Suppression of the molecular ultra-fast dissociation in bromomethane clusters.

We address the influence of clustering on the ultra-fast dissociation of bromomethane. Valence and core photo-electron spectroscopy, partial electron yield absorption, and resonant Auger spectroscopy have been used together with ab initio calculations to investigate the properties of the ultra-fast dissociation. The ratio of ultra-fast dissociation of molecules in clusters as compared to free molecules is determined to be significantly reduced. We propose partial delocalization of the excited electronic state as being responsible for this behavior.

Vitamin D deficiency as a risk factor for cystic fibrosis-related diabetes in the Scandinavian Cystic Fibrosis Nutritional Study.

AIMS/HYPOTHESIS: Many cystic fibrosis patients are vitamin D-insufficient. Cystic fibrosis-related diabetes is a major complication of cystic fibrosis. The literature suggests that vitamin D might possess certain glucose-lowering properties. We aimed to assess the relationship between vitamin D and cystic fibrosis-related glucose intolerance. METHODS: We enrolled 898 cystic fibrosis patients from Sweden, Norway and Denmark. Vitamin D intake was assessed using a seven-day food record. Serum 25-hydroxyvitamin D (s25OHD) and HbA(1c) were measured, and an OGTT was carried out. Multiple linear and logistic regressions were used for HbA(1c) and cystic fibrosis-related diabetes/OGTT result as outcome variables, respectively. Each model was controlled for country, and for known cystic fibrosis-related diabetes risk factors: age, sex, genotype, liver dysfunction, long-term corticosteroid treatment, and lung and pancreatic function. RESULTS: Degree of vitamin D insufficiency (OR 1.36; p = 0.032) and s25OHD < 30 nmol/l (OR 1.79; p = 0.042) were significant risk factors for cystic fibrosis-related diabetes. Accordingly, HbA(1c) value was positively associated with s25OHD < 30 nmol/l and < 50 nmol/l, as well as with degree of vitamin D insufficiency (adjusted R (2) = 20.5% and p < 0.05 in all). In subgroup analyses, s25OHD < 30 nmol/l determined the HbA(1c) value in paediatric patients (adjusted R (2) = 20.2%; p = 0.017), but not in adults. CONCLUSIONS/INTERPRETATION: Vitamin D status is associated with HbA(1c) and diabetes in cystic fibrosis, particularly in children. The study justifies prospective studies on the proposed role of vitamin D deficiency in the pathophysiology of diabetes mellitus.

Large tunable Rashba spin splitting of a two-dimensional electron gas in Bi2Se3.

We report a Rashba spin splitting of a two-dimensional electron gas in the topological insulator Bi(2)Se(3) from angle-resolved photoemission spectroscopy. We further demonstrate its electrostatic control, and show that spin splittings can be achieved which are at least an order-of-magnitude larger than in other semiconductors. Together these results show promise for the miniaturization of spintronic devices to the nanoscale and their operation at room temperature.

Size of free neutral CO2 clusters from carbon 1s ionization energies.

Free neutral CO(2) clusters were produced by adiabatic expansion and characterized by carbon 1s (C1s) photoelectron spectroscopy using synchrotron radiation. The shift in C1s ionization energy (IE) between the cluster and the monomer, i.e., ΔIE = IE(cluster) - IE(monomer), was found to vary systematically with the experimental conditions. A functional relationship is established between the mean cluster size in the beam, , and ΔIE, in good agreement with theoretical calculations of shifts in ionization energy for model clusters. This makes it possible to use core-level photoelectron spectroscopy to monitor the mean cluster size and also to estimate from expansion conditions.

Increased vitamin plasma levels in Swedish military personnel treated with nutrients prior to automatic weapon training.

