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Journal of Neuro-Oncology - Perifosine (PRF) is an oral alkylphospholipid with antineoplastic effects and reasonable tolerability. It inhibits signaling through the PI3/AKT axis and other cascades...  相似文献   
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Our understanding of human evolution has improved rapidly over recent decades, facilitated by large‐scale cataloguing of genomic variability amongst both modern and archaic humans. It seems clear that the evolution of the ancestors of chimpanzees and hominins separated 7–9 million years ago with some migration out of Africa by the earlier hominins; Homo sapiens slowly emerged as climate change resulted in drier, less forested African conditions. The African populations expanded and evolved in many different conditions with slow mutation and selection rates in the human genome, but with much more rapid mutation occurring in mitochondrial DNA. We now have evidence stretching back 300 000 years of humans in their current form, but there are clearly four very different large African language groups that correlate with population DNA differences. Then, about 50 000–100 000 years ago a small subset of modern humans also migrated out of Africa resulting in a persistent signature of more limited genetic diversity amongst non‐African populations. Hybridization with archaic hominins occurred around this time such that all non‐African modern humans possess some Neanderthal ancestry and Melanesian populations additionally possess some Denisovan ancestry. Human populations both within and outside Africa also adapted to diverse aspects of their local environment including altitude, climate, UV exposure, diet and pathogens, in some cases leaving clear signatures of patterns of genetic variation. Notable examples include haemoglobin changes conferring resistance to malaria, other immune changes and the skin adaptations favouring the synthesis of vitamin D. As humans migrated across Eurasia, further major mitochondrial changes occurred with some interbreeding with ancient hominins and the development of alcohol intolerance. More recently, an ability to retain lactase persistence into adulthood has evolved rapidly under the environmental stimulus of pastoralism with the ability to husband lactating ruminants. Increased amylase copy numbers seem to relate to the availability of starchy foods, whereas the capacity to desaturase and elongate monounsaturated fatty acids in different societies seems to be influenced by whether there is a lack of supply of readily available dietary sources of long‐chain polyunsaturated fatty acids. The process of human evolution includes genetic drift and adaptation to local environments, in part through changes in mitochondrial and nuclear DNA. These genetic changes may underlie susceptibilities to some modern human pathologies including folate‐responsive neural tube defects, diabetes, other age‐related pathologies and mental health disorders.  相似文献   
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Background

Parents’ attitudes and beliefs in vaccination are important to understand for shaping vaccine acceptance and demand interventions. Little research has focused on developing a validated scale to measure parents’ attitudes towards vaccinations in low and middle-income countries; Ghana provided an opportunity develop a caregiver vaccination attitudes scale (CVAS) validated against childhood vaccine compliance.

Methods

We conducted a cluster survey of 373 households with children aged 12–35?months of age from Northern Region, Ghana. Caregivers responded to 22 vaccination behavior and belief survey items and provided the child’s vaccination status. In exploratory factor analysis (EFA) to assess CVAS content validity, we used parallel analysis to guide the number of factors to extract and principal axis factor analysis for factor extraction. Reliability of the scale was assessed using McDonald’s Omega coefficient. Criterion validity of scale and subscales was assessed against receipt of vaccinations by 12?months of age and vaccination delay, using number of days undervaccinated.

Results

EFA of CVAS responses resulted in removing 11 of 22 survey items due to loadings <0.30 and development of a 5-factor structure with subscales for Vaccine-Preventable Disease (VPD) Awareness, Vaccine Benefits, Past Behavior, Vaccine Efficacy and Safety, and Trust. The 5 factors accounted for 69% of the common variance and omega coefficients were >0.73 for all subscales. Validity analysis indicated that for every unit increase in the parent’s scale score, the odds of the child being vaccinated decreased by 0.58 (95% confidence interval [CI]: 0.37, 0.68) and the number of days under-vaccinated increased by 86 (95%CI: 28, 143). The final 3-factor scale included Vaccine Benefits, Past Behavior, and Vaccine Efficacy and Safety.

Discussion

The final CVAS included three factors associated with vaccine compliance in Ghana, although several survey items suggested for use in vaccine acceptance scales were dropped. Replicating this study in several country settings will provide additional evidence to assist in refining a tool for use in routine vaccine acceptance and demand surveillance efforts.  相似文献   
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