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The investigators hypothesize that chronic insufficient sleep is associated with diminished endothelium-dependent nitric oxide-mediated vasodilation and tissue-type plasminogen activator release in anti-retroviral (ART)-treated HIV-1-seropositive adults. Furthermore, the investigators hypothesize that the postulated diminishment in endothelial vasodilator and fibrinolytic function with insufficient sleep will be due, at least in part, to increased oxidative stress. Moreover, increasing sleep duration and improving sleep quality will increase both endothelium-dependent nitric oxide-mediated vasodilation and endothelial tissue-type plasminogen activator release in ART-treated HIV-1-seropositive adults. Increases in endothelial vasodilator and fibrinolytic function will be due, at least in part, to reduced oxidative stress.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase 1 | No Intervention | Phase 1 is a cross-sectional study to compare endothelial vasodilator and fibrinolytic function in ART-treated HIV-1-seropositive adults who habitually sleep more than 7 hours/night (normal sleep) and those who habitually sleep less than 7 hours/night (short sleep). | |
| Phase 2 | Experimental | Phase 2 is an intervention study to determine the effects of individualized targeted sleep interventions that increase sleep duration and improve sleep quality on endothelial vasodilator and fibrinolytic function in ART-treated HIV-1-seropositive adults who habitually sleep less than 7 hours/night. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Individualized Targeted Sleep | Behavioral | The investigators will employ an 8-week individualized targeted sleep intervention. Individualized targeted interventions have the advantage of improving adherence, reducing attrition, and making the strategy personally meaningful. |
| Measure | Description | Time Frame |
|---|---|---|
| Phase 1: Forearm Blood Flow (FBF) Response to Acetylcholine (ACh) | FBF was measured via strain-gauge venous occlusion plethysmography in response to saline for 5 minutes and then to ACh (4.0, 8.0 and 16.0 ug/100 mL tissue/min; the doses of Acetylcholine infused into the brachial artery) for 5 minutes at each dose. Flows during the last minute of saline and each drug dose were measured and the mean value reported. Values after saline and after ACh 4.0, 8.0 and 16.0 at week 3 are reported. | FBF response to ACh will be measured during Phase 1 at the participants visit 3 which is ~3 weeks from their respective start date. |
| Phase 2: FBF Response to Acetylcholine (ACh) | FBF to ACh will be measured following the participants 8 week sleep intervention. | FBF response to ACh will be measured during Phase 2 at the participants visit 9 which is ~11 weeks from their respective start date |
| Phase 1: Forearm Blood Flow (FBF) Response to Sodium Nitroprusside (NTP) | FBF response to NTP will be measured during Phase 1 at the participants visit 3 which is ~3 weeks from their respective start date. | |
| Phase 2: Forearm Blood Flow (FBF) Response to Sodium Nitroprusside (NTP) | FBF to NTP will me measured following the participants 8 week sleep intervention | FBF response to NTP will be measured during Phase 2 at the participants visit 9 which is ~11 weeks from their respective start date |
| Phase 1: Endothelial Tissue Type Plasminogen Activator (t-PA) Release in Response to Bradykinin (BDK) | Net endothelial release of t-PA antigen in response to BDK was calculated using the following equation: Net release = (Cv-Ca) x (FBF x [101-hematocrit/100]) where Cv and Ca represent the concentration in the vein and artery respectively. A positive difference indicated a net release and a negative difference, net uptake. Arterial and venous blood samples were collected simultaneously at the end of saline and each dose of BDK (12.5, 25.0 and 50.0 ng/100mL tissue/min). Enzyme immunoassay was used to determine t-PA antigen concentrations. Hematocrit was measured in triplicate using the standard microhematocrit technique and corrected for trapped plasma volume within the red blood cells. |
| Measure | Description | Time Frame |
|---|---|---|
| Nightly Sleep Duration | Nightly sleep duration was calculated as the weighted average of weeknights and weekend values [(5 x weekday sleep duration)+(2 x weekend sleep duration)/7]. | Baseline |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Christopher DeSouza, PhD | University of Colorado, Boulder | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UC-Boulder Clinical and Translational Research Center | Boulder | Colorado | 80309 | United States |
Based on the participants nightly sleep duration they were enrolled either in Phase 1: No Intervention: Normal Sleep Group or Phase 1: No Intervention: Short Sleep Group. 10 participants with short nightly sleep duration were recruited separately and enrolled into Phase 2. After participants sign the informed consent, they complete a blood draw and a graded exercise stress test.
