Optimized Structural Data at the Complete Basis Set Limit via Successive Quadratic Minimizations.

Two variants of a successive quadratic minimization method (SQM and c-SQM) are suggested to calculate the structural properties of molecular systems at the complete basis set (CBS) limit. When applied to H3+, H2O, CH2O, SH2, and SO2, they revealed CBS/(x1, x2) structural parameters that significantly surpass the raw ones calculated at the x2 basis set level. Such a performance has also been verified for the intricate case of the water dimer. Because the c-SQM method is system specific, thus showing somewhat enhanced results relative to the general SQM protocol, it can be of higher cost depending on the level of calibration used. Yet, it hardly surpasses the general quality of the results obtained with the cost-effective SQM method. Since the number of cycles required to reach convergence is relatively small, both schemes are simple to use and easily adaptable to any of the existing extrapolation schemes for the Hartree-Fock and correlation energies.

Optimal basis sets for CBS extrapolation of the correlation energy: oVxZ and oV(x+d)Z.

We seek correlation consistent double- and triple-zeta basis sets that perform optimally for extrapolating the correlation energy to the one-electron complete basis set limit. Since the methods used are approximate, the novel basis sets become method specific in the sense of performing best for the chosen level of theory. Such basis sets are also shown to perform accurately for tensorial properties and do not significantly alter the Hartree-Fock energy. Quantitatively, the extrapolated correlation energies from (oVdZ, oVtZ) outperform typically by three- to fivefold those obtained from traditional ansatzes with similar flexibility, thus being (VtZ, VqZ) type or even better. They may even outperform explicitly correlated ones. Not surprisingly, the outperformance in relative energies (e.g., atomization and dissociation energies, and ionization potential) is somewhat downscaled, albeit consistently better than with traditional basis sets. As a case study, we also consider the polarizability of p-nitroaniline, a sizeable system for which complete basis set (CBS)(oVdZ, oVtZ) calculations are shown to outperform equally expensive CBS(VdZ, VtZ) results.

Molecules under external electric field: On the changes in the electronic structure and validity limits of the theoretical predictions.

A detailed analysis of the electronic structure of the ground and first excited spin state of three diatomic molecules ( N2, BH and CO) under static applied electric field is performed at CCSD(T), DFT, MRCI and MRCI(Q) levels of theory. Our findings have revealed that by boosting the applied field one induces changes in the occupation numbers of molecular orbitals, giving rise to changes in the equilibrium geometry and in the HOMO-LUMO energy gap. Specifically, singlet to triplet spin transition can be induced by increasing the applied electric field beyond a critical value. Accordingly, affecting the accuracy of the widely used expression of energy expanded in Taylor series with respect to the applied electric field. © 2018 Wiley Periodicals, Inc.

Effects of All-Electron Basis Sets and the Scalar Relativistic Corrections in the Structure and Electronic Properties of Niobium Clusters.

In this paper, an augmented all-electron double-ζ basis set is used in calculations of the structure and electronic properties of small niobium clusters. The B3PW91 and M06 DFT functionals with and without second order Douglas-Kroll-Hess (DKH) scalar relativistic corrections are also utilized. Furthermore, an additional d Gaussian type function is introduced in the standard basis sets in order to improve the description of the clusters orbitals in the valence band. Our findings show that the extra d function is important to yield accurate results of electronic properties and, in addition, the DKH corrections can be relevant when the all-electron basis sets are used in the calculations. Our best results are obtained with the M06 functional together with the DKH second order corrections and with the extra d function added to the all-electron basis set.

Application of the unified singlet and triplet electron-pair extrapolation scheme with basis set rehierarchization to tensorial properties.

A method previously suggested to calculate the correlation energy at the complete one-electron basis set limit by reassigning the basis hierarchical numbers and using the unified singlet- and triplet-pair extrapolation scheme is here utilized to extrapolate tensorial properties, with specific use for the polarizabilities of eight molecules whose raw values are obtained with second-order Møller-Plesset perturbation theory and coupled-cluster singles and doubles excitation methods, both without and with inclusion of the perturbative triples correction. Good agreement is obtained with the best available estimates even when the (d, t) pair of hierarchical numbers is utilized to perform the extrapolations. This conceivably reinforces our previous finding that there is no good reason to exclude double-ζ results in extrapolations, especially if the basis is calibrated to comply with the theoretical model.