Noise-induced hearing loss (NIHL) is a significant clinical, social, and economic issue. The development of novel therapeutic agents to reduce NIHL will potentially benefit multiple very large noise-exposed populations. Oxidative stress has been identified as a significant contributor to noise-induced sensory cell death and NIHL, and several antioxidant strategies have now been suggested for potential translation to human subjects. One such strategy is a combination of beta-carotene, vitamins C and E, and magnesium, which has shown promise for protection against NIHL in rodent models, and is being evaluated in a series of international human clinical trials using temporary (military gunfire, audio player use) and permanent (stamping factory, military airbase) threshold shift models (NCT00808470). The noise exposures used in the recently completed Swedish military gunfire study described in this report did not, on average, result in measurable changes in auditory function using conventional pure-tone thresholds and distortion product otoacoustic emission (DPOAE) amplitudes as metrics. However, analysis of the plasma samples confirmed significant elevations in the bloodstream 2 hours after oral consumption of active clinical supplies, indicating the dose is realistic. The plasma outcomes are encouraging, but clinical acceptance of any novel therapeutic critically depends on demonstration that the agent reduces noise-induced threshold shift in randomized, placebo-controlled, prospective human clinical trials. Although this noise insult did not induce hearing loss, the trial design and study protocol can be applied to other populations exposed to different noise insults.

Valence photoelectron spectroscopy of N2 and CO: recoil-induced rotational excitation, relative intensities, and atomic orbital composition of molecular orbitals.

Recoil-induced rotational excitation accompanying photoionization has been measured for the X, A, and B states of N(2)(+) and CO(+) over a range of photon energies from 60 to 900 eV. The mean recoil excitation increases linearly with the kinetic energy of the photoelectron, with slopes ranging from 0.73×10(-5) to 1.40×10(-5). These slopes are generally (but not completely) in accord with a simple model that treats the electrons as if they were emitted from isolated atoms. This treatment takes into account the atom from which the electron is emitted, the molecular-frame angular distribution of the electron, and the dependence of the photoelectron cross section on photon energy, on atomic identity, and on the type of atomic orbital from which the electron is ejected. These measurements thus provide a tool for investigating the atomic orbital composition of the molecular orbitals. Additional insight into this composition is obtained from the relative intensities of the various photolines in the spectrum and their variation with photon energy. Although there are some discrepancies between the predictions of the model and the observations, many of these can be understood qualitatively from a comparison of atomic and molecular wavefunctions. A quantum-mechanical treatment of recoil-induced excitation predicts an oscillatory variation with photon energy of the excitation. However, the predicted oscillations are small compared with the uncertainties in the data, and, as a result, the currently available results cannot provide confirmation of the quantum-mechanical theory.

The use, feasibility and psychometric properties of an individualised quality-of-life instrument: a systematic review of the SEIQoL-DW.

PURPOSE: To review published studies regarding the use, feasibility and psychometric performance of the schedule for the evaluation of individual quality of life-direct weighting (SEIQoL-DW) in clinical research. METHODS: Systematic literature review. Studies using the SEIQoL-DW were included if they were published in English and employed a quantitative design. A pre-defined checklist was used to analyse the reported results. RESULTS: Thirty-nine relevant articles were identified. The SEIQoL-DW has been included in studies relating to a variety of populations, including those who are severely ill. The results of convergent and discriminant validity support our hypotheses in which SEIQoL-DW was expected to correlate moderately to high with measures of global QoL, life satisfaction and mental health and weakly with measures of functional status and health. CONCLUSION: The SEIQoL-DW appears to be a feasible and valid instrument. The lack of association between the Index score and health, functional status, demographic and clinical parameters may be explained by the instrument's focus on global QoL and by that of the idiographic measurement approach reflecting the capacity of a patient to value domains other than health in life, despite having health problems. Nevertheless, continued psychometric evaluation in large populations with a longitudinal design is recommended.

A dose dependence study of O(2) adsorbed on large Ar clusters.

An investigation of the behavior of O(2) molecules in and on O(2)-doped large (N approximately 8000) Ar host clusters has been performed by means of core and valence photoelectron spectroscopy. Data from pure O(2) and Ar clusters, as well as from O(2)-doped Ar clusters, are presented. The experimental data together with calculations of the binding energy shifts of oxygen molecular ions in and on the surface of a large host Ar cluster show that the diffusion behavior has a strong dependence on the doping pressure. We conclude that the oxygen molecules in the doped Ar host do not partake in band formation, since there is clear vibrational resolution in the spectral features stemming from screened O(2) (+) ions. This implies that valence photoelectron spectroscopy can be used to determine the geometrical structure of this and certain, similar, cluster systems.