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| ID | Title | Description |
|---|---|---|
| FG000 | No Intervention: Phase 1 Normal Sleep Group | Phase 1 is a cross-sectional study designed to compare endothelial vasodilator (forearm blood flow) and fibrinolytic function (t-PA release) in ART-treated HIV-1-seropositive adults who habitually sleep more than 7 hours/night (normal sleep) and those who habitually sleep less than 7 hours/night (short sleep). |
| FG001 | No Intervention: Phase 1 Short Sleep Group | Phase 1 is a cross-sectional study designed to compare endothelial vasodilator (forearm blood flow) and fibrinolytic function (t-PA release) in ART-treated HIV-1-seropositive adults who habitually sleep more than 7 hours/night (normal sleep) and those who habitually sleep less than 7 hours/night (short sleep). |
| FG002 | Experimental: Phase 2 | Phase 2 is an intervention study designed to determine the effects of individualized targeted sleep interventions that increase sleep duration and improve sleep quality on endothelial vasodilator (forearm blood flow) and fibrinolytic function (t-PA release) in ART-treated HIV-1-seropositive adults who habitually sleep less than 7 hours/night. . |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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After participants sign the informed consent, they complete a blood draw and a graded exercise stress test. Based on the participants nightly sleep duration they were either in Phase 1: No Intervention: Normal Sleep Group or Phase 1: No Intervention: Short Sleep Group. 10 participants with short nightly sleep duration were recruited separately and enrolled in Phase 2. These 10 participants are only counted in the Phase 2 Sleep Intervention Study.
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| ID | Title | Description |
|---|---|---|
| BG000 | No Intervention: Phase 1 Normal Sleep Group | Phase 1 is a cross-sectional study designed to compare endothelial vasodilator (forearm blood flow) and fibrinolytic function (t-PA release) in ART-treated HIV-1-seropositive adults who habitually sleep more than 7 hours/night (normal sleep) and those who habitually sleep less than 7 hours/night (short sleep). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Phase 1: Forearm Blood Flow (FBF) Response to Acetylcholine (ACh) | FBF was measured via strain-gauge venous occlusion plethysmography in response to saline for 5 minutes and then to ACh (4.0, 8.0 and 16.0 ug/100 mL tissue/min; the doses of Acetylcholine infused into the brachial artery) for 5 minutes at each dose. Flows during the last minute of saline and each drug dose were measured and the mean value reported. Values after saline and after ACh 4.0, 8.0 and 16.0 at week 3 are reported. | The number or participants analyzed is different than the participant flow module as these are the participants who completed visit 3. | Posted | Mean | Standard Error | mL/100 mL tissue/min | FBF response to ACh will be measured during Phase 1 at the participants visit 3 which is ~3 weeks from their respective start date. |
|
Data was collected for participants while they were enrolled in the study. Each participant was in the study for a maximum of 4 months.
