New and Practical Formulation for Overlaps of Bogoliubov Vacua.

In this Letter, we present a new expression for the overlaps of wave functions in Hartree-Fock-Bogoliubov based theories. Starting from the Pfaffian formula by Bertsch et al. [1], an exact and computationally stable formula for overlaps is derived. We illustrate the convenience of this new formulation with a numerical application in the context of the particle-number projection method. This new formula allows for substantially increased precision and versatility in chemical, atomic, and nuclear physics applications, particularly for methods dealing with superfluidity, symmetry restoration, and uses of nonorthogonal many-body basis states.

Spectroscopy along Flerovium Decay Chains: Discovery of

A nuclear spectroscopy experiment was conducted to study α-decay chains stemming from isotopes of flerovium (element Z=114). An upgraded TASISpec decay station was placed behind the gas-filled separator TASCA at the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt, Germany. The fusion-evaporation reactions ^{48}Ca+^{242}Pu and ^{48}Ca+^{244}Pu provided a total of 32 flerovium-candidate decay chains, of which two and eleven were firmly assigned to ^{286}Fl and ^{288}Fl, respectively. A prompt coincidence between a 9.60(1)-MeV α particle event and a 0.36(1)-MeV conversion electron marked the first observation of an excited state in an even-even isotope of the heaviest man-made elements, namely ^{282}Cn. Spectroscopy of ^{288}Fl decay chains fixed Q_{α}=10.06(1) MeV. In one case, a Q_{α}=9.46(1)-MeV decay from ^{284}Cn into ^{280}Ds was observed, with ^{280}Ds fissioning after only 518 µs. The impact of these findings, aggregated with existing data on decay chains of ^{286,288}Fl, on the size of an anticipated shell gap at proton number Z=114 is discussed in light of predictions from two beyond-mean-field calculations, which take into account triaxial deformation.

Plasma concentrations of etonogestrel in women using oral desogestrel before and after Roux-en-Y gastric bypass surgery: a pharmacokinetic study.

OBJECTIVE: To investigate whether Roux-en-Y gastric bypass (RYGB) affects oral desogestrel (etonogestrel) pharmacokinetics. DESIGN: Single centre, open label, phase-2 pharmacokinetic study. SETTING: University hospital of Linköping, Sweden. POPULATION: Fourteen women with planned RYGB surgery were included; nine women aged 18-45 years using 75 micrograms desogestrel completed the study. METHODS: Steady-state etonogestrel pharmacokinetic (PK) parameters were measured on three occasions for each individual (at 8 ± 6 weeks before surgery, and at 12 ± 2 and 52 ± 2 weeks after surgery). Each patient served as her own control. On each occasion, serum samples were collected during a 24-hour period and etonogestrel concentrations were determined with ultra-performance liquid chromatography/tandem mass spectrometry. MAIN OUTCOME MEASURES: Area under the plasma concentration time curve of etonogestrel (AUC0-24 hours ). RESULTS: All women had significant postoperative weight loss. There were no significant differences in AUC0-24 hours , terminal half-lives (t½ ), time to peak serum concentrations (Tmax ), or apparent oral clearances of etonogestrel (CLoral ) before and after gastric bypass surgery on any occasion. Peak serum concentrations (Cmax ) increased after 52 ± 2 weeks compared with preoperative values (0.817 ng/ml versus 0.590 ng/ml, P = 0.024). CONCLUSION: To our knowledge, this is the first study to investigate the effects on desogestrel pharmacokinetics after RYGB. This study did not reveal any clinically significant changes in etonogestrel pharmacokinetics, suggesting that oral desogestrel may be used by women after RYGB surgery. The sample size was limited, however, and therefore the results should be interpreted cautiously. TWEETABLE ABSTRACT: The pharmacokinetics of oral desogestrel does not appear to change after gastric bypass surgery.

High target attainment for ß-lactam antibiotics in intensive care unit patients when actual minimum inhibitory concentrations are applied.