Multiple-breath inert gas washout and spirometry versus structural lung disease in cystic fibrosis.

BACKGROUND: A sensitive and valid non-invasive marker of early cystic fibrosis (CF) lung disease is sought. The lung clearance index (LCI) from multiple-breath washout (MBW) is known to detect abnormal lung function more readily than spirometry in children and teenagers with CF, but its relationship to structural lung abnormalities is unknown. A study was undertaken to determine the agreements between LCI and spirometry, respectively, with structural lung disease as measured by high-resolution computed tomography (HRCT) in children and teenagers with CF. METHODS: A retrospective study was performed in 44 consecutive patients with CF aged 5-19 years (mean 12 years). At an annual check-up inspiratory and expiratory HRCT scans, LCI and spirometric parameters (forced expiratory volume in 1 s (FEV1) and maximal expiratory flow when 75% of forced vital capacity was expired (FEF75)) were recorded. Abnormal structure was defined as a composite HRCT score of >5%, the presence of bronchiectasis or air trapping >30%. Abnormal lung function was defined as LCI above the predicted mean +1.96 residual standard deviations (RSD), or FEV1 or FEF75 below the predicted mean -1.96 RSD. Sensitivity/specificity assessments and correlation analyses were done. RESULTS: The sensitivity to detect abnormal lung structure was 85-94% for LCI, 19-26% for FEV1 and 62-75% for FEF75. Specificity was 43-65% for LCI, 89-100% for FEV1 and 75-88% for FEF75. LCI correlated better with HRCT scores (Rs +0.85) than FEV1 (-0.62) or FEF75 (-0.66). CONCLUSIONS: LCI is a more sensitive indicator than FEV1 or FEF75 for detecting structural lung disease in CF, and a normal LCI almost excludes HRCT abnormalities. The finding of an abnormal LCI in some patients with normal HRCT scans suggests that LCI may be even more sensitive than HRCT scanning for detecting lung involvement in CF.

Testing the validity of a translated pharmaceutical therapy-related quality of life instrument, using qualitative 'think aloud' methodology.

BACKGROUND AND OBJECTIVE: In pharmacy practice, there is a need for valid and reliable instruments to study patient-reported outcomes. One potential candidate is a pharmaceutical therapy-related quality of life (PTRQoL) instrument. This study explored the face and content validity, including cognitive aspects of question answering of a PTRQoL instrument, translated from English to Swedish. METHOD: A sample of 16 customers at Swedish community pharmacies, was asked to fill in the PTRQoL instrument while constantly reporting how they reasoned. The resulting interviews and concurrent probing, were audio-taped, transcribed verbatim and analysed using constant comparison method. RESULTS AND DISCUSSION: The relation between the measurement and its theoretical underpinning was challenged. Respondents neglected to read the instructions, used response options in an unpredictable way, and varied in their interpretations of the items. CONCLUSION: The combination of 'think-aloud', retrospective probing and qualitative analysis informed on the validity of the PTRQoL instrument and was valuable in questionnaire development. The study also identified specific problems that could be relevant for other instruments probing patients' medicines-related attitudes and behaviour.

Follow-up of patients receiving a pharmaceutical care service in Sweden.

BACKGROUND: Pharmaceutical care (PC) services are increasingly provided in community pharmacies in the western world. Evaluations are often conducted as trials in highly controlled conditions measuring the efficacy of the service in terms of the economical, clinical and humanistic outcomes. Little is known about the real world provision of PC services and the factors associated with follow-up. OBJECTIVE: To characterize patients receiving a PC service, to explore factors associated with follow-up evaluations, and to describe the results of pharmacists' interventions. METHODS: A non-experimental, retrospective study using the Swedish national patient medication records data base. Patients receiving follow-up evaluations or one consultation within the service were compared using logistic regression. RESULTS: A total of 3298 patients received the PC service at 240 community pharmacies. Patient characteristics included: 66.3% female, mean age 71.1 years, mean number of prescription drugs used 10.5, with 86.2% of patients using >or=1 cardiovascular drugs. A quarter (25.8%) of patients had >or=1 drug-related problems, most commonly side effects. Follow-up evaluations were carried out for 46.6% of the patients, who were more likely to use a compliance aid. Patients receiving the PC service at pharmacies that had enrolled more than the mean number of patients (13.7) had twice as high a chance of receiving follow-up than those registered with pharmacies with fewer patients (i.e. below the mean) enrolled. Followed-up interventions led to a better perceived outcome in 46.3% of cases, no change in 48.5% and a worse outcome in 5.2%. CONCLUSIONS: This study demonstrates that the total number of patients enrolled in a PC service predicts whether follow-up evaluations will take place or not more than do patient characteristics.

