Linking Life Skills and Norms with adolescent substance use and delinquency in South Africa

We examined factors targeted in two popular prevention approaches with adolescent drug use and delinquency in South Africa. We hypothesized adolescent life skills to be inversely related, and perceived norms to be directly related to later drug use and delinquency. Multiple regression and a relative weights approach were conducted for each outcome using a sample of 714 South African adolescents ages 15 to 19 years (M = 15.8 years, 57% female). Perceived norms predicted gateway drug use. Conflict resolution skills (inversely) and perceived peer acceptability (directly) predicted harder drug use and delinquency. The “culture of violence” within some South African schools may make conflict resolution skills more salient for preventing harder drug use and delinquency.Department of HE and Training approved lis

Translational research in South Africa: evaluating implementation quality using a factorial design

Background: HealthWise South Africa: Life Skills for Adolescents (HW) is an evidence- based substance use and sexual risk prevention program that emphasizes the positive use of leisure time. Since 2000, this program has evolved from pilot testing through an efficacy trial involving over 7,000 youth in the Cape Town area. Beginning in 2011, through 2015, we are undertaking a new study that expands HW to all schools in the Metro South Education District. Objective: This paper describes a research study designed in partnership with our South African collaborators that examines three factors hypothesized to affect the quality and fidelity of HW implementation: enhanced teacher training; teacher support, structure and supervision; and enhanced school environment. Methods: Teachers and students from 56 schools in the Cape Town area will participate in this study. Teacher observations are the primary means of collecting data on factors affecting implementation quality. These factors address the practical concerns of teachers and schools related to likelihood of use and cost-effectiveness, and are hypothesized to be "active ingredients" related to high-quality program implementation in real-world settings. An innovative factorial experimental design was chosen to enable estimation of the individual effect of each of the three factors. Results: Because this paper describes the conceptualization of our study, results are not yet available. Conclusions: The results of this study may have both substantive and methodological implications for advancing Type 2 translational research

Regional Multiple Pathology Scores Are Associated with Cognitive Decline in Lewy Body Dementias.

Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are characterized by the presence of α-synuclein-containing Lewy bodies and Lewy neurites. However, both dementias also show variable degrees of Alzheimer's disease (AD) pathology (senile plaques and neurofibrillary tangles), particularly in areas of the cortex associated with higher cognitive functions. This study investigates the contribution of the individual and combined pathologies in determining the rate of cognitive decline. Cortical α-synuclein, phosphorylated tau (phosphotau) and Aβ plaque pathology in 34 PDD and 55 DLB patients was assessed semi-quantitatively in four regions of the neocortex. The decline in cognition, assessed by Mini Mental State Examination, correlated positively with the cortical α-synuclein load. Patients also had varying degrees of senile Aβ plaque and phosphotau pathology. Regression analyses pointed to a combined pathology (Aβ plaque plus phosphotau plus α-synuclein-positive features), particularly in the prefrontal cortex (BA9) and temporal lobe neocortex with the superior and middle temporal gyrus (BA21, 22), being a major determining factor in the development of dementia. Thus, cognitive decline in Lewy body dementias is not a consequence of α-synuclein-induced neurodegeneration alone but senile plaque and phosphorylated tau pathology also contribute to the overall deficits.The main fundingwas provided by the Alzheimer’s SocietyUK and the BUPA Foundation. The research in Newcastle was supported in part by the Dunhill Medical Trust (R173/1110). Tissue for this study was provided by (i) the Newcastle Brain Tissue Resource; (ii) the London Neurodegenerative Brain Bank; and (iii) the Thomas Willis Oxford Brain Collection. All three resources are funded in part by grants from the UK Medical Research Council and by Brains for Dementia Research, a joint venture between Alzheimer’s Society and Alzheimer’s Research UK. In Singapore, funding was provided by a Centre grant (NMRC/CG/NUHS/2010) and a Clinical Scientist Award (NMRC/CSA/032/2011) from the National Medical Research Council.This is the final published version. It first appeared at http://onlinelibrary.wiley.com/doi/10.1111/bpa.12182/abstract

