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by Macmillan Dictionary
Written by Macmillan Dictionary
1. a group of states or countries that join together
2. a group of states or countries under the control of one government
3. the Northern States of the US during the American Civil War
View the full definition in the Macmillan Dictionary.
Origin and usage
The noun union comes from words in Latin and French meaning 'unity' or 'oneness'. It was first used in English in the 15th century. The meaning of a group of people with a common aim or interest dates from the 17th century, while that referring to an organized group of workers or an organization that represents them, often used instead of the full form trade union, was first recorded in the early 1800s.
Europe Day, which is celebrated on 9th May, commemorates the 1950 Shuman Declaration which proposed the setting up of European Coal and Steel Community, the forerunner of the European Union. The EU is one of several types of state union: its meanings include a group of states controlled by one government, such as the former Soviet Union; the Northern States of the US during the Civil War; and the United States as a whole. The Union of Crowns, which took place in 1603, occurred when James VI of Scotland succeeded to the English throne following the death of Elizabeth I, bringing England, Ireland and Scotland under a single monarchy. The Union Jack or Union flag, which combined the flags of England and Scotland, was created a few years later in 1606.
"Join the union, girls, and together say Equal Pay for Equal Work."
(Susan B Anthony)
"Form and function should be one, joined in a spiritual union."
(Frank Lloyd Wright)
bloc, commonwealth, superstate
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search filter All ContentAll JournalsBlood Advances
About Blood Advances
TRANSPLANTATION| December 6, 2021
Impact of cryopreservation and transit times of allogeneic grafts on hematopoietic and immune reconstitution
Katie Maurer,
Katie Maurer
1Department of Medical Oncology and
Haesook T. Kim,
Haesook T. Kim
2Department of Data Science, Dana-Farber Cancer Institute, Harvard School of Public Health, Boston, MA; and
Thomas M. Kuczmarski,
Thomas M. Kuczmarski
3Department of Medicine, Brigham and Women's Hospital, Boston, MA
Heather M. Garrity,
Heather M. Garrity
Augustine Weber,
Augustine Weber
Carol G. Reynolds,
Carol G. Reynolds
Deborah Liney,
Deborah Liney
Corey Cutler,
Corey Cutler
Joseph H. Antin,
Joseph H. Antin
John Koreth,
John Koreth
Jerome Ritz,
Jerome Ritz
Roman M. Shapiro,
Roman M. Shapiro
Rizwan Romee,
Rizwan Romee
Catherine J. Wu,
Catherine J. Wu
Robert J. Soiffer,
Robert J. Soiffer
Sarah Nikiforow,
Sarah Nikiforow
Vincent T. Ho,
Vincent T. Ho
Mahasweta Gooptu
Blood Adv (2021) 5 (23): 5140–5149.
https://doi.org/10.1182/bloodadvances.2021005139
Katie Maurer, Haesook T. Kim, Thomas M. Kuczmarski, Heather M. Garrity, Augustine Weber, Carol G. Reynolds, Deborah Liney, Corey Cutler, Joseph H. Antin, John Koreth, Jerome Ritz, Roman M. Shapiro, Rizwan Romee, Catherine J. Wu, Robert J. Soiffer, Sarah Nikiforow, Vincent T. Ho, Mahasweta Gooptu; Impact of cryopreservation and transit times of allogeneic grafts on hematopoietic and immune reconstitution. Blood Adv 2021; 5 (23): 5140–5149. doi: https://doi.org/10.1182/bloodadvances.2021005139
Recipients of cryopreserved PBSCs had lower T-cell chimerism, white blood cell count and T-cell reconstitution at days +30 and +100.
Greater age of product at infusion is linked with increased graft failure independent of cryopreservation.
Clinical Trials and Observations, Hematopoiesis and Stem Cells, Transplantation
Visual Abstract
We sought to evaluate the impact of cryopreservation of unrelated donor (URD) peripheral blood stem cell (PBSC) grafts on engraftment, chimerism, and immune reconstitution in the context of the COVID-19 pandemic. We reviewed stem cell product characteristics and clinical outcomes in 101 patients receiving cryopreserved PBSCs from URDs between January 1, 2019 and 31 December, 2020, compared with 203 patients receiving fresh URD PBSCs. We observed no differences in 6-month overall survival, progression-free survival, or nonrelapse mortality. Patients receiving cryopreserved PBSCs had delayed platelet engraftment and impaired reconstitution of white blood cells and T-cell subsets at day 30. Thirty-four percent of patients receiving cryopreserved grafts had CD3 chimerism <50% at day 30 after transplantation, compared with 14% of patients receiving fresh PBSCs (P = .0002). At day 100, this difference persisted (CD3+ chimerism <50%: 17% of cryopreserved cohort vs 6% of fresh cohort; P = .016). Greater product age at infusion was associated with increased graft failure, independent of cryopreservation. Receipt of grafts >48 hours old at time of cryopreservation or infusion significantly increased the risk of graft failure (subdistribution hazard ratio = 4.57; 95% confidence interval, 1.71-12.3; P = .0025). Our data indicate that cryopreservation is associated with similar overall short-term clinical outcomes compared with fresh PBSC. However, patients must be monitored closely for increased risk of other potentially adverse outcomes, including graft failure and poor immune recovery, particularly for grafts with older overall age at infusion. Longer-term follow-up is needed to determine impact on relapse and survival.
Prior to the COVID-19 pandemic, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was typically performed using fresh stem cell grafts shipped directly from site of collection to site of infusion. With the emergence of COVID-19, practices shifted to products being shipped to central national hubs and cryopreserved, either at the site of collection or at infusion.
Previously published data on allogeneic stem cell cryopreservation suggested a modest effect of cryopreservation on stem cell viability and yield upon thaw.1 Some studies have found an association of cryopreservation with impaired CD34+ cell recovery and subsequent impairment in engraftment,2-5 whereas others did not.6,7 A 2020 study suggested that cryopreservation may have a more detrimental effect on CD34+ cell recovery than initially thought.8 The Center for International Blood and Marrow Transplant Research recently published a retrospective analysis of patients undergoing allo-HSCT with cryopreserved vs fresh grafts associating cryopreservation with delayed neutrophil and platelet engraftment, increased risk of grade II to IV acute graft-versus-host disease (aGVHD), and increased risk of nonrelapse mortality (NRM), and relapse, with decreased overall survival (OS) and progression-free survival (PFS).9 However, a similar analysis in patients who received posttransplant cyclophosphamide (PTCy) for graft-versus-host prophylaxis found no deleterious effects of cryopreservation.10 Another Center for International Blood and Marrow Transplant Research report in patients with aplastic anemia found that cryopreservation of bone marrow grafts is associated with increased risk of engraftment failure and reduced OS in severe aplastic anemia patients.11 Given these conflicting data, additional studies are needed to assess the potential risks and benefits associated with cryopreservation of stem cell grafts.
We and others have described experiences with safe continuation of allo-HSCT practices throughout the COVID-19 pandemic and shared best practices.12-16 We previously demonstrated an association between cryopreservation and lower CD3 chimerism at 30- and 100-days after allo-HSCT at our institution.12 This observation was made in a small patient cohort and requires further investigation.
In the present study, we assessed the impact of changes in stem cell processing due to the pandemic, including age of product prior to cryopreservation (a summation of transit time, holding time, and processing time), and cryopreservation of unrelated donor (URD) peripheral blood stem cells (PBSCs) on early clinical outcomes, including hematopoietic engraftment, OS, progression-free survival (PFS), relapse, NRM, aGVHD incidence, and chimerism at 30 and 100 days after transplantation. We also report the impact of cryopreservation on immune reconstitution. Outcomes were compared with those of patients receiving fresh stem cell products unrelated to PBSCs at our center during a contemporaneous period.
This study was approved by the Institutional Review Board of the Dana-Farber/Harvard Cancer Center (DFCI/HCC) and was conducted in accordance with the Declaration of Helsinki. We analyzed all adult patients who underwent first allo-HSCT with URD PBSC grafts between 1 January, 2019 and 31 December, 2020, including 101 patients who received a cryopreserved PBSC during this time period. The control cohort consisted of 203 patients receiving fresh PBSCs from an URD in this same period. Of the current study consisting of 304 patients, one-third (n = 104) were included in our initial report of transplantation during the early phase of the pandemic.12 During the study period at our center, no related donor products were cryopreserved. Most transplants utilizing fresh products occurred during 2019, whereas most transplants with cryopreserved product occurred during 2020. We therefore focused our analysis on short-term outcomes. The COVID-19 pandemic was the reason for cryopreservation for 93 of the grafts. The remaining 8 cryopreserved grafts were due to unplanned delays in transplant.
Stem cell processing
Stem cell products were processed according to standardized protocols in use by the DFCI Cell Manipulation Core Facility. Upon receipt, products were assessed for correct labeling and identifiers, weighed, and underwent quality control testing (including ABO testing, total nucleated cell count [TNC], and TNC viability [trypan blue]) and sampling for product sterility. Cells were inspected for quality and transferred to bags with appropriate ports for infusion. The final stem cell product was then counted (TNC and CD34), assessed for TNC viability (trypan blue and 7-Aminoactinomycin D (7AAD)) and CD34 viability (7AAD), sampled again for sterility, relabeled, and delivered to the infusion or cryopreserved. Processing of fresh unmanipulated stem cell products required ∼1 hour. In the case of a major or minor ABO mismatch with >30 mL red blood cells (RBCs), products underwent plasma or RBC reduction by centrifugation, respectively. Plasma or RBC reduction added ∼90 minutes and 2 hours, respectively, to processing times. We defined overall age of product as total time in hours between end of collection at the donation site to end of processing at our center. We further broke down age of product into 3 component parts: "transit time" (time in hours between end of collection at the donation site to receipt at our center), "holding time" (time in hours between receipt and beginning of processing), and "processing time" (time in hours between initial processing sample and final processing sample). Prepandemic, stem cell products were typically shipped directly from collection site to infusion site and processed immediately upon receipt. During the pandemic, transit practices shifted to a hub-and-spoke model, and our institutional practice shifted to holding overnight any products destined for cryopreservation if they were received after normal laboratory hours for freezing the following morning. Typically, no more than 30 minutes elapsed between final sampling and product infusion or cryopreservation. No maximum CD34+ dose limit was enforced at our center.
Stem cell cryopreservation and thawing
All products destined for cryopreservation were resuspended at a total volume of 100 mL in isotonic Plasma-lyte A solution (Baxter). After final QC testing for cell counts and viability, cells were resuspended in 10% dimethyl sulfoxide cryoprotectant media (10% CryoPure [OriGEN], 5% human serum albumin [Baxter, Grifols, or equivalent] in Plasma-lyte A) at which point final sterility was assessed. Cells were then aliquoted into the desired number of bags (OriGEN CS500 CryoStore Freezing Bags) based on TNC values with maximum final cell concentration of 5 × 108 cells per mL. Preparation for cryopreservation added ∼30 minutes to processing times. Bags in metal cassettes were then frozen in a controlled rate freezer (Kryo 560-16, Planer) over ∼75 minutes and placed in liquid nitrogen storage, vapor phase at less than −150°C. Controlled rate freezer freezing curve was programmed for 1°C drop per minute to −20°C and then 2°C drop per minute to −80°C with holds of 5 and 10 minutes at −20°C and −80°C, respectively. Resulting heat/enthalpy of fusion was approximately −35°C. Products were stored for days to weeks, as required for each individual transplant. On the day of planned stem cell infusion, cells were thawed in a 37°C water bath over 3 to 5 minutes, transferred to a new bag for reinfusion, and a QC sample was assessed for TNC viability (trypan blue) and sterility prior to release of the stem cell product to the patient floor. CD34 cell viability was not rechecked postthaw unless postthaw trypan blue viability was <60%, which did not occur in any products in this study. Expiration time by which cell infusion should be completed was 90 minutes after initiation of thaw.
Immune reconstitution monitoring by flow cytometry
A panel of directly conjugated monoclonal antibodies was used to define functionally distinct T-cell subsets (supplemental Table 1). After staining, cells were acquired on a Fortessa LSR flow cytometer (BD) and analyzed using FlowJo software. The gating strategy used for T-cell subset definition is described in supplemental Figure 1.
Baseline and pretransplant operational characteristics were reported descriptively and compared using Fisher's exact test, χ2 test, or Wilcoxon rank-sum test, as appropriate. Clinical outcomes of interest included OS, PFS, NRM, relapse, infection, engraftment, graft failure, aGVHD, chimerism, and toxicity. Neutrophil engraftment was defined as the first of 2 consecutive days with ANC > 500 cells per µL, and platelet engraftment was defined as the first of 3 consecutive days with platelet count >20 000 platelets per µL. Because of low overall incidence of graft failure, statistical analysis included all cases rather than distinguishing between early and late or primary and secondary graft failure. OS was defined as the time from stem cell infusion to death from any cause. Patients who were alive were censored at the time last seen alive. PFS was defined as the time from stem cell infusion to disease relapse, progression, or death from any cause, whichever occurred first. Patients who were alive without disease relapse or progression were censored at the time last seen alive and relapse or progression free. The Kaplan-Meier method was used to estimate PFS and OS, whereas cumulative incidence of NRM, relapse, graft failure, and graft-versus-host disease (GVHD) was estimated in the context of a competing risks framework. NRM and relapse were treated as a competing event to each other, and death or relapse without developing GVHD served as a competing event for GVHD. For graft failure, death without graft failure was treated as a competing event. The log-rank test and Gray test were used for group comparison of PFS and OS and cumulative incidence of NRM, relapse, graft failure, and GVHD, respectively. To assess the effect of cryopreservation and age of product on time to events in the presence of other risk factors, multivariable Cox and Fine and Gray regression analyses were performed. Prior to modeling, linearity assumption for continuous variables and the proportional hazards assumption were examined. For day 30 CD3+ chimerism (≥50% vs <50%), multivariable logistic regression analysis was performed. All P values were 2-sided at a significance level of 0.05, and multiplicity was not considered. All calculations were performed using SAS 9.3 (SAS Institute, Inc, Cary, NC) and R version 3.3.2.
Patients receiving fresh and cryopreserved products are similar at baseline
In our study, 101 patients received cryopreserved grafts, and 203 patients received fresh grafts from URDs. Characteristics of patients are shown in Table 1. The cryopreserved and fresh product cohorts were similar overall in terms of donor/recipient age and sex, diagnosis, disease status at transplant, disease risk index (DRI), hematopoietic cell transplantation-specific comorbidity index, cytomegalovirus (CMV) serological status (donor/recipient), HLA match, and conditioning intensity. Patients in the cryopreserved group were more likely to have received a GVHD prophylaxis regimen of PTCy/tacrolimus/mycophenolate mofetil compared with the control group (22.8% vs 12.3%, P = .008), reflecting changes in institution and field practice over time. All patients received URD product. There were similar proportions of international vs domestic donors.
Recipient, transplant, and donor characteristics
Patient characteristics .
Fresh .
Cryopreserved .
Patients, n 203 101
Age, y, median (range) 65 (21, 78) 63 (25, 77) .2
Sex, n (%) .9
Male 121 (59.6) 59 (58.4)
Female 82 (40.4) 42 (41.6)
Diagnosis, n (%) .98
ALL 23 (11.3) 12 (11.9)
AML 80 (39.4) 38 (37.6)
Atypical leukemia 1 (0.5) 0 (0)
CLL 2 (1) 1 (1)
CML 1 (0.5) 2 (2)
HLH 2 (1) 2 (2)
MDS 41 (20.2) 17 (16.8)
MDS/MPN 2 (1) 1 (1)
MPAL 1 (0.5) 0 (0)
MPN 29 (14.3) 16 (15.8)
NHL 17 (8.4) 10 (9.9)
T-PLL 4 (2) 2 (2)
Disease status at transplant, n (%) .59
Complete response 118 (58.2) 63 (62.4)
Partial response 15 (7.4) 6 (5.9)
Stable disease 42 (20.7) 24 (23.8)
Progressive disease 2 (1) 2 (2)
Induction failure 18 (8.9) 4 (4)
Untreated 6 (3) 2 (2)
NA 2 (1) 0 (0)
Recipient/donor CMV serological status, n (%) .3
R−/D− 71 (35) 39 (38.6)
R−/D+ 52 (25.6) 17 (16.8)
R+/D− 47 (23.2) 25 (24.8)
R+/D+ 33 (16.3) 19 (18.8)
Unknown 0 (0) 1 (1)
Hematopoietic cell transplantation-specific comorbidity index, n (%) .73
0 to 2 67 (33.1) 32 (31.8)
≥3 136 (67) 69 (68.3)
Median (range) 4 (0, 10) 4 (0, 10)
DRI, n (%) .39
Low 9 (4.4) 9 (8.9)
Intermediate 113 (55.7) 58 (57.4)
High 74 (36.5) 31 (30.7)
Very high 7 (3.4) 3 (3)
KPS, n (%) 1
<90 108 (53.2) 54 (53.5)
100 to 90 95 (46.8) 47 (46.5)
Transplant characteristics
Conditioning intensity, n (%) .08
Myeloablative (MAC) 50 (24.6) 35 (34.7)
Reduced intensity (RIC) 153 (75.4) 66 (65.3)
aGVHD prophylaxis regimen, n (%) .008
Tacrolimus/MMF/cyclophosphamide 25 (12.3) 23 (22.8)
Tacrolimus/methotrexate 123 (60.6) 65 (64.4)
Tacrolimus/rapamycin/methotrexate 50 (24.6) 13 (12.9)
Tacrolimus/rapamycin 5 (2.5) 0 (0)
Year of transplant
2019 147 (72.4) 6 (5.9) <.05
2020 56 (27.6) 95 (94.1)
Donor characteristics
HLA match, n (%) .77
10/10 170 (83.7) 84 (83.2)
<10/10 33 (16.3) 17 (16.9)
Donor origin, n (%) .72
Domestic 106 (52.2) 55 (54.5)
International 97 (47.8) 46 (45.5)
Donor age, y, median (range) 28 (19, 54) 28 (19, 64) .09
Donor sex 1
Male recipient/female donor, n (%) 29 (14.3) 19 (18.8) .32
ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; CLL, chronic lymphocytic leukemia; CML, chronic myeloid leukemia; HLH, hemophagocytic lymphohistiocytosis; KPS, Karnofsky performance score; MDS, myelodysplastic syndrome; MMF, mycophenolate mofetil; MPAL, mixed phenotype acute leukemia; MPN, myeloproliferative neoplasms; NHL, non-Hodgkin lymphoma; T-PLL, T-cell prolymphocytic leukemia.
International PBSCs have longer transit times and overall product age
Characteristics of stem cell products in the cryopreserved and fresh cohorts stratified by domestic or international origin are shown in Table 2. Products destined for cryopreservation were significantly older at the time of processing compared with fresh products (Table 2). Initial TNC concentration and viability were similar between cryopreserved vs fresh products (data not shown). Following processing, final TNC dose (median 7.1 × 108 cells per kg vs 8.0 × 108 cells per kg), final CD34+ dose (7.6 × 106 cells per kg vs 7.7 × 106 cells per kg), and final CD34+ viability (98.0% vs 98.8%) were similar between the cryopreserved vs fresh cohort, respectively. However, final TNC viability was slightly lower in grafts destined for cryopreservation compared with fresh grafts (median 90.2% vs 94.5%; P < .001). For cryopreserved products, TNC viability was measured by trypan blue after thawing prior to infusion. Median viability was 80% (range, 62% to 96%).
Domestic .
International .
Product characteristics .
Median (range) .
Overall age of product (h) 21 (2-71) 36 (15-65) 24 (4-61) 58 (3 −84) <.001
Final TNC dose (108 cells/kg)* 8 (3.8-17.4) 7.9 (2.4-14.8) 8 (3.6-16) 6.9 (2.3-13.8) .01
Final TNC viability by 7AAD (%)* 96.2 (37.4-99.4) 92.9 (77.2-98.9) 92.6 (71-99.3) 86.5 (67.8-95.7) <.001
Final CD34 dose (106 cells/kg)* 8.1 (1.5-32.5) 7 (0.8-22.3) 7.8 (2.1-26.1) 7.5 (1.4-27.2) .052
Final CD34 viability by 7AAD (%)* 98.6 (74.8-99.8) 98.9 (49.7-99.9) 98.2 (62.2-99.5) 98 (92.2-99.7) .19
Post-thaw TNC viability by TB (%) N/A N/A 80 (62-94) 79 (67-96) N/A
Age of product breakdown (h)
Transit time, median (range) 9.1 (0.9, 68.2) 33.8 (13.9, 58.8) 12.2 (1.5, 58.4) 43.7 (22.2, 82) <.0001
Holding time, median (range) 9.7 (0.4, 27) 1.2 (0.2, 21.5) 11.2 (0.4, 22.7) 12.5 (0.3, 31.2) <.0001
Processing time, median (range) 1.0 (1.0, 3.6) 1.0 (1.0, 2.8) 1.8 (1.0, 2.5) 1.8 (1.0, 2) <.0001
N/A, not applicable.
Final TNC and CD34 dose and viability are measured immediately after product processing (performed at our institution) and, in the case of fresh products, immediately prior to delivery to the patient floor for infusion. For cryopreserved products, these are measured after product processing immediately prior to cryopreservation. Upon thaw of cryopreserved products, TNC viability is measured by trypan blue (TB) prior to delivery to patient floor for infusion.
The distribution in overall age of product (between collection and end of processing for either infusion or freezing) was widely different between cryopreserved and fresh grafts (Table 2). Of products intended for cryopreservation, 40.6% was >48 hours old at the end of processing, compared with only 7% of fresh products; 16.8% of cryopreserved products had an age of >60 hours, compared with just 2% of fresh products (P < .0001) (Figure 1A). This increase in overall product age was particularly pronounced for international products from the cryopreserved group (Figure 1B; supplemental Figure 2). Median transit time (from end of collection to receipt at our facility) was increased for cryopreserved products vs fresh (domestic products: 12.2 hours vs 9.1 hours, international products: 43.7 hours vs 33.8 hours; P < .0001), and an increase in holding time (between receipt and beginning of processing) between cryopreserved vs fresh products (domestic products: 11.2 hours vs 9.7 hours, international products: 12.5 hours vs 1.2 hours; P < .0001) accounted for the largest differences in age of product (Table 2).
Graft ages. (A) Overall age of product (defined as time in hours from collection to end of processing) varied between fresh (red) and cryopreserved (blue) cohorts. Products in the cryopreserved group were more likely to be ≥48 hours old at end of processing, reflecting longer intervals at all stages: transit, holding, and processing times. Of cryopreserved products, 16.8% was >60 hours old at the end of processing compared with 2% of fresh products (P < .0001). (B) International products (blue) tended to be older than domestic products (red). This difference in length of transit time is particularly pronounced in the cryopreserved group, reflective of changes in transit time during the COVID-19 pandemic. Cryo, cryopreserved.
Patients receiving cryopreserved grafts have slower platelet engraftment and higher incidence of aGVHD