Patients in the intensive care unit (ICU) are at risk for suboptimal levels of ß-lactam antibiotics, possibly leading to poor efficacy. Our aim was to investigate whether the actual minimum inhibitory concentration (MIC) compared to the more commonly used arbitrary epidemiological cut-off values (ECOFFs) would affect target attainment in ICU patients on empirical treatment with broad-spectrum ß-lactam antibiotics and to identify risk factors for not reaching target. In a prospective, multicenter study, ICU patients ≥18 years old and treated with piperacillin/tazobactam, meropenem, or cefotaxime were included. Clinical and laboratory data were recorded. Serum trough antibiotic levels from three consecutive days were analyzed by liquid chromatography-mass spectrometry (LC-MS). The target was defined as the free trough concentration above the MIC (100% fT>MIC). MICECOFF was used as the target and, when available, the actual MIC (MICACTUAL) was applied. The median age of the patients was 70 years old, 52% (58/111) were males, and the median estimated glomerular filtration rate (eGFR) was 48.0 mL/min/1.73 m2. The rate of patients reaching 100% fT > MICACTUAL was higher (89%, 31/35) compared to the same patients using MICECOFF (60%, p = 0.002). In total, 55% (61/111) reached 100% fT > MICECOFF. Increased renal clearance was independently associated to not reaching 100% fT > MICECOFF. On repeated sampling, >77% of patients had stable serum drug levels around the MICECOFF. Serum concentrations of ß-lactam antibiotics vary extensively between ICU patients. The rate of patients not reaching target was markedly lower for the actual MIC than when the arbitrary MIC based on the ECOFF was used, which is important to consider in future studies.

Influence of CYP2D6 and CYP2C19 genotypes on venlafaxine metabolic ratios and stereoselective metabolism in forensic autopsy cases.

We investigated whether polymorphisms in the CYP2D6 and CYP2C19 genes influence the metabolic ratios and enantiomeric S/R ratios of venlafaxine (VEN) and its metabolites O-desmethylvenlafaxine (ODV), N-desmethylvenlafaxine (NDV) and N,O-didesmethylvenlafaxine (DDV) in blood from forensic autopsy cases. In all, 94 postmortem cases found positive for VEN during toxicological screening were included. The CYP2D6 genotype was shown to significantly influence the ODV/VEN (P=0.003), DDV/NDV (P=0.010) and DDV/ODV (P=0.034) ratios. The DDV/ODV (P=0.013) and DDV/VEN (P=0.021) ratios were significantly influenced by the CYP2C19 genotype. The S/R ratios of VEN were significantly influenced by both CYP2D6 and CYP2C19 genotypes. CYP2D6 poor metabolizers (PMs) had lower S/R VEN ratios and CYP2C19 PMs had high S/R ratios of VEN in comparison. Our results show that the CYP2D6 genotype influences the O-demethylation whereas CYP2C19 influences the N-demethylation of VEN and its metabolites. In addition, we show a stereoselective metabolism where CYP2D6 favours the R-enantiomer whereas CYP2C19 favours the S-enantiomer.

Spectroscopic properties of nuclear skyrme energy density functionals.

We address the question of how to improve the agreement between theoretical nuclear single-particle energies (SPEs) and observations. Empirically, in doubly magic nuclei, the SPEs can be deduced from spectroscopic properties of odd nuclei that have one more or one less neutron or proton. Theoretically, bare SPEs, before being confronted with observations, must be corrected for the effects of the particle vibration coupling (PVC). In the present work, we determine the PVC corrections in a fully self-consistent way. Then, we adjust the SPEs, with PVC corrections included, to empirical data. In this way, the agreement with observations, on average, improves; nevertheless, large discrepancies still remain. We conclude that the main source of disagreement is still in the underlying mean fields, and not in including or neglecting the PVC corrections.

Effects of three-nucleon forces and two-body currents on Gamow-Teller strengths.

We optimize chiral interactions at next-to-next-to leading order to observables in two- and three-nucleon systems and compute Gamow-Teller transitions in 14C and (22,24)O using consistent two-body currents. We compute spectra of the daughter nuclei 14N and (22,24)F via an isospin-breaking coupled-cluster technique, with several predictions. The two-body currents reduce the Ikeda sum rule, corresponding to a quenching factor q2≈0.84-0.92 of the axial-vector coupling. The half-life of 14C depends on the energy of the first excited 1+ state, the three-nucleon force, and the two-body current.

Lessons learnt from evaluating full-scale ammonium feedback control in three large wastewater treatment plants.

Three large wastewater treatment plants in Sweden participate in a project evaluating different types of ammonium feedback controllers in full-scale operation. The goal is to improve process monitoring, maintain effluent water quality and save energy. The paper presents the outcome of the long-term evaluation of controllers. Based on the experiences gained from the full-scale implementations, a discussion is provided about energy assessment for the purpose of comparing control strategies. The most important conclusions are the importance of long-term experiments and the difficulty of comparing energy consumption based on air flow rate measurements.

Instrumentation, control and automation in wastewater--from London 1973 to Narbonne 2013.

