and self-reported sociosexuality, dominance and extraversion in men and women. Thus, personality might at least partly be expressed in people’s voice pitch. Evidence for an association between formant frequencies and self-reported personality traits is not compelling but remains uncertain. We discuss potential underlying biological mechanisms of our effects and suggest a number of implications for future research.

Purpose. To evaluate the frequency and types of Hb abnormalities in CBU collected by the NCBP at the New York Blood Center. Background and Methods. Established in 1992, NCBP has collected and tested over 76,000 ethnically diverse CBU and manages an inventory of over 60,000 clinical grade CB products, including the first FDA-licensed (HEMACORD®). NCBP has released over 5,600 CBU for transplantation worldwide. To prevent transplants from donors affected with clinically significant hemoglobinopathy (HP), current Good Tissue Practices (cGTP) require Hb screening of all CBU before they are accepted to the public CB inventories. Clinically significant Hb disorders are caused by either structurally abnormal Hb variants (e.g., Hb S, Hb C, Hb E) or by decreased or absent production of α- or β-globin chains (thalassemia). Evaluation of NCBP CBU for possible HP includes: a) detailed family history for HP; b) complete blood count (CBC) and RBC indices, particularly mean corpuscular volume (MCV); c) screening using High-Performance Liquid Chromatography (HPLC) and d) confirmatory diagnostic testing using molecular methods (Hemoglobinopathy Reference Laboratory, Oakland, CA). To date, 76,312 CBU have been screened at the NCBP with the Bio-Rad Variant HPLC system using the Sickle Cell Short Program, a 3-min assay, specifically designed and FDA approved to provide a qualitative result for the presence of Hbs A, F, S, C, D and/or E in the neonate. Results.The HPLC chromatographic patterns were normal (Hb FA, where F is fetal and A is adult Hb) in 73,163 CBU (95.87%), and revealed an abnormal Hb in the remaining 3,149 CBU (4.13%), the majority of which were not clinically significant. The most frequent abnormal Hb phenotypes were, sickle cell trait (FAS): 1,755 CBU (57%), Hb E trait (FAE): 562 (18%) and Hb C trait (FAC): 506 (17%). Among the 3,149 CBU with abnormal Hb, 87 carried two genes for Hb disorders of clinical relevance, of which 54 were homozygous for sickle hemoglobin (Hb FS), 6 for Hb C (Hb FC) and 19 were double heterozygotes (Hb FSC). The HPLC results of all CBU with Hb traits and homozygous patterns were confirmed on repeat testing. In addition, all homozygous HPLC results were confirmed by molecular testing. Thalassemia and other abnormalities. Hb Barts (γ4) elutes "Fast" in the HPLC chromatogram. Its normally low concentration in CB increases when γ-chains replace non-functional or deleted α-globin chains in α-thalassemia (α-thal). Testing of all 76,312 NCBP CBU showed levels of Hb Barts from 0.5% to 34% of total Hb: 69.3% of the samples had Hb Barts level below 2.5%, 29.9% between 2.6 and 6.0% and 0.8% greater than 6.1%. Accordingly, for presumptive identification of α- or β-thalassemia, HPLC results must be interpreted together with red cell indices and family history. Of 788 CBU samples submitted for molecular (DNA) analyses as "possible thalassemia carriers", one was confirmed as Hb H disease (three α-globin genes deleted), 270 had α-thal trait (two α-globin gene deletions) and 517 had one or no α-globin gene deletion. The 270 CBU with α-thal trait had Hb Barts levels between 4.0% (above 6% in most cases) and 18.9% of total Hb. Further, 258 (95.6%) of the CBU with α-thal trait had MCV below 105 fL (range: 79.9 - 104.8 fL); only 12 cases (4.4%) had MCV >105 fL, all of which had levels of Hb Barts > 5%. The Hb H disease case had Fast Hb 34.2% (by HPLC) and MCV was 76.1 fL. β-thalassemia (β-thal): 4 CBU had β-thal major and in those, only Hb F (no Hb A) was seen in the HPLC result. Among 26 CBU found to have β-thal trait by the reference lab's DNA analysis, 16 (61.5%) were tested because of positive family history and 10 (38.5%) because of MCV <105 fL (seven CBU had both, low MCV and family history of thalassemia). Another CBU with a still-uncharacterized β-globin gene mutation had MCV <105 fL. HPLC patterns disclosing "Unknown Hbs" as "traits" in 5 CBU, were confirmed by molecular testing. Conclusions. HPLC is a simple to perform, accurate, comprehensive, inexpensive and fast screening method for HP in cord blood. All homozygous Hb detected by HPLC were confirmed by the reference lab. This is particularly relevant for sickle cell disease, as it is the most common HP in ethnic minority donors. Screening with HPLC, when used in combination with CBC and family history, is a useful tool to identify possible α- and β-thalassemia carriers in CBU. Molecular DNA testing is diagnostic in confirming and identifying globin gene deletions and mutations. Disclosures No relevant conflicts of interest to declare.