The median follow-up time among survivors was 16 months (range, 3-25) in the fresh group and 8 months (range, 3-20) in the cryopreserved group. No differences were observed in short-term OS, PFS, NRM, and relapse. One-hundred-day OS was 96% vs 96.5%; PFS was 84% vs 88%. NRM was 2% vs 2%, and relapse was 16% vs 12% in the patients receiving cryopreserved and fresh grafts, respectively (Figure 2A-B; Table 3). International vs domestic origin of product did not lead to differences in these outcomes (supplemental Table 2). Similarly, 6-month OS was 89% vs 89%; PFS was 78% vs 79%. NRM was 2% vs 4.6%, and relapse was 22% vs 20% in the cryopreserved and fresh cohorts, respectively. Multivariable analysis demonstrated that neither conditioning intensity (RIC vs MAC) nor PTCy for GVHD prophylaxis affected OS, PFS, NRM, or relapse (supplemental Table 3). There was no difference in days to neutrophil engraftment (median 15 days vs 14 days), but patients receiving cryopreserved product had slower platelet engraftment compared with fresh (median 21 days vs 18 days, P = .044) (Table 3; Figure 2C-D; supplemental Figure 3). Median days to platelet engraftment between fresh and cryopreserved patients receiving PTCy were not statistically different (21 days vs 25 days; P = .27). Incidence of grade II to IV aGVHD was higher in patients receiving cryopreserved product compared with fresh (100-day cumulative incidence: 17% vs 9%; P = .014) (Table 3; Figure 2E). Increased aGVHD was observed across the spectrum of aGVHD manifestations; however, incidence rates in each organ system are low, limiting statistical analysis (data not shown). Neither PTCy use nor HLA matching was significantly associated with grade II to IV aGVHD (data not shown). There was no difference in incidence of viral reactivations (ie, CMV, adenovirus, BK virus), or fungal infections in the first 100 days between cohorts (supplemental Table 4).
Clinical outcomes of patients receiving cryopreserved vs fresh stem cell products. OS (A) and PFS (B) were similar in patients receiving fresh products (blue line) and cryopreserved products (red line). Patients receiving cryopreserved products had a 1-day delay in neutrophil engraftment (defined as first of 2 consecutive days of ANC > 500 cells per µL) (median 15 days vs 14 days; P = .02) (C) but slower platelet engraftment (defined as first of 3 consecutive days of platelet count >20 000) (median 24 days vs 18 days; P = .044) (D) compared with patients receiving fresh products. (E) Incidence of grade II to IV aGVHD was higher in patients receiving cryopreserved product compared with fresh (100-day cumulative incidence: 17% vs 9%; P = .014).
Outcomes and engraftment .
Fresh (n = 203) .
Cryopreserved (n = 101) .
OS, % (95% CI) .22
100 d 96.5 (93, 98) 96 (90, 98)
6 mo 89 (84, 93) 89 (81, 94)
PFS, % (95% CI) .93
100 d 88 (83, 92) 84 (75, 90)
NRM, % (95% CI) .23
100 d 2 (0.7, 5) 2 (0.4, 6)
6 mo 4.6 (2, 8) 2 (0.4, 6)
Relapse, % (95% CI) .94
100 d 12 (8, 17) 16 (10, 24)
Acute grade II-IV GVHD, % (95% CI) .014
100 d 9 (5, 13) 17 (10, 25)
6 mo 10.5 (7, 15) 21 (13, 30)
Acute grade III-IV GVHD, % (95% CI) .17
100 d 4.5 (2.2, 8) 6 (2.5, 12)
6 mo 5.5 (3, 9) 10 (5, 17)
Neutrophil engraftment .08*
No engraftment, n (%) 1 (0.5) 3 (3)
Engrafted, n (%) 199 (97.5) 98 (97)
Days to engraftment, median (range) 14 (6, 28) 15 (10, 33) .02†
Never nadir, n (%) 4 (2) 0 (0)
Platelet engraftment .14*
No engraftment, n (%) 5 (2.5) 7 (6.9)
Engrafted, n (%) 138 (68) 69 (68.3)
Days to engraftment, median (range) 18 (9, 109) 21 (10, 139) .044†
Never nadir, n (%) 60 (29.6) 25 (24.8)
Graft failure .11
No, n (%) 195 (96.1) 92 (91.1)
Yes, n (%) 7 (3.4) 9 (8.9)
Died prior to count recovery, n (%) 1 (0.5) 0 (0)
Graft failure: early vs late .04
Early (<100 d), n 3 7
Late (>100 d), n 4 2
Effect of age of product on graft failure sHR (95% CI) P
Overall age of product: ≥48 h vs <48 h 4.57 (1.71, 12.3) .0025
HLA matching: 10/10 vs <10/10 1.2 (0.35, 4.2) .77
Due to the small number of events (N = 16), univariable analysis was performed using the Fine and Gray model treating death without GF as a competing event.
P value for comparison for 3 categories (no engraftment, engrafted, never nadir).
P value for comparison of time to engraftment for engrafted only.
Patients receiving older grafts have higher incidence of graft failure
Older overall age of product was associated with an increase in graft failure, independent of cryopreservation (Table 3). Of patients who received a product ≥48 hours old, 13.6% experienced graft failure compared with 3.3% of patients receiving a product <48 hours old. The subdistribution hazard ratio (sHR) of age of product ≥48 hours relative to <48 hours for graft failure was 4.57 (95% confidence interval [CI] 1.71-12.3; P = .0025). Patients receiving cryopreserved product had a 2.5-fold higher incidence of graft failure (early or late), although this was not statistically significant (8.9% vs 3.4%; P = .11). Because the incidence rate of graft failure was low (5%), we performed a competing risks regression analysis including PTCy and cryopreservation only (ie, a parsimonious model). In testing main effects, cryopreservation status was significant (P = .02) and PTCy was not significant (data not shown); however, given the small sample size here, this warrants further investigation in future larger studies to confirm. HLA matching was not significantly associated with graft failure (sHR 1.2, 95% CI 0.35, 4.2; P = .77). Because of the small event size, a parsimonious model was used; that is, only HLA matching status and cryopreservation status were included. In this model, cryopreserved product was significantly associated with graft failure (sHR 3.1, 95% CI 1.2, 8.2; P = .02).
Cryopreservation and product age are associated with lower CD3+ chimerism
Patients receiving cryopreserved products were significantly more likely to have CD3+ chimerism ≤50% at both day 30 and day 100 (day 30: 34% cryo vs 14% fresh; P = .0002; day 100: 17% vs 6%; P = .016) (Table 4; supplemental Table 5; supplemental Figure 4A-B). Older overall age of product, lower TNC viability by 7AAD at the end of cell processing, and international product origin were all associated with day 30 CD3+ chimerism ≤50% in univariate analysis (Table 5; supplemental Figure 4C-D). Multivariable logistic analysis shows that cryopreservation conferred the greatest odds for CD3+ chimerism ≤50% at 30 days (odds ratio [OR] 3.19, 95% CI, 1.56-6.52; P = .0015) (Table 6). Age of product ≥48 hours also had greater odds of lower CD3+ chimerism at day 30, although this was not statistically significant (OR 2.46, 95% CI, 0.99-6.10; P = .052) (Table 6). RIC vs MAC conditioning was not associated with lower CD3+ chimerism. PTCy was controlled in multivariable models for day 30 CD3+ chimerism using logistic regression analysis and was not associated with day 30 CD3+ chimerism ≤50% (OR 1.7, 95% CI, 0.7-4.14; P = .24).
Day 30 and 100 CD3 chimerism
Day 30 CD3 donor chimerism, n (%) .0002
≤50% 28 (14) 34 (34)
51% to 75% 61 (31) 18 (18)
>75% 109 (55) 47 (47)
Day 100 CD3 donor chimerism, n (%) .016
≤50% 11 (6) 16 (17)
Factors influencing D30 CD3 chimerism
D30 CD3 chimerism .
>50% .
≤50% .
Age of product, n (%) <.001
<48 h 202 (86) 37 (59.7)
≥48 h 33 (14) 25 (40.3)
%TNC viability-7AAD, n (%)
<90% 60 (25.5) 27 (43.5) .008
≥90% 175 (74.5) 35 (56.5)
Product origin, n (%) .03
International 102 (43.4) 37 (59.7)
Multivariable model for D30 CD3+ chimerism ≤50%
Comparison .
OR .
Cryopreserved vs fresh 3.19 1.56 6.52 .0015
Overall age of product: ≥48 h vs <48 h 2.46 0.99 6.10 .052
DRI: high/very high vs low/intermediate 2.23 1.14 4.39 .02
Conditioning intensity: RIC vs MAC 2.28 0.89 5.85 .09
Cryopreservation is associated with impaired reconstitution of WBC and T-cell numbers
Analysis of total white blood cell count (WBC) and cell subsets demonstrated that at day 30 after transplantation, WBC was significantly lower in patients receiving cryopreserved products compared with fresh (median WBC 3850 cells per µL vs 6260 cells per µL; P = .0079) (Figure 3A). Absolute numbers of all 3 major cell subsets were decreased in patients receiving cryopreserved products compared with fresh, although the difference in absolute lymphocyte count and absolute monocyte count between cohorts was not statistically significant (supplemental Tables 6 and 7 ). The effect of cryopreservation in multivariable linear regression analysis (after log-transformation) is consistent with the results from univariable analysis.
Immune reconstitution. (A) Patients receiving cryopreserved stem cells (blue bars) had lower WBC and neutrophil count (ANC) at 30 days after transplant compared with patients receiving fresh (red bars) (median WBC 3850 cells per µL vs 6260 cells per µL; P = .0079, median ANC 2240 cells per µL vs 3300 cells per µL; P = .016). There were trends toward lower absolute lymphocyte (ALC) and monocyte (AMC) counts in patients receiving cryopreserved grafts, but these were not statistically significant. (B) Similarly, CD3+, CD4+ Tcon and Treg, and CD8+ subsets also had trends toward lower values in cryopreserved vs fresh.
Given the significant differences in CD3+ chimerism at day 30 and day 100, we investigated immune reconstitution of T-cell subsets between patients receiving cryopreserved or fresh products. There was a trend toward decreased total numbers of CD3+, CD4+ T regulatory (Treg), CD4+ conventional T cells, and CD8+ cells in patients receiving cryopreserved grafts at day 30 after transplantation (Figure 3B). Patients who received a cryopreserved product had lower absolute numbers of conventional CD4+ naive T cells and CD4+ effector memory cells at day 30 (supplemental Table 6). In the Treg compartment, cryopreservation of product was associated with lower absolute numbers of naive, effector memory, and terminally differentiated T effector memory RA cells (supplemental Figures 5-6; supplemental Table 4). There were no differences observed in other CD4+ or CD8+ subsets or in ratios of Tregs to CD8+ or CD4+ T cells. The same analysis was performed on peripheral blood mononuclear cells from a subset of patients at day 100 after transplant, at which time WBC and T-cell recovery in the cryopreserved group had improved somewhat, but remained lower than fresh products at day 100, particularly in the CD4+ Treg and CD4+ Tcon and Treg as opposed to the total CD3+ and CD8+ T-cell compartments (supplemental Table 6).
The worldwide spread of COVID-19 and ensuing pandemic necessitated swift action on the part of transplant centers and national donor registries to adopt practices to enable continued safe delivery of stem cell transplantations. Cryopreservation of allogeneic PBSCs became a practical option during the pandemic to ensure delivery of grafts in a timely manner and allow patients to continue undergoing this procedure. Here, we analyzed our single-institution experience with cryopreserved vs fresh PBSCs from 2019 to 2020, a period spanning ∼1 year before and after the start of the pandemic. Although short-term outcomes were similar in recipients of fresh or cryopreserved grafts, we noted a trend toward increased graft failure, particularly for grafts with overall product age ≥48 hours, and impaired immune reconstitution among recipients of cryopreserved grafts. In addition, we observed delayed platelet engraftment in the cryopreserved cohort compared with controls, as well as an increase in the incidence of acute grade II to IV GVHD. Whether there will be any difference in long-term outcomes, such as chronic GVHD, disease relapse, and NRM, will require extended follow-up. A prior study on outcomes using cryopreserved PBSCs did not show a difference in clinical outcomes despite having a longer follow-up interval.6 However, cryopreserved grafts were composed mostly of related donor products, so these likely experienced shorter transit and holding times, which may explain the differences observed.
Peripheral blood CD3+ chimerism was significantly impaired at day 30 and 100 after transplant in patients receiving cryopreserved PBSCs, with 34% of patients having CD3+ chimerism ≤50%, compared with 14% patients who received fresh PBSCs. This effect appears to be independent of conditioning regimen intensity and exposure to PTCy. As we and others have previously reported, low CD3+ chimerism early after transplant predicts worse OS and higher rates of relapse 1 to 5 years after transplant, particularly for patients receiving reduced-intensity conditioning.17-21 Thus, given the relatively short follow-up reported here, deleterious effects associated with lower chimerism following receipt of cryopreserved stem cell products may not yet be evident. Longer follow-up is required to fully assess the safety of using cryopreserved stem cell products reflected by late relapse, cGVHD, and OS.
In addition to the widespread adoption of cryopreservation, the COVID-19 pandemic led to disruptions in air travel, complicating stem cell product delivery, particularly across international lines. In the United States, the National Donor Marrow Program developed alternate routes for delivery of cells along a regional hub model in collaboration with international donor networks. Despite these heroic efforts, our data indicate that transit times were longer during the pandemic compared with prepandemic controls, and this difference disproportionately affected international products compared with domestic. Older product ages showed a trend toward lower day 30 CD3+ chimerism in addition to the impact of cryopreservation. Overall product age ≥48 hours also conferred an sHR of 4.57 for graft failure, whereas cryopreservation yielded a 2.5-fold increase in failure rate that was not significant. These results suggest that patients who receive older products, especially if also cryopreserved, should be monitored carefully for graft failure and T-cell engraftment after transplantation.
Finally, cryopreservation is associated with lower total WBC at 30 days after transplantation, as well as decreases in several T-cell subsets. We have previously shown that lower WBC at 1 to 3 months after transplant was associated with lower 5-year OS and PFS.22 The impairment in reconstitution of various T-cell subsets, particularly the Treg cells, is striking. Given the important role previously described for adequate Treg reconstitution in predicting improved OS,23 lower incidence of GVHD,24 and mediation of a GVL effect,25 the impairment in Treg reconstitution described may be of clinical significance and warrants further investigation. Cryopreservation is known to alter surface expression of molecules such as L-Selectin (CD62L) that mediate homing to various tissues.26 This may affect engraftment of mature cells as well as immature cells in stem cell products and may help explain some of the changes in immune recovery observed with cryopreserved products.
Our study has several limitations, primarily having a relatively small number of patients treated at a single center. Stem cell products were handled and under one processing laboratory's standard operating procedures, which may limit generalizability of our data to other centers and practices. Nevertheless, the data shown here provide compelling evidence that cryopreservation of PBSCs and age of products derived from URDs may have negative consequences, and the choice of whether to cryopreserve a PBSC graft should be carefully considered for each individual transplant recipient.
The COVID-19 pandemic had far-reaching influences on clinical practice across myriad specialties. In the field of stem cell transplantation, operations required effective multidisciplinary international collaborative efforts to ensure continued delivery of stem cell products and patient care. When the pandemic abates, many aspects of transplantation, such as delays in international delivery of stem cell products, are likely to return to pre–COVID-19 norms. However, other practices may remain. Cryopreservation of stem cell products offers an opportunity for increased flexibility in coordination of stem cell donation and delivery as well as timing of conditioning chemotherapy, and data published thus far suggest that short-term clinical outcomes are similar compared with transplants using fresh products. However, our data indicate that caution is necessary in utilizing cryopreserved stem cell products for allogeneic transplantation, particularly those requiring longer times in transit holding and thus of older overall product age at end of processing. Although early clinical outcomes do not appear to be compromised, T-cell chimerism and reconstitution are impaired, which may lead to compromise in longer-term outcomes. Longer follow-up and further investigation into these findings are required to fully explore how cryopreservation and age of allogeneic stem cell products may impact transplant safety and efficacy.
The authors acknowledge the National Donor Marrow Program (NMDP) for their efforts to maintain access to donors throughout the ongoing pandemic and the DFCI/HCC clinical oncology support staff for continued care of these patients. The authors thank the Ted and Eileen Pasquarello Tissue Bank and Doreen Hearsey for prospective collection and processing of serial blood samples. The authors also thank the Connell and O'Reilly Families Cell Manipulation Core Facility (CMCF) at DFCI for continuous efforts in processing stem cell products and for providing data for this paper.
This work was supported by the National Institutes of Health, National Cancer Institute grant P01CA229092.
Contribution: K.M., T.M.K., R.J.S., M.G., and V.T.H. conceived the project and designed the study; H.T.K. designed, performed, and interpreted the statistical analysis; K.M., T.M.K., H.M.G., and D.L. participated in identification, collection, and interpretation of patient information; A.W. and C.G.R. performed flow cytometry data acquisition and analysis; H.M.G. and S.N. provided cell product data and processing methodology; K.M., H.T.K., T.M.K., H.M.G., D.L., C.C., J.H.A., J.K., J.R., R.M.S., R.R., C.J.W., R.J.S, S.N., V.T.H., and M.G. participated in manuscript writing and review and all authors provided final approval of the manuscript.
Conflict-of-interest disclosure: C.J.W. holds equity in BioNTech and receives research funding from Pharmacyclics. J.R. received research funding from Amgen, Equillium, Kite Pharma, and Novartis and served on advisory boards for Akron, Avrobio, Clade, Garuda, Immunitas, LifeVault, Rheos, Talaris, and TScan. J.K. reports research support from Amgen, Equillium, BMS, Miltenyi Biotec, Regeneron, and Clinigen and consulting income from Amgen, Equillium, and Moderna Therapeutics, and is a scientific advisory board member for Cugene and Therakos. S.N. reports ad hoc advisory boards for Novartis, Kite/Gilead, and Nkarta. R.J.S. serves on the board of directors for Kiadis and Be The Match/National Marrow Donor Program; provided consulting for Gilead, Rheos Therapeutics, Jazz, and VOR Biopharma; and is on the Data Safety Monitoring board for Juno. The remaining authors declare no competing financial interests.
Correspondence: Mahasweta Gooptu, 450 Brookline Ave, Boston, MA 02215; e-mail: Mahasweta_Gooptu@dfci.harvard.edu.
Validation of short-term handling and storage conditions for marrow and peripheral blood stem cell products
Transfusion.
Khuu
David-Ocampo
Analysis of the recovery of cryopreserved and thawed CD34+ and CD3+ cells collected for hematopoietic transplantation
Lioznov
Dellbrügger
Sputtek
Fehse
Transportation and cryopreservation may impair haematopoietic stem cell function and engraftment of allogeneic PBSCs, but not BM
Bone Marrow Transplant.
Medd
Hollyman
Malladi
Cryopreservation of allogeneic PBSC from related and unrelated donors is associated with delayed platelet engraftment but has no impact on survival
Dagdas
Gunes
Falay
Comparison of allogenic stem cell transplantations performed with frozen or fresh stem cell products with regard to GVHD and mortality
Alotaibi
Fresh vs. frozen allogeneic peripheral blood stem cell grafts: A successful timely option [published correction appears in Am J Hematol. 2021; online head of print 11 June 2021]
Am J Hematol.
Saragosa
Similar outcomes of cryopreserved allogeneic peripheral stem cell transplants (PBSCT) compared to fresh allografts
Biol Blood Marrow Transplant.
Purtill
Antonenas
Chiappini
Variable CD34+ recovery of cryopreserved allogeneic HPC products: transplant implications during the COVID-19 pandemic
Blood Adv.
Farhadfar
Murthy
The effect of donor graft cryopreservation on allogeneic hematopoietic cell transplantation outcomes: a Center for International Blood and Marrow Transplant Research Analysis. Implications during the COVID-19 pandemic
Transplant Cell Ther.
Hamadani
Graft cryopreservation does not impact overall survival after allogeneic hematopoietic cell transplantation using post-transplantation cyclophosphamide for graft-versus-host disease prophylaxis
Eapen
Hematopoietic cell transplantation with cryopreserved grafts for severe aplastic anemia
Saucier
COVID-19 and hematopoietic stem cell transplantation and immune effector cell therapy: a US cancer center experience
Chiusolo
Coronavirus disease 2019 pandemic and allogeneic hematopoietic stem cell transplantation: a single center reappraisal
Cytotherapy.
Transplantation of allogeneic cryopreserved hematopoietic cell grafts during the Covid-19 pandemic: a National Marrow Donor Program perspective
Waghmare
Abidi
Boeckh
Guidelines for COVID-19 management in hematopoietic cell transplantation and cellular therapy recipients
Dignan
The NICE COVID-19 rapid guideline on haematopoietic stem cell transplantation: development, implementation and impact
Br J Haematol.
Koreth
Nikiforow
Donor chimerism early after reduced-intensity conditioning hematopoietic stem cell transplantation predicts relapse and survival
Gudger
Very early lineage-specific chimerism after reduced intensity stem cell transplantation is highly predictive of clinical outcome for patients with myeloid disease [published online ahead of print 18 June 2021]
Leuk Res.
Mixed T lymphocyte chimerism after allogeneic hematopoietic transplantation is predictive for relapse of acute myeloid leukemia and myelodysplastic syndromes
Stingo
Long-term follow-up of patients receiving allogeneic stem cell transplant for chronic lymphocytic leukaemia: mixed T-cell chimerism is associated with high relapse risk and inferior survival
Golmard
Chimerism analysis in peripheral blood using indel quantitative real-time PCR is a useful tool to predict post-transplant relapse in acute leukemia
White blood cell recovery after allogeneic hematopoietic cell transplantation predicts clinical outcome
High proportions of regulatory T cells in PBSC grafts predict improved survival after allogeneic haematopoietic SCT
The absolute number of regulatory T cells in unmanipulated peripheral blood grafts predicts the occurrence of acute graft-versus-host disease post haplo-identical hematopoietic stem cell transplantation
Di Ianni
Olioso
Giancola
Treg-protected donor lymphocyte infusions: a new tool to address the graft-versus-leukemia effect in the absence of graft-versus-host disease in patients relapsed after HSCT
Int J Hematol.
Van der Wall
Schuurhuis
Changes in L-selectin expression on CD34-positive cells upon cryopreservation of peripheral blood stem cell transplants
Data sharing will be made available by e-mails to the corresponding author upon request: Mahasweta_Gooptu@dfci.harvard.edu.
The full-text version of this article contains a data supplement.
© 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.
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The Mesa College Theatre Company (MCTC) performed a rendition of the Tony award-winning play this October in 2015. Under the direction of Professor George Ye, students of San Diego Mesa College presented The Elephant Man. I went to see the MCTC's performance on October 10th. This historical drama was written by Bernard Pomerance in 1977. It's based on the true life of Joseph Derrick who lived in 19th century London. Keep Reading!