Planning study to compare dynamic and rapid arc techniques for postprostatectomy radiotherapy of prostate cancer.

PURPOSE: To compare our standard technique for postprostatectomy radiotherapy of prostate cancer, i.e. using two lateral conformal dynamic arcs with volumetric-modulated arc therapy (VMAT) performed with the RapidArc(®) (Varian Medical Systems, Palo Alto, CA, USA). The plans were referred to as DA and RA, respectively. MATERIALS AND METHODS: The treatment plans of 44 patients receiving adjuvant/salvage radiotherapy in the first months of 2010 were compared. In all cases, the prescribed total dose was 66-68.2 Gy (2.2 Gy per fraction). Both DA and RA plans were optimized in terms of dose coverage and constraints. RESULTS: Small differences between the techniques were observed for planning target volume (PTV) dose distribution, whereas significant differences in sparing of organs at risk (OARs) were recorded (p < 0.0001). The OAR values (median; 95 % confidence interval, CI) were: rectum: D30 % = 60.7 Gy (59.40-62.04 Gy) and 48.2 Gy (46.40-52.72 Gy), D60 % = 34.1 Gy (28.50-38.92 Gy) and 27.7 Gy (21.80-31.51 Gy); bladder: D30 % = 57.3 Gy (45.83-64.53 Gy) and 46.4 Gy (33.23-61.48 Gy), D50 % = 16.4 Gy (11.89-42.38 Gy) and 17.2 Gy (10.97-27.90 Gy), for DA and RA, respectively. Treatment times were very similar, whereas the monitor units (MU) were 550 ± 29 versus 277 ± 3 for RA and DA, respectively. CONCLUSION: Dose-volume histograms (DVHs) show improvements in OAR sparing with RA. However, the RA technique is associated with almost double the number of MUs compared to DA. Regarding the PTV, DA is slightly superior in terms of D2 % and dose homogeneity. On the whole, the results suggest that RA be the favorable technique.

Narrowing the error in electron correlation calculations by basis set re-hierarchization and use of the unified singlet and triplet electron-pair extrapolation scheme: application to a test set of 106 systems.

A method previously suggested to calculate the correlation energy at the complete one-electron basis set limit by reassignment of the basis hierarchical numbers and use of the unified singlet- and triplet-pair extrapolation scheme is applied to a test set of 106 systems, some with up to 48 electrons. The approach is utilized to obtain extrapolated correlation energies from raw values calculated with second-order Møller-Plesset perturbation theory and the coupled-cluster singles and doubles excitations method, some of the latter also with the perturbative triples corrections. The calculated correlation energies have also been used to predict atomization energies within an additive scheme. Good agreement is obtained with the best available estimates even when the (d, t) pair of hierarchical numbers is utilized to perform the extrapolations. This conceivably justifies that there is no strong reason to exclude double-zeta energies in extrapolations, especially if the basis is calibrated to comply with the theoretical model.

Acute and intermediate toxicity of 3-week radiotherapy with simultaneous integrated boost using TomoDirect: prospective series of 287 early breast cancer patients.

