RESUMEN
Estrogens have inconsistent effects on learning and memory in both the clinical and preclinical literature. Preclinical literature has the advantage of investigating an array of potentially important factors contributing to the varied effects of estrogens on learning and memory, with stringently controlled studies. This study set out to identify specific factors in the animal literature that influence the effects of estrogens on cognition, for possible translation back to clinical practice. The literature was screened and studies meeting strict inclusion criteria were included in the analysis. Eligible studies included female ovariectomized rodents with an adequate vehicle for the estrogen treatment, with an outcome of spatial learning and memory in the Morris water maze. Training days of the Morris water maze were used to assess acquisition of spatial learning, and the probe trial was used to evaluate spatial memory recall. Continuous outcomes were pooled using a random effects inverse variance method and reported as standardized mean differences with 95 % confidence intervals. Subgroup analyses were developed a priori to assess important factors. The overall analysis favoured treatment for the later stages of training and for the probe trial. Factors including the type of estrogen, route, schedule of administration, age of animals, timing relative to ovariectomy, and duration of treatment were all found to be important. The subgroup analyses showed that chronic treatment with 17ß-estradiol, either cyclically or continuously, to young animals improved spatial recall. These results, observed in animals, can inform and guide further clinical research on hormone replacement therapy for cognitive benefits.
RESUMEN
Improved upstream titres in therapeutic monoclonal antibody (mAb) production have shifted capacity constraints to the downstream process. The consideration of membrane-based chromatographic devices as a debottlenecking option is gaining increasing attention with the recent introduction of high-capacity bind and elute membranes. We have evaluated the performance and scalability of the Sartobind® Rapid A affinity membrane (1 mL) for high-productivity mAb capture. For scalability assessment, a 75 mL prototype device was used to process 100 L of clarified cell culture harvest (CH) on a novel multi-use rapid cycling chromatography system (MU-RCC). MabSelect™ PrismA (4.7 mL) was used as a benchmark comparator for Protein A (ProtA) resin studies. Results show that in addition to a productivity gain of >10×, process and product quality attributes were either improved or comparable to the benchmark. Concentrations of eluate pools were 7.5× less than that of the benchmark, with the comparatively higher bulk volume likely to cause handling challenges at process scale. The MU-RCC system is capable of membrane operation at pilot scale with comparable product quality profile to the 1 mL device. The Sartobind® Rapid A membrane is a scalable alternative to conventional ProtA resin chromatography for the isolation and purification of mAbs from harvested cell culture media.
RESUMEN
Adaptive behaviour is a crucial area of assessment for individuals with Autism Spectrum Disorder (ASD). This study examined the adaptive behaviour profile of 77 young children with ASD using the Vineland-II, and analysed factors associated with adaptive functioning. Consistent with previous research with the original Vineland a distinct autism profile of Vineland-II age equivalent scores, but not standard scores, was found. Highest scores were in motor skills and lowest scores were in socialisation. The addition of the Autism Diagnostic Observation Schedule calibrated severity score did not contribute significant variance to Vineland-II scores beyond that accounted for by age and nonverbal ability. Limitations, future directions, and implications are discussed.