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Easter House v. Felder, No. 86-2164
Writing for the Court Before BAUER, Chief Judge, and CUMMINGS, WOOD, Jr., CUDAHY, POSNER, COFFEY, FLAUM, EASTERBROOK, RIPPLE, MANION and KANNE; KANNE; EASTERBROOK; CUDAHY, Circuit Judge, with whom CUMMINGS and POSNER
Citation 910 F.2d 1387
Parties EASTER HOUSE, an Illinois not-for-profit corporation, Plaintiff-Appellee, v. Thomas FELDER, Florence McGuire and Joan Satoloe, Defendants-Appellants.
Docket Number No. 86-2164
Decision Date 14 August 1990
910 F.2d 1387 59 USLW 2141 EASTER HOUSE, an Illinois not-for-profit corporation,
Plaintiff-Appellee,
Thomas FELDER, Florence McGuire and Joan Satoloe,
Defendants-Appellants. No. 86-2164. United States Court of Appeals,
Seventh Circuit. Aug. 14, 1990.
James Figliulo, Foran, Wiss & Schultz, Chicago, Ill., for plaintiff-appellee.
Thomas A. Ioppolo, Asst. Atty. Gen., Office of Atty. Gen., Chicago, Ill., for defendants-appellants.
Before BAUER, Chief Judge, and CUMMINGS, WOOD, Jr., CUDAHY, POSNER, COFFEY, FLAUM, EASTERBROOK, RIPPLE, MANION and KANNE, Circuit Judges.
KANNE, Circuit Judge.
The en banc review which we undertake today constitutes the second of its sort for this case. Our original en banc decision in this case was Easter House v. Felder, 879 F.2d 1458 (7th Cir.1989). In that decision, we concluded that Easter House could not pursue a remedy under Sec. 1983 for either of two alleged deprivations of property which purportedly resulted from actions taken by the appellants as employees of the Illinois Department of Children and Family Services. With regard to the first alleged deprivation, we held that Parratt v. Taylor, 451 U.S. 527, 101 S.Ct. 1908, 68 L.Ed.2d 420 (1981) and its progeny precluded the imposition
of Sec. 1983 liability in that the appellants' conduct was "random and unauthorized" and adequate state law remedies provided all the process which was due under the fourteenth amendment. A second alleged deprivation of property was dismissed in that Easter House had not identified a property interest of which it had been deprived. That decision, however, has been vacated by the Supreme Court and remanded for reexamination in light of Zinermon v. Burch, --- U.S. ----, 110 S.Ct. 975, 108 L.Ed.2d 100 (1990). We have conducted that reexamination and conclude that our original en banc decision is consistent not only with the dictates of Parratt v. Taylor, but also with the holding in Zinermon. Accordingly, we modify our original en banc opinion to account for the Court's pronouncements in Zinermon, but reaffirm our previous disposition of these issues.
I. BACKGROUND 1
Easter House is a Chicago-based adoption agency, owned and operated by Seymour Kurtz and licensed by the Illinois Department of Children and Family Services ("DCFS"). This suit arises from a series of events involving (1) Easter House's application for a renewal license, (2) its Executive Director's decision to depart while the application was pending and open a rival adoption agency with a similar name, (3) the appellants' decisions, as DCFS employees, to delay action upon Easter House's renewal license and to expedite action upon the former director's application to start a new agency, and (4) the appellants' decision to order various investigations of Easter House's operating procedures approximately two years later. According to Easter House, the appellants' actions were taken under color of state law and deprived Easter House of identifiable constitutionally-protected property interests in violation of 42 U.S.C. Sec. 1983. We will treat Easter House's claims as involving two separate conspiracies and set forth the facts supporting each.
A. The Licensing Conspiracy
Easter House alleged that the appellants conspired with Easter House's former Executive Director to deprive it of, among other things, its operating license. This conspiracy involved two separate and distinct prongs. First, Easter House alleged that the appellants acted improperly in delaying action upon Easter House's application for a renewal license. Second, Easter House contended that the appellants improperly granted a license to Easter House's former Executive Director in an expeditious manner. Easter House claimed that together these two courses of action resulted in a property deprivation in violation of Sec. 1983.
1. Easter House's Application for a Renewal License
Easter House's operating license was scheduled to expire on November 30, 1974. In late November, Easter House began preparing for renewal of that license. Joan Satoloe, a licensing representative assigned to the DCFS's Chicago office, prepared a relicensing study which recommended renewal of Easter House's license for the two-year period beginning December 1, 1974. This recommendation was forwarded to the DCFS's main office in Springfield, Illinois, where the final licensing decisions are made and the licenses ultimately issued.
While Easter House's license was pending, its Executive Director, Millicent Smith, decided to leave, apparently on less than amicable terms. On December 30, 1974, while Satoloe was on vacation, Smith met with Satoloe's immediate supervisor, Florence McGuire, the licensing supervisor for the DCFS's central district, to tell her of her plans to leave Easter House and start a new adoption agency. 2
At that meeting, Smith described the reasons for her growing disenchantment with Easter House. 3 She informed McGuire that she had been planning to leave Easter House for some time, but had delayed her action until Kurtz, Easter House's owner, had left on a year-end vacation. Apparently, his absence would facilitate her ability to start a rival adoption agency called the Easter House Adoption Agency, Inc. ("Easter House II"). 4 She told McGuire that she had decided to use a name closely resembling Easter House and to take Easter House's files 5 to ensure that her leaving would not deprive her of the rewards to which she felt entitled based upon her long tenure at Easter House.
After the meeting, McGuire called the DCFS's Springfield office to request a delay in the mailing of Easter House's renewed license. On the following day, December 31, 1974, Smith wrote to Satoloe and Thomas Felder, the chief of the DCFS for the central district. In that letter, she described the prior day's meeting and stressed the importance of rapid action upon Easter House II's charter application. In a separate letter to McGuire, Smith indicated that Fran Riley, Easter House's only other trained social worker, had decided to leave Easter House and join Easter House II. Smith also thanked McGuire for withholding Easter House's license. On that same day, Smith wrote to Kurtz resigning her position at Easter House.
After discussing Easter House's situation with McGuire, Felder agreed with McGuire that Easter House's renewed license should remain on hold at the Springfield office. On January 6, 1975, Felder wrote to Kurtz, informing him that the departures of Smith and Riley, Easter House's only trained social workers, had put the agency out of compliance with the DCFS's licensing standards. See DCFS Regulation 5.10 (1970) (child welfare agencies must have at least one employee with a Master of Social Work degree and two years of supervisory experience in social work). He also stated that if Easter House wished to resume operations it would have to reattain minimum standards and reapply for a license. 6
On January 8, 1975, upon the advice of a DCFS attorney, Felder wrote a second letter to Kurtz. In this letter, he informed Kurtz that the January 6th letter had been incorrect and that, pursuant to the Illinois Child Care Act of 1969, Easter House would have ten days from receipt of the second letter to request a hearing before the DCFS's refusal to issue a renewal license would become final. However, the second letter did not offer to provide the assistance required by the DCFS's regulations and enforcement manual. See supra note 6.
During the period between the decision to withhold renewal and Kurtz's response on January 22, 1975, the DCFS received two inquiries about the status of Easter House; one from a lawyer representing prospective clients and one from a social worker interested in applying for the position which Smith previously had held. Both callers were told that Easter House had no license. The DCFS further informed the prospective job applicant that the DCFS was in the process of reviewing Easter House's "entire program." In addition, Felder notified Judge Comerford, then the Chief Judge dealing with adoptions in Cook County, that Easter House was no longer licensed to make adoption placements.
Kurtz received both of Felder's letters on January 12, 1975. On January 22, Kurtz wrote the DCFS requesting a hearing and a written statement of charges. On February 4, two weeks after he had hired a new Executive Director, Kurtz met with Felder to discuss information which Kurtz had obtained about Smith's new operation and the relicensing of Easter House. At that meeting, Kurtz waived the hearing which had been offered in the January 8th letter after Felder assured him that the absence of proper staff was the only barrier to the issuance of Easter House's license. Soon thereafter, Satoloe visited Easter House and approved the new Executive Director's credentials. On February 19, 1975, Easter House received its renewed license to operate as a child welfare agency during the period from December 1, 1974, through November 30, 1975--in effect, never losing its legal authority to operate as an adoption agency.
2. Easter House II's Charter Application
The alleged conspiracy to deprive Easter House of its license had a second part. Easter House contended below that the DCFS's actions in granting Smith's license for Easter House II were so irregular as to evidence the DCFS's intent to aid Smith in destroying Easter House.
In Illinois, child welfare agencies such as Easter House and Easter House II must apply to the Illinois Department of State for a charter which operates essentially as a certificate of incorporation. However, unlike ordinary corporations, child welfare agencies are subjected to charter studies by the DCFS in addition to the usual processing by the Illinois Department of State. According to testimony at trial, charter studies for child welfare agencies are intended to ensure that new agencies will serve the public...
Belcher v. Norton, No. 06-3174.
United States Courts of Appeals. United States Court of Appeals (7th Circuit)
...of a litigant's procedural due process rights where the state provides "a meaningful post-deprivation remedy." Easter House v. Felder, 910 F.2d 1387, 1396 (7th Cir. 1990) (internal citations omitted). Therefore, 497 F.3d 751 Deputy Marshal Norton's depriving Ms. Gleason of her vehicle does ......
Soldal v. County of Cook, No. 89-3631
...1908, 68 L.Ed.2d 420 (1981); Zinermon v. Burch, 494 U.S. 113, 110 S.Ct. 975, 108 L.Ed.2d 100 (1990); see also Easter House v. Felder, 910 F.2d 1387, 1396-97 (7th Cir.1990) (en Page 1076 banc). Illinois law entitled the Soldals to sue Terrace Properties and Mrs. Hale for the damages caused b......
Jones v. Dane County, No. 92-0946
Court of Appeals of Wisconsin
...662, 664-65, 88 L.Ed.2d 662 (1986). Chorlton's failure to comply with § 48.357(1) is therefore a random act. In Easter House v. Felder, 910 F.2d 1387, 1404 (7th Cir.1990), cert. denied, 498 U.S. 1067, 111 S.Ct. 783, 112 L.Ed.2d 846 (1991), the court Section 1983 must be preserved to remedy ......
Daily Servs., LLC v. Valentino, No. 13–4157.
...(1st Cir.) (rejecting that proposition); Johnson v. La. Dep't of Agric., 18 F.3d 318, 322 (5th Cir.1994) (same); Easter House v. Felder, 910 F.2d 1387, 1400 (7th Cir.1990) (en banc) (same). Regardless of their positions, the defendants were not authorized to effect deprivations in the way t......