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Cryopreserved HPC, CB products are maintained in long-term storage for future clinical use. To evaluate the impact of cryopreservation and storage over time on the quality and potency of the CBU as well as fulfill the FDA requirements for licensed products, stability studies are performed annually. These in vitro studies compare CBU stored for several years to recently processed ones with respect to HPCrecovery, potency, bacteriology, identity and integrity. This analysis summarizes the 2010-2015 annual stability evaluations including45 clinical CBU randomly selected among those processed by NCBP during the period 2006-2015 and stored inBioArchivefreezers.Pre-cryopreservation results, i.e., tests performed prior to freezing after CBU processing with the AXP system, are compared to post-thaw values of the CBU bag, and those of the CBU segment. We also present the quality assessment of segments (N=1924) of CBU processed during the same period that were released for transplantation. Methods:CBU bags were thawed and underwent albumin dextran reconstitution (dilution 1:7).Total nucleated cell (TNC) counts were measured in aSysmexXE2100 analyzer. CD45+/CD34+ counts and viability were evaluated using single platform, 3-color flow cytometry with 7-AAD, and ISHAGE gating strategy.CFU assays were evaluated using the NCBP CFU strategy (Albano et al, ASH 2008).The same assays were used for segment evaluation. Recovery was expressed as the ratio of post-thaw to pre-cryopreservation values. The segment "yield" was calculated as the ratio of segment results to the pre-cryopreservation or post-thaw bag values. Results: All CBU met acceptance criteria for identity, sterility and container integrity. Post-thaw CBU bag TNC recovery averaged 100.5% (SD: 6.2%). The range was 87%-114.5%; only one sample had recovery below 90%. TNC was not measured routinely in the segments. Average post-thaw bag CD34+ viability was 93.1% (SD: 3.2%). While the lowest value was 83.5%, 41/45 samples had viability above 90%. Segment post-thaw mean CD34+ viability was 94.7% (SD: 3.8%); 42 samples had values above 90%. The difference between segment and bag averaged 1.6% (SD: 2.5%; range: -3.1% to 7.5%). This change was statistically significant but too small to impact product quality. CD34+ and CFU recoveries (mean and SD) are shown in the Table. Post-thaw recovery of viable (v) CD34+ cells from theCBUbag ranged 60-133%, while the segment yield was 48-106%. For the 30 CBU with pre-cryopreservation CFU results, mean CBU bag recovery was 71% (range: 34%-120%) and segment CFU yield was 75% (range: 23%-125%). Segment and bag CD34+ and CFU results correlated well (p<0.01). In agreement with the stability studies, CD34+ viability evaluation of 1924 CBU segments showed average of 95.7% (SD: 3.5%; only 5% of the samples had CD34+ viability below 90%). These segments were evaluated prior to CBU release for transplant; median time in the freezer was 2.3 years (range: 0.1-9.5), and they represent 4% of the total AXP-processed CBU in the NCBP inventory. The segment yield of vCD34+ cells was 79% (SD: 25%). Further, a strong correlation was seen between pre-cryopreservation and segment vCD34+ counts (r: 0.87; p<0.01). CFU values of the segment and pre-cryopreservation also showed good correlation (r: 0.72; p<0.01) and the average CFU segment yield was 71% (SD: 24%). CBU processed with manual method (period 1993-2006) are also included in annual stability studies and have met acceptance criteria (data not shown). Further, analysis of 684 segments of manually processed CBU stored for a median of 10 years (range: 6.3-21) showed mean CD34+ viability 94.2% (SD: 4.3%; 11% with viability below 90%); results that compare favorably to those of recently processed CBU. In conclusion, systematic evaluation of NCBP CBU processed in different periods demonstrates that quality/potency can be maintained with storage over many years. The stability studies for the AXP-CBU (2006-to date) and the pre-release segment evaluation show high CD34+ viability and consistently high recovery of HPC, indicating that the process is under control, and set the standard for future studies and other potency assays. The strong correlations between post-thaw bag and segment results demonstrate that the segment is a representative sample of the cryopreserved CBU and its evaluation can predict reliably the potency of the thawed product. Table. Table. Disclosures No relevant conflicts of interest to declare.