Key developments of instrumentation, control and automation (ICA) applications in wastewater systems during the past 40 years are highlighted in this paper. From the first ICA conference in 1973 through to today there has been a tremendous increase in the understanding of the processes, instrumentation, computer systems and control theory. However, many developments have not been addressed here, such as sewer control, drinking water treatment and water distribution control. It is hoped that this review can stimulate new attempts to more effectively apply control and automation in water systems in the coming years.

Obtaining regulatory T cells from uraemic patients awaiting kidney transplantation for use in clinical trials.

Adoptive transfer of regulatory T cells (T(regs)) has been proposed for use as a cellular therapy to induce transplantation tolerance. Preclinical data are encouraging, and clinical trials with T(reg) therapy are anticipated. In this study, we investigate different strategies for the isolation and expansion of CD4(+) CD25(high) CD127(low) T(regs) from uraemic patients. We use allogeneic dendritic cells (DCs) as feeder cells for the expansion and compare T(reg) preparations isolated by either fluorescence activated cell sorting (FACS) or magnetic activated cell sorting (MACS) that have been expanded subsequently with either mature or tolerogenic DCs. Expanded T(reg) preparations have been characterized by their purity, cytokine production and in-vitro suppressive ability. The results show that T(reg) preparations can be isolated from uraemic patients by both FACS and MACS. Also, the type of feeder cells used in the expansion affects both the purity and the functional properties of the T(reg) preparations. In particular, FACS-sorted T(reg) preparations expanded with mature DCs secrete more interleukin (IL)-10 and granzyme B than FACS-sorted T(reg) preparations expanded with tolerogenic DCs. This is a direct comparison between different isolation techniques and expansion protocols with T(regs) from uraemic patients that may guide future efforts to produce clinical-grade T(regs) for use in kidney transplantation.

Spectroscopy of element 115 decay chains.

A high-resolution α, x-ray, and γ-ray coincidence spectroscopy experiment was conducted at the GSI Helmholtzzentrum für Schwerionenforschung. Thirty correlated α-decay chains were detected following the fusion-evaporation reaction 48Ca + 243Am. The observations are consistent with previous assignments of similar decay chains to originate from element Z=115. For the first time, precise spectroscopy allows the derivation of excitation schemes of isotopes along the decay chains starting with elements Z>112. Comprehensive Monte Carlo simulations accompany the data analysis. Nuclear structure models provide a first level interpretation.

Plasminogen activator inhibitor-1 levels and activity decrease after intervention in patients with critical limb ischaemia.

OBJECTIVE/BACKGROUND: Patients with peripheral arterial occlusive disease (PAOD), in particular critical limb ischaemia (CLI), carry a high risk of thrombotic events. We hypothesised that patients undergoing conservative, endovascular, or open surgical treatment for CLI have increased levels of plasminogen activator inhibitor-1 (PAI-1), leading to a prothrombotic state. The objective was to determine levels of PAI-1 in patients with acute or chronic PAOD/CLI. METHODS: Thirty-two patients with a median age of 74 (49-90) years were included. Three underwent thrombolysis for acute limb-threatening ischaemia. Twenty-six patients with chronic ischaemia received endovascular (n = 20) or open (n = 6) surgical treatment. Three were treated conservatively. Biomarkers and ankle brachial index (ABI) were measured before and up to 1 month after intervention. Patency was studied with repeated duplex ultrasound. RESULTS: Ankle pressure and ABI improved after intervention (p < .001). C-reactive protein (CRP) increased from a median of 7.90 mg/L at baseline to 31.5 on day 1 (p < .001), 28.0 on day 6 (p < .001), and returned to baseline levels on day 30. PAI-1 antigen and activity decreased from day 6 and onwards post-intervention compared with baseline (p < .05). A great individual variability in PAI-1 antigen and activity was observed. Although most actively treated patients had normal PAI-1 activity, 11/29 (38%) were above that level of normality at baseline, 10/24 (42%) on day 1, 3/23 (13%) on day 6, and 5/27 (19%) on day 30 after intervention. CONCLUSION: Endovascular and open surgical treatment resulted in improved ankle pressure and ABI. The intervention was followed by a transient increase in CRP and a sustained reduction in PAI-1 levels and activity.

ABCB1 gene polymorphisms are associated with fatal intoxications involving venlafaxine but not citalopram.

