Bringing Forecasting Into the Future: Using Google to Predict Visitation in U.S. National Parks

In recent years, visitation to U.S. National Parks has been increasing, with the majority of this increase occurring in a subset of parks. As a result, managers in these parks must respond quickly to increasing visitor-related challenges. Improved visitation forecasting would allow managers to more proactively plan for such increases. In this study, we leverage internet search data that is freely available through Google Trends to create a forecasting model. We compare this Google Trends model to a traditional autoregressive forecasting model. Overall, our Google Trends model accurately predicted 97% of the total visitation variation to all parks one year in advance from 2013 to 2017 and outperformed the autoregressive model by all metrics. While our Google Trends model performs better overall, this was not the case for each park unit individually; the accuracy of this model varied significantly from park to park. We hypothesized that park attributes related to trip planning would correlate with the accuracy of our Google Trends model, but none of the variables tested produced overly compelling results. Future research can continue exploring the utility of Google Trends to forecast visitor use in protected areas, or use methods demonstrated in this paper to explore alternative data sources to improve visitation forecasting in U.S. National Parks

DNA Repair Biomarker for Lung Cancer Risk and its Correlation With Airway Cells Gene Expression.

Background: Improving lung cancer risk assessment is required because current early-detection screening criteria miss most cases. We therefore examined the utility for lung cancer risk assessment of a DNA Repair score obtained from OGG1, MPG, and APE1 blood tests. In addition, we examined the relationship between the level of DNA repair and global gene expression. Methods: We conducted a blinded case-control study with 150 non-small cell lung cancer case patients and 143 control individuals. DNA Repair activity was measured in peripheral blood mononuclear cells, and the transcriptome of nasal and bronchial cells was determined by RNA sequencing. A combined DNA Repair score was formed using logistic regression, and its correlation with disease was assessed using cross-validation; correlation of expression to DNA Repair was analyzed using Gene Ontology enrichment. Results: DNA Repair score was lower in case patients than in control individuals, regardless of the case's disease stage. Individuals at the lowest tertile of DNA Repair score had an increased risk of lung cancer compared to individuals at the highest tertile, with an odds ratio (OR) of 7.2 (95% confidence interval [CI] = 3.0 to 17.5; P < .001), and independent of smoking. Receiver operating characteristic analysis yielded an area under the curve  of 0.89 (95% CI = 0.82 to 0.93). Remarkably, low DNA Repair score correlated with a broad upregulation of gene expression of immune pathways in patients but not in control individuals. Conclusions: The DNA Repair score, previously shown to be a lung cancer risk factor in the Israeli population, was validated in this independent study as a mechanism-based cancer risk biomarker and can substantially improve current lung cancer risk prediction, assisting prevention and early detection by computed tomography scanning.This work was funded by grants from NIH/NCI/EDRN (#1 U01 CA111219), the Flight Attendant Medical Research Institute, Florida, the Mike Rosenbloom Foundation and Weizmann Institute of Science to ZL and TPE; and by grants from Cancer Research UK to BP and to the Cancer Research UK Cambridge Centre; and by a UK National Institute for Health Research Senior Fellowship to BP; and by the Cambridge Biomedical Research Centre and the Cancer Research UK Cambridge Centre to RCR. Volunteer participant recruitment through the Cambridge Bioresource was funded by the Cambridge Biomedical Research Centre

Oligonucleotide-assisted cleavage and ligation: a novel directional DNA cloning technology to capture cDNAs. Application in the construction of a human immune antibody phage-display library

The use of oligonucleotide-assisted cleavage and ligation (ONCL), a novel approach to the capture of gene repertoires, in the construction of a phage-display immune antibody library is described. ONCL begins with rapid amplification of cDNA ends to amplify all members equally. A single, specific cut near 5′ and/or 3′ end of each gene fragment (in single stranded form) is facilitated by hybridization with an appropriate oligonucleotide adapter. Directional cloning of targeted DNA is accomplished by ligation of a partially duplex DNA molecule (containing suitable restriction sites) and amplification with primers in constant regions. To demonstrate utility and reliability of ONCL, a human antibody repertoire was cloned from IgG mRNA extracted from human B-lymphocytes engrafted in Trimera mice. These mice were transplanted with peripheral blood lymphocytes from Candida albicans infected individuals and subsequently immunized with C.albicans glyceraldehyde-3-phosphate dehydrogenase (GAPDH). DNA sequencing showed that ONCL resulted in efficient capture of gene repertoires. Indeed, full representation of all V(H) families/segments was observed showing that ONCL did not introduce cloning biases for or against any V(H) family. We validated the efficiency of ONCL by creating a functional Fab phage-display library with a size of 3.3 × 10(10) and by selecting five unique Fabs against GAPDH antigen

De-Suppression of Mesenchymal Cell Identities and Variable Phenotypic Outcomes Associated with Knockout of Bbs1