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General Military Questions
Navy vs. Air Force
Posted on Last Updated: January 16, 2020 January 16, 2020 Author Rob V. Comment(0) 129 Views
The Navy and Air Force are both Military branches that fall under the Department of the Navy and Department of the Air Force, respectively.
These departments fall under the Department of Defense and have different responsibilities when it comes to protecting the United States.
If you are considering joining the military and have narrowed your decision down to the Navy or the Air Force, you may be wondering what the difference is.
Below we will discuss what the Navy is, what the Air Force is, details about them both and 5 key differences between them.
Continue reading for more on Navy vs. Air Force.
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What is the US Navy?
What is the Air Force?
Navy vs. Air Force: 5 Key Differences
US Navy ship stopping at Guantanamo Bay for fuel. Image: flickr
The US Navy is a Department of Defense Military Branch that serves its main duties on the sea.
The Navy has ships, aircraft, and submarines that allow for an advantage in warfare.
It is one of the largest naval forces in the world with its surprisingly capable sea and air abilities.
Currently, the Navy has 293 deployable battle force ships.
Of those 293 deployable ships, 89 are currently deployed, including submarines.
The Navy has multiple aircraft carriers in the Atlantic, Pacific, 5th Fleet, and 6th Fleet.
They also have an Amphibious Assault Ship currently underway.
The US Navy is a multiple force threat that has the ability to mobilize at a moment's notice.
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How big is the Navy?
The US Navy currently has 336,706 active duty personnel.
Of the active duty personnel, 55,064 are officers, 277,192 are enlisted, and 4,450 are midshipmen.
The US Navy also has 103,675 individuals in the Ready Reserve.
They have 59,574 Selected Reserve and 44,101 Individual Ready Reserve.
What does the Navy do?
The US Navy has the capability to support battles in the sea, in the air, and on the ground.
They have one of the largest naval fleets allowing them to detect, neutralize, and attack threats.
Their capabilities include air strikes with their multiple aircraft carriers and large air force.
Navy personnel are also trained on ground equipment and vehicles to support ground operations when needed.
What are their responsibilities?
The Navy is responsible for protecting the US soil at ports and on the sea.
Naval ships patrol international waters to protect the US.
Having the capability of a naval presence allows for an existing fighting force in the event the main-land is attacked and under siege.
Their responsibilities include maritime security, providing naval warfare capabilities, and deterring attacks.
The Navy uses aircraft carriers, amphibious assault ships, cruisers, littoral combat ships, destroyers, and submarines to deploy troops, engage targets, provide near-shore and open water operations, and carry out underwater missions.
Related Article – Navy Uniform Regulations 2020
What is their command structure?
The Navy is one component of the Department of the Navy, (the Marine Corps is the other component).
It has one of the more complex command structures out of all of the US armed forces.
The Navy is broken into a dual command structure including an administrative structure and an operational structure.
The purpose of this is to alleviate operational commanders from administrative functions that might inhibit their ability to fully focus on commanding combat forces.
Administrative Organization
The administrative organization is responsible for training, research, maintenance, personnel, and supply chain.
The administrative organization begins with the Secretary of Defense and is followed by the Secretary of the Navy, the Chief of Naval Operations (CNO), and then the Commanders in Chief along with the Commander of the Naval Reserve Force.
The types of commands include:
Shore Command- Installations that are on-shore who complete supporting operations such as repairs, training or medical.
Systems Command- 5 Commands that assist with technical requirements
Type Command- This command supports personnel, training, and repair on Navy fleets. This can be broken down further into smaller command types.
Operational Organization
The Secretary of Defense issues orders to the combatant commands, who then issue orders to the component commanders.
The component commands include the Pacific Fleet, Naval Forces Central Command, Fleet Forces Command, and Naval Forces Command.
Component commanders control numbered fleet commanders.
Numbered fleet commanders command ships, submarines, and aircraft known as fleets.
There are six fleets in the Navy that are divided into task forces, task groups, task units, and then task elements.
The Navy also has squadrons for aviation units and Naval Construction Battalions (SeaBees).
Related Article – Pros and Cons Of Joining The Navy
F-35A Lightning II aircraft receiving fuel from a KC-10 Extender. Image: af.mil
The US Air Force is a Department of Defense Military branch that primarily focuses on air, space, and cyberspace battles.
The Air Force was established in 1947 with the National Security Act of 1947 and Executive Order 9877.
The US Air Force is responsible for creating a superior air and space enforcement.
It is comprised of active, reserve, and guard units.
How big is the Air Force?
As of September 2019, the Air Force had 328,049 Active Duty members.
These demographics do not include Guard, Reserve, or Academy members.
Of the 328,049 members, 63,902 are officers and 264,147 are enlisted.
There are 12,323 pilots, 3,265 navigators, and 1,306 air battle managers that are grade lieutenant colonel and below.
The Air Force currently has 312 operational squadrons with 121 Total Force Associations.
There are 69,200 individuals in the Air Force Reserves.
What does the Air Force do?
They use intelligence, surveillance, and reconnaissance (ISR) to patrol and protect.
Air Force members protect the ground, air, space, and cyberspace.
The use of multiple aircraft provides the ability to counter land and air strikes as well as deliver global strikes and rapid mobility.
This provides support and protection for ground troops below.
The USAF also has space operations that allow for missile warning, GPS, Space Situational Awareness, and to protect communications.
Related Article – Air Force Aerospace Propulsion (2A6X1): Career Details
The main responsibilities of the Air Force include defending and fighting in air, space, and cyberspace.
Air Force members work both in the air and on the ground.
Ground members work in positions that support the mission through mechanical work, intelligence gathering, policing, protecting, and more.
The USAF is responsible for being available for air strikes whenever necessary and being vigilant on protecting against air strikes or cyber attacks.
They ensure communication is secure and GPS are working properly.
Under the President and Secretary of Defense, the Air Force has the Military Departments and Unified Commands.
Air Force commands include:
Air Mobility Command
Air Combat Command
Air Force Global Strike Command
Air Force Special Operations Command
Air Force Materiel Command
Air Force Space Command
Air Education & Training Command
Under commands, the structure follows similar to other branches of the Military.
Wings, or Numbered Air Force, generally report to commands.
Groups make up wings, squadrons make up groups, flights make up squadrons, and squadrons consist of sections.
Related Article – Pros And Cons Of Joining The Air Force
Navy EA-18G Growler assigned to the USS Carl Vinson. Image: wikimedia
Difference #1: Responsibilities
Probably the most recognizable difference between the Navy and the Air Force is their responsibilities.
The Navy is responsible for protecting ports and the sea.
It consists of deployable ships and other water vessels.
Air Force members protect the sky and space.
Their force is made of mostly aircraft.
Both the Navy and Air Force will have ground positions on soil, but their main responsibilities are elsewhere.
They will both have positions that are in fields such as medic and policing and both have aircraft pilots.
But even with similar career fields, the responsibilities of those specific individuals are different.
The Air Force is known for its medical evacuation by aircraft.
While the Navy has positions in naval cyber warfare, protecting cyberspace is one of the key responsibilities given to the Air Force.
Even though their responsibilities differ, they will work together when needed.
Difference #2: Command
Another difference between the Air Force and the Navy is their command structure.
The active duty components of each branch fall under Title 10 of the US Code, but that may be all that is similar between their command structures.
The Air Force has a command structure that is similar to that of the Army.
Individuals in the Air Force fall under different commands, depending on their specific job.
They are organized using squadrons that are based on job function.
The Navy's command is broken into two different functions: operational and administrative.
Navy members can actually fall under both commands simultaneously.
Operational commands consist of combatant commands that have primary duties of operations and exercises.
Administrative commands consist of commands that have the primary duty of all administrative functions such as training, repairs, and medical.
The Air Force commands all fall under the same structure, while the Navy breaks it into two separate commanding units to allow operational commands to focus on operation duties without the distraction of administrative functions.
Difference #3: Fighter Pilots
Despite the Navy having the main responsibility of protecting the US at sea, they also have fighter pilots.
Fighter pilots in the Navy are not the same as fighter pilots in the Air Force.
The training to become a fighter pilot in the Navy is shorter than training in the Air Force.
A large difference in fighter pilot training is that Navy members must become skilled in landing and taking off from an aircraft carrier.
Both have bases where they land aircraft in the United States, but the Air Force has more bases for aircraft to land, both in the United States and out of it.
Fighter pilots in the Navy and Air Force also fly different aircraft.
Related Article – Navy Undesignated Seaman (SN): Career Details
Difference #4: Promotions
Both the Air Force and the Navy follow the Congress recommendations for how many enlisted personnel can be on active duty and how many can be serving above an E-4.
For the Air Force, E-5 and above positions are competitive, and individuals must apply to open positions.
This means that an individual must take a position where someone has retired, been promoted, left for other reasons, or new positions have been allotted.
The Navy has also opened E-4 positions as competitive positions that must be applied for.
Lower promotions generally occur automatically based on time in service or time in rate, while higher ones will include a minimum time requirement in addition to testing requirements.
Additionally, the Navy does not have ranks, they are referred to as rates.
A pay grade and occupational specialty will determine an enlisted member's rate.
An important difference in the promotional process is the ability for Air Force members to enlist at higher ranks if they agree to a longer enlistment.
This is something that is not offered in the Navy.
Related Article: Air Force Ranks And Pay
Difference #5: National Guard and Reserve
Another difference between the Navy and the Air Force is their National Guard and Reserve components.
The Air Force has a National Guard, referred to as Air National Guard.
Air National Guard has 54 organizations between states, territories, and the District of Columbia.
The Navy does not have an official National Guard component.
Both the Navy and the Air Force have reserve components.
There are several differences between the reserve components including size, base locations, and specific jobs.
Navy and Air Force aircraft fly over the USS Kitty Hawk during a photo exercise. Image: wikimedia
It can be difficult to make a decision between the Navy vs. Air Force.
The Navy mainly supports operations in the sea but has a large air component as well.
The Air Force is responsible for protecting the United States through air operations, cyberspace, and space.
Above, we discussed what each branch does, what their responsibilities are, their size and their command structure.
Just as important, is the differences between the two branches.
Understanding what each branch does and what their differences may be will help make an informed decision on your future.
Related Article – Air Force Grooming Standards: Haircuts, Mustaches, Beards, And More
Status of the Navy
Military Unit Organization
About the Air Force
Air Force Demographics
Tagged air force or navy, air force vs navy, navy vs air force
Dave and Buster's Military Discount
KOA Campground Military Discount