AIMS: To report toxicity of a hypofractionated scheme of whole-breast (WB) intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) to the tumor bed (TB) using Tomotherapy® with Direct modality. METHODS: Patients with early breast cancer, undergoing radiotherapy (RT) in 15 daily fractions to WB (prescription dose 40.05 Gy) and SIB to the TB (48 Gy), between 2013 and 2017, was analyzed. Primary endpoint was acute and intermediate toxicity assessed at the end and within 6 months from RT, according to Radiation Therapy Oncology Group (RTOG) scale. Secondary endpoints included early chronic toxicity at 12-months follow-up, using the Late Effects Normal Tissue Task Subjective, Objective, Management, and Analytic (LENT-SOMA) scale, and cosmesis using Harvard criteria. RESULTS: The study population was of 287 patients. Acute and intermediate toxicity was collected among 183 patients with data available at the end of RT and within 6 months, 85 (46%) experienced G2 toxicity and 84 (46%) G1 toxicity, while 14 (8%) did not report toxicity at any time. A significant reduction of any grade toxicity was observed between the two time points, with the majority of patients reporting no clinically relevant toxicity at 6 months. At univariate analysis, age < 40 years, breast volume > 1000 cm3 and Dmax ≤ 115% of prescription dose were predictive factors of clinically relevant acute toxicity (G ≥ 2) at any time. At multivariable analysis, only age and breast volume were confirmed as predictive factors, with Relative Risks (95% Confidence Intervals): 2.02 (1.13-3.63) and 1.84 (1.26-2.67), respectively. At 12-month follow-up, 113 patients had complete information on any toxicity with 53% of toxicity G < 2, while cosmetic evaluation, available for 102 patients, reported a good-excellent result for 86% of patients. CONCLUSIONS: Hypofractionated WB IMRT with a SIB to the TB, delivered with TomoDirect modality, is safe and well-tolerated. Most patients reported no toxicity after 6 months and good-excellent cosmesis. Predictive factors of clinically relevant toxicity might be considered during treatment planning in order to further reduce side effects.

Stereotactic radiation therapy in oligometastatic colorectal cancer: outcome of 102 patients and 150 lesions.

To evaluate the local control (LC), progression free survival (PFS), out-field PFS, overall survival (OS), toxicity and failure predictors of SRT in a series of various sites oligometastatic CRC patients. Patients with oligometastatic CRC disease were analyzed retrospectively. The SRT prescribed dose was dependent on the lesion volume and its location. 102 consecutive oligometastatic CRC patients (150 lesions) were included. They underwent SRT between 2012 and 2015. Median prescription dose was 45 Gy (median dose/fraction was 15 Gy/3 fractions biological equivalent dose (BED10) 112.5 Gy). Median follow-up was 11.4 months. No patients experienced G3 and G4 toxicity. No progression was found in 82% (radiological response at 3 months) and 85% (best radiological response) out of 150 evaluable lesions. At 1 and 2 years: LC was 70% and 55%; OS was 90% and 90%; PFS was 37% and 27%; out-field PFS was 37% and 23% respectively. Progressive disease was correlated with BED10 (better LC when BED10 was ≥ 75 Gy (p < 0.0001)). In multivariate analysis, LC was higher in lesions with a Plpnning target volume (PTV) volume < 42 cm3 and BED10 ≥ 75 Gy. Patients with Karnofsky performance status < 90 showed higher out-field progression. SRT is an effective treatment for patients with oligometastases from CRC. Its low treatment-associated morbidity and acceptable LC make of SRT an option not only in selected cases. Further studies should be focused to clarify which patient subgroup will benefit most from this treatment modality and to define the optimal dose to improve LC while maintaining low toxicity profile.

[Patient satisfaction in hemodialysis: a pilot cross-sectional analysis and a review]. / Valutazione del grado di soddisfazione da trattamento nel paziente in emodialisi: metologia di ricerca, strumenti, limiti e studio pilota trasversale.

BACKGROUND: Assessment of patient satisfaction is not performed routinely in many healthcare institutions. In this review, we discuss methodological aspects of assessment of patient satisfaction in hemodialysis. We also present a pilot study conducted in the Gambro Healthcare Italy dialysis clinics network. METHODS: Patient satisfaction was assessed in a network of hemodialysis units by using an internally validated Italian translation of the Choices for Healthy Outcomes in Caring for ESRD (CHOICE) questionnaire. A cross-sectional analytic study design was used and data analysed with univariate and multivariate hierarchical logistic regression to explore correlates of the risk of being unsatisfied with dialysis treatment. Covariates which were considered include a series of over 20 clinical, demographic, organizational and structural aspects. In addition, unexplained inter-centre residual variability due to 'case-mix' was explored and plotted. RESULTS: Seventeen dialysis units participated in this cross-sectional analysis and 758/1001 (75.7%) provided answers to the questionnaires. There was a statistically significant association on multivariate hierarchical analysis between the risk of being unsatisfied with dialysis treatment and interdialysis body weight gain (unit of increase: 1 kg, p=0.004). On the contrary, the risk of unsatisfaction with dialysis treatment was significantly lower in patients with higher dry weight (unit of increase: 1 kg, p=0.002). Our multivariate hierarchical analysis identified some residual variability between dialysis units (n=6 outliers) which may not be explained by any of over 20 potential confounding covariates which were explored. CONCLUSIONS: Assessment of ''customer satisfaction'' is standard practice in private for profit product companies in general but needs to be increasingly recognized as a standard in both public and private providers of healthcare services. Social research methods, which are used for this type of analysis, need to be fine tuned and actively implemented in order to better understand how we may influence the quality of service we provide to our patients and the level at which they rate it.