P-glycoprotein (P-gp), encoded by the ABCB1/MDR1 gene, is a drug transporter at the blood-brain barrier. Several polymorphisms in the ABCB1 gene are known to affect the activity and/or expression of P-gp, thereby influencing the treatment response and toxicity of P-gp substrates like citalopram and venlafaxine. In this study, we aimed to investigate the frequency of ABCB1 genotypes in forensic autopsy cases involving these two antidepressants. Further, the distribution of ABCB1 genotypes in deaths related to intoxication was compared to cases not associated to drug intoxication. The study included 228 forensic autopsy cases with different causes and manners of deaths. The ABCB1 single nucleotide polymorphisms (SNPs) G1199A, C1236T, C3435T and G2677T/A for these individuals were determined. The SNPs C1236T and C3435T in venlafaxine-positive cases were significantly different between the intoxication cases and non-intoxications. This was not seen for cases involving citalopram, indicating that the effect of genetic variants might be substrate specific. This novel finding should, however, be confirmed in future studies with larger number of cases.

The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia.

Diamond-Blackfan anaemia (DBA) is a constitutional erythroblastopenia characterized by absent or decreased erythroid precursors. The disease, previously mapped to human chromosome 19q13, is frequently associated with a variety of malformations. To identify the gene involved in DBA, we cloned the chromosome 19q13 breakpoint in a patient with a reciprocal X;19 chromosome translocation. The breakpoint occurred in the gene encoding ribosomal protein S19. Furthermore, we identified mutations in RPS19 in 10 of 40 unrelated DBA patients, including nonsense, frameshift, splice site and missense mutations, as well as two intragenic deletions. These mutations are associated with clinical features that suggest a function for RPS19 in erythropoiesis and embryogenesis.

The optimal dissolved oxygen profile in a nitrifying activated sludge process - comparisons with ammonium feedback control.

Ammonium feedback control is increasingly used to determine the dissolved oxygen (DO) set-point in aerated activated sludge processes for nitrogen removal. This study compares proportional-integral (PI) ammonium feedback control with a DO profile created from a mathematical minimisation of the daily air flow rate. All simulated scenarios are set to reach the same treatment level of ammonium, based on a daily average concentration. The influent includes daily variations only and the model has three aerated zones. Comparisons are made at different plant loads and DO concentrations, and the placement of the ammonium sensor is investigated. The results show that ammonium PI control can achieve the best performance if the DO set-point is limited at a maximum value and with little integral action in the controller. Compared with constant DO control the best-performing ammonium controller can achieve 1-3.5% savings in the air flow rate, while the optimal solution can achieve a 3-7% saving. Energy savings are larger when operating at higher DO concentrations.

Aeration control - a review.

This review covers automatic control of continuous aeration systems in municipal wastewater treatment plants. The review focuses on published research in the 21st century and describes research into various methods to decide and control the dissolved oxygen (DO) concentration and to control the aerobic volume with special focus on plants with nitrogen removal. Important aspects of control system implementation and success are discussed, together with a critical review of published research on the topic. With respect to DO control and determination, the strategies used for control span from modifications and developments of conventional control methods which have been explored since the 1970s, to advanced control such as model-based predictive and optimal controllers. The review is supplemented with a summary of comparisons between control strategies evaluated in full-scale, pilot-scale and in simulations.

Availability of insulin pump therapy in clinical practice.

AIM: To examine the availability of insulin pump therapy in patients with Type 1 diabetes. METHODS: Patients using insulin pumps among a cohort of 7224 patients with Type 1 diabetes were studied. RESULTS: In logistic regression, used to evaluate variables not changing over time among the total cohort, use of insulin pumps varied by outpatient clinic (P<0.001) and sex (P<0.001). Cox regression analysis in 5854 patients with detailed patient data prior to use of an insulin pump showed higher HbA(1c) (P<0.0001), lower creatinine (P=0.002), high and low insulin doses (P<0.0001), younger age (P<0.0001) and female sex (P<0.0001) to be associated with use of an insulin pump. Women were 1.5-fold more likely to start using an insulin pump (hazard ratio 1.52, 95% confidence interval 1.29-1.79) and patients in the 20- to 30-years age range were more than twice as likely to begin use of an insulin pump than patients aged 40-50 years (hazard ratio 8.63, 95% confidence interval 5.91-12.59 and hazard ratio 3.98, 95% confidence interval 2.80-5.64, respectively). A 10-µmol/l higher level of creatinine was associated with a hazard ratio of 0.56 (95% confidence interval 0.39-0.81) of starting use of an insulin pump. CONCLUSIONS: At 10 hospital outpatient clinics in Sweden, use of insulin pumps therapy varied by clinic. A higher proportion of women began using insulin pumps. Younger patients and patients with fewer complications were also more likely to start using an insulin pump. Further research is needed to confirm these findings in other geographical regions and to understand whether the availability of insulin pumps today is optimized.