Bardet–Biedl syndrome (BBS) is an archetypal ciliopathy caused by dysfunction of primary cilia. BBS affects multiple tissues, including the kidney, eye and hypothalamic satiety response. Understanding pan-tissue mechanisms of pathogenesis versus those which are tissue-specific, as well as gauging their associated inter-individual variation owing to genetic background and stochastic processes, is of paramount importance in syndromology. The BBSome is a membrane-trafficking and intraflagellar transport (IFT) adaptor protein complex formed by eight BBS proteins, including BBS1, which is the most commonly mutated gene in BBS. To investigate disease pathogenesis, we generated a series of clonal renal collecting duct IMCD3 cell lines carrying defined biallelic nonsense or frameshift mutations in Bbs1, as well as a panel of matching wild-type CRISPR control clones. Using a phenotypic screen and an unbiased multi-omics approach, we note significant clonal variability for all assays, emphasising the importance of analysing panels of genetically defined clones. Our results suggest that BBS1 is required for the suppression of mesenchymal cell identities as the IMCD3 cell passage number increases. This was associated with a failure to express epithelial cell markers and tight junction formation, which was variable amongst clones. Transcriptomic analysis of hypothalamic preparations from BBS mutant mice, as well as BBS patient fibroblasts, suggested that dysregulation of epithelial-to-mesenchymal transition (EMT) genes is a general predisposing feature of BBS across tissues. Collectively, this work suggests that the dynamic stability of the BBSome is essential for the suppression of mesenchymal cell identities as epithelial cells differentiate

Effect of Pneumococcal Conjugate Vaccination on Serotype-Specific Carriage and Invasive Disease in England: A Cross-Sectional Study

A cross sectional study by Stefan Flasche and coworkers document the serotype replacement of Streptococcus pneumoniae that has occurred in England since the introduction of PCV7 vaccination

Rates of acquisition and clearance of pneumococcal serotypes in the nasopharynges of children in Kilifi District, Kenya.

BACKGROUND: To understand and model the impact of pneumococcal conjugate vaccines at the population level, we need to know the transmission dynamics of individual pneumococcal serotypes. We estimated serotype-specific clearance and acquisition rates of nasopharyngeal colonization among Kenyan children. METHODS: Children aged 3-59 months who were identified as carriers in a cross-sectional survey were followed-up approximately 1, 2, 4, 8, 16, and 32 days later and monthly thereafter until culture of 2 consecutive swabs yielded an alternative serotype or no pneumococcus. Serotype-specific clearance rates were estimated by exponential regression of interval-censored carriage durations. Duration was estimated as the reciprocal of the clearance rate, and acquisition rates were estimated on the basis of prevalence and duration, assuming an equilibrium state. RESULTS: Of 2840 children sampled between October 2006 and December 2008, 1868 were carriers. The clearance rate was 0.032 episodes/day (95% confidence interval [CI], .030-.034), for a carriage duration of 31.3 days, and the rate varied by serotype (P< .0005). Carriage durations for the 28 serotypes with ≥ 10 carriers ranged from 6.7 to 50 days. Clearance rates increased with year of age, adjusted for serotype (hazard ratio, 1.21; 95% CI, 1.15-1.27). The acquisition rate was 0.061 episodes/day (95% CI, .055-.067), which did not vary with age. Serotype-specific acquisition rates varied from 0.0002 to 0.0022 episodes/day. Serotype-specific acquisition rates correlated with prevalence (r=0.91; P< .00005) and with acquisition rates measured in a separate study involving 1404 newborns in Kilifi (r=0.87; P< .00005). CONCLUSIONS: The large sample size and short swabbing intervals provide a precise description of the prevalence, duration, and acquisition of carriage of 28 pneumococcal serotypes. In Kilifi, young children experience approximately 8 episodes of carriage per year. The declining prevalence with age is attributable to increasing clearance rates

S. pneumoniae transmission according to inclusion in conjugate vaccines: Bayesian analysis of a longitudinal follow-up in schools

BACKGROUND: Recent trends of pneumococcal colonization in the United States, following the introduction of conjugate vaccination, indicate that non-vaccine serotypes tend to replace vaccine serotypes. The eventual extent of this replacement is however unknown and depends on serotype-specific carriage and transmission characteristics. METHODS: Here, some of these characteristics were estimated for vaccine and non-vaccine serotypes from the follow-up of 4,488 schoolchildren in France in 2000. A Bayesian approach using Markov chain Monte Carlo data augmentation techniques was used for estimation. RESULTS: Vaccine and non-vaccine serotypes were found to have similar characteristics: the mean duration of carriage was 23 days (95% credible interval (CI): 21, 25 days) for vaccine serotypes and 22 days (95% CI: 20, 24 days) for non-vaccine serotypes; within a school of size 100, the Secondary Attack Rate was 1.1% (95% CI: 1.0%, 1.2%) for both vaccine and non-vaccine serotypes. CONCLUSION: This study supports that, in 3–6 years old children, no competitive advantage exists for vaccine serotypes compared to non-vaccine serotypes. This is an argument in favour of important serotype replacement. It would be important to validate the result for infants, who are known to be the main reservoir in maintaining transmission. Overall reduction in pathogenicity should also be taken into account in forecasting the future burden of pneumococcal colonization in vaccinated populations

Response to sunitinib in combination with proton beam radiation in a patient with chondrosarcoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Chondrosarcoma is well-known to be primarily resistant to conventional radiation and chemotherapy.</p> <p>Case presentation</p> <p>We present the case of a 32-year-old Caucasian man with clear cell chondrosarcoma who presented with symptomatic recurrence in his pelvis and metastases to his skull and lungs. Our patient underwent systemic therapy with sunitinib and then consolidation with proton beam radiation to his symptomatic site. He achieved complete symptomatic relief with a significantly improved performance status and had an almost complete and durable metabolic response on fluorine-18-fluorodeoxyglucose positron emission tomography.</p> <p>Conclusions</p> <p>Our findings have important clinical implications and suggest novel clinical trials for this difficult to treat disease.</p