Antimicrobial agents and catheter-related interventions to prevent peritonitis in peritoneal dialysis: Using evidence in the context of clinical practice.

BACKGROUND: Peritonitis still represents a common and major complication of peritoneal dialysis. The broader adoption of several strategies, including antimicrobial and catheter related interventions, has been advocated to prevent or reduce the risk of peritonitis in peritoneal dialysis. METHODS: In this article we start with the presentation of a clinical case where concern exists about the strategies for preventing peritoneal dialysis peritonitis. We then look at the available evidence in the form of systematic reviews of randomized trials and individual randomized trials of interventions to prevent peritonitis in peritoneal dialysis. A summary of the evidence is provided and then put in context with the clinical case scenario. RESULTS: Nineteen eligible trials (1949 patients) of antimicrobial agents and 37 (2822 patients) of catheter related interventions to prevent peritonitis in peritoneal dialysis were identified. Nasal mupirocin compared with placebo significantly reduced the exit-site and tunnel infection rate (1 trial, 2716 patient months, RR 0.58, 95% CI 0.40 to 0.85) but not peritonitis rate (1 trial, 2716 patient months, RR 0.84, 95% CI 0.44 to 1.60). As for antimicrobial strategies, perioperative intravenous antibiotics compared with no treatment significantly reduced the risk of early peritonitis (4 trials, 335 patients, RR 0.35, 95% CI 0.15 to 0.80) but not exit site and tunnel infection (3 trials, 114 patients, RR 0.32, 95% CI 0.02 to 4.81). As for catheter related strategies, Y-set and twin-bag systems were superior to conventional spike systems (7 trials, 485 patients, RR 0.64, 95% CI 0.53 to 0.77) and no other catheter-related intervention was demonstrated to prevent peritonitis in PD. CONCLUSIONS: Evidence exists to support the use of perioperative intravenous antibiotic prophylaxis at the time of catheter placement, the twin-bag and Y-set system, as well as prophylaxis with mupirocin in Staphylococcus aureus nasal carriers. Despite lack of evidence, several other agents are used and recommended in major international guidelines, which is reasonable but requires further investigation.

VERO® radiotherapy for low burden cancer: 789 patients with 957 lesions.

PURPOSE: The aim of this retrospective study is to evaluate patient profile, feasibility, and acute toxicity of RadioTherapy (RT) delivered by VERO® in the first 20 months of clinical activity. METHODS: Inclusion criteria: 1) adult patients; 2) limited volume cancer (M0 or oligometastatic); 3) small extracranial lesions; 4) treatment between April 2012 and December 2013 and 5) written informed consent. Two techniques were employed: intensity modulated radiotherapy (IMRT) and stereotactic body radiotherapy (SBRT). Toxicity was evaluated using Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer (RTOG/EORTC) criteria. RESULTS: Between April 2012 and December 2013, 789 consecutive patients (957 lesions) were treated. In 84% of them one lesion was treated and in 16% more than one lesion were treated synchronously/metachronously; first radiotherapy course in 85%, re-irradiation in 13%, and boost in 2% of cases. The treated region included pelvis 46%, thorax 38%, upper abdomen 15%, and neck 1%. Radiotherapy schedules included <5 and >5 fractions in 75% and 25% respectively. All patients completed the planned treatment and an acceptable acute toxicity was observed. CONCLUSIONS: RT delivered by VERO® was administrated predominantly to thoracic and pelvic lesions (lung and urologic tumours) using hypofractionation. It is a feasible approach for limited burden cancer offering short and well accepted treatment with favourable acute toxicity profile. Further investigation including dose escalation and other available VERO® functionalities such as real-time dynamic tumour tracking is warranted in order to fully evaluate this innovative radiotherapy system.