text:
Liberty Men's Track Captures 10th-Straight Big South Indoor Title; Lady Flames Finish Second
For the 10th-consecutive season, the Liberty men's track and field team hoisted the team championship trophy at the New Balance Big South Indoor Track Championships presented by Mondo, UCS and the Stick on Sunday. Meanwhile, the Lady Flames finished as runner-up behind Coastal Carolina for the second-straight year at the event hosted by Clemson.
Liberty Men and Women Lead After Day One of Big South Indoor Track Championships
The Liberty men's and women's track and field teams both lead after the first day of competition at the New Balance Big South Indoor Track Championships presented by Mondo, UCS and the Stick. Four Flames took event titles on Saturday at Clemson.
Live Results, Video Streaming Available For Big South Indoor Track and Field Championships
Fans of the Liberty men's and women's track and field teams can follow the Flames' progress at Saturday and Sunday's Big South Conference Indoor Track and Field Championships through live results and video streaming, both of which will be available through the conference website.
McDougal Wins Second Big South Indoor Track Athlete of the Week Honor
Liberty junior Josh McDougal, who broke his own school and Big South record in the 5,000 meters at Saturday's Washington Husky Invitational, has been named the Big South Conference Choice Hotels Men's Indoor Track Athlete of the Week for the second time this season.
McDougal Breaks School 5K Record in Seattle
After two Liberty school records went down Friday during the Liberty Quad, a third was bettered Saturday afternoon at the Washington Husky Invitational. Junior Josh McDougal ran the fastest 5,000-meter time ever by a Flame athlete, indoors or outdoors, running a personal-best 13:52.13.
Beckles, Hart and Leineweber Set Records at Liberty Quad
Liberty athletes set a trio of records at Friday evening's Liberty Quad at the Tolsma Indoor Track Center in the Flames' final tune-up for next weekend's Big South Championships. Andrea Beckles (60-meter dash) and Jon Hart (weight throw) broke program records, and Philip Leineweber eclipsed the facility record at 400 meters.
Hart Receives Big South Indoor Track Athlete of the Week Award
For the second-consecutive week, a junior on the Liberty men's track and field team has been named Big South Conference Choice Hotels Men's Indoor Track Athlete of the Week. This time, the honoree is Jon Hart, who finished third in the weight throw at the New Balance Collegiate Invitational last Saturday.
Liberty Set to Host Final Conference Tune-Up; McDougal Brothers to Run in Seattle
The Liberty men's and women's track and field teams will host their final indoor meet of the season, the Liberty Quad, Friday evening at the Tolsma Indoor Track Center. While most of the Flames' athletes will tune up for the conference meet in Lynchburg this weekend, Josh and Jordan McDougal will chase a fast 5,000-meter time at the Washington Husky Classic on Saturday.


