Comparison of anatomy-based, fluence-based and aperture-based treatment planning approaches for VMAT

Volumetric modulated arc therapy (VMAT) has the potential to reduce treatment times while producing comparable or improved dose distributions relative to fixed-field intensity-modulated radiation therapy. In order to take full advantage of the VMAT delivery technique, one must select a robust inverse planning tool. The purpose of this study was to evaluate the effectiveness and efficiency of VMAT planning techniques of three categories: anatomy-based, fluence-based and aperture-based inverse planning. We have compared these techniques in terms of the plan quality, planning efficiency and delivery efficiency. Fourteen patients were selected for this study including six head-and-neck (HN) cases, and two cases each of prostate, pancreas, lung and partial brain. For each case, three VMAT plans were created. The first VMAT plan was generated based on the anatomical geometry. In the Elekta ERGO++ treatment planning system (TPS), segments were generated based on the beam's eye view (BEV) of the target and the organs at risk. The segment shapes were then exported to Pinnacle TPS followed by segment weight optimization and final dose calculation. The second VMAT plan was generated by converting optimized fluence maps (calculated by the Pinnacle TPS) into deliverable arcs using an in-house arc sequencer. The third VMAT plan was generated using the Pinnacle SmartArc IMRT module which is an aperture-based optimization method. All VMAT plans were delivered using an Elekta Synergy linear accelerator and the plan comparisons were made in terms of plan quality and delivery efficiency. The results show that for cases of little or modest complexity such as prostate, pancreas, lung and brain, the anatomy-based approach provides similar target coverage and critical structure sparing, but less conformal dose distributions as compared to the other two approaches. For more complex HN cases, the anatomy-based approach is not able to provide clinically acceptable VMAT plans while highly conformal dose distributions were obtained using both aperture-based and fluence-based inverse planning techniques. The aperture-based approach provides improved dose conformity than the fluence-based technique in complex cases.     

Improved HIV-related outcomes associated with implementation of a novel public health information exchange

PurposeThe purpose of this study was to evaluate HIV-related outcomes associated with use of a novel public health information exchange that was designed to identify out of care HIV-infected individuals seen within a large, integrated delivery network (IDN).MethodsA novel, secure, bidirectional health care delivery-public health information exchange, the Louisiana Public Health Information Exchange (LaPHIE) was developed between a multi-geographical IDN and the Louisiana public health authority in response to the high proportion of out of care HIV-infected persons. The system provides real-time provider alerts when any HIV-infected person who has not had CD4 or HIV viral load (VL) monitoring in >1 year receives non-HIV care within the IDN, allowing immediate linkage to HIV specialty care. Persons identified over the first 30 months of the system's implementation were characterized using a case-cohort approach to compare out-of-care individuals with randomly sampled, time-matched in-care controls.ResultsBetween 2/1/09 and 7/31/11, 549 alerts identified 419 unduplicated HIV-infected individuals without a CD4 count or VL in >1 year. Patients were identified at 60 clinics and alerts shown to 223 clinicians in 7 participating facilities. A quarter (24%) of those identified had not had a CD4 count or VL conducted since their initial diagnosis. Of the remaining 76% who had been in care previously, over half (55%) had been out of care for ≥18 months, with a median time of 19.4 months [IQR 15.0–32.5] since their previous visit. Following LaPHIE identification, 42% had CD4 counts < 200 cells/mm³ and 62% had VL > 10,000 RNA copies/mL. Of the 344 patients with at least 6 months of follow up, 85% had at least one CD4 and/or VL test after being identified.ConclusionsThe results of this study demonstrate that an information exchange can effectively facilitate engagement, re-engagement, and retention of out-of care HIV-infected persons in HIV specialty care. Within two years, we were able to observe significant improvements in HIV-related utilization and disease progression indices. Future programs should consider adopting this innovative strategy to improve HIV care at both the individual and population levels.     

Blockade of SK-type Ca2+-activated K+ channels uncovers a Ca2+-dependent slow afterdepolarization in nigral dopamine neurons

