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Rationale: Despite oxygen's classification as an essential medication by the World Health Organization, it is inconsistently available in many resource-constrained settings. Hypoxemia is associated with increased mortality, and mounting evidence suggests that hyperoxia may also be associated with adverse outcomes. Objectives: To determine if overuse of oxygen for some patients in a Rwandan tertiary care hospital emergency department might coexist with oxygen shortages and underuse of oxygen for other patients, and whether an educational intervention coupled with provision of pulse oximeters could improve the distribution of limited oxygen resources. Methods: We screened all patients in the adult emergency department (ED) of the University Teaching Hospital of Kigali for hypoxemia and receipt of oxygen therapy for 5 weeks. After completing baseline data collection, we provided pulse oximeters and conducted a didactic training with pre- and posttests on oxygen titration, with a chosen target oxygen saturation (SpO2) of 90% to 95%. Four and 12 weeks after the intervention, we evaluated all patients in the ED again for SpO2and receipt of oxygen therapy for 4 weeks each period.We also recorded ED oxygen use and availability of reserve oxygen for the hospital during the three study periods. Results: During all data collection periods, 214 of 1,765 (12.1%) unique patients screened were hypoxemic. The proportion of patient-days with appropriately titrated oxygen therapy (SpO2, 90-95%) increased from 18.7% at baseline to 38.5% and 42.0% at 4 and 12 weeks postintervention (P<0.001). On a multiple-choice examination testing knowledge of appropriate oxygen titration, clinicians' scores improved from average 60% (interquartile range [IQR], 40-80%) correct to 80% (IQR, 60-80%) correct immediately after the educational intervention (P<0.001). Oxygen use in the ED decreased from amedian of 32.0 (IQR, 28.0-35.0) tanks per day to 25.5 (IQR, 24.0-29.0) and 16.0 (IQR, 12.5-21.0) tanks, SCOPUS: ar.j, DecretOANoAutActif, info:eu-repo/semantics/published

Purpose The role of temporary ovarian suppression with gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy as a strategy to preserve ovarian function and fertility in premenopausal women remains controversial. This systematic review and meta-analysis using individual patient–level data was conducted to better assess the efficacy and safety of this strategy in patients with early breast cancer. Methods The trials in which premenopausal women with early breast cancer were randomly assigned to receive (neo)adjuvant chemotherapy alone or with concurrent GnRHa were eligible for inclusion. Primary end points were premature ovarian insufficiency (POI) rate and post-treatment pregnancy rate. Disease-free survival and overall survival were secondary end points. Because each study represents a cluster, statistical analyses were performed using a random effects model. Results A total of 873 patients from five trials were included. POI rate was 14.1% in the GnRHa group and 30.9% in the control group (adjusted odds ratio, 0.38; 95% CI, 0.26 to 0.57; P, 001). A total of 37 (10.3%) patients had at least one post-treatment pregnancy in the GnRHa group and 20 (5.5%) in the control group (incidence rate ratio, 1.83; 95% CI, 1.06 to 3.15; P = .030). No significant differences in disease-free survival (adjusted hazard ratio, 1.01; 95% CI, 0.72 to 1.42; P = .999) and overall survival (adjusted hazard ratio, 0.67; 95% CI, 0.42 to 1.06; P = .083) were observed between groups. Conclusion Our findings provide evidence for the efficacy and safety of temporary ovarian suppression with GnRHa during chemotherapy as an available option to reduce the likelihood of chemotherapy-induced POI and potentially improve future fertility in premenopausal patients with early breast cancer., SCOPUS: re.j, info:eu-repo/semantics/published

