Recognition of genetic predisposition in pediatric cancer patients: An easy-to-use selection tool

Genetic predisposition for childhood cancer is under diagnosed. Identifying these patients may lead to therapy adjustments in case of syndrome-related increased toxicity or resistant disease and syndrome-specific screening programs may lead to early detection of a further independent malignancy. Cancer surveillance might also be warranted for affected relatives and detection of a genetic mutation can allow for reproductive counseling.Here we present an easy-to-use selection tool, based on a systematic review of pediatric cancer predisposing syndromes, to identify patients who may benefit from genetic counseling. The selection tool involves five questions concerning family history, the type of malignancy, multiple primary malignancies, specific features and excessive toxicity, which results in the selection of those patients that may benefit from referral to a clinical geneticist

Abca1 deficiency protects the heart against myocardial infarction-induced injury

Background and aims We explored the role of ATP-binding cassette transporter A1 (Abca1), in post-myocardial infarction (MI) cardiac injury. Methods In Abca1–/– mice, wild type (WT) mice, and WT mice transplanted with Abca1–/– or WT bone marrow, an MI was induced in vivo. Furthermore, an ex vivo MI was induced in isolated Abca1–/– and WT hearts. Results Twenty-four hours and two weeks after in vivo MI induction, MI size was reduced in Abca1–/– (−58%, p = 0.007; −59%, p = 0.03) compared to WT. Ex vivo MI induction showed no effect of Abca1–/– on infarct size. Interestingly, two weeks after MI, Abca1–/– mice showed higher circulating levels of B-cells (+3.0 fold, p = 0.02) and T-cells (+4.2 fold, p = 0.002) compared to WT. Bone marrow-specific Abca1–/– tended to reduce infarct size (−43%, p = 0.12), suggesting a detrimental role for hematopoietic Abca1 after MI. Conclusions Although Abca1 has a protective role in atherosclerosis, it exerts detrimental effects on cardiac function after MI. Keywords * Abca1 deficiency; * Myocardial infarction; * Immune cells; * Mic

Studying Millisecond Pulsars in X-rays

Millisecond pulsars represent an evolutionarily distinct group among rotation-powered pulsars. Outside the radio band, the soft X-ray range ($\sim 0.1$--10 keV) is most suitable for studying radiative mechanisms operating in these fascinating objects. X-ray observations revealed diverse properties of emission from millisecond pulsars. For the most of them, the bulk of radiation is of a thermal origin, emitted from small spots (polar caps) on the neutron star surface heated by relativistic particles produced in pulsar acceleration zones. On the other hand, a few other very fast rotating pulsars exhibit almost pure nonthermal emission generated, most probably, in pulsar magnetospheres. There are also examples of nonthermal emission detected from X-ray nebulae powered by millisecond pulsars, as well as from pulsar winds shocked in binary systems with millisecond pulsars as companions. These and other most important results obtained from X-ray observations of millisecond pulsars are reviewed in this paper, as well as results from the search for millisecond pulsations in X-ray flux of the radio-quite neutron star RX J1856.5-3754

Repeated cervical length measurements for the verification of short cervical length

Research into fetal development and medicin

Adjuvant Hepatic Arterial Infusion Pump Chemotherapy After Resection of Colorectal Liver Metastases: Results of a Safety and Feasibility Study in The Netherlands

Background: The 10-year overall survival with adjuvant hepatic arterial infusion pump (HAIP) chemotherapy after resection of colorectal liver metastases (CRLMs) was 61% in clinical trials from Memorial Sloan Kettering Cancer Center. A pilot study was performed to evaluate the safety and feasibility of adjuvant HAIP chemotherapy in patients with resectable CRLMs. Study Design: A phase II study was performed in two centers in The Netherlands. Patients with resectable CRLM without extrahepatic disease were eligible. All patients underwent complete resection and/or ablation of CRLMs and pump implantation. Safety was determined by the 90-day HAIP-related postoperative complications from the day of pump placement (Clavien–Dindo classification, grade III or higher) and feasibility by the successful administration of the first cycle of HAIP chemotherapy. Results: A total of 20 patients, with a median age of 57 years (interquartile range [IQR] 51–64) were included. Grade III or higher HAIP-related postoperative complications were found in two patients (10%), both of whom had a reoperation (without laparotomy) to replace a pump with a slow flow rate or to reposition a flipped pump. No arterial bleeding, arterial dissection, arterial thrombosis, extrahepatic perfusion, pump pocket hematoma, or pump pocket infections were found within 90 days after surgery. After a median of 43 days (IQR 29–52) following surgery, all patients received the first dose of HAIP chemotherapy, which was completed un

