Achieving ultra-low and -uniform residual magnetic fields in a very large magnetically shielded room for fundamental physics experiments.

High-precision searches for an electric dipole moment of the neutron (nEDM) require stable and uniform magnetic field environments. We present the recent achievements of degaussing and equilibrating the magnetically shielded room (MSR) for the n2EDM experiment at the Paul Scherrer Institute. We present the final degaussing configuration that will be used for n2EDM after numerous studies. The optimized procedure results in a residual magnetic field that has been reduced by a factor of two. The ultra-low field is achieved with the full magnetic-field-coil system, and a large vacuum vessel installed, both in the MSR. In the inner volume of ∼1.4m3, the field is now more uniform and below 300 pT. In addition, the procedure is faster and dissipates less heat into the magnetic environment, which in turn, reduces its thermal relaxation time from 12h down to 1.5h.

A large 'Active Magnetic Shield' for a high-precision experiment: nEDM collaboration.

We present a novel Active Magnetic Shield (AMS), designed and implemented for the n2EDM experiment at the Paul Scherrer Institute. The experiment will perform a high-sensitivity search for the electric dipole moment of the neutron. Magnetic-field stability and control is of key importance for n2EDM. A large, cubic, 5 m side length, magnetically shielded room (MSR) provides a passive, quasi-static shielding-factor of about 105 for its inner sensitive volume. The AMS consists of a system of eight complex, feedback-controlled compensation coils constructed on an irregular grid spanned on a volume of less than 1000 m3 around the MSR. The AMS is designed to provide a stable and uniform magnetic-field environment around the MSR, while being reasonably compact. The system can compensate static and variable magnetic fields up to ±50µT (homogeneous components) and ±5µT/m (first-order gradients), suppressing them to a few µT in the sub-Hertz frequency range. The presented design concept and implementation of the AMS fulfills the requirements of the n2EDM experiment and can be useful for other applications, where magnetically silent environments are important and spatial constraints inhibit simpler geometrical solutions.

The very large n2EDM magnetically shielded room with an exceptional performance for fundamental physics measurements.

We present the magnetically shielded room (MSR) for the n2EDM experiment at the Paul Scherrer Institute, which features an interior cubic volume with each side of length 2.92 m, thus providing an accessible space of 25 m3. The MSR has 87 openings of diameter up to 220 mm for operating the experimental apparatus inside and an intermediate space between the layers for housing sensitive signal processing electronics. The characterization measurements show a remanent magnetic field in the central 1 m3 below 100 pT and a field below 600 pT in the entire inner volume, up to 4 cm to the walls. The quasi-static shielding factor at 0.01 Hz measured with a sinusoidal 2 µT peak-to-peak signal is about 100 000 in all three spatial directions and increases rapidly with frequency to reach 108 above 1 Hz.

The design of the n2EDM experiment: nEDM Collaboration.

We present the design of a next-generation experiment, n2EDM, currently under construction at the ultracold neutron source at the Paul Scherrer Institute (PSI) with the aim of carrying out a high-precision search for an electric dipole moment of the neutron. The project builds on experience gained with the previous apparatus operated at PSI until 2017, and is expected to deliver an order of magnitude better sensitivity with provision for further substantial improvements. An overview is of the experimental method and setup is given, the sensitivity requirements for the apparatus are derived, and its technical design is described.

Data blinding for the nEDM experiment at PSI.

Psychological bias towards, or away from, prior measurements or theory predictions is an intrinsic threat to any data analysis. While various methods can be used to try to avoid such a bias, e.g. actively avoiding looking at the result, only data blinding is a traceable and trustworthy method that can circumvent the bias and convince a public audience that there is not even an accidental psychological bias. Data blinding is nowadays a standard practice in particle physics, but it is particularly difficult for experiments searching for the neutron electric dipole moment (nEDM), as several cross measurements, in particular of the magnetic field, create a self-consistent network into which it is hard to inject a false signal. We present an algorithm that modifies the data without influencing the experiment. Results of an automated analysis of the data are used to change the recorded spin state of a few neutrons within each measurement cycle. The flexible algorithm may be applied twice (or more) to the data, thus providing the option of sequentially applying various blinding offsets for separate analysis steps with independent teams. The subtle manner in which the data are modified allows one subsequently to adjust the algorithm and to produce a re-blinded data set without revealing the initial blinding offset. The method was designed for the 2015/2016 measurement campaign of the nEDM experiment at the Paul Scherrer Institute. However, it can be re-used with minor modification for the follow-up experiment n2EDM, and may be suitable for comparable projects elsewhere.