text:
Q: Does this postfix config cause open relay? [root@server ~]# postconf -n
alias_database = hash:/etc/aliases
alias_maps = hash:/etc/aliases
command_directory = /usr/sbin
config_directory = /etc/postfix
daemon_directory = /usr/libexec/postfix
data_directory = /var/lib/postfix
debug_peer_level = 2
debugger_command = PATH=/bin:/usr/bin:/usr/local/bin:/usr/X11R6/bin ddd $daemon_directory/$process_name $process_id & sleep 5
html_directory = no
inet_interfaces = localhost
inet_protocols = all
mail_owner = postfix
mailq_path = /usr/bin/mailq.postfix
manpage_directory = /usr/share/man
mydestination = $myhostname, localhost.$mydomain, localhost
mydomain = foo.bar.com
myhostname = server.foo.bar.com
mynetworks = 127.0.0.0/8
myorigin = $mydomain
newaliases_path = /usr/bin/newaliases.postfix
queue_directory = /var/spool/postfix
readme_directory = /usr/share/doc/postfix-2.10.1/README_FILES
relayhost = 1.2.3.4
sample_directory = /usr/share/doc/postfix-2.10.1/samples
sendmail_path = /usr/sbin/sendmail.postfix
setgid_group = postdrop
smtp_connect_timeout = 600s
smtp_tls_note_starttls_offer = yes
smtp_tls_security_level = may
unknown_local_recipient_reject_code = 550
[root@server ~]#
[root@server ~]# cat /etc/redhat-release
Red Hat Enterprise Linux Server release 7.2 (Maipo)
[root@server ~]#
[root@server ~]# rpm -qa|grep -i postfix
postfix-2.10.1-6.el7.x86_64
[root@server ~]#

