Development in helicopter tail boom strake applications in the US

The use of a strake or spoiler on a helicopter tail boom to beneficially change helicopter tail boom air loads was suggested in the United States in 1975. The anticipated benefits were a change of tail boom loads to reduce required tail rotor thrust and power and improve directional control. High tail boom air loads experienced by the YAH-64 and described in 1978 led to a wind tunnel investigation of the usefullness of strakes in altering such loads on the AH-64, UH-60, and UH-1 helicopters. The wind tunnel tests of 2-D cross sections of the tail boom of each demonstrated that a strake or strakes would be effective. Several limited test programs with the U.S. Army's OH-58A, AH-64, and UH-60A were conducted which showed the effects of strakes were modest for those helicopters. The most recent flight test program, with a Bell 204B, disclosed that for the 204B the tail boom strake or strakes would provide more than a modest improvement in directional control and reduction in tail rotor power

Burden of Psychosocial and Cognitive Impairment in Patients With Atrial Fibrillation

BACKGROUND: Impairments in psychosocial status and cognition relate to poor clinical outcomes in patients with atrial fibrillation (AF). However, how often these conditions co-occur and associations between burden of psychosocial and cognitive impairment and quality of life (QoL) have not been systematically examined in patients with AF. METHODS: A total of 218 patients with symptomatic AF were enrolled in a prospective study of AF and psychosocial factors between May 2013 and October 2014 at the University of Massachusetts Medical Center. Cognitive function, depression, and anxiety were assessed at baseline and AF-specific QoL was assessed 6 months after enrollment using validated instruments. Demographic and clinical information were obtained from a structured interview and medical record review. RESULTS: The mean age of the study participants was 63.5 +/- 10.2 years, 35% were male, and 81% had paroxysmal AF. Prevalences of impairment in 1, 2, and 3 psychosocial/cognitive domains (eg, depression, anxiety, or cognition) were 75 (34.4%), 51 (23.4%), and 16 (7.3%), respectively. Patients with co-occurring psychosocial/cognitive impairments (eg, \u3e 1 domain) were older, more likely to smoke, had less education, and were more likely to have heart failure (all P \u3c 0.05). Compared with participants with no psychosocial/cognitive impairments, AF-specific QoL at 6 months was significantly poorer among participants with baseline impairment in 2 (B = -13.6, 95% CI: -21.7 to -5.4) or 3 (B = -15.1, 95% CI: -28.0 to -2.2) psychosocial/cognitive domains. CONCLUSION: Depression, anxiety, and impaired cognition were common in our cohort of patients with symptomatic AF and often co-occurred. Higher burden of psychosocial/cognitive impairment was associated with poorer AF-specific QoL

Effect of Left Atrial Function Index on Late Atrial Fibrillation Recurrence after Pulmonary Vein Isolation

Background: Although the rates of catheter ablation (CA) for atrial fibrillation (AF) are rapidly increasing, there are few predictors of outcome to help inform appropriate patient selection for this procedure. Traditional echocardiographic measures of atrial structure do not significantly reclassify risk of AF recurrence over and above the clinical risk factors. Left Atrial Function Index (LAFI) is a rhythm-independent measure of atrial function. We hypothesized that baseline LAFI would relate to AF recurrence after CA. Methods: Pre-procedural echocardiograms from 170 participants, who underwent CA for AF and were enrolled in the UMMC AF Treatment Registry, were analyzed. LAFI was calculated by a previously validated formula. Primary outcome was late or clinically significant AF recurrence 3-12 months after CA. Baseline clinical, laboratory and echocardiographic variables were compared between the recurrence and non-recurrence groups. Results: Study participants were middle aged (60+/10 years) and had a moderate-to-severe burden of cardiovascular comorbidities. 78 participants (46%) experienced late AF recurrence. Mean LAFI was 0.26+/-0.18. In multivariate analysis, lower LAFI was independently associated with the risk of recurrence (0.23 in recurrence group vs 0.29 in non-recurrence group, p \u3c 0.01). Predictive value of LAFI for AF recurrence was similar to CHADS2 score (c-statistic 0.60 vs 0.58, p 0.76). In subgroup of patients with persistent AF, LAFI predicted AF recurrence more strongly than CHADS2 score (c-statistic: 0.79 vs 0.58, p 0.02). Conclusions: In our cohort of 170 participants with AF undergoing index CA ablation, we observed that LAFI related to late AF recurrence after CA, independent of the traditional risk factors. Since LAFI can be calculated from almost any traditional echocardiographic recording, our findings suggest that LAFI may help guide therapeutic decision-making regarding application of CA, particularly among challenging patients with symptomatic persistent AF

Addition of B-Type Natriuretic Peptide to Existing Clinical Risk Scores Enhances Identification of Patients at Risk for Atrial Fibrillation Recurrence After Pulmonary Vein Isolation