For simplicity in the reporting of the results with regards to the Adverse Event Table, Phase 1 the normal sleep duration group and the short sleep duration group are combined since no adverse events occurred or were reported.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Phase 1: Cross-sectional Study | Phase 1 is a cross-sectional study to compare endothelial vasodilator (forearm blood flow) and fibrinolytic function (t-PA release) in ART-treated HIV-1-seropositive adults who habitually sleep more than 7 hours/night (normal sleep) and those who habitually sleep less than 7 hours/night (short sleep). |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Christopher DeSouza Ph.D. | University of Colorado | 303-492-2988 | desouzac@colorado.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 8, 2018 | Nov 5, 2021 | Prot_SAP_000.pdf |
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| t-PA release will be measured during Phase 1 at the participants visit 3 which is ~3 weeks from their respective start date. |
| Phase 2: Endothelial t-PA Release in Response to Bradykinin (BDK) | Endothelial t-PA release will me measured following the participants 8 week sleep intervention. Net endothelial release of t-PA antigen in response to BDK was calculated using the following equation: Net release = (Cv-Ca) x (FBF x [101-hematocrit/100]) where Cv and Ca represent the concentration in the vein and artery respectively. A positive difference indicated a net release and a negative difference, net uptake. Arterial and venous blood samples were collected simultaneously at the end of saline and each dose of BDK (12.5, 25.0 and 50.0 ng/100mL tissue/min). Enzyme immunoassay was used to determine t-PA antigen concentrations. Hematocrit was measured in triplicate using the standard microhematocrit technique and corrected for trapped plasma volume within the red blood cells. | t-PA release will be measured during Phase 2 at the participants visit 9 which is ~11 weeks from their respective start date |
| Phase 1: FBF Response to ACh+Ng-monomethyl-L-arginine (L-NMMA) | To determine the contribution of nitric oxide to ACh-mediated vasodilation, FBF to ACh was quantified before and after infusion of L-NMMA. After ACh was infused as described in Outcome measure 1 the ACh dose response was repeated with the continuous infusion of L-NMMA. | FBF response to ACh+L-NMMA will be measured during Phase 1 at the participants visit 3 which is ~3 weeks from their respective start date. |
| Phase 1: FBF Response to ACh+Vitamin C | After allowing sufficient time (45 minutes) for FBF to return to levels similar to that of saline Vitamin C was infused at a constant rate (12 mg/100 mL tissue/min) for 5 minutes. This vitamin C concentration has been show to improve endothelium dependent vasodilation in conditions associated with oxidative stress. Vitamin C infusion was maintained at the same rate while the ACh dose response was repeated. | FBF response to ACh+Vitamin C will be measured during Phase 1 at the participants visit 3 which is ~3 weeks from their respective start date. |
| Phase 2: FBF Response to ACh+L-NMMA | FBF to ACh+L-NMMA will me measured following the participants 8 week sleep intervention. To determine the contribution of nitric oxide to ACh-mediated vasodilation, FBF to ACh was quantified before and after infusion of L-NMMA. After ACh was infused as described in Outcome measure 1 the ACh dose response was repeated with the continuous infusion of L-NMMA. | FBF response to ACh+L-NMMA will be measured during Phase 2 at the participants visit 9 which is ~11 weeks from their respective start date |
| Phase 2: FBF Response to ACh+Vitamin C | FBF to ACh+Vitamin C will me measured following the participants 8 week sleep intervention. After allowing sufficient time (45 minutes) for FBF to return to levels similar to that of saline Vitamin C was infused at a constant rate (12 mg/100 mL tissue/min) for 5 minutes. This vitamin C concentration has been show to improve endothelium dependent vasodilation in conditions associated with oxidative stress. Vitamin C infusion was maintained at the same rate while the ACh dose response was repeated. | FBF response to ACh+Vitamin C will be measured during Phase 2 at the participants visit 9 which is ~11 weeks from their respective start date |
| BG001 |
| No Intervention: Phase 1 Short Sleep Group |
Phase 1 is a cross-sectional study designed to compare endothelial vasodilator (forearm blood flow) and fibrinolytic function (t-PA release) in ART-treated HIV-1-seropositive adults who habitually sleep more than 7 hours/night (normal sleep) and those who habitually sleep less than 7 hours/night (short sleep). |