Background: CBU selection for transplant is based on HLA match and potency/quality determinations associated with the speed of hematopoietic engraftment. Total Nucleated Cell (TNC) count, viable (v) CD45+ and CD34+ cells and Colony Forming Units (CFU) have been used as surrogate markers of hematopoietic stem cells. However, besides TNC measurements, most of the assays still have poor standardization among laboratories. The NCBP has manufactured over 60,000 clinical CBU (as of 07/2018). Of those, 32,413 CBU had pre-cryopreservation samples tested prospectively (period: 03/2008-04/2018) using validated assays for TNC (Sysmex XE-2100), vCD45+ and vCD34+ cells (single platform flow cytometry using ISHAGE strategy and 7-AAD for viability) and HRDI-CFU assay (High Resolution Digital Imaging CFU strategy, Albano et al, Blood 2011;118:485). Among those, 754 CBU have been shipped to US Transplant Centers (TC) for single or double unit transplants. Prior to release for clinical use, CBU had also quality/potency tests conducted prospectively in post-thaw samples from attached segments, using the same assays. Aims and study design: 1) to evaluate the quality/potency of 754 NCBP CBU provided for transplantation (period: 03/24/2008-12/31/2017) by pre-cryopreservation characteristics, post-thaw segment evaluations and their correlations, and 2) to assess their impact on engraftment in two patient subsets after myeloablation: cohort 1, N=99 patients (pts), who received single CBU transplants, and cohort 2, N=139 pts with double unit grafts, who engrafted with the NCBP CBU. All laboratory evaluations were performed by NCBP. Clinical data were provided by CIBMTR; only pts with information on time to engraftment (ANC>500) and established donor chimerism were analyzed. Results: The 754 CBU selected by TC had quality/potency parameters showing a strong correlation between cell numbers and function pre-cryopreservation and post-thaw (Table 1; Pearson correlation). Segment post-thaw median recoveries were 73% (SD: 21.8%) for vCD45+ cells; 69% (SD: 20.7%) for vCD34+ cells and 60% (SD: 22.9%) for CFU, with a strong correlation between pre-cryopreservation and post-thaw values (Pair T Test: 0.74; 0.87 and 0.79, respectively; all P<0.001) and excellent segment post-thaw CD34+ viability (median: 95.8%; SD: 3.5%). There were no differences between CBU released as FDA-licensed products (N=208) or those under IND (N=546). Median time from CBU collection to transplant was 2.1 years (range: 0.1-9.6). Median time to engraftment was 19 days (range: 14-205) for the pts that received myeloablative regimens (N=238 total). Cohort 1 included primarily children with average age 9 years, average weight 24 kg (range 3-116), who received median pre-cryopreservation TNC 8.6x10^7/kg and vCD34+ 3.4x10^5/kg. Median time to ANC>500 was 16 days (range: 7-45). Cohort 2 had 85% adult pts with average age 33 years, average weight 69 kg (range: 11-129) and median time to ANC>500 19 days (range: 6-68). Engrafting CBU median pre-cryopreservation TNC was 2.6x10^7/kg and vCD34+ 1.4x10^5/kg. CBU pre-cryopreservation and segment quality/potency markers showed very good correlation also (Table 1). In cohort 1 all pre-cryopreservation cell doses and segment vCD34+ and CFU correlated with neutrophil engraftment (Table 2). Pts with earlier engraftment (≤16 vs >17 days) received CBU with significantly higher doses of TNC, vCD34+, vCD45+ and CFU (pre-cryopreservation and post-thaw tests). In the recipients of double CB transplants, the engrafting CBU TNC and vCD45+ cell doses did not correlate with neutrophil engraftment, but the vCD34+ and CFU did (Table 2). Similarly, pts with earlier engraftment (≤19 vs >20 days) received CBU with higher doses of vCD34+ and CFU, but not TNC or CD45+. Conclusions: Prospective testing of HPC, CB products manufactured by a single CB Bank over a 10-year period and provided for transplant show consistent, highly significant correlation among pre-cryopreservation graft characteristics and segment measurements. Pre-cryopreservation values were predictive of time to ANC>500 in myeloablated recipients; in those cases, segment evaluation did not improve the correlations. Notably, vCD34+ and CFU correlations are consistently maintained after cryopreservation and thaw ensuring a HPC, CB product with reliable performance for transplantation, cell therapies or use with expansion technologies. Disclosures No relevant conflicts of interest to declare.

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