Narrowband Searches for Continuous and Long-duration Transient Gravitational Waves from Known Pulsars in the LIGO-Virgo Third Observing Run

Isolated neutron stars that are asymmetric with respect to their spin axis are possible sources of detectable continuous gravitational waves. This paper presents a fully coherent search for such signals from eighteen pulsars in data from LIGO and Virgo's third observing run (O3). For known pulsars, efficient and sensitive matched-filter searches can be carried out if one assumes the gravitational radiation is phase-locked to the electromagnetic emission. In the search presented here, we relax this assumption and allow both the frequency and the time derivative of the frequency of the gravitational waves to vary in a small range around those inferred from electromagnetic observations. We find no evidence for continuous gravitational waves, and set upper limits on the strain amplitude for each target. These limits are more constraining for seven of the targets than the spin-down limit defined by ascribing all rotational energy loss to gravitational radiation. In an additional search, we look in O3 data for long-duration (hours-months) transient gravitational waves in the aftermath of pulsar glitches for six targets with a total of nine glitches. We report two marginal outliers from this search, but find no clear evidence for such emission either. The resulting duration-dependent strain upper limits do not surpass indirect energy constraints for any of these targets. © 2022. The Author(s). Published by the American Astronomical Society

Adjuvant hepatic arterial infusion pump chemotherapy and resection versus resection alone in patients with low-risk resectable colorectal liver metastases - the multicenter randomized controlled PUMP trial

Background Recurrences are reported in 70% of all patients after resection of colorectal liver metastases (CRLM), in which half are confined to the liver. Adjuvant hepatic arterial infusion pump (HAIP) chemotherapy aims to reduce the risk of intrahepatic recurrence. A large retrospective propensity score analysis demonstrated that HAIP chemotherapy is particularly effective in patients with low-risk oncological features. The aim of this randomized controlled trial (RCT) --the PUMP trial-- is to investigate the efficacy of adjuvant HAIP chemotherapy in low-risk patients with resectable CRLM. Methods This is an open label multicenter RCT. A total of 230 patients with resectable CRLM without extrahepatic disease will be included. Only patients with a clinical risk score (CRS) of 0 to 2 are eligible, meaning: patients are allowed to have no more than two out of five poor prognostic factors (disease-free interval less than 12 months, node-positive colorectal cancer, more than 1 CRLM, largest CRLM more than 5 cm in diameter, serum Carcinoembryonic Antigen above 200 μg/L). Patients randomized to arm A undergo complete resection of CRLM without any adjuvant treatment, which is the standard of care in the Netherlands. Patients in arm B receive an implantable pump at the time of CRLM resection and start adjuvant HAIP chemotherapy 4–12 weeks after surgery, with 6 cycles of floxuridine scheduled. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival, hepatic PFS, safety, quality of life, and cost-effectiveness. Pharmacokinetics of intra-arterial administration of floxuridine will be investigated as well as predictive biomarkers for the efficacy of HAIP chemotherapy. In a side study, the accuracy of CT angiography will be compared to radionuclide scintigraphy to detect extrahepatic perfusion. We hypothesize that adjuvant HAIP chemotherapy leads to improved survival, improved quality of life, and

Development and applications of very high flux microfiltration membranes

Inorganic microfiltration membranes with a pore size down to 0.1 ¿m have been made using laser interference lithography and silicon micro machining technology. The membranes have an extremely small flow resistance due to a thickness smaller than the pore size, a high porosity and a very narrow pore size distribution. They are relatively insensible to fouling, because they have a smooth surface, short pore channels and because they can be operated in cross flow configuration at very low transmembrane pressures. Experiments with yeast cell filtration of beer show a minimal fouling tendency and a flux that is about 40 times higher than in conventional diatomaceous earth filtration. The uniform pore distribution makes the membranes suitable for many other applications like critical cell to cell separation, particle analysis systems, absolute filtrations and model experiments