Needs Assessment: Northeast Philly Opioid Epidemic

Introduction: Philadelphia has the 3rd highest rate of opioid-related overdoses in the nation. This crisis is worsening in Northeast Philadelphia and the Department of Public Health lacks necessary information to intervene in an informed manner. Objective: This study aims to better understand the crisis in this community and to provide key information to guide future harm reduction interventions in the Northeast Philadelphia region. Methods: Using a designed discussion guide, qualitative interviews were completed with key stakeholders and community members. Information regarding personal experiences and opinions about the epidemic was gathered and interviews were analyzed using narrative analysis. In addition, needle counts were completed in public spaces. These counts were used to measure the free needle burden in this community. The findings of this study will be reported to the Department of Public Health. Results: Community member and stakeholder interviews produced a spectrum of opinions surrounding this issue. Major themes include the need for better access to needle exchange services and the idea that the harm reduction needed in this community differs from what would be accepted by its community members. The needle counts reveal that there is not a serious burden in the community, suggesting little need for further needle disposal kiosks in the area. Conclusion: In conclusion, future interventions should be centered around increasing needle exchange services and improving access and visibility of treatment centers in this community. Furthermore, further action should be taken to address the stigma of substance abuse in this community

Advanced prostate cancer experimental radioactive treatment-clinical trial decision making: patient experiences.

ObjectivesNested qualitative studies within clinical trials provide the opportunity to better understand participant experiences of participation and identify areas where improved support is required. The purpose of this qualitative study is to describe the lived experiences of men with advanced prostate cancer participating in the TheraP trial; a randomised trial of 177Lu-PSMA-617 compared with cabazitaxel chemotherapy.MethodsFifteen men with advanced prostate cancer were recruited from the TheraP clinical trial and interviewed at three time points during the trial. Interviews were inductively analysed using thematic analysis. This research paper reports the results from the baseline interview at commencement of the trial, focusing specifically on participants' enrolment experiences.ResultsFour themes were identified representing the lived experiences of men with advanced prostate cancer deciding to participate in the TheraP trial: (1) hoping to survive; (2) needing to feel informed; (3) choosing to participate and (4) being randomised. The process of deciding to enrol in a clinical trial is filled with indecision, emotional difficulties and focused on a desire to live.ConclusionsFor men with advanced prostate cancer, the experience of deciding to enrol in a clinical trial is principally driven by a desire to survive but interlinked with the need to make an informed decision as participants in this study expressed a preference for allocation to the experimental arm. Men seeking to enrol in clinical trials of new prostate cancer treatments would benefit from improved informational and decision support.Trial registration numberNCT03392428, ANZUP1603

The new very small angle neutron scattering spectrometer at Laboratoire Leon Brillouin

The design and characteristics of the new very small angle neutron scattering spectrometer under construction at the Laboratoire Leon Brillouin is described. Its goal is to extend the range of scattering vectors magnitudes towards 2x10{-4} /A. The unique feature of this new spectrometer is a high resolution two dimensional image plate detector sensitive to neutrons. The wavelength selection is achieved by a double reflection supermirror monochromator and the collimator uses a novel multibeam design

Regulation and Rose of Heme Oxygenase-1 (HO-1) During Inflammation in Human Gingival Fibroblasts (HGF)

Periodontitis is the most common cause of adult tooth loss in the U.S., with an estimated 1 in 3 adults suffering from some form and 10-15% of adults developing severe forms. In addition to its direct impact, periodontitis also contributes to the development of several other diseases, including cardiovascular disease, pre-term low birth weight, and diabetes. Although the primary function of HO-1 is the breakdown of heme to carbon monoxide, iron and bilirubin, it has also been shown to play an important role in wound repair and the resolution of inflammation by mechanisms involving homeostatic regulation of the redox state of cells. A series of experiments has been designed to determine whether and to what extent the levels of HO-1 mRNA and protein are regulated by inflammatory cytokines in HGF isolated from individuals with or without periodontitis. Preliminary results show that HO-1 mRNA is expressed in HGF cultures derived from patients with periodontitis and that mRNA levels are inhibited over 60% by Interleukin-1 at 6 hours (10 ng/ml, p \u3c 0.001). Interestingly however, HO-1 protein levels as measured by ELISA are not decreased by IL-1. Experiments are currently underway to address this apparent paradox, as well as the potential role of HO-1 in the regulation of inflammatory mediators in HGF