Concentration variability of potent allergens of p-tert-butylphenol-formaldehyde resin (PTBP-FR) in patch test preparations and commercially available PTBP-FR.

BACKGROUND: p-tert-Butylphenol-formaldehyde resin (PTBP-FR) is a common component of glues used in the manufacturing of many plastic, electronic, rubber, wood and leather products. Two main allergens of PTBP-FR have been described. OBJECTIVES: To determine the concentrations of the two main allergens of PTBP-FR in diagnostic patch testing preparations and PTBP-FR available to glue and adhesive manufacturers. METHODS: Nuclear magnetic resonance spectrometry was used to confirm the identity and determine the purity of reference materials. High-pressure liquid chromatography was used to analyse patch test preparations and commercially available PTBP-FR. RESULTS: In the PTBP-FR in analysed patch test preparations the highest concentration of the allergenic dimer 4-tert-butyl-2-(5-tert-butyl-2-hydroxy-3-hydroxymethyl-benzyloxymethyl)-6-hydroxymethylphenol found was 1·79% and the lowest 0·21%. The highest concentration of the allergenic dimer 4-tert-butyl-2-(5-tert-butyl-2-hydroxy-benzyloxymethyl)-6-hydroxymethylphenol found in PTBP-FR of analysed patch test preparations was 0·50% and the lowest concentration found was 0·04%. In commercially available PTBP-FR the highest concentration of 4-tert-butyl-2-(5-tert-butyl-2-hydroxy-3-hydroxymethyl-benzyloxymethyl)-6-hydroxymethylphenol found was 3·7% and the highest concentration of 4-tert-butyl-2-(5-tert-butyl-2-hydroxy-benzyloxymethyl)-6-hydroxymethylphenol found was 1·1%. In three PTBP-FR samples neither allergen could be detected. CONCLUSIONS: Our data suggest that reporting resin concentration in petrolatum is not predictive of a consistent concentration of the two main allergens of PTBP-FR. The 10-fold difference in allergen concentration between different patch test preparations has significant ramifications for maintaining consistent dose of delivered allergen. The results of this study reinforce the need for patch test product standardization in the contact dermatitis community.

Associations of markers in 11 obesity candidate genes with maximal weight loss and weight regain in the SOS bariatric surgery cases.

PURPOSE: To test whether DNA sequence variation in 11 obesity genes is associated with maximum weight loss and weight regain over 6 years of follow-up in bariatric surgery patients of the Swedish obese subjects (SOS) intervention study. METHODS: A total of 1443 subjects were available for analysis (vertical banded gastroplasty: n = 966, banding: n = 293 and gastric bypass: n = 184). Single-nucleotide polymorphisms (SNPs) from the following 11 genes were included: ADIPOQ, BDNF, FTO, GNB3, LEP, LEPR, MC4R, NR3C1, PPARG, PPARGC1A and TNF. General linear models were used to analyze associations between the SNPs and maximum weight loss and weight regain. RESULTS: The average maximum weight loss was 33.7 kg (s.d. 13.3; min -95.5 kg, max +2.0 kg), which was reached 2.2 (s.d. 1.6) years after the surgery. Subjects regained approximately 12 kg (range 0.0-51.4 kg) by year 6. After correcting for multiple testing, the FTO SNP rs16945088 remained significantly associated with maximum weight loss (P = 0.0002), as minor allele carriers lost approximately 3 kg less compared with common allele homozygotes. This association was particularly evident in the banding surgery patients (P < 0.0001), whereas no significant association was found in the gastric bypass subjects. No other SNPs were associated with maximum weight loss. Furthermore, no SNPs were significantly associated with weight regain. CONCLUSION: The FTO SNP rs16945088 was associated with maximum weight loss after banding surgery. We found no evidence that obesity-risk SNPs in FTO or other obesity candidate genes derived from genome-wide association studies are associated with maximum weight loss or weight regain over 6 years of follow-up in bariatric surgery patients. The potential role of other obesity genes remains to be investigated.

Convergence of density-matrix expansions for nuclear interactions.

We extend density-matrix expansions in nuclei to higher orders in derivatives of densities and test their convergence properties. The expansions allow for converting the interaction energies characteristic to finite- and short-range nuclear effective forces into quasilocal density functionals. We also propose a new type of expansion that has excellent convergence properties when benchmarked against the binding energies obtained for the Gogny interaction.