Seasonal onset of the menopause.

OBJECTIVES: A seasonal rhythm of reproduction is evident in humans. Herein it was investigated whether also the cessation of woman's fertile life follows a seasonal rhythm. METHODS: A retrospective study was performed on 2436 women in postmenopause for more than 12 months, in our menopause centres. Time of menopause was stratified for month and season. The variation was compared to the seasonal rhythm of 14,310 conceptions. RESULTS: The onset of menopause was more frequent (p<0.0001) in winter (32.5%) than in spring (20.8%), autumn (20.3%) and summer (26.2%), in which a minor peak was also observed (p<0.0001 vs. spring and autumn). The two peaks were temporally coincident with the transitions between the high to low and low to high rate of conceptions. CONCLUSIONS: The present data show that in women, like reproduction also the onset of menopause shows a seasonal modulation.

Relative influence of menopausal status, age, and body mass index on blood pressure.

The objective of this study was to assess the influence of menopausal status on blood pressure levels in a cross-sectional population study in the setting of a preventive health care program clinically conducted in Ferrara, Italy. The patients were 2397 healthy women 35 to 65 years old (489 in premenopause, 847 in perimenopause, 887 in spontaneous menopause, and 174 in surgical menopause); subgroups were also obtained with increasing duration of menopause (1 to > 5 years) matched with premenopausal and perimenopausal women by chronological age at onset of menopause. Measurements of sphygmomanometric blood pressure, age, age at menopause, duration of menopause, and body mass index were made. Postmenopausal women had higher blood pressure than premenopausal and perimenopausal subjects. After adjustment for body mass index, the blood pressure changes with menopausal status were still significant, but not after correction by age. The increased risk of hypertension of postmenopausal women also lost statistical significance after adjustment for age and body mass index. At multivariate analysis, blood pressure showed no significant relation with the duration of menopause, whereas age was a significant covariant for systolic blood pressure, and body mass index for systolic and diastolic blood pressure. A transient initial rise in blood pressure and body mass index was detected in surgical but not in spontaneous menopause. Blood pressure rises after menopause appear to be due more to increased body mass index and aging than ovarian failure per se.

Influence of estrogens on serum free fatty acid levels in women.

A relationship between plasma levels of FFA and incidence of hormone-dependent breast cancer has been suggested. This observation has drawn our attention to possible complementary actions of ovarian steroids on circulating FFA levels. Measurements taken in normal women during the menstrual cycle and in ovariectomized women with and without estrogen replacement therapy demonstrate that 1) levels of FFA present in serum are lower during the luteal phase than during the follicular phase; 2) levels of FFA are significantly higher after ovariectomy; and 3) these are again reduced by substitutive estrogen therapy.

The effect of menopause on blood lipid and lipoprotein levels. The Icarus Study Group.

There is increasing evidence from epidemiological studies that exogenous estrogen (hormone replacement therapy) protects against the elevated risk of cardiovascular disease in women after the menopause. However, it is still uncertain whether the postmenopausal decrease in endogenous estrogen in itself contributes significantly to this increase in risk. Most of the studies that have provided evidence linking cardiovascular disease with menopause have involved North American women, who may differ significantly from Europeans in terms of lifestyle and diet. ICARUS (Italian Climacteric Research Group Study) is an observational study that involves Italian Menopause Clinics, with the objective of collecting observational data on menopause and its management. The results of a cross-sectional analysis of 9309 women, free from any hormonal treatment and enrolled up to March 1997, are reported here. Data show that the menopause has a marked effect on the circulating levels of lipids and lipoproteins. From pre- to post-menopause there are significant increases in total cholesterol (6.9% before and 4.4% after adjustment for covariates including chronological age, educational level, center, BMI, smoking habits, hypertension and diabetes, previous contraceptive use, and time since menopause), LDL (7.5% before, 4.0% after), and triglycerides (9.0% before, 3.2% (ns) after). However, there is no significant change in HDL. Among postmenopausal women, no effect on lipid profile of time since menopause was observed.

Ovarian steroids modulate the action of calcitonin in women.