Q: does this config cause an open relay? How could I know?

A: Does this config cause an open relay?
This question is a bit hard to answer without seeing the whole picture, the best way to find out is to test your config for open relay (more on that further down).
That being said let me make a note on
relayhost = 1.2.3.4

As per postfix documentation this is "The next-hop destination of non-local mail" so any mail that is not for local delivery will be sent to 1.2.3.4, which potentially can cause postfix (in conjunction with 1.2.3.4) to act as open relay.
Probably you have already looked at Postfix documentation, but let me give you some pointers.
This is a good starting point with few defaults with explanation of what each line does.
http://www.postfix.org/STANDARD_CONFIGURATION_README.html
This is also a good read regarding relay and access control.
http://www.postfix.org/SMTPD_ACCESS_README.html
How could I know?
You should really test you setup. There are number of online tools like http://mxtoolbox.com/diagnostic.aspx that will check if your server acts as open relay (obviusly for that you need configured and exposed to Internet server).
If your server isn't yet connected to Internet or if you want to test how your server acts for clients on the local network (mynetworks directive can specify trusted clients) you can use telnet to send emails and test for open relay.
Here is example (personal information obscured) where I try to send mail from gmail account to gmail account on server that has nothing to do with gmail. obviously the email was rejected.
[root@db ~]# telnet xxxx.domain.com 25
Trying 192.168.1.1...
Connected to xxxx.domain.com.
Escape character is '^]'.
220 mail.domain.com Microsoft ESMTP MAIL Service ready at Tue, 31 Jan 2017 12:45:31 +0200
helo localhost
250 xxxx.domain.com Hello [10.191.1.1]
mail from: filip.xxxx@gmail.com
250 2.1.0 Sender OK
rcpt to: filip.xxxx@gmail.com
550 5.7.1 Unable to relay
quit
221 2.0.0 Service closing transmission channel
Connection closed by foreign host.

In a well designed smtp server you will probably want to have clients authenticate before sending email through your server to the outside world or define trusted networks that can send email regardless (that is if you trust the users on your network).

redpajama_set_name: RedPajamaStackExchange


The Victoria camisole by Arianne Lingerie has elegant lace non-adjustable straps along with a lace trim adorning the hem. It is perfect to wear with your favorite pair of pants or a skirt. Made in Canada.


Lightweight Two-Tone Parka - ANNE WEYBURN Two-tone parka. A must-have early on in the season! Lined hood. Two-tone piping around the hood and along the zip fastening. Enclosed drawcord. Flap pockets. Long sleeves with two-tone permanent turn-ups on the cuffs. Braided inside.
Fabric: 100% polyester microfibre, water-repellent and stain-resistant.


