Effects of gas-filled temporary breast tissue expanders on radiation dose from modulated rotational photon beams

Gas-filled temporary tissue expanders (TTEs), implanted to assist in post mastectomy breast reconstructions, are expected to produce increased dosimetric uncertainty in breast radiotherapy treatments, due to their containing both a substantial metallic component and a comparatively large volume of gas. This study therefore builds on previous investigations of the dosimetric effects of gas-filled TTEs in static photon and electron beams, by examining the effects of these implants on dose distributions from common modulated rotational treatment techniques; volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT). Radiochromic film measurements were used to evaluate the accuracy of VMAT and HT dose calculations, for a humanoid phantom augmented with a sample Aeroform CO₂-filled TTE (AirXpanders Inc, San Jose, USA) as well as purpose-designed and 3D printed “breast tissue.” Results showed that the TomoTherapy Hi-Art VoLO convolution-superposition algorithm (Accuray Inc, Sunnyvale, USA) produced comparatively accurate calculations of treatment dose within this complex phantom, including immediately anterior and posterior to the TTE. The Varian Eclipse Acuros (AXB) algorithm generally showed better agreement with the film measurement than the Varian Eclipse AAA algorithm (Varian Medical Systems, Palo Alto, USA), although the film measurements showed regions of 5% to 10% disagreement with both AAA and AXB in the dosimetrically-challenging region on the anterior side of the implant. Although the Aeroform CO₂-filled TTE has substantial and obvious effects on the downstream dose from a static photon beam, the results of this study showed how inverse-planning of modulated rotational radiotherapy treatments can produce modulated fluence distributions that compensate for the dramatic density heterogeneities in the implant. Despite some disagreements with the planned dose, all film measurements showed that the use of inverse-planned modulated rotational photon beams resulted in comparatively homogeneous coverage of the radiotherapy target, in the complex patient-like phantom with a gas-filled TTE. Due to the importance of matching each planned fluence distribution to the density distribution within each TTE, careful use of available 3D imaging techniques is advisable, when modulated rotational radiotherapy treatments are delivered to patients with gas-filled TTEs.     

PAK1 Positively Regulates Oligodendrocyte Morphology and Myelination

The actin cytoskeleton is crucial for oligodendrocyte differentiation and myelination. Here we show that p21-activated kinase 1 (PAK1), a well-known actin regulator, promotes oligodendrocyte morphologic change and myelin production in the CNS. A combination of in vitro and in vivo models demonstrated that PAK1 is expressed throughout the oligodendrocyte lineage with highest expression in differentiated oligodendrocytes. Inhibiting PAK1 early in oligodendrocyte development decreased oligodendrocyte morphologic complexity and altered F-actin spreading at the tips of oligodendrocyte progenitor cell processes. Constitutively activating AKT in oligodendrocytes in male and female mice, which leads to excessive myelin wrapping, increased PAK1 expression, suggesting an impact of PAK1 during active myelin wrapping. Furthermore, constitutively activating PAK1 in oligodendrocytes in zebrafish led to an increase in myelin internode length while inhibiting PAK1 during active myelination decreased internode length. As myelin parameters influence conduction velocity, these data suggest that PAK1 may influence communication within the CNS. These data support a model in which PAK1 is a positive regulator of CNS myelination.SIGNIFICANCE STATEMENT Myelin is a critical component of the CNS that provides metabolic support to neurons and also facilitates communication between cells in the CNS. Recent data demonstrate that actin dynamics drives myelin wrapping, but how actin is regulated during myelin wrapping is unknown. The authors investigate the role of the cytoskeletal modulator PAK1 during differentiation and myelination by oligodendrocytes, the myelinating cells of the CNS. They demonstrate that PAK1 promotes oligodendrocyte differentiation and myelination by modulating the cytoskeleton and thereby internode length, thus playing a critical role in the function of the CNS.     

Risk factors for enterococcal urinary tract infections: a multinational,retrospective cohort study

European Journal of Clinical Microbiology & Infectious Diseases - Complicated urinary tract infection (cUTI) is a frequent cause of morbidity. In this multinational retrospective cohort study,...     

Behavioral,cognitive, and adaptive development in infants with autism spectrum disorder in the first 2?years of life

Background

To delineate the early progression of autism spectrum disorder (ASD) symptoms, this study investigated developmental characteristics of infants at high familial risk for ASD (HR), and infants at low risk (LR).

Methods

Participants included 210 HR and 98 LR infants across 4 sites with comparable behavioral data at age 6, 12, and 24 months assessed in the domains of cognitive development (Mullen Scales of Early Learning), adaptive skills (Vineland Adaptive Behavioral Scales), and early behavioral features of ASD (Autism Observation Scale for Infants). Participants evaluated according to the DSM-IV-TR criteria at 24 months and categorized as ASD-positive or ASD-negative were further stratified by empirically derived cutoff scores using the Autism Diagnostic Observation Schedule yielding four groups: HR-ASD-High, HR-ASD-Moderate (HR-ASD-Mod), HR-ASD-Negative (HR-Neg), and LR-ASD-Negative (LR-Neg).

Results

The four groups demonstrated different developmental trajectories that became increasingly distinct from 6 to 24 months across all domains. At 6 months, the HR-ASD-High group demonstrated less advanced Gross Motor and Visual Reception skills compared with the LR-Neg group. By 12 months, the HR-ASD-High group demonstrated increased behavioral features of ASD and decreased cognitive and adaptive functioning compared to the HR-Neg and LR-Neg groups. By 24 months, both the HR-ASD-High and HR-ASD-Moderate groups demonstrated differences from the LR- and HR-Neg groups in all domains.

Conclusions

These findings reveal atypical sensorimotor development at 6 months of age which is associated with ASD at 24 months in the most severely affected group of infants. Sensorimotor differences precede the unfolding of cognitive and adaptive deficits and behavioral features of autism across the 6- to 24-month interval. The less severely affected group demonstrates later symptom onset, in the second year of life, with initial differences in the social-communication domain.

Electronic supplementary material

The online version of this article (doi:10.1186/s11689-015-9117-6) contains supplementary material, which is available to authorized users.