Regional Multiple Pathology Scores Are Associated with Cognitive Decline in Lewy Body Dementias

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High Energy Neutrino Signals of Four Neutrino Mixing

We evaluate the upward shower and muon event rates for two characteristic four neutrino mixing models for extragalactic neutrinos, as well as for the atmospheric neutrinos, with energy thresholds of 1 TeV, 10 TeV and 100 TeV. We show that by comparing the shower to muon event rates, one can distinguish between oscillation and no-oscillation models. By measuring shower and muon event rates for energy thresholds of 10 TeV and 100 TeV, and by considering their ratio, it is possible to use extragalactic neutrino sources to determine the type of four-flavor mixing pattern. We find that one to ten years of data taking with kilometer-size detector has a very good chance of providing valuable information about the physics beyond the Standard Model.Comment: version accepted for publication in Phys. Rev.

Miniature Low-Noise G-Band I-Q Receiver

Weather forecasting, hurricane tracking, and atmospheric science applications depend on humidity sounding of atmosphere. Current instruments provide these measurements from groundbased, airborne, and low Earth orbit (LEO) satellites by measuring radiometric temperature on the flanks of the 183-GHz water vapor line. Miniature, low-noise receivers have been designed that will enable these measurements from a geostationary, thinned array sounder, which is based on hundreds of low-noise receivers that convert the 180-GHz signal directly to baseband in-phase and in-quadrature signals for digitization and correlation. The developed receivers provide a noise temperature of 450 K from 165 to 183 GHz (NF = 4.1 dB), and have a mass of 3 g while consuming 24 mW of power. These are the most sensitive broadband I-Q receivers at this frequency range that operate at room temperature, and are significantly lower in mass and power consumption than previously reported receivers

Neutrino Interactions at Ultrahigh Energies

We report new calculations of the cross sections for deeply inelastic neutrino-nucleon scattering at neutrino energies between 10^{9}\ev and 10^{21}\ev. We compare with results in the literature and assess the reliability of our predictions. For completeness, we briefly review the cross sections for neutrino interactions with atomic electrons, emphasizing the role of the $W$-boson resonance in $\bar{\nu}_{e}e$ interactions for neutrino energies in the neighborhood of 6.3\pev. Adopting model predictions for extraterrestrial neutrino fluxes from active galactic nuclei, gamma-ray bursters, and the collapse of topological defects, we estimate event rates in large-volume water \v{C}erenkov detectors and large-area ground arrays.Comment: 32 pages, 11 figures, uses RevTeX and boxedep

Tau Neutrinos Underground: Signals of νμ→ντ\nu_\mu \to \nu_\tau Oscillations with Extragalactic Neutrinos

The appearance of high energy tau neutrinos due to $\nu_\mu \to \nu_\tau$ oscillations of extragalactic neutrinos can be observed by measuring the neutrino induced upward hadronic and electromagnetic showers and upward muons. We evaluate quantitatively the tau neutrino regeneration in the Earth for a variety of extragalactic neutrino fluxes. Charged-current interactions of the upward tau neutrinos below and in the detector, and the subsequent tau decay create muons or hadronic and electromagnetic showers. The background for these events are muon neutrino and electron neutrino charged-current and neutral-current interactions, where in addition to extragalactic neutrinos, we consider atmospheric neutrinos. We find significant signal to background ratios for the hadronic/electromagnetic showers with energies above 10 TeV to 100 TeV initiated by the extragalactic neutrinos. We show that the tau neutrinos from point sources also have the potential for discovery above a 1 TeV threshold. A kilometer-size neutrino telescope has a very good chance of detecting the appearance of tau neutrinos when both muon and hadronic/electromagnetic showers are detected.Comment: section added and two new figs; accepted for publication in Physical Review

Early pneumothorax as a feature of response to crizotinib therapy in a patient with ALK rearranged lung adenocarcinoma.