Sharp electrode current-clamp recording techniques were used to characterize the response of nigral dopamine (DA)-containing neurons in rat brain slices to injected current pulses applied in the presence of TTX (2 microM) and under conditions in which apamin-sensitive Ca2+-activated K+ channels were blocked. Addition of apamin (100-300 nM) to perfusion solutions containing TTX blocked the pacemaker oscillation in membrane voltage evoked by depolarizing current pulses and revealed an afterdepolarization (ADP) that appeared as a shoulder on the falling phase of the voltage response. ADP were preceded by a ramp-shaped slow depolarization and followed by an apamin-insensitive hyperpolarizing afterpotential (HAP). Although ADPs were observed in all apamin-treated cells, the duration of the response varied considerably between individual neurons and was strongly potentiated by the addition of TEA (2-3 mM). In the presence of TTX, TEA, and apamin, optimal stimulus parameters (0.1 nA, 200-ms duration at -55 to -68 mV) evoked ADP ranging from 80 to 1,020 ms in duration (355.3 +/- 56.5 ms, n = 16). Both the ramp-shaped slow depolarization and the ensuing ADP were markedly voltage dependent but appeared to be mediated by separate conductance mechanisms. Thus, although bath application of nifedipine (10-30 microM) or low Ca2+, high Mg2+ Ringer blocked the ADP without affecting the ramp potential, equimolar substitution of Co2+ for Ca2+ blocked both components of the voltage response. Nominal Ca2+ Ringer containing Co2+ also blocked the HAP evoked between -55 and -68 mV. We conclude that the ADP elicited in DA neurons after blockade of apamin-sensitive Ca2+-activated K+ channels is mediated by a voltage-dependent, L-type Ca2+ channel and represents a transient form of the regenerative plateau oscillation in membrane potential previously shown to underlie apamin-induced bursting activity. These data provide further support for the notion that modulation of apamin-sensitive Ca2+-activated K+ channels in DA neurons exerts a permissive effect on the conductances that are involved in the expression of phasic activity.     

Unbearability of suffering at the end of life: the development of a new measuring device, the SOS-V

Background  

Unbearable suffering is an important issue in end-of-life decisions. However, there has been no systematic, prospective, patient-oriented research which has focused on unbearable suffering, nor is there a suitable measurement instrument. This article describes the methodological development of a quantitative instrument to measure the nature and intensity of unbearable suffering, practical aspects of its use in end-stage cancer patients in general practice, and studies content validity and psychometric properties.     

Unusual association of a unique CAG interruption in 5′ of DM1 CTG repeats with intergenerational contractions and low somatic mosaicism

Myotonic dystrophy type 1 (DM1) is a dominant multisystemic disorder associated with high variability of symptoms and anticipation. DM1 is caused by an unstable CTG repeat expansion that usually increases in successive generations and tissues. DM1 family pedigrees have shown that ～90% and 10% of transmissions result in expansions and contractions of the CTG repeat, respectively. To date, the mechanisms of CTG repeat contraction remain poorly documented in DM1. In this report, we identified two new DM1 families with apparent contractions and no worsening of DM1 symptoms in two and three successive maternal transmissions. A new and unique CAG interruption was found in 5′ of the CTG expansion in one family, whereas multiple 5′ CCG interruptions were detected in the second family. We showed that these interruptions are associated with maternal intergenerational contractions and low somatic mosaicism in blood. By specific triplet‐prime PCR, we observed that CTG repeat changes (contractions/expansions) occur preferentially in 3′ of the interruptions for both families.     

Phylogenetic analysis of human G9P[8] rotavirus strains circulating in Jiangsu,China between 2010 and 2016

Rotavirus A (RVA) is the leading cause of acute viral gastroenteritis in children under 5 years of age worldwide. G9P[8] is a common RVA genotype that has been persistently prevalent in Jiangsu, China. To determine the genetic diversity of G9P[8] RVAs, 7 representative G9P[8] strains collected from Suzhou Children’s Hospital between 2010 and 2016 (named JS2010‐JS2016) were analyzed through whole‐genome sequencing. All evaluated strains showed the Wa‐like constellation G9‐P[8]‐I1‐R1‐C1‐M1‐A1‐N1‐T1‐E1‐H1. Furthermore, phylogenetic analysis revealed that the VP7 genes of all strains clustered into lineage G9‐III and G9‐VI. With the exception of strain JS2012 (P[8]‐4), the VP4 sequences of all strains belonged to the P[8]‐3 lineage. Sequencing further revealed that amino acid substitutions were present in the antigenic regions of the VP7 and VP4 genes of all strains. Moreover, there were multiple substitutions in antigenic sites I and II of the nonstructural protein 4 (NSP4) genes, whereas the other NSP genes were relatively conserved. In conclusion, our phylogenetic analysis of these 7 G9P[8] strains suggests that RVA varied across regions and time. Therefore, our findings suggest that continued surveillance is necessary to explore the molecular evolutionary characteristics of RVA for better prevention and treatment of acute viral gastroenteritis.     

Implementation of the NCAA Sickle Cell Trait Screening Policy: A Survey of Athletic Staff and Student-athletes

Objective

To describe the perspectives and experiences of athletic trainers, coaches, and student-athletes approximately three years post-implementation of the NCAA sickle cell trait (SCT) screening policy.