Applying ecological systems theory to juvenile legal system interventions outcomes research: a measurement framework

Intervention research and development for youth in the juvenile legal system (JLS) has often focused on recidivism as the primary outcome of interest. Although recidivism is an important outcome, it is ultimately a downstream marker of success and is affected by changes in other domains of youths’ lives (e.g., family and peer relations, neighborhood safety, local and state-level policies). Thus, the present manuscript proposes the application of ecological systems theory to selecting outcomes to assess intervention effects in JLS intervention research to better capture proximal and distal influences on youth behavior. To that end, we first provide an overview of the strengths and limitations of using recidivism as an outcome measure. Next, the current application of social ecology theory to existing research on both risk and protective factors of JLS involvement is discussed, as well as existing work on assessing social-ecological domains within intervention studies. Then, a measurement framework is introduced for selecting pertinent domains of youths’ social ecologies to assess as intervention outcomes, moderators, and mediators. To facilitate this, we provide examples of concrete constructs and measures that researchers may select. We conclude with potential new avenues of research to which our proposed framework could lead, as well as potential limitations of implementing our framework

A prospective, randomized clinical trial of antiretroviral therapies on carotid wall thickness

Objective: This article compares the effects of initiating three contemporary antiretroviral therapy (ART) regimens on progression of carotid artery intima-media thickness (IMT) over 3 years. Design: Randomized clinical trial. Setting: Multicenter (26 institutions). Patients: ART-naive HIV-infected individuals (n ¼ 328) without known cardiovascular disease or diabetes mellitus. Intervention: Random assignment to tenofovir/emtricitabine along with atazanavir/ ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or raltegravir (RAL). Main outcome measures: Right-sided carotid IMT was evaluated by B-mode ultrasonography before ART initiation, and then after 48, 96, and 144 weeks. Comparisons of yearly rates of change in carotid IMT used mixed-effects linear regression models that permitted not only evaluation of the effects of ART on carotid IMT progression but also how ART-associated changes in traditional risk factors, bilirubin, and markers of HIV infection were associated carotid IMT progression. Results: HIV-1 RNA suppression rates were high in all arms (>85%) over 144 weeks. Modest increases in triglycerides and non-high-density lipoprotein cholesterol levels were observed in the protease inhibitor-containing arms compared with decreases with RAL. In contrast, carotid IMT progressed more slowly on ATV/r [8.2, 95% confidence interval (5.6, 10.8) mm/year] than DRV/r [12.9 (10.3, 15.5) mm/year, P ¼ 0.013]; changes with RAL were intermediate [10.7 (9.2, 12.2) mm/year, P ¼ 0.15 vs. ATV/r; P ¼ 0.31 vs. DRV/r]. Bilirubin and non-high-density lipoprotein cholesterol levels appeared to influence carotid IMT progression rates. Conclusion: In ART-naive HIV-infected individuals at low cardiovascular disease risk, carotid IMT progressed more slowly in participants initiating ATV/r than those initiating DRV/r, with intermediate changes associated with RAL. This effect may be due, in part, to hyperbilirubinemia

Diagnosis and treatment of urticaria and angioedema: a worldwide perspective

Urticaria and angioedema are common clinical conditions representing a major concern for physicians and patients alike. The World Allergy Organization (WAO), recognizing the importance of these diseases, has contributed to previous guidelines for the diagnosis and management of urticaria. The Scientific and Clinical Issues Council of WAO proposed the development of this global Position Paper to further enhance the clinical management of these disorders through the participation of renowned experts from all WAO regions of the world. Sections on definition and classification, prevalence, etiology and pathogenesis, diagnosis, treatment, and prognosis are based on the best scientific evidence presently available. Additional sections devoted to urticaria and angioedema in children and pregnant women, quality of life and patient-reported outcomes, and physical urticarias have been incorporated into this document. It is expected that this article will supplement recent international guidelines with the contribution of an expert panel designated by the WAO, increasing awareness of the importance of urticaria and angioedema in medical practice and will become a useful source of information for optimum patient management worldwide

<i>hTERT</i> Epigenetics Provides New Perspectives for Diagnosis and Evidence-Based Guidance of Chemotherapy in Cancer

Strong epigenetic pan-cancer biomarkers are required to meet several current, urgent clinical needs and to further improve the present chemotherapeutic standard. We have concentrated on the investigation of epigenetic alteration of the hTERT gene, which is frequently epigenetically dysregulated in a number of cancers in specific developmental stages. Distinct DNA methylation profiles were identified in our data on early urothelial cancer. An efficient EpihTERT assay could be developed utilizing suitable combinations with sequence-dependent thermodynamic parameters to distinguish between differentially methylated states. We infer from this data set, the epigenetic context, and the related literature that a CpG-rich, 2800 bp region, a prominent CpG island, surrounding the transcription start of the hTERT gene is the crucial epigenetic zone for the development of a potent biomarker. In order to accurately describe this region, we have named it “Acheron” (Ἀχέρων). In Greek mythology, this is the river of woe and misery and the path to the underworld. Exploitation of the DNA methylation profiles focused on this region, e.g., idiolocal normalized Methylation Specific PCR (IDLN-MSP), opens up a wide range of new possibilities for diagnosis, determination of prognosis, follow-up, and detection of residual disease. It may also have broad implications for the choice of chemotherapy