Background: Single arm phase 1 and 2 studies on Crizotinib in ALK-positive patients so far have shown rapid and durable responses. Spontaneous pneumothoraces as a result of response to anti-cancer therapy are rare in oncology but have been documented in a number of tumour types including lung cancer. This includes cytotoxic chemotherapy as well as molecular targeted agents such as gefitinib and Bevacizumab. These often require chest drain insertion or surgical intervention with associated morbidity and mortality. They have also been associated with response to treatment. This is the first report we are aware of documenting pneumothorax as response to crizotinib therapy.Case presentation: A 48-year-old Caucasian male presented with a Stage IV, TTF1 positive, EGFR wild-type adenocarcinoma of the lung. He received first line chemotherapy with three cycles of cisplatin-pemetrexed chemotherapy with a differential response, and then second-line erlotinib for two months before further radiological evidence of disease progression. Further analysis of his diagnostic specimen identified an ALK rearrangement by fluorescence in situ hybridization (FISH). He was commenced on crizotinib therapy 250 mg orally twice daily. At his 4-week assessment he had a chest radiograph that identified a large left-sided pneumothorax with disease response evident on the right. Chest CT confirmed a 50% left-sided pneumothorax on a background of overall disease response. A chest tube was inserted with complete resolution of the pneumothorax that did not recur following its removal.Conclusion: Our case demonstrates this potential complication of crizotinib therapy and we therefore recommend that pneumothorax be considered in patients on crizotinib presenting with high lung metastatic burden and with worsening dyspnoea. © 2013 Gennatas et al.; licensee BioMed Central Ltd

Oxaliplatin induces drug resistance more rapidly than cisplatin in H69 small cell lung cancer cells

Cisplatin produces good responses in solid tumours including small cell lung cancer (SCLC) but this is limited by the development of resistance. Oxaliplatin is reported to show activity against some cisplatin-resistant cancers but there is little known about oxaliplatin in SCLC and there are no reports of oxaliplatin resistant SCLC cell lines. Studies of drug resistance mainly focus on the cellular resistance mechanisms rather than how the cells develop resistance. This study examines the development of cisplatin and oxaliplatin resistance in H69 human SCLC cells in response to repeated treatment with clinically relevant doses of cisplatin or oxaliplatin for either 4 days or 2h. Treatments with 200ng/ml cisplatin or 400ng/ml oxaliplatin for 4 days produced sublines (H69CIS200 and H69OX400 respectively) that showed low level (approximately 2-fold) resistance after 8 treatments. Treatments with 1000ng/ml cisplatin or 2000ng/ml oxaliplatin for 2h also produced sublines, however these were not stably resistant suggesting shorter treatment pulses of drug may be more effective. Cells survived the first five treatments without any increase in resistance, by arresting their growth for a period and then regrowing. The period of growth arrest was reduced after the sixth treatment and the H69CIS200 and H69OX400 sublines showed a reduced growth arrest in response to cisplatin and oxaliplatin treatment suggesting that "regrowth resistance" initially protected against drug treatment and this was further upregulated and became part of the resistance phenotype of these sublines. Oxaliplatin dose escalation produced more surviving sublines than cisplatin dose escalation but neither set of sublines were associated with increased resistance as determined by 5-day cytotoxicity assays, also suggesting the involvement of regrowth resistance. The resistant sublines showed no change in platinum accumulation or glutathione levels even though the H69OX400 subline was more sensitive to buthionine sulfoximine treatment. The H69CIS200 cells were cross-resistant to oxaliplatin demonstrating that oxaliplatin does not have activity against low level cisplatin resistance. Relative to the H69 cells, the H69CIS200 and H69OX400 sublines were more sensitive to paclitaxel and taxotere suggests the taxanes may be useful in the treatment of platinum resistant SCLC. These novel cellular models of cisplatin and oxaliplatin resistant SCLC will be useful in developing strategies to treat platinum-resistant SCLC