Demonstration of Muon-Beam Transverse Phase-Space Compression.

We demonstrate efficient transverse compression of a 12.5 MeV/c muon beam stopped in a helium gas target featuring a vertical density gradient and crossed electric and magnetic fields. The muon stop distribution extending vertically over 14 mm was reduced to a 0.25 mm size (rms) within 3.5 µs. The simulation including cross sections for low-energy µ^{+}-He elastic and charge exchange (µ^{+}↔ muonium) collisions describes the measurements well. By combining the transverse compression stage with a previously demonstrated longitudinal compression stage, we can improve the phase space density of a µ^{+} beam by a factor of 10^{10} with 10^{-3} efficiency.

Measurement of the Permanent Electric Dipole Moment of the Neutron.

We present the result of an experiment to measure the electric dipole moment (EDM) of the neutron at the Paul Scherrer Institute using Ramsey's method of separated oscillating magnetic fields with ultracold neutrons. Our measurement stands in the long history of EDM experiments probing physics violating time-reversal invariance. The salient features of this experiment were the use of a ^{199}Hg comagnetometer and an array of optically pumped cesium vapor magnetometers to cancel and correct for magnetic-field changes. The statistical analysis was performed on blinded datasets by two separate groups, while the estimation of systematic effects profited from an unprecedented knowledge of the magnetic field. The measured value of the neutron EDM is d_{n}=(0.0±1.1_{stat}±0.2_{sys})×10^{-26} e.cm.

Fetal endoscopic tracheal occlusion reduces pulmonary hypertension in severe congenital diaphragmatic hernia.

OBJECTIVE: Fetal endoscopic tracheal occlusion (FETO) is associated with increased perinatal survival and reduced need for extracorporeal membrane oxygenation (ECMO) in fetuses with severe congenital diaphragmatic hernia (CDH). This study evaluates the impact of FETO on the resolution of pulmonary hypertension (PH) in fetuses with isolated CDH. METHODS: We reviewed retrospectively the medical records of all fetuses evaluated for CDH between January 2004 and July 2017 at a single institution. Fetuses with additional major structural or chromosomal abnormalities were excluded. CDH cases were classified retrospectively into mild, moderate and severe groups based on prenatal magnetic resonance imaging indices (observed-to-expected total fetal lung volume and percentage of intrathoracic liver herniation). Presence of PH was determined based on postnatal echocardiograms. Logistic regression analyses were performed to evaluate the relationship between FETO and resolution of PH by 1 year of age while controlling for side of the CDH, use of ECMO, gestational age at diagnosis, gestational age at delivery, fetal gender, sildenafil use at discharge and CDH severity. Resolution of PH by 1 year of age was compared between a cohort of fetuses with severe CDH that underwent FETO and a cohort that did not have the procedure (non-FETO). A subanalysis was performed restricting the analysis to isolated left CDH. Parametric and non-parametric tests were used for comparisons. RESULTS: Of 257 CDH cases evaluated, 72% (n = 184) had no major structural or chromosomal anomalies of which 58% (n = 107) met the study inclusion criteria. The FETO cohort consisted of 19 CDH cases and the non-FETO cohort (n = 88) consisted of 31 (35%) mild, 32 (36%) moderate and 25 (28%) severe CDH cases. All infants with severe CDH, regardless of whether they underwent FETO, had evidence of neonatal PH. FETO (OR, 3.57; 95% CI, 1.05-12.10; P = 0.041) and ECMO (OR, 5.01; 95% CI, 2.10-11.96; P < 0.001) were independent predictors of resolution of PH by 1 year of age. A higher proportion of infants with severe CDH that underwent FETO had resolution of PH by 1 year after birth compared with infants with severe CDH in the non-FETO cohort (69% (11/16) vs 28% (7/25); P = 0.017). Similar results were observed when the analysis was restricted to cases with left-sided CDH (PH resolution in 69% (11/16) vs 28% (5/18); P = 0.032). CONCLUSION: In infants with severe CDH, FETO and ECMO are independently associated with increased resolution of PH by 1 year of age. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

NF-κB decoy polyplexes decrease P-glycoprotein-mediated multidrug resistance in colorectal cancer cells.