Lavender - The familiar lavender fragrance. This one is sharp out of bottle, a little goes a long way. Needs a couple of days to cure to lose the sharpness. The hot scent throw is very pleasant and sweet.
Works very well at 1/4 oz per pound of wax!
Suggested Color: Lavender or purple.


Wednesday, Wednesday, October 01, 2014, 43 U.S. common stocks are scheduled to go ex-dividend. The dividend yields on these stocks range from 0.3% to 29%. All of these stocks can be found on our stocks going ex-dividend section of our dividend calendar.
Owners of American Municipal Income Portfolio (NYSE: XAA) shares, as of market close today, will be eligible for a dividend of 14 cents per share. At a price of $14.63 as of 3:59 p.m. ET, the dividend yield is 11.5%.
The average volume for American Municipal Income Portfolio has been 16,100 shares per day over the past 30 days. American Municipal Income Portfolio has a market cap of $83.2 million and is part of the financial services industry. Shares are up 12.1% year-to-date as of the close of trading on Friday.
The company has a P/E ratio of 14.17.
Owners of Voya Natural Resources Equity Income Fund (NYSE: IRR) shares, as of market close today, will be eligible for a dividend of 25 cents per share. At a price of $10.65 as of 9:34 a.m. ET, the dividend yield is 9.3%.
The average volume for Voya Natural Resources Equity Income Fund has been 84,600 shares per day over the past 30 days. Voya Natural Resources Equity Income Fund has a market cap of $246.8 million and is part of the financial services industry. Shares are up 7.5% year-to-date as of the close of trading on Monday.
Owners of AllianceBernstein Global High Income Fund I (NYSE: AWF) shares, as of market close today, will be eligible for a dividend of 8 cents per share. At a price of $13.44 as of 9:39 a.m. ET, the dividend yield is 7.2%.
The average volume for AllianceBernstein Global High Income Fund I has been 241,900 shares per day over the past 30 days. AllianceBernstein Global High Income Fund I has a market cap of $1.2 billion and is part of the financial services industry. Shares are down 6% year-to-date as of the close of trading on Monday.


text:
Deux femmes courant sur la plage (La course) (Two Women Running on the Beach (The Race)
Gouache on plywood
Musée national picasso
12 13/16 x 16 3/16 in
© Succession Picasso 2010 - Gestion droits d'auteur
Two Women Running on the Beach asserts itself in a post-war series of colossal figures with traditional religious connotations: a general reaction against the pre-war excesses and violent origins of Cubism and Expressionism. The vivid blues and the flowing hair of the women are anchored in their elongated, contorted yet supple limbs. There's a sense of fullness that makes the viewer feel that this is how life must be lived: fast paced and continuously, while war must be abandoned.


text:
<?php

namespace Cardinity\Method\Validators;

use Symfony\Component\Validator\Constraint;
use Symfony\Component\Validator\ConstraintValidator;
use Symfony\Component\Validator\Exception\UnexpectedTypeException;
use Symfony\Component\Validator\Exception\UnexpectedValueException;

class CallbackUrlConstraintValidator extends ConstraintValidator
{

    public function validate($value, Constraint $constraint) {
        if (!$constraint instanceof CallbackUrlConstraint) {
            throw new UnexpectedTypeException($constraint, CallbackUrlConstraint::class);
        }
        if (null === $value || '' === $value) {
            return;
        }
        if (!is_string($value)) {
            throw new UnexpectedValueException($value, 'string');
        }
        if (strpos($value, $constraint::RESTRICTED_DOMAIN) ||
            strpos($value, $constraint::RESTRICTED_IP)
        ) {
            $this->context->buildViolation($constraint->message)
                ->setParameter('{{ param }}', $value)
                ->addViolation();
        }
    }
}

redpajama_set_name: RedPajamaGithub


text:
Veterans-For-Change.org
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You are here: Home News Mental Health Care Must Teens With Autism Register for Selective Service?
Must Teens With Autism Register for Selective Service?
Published: 07 July 2018 | Written by Lisa Jo Rudy | Print	| Email	| Hits: 570
Parents may feel that their son with an autism spectrum diagnosis should be exempt from the American military, and from selective service registration. After all, autism is a sometimes-severe lifelong disability that impairs critical skills such as speech, social communication, and physical coordination.
But it's not that easy.
Registration Is Probably Required
Unless a young man is institutionalized, homebound, or "in such a physical or mental condition that he would not comprehend the nature of his registration with the Selective Service System," he is required to register with Selective Service.
While there are some young men with autism who would fit this description, most would not.
Here is how the military discusses the issue:
The only process now in effect is that men, between the ages of 18 through 25, register with Selective Service and keep their registration record current during that period. Neither the Military Selective Service Act nor the Presidential proclamation provide an exemption from registration because of a man's mental or physical condition unless Selective Service is provided with documented evidence that the man is hospitalized or institutionalized; or home-bound and unable to function outside the home, with or without physical assistance; or is in such a physical or mental condition that he would not comprehend the nature of his registration with the Selective Service System. A determination is then made by Selective Service as to whether or not the man qualifies for exemption from registration.
You may feel that your son meets this criteria because he is intellectually challenged or unable to respond verbally to your description of Selective Service. If that is the case, you would need written documentation from a doctor that supports your argument.
In the Event of a Draft...
While your son will very likely need to register for Selective Service, he is not automatically considered to be eligible for military service.
Rather, he is entering his information into a database of from which the military could potentially pull in the event of a draft. If, after review, your son doesn't meet the military's criteria, he will not be drafted.
Do People With Autism Meet Military Criteria?
While the military is slightly behind the times with their diagnostic information, it is safe to say that as of now people with autism spectrum disorders are not eligible for military service:
According to Department of Defense Instruction 6130.03 (Medical Standards for Appointment, Enlistment, or Induction in the Military Services) persons with the following would not be medically fit for military service: pervasive developmental disorders, including Asperger Syndrome, autistic spectrum disorders, and pervasive developmental disorder-not otherwise specified does not meet the standard by virtue of current diagnosis, or for which the candidate has a verified past medical history.
What If Someone With Autism Wants to Serve?
It seems likely that there are many people with the symptoms of autism spectrum disorder who not only serve but serve with distinction. It is unlikely, however, that those people were officially diagnosed by a medical professional.
A young adult with an autism diagnosis can certainly volunteer for the military and undergo evaluation. It is possible that, in certain situations, a waiver might be issued. In general, however, a verified diagnosis will probably mean he or she would be turned down.


text:
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Another Court Win for PSR November 19, 2020
Photo: WildEarth Guardians
In another court win for PSR, a federal court ruled that the U.S. Department of the Interior's Bureau of Land Management (BLM), in violation of federal law, failed to disclose the climate impacts of leasing more than 300,000 acres of public lands for fracking and oil and gas extraction in Wyoming.
The decision declares the sale of those oil and gas leases illegal and blocks future drilling on that acreage, which comes to 475 square miles.
PSR and our co-plaintiffs WildEarth Guardians and the Western Environmental Law Center initially won the lawsuit in March 2019. That ruling, issued by Judge Rudolph Contreras of the U.S. District Court for the District of Columbia, was hailed as a landmark victory for the climate.
However, in response, the BLM refused to comply with the court order, attempting to paper over its violations with a hasty climate assessment that sought to re-approve the same decision deemed illegal by the court.
This month, Judge Contreras found that BLM again failed to account for the climate consequences of selling public lands for oil and gas extraction. The judge stated that BLM's climate assessment was "a sloppy and rushed process" and fell "short of what NEPA [the National Environmental Policy Act] requires and what the Court ordered."
The Judge also ordered an injunction on drilling the oil and gas leases at issue, effectively banning new oil and gas development on the Wyoming public lands involved in the case.
This latest victory helps to cement the requirement that the federal government take into account the climate impacts of the drilling and fracking it allows on public lands. Leasing affords private companies the right to drill, frack, and produce oil and gas, the burning of which contributes heavily to climate change.
The ruling is further significant because, while centered on Wyoming, it implicates federal oil and gas leasing on public lands across the country. It found, among other things, that BLM failed to properly account for oil and gas leasing occurring beyond Wyoming, including in neighboring states. Judge Contreras faulted the agency for "[f]ailing to analyze the lease sales in the region, and other reasonably foreseeable lease sales in the country."
PSR is proud to have placed a significant roadblock in the path of the Trump administration's "energy dominance" agenda, which prioritized fossil fuel extraction on public lands and waters in the U.S. Under President Trump, the Department of the Interior and BLM have fast-tracked leasing, selling millions of acres to oil and gas companies, mostly in the American West.
A 2018 U.S. Geological Survey report found that oil and gas produced from public lands and waters contributes to 10 percent of all U.S. greenhouse gas emissions. A 2018 report by the Stockholm Environmental Institute also confirmed that ending public lands fossil fuel production could significantly reduce nationwide greenhouse gas emissions.
Ending the sale of public lands for fracking would also yield enormous health benefits. Besides impacting the climate, the fracking Compendium released in June 2019 by PSR and Concerned Health Professionals of New York documented extensive health risks associated with oil and gas extraction, including cancer, asthma, pre-term birth, and more.
President-elect Biden has explicitly committed to ending oil and gas leasing as part of his climate and clean energy agenda. Biden has pledged that on Day One of his administration, he will ban oil and gas leasing on public lands and waters across the U.S.
WildEarth Guardians, Physicians for Social Responsibility, and the Western Environmental Law Center have been at the forefront of defending the climate from rampant oil and gas leasing on public lands in the American West.
In addition to the current case, the groups filed suit in January 2020 over nearly two million acres of oil and gas leasing under the Trump administration. This fall, the Bureau acknowledged the failures of its decisions and sought a voluntary remand for nearly all of those leased lands, which was granted by the court. The few remaining leases in that case remain pending.
Campaign Update
climate change, environment & health, federal government, fracking & methane
More Campaign Update
Scientists and experts warn us humanity is closer to 'doomsday' than ever before
On January 24, 2023, the Bulletin of the Atomic Scientists unveiled the new setting of their Doomsday Clock. The Doomsday Clock serves as a warning...
Looking Ahead: What to Expect in the World of Nuclear Weapons Abolition in the New Year
2023 is right around the corner, and PSR is here to give you a sneak peak at what to expect in January 2023. Keep reading...
PSR Board Member, Natasha DeJarnett, PhD, Accepts White House Fellowship
We are thrilled to announce that PSR Board Member Natasha DeJarnett, PhD is joining the White House Council on Environmental Quality. There, Dr. DeJarnett will...
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