A GridPix TPC readout for the ILD experiment at the future International Linear Collider

In the quest for a more complete theory of nature, the precise investigation of the Higgs boson at a future electron positron collider has the highest priority. The best tracking performance for a TPC at the proposed International Linear Collider is offered by a TPC with a GridPix readout. The viability of a GridPix TPC readout has been demonstrated in the two detector tests described in this thesis, and the expected performance is established in a comprehensive simulation. In conclusion, the GridPix has a lot of potential for experiments at the next generation of high-energy electron positron colliders

INR reduction after prothrombin complex concentrate (Co-Fact) administration.:Comparison of INR outcomes in different patient categories at the emergency department

BACKGROUND: Co-fact(©), prothrombin complex concentrate, is used for restoring the international normalized ratio (INR) in patients on vitamin K antagonists (VKA) presenting with acute bleeding. In this prospective cohort study, we evaluated whether adequate INR values were reached in ED patients using the Sanquin (Federation of Dutch Thrombosis Services) treatment protocol. METHODS: We evaluated this protocol for two target INR groups: group 1, target INR ≤ 1.5 (for life-threatening bleeding/immediate intervention); group 2, target INR 1.6-2.1 (in cases of a minor urgent surgery or serious overdosing of anticoagulant). We specifically wanted to identify both under- and over-treated patients. Reversing VKA anticoagulation therapy to unnecessarily low INR values may involve thrombotic risks. Apart from this risk, the patient is also administered an excess amount of the drug. This means unnecessary costs and may present problems with restoring an anticoagulated state at a later time. RESULTS: In our cohort, the Sanquin dosing protocol was followed for 45/60 patients. It appeared that out of the 41 patients in group 1 (target INR ≤ 1.5), 35 (85%) achieved the goal INR. This occurred more often than for the 19 patients in group 2 (target INR 1.6–2.1), where only 6 (32%) achieved the goal INR. Using the protocol resulted in a positive trend toward better INR reversal in group 1. In group 2, no relation between using the protocol and achieving the desired INR value was detected. Physicians ignoring the proposed dose of Co-fact(©) prescribed significantly less Co-fact(©) (even when correcting for patient weight). It appeared that patients in group 1 had a significantly lower baseline INR than patients in group 2. Group 2 patients, on the other hand, had a baseline INR > 7.5 in 53% of the cases. CONCLUSION: In our cohort, for most patients in INR group 2 treated with Co-fact(©), the achieved INR value was outside the desired range of 1.6-2.1. The supra-therapeutic range of baseline INR in group 2 may have contributed to the different kind of bleeding witnessed in this patient group. Our results support the idea that treatment of patients on vitamin K antagonists with Co-fact(©) could benefit from a slightly different approach, taking into account the INR value to which the patient needs to be reversed

The caval index:an adequate non-invasive ultrasound parameter to predict fluid responsiveness in the emergency department?

Background: Fluid therapy is the first important step in patients with signs of shock but assessment of the volume status is difficult and invasive measurements are not readily available in the emergency department. We have investigated whether the respiratory variation in diameter of the inferior vena cava is a reliable parameter to predict fluid responsiveness in spontaneous breathing emergency department patients with signs of shock. Methods: All patients admitted to the emergency department during a 15 week period were screened for signs of shock. If the attending physician planned to give a fluid challenge, the caval index was determined by transabdominal ultrasonography in supine position. Immediately afterwards 500 ml NaCl 0.9% was administered in 15 minutes and the clinical response was observed. An adequate response was defined as an increase in systolic blood pressure of at least 10 mm Hg. Based on this definition patients were divided into responders and non-responders. Results: After selection a total number of 45 patients was included. A low caval index (<36.5%) in patients with signs of shock reliably predicted the absence of an adequate response to fluid therapy (negative predictive value 92%). The positive predictive value of a high caval index was much lower (48%) despite the fact that responders had a significantly higher pre-infusion caval index than non-responders (48.7% vs 31.8%, p 0.014). Conclusions: In spontaneously breathing patients with signs of shock in the emergency department, a high caval index (>36.5%) does not reliably predict fluid responsiveness in our study, while a low caval index (<36.5%) makes fluid responsiveness unlikely. An explanation for the absence of a blood pressure response in the group of patients with a low high caval index might be that these patients represent a group requiring more volume therapy than 500 ml

Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood appr

Assessing Associations between the AURKA-HMMR-TPX2-TUBG1 Functional Module and Breast Cancer Risk in BRCA1/2 Mutation Carriers

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 - 1.15, p = 1.9 x 10(-4) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted p(interaction) values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.Peer reviewe

Improving background estimation in events with multiple jets and at least one charged lepton

The ATLAS experiment searches for SUSY signal events with many jets and at least one charged lepton. The backgrounds for these signals are not well described by Monte Carlo generators. For the dominant $t\bar{t}$ background, the performance of several generators is compared. For the $W+$jets background, the charge asymmetry method as a tool for background estimation is investigated. Chances to improve the estimations of both backgrounds are indicated