SCOPUS: le.j, info:eu-repo/semantics/published

Contains fulltext : 167177.pdf (publisher's version ) (Open Access), BACKGROUND: Regulatory T (Treg) cells, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and, thus, variants in genes encoding Treg cell immune molecules could be associated with ovarian cancer. METHODS: In a population of 15,596 epithelial ovarian cancer (EOC) cases and 23,236 controls, we measured genetic associations of 1,351 SNPs in Treg cell pathway genes with odds of ovarian cancer and tested pathway and gene-level associations, overall and by histotype, for the 25 genes, using the admixture likelihood (AML) method. The most significant single SNP associations were tested for correlation with expression levels in 44 ovarian cancer patients. RESULTS: The most significant global associations for all genes in the pathway were seen in endometrioid (p = 0.082) and clear cell (p = 0.083), with the most significant gene level association seen with TGFBR2 (p = 0.001) and clear cell EOC. Gene associations with histotypes at p < 0.05 included: IL12 (p = 0.005 and p = 0.008, serous and high-grade serous, respectively), IL8RA (p = 0.035, endometrioid and mucinous), LGALS1 (p = 0.03, mucinous), STAT5B (p = 0.022, clear cell), TGFBR1 (p = 0.021 endometrioid) and TGFBR2 (p = 0.017 and p = 0.025, endometrioid and mucinous, respectively). CONCLUSIONS: Common inherited gene variation in Treg cell pathways shows some evidence of germline genetic contribution to odds of EOC that varies by histologic subtype and may be associated with mRNA expression of immune-complex receptor in EOC patients.

Contains fulltext : 167177.pdf (publisher's version ) (Open Access), BACKGROUND: Regulatory T (Treg) cells, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and, thus, variants in genes encoding Treg cell immune molecules could be associated with ovarian cancer. METHODS: In a population of 15,596 epithelial ovarian cancer (EOC) cases and 23,236 controls, we measured genetic associations of 1,351 SNPs in Treg cell pathway genes with odds of ovarian cancer and tested pathway and gene-level associations, overall and by histotype, for the 25 genes, using the admixture likelihood (AML) method. The most significant single SNP associations were tested for correlation with expression levels in 44 ovarian cancer patients. RESULTS: The most significant global associations for all genes in the pathway were seen in endometrioid (p = 0.082) and clear cell (p = 0.083), with the most significant gene level association seen with TGFBR2 (p = 0.001) and clear cell EOC. Gene associations with histotypes at p < 0.05 included: IL12 (p = 0.005 and p = 0.008, serous and high-grade serous, respectively), IL8RA (p = 0.035, endometrioid and mucinous), LGALS1 (p = 0.03, mucinous), STAT5B (p = 0.022, clear cell), TGFBR1 (p = 0.021 endometrioid) and TGFBR2 (p = 0.017 and p = 0.025, endometrioid and mucinous, respectively). CONCLUSIONS: Common inherited gene variation in Treg cell pathways shows some evidence of germline genetic contribution to odds of EOC that varies by histologic subtype and may be associated with mRNA expression of immune-complex receptor in EOC patients.

Contains fulltext : 167177.pdf (publisher's version ) (Open Access), BACKGROUND: Regulatory T (Treg) cells, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and, thus, variants in genes encoding Treg cell immune molecules could be associated with ovarian cancer. METHODS: In a population of 15,596 epithelial ovarian cancer (EOC) cases and 23,236 controls, we measured genetic associations of 1,351 SNPs in Treg cell pathway genes with odds of ovarian cancer and tested pathway and gene-level associations, overall and by histotype, for the 25 genes, using the admixture likelihood (AML) method. The most significant single SNP associations were tested for correlation with expression levels in 44 ovarian cancer patients. RESULTS: The most significant global associations for all genes in the pathway were seen in endometrioid (p = 0.082) and clear cell (p = 0.083), with the most significant gene level association seen with TGFBR2 (p = 0.001) and clear cell EOC. Gene associations with histotypes at p < 0.05 included: IL12 (p = 0.005 and p = 0.008, serous and high-grade serous, respectively), IL8RA (p = 0.035, endometrioid and mucinous), LGALS1 (p = 0.03, mucinous), STAT5B (p = 0.022, clear cell), TGFBR1 (p = 0.021 endometrioid) and TGFBR2 (p = 0.017 and p = 0.025, endometrioid and mucinous, respectively). CONCLUSIONS: Common inherited gene variation in Treg cell pathways shows some evidence of germline genetic contribution to odds of EOC that varies by histologic subtype and may be associated with mRNA expression of immune-complex receptor in EOC patients.