INTRODUCTION: Predicting which patients will be free from atrial fibrillation (AF) after pulmonary vein isolation (PVI) remains challenging. Clinical risk prediction scores show modest ability to identify patients at risk for AF recurrence after PVI. B-type natriuretic peptide (BNP) is associated with risk for incident and recurrent AF but is not currently included in existing AF risk scores. We sought to evaluate the incremental benefit of adding preoperative BNP to existing risk scores for predicting AF recurrence during the 6 months after PVI. METHODS: One hundred sixty-one patients with paroxysmal or persistent AF underwent an index PVI procedure between 2010 and 2013; 77 patients (48%) had late AF recurrence after PVI ( \u3e 3 months post-PVI) over the 6-month follow-up period. RESULTS: A BNP greater than or equal to 100 pg/dL (P = 0.01) and AF recurrence within 3 months after PVI (P \u3c 0.001) were associated with late AF recurrence in multivariate analyses. Addition of BNP to existing clinical risk scores significantly improved the areas under the curve for each score, with an integrated discrimination improvement of 0.08 (P = 0.001) and a net reclassification improvement of 60% (P = 0.001) for all risk scores. CONCLUSIONS: Circulating BNP levels are independently associated with late AF recurrence after PVI. Inclusion of BNP significantly improves the discriminative ability of CHADS2, CHA2DS2-VASc, R2CHADS2, and the HATCH score in predicting clinically significant, late AF recurrence after PVI and should be incorporated in decision-making algorithms for management of AF. B-R2CHADS2 is the best score model for prediction of late AF recurrence

Integration-specific In Vitro Evaluation of Lentivirally Transduced Rhesus CD34+ Cells Correlates With In Vivo Vector Copy Number

Hematopoietic stem cell (HSC) gene therapy using integrating vectors has a potential leukemogenic risk due to insertional mutagenesis. To reduce this risk, a limitation of ≤2 average vector copy number (VCN) per cell is generally accepted. We developed an assay for VCN among transduced CD34+ cells that reliably predicts in vivo VCN in 16 rhesus recipients of CD34+ cells transduced with a green fluorescent protein (GFP) (or yellow fluorescent protein (YFP))-encoding lentiviral vector. Using GFP (or YFP)-specific probe/primers by real-time PCR, VCN among transduced CD34+ cells had no correlation with VCN among granulocytes or lymphocytes in vivo assayed 6 months post-transplantation. This was a likely result of residual plasmids present in the vector preparation. We then designed self-inactivating long terminal repeat (SIN-LTR)-specific probe/primers, which detect only integrated provirus. Evaluation with SIN-LTR probe/primers resulted in a positive correlation of VCN among transduced CD34+ cells with granulocytes and lymphocytes in vivo. The transduced CD34+ cells had higher VCN (25.1 ± 5.6) as compared with granulocytes (2.8 ± 1) and lymphocytes (2.4 ± 0.7). In summary, an integrated provirus-specific real-time PCR system demonstrated nine- to tenfold higher VCN in transduced CD34+ cells in vitro, as compared with VCN in vivo. Therefore, the restriction of ≤2 VCN before infusion might unnecessarily limit gene transfer efficacy

Dynamics of HSPC repopulation in nonhuman primates revealed by a decade-long clonal-tracking study.

In mice, clonal tracking of hematopoietic stem cells (HSCs) has revealed variations in repopulation characteristics. However, it is unclear whether similar properties apply in primates. Here, we examined this issue through tracking of thousands of hematopoietic stem and progenitor cells (HSPCs) in rhesus macaques for up to 12 years. Approximately half of the clones analyzed contributed to long-term repopulation (over 3-10 years), arising in sequential groups and likely representing self-renewing HSCs. The remainder contributed primarily for the first year. The long-lived clones could be further subdivided into functional groups contributing primarily to myeloid, lymphoid, or both myeloid and lymphoid lineages. Over time, the 4%-10% of clones with robust dual lineage contribution predominated in repopulation. HSPCs expressing a CCR5 shRNA transgene behaved similarly to controls. Our study therefore documents HSPC behavior in a clinically relevant model over a long time frame and provides a substantial system-level data set that is a reference point for future work

Dynamics of HSPC repopulation in nonhuman primates revealed by a decade-long clonal-tracking study.

In mice, clonal tracking of hematopoietic stem cells (HSCs) has revealed variations in repopulation characteristics. However, it is unclear whether similar properties apply in primates. Here, we examined this issue through tracking of thousands of hematopoietic stem and progenitor cells (HSPCs) in rhesus macaques for up to 12 years. Approximately half of the clones analyzed contributed to long-term repopulation (over 3-10 years), arising in sequential groups and likely representing self-renewing HSCs. The remainder contributed primarily for the first year. The long-lived clones could be further subdivided into functional groups contributing primarily to myeloid, lymphoid, or both myeloid and lymphoid lineages. Over time, the 4%-10% of clones with robust dual lineage contribution predominated in repopulation. HSPCs expressing a CCR5 shRNA transgene behaved similarly to controls. Our study therefore documents HSPC behavior in a clinically relevant model over a long time frame and provides a substantial system-level data set that is a reference point for future work