Ab initio study of magnetism at the TiO2/LaAlO3 interface

In this paper we study the possible relation between the electronic and magnetic structure of the TiO2/LaAlO3 interface and the unexpected magnetism found in undoped TiO2 films grown on LaAlO$_3$. We concentrate on the role played by structural relaxation and interfacial oxygen vacancies. LaAlO3 has a layered structure along the (001) direction with alternating LaO and AlO2 planes, with nominal charges of +1 and -1, respectively. As a consequence of that, an oxygen deficient TiO2 film with anatase structure will grow preferently on the AlO2 surface layer. We have therefore performed ab-initio calculations for superlattices with TiO2/AlO2 interfaces with interfacial oxygen vacancies. Our main results are that vacancies lead to a change in the valence state of neighbour Ti atoms but not necessarily to a magnetic solution and that the appearance of magnetism depends also on structural details, such as second neighbor positions. These results are obtained using both the LSDA and LSDA+U approximations.Comment: Accepted for publication in Journal of Materials Scienc

A multicenter case registry study on medication-related osteonecrosis of the jaw in patients with advanced cancer

PURPOSE: This observational case registry study was designed to describe the natural history of cancer patients with medication-related osteonecrosis of the jaw (ONJ) and evaluate the ONJ resolution rate. METHODS: Adults with a diagnosis of cancer and with a new diagnosis of ONJ were enrolled and evaluated by a dental specialist at baseline and every 3 months for 2 years and then every 6 months for 3 years until death, consent withdrawal, or loss to follow-up. The primary endpoint was the rate and time course of ONJ resolution. Secondary endpoints included frequency of incident ONJ risk factors, ONJ treatment patterns, and treatment patterns of antiresorptive agents for subsequent ONJ. RESULTS: Overall, 327 patients were enrolled; 207 (63%) were continuing on study at data cutoff. Up to 69% of evaluable patients with ONJ had resolution or improvement during the study. ONJ resolution (AAOMS ONJ staging criteria) was observed in 114 patients (35%); median (interquartile range) time from ONJ onset to resolution was 7.3 (4.5-11.4) months. Most patients (97%) had received antiresorptive medication before ONJ development, 9 patients (3%) had not; 68% had received zoledronic acid, 38% had received denosumab, and 10% had received pamidronate (56% had received bisphosphonates only, 18% had received denosumab only, and 21% had exposure to both). CONCLUSIONS: These results are consistent with those observed in clinical trials evaluating skeletal-related events in patients with advanced malignancy involving bone. Longer follow-up will provide further information on ONJ recurrence and resolution rates between medically and surgically managed patients

A direct physical interaction between Nanog and Sox2 regulates embryonic stem cell self-renewal

Embryonic stem (ES) cell self-renewal efficiency is determined by the Nanog protein level. However, the protein partners of Nanog that function to direct self-renewal are unclear. Here, we identify a Nanog interactome of over 130 proteins including transcription factors, chromatin modifying complexes, phosphorylation and ubiquitination enzymes, basal transcriptional machinery members, and RNA processing factors. Sox2 was identified as a robust interacting partner of Nanog. The purified Nanog–Sox2 complex identified a DNA recognition sequence present in multiple overlapping Nanog/Sox2 ChIP-Seq data sets. The Nanog tryptophan repeat region is necessary and sufficient for interaction with Sox2, with tryptophan residues required. In Sox2, tyrosine to alanine mutations within a triple-repeat motif (S X T/S Y) abrogates the Nanog–Sox2 interaction, alters expression of genes associated with the Nanog-Sox2 cognate sequence, and reduces the ability of Sox2 to rescue ES cell differentiation induced by endogenous Sox2 deletion. Substitution of the tyrosines with phenylalanine rescues both the Sox2–Nanog interaction and efficient self-renewal. These results suggest that aromatic stacking of Nanog tryptophans and Sox2 tyrosines mediates an interaction central to ES cell self-renewal