Slow i.v. infusion of salmon calcitonin into normal women led to a transient increase in plasma concentrations of cyclic AMP and to a decrease in plasma calcium, which was maintained for at least 2 h. These responses were significantly reduced in the same patients after hysterectomy and ovariectomy. In contrast, maintenance of the ovaries at the time of surgery, or substitutive hormonal therapy, seemed to restore the sensitivity to exogenous calcitonin, suggesting a permissive role of ovarian steroids in the effect of calcitonin. The most likely explanation for this phenomenon is that these hormones influence either the number of calcitonin receptors or the coupling of the receptors to the functional unit of bone adenylate cyclase.

Multiple molecular forms of prolactin during pregnancy in women.

The distribution of isomorphic forms of prolactin in the serum of pregnant women was studied by gel filtration chromatography. Using this technique we were able to resolve three peaks, detected by radioimmunoassay: they were termed 'big-big', 'big' and 'little' prolactin in order of decreasing size, with approximate molecular weights greater than 100 000, 50 000 and 21 000 respectively. They displayed a comparable immunoreactivity to the antiserum employed in the radioimmunoassay, as determined in competition experiments. The relative amount of each hormone form in serum changed during the third trimester of pregnancy. At week 33 of pregnancy, 'little' prolactin accounted for 63.2 +/- 7.7% of the total circulating hormone present in the serum of five normal pregnant women. During the progression of pregnancy, there was a gradual increase in the low molecular weight prolactin, so that, at the time of delivery, the larger forms of the hormone were present only in small amounts.

The effect of dietary soy supplementation on hot flushes.

OBJECTIVE: To assess the effect of daily dietary supplementation of soy protein isolate powder on hot flushes in postmenopausal women. METHODS: We carried out a double-blind, parallel, multicenter, randomized placebo-controlled trial of 104 postmenopausal women. Fifty-one patients (age range 48-61 years) took 60 g of products containing 40 g of isolated soy protein [corrected] daily and 53 patients (age range 45-62 years) took 60 g of placebo (casein) daily. The study lasted 12 weeks. Using analysis of covariance, we analyzed changes from baseline in mean number of moderate to severe hot flushes (including night sweats) during treatment. RESULTS: Soy was significantly superior to placebo (P < .01 in reducing the mean number of hot flushes per 24 hours after 4, 8, and 12 weeks of treatment. In particular, women taking soy had a 26% reduction in the mean number of hot flushes by week 3 and a 33% reduction by week 4 (P < .001 by the Wilcoxon exact test). By the end of the 12th week, patients taking soy had a 45% reduction in their daily hot flushes versus a 30% reduction obtained with the placebo (P < .01). The overall rates of adverse effects were similar for soy and casein-placebo. Twenty-five patients dropped out of the study: 11 in the soy group and 14 in the placebo group. Gastrointestinal side effects were the most common cause of premature withdrawal from the study (seven patients in each group). CONCLUSION: Soy protein isolate added daily to the diet substantially reduced the frequency of hot flushes in climacteric women.

Dietary soy supplementation and phytoestrogen levels.

OBJECTIVE: To investigate the relationship between levels of phytoestrogens in blood and urine and symptom control in postmenopausal women whose diets were supplemented with soy containing high levels of phytoestrogen. METHODS: Phytoestrogen levels in blood and urine were correlated with the number of hot flushes and vaginal maturation indices in 104 postmenopausal women whose diets were supplemented with 60 g of soy powder daily for 3 months in a double-masked, parallel, placebo-controlled trial. The effect of soy supplementation on menopausal symptoms in this study population was reported previously. RESULTS: Serum levels of genistin, daidzin, and equol were significantly higher in women after soy diet supplementation (+756%, +593%, +1008%, and 57% respectively). The concentration of enterolactone in the soy group was increased by 57% compared with baseline, but the difference with placebo was not statistically significant. The increase in phytoestrogen levels in the soy group in blood or urine did not correlate with fewer hot flushes. Vaginal maturation indices did not change in the soy group. CONCLUSION: Phytoestrogen levels increased in women who consumed soy supplement, but that does not fully explain climacteric symptom reduction. It is possible that other types of yet unknown phytoestrogens or components in soy other than phytoestrogen influence hot flushes.