The massive use of private cars causes serious problems. Despite parking problems and traffic congestions, for many the private car remains favourable. As an alternative, a new type of public intercity transport has been proposed, called Fast Transport on Request (FTR). Specific elements are: dedicated tracks for high speed bus driving between the cities; booking via Internet or intelligent telephone; intelligent logistics control reducing the number of stops and excluding detours; adaptive seats and digital facilities.

The remarks by professor Weidmann concern: (1) Trip booking (discussed in III); The unmanageable number of O/D-relations (discussed in I); (2) Relations with other PTmodalities (discussed in II); (3) Capacity (see I and Profile paper: ‘State of art of fast transport by buses’); (4) Political feasibility (discussed in V and VI); (5) Speed (discussed in II) and (6) Infrastructure (discussed in II, VI and VII). The remarks of professor Bookhuis concern: (1) FTR as an alternative for car travelling (discussed in IV) and (2) Opportunities (discussed in VII). The author thanks professor Brookhuis and professor Weidmann for their interesting and stimulating remarks.

This study concerns the deployment of large numbers of container transporting vehicles on a network consisting of (dedicated) roads and logistic sites such as container terminals. Each site is managed autonomously by a site manager. The fleet of vehicles is deployed by a fleet manager. On request of the site managers, the fleet manager allocates vehicles to be hired by the site managers. Next, within these allocations, each site manager issues transportation jobs and assigns these jobs to the allocated vehicles. The objective of the fleet manager is to avoid unpaid empty driving and to keep the size of its fleet just large enough the serve the demand for vehicles. The objective of the site managers is to minimize the operational costs. In this context a new coordination system is proposed to allocate vehicle capacity, operating on the basis of a win-win situation for all actors. The coordination takes place at two levels. One level concerns the drawing up of an adaptive fleet deployment plan. The other level resides under control of the individual site managers and concerns the assignment of transportation jobs to vehicles, given the allocations of the fleet deployment plan. Both use repetitive linear programming procedures. Small size simulation experiments show that the approach might be effective.

Objective: The objective of the study was to achieve limb salvage in patients with locally advanced soft tissue sarcomas that can only be treated by amputation or functionally mutilating surgery by performing an isolated limb perfusion (ILP) with tumor necrosis factor (TNF) + melphalan (M) as induction biochemotherapy to obtain local control and make limb-sparing surgery possible. Summary Background Data: To increase the number of limb- sparing resections in the treatment of locally advanced extremity soft tissue sarcoma, preoperative radiation therapy or chemotherapy or a combination of the two often are applied. The ILP with cytostatic agents alone is another option but rarely is used because of rather poor results. The efficacy of the application of TNF in ILP markedly has changed this situation. Methods: In 8 cancer centers, 186 patients were treated over a period of almost 4.5 years. There were 107 (57%) primary and 79 (43%) recurrent sarcomas, mostly high grade (110 grade III; 51 grade II; and 25 very large, recurrent, or multiple grade I sarcomas). The composition of this series of patients is unusual: 42 patients (23%) had multifocal primary or multiple recurrent tumors; median tumor size was very large (16 cm); 25 patients (13%) had known systemic metastases at the time of the ILP. Patients underwent a 90-minute ILP at 39 to 40 C with TNF + melphalan. The first 55 patients also received interferon- τ. A delayed marginal resection of the tumor remnant was done 2 to 4 months after ILP. Results: A major tumor response was seen in 82% of the patients rendering these large sarcomas resectable in most cases. Clinical response rates were: 33 complete response (CR) (18%), 106 partial response (PR) (57%), 42 no change (NC) (22%), and 5 progressive disease (PD) (3%). Final outcome was defined by clinical and pathologic response: 54 CR (29%), 99 PR (53%), 29 NC (16%), and 4 PD (2%). At a median follow up of almost 2 years (22 months; range, 6-58 months), limb salvage, SCOPUS: ar.j, info:eu-repo/semantics/published