| BG002 | Experimental: Phase 2 Sleep Intervention Study | Phase 2 is an intervention study designed to determine the effects of individualized targeted sleep interventions that increase sleep duration and improve sleep quality on endothelial vasodilator (forearm blood flow) and fibrinolytic function (t-PA release) in ART-treated HIV-1-seropositive adults who habitually sleep less than 7 hours/night. |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Short Sleep Duration | Short Sleep Duration group slept <7h/night. |
|
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| Primary | Phase 2: FBF Response to Acetylcholine (ACh) | FBF to ACh will be measured following the participants 8 week sleep intervention. | Posted | Mean | Standard Error | mL/100 mL tissue/min | FBF response to ACh will be measured during Phase 2 at the participants visit 9 which is ~11 weeks from their respective start date |
|
|
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| Primary | Phase 1: Forearm Blood Flow (FBF) Response to Sodium Nitroprusside (NTP) | The number or participants analyzed is different than the participant flow module due to availability of Sodium Nitroprusside. | Posted | Mean | Standard Error | mL/100 mL tissue/min | FBF response to NTP will be measured during Phase 1 at the participants visit 3 which is ~3 weeks from their respective start date. |
|
|
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| Primary | Phase 2: Forearm Blood Flow (FBF) Response to Sodium Nitroprusside (NTP) | FBF to NTP will me measured following the participants 8 week sleep intervention | Posted | Mean | Standard Error | mL/100 mL tissue/min | FBF response to NTP will be measured during Phase 2 at the participants visit 9 which is ~11 weeks from their respective start date |
|
|
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| Primary | Phase 1: Endothelial Tissue Type Plasminogen Activator (t-PA) Release in Response to Bradykinin (BDK) | Net endothelial release of t-PA antigen in response to BDK was calculated using the following equation: Net release = (Cv-Ca) x (FBF x [101-hematocrit/100]) where Cv and Ca represent the concentration in the vein and artery respectively. A positive difference indicated a net release and a negative difference, net uptake. Arterial and venous blood samples were collected simultaneously at the end of saline and each dose of BDK (12.5, 25.0 and 50.0 ng/100mL tissue/min). Enzyme immunoassay was used to determine t-PA antigen concentrations. Hematocrit was measured in triplicate using the standard microhematocrit technique and corrected for trapped plasma volume within the red blood cells. | The number of participants analyzed is different than reported in the participant flow module due to the availability of BDK during the clinical trial. | Posted | Mean | Standard Error | ng/100 mL tissue/min | t-PA release will be measured during Phase 1 at the participants visit 3 which is ~3 weeks from their respective start date. |
|
|
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| Primary | Phase 2: Endothelial t-PA Release in Response to Bradykinin (BDK) | Endothelial t-PA release will me measured following the participants 8 week sleep intervention. Net endothelial release of t-PA antigen in response to BDK was calculated using the following equation: Net release = (Cv-Ca) x (FBF x [101-hematocrit/100]) where Cv and Ca represent the concentration in the vein and artery respectively. A positive difference indicated a net release and a negative difference, net uptake. Arterial and venous blood samples were collected simultaneously at the end of saline and each dose of BDK (12.5, 25.0 and 50.0 ng/100mL tissue/min). Enzyme immunoassay was used to determine t-PA antigen concentrations. Hematocrit was measured in triplicate using the standard microhematocrit technique and corrected for trapped plasma volume within the red blood cells. | Posted | Mean | Standard Error | ng/100 mL tissue/min | t-PA release will be measured during Phase 2 at the participants visit 9 which is ~11 weeks from their respective start date |
|
|
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| Primary | Phase 1: FBF Response to ACh+Ng-monomethyl-L-arginine (L-NMMA) | To determine the contribution of nitric oxide to ACh-mediated vasodilation, FBF to ACh was quantified before and after infusion of L-NMMA. After ACh was infused as described in Outcome measure 1 the ACh dose response was repeated with the continuous infusion of L-NMMA. | Posted | Mean | Standard Error | mL/100 mL tissue/min | FBF response to ACh+L-NMMA will be measured during Phase 1 at the participants visit 3 which is ~3 weeks from their respective start date. |