Multidrug resistance (MDR), a major cause for chemotherapy failure, has been linked to upregulation of ATP-dependent membrane efflux systems that limit intracellular accumulation of cytotoxic anticancer agents. P-glycoprotein (P-gp) encoded by the human ABCB1 gene was the first efflux transporter identified to contribute to MDR. ABCB1 gene expression is correlated with constitutive activation of the NF-κB signaling pathway in tumor cells. The objective of this research is to modulate P-gp activity in colon cancer cells using NF-κB decoy oligodeoxynucleotides (ODNs) that are effectively delivered into the nucleus of colorectal cancer cells by self-assembling nonviral nanoparticles comprising the novel poly[N-(2-hydroxypropyl)methacrylamide]-poly(N,N-dimethylaminoethylmethacrylate) diblock copolymer (pHPMA-b-pDMAEMA). Ethidium bromide intercalation and gel retardation assays demonstrated high DNA condensation capacity of pHPMA-b-pDMAEMA. Nanoparticles prepared with and without decoy ODNs did not significantly compromise cellular safety at N/P ratios ⩽4. Transfection efficiency of pHPMA-b-pDMAEMA polyplexes (N/P=4) in Caco-2 cells was comparable to TurboFect transfection standard, resulting in a 98% reduction in P-gp protein levels. As a pharmacodynamic consequence, intracellular accumulation of the P-gp substrate Rhodamine123 significantly increased by almost twofold. In conclusion, NF-κB ODN polyplexes fabricated with pHPMA-b-pDMAEMA polymer effectively reduced P-gp-mediated efflux activity in Caco-2 cells, suggesting successful interference with NF-κB-binding sites in the promoter region of the ABCB1 gene.

Pilot study of chronic maternal hyperoxygenation and effect on aortic and mitral valve annular dimensions in fetuses with left heart hypoplasia.

OBJECTIVE: Acute maternal hyperoxygenation (AMH) results in increased fetal left heart blood flow. Our aim was to perform a pilot study to determine the safety, feasibility and direction and magnitude of effect of chronic maternal hyperoxygenation (CMH) on mitral and aortic valve annular dimensions in fetuses with left heart hypoplasia (LHH) after CMH. METHODS: Gravidae with fetal LHH were eligible for inclusion in a prospective evaluation of CMH. LHH was defined as: sum of aortic and mitral valve annuli Z-scores < -4.5, arch flow reversal and left-to-right or bidirectional atrial level shunting without hypoplastic left heart syndrome or severe aortic stenosis. Gravidae with an affected fetus and with ≥ 10% increase in aortic/combined cardiac output flow after 10 min of AMH at 8 L/min 100% fraction of inspired oxygen were offered enrollment. Nine gravidae were enrolled from February 2014 to January 2015. The goal therapy was ≥ 8 h daily CMH from enrollment until delivery. Gravidae who were cared for from July 2012 to October 2014 with fetal LHH and no CMH were identified as historical controls (n = 9). Rates of growth in aortic and mitral annuli over the final trimester were compared between groups using longitudinal regression. RESULTS: There were no significant maternal or fetal complications in the CMH cohort. Mean gestational age at study initiation was 29.6 ± 3.2 weeks for the intervention group and 28.4 ± 1.8 weeks for controls (P = 0.35). Mean relative increase in aortic/combined cardiac output after AMH was 35.3% (range, 18.1-47.9%). Median number of hours per day on CMH therapy was 9.3 (range, 6.5-14.6) and median duration of CMH was 48 (range, 33-84) days. Mean mitral annular growth was 0.19 ± 0.05 mm/week compared with 0.14 ± 0.05 mm/week in CMH vs controls (mean difference 0.05 ± 0.05 mm/week, P = 0.33). Mean aortic annular growth was 0.14 ± 0.03 mm/week compared with 0.13 ± 0.03 mm/week in CMH vs controls (mean difference 0.01 ± 0.03 mm/week, P = 0.75). More than 9 h CMH daily (n = 6) was associated with better growth of the aortic annulus in intervention fetuses (0.16 ± 0.03 vs 0.08 ± 0.02 mm/week, P = 0.014). CONCLUSIONS: CMH is both safe and feasible for continued research. In this pilot study, the effect estimates of annular growth, using the studied method of delivery and dose of oxygen, were small. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Observation of Gravitationally Induced Vertical Striation of Polarized Ultracold Neutrons by Spin-Echo Spectroscopy.

