Vaccination coverage rates have been key to evaluating childhood immunization programs. The objectives of this study were to assess the immunization coverage of children aged 5–6 years and 13–14 ...years during the 2017–2018 school year, and to identify sociodemographic factors associated with full immunization in these children.
A descriptive cross-sectional school-based study was carried out. The population under study was a sample of schoolchildren aged 5–6 years and 13–14 years attending the second and 10th grades of primary and middle schools, respectively, located in the canton of Geneva, Switzerland. The data extracted from the vaccination cards included dates of administration of all doses of diphtheria, tetanus, pertussis, polio (DTP), Haemophilus influenzae type B (Hib), measles, mumps, rubella (MMR) and hepatitis B (HBV).
We collected 1994 records of second- and 10th-grade children. Results show that 52% of our samples were fully vaccinated for DTP, MMR, Hib, and HBV. For all the vaccines examined in this study, the rates of immunization were significantly better for the second-grade than for the 10th-grade children (P<0.0001). More Spanish children were inoculated than children of Swiss nationality: OR=1.90,95% CI (1.05–3.42). More children with parents who were workers were inoculated: OR=1.35 95% CI (1.04–1.75).
This study suggests that full coverage in our sample was suboptimal. For children in the second grade, we observed high coverage rates for specific vaccines, yet the rates of MMR vaccination were lower than the level required for a herd immunity. Data collection using vaccination cards allows for regular surveillance of the vaccination coverage of school pupils and can be easily carried out in schools.
We aimed at identifying deleterious genomic alterations from untreated head and neck squamous cell carcinoma (HNSCC) patients, and assessing their prognostic value.
We retrieved 122 HNSCC patients ...who underwent primary surgery. Targeted NGS was used to analyse a panel of 100 genes selected among the most frequently altered genes in HNSCC and potential therapeutic targets. We selected only deleterious (activating or inactivating) single nucleotide variations, and copy number variations for analysis. Univariate and multivariate analyses were performed to assess the prognostic value of altered genes.
A median of 2 (range: 0–10) genomic alterations per sample was observed. Most frequently altered genes involved the cell cycle pathway (TP53 60%, CCND1 30%, CDKN2A 25%), the PI3K/AKT/MTOR pathway (PIK3CA 12%), tyrosine kinase receptors (EGFR 9%, FGFR1 5%) and cell differentiation (FAT1 7%, NOTCH1 4%). TP53 mutations (p = 0.003), CCND1 amplifications (p = 0.04), CDKN2A alterations (p = 0.02) and FGFR1 amplifications (p = 0.003), correlated with shorter overall survival (OS). The number of genomic alterations was significantly higher in the HPV-negative population (p = 0.029) and correlated with a shorter OS (p < 0.0001). Only TP53 mutation and FGFR1 amplification status remained statistically significant in the multivariate analysis.
These results suggest that genomic alterations involving the cell cycle (TP53, CCND1, CDKN2A), as well as FGFR1 amplifications and tumour genomic alterations burden are prognostic biomarkers and might be therapeutic targets for patients with HNSCC.
•Poor overall survival is observed in head and neck squamous cell carcinoma harbouring the following alterations.•Genomic alterations involving the cell cycle (TP53, CCND1, CDKN2A).•FGFR1 amplifications.•High tumour genomic alterations burden.
Chemoradiotherapy (CRT) is the standard of care for patients diagnosed with locally advanced cervical cancer (LACC), a human papillomavirus (HPV)-related cancer that relapses in 30%-60% of patients. ...This study aimed to (i) design HPV droplet digital PCR (ddPCR) assays for blood detection (including rare genotypes) and (ii) monitor blood HPV circulating tumor DNA (HPV ctDNA) levels during CRT in patients with LACC.
We analyzed blood and tumor samples from 55 patients with HPV-positive LACC treated by CRT in a retrospective cohort (n = 41) and a prospective cohort (n = 14). HPV-ctDNA detection was carried out by genotype-specific ddPCR.
HPV ctDNA was successfully detected in 69% of patients (n = 38/55) before CRT for LACC, including nine patients with a rare genotype. HPV-ctDNA level was correlated with HPV copy number in the tumor (r = 0.41, P < 0.001). HPV-ctDNA positivity for HPV18 (20%, n = 2/10) was significantly lower than for HPV16 (77%, n = 27/35) or other types (90%, n = 9/10, P = 0.002). HPV-ctDNA detection (positive versus negative) before CRT was associated with tumor stage (P = 0.037) and lymph node status (P = 0.02). Taking into account all samples from the end of CRT and during follow-up in the prospective cohort, positive HPV-ctDNA detection was associated with lower disease-free survival (DFS) (P = 0.048) and overall survival (OS) (P = 0.0013).
This is one of the largest studies to report HPV-ctDNA detection before CRT and showed clearance of HPV ctDNA at the end of treatment in most patients. Residual HPV ctDNA at the end of CRT or during follow-up could help to identify patients more likely to experience subsequent relapse.
