Runaway Dynamics in Douglas County: Examining First-time and Repeat Runaway Behavior

CPACS Urban Research Awards Part of the mission of the College of Public Affairs and Community Service (CPACS) is to conduct research, especially as it relates to concerns of our local and statewide constituencies. CPACS has always had an urban mission, and one way that mission is served is to preform applied research relevant to urban society in general, and the Omaha metropolitan area and other Nebraska urban communities in particular. Beginning in 2014, the CPACS Dean provided funding for the projects with high relevance to current urban issues, with the potential to apply the findings to practice in Nebraska, Iowa, and beyond

Biocompatibilità e durata in vivo di cinque nuovi polimeri sintetici testati su coniglio

I materiali alloplastici vengono frequentemente utilizzati negli interventi di chirurgia plastica sul volto, quali la rinoplastica e la chirurgia ricostruttiva del naso. Ad oggi non è stato ancora individuato un materiale alloplastico con caratteristiche ottimali. Il presente studio sperimentale si propone di valutare la risposta tissutale e la resistenza nel tempo di cinque nuovi polimeri proposti come materiali alloplastici. Il presente studio è stato condotto presso un ospedale universitario di terzo livello. Sono state ricavate sei tasche sottocutanee sul dorso di 10 conigli che sono state usate per l’impianto di ciascuno dei polimeri testati più una tasca di controllo. Ciascuna delle tasche è stata escissa congiuntamente al tessuto circostante dopo tre mesi, ed è stata sottoposta ad un esame istopatologico. È stata quindi condotta una valutazione semi quantitativa con focus su neo angiogenesi, infiammazione, fibrosi, formazione di ascessi, presenza di cellule giganti multinucleate contenenti corpi estranei e stato dei polimeri testati. E’ stata inoltre effettuata una valutazione statistica, che per quanto riguarda la comparazione diretta fra la tasca di controllo e i polimeri II, III e IV non ha mostrato differenze significative in merito alla neo vascolarizzazione, all’infiammazione, alla fibrosi, alla presenza di ascessi ed alla presenza di cellule giganti multinucleate. Il polimero I ha invece mostrato un grado di fibrosi inferiore rispetto alla tasca di controllo (p = .027) and V (p = .018), benché le altre variabili prese in considerazione fossero sostanzialmente uguali. L’integrità nel tempo dei polimeri III (9 intatti, uno frammentato) e IV (8 intatti, 2 assenti) è stata migliore di quella ottenuta con gli altri polimeri testati. Questo gruppo di nuovi polimeri può essere considerato interessante per future applicazioni cliniche. Tutti i polimeri hanno mostrato risultati accettabili in termini di risposta dei tessuti, tuttavia i fenomeni di integrazione fibrovascolare sono stati maggiori nel caso dei polimeri II, III e IV. Inoltre la durata nel tempo dei polimeri III e IV è stata la migliore in assoluto

Recurrent mutation of IGF signalling genes and distinct patterns of genomic rearrangement in osteosarcoma

Osteosarcoma is a primary malignancy of bone that affects children and adults. Here, we present the largest sequencing study of osteosarcoma to date, comprising 112 childhood and adult tumours encompassing all major histological subtypes. A key finding of our study is the identification of mutations in insulin-like growth factor (IGF) signalling genes in 8/112 (7%) of cases. We validate this observation using fluorescence in situ hybridization (FISH) in an additional 87 osteosarcomas, with IGF1 receptor (IGF1R) amplification observed in 14% of tumours. These findings may inform patient selection in future trials of IGF1R inhibitors in osteosarcoma. Analysing patterns of mutation, we identify distinct rearrangement profiles including a process characterized by chromothripsis and amplification. This process operates recurrently at discrete genomic regions and generates driver mutations. It may represent an age-independent mutational mechanism that contributes to the development of osteosarcoma in children and adults alike

High-Dose Mannose-Binding Lectin Therapy for Ebola Virus Infection

Mannose-binding lectin (MBL) targets diverse microorganisms for phagocytosis and complement-mediated lysis by binding specific surface glycans. Although recombinant human MBL (rhMBL) trials have focused on reconstitution therapy, safety studies have identified no barriers to its use at higher levels. Ebola viruses cause fatal hemorrhagic fevers for which no treatment exists and that are feared as potential biothreat agents. We found that mice whose rhMBL serum concentrations were increased ≥7-fold above average human levels survived otherwise fatal Ebola virus infections and became immune to virus rechallenge. Because Ebola glycoproteins potentially model other glycosylated viruses, rhMBL may offer a novel broad-spectrum antiviral approach

The genetic heterogeneity and mutational burden of engineered melanomas in zebrafish models.

