Radiation therapy (RT) is an integral component of the treatment of many sarcomas and relies on accurate targeting of tumor tissue. Despite conventional treatment planning and RT, local failure rates ...of 10% to 28% at 5 years have been reported for locally advanced, unresectable sarcomas, due in part to limitations in the cumulative RT dose that may be safely delivered. We describe studies of the potential usefulness of gold nanoparticles modified for durable systemic circulation (through polyethylene glycosylation; hereinafter "P-GNPs") as adjuvants for RT of sarcomas. In studies of two human sarcoma-derived cell lines, P-GNP in conjunction with RT caused increased unrepaired DNA damage, reflected by approximately 1.61-fold increase in γ-H2AX (histone phosphorylated on Ser(139)) foci density compared with RT alone. The combined RT and P-GNP also led to significantly reduced clonogenic survival of tumor cells, compared to RT alone, with dose-enhancement ratios of 1.08 to 1.16. In mice engrafted with human sarcoma tumor cells, the P-GNP selectively accumulated in the tumor and enabled durable imaging, potentially aiding radiosensitization as well as treatment planning. Mice pretreated with P-GNP before targeted RT of their tumors exhibited significantly improved tumor regression and overall survival, with long-term survival in one third of mice in this treatment group compared to none with RT only. Interestingly, prior RT of sarcoma tumors increased subsequent extravasation and in-tumor deposition of P-GNP. These results together suggest P-GNP may be integrated into the RT of sarcomas, potentially improving target imaging and radiosensitization of tumor while minimizing dose to normal tissues.
Youths perinatally infected with HIV often receive psychotropic medication and behavioral treatment for emotional and behavioral symptoms. We describe patterns of intervention for HIV-positive youth ...and youth in a control group in the United States.
Three hundred nineteen HIV-positive youth and 256 controls, aged 6 to 17 years, enrolled in the International Maternal Adolescent AIDS Clinical Trials 1055, a prospective, 2-year observational study of psychiatric symptoms. One hundred seventy-four youth in the control group were perinatally exposed to HIV, and 82 youth were uninfected children living in households with HIV-positive members. Youth and their primary caregivers completed Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-referenced symptom-rating scales. Children's medication and behavioral psychiatric intervention histories were collected at entry. We evaluated the association of past or current psychiatric treatment with HIV status, baseline symptoms, and impairment by using multiple logistic regression, controlling for potential confounders.
HIV-positive youth and youth in the control group had a similar prevalence of psychiatric symptoms (61%) and impairment (14% to 15%). One hundred four (18%) participants received psychotropic medications (stimulants 14%, antidepressants 6%, and neuroleptic agents 4%), and 127 (22%) received behavioral treatment. More HIV-positive youth than youth in the control group received psychotropic medication (23% vs 12%) and behavioral treatment (27% vs 17%). After adjusting for symptom class and confounders, HIV-positive children had twice the odds of children in the control group of having received stimulants and >4 times the odds of having received antidepressants. Caregiver-reported symptoms or impairment were associated with higher odds of intervention than reports by children alone.
HIV-positive children are more likely to receive mental health interventions than control-group children. Pediatricians and caregivers should consider available mental health treatment options for all children living in families affected by HIV.
Radiation therapy (RT) is an integral component of the treatment of many sarcomas and relies on accurate targeting of tumor tissue. Despite conventional treatment planning and RT, local failure rates ...of 10% to 28% at 5 years have been reported for locally advanced, unresectable sarcomas, due in part to limitations in the cumulative RT dose that may be safely delivered. We describe studies of the potential usefulness of gold nanoparticles modified for durable systemic circulation (through polyethylene glycosylation; hereinafter “P-GNPs”) as adjuvants for RT of sarcomas. In studies of two human sarcoma-derived cell lines, P-GNP in conjunction with RT caused increased unrepaired DNA damage, reflected by approximately 1.61-fold increase in γ-H2AX (histone phosphorylated on Ser
139
) foci density compared with RT alone. The combined RT and P-GNP also led to significantly reduced clonogenic survival of tumor cells, compared to RT alone, with dose-enhancement ratios of 1.08 to 1.16. In mice engrafted with human sarcoma tumor cells, the P-GNP selectively accumulated in the tumor and enabled durable imaging, potentially aiding radiosensitization as well as treatment planning. Mice pretreated with P-GNP before targeted RT of their tumors exhibited significantly improved tumor regression and overall survival, with long-term survival in one third of mice in this treatment group compared to none with RT only. Interestingly, prior RT of sarcoma tumors increased subsequent extravasation and in-tumor deposition of P-GNP. These results together suggest P-GNP may be integrated into the RT of sarcomas, potentially improving target imaging and radiosensitization of tumor while minimizing dose to normal tissues.
The next time you're leafing through a scientific journal, pick a paper and focus on the description of the data analysis. As statisticians, it's the analysis that naturally draws readers' attention, ...but pay attention to whether the authors provided you with sufficient information to recreate their data analysis starting with the raw data set and continuing through to the last p-value. An analysis that can be passed from one person to another and, using the same data, generate the same results in an unambiguous manner is reproducible. While the ultimate goal of teaching in a reproducible paradigm is to prepare students to be responsible scientists in the future, you don't have to wait until your students go off on scientific careers to see the fruits of your labor. Five concrete reasons why your students should be learning to analyze data in the reproducible paradigm, using R Markdown to illustrate them, are discussed. R Markdown is based on the free and open source statistical programming language R.
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