•HPV ctDNA can be detected before CRT in patients with LACC (69%).•HPV-ctDNA detection was associated with tumor stage and lymph node status.•A lower detection rate of HPV ctDNA was observed for HPV18 genotype.•Residual ctDNA levels after CRT and during follow-up had a prognostic impact.
Scheduling stochastic workloads is a difficult task. In order to design efficient scheduling algorithms for such workloads, it is required to have a good in-depth knowledge of basic random scheduling ...strategies. This paper analyzes the distribution of sequential jobs and the system behavior in heterogeneous computational grid environments where the brokering is done in such a way that each computing element has a probability to be chosen proportional to its number of CPUs and (new from the previous paper) its relative speed. We provide the asymptotic behavior for several metrics (queue-sizes, slowdowns, etc.) or, in some cases, an approximation of this behavior. We study these metrics for a variety of workload configurations (load, distribution, etc.). We compare our probabilistic analysis to simulations in order to validate our results. These results provide a good understanding of the system behavior for each metric proposed. This enables us to design advanced and efficient algorithms for more complex cases.
Oral cavity is the most prevalent site of head and neck squamous cell carcinomas (HNSCCs). Most often diagnosed at a locally advanced stage, treatment is multimodal with surgery as the cornerstone. ...The aim of this study was to explore the molecular landscape of a homogenous cohort of oral cavity squamous cell carcinomas (OCSCCs), and to assess the prognostic value of tumor mutational burden (TMB), along with classical molecular and clinical parameters.
One hundred and fifty-one consecutive patients with OCSCC treated with upfront surgery at the Institut Curie were analyzed. Sequencing of tumor DNA from frozen specimens was carried out using an in-house targeted next-generation sequencing panel (571 genes). The impact of molecular alterations and TMB on disease-free survival (DFS) and overall survival (OS) was evaluated in univariate and multivariate analyses.
Pathological tumor stage, extranodal spread, vascular emboli, and perineural invasion were associated with both DFS and OS. TP53 was the most mutated gene (71%). Other frequent molecular alterations included the TERT promoter (50%), CDKN2A (25%), FAT1 (17%), PIK3CA (14%), and NOTCH1 (15%) genes. Transforming growth factor-β pathway alterations (4%) were associated with poor OS (P = 0.01) and DFS (P = 0.02) in univariate and multivariate analyses. High TMB was associated with prolonged OS (P = 0.01 and P = 0.02, in the highest 10% and 20% TMB values, respectively), but not with DFS. Correlation of TMB with OS remained significant in multivariate analysis (P = 0.01 and P = 0.005 in the highest 10% and 20% TMB values, respectively). Pathological tumor stage combined with high TMB was associated with good prognosis.
Our results suggest that a high TMB is associated with a favorable prognosis in patients with OCSCC treated with upfront surgery.
•High TMB is associated with a favorable prognosis in patients with OCSCC treated with upfront surgery•Pathological tumor stage combined with high TMB is associated with good prognosis•TP53 was the most mutated gene (71%). Other frequent molecular alterations included the TERT promoter (50%)•TGFβ pathway alterations were associated with poor outcomes, although it was only observed in 4% of the patients
To determine the prevalence and factors associated with syphilis, human immunodeficiency virus (HIV), hepatitis B (HBV) and herpes type 2 (HSV2) among women in the prison of San Sebastian in ...Cochabamba (Bolivia).
We carried out a cross-sectional study including a standardized questionnaire to assess socio-demographics characteristics and risk factors (sexual practices and exposure to blood); and serological tests for syphilis, HSV2, VIH, and HBV. We performed bivariate and multivariate analyses to test the associations between variables of interest and infections.
A total of 219 out of 220 prisoners (99.5%) participated in the study. For syphilis, 12.8% of participants had both reactive tests (RPR+/TPPA+). The prevalence of HSV2 and VIH was 62.6% and 1.4%, respectively. Anti-HBc, indicating a resolved or chronic HBV, was positive in 11.9% of participants and 0.5% had active HBV (HBsAg positive). A low level of education was associated with syphilis, HSV2 and HBV. Having occasional sexual partners was associated with syphilis and HSV2. Being over 36 years old and having more than 3 children were associated with HBV. The number of sexual partners, history of prostitution and rape, having sexual intercourses in prison and detention time were not associated with any of these infections.
The prevalence of syphilis, HIV, HSV2 and HBV was higher in this vulnerable female population than in the general population in Bolivia. Control measures in detention are needed to limit the spread of these infections both in prisons and in the community.
An abstract of the study by Kamal et al evaluating large-scale pharmacological screenings of cancer cell lines to enlarge cancer treatment options is presented. In this study, they performed ...pharmacological profiling of a panel of 20 original cervical cancer cell lines and attempt to correlate drug responsiveness with genomic markers. Results, the number of druggable mutations detected in each of the 20 cell lines varied between 5 and 21 while the range of genetic variants identified by full exome sequencing was 500 and 2000. Furthermore, strategies envisioning to enlarge cancer treatment options will need to take into account include, correlations between mutational data and drug response in cell line screening.
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