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| Primary | Phase 1: FBF Response to ACh+Vitamin C | After allowing sufficient time (45 minutes) for FBF to return to levels similar to that of saline Vitamin C was infused at a constant rate (12 mg/100 mL tissue/min) for 5 minutes. This vitamin C concentration has been show to improve endothelium dependent vasodilation in conditions associated with oxidative stress. Vitamin C infusion was maintained at the same rate while the ACh dose response was repeated. | Posted | Mean | Standard Error | mL/100 mL tissue/min | FBF response to ACh+Vitamin C will be measured during Phase 1 at the participants visit 3 which is ~3 weeks from their respective start date. |
|
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| Primary | Phase 2: FBF Response to ACh+L-NMMA | FBF to ACh+L-NMMA will me measured following the participants 8 week sleep intervention. To determine the contribution of nitric oxide to ACh-mediated vasodilation, FBF to ACh was quantified before and after infusion of L-NMMA. After ACh was infused as described in Outcome measure 1 the ACh dose response was repeated with the continuous infusion of L-NMMA. | Posted | Mean | Standard Error | mL/100 mL tissue/min | FBF response to ACh+L-NMMA will be measured during Phase 2 at the participants visit 9 which is ~11 weeks from their respective start date |
|
|
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| Primary | Phase 2: FBF Response to ACh+Vitamin C | FBF to ACh+Vitamin C will me measured following the participants 8 week sleep intervention. After allowing sufficient time (45 minutes) for FBF to return to levels similar to that of saline Vitamin C was infused at a constant rate (12 mg/100 mL tissue/min) for 5 minutes. This vitamin C concentration has been show to improve endothelium dependent vasodilation in conditions associated with oxidative stress. Vitamin C infusion was maintained at the same rate while the ACh dose response was repeated. | Posted | Mean | Standard Error | mL/100 mL tissue/min | FBF response to ACh+Vitamin C will be measured during Phase 2 at the participants visit 9 which is ~11 weeks from their respective start date |
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| Secondary | Nightly Sleep Duration | Nightly sleep duration was calculated as the weighted average of weeknights and weekend values [(5 x weekday sleep duration)+(2 x weekend sleep duration)/7]. | Nightly sleep duration was measured during Phase 1 at the participants initial visit. | Posted | Mean | Standard Error | hours/night | Baseline |
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|
| 0 |
| 78 |
| 0 |
| 78 |
| 0 |
| 78 |
| EG001 | Phase 2: Intervention Study | Phase 2 is an intervention study to determine the effects of individualized targeted sleep interventions that increase sleep duration and improve sleep quality on endothelial vasodilator (forearm blood flow) and fibrinolytic function (t-PA release) in ART-treated HIV-1-seropositive adults who habitually sleep less than 7 hours/night (short sleep). Participants from phase 1 were invited to take part in phase 2. | 0 | 10 | 0 | 10 | 0 | 10 |
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| Ach 8.0 |
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| Ach 16.0 |
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| NTP 2.0 |
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| NTP 4.0 |
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| NTP 2.0 |
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| NTP 4.0 |
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| BDK 25.0 |
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| BDK 50.0 |
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| BDK 25.0 |
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| BDK 50.0 |
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| ACh 4.0 |
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| ACh 8.0 |
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| ACh 16.0 |
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| Ach 4.0 |
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| Ach 8.0 |
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| Ach 16.0 |
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| ACh 4.0 |
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| ACh 8.0 |
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| ACh 16.0 |
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| ACh 4.0 |
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| ACh 8.0 |
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| ACh 16.0 |
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