BACKGROUND: Melanoma is the most deadly form of skin cancer. Expression of oncogenic BRAF or NRAS, which are frequently mutated in human melanomas, promote the formation of nevi but are not sufficient for tumorigenesis. Even with germline mutated p53, these engineered melanomas present with variable onset and pathology, implicating additional somatic mutations in a multi-hit tumorigenic process. RESULTS: To decipher the genetics of these melanomas, we sequence the protein coding exons of 53 primary melanomas generated from several BRAF(V600E) or NRAS(Q61K) driven transgenic zebrafish lines. We find that engineered zebrafish melanomas show an overall low mutation burden, which has a strong, inverse association with the number of initiating germline drivers. Although tumors reveal distinct mutation spectrums, they show mostly C > T transitions without UV light exposure, and enrichment of mutations in melanogenesis, p53 and MAPK signaling. Importantly, a recurrent amplification occurring with pre-configured drivers BRAF(V600E) and p53-/- suggests a novel path of BRAF cooperativity through the protein kinase A pathway. CONCLUSION: This is the first analysis of a melanoma mutational landscape in the absence of UV light, where tumors manifest with remarkably low mutation burden and high heterogeneity. Genotype specific amplification of protein kinase A in cooperation with BRAF and p53 mutation suggests the involvement of melanogenesis in these tumors. This work is important for defining the spectrum of events in BRAF or NRAS driven melanoma in the absence of UV light, and for informed exploitation of models such as transgenic zebrafish to better understand mechanisms leading to human melanoma formation

Do salivary bypass tubes lower the incidence of pharyngocutaneous fistula following total laryngectomy? A retrospective analysis of predictive factors using multivariate analysis

Salivary bypass tubes (SBT) are increasingly used to prevent pharyngocutaneous fistula (PCF) following laryngectomy and pharyngolaryngectomy. There is minimal evidence as to their efficacy and literature is limited. The aim of the study was to determine if SBT prevent PCF. The study was a multicentre retrospective case control series (level of evidence 3b). Patients who underwent laryngectomy or pharyngolaryngectomy for cancer or following cancer treatment between 2011 and 2014 were included in the study. The primary outcome was development of a PCF. Other variables recorded were age, sex, prior radiotherapy or chemoradiotherapy, prior tracheostomy, type of procedure, concurrent neck dissection, use of flap reconstruction, use of prophylactic antibiotics, the suture material used for the anastomosis, tumour T stage, histological margins, day one post-operative haemoglobin and whether a salivary bypass tube was used. Univariate and multivariate analysis were performed. A total of 199 patients were included and 24 received salivary bypass tubes. Fistula rates were 8.3% in the SBT group (2/24) and 24.6% in the control group (43/175). This was not statistically significant on univariate (p value 0.115) or multivariate analysis (p value 0.076). In addition, no other co-variables were found to be significant. No group has proven a benefit of salivary bypass tubes on multivariate analysis. The study was limited by a small case group, variations in tube duration and subjects given a tube may have been identified as high risk of fistula. Further prospective studies are warranted prior to recommendation of salivary bypass tubes following laryngectomy

Radiological progression of cerebral metastases after radiosurgery: assessment of perfusion MRI for differentiating between necrosis and recurrence

To assess the capability of perfusion MRI to differentiate between necrosis and tumor recurrence in patients showing radiological progression of cerebral metastases treated with stereotactic radiosurgery (SRS). From 2004 to 2006 dynamic susceptibility-weighted contrast-enhanced perfusion MRI scans were performed on patients with cerebral metastasis showing radiological progression after SRS during follow-up. Several perfusion MRI characteristics were examined: a subjective visual score of the relative cerebral blood volume (rCBV) map and quantitative rCBV measurements of the contrast-enhanced areas of maximal perfusion. For a total of 34 lesions in 31 patients a perfusion MRI was performed. Diagnoses were based on histology, definite radiological decrease or a combination of radiological and clinical follow-up. The diagnosis of tumor recurrence was obtained in 20 of 34 lesions, and tumor necrosis in 14 of 34. Regression analyses for all measures proved statistically significant (χ2 = 11.6–21.6, P < 0.001–0.0001). Visual inspection of the rCBV map yielded a sensitivity and specificity of 70.0 respectively 92.9%. The optimal cutoff point for maximal tumor rCBV relative to white matter was 2.00 (improving the sensibility to 85.0%) and 1.85 relative to grey matter (GM), improving the specificity to 100%, with a corresponding sensitivity of 70.0%. Perfusion MRI seems to be a useful tool in the differentiation of necrosis and tumor recurrence after SRS. For the patients displaying a rCBV-GM greater than 1.85, the diagnosis of necrosis was excluded. Salvage treatment can be initiated for these patients in an attempt to prolong survival