Carbon stock growth in a forest stand: the power of age

BACKGROUND: Understanding the relationship between the age of a forest stand and its biomass is essential for managing the forest component of the global carbon cycle. Since biomass increases with stand age, postponing harvesting to the age of biological maturity may result in the formation of a large carbon sink. This article quantifies the carbon sequestration capacity of forests by suggesting a default rule to link carbon stock and stand age. RESULTS: The age dependence of forest biomass is shown to be a power-law monomial where the power of age is theoretically estimated to be 4/5. This theoretical estimate is close to the known empirical estimate; therefore, it provides a scientific basis for a quick and transparent assessment of the benefits of postponing the harvest, suggesting that the annual magnitude of the sink induced by delayed harvest lies in the range of 1–2% of the baseline carbon stock. CONCLUSION: The results of this study imply that forest age could be used as an easily understood and scientifically sound measure of the progress in complying with national targets on the protection and enhancement of forest carbon sinks

The anti-sigma factor RsrA responds to oxidative stress by reburying its hydrophobic core

Redox-regulated effector systems that counteract oxidative stress are essential for all forms of life. Here we uncover a new paradigm for sensing oxidative stress centred on the hydrophobic core of a sensor protein. RsrA is an archetypal zinc-binding anti-sigma factor that responds to disulfide stress in the cytoplasm of Actinobacteria. We show that RsrA utilizes its hydrophobic core to bind the sigma factor σ R preventing its association with RNA polymerase, and that zinc plays a central role in maintaining this high-affinity complex. Oxidation of RsrA is limited by the rate of zinc release, which weakens the RsrA-σ R complex by accelerating its dissociation. The subsequent trigger disulfide, formed between specific combinations of RsrA's three zinc-binding cysteines, precipitates structural collapse to a compact state where all σ R-binding residues are sequestered back into its hydrophobic core, releasing σ R to activate transcription of anti-oxidant genes

Variations in Multiple Birth Rates and Impact on Perinatal Outcomes in Europe

Objective Infants from multiple pregnancies have higher rates of preterm birth, stillbirth and neonatal death and differences in multiple birth rates (MBR) exist between countries. We aimed to describe differences in MBR in Europe and to investigate the impact of these differences on adverse perinatal outcomes at a population level. Methods We used national aggregate birth data on multiple pregnancies, maternal age, gestational age (GA), stillbirth and neonatal death collected in the Euro-Peristat project (29 countries in 2010, N = 5 074 643 births). We also used European Society of Human Reproduction and Embryology (ESHRE) data on assisted conception and single embryo transfer (SET). The impact of MBR on outcomes was studied using meta-analysis techniques with random-effects models to derive pooled risk ratios (pRR) overall and for four groups of country defined by their MBR. We computed population attributable risks (PAR) for these groups. Results In 2010, the average MBR was 16.8 per 1000 women giving birth, ranging from 9.1 (Romania) to 26.5 (Cyprus). Compared to singletons, multiples had a nine-fold increased risk (pRR 9.4, 95% Cl 9.1–9.8) of preterm birth (<37 weeks GA), an almost 12-fold increased risk (pRR 11.7, 95% CI 11.0–12.4) of very preterm birth (<32 weeks GA). Pooled RR were 2.4 (95% Cl 1.5–3.6) for fetal mortality at or after 28 weeks GA and 7.0 (95% Cl 6.1–8.0) for neonatal mortality. PAR of neonatal death and very preterm birth were higher in countries with high MBR compared to low MBR (17.1% (95% CI 13.8–20.2) versus 9.8% (95% Cl 9.6–11.0) for neonatal death and 29.6% (96% CI 28.5–30.6) versus 17.5% (95% CI 15.7–18.3) for very preterm births, respectively). Conclusions Wide variations in MBR and their impact on population outcomes imply that efforts by countries to reduce MBR could improve perinatal outcomes, enabling better long-term child health