We describe a spin-echo method for ultracold neutrons (UCNs) confined in a precession chamber and exposed to a |B0|=1 µT magnetic field. We have demonstrated that the analysis of UCN spin-echo resonance signals in combination with knowledge of the ambient magnetic field provides an excellent method by which to reconstruct the energy spectrum of a confined ensemble of neutrons. The method takes advantage of the relative dephasing of spins arising from a gravitationally induced striation of stored UCNs of different energies, and also permits an improved determination of the vertical magnetic-field gradient with an exceptional accuracy of 1.1 pT/cm. This novel combination of a well-known nuclear resonance method and gravitationally induced vertical striation is unique in the realm of nuclear and particle physics and should prove to be invaluable for the assessment of systematic effects in precision experiments such as searches for an electric dipole moment of the neutron or the measurement of the neutron lifetime.

Congenital heart anomaly in newborns with congenital diaphragmatic hernia: a single-center experience.

OBJECTIVE: To evaluate the impact of the presence of a congenital heart anomaly (CHA) and its potential contribution to morbidity and mortality in infants with congenital diaphragmatic hernia (CDH). METHODS: In this retrospective cohort study, prenatal and postnatal data of all newborns diagnosed with CDH between January 2004 and December 2012 in a single center were reviewed. Cases were classified into two groups: those with 'isolated' CDH and those with both CDH and CHA. Patients with CHA were further subclassified into those with a major or minor CHA based on the Risk Adjustment for Congenital Heart Surgery-1 (RACHS-1), and the Society of Thoracic Surgeons-European Association for Cardiothoracic Surgery (STS-EACTS) scoring systems. Patients with associated non-cardiac anomalies, including 'syndromic cases', were excluded from the analysis. Primary and secondary outcomes were survival up to 1 year of age and a need for extracorporeal membrane oxygenation (ECMO), respectively. RESULTS: Of the 180 infants with CDH, 41 were excluded because of the presence of non-cardiac associated anomalies, 118 had isolated CDH and 21 had CDH with CHA (16 with minor and five with major CHA). Receiver-operating characteristics curve analysis demonstrated that the best cut-off for survival was when the score for CHA was ≤ 2 for both RACHS-1 (area under the curve (AUC), 0.74 (P = 0.04); sensitivity, 80.0%; specificity, 87.5%) and STS-EACTS (AUC, 0.83 (P = 0.03); sensitivity, 100%; specificity, 87.5%). Survival rate at 1 year was significantly lower in those with CHD and a major CHA (40.0%; P = 0.04) than in those with isolated CDH (77.1%) and those with CDH and a minor CHA (81.3%). We found no significant differences among the groups with regard to the need for ECMO. CONCLUSIONS: In general, a milder form of CHA does not appear to have a negative impact on the survival of infants with CDH. However, mortality appears to be significantly higher in infants with CDH and a major form of CHA. The scoring systems appear to be useful as predictors for classifying the effects of CHA in this population of patients.

Polymer Brushes Containing Sulfonated Sugar Repeat Units: Synthesis, Characterization and In Vitro Testing of Blood Coagulation Activation.

A new polymer brush chemistry containing sulfonated carbohydrate repeat units has been synthesized from silicon substrates using ATRP methods and characterized both in bulk and using surface analysis. The polymer brush was designed to act as a mimic for the naturally occurring sulfonated glycosaminoglycan, heparin, commonly used for modifying blood-contacting surfaces both in vitro and in vivo. Surface analysis showed conversion of brush saccharide precursor chemistry to the desired sulfonated polymer product. The sulfonated polymer brush surface was further analyzed using three conventional in vitro tests for blood compatibility -- plasma recalcification times, complement activation, and thrombin generation. The sulfonated polymer brush films on silicon oxide wafers exhibited better assay performance in these blood component assays than the unsulfonated sugar functionalized polymer brush in all tests performed.

Safety and efficacy of intravenous contrast imaging in pediatric echocardiography.

This study was performed to determine the safety and efficacy of intravenous contrast echocardiography in children attending a tertiary cardiac center. This was a prospective study to evaluate the use of Optison contrast agent in children with severely limited transthoracic echocardiographic windows. Twenty children (median age, 15 years; range, 9-18) underwent fundamental imaging (FI), harmonic imaging (HI), and HI with intravenous contrast (Optison FS-069). Endocardial border delineation was determined based on a visual qualitative scoring system (0, none: 4, excellent). Endocardial border definition was significantly improved in all patients using contrast echocardiography (FI vs Optison, p < 0.001 for each). Improved border definition was most dramatic in the apical and left ventricular (LV) free wall regions. Left ventricular ejection fraction (LVEF) was measurable in 20 patients (100%) using contrast compared to 11 (55%) with FI or HI (p < 0.05). The echocardiographic diagnosis was correctly delineated in 1 patient with a severely dyskinetic LV segment only with use of intravenous contrast and HI. No patients suffered adverse hemodynamic effects, changes in taste, or flushing episodes. Three patients experienced transient headaches. Intravenous contrast echocardiography offers an additional tool in evaluating children with very poor transthoracic echocardiographic windows. Such a strategy increases diagnostic accuracy and allows accurate LVEF determination. Adverse hemodynamic effects related to intravenous contrast are exceedingly rare.

Risk factors for neo-aortic root enlargement and aortic regurgitation following arterial switch operation.

The objectives of this study were to evaluate changes in dimension of the neo-aortic annulus, aortic root, and aortic anastomosis following arterial switch operation (ASO) and to identify risk factors for developing abnormal neo-aortic root enlargement and aortic regurgitation (AR). Prior studies report development of neo-aortic root dilatation and AR in a small subset of patients after ASO. Predisposing factors for neo-aortic root dilatation and development of moderate/severe AR are poorly understood. We performed a retrospective review of all patients with d-transposition of the great arteries (d-TGA) or double-outlet right ventricle with subpulmonary ventricular septal defect (VSD) who underwent ASO from May 1986 to January 2001. Serial echocardiograms were reviewed to measure neo-aortic annulus, root, and anastomosis diameter (z scores) and to determine progression of AR. Potential risk factors were assessed for developing neo-aortic root enlargement and AR. There were 119 patients (44 female and 75 male): 73 patients had simple d-TGA, 36 had d-TGA with ventricular septal defect, and 10 had a Taussig-Bing heart. The median duration of follow-up was 65 months (range, 12-180). The median neo-aortic root (z = 0.55+/-2.2; p < 0.01) and aortic annulus dimensions (z = 1.57+/-1.75; p < 0.01) were significantly increased over the study period. Aortic anastomosis diameter correlated with growth of the ascending aorta (z = 0.55+/-1.24). Development of severe neo-aortic root enlargement was associated with prior pulmonary artery (PA) banding (p < 0.01), the presence of a VSD (p = 0.03), and Taussig-Bing anatomy (p < 0.01) but was independent of coronary arterial anatomy, coronary arterial transfer technique, or associated lesions (p > 0.05). At latest follow-up, there was no or trivial AR in 88 patients, mild AR in 29 patients, and moderate to severe AR in 3 patients. Risk factors for developing mild or worse AR included severe or rapid neo-aortic root dilatation (p < 0.01). Only 3 patients required surgical intervention for AR. Despite the significant prevalence of neo-aortic root enlargement at intermediate follow-up after ASO, there is a low incidence of significant AR. Prior PA banding, the presence of VSD, and Taussig-Bing anatomy are risk factors for severe root enlargement. Surgical intervention for AR was rare (2%), however, serial surveillance of such patients is vital to monitor for neo-aortic root enlargement and potential aortic valve dysfunction.

Harmonic imaging in fetal echocardiography.

Noncontrast harmonic imaging (HI) has been shown to improve image quality in adults with poor acoustic windows. The utility of fetal echocardiography may be limited by suboptimal acoustic windows, and the use of HI in fetal echocardiography has not previously been defined. The purpose of this study was to compare the quality of fundamental imaging (FI) and HI in fetal echocardiography. Sixty-two fetal echocardiograms, including 44 (71%) with limited acoustic windows, were performed with the use of FI and HI. Image quality and visualization of the ventricles, valves, and the aortic and ductal arches were evaluated and compared between FI and HI. Mean HI scores were higher than mean FI scores for all the structures evaluated. Compared with FI, HI improved the image quality and visualization of cardiac structures in this group of fetuses with predominantly suboptimal acoustic windows. Harmonic imaging is a useful adjunct to FI in echocardiography, and the benefits of HI extend to cardiac imaging in the fetus.

Cardiac rhabdomyoma: a report of alternative strategies to surgical resection.

Cardiac rhabdomyoma represents the commonest primary cardiac tumour. Its natural history is generally favourable, with resolution in the majority of cases. Surgical resection has been described for intractable arrhythmia, severe obstruction of the inflow or outflow tracts sufficient to compromise cardiac output, and systemic embolization. We describe an alternative palliative strategy, which was associated with regression of the tumour.