Novel methodology to perform sulfur hexafluoride (SF6)-based multiple-breath wash-in and washout in infants using current commercially available equipment.

Multiple-breath inert gas washout (MBW) is ideally suited for early detection and monitoring of serious lung disease, such as cystic fibrosis, in infants and young children. Validated commercial options for the MBW technique are limited, and suitability of nitrogen (N2)-based MBW is of concern given the detrimental effect of exposure to pure O2 on infant breathing pattern. We propose novel methodology using commercially available N2 MBW equipment to facilitate 4% sulfur hexafluoride (SF6) multiple-breath inert gas wash-in and washout suitable for the infant age range. CO2, O2, and sidestream molar mass sensor signals were used to accurately calculate SF6 concentrations. An improved dynamic method for synchronization of gas and respiratory flow was developed to take into account variations in sidestream sample flow during MBW measurement. In vitro validation of triplicate functional residual capacity (FRC) assessments was undertaken under dry ambient conditions using lung models ranging from 90 to 267 ml, with tidal volumes of 28-79 ml, and respiratory rates 20-60 per minute. The relative mean (SD, 95% confidence interval) error of triplicate FRC determinations by washout was -0.26 (1.84, -3.86 to +3.35)% and by wash-in was 0.57 (2.66, -4.66 to +5.79)%. The standard deviations [mean (SD)] of percentage error among FRC triplicates were 1.40 (1.14) and 1.38 (1.32) for washout and wash-in, respectively. The novel methodology presented achieved FRC accuracy as outlined by current MBW consensus recommendations (95% of measurements within 5% accuracy). Further clinical evaluation is required, but this new technique, using existing commercially available equipment, has exciting potential for research and clinical use.

A prospective evaluation of hepatic resection for colorectal carcinoma metastases to the liver: Gastrointestinal Tumor Study Group Protocol 6584.

We report here the results of the first multiinstitutional prospective evaluation of patients considered to have potentially resectable hepatic metastases from colorectal carcinoma. One hundred fifty-six patients were enrolled from 15 institutions. Six patients were subsequently excluded. One hundred fifty patients underwent surgery and are evaluable for analysis (median follow-up time, 3.1 years; range, 4 months to 5.1 years). Curative resection could be performed on 46% of patients (69 of 150), noncurative resection on 12% (18 of 150), while 42% were found to be unresectable (63 of 150). Thirty-day surgical mortality and morbidity rates in patients with attempted resection were 2.7% and 13%, respectively. The curative resection group was observed to have an improved median survival (37.1 months) compared with the noncurative resection group (21.2 months) and the unresectable group (16.5 months) (P less than .01). Computed tomographic (CT) scan was a poor predictor for resectability, and age was not a contraindication to curative resection. Preoperative carcinoembryonic antigen (CEA) values were also a poor predictor for resectability. However, the median CEA value 61 to 180 days postsurgery was significantly higher in unresectable patients compared with median CEA levels in noncuratively and curatively resected groups (P less than .01). Our results imply that curative resection leads to an increase in median survival. Noncurative resection provides no benefit to asymptomatic patients, since unresectable and noncurative resection groups have similar life expectancies. Longer follow-up will be needed to demonstrate the ultimate impact of curative resection on survival.

Genotyping of Pseudomonas aeruginosa reveals high diversity, stability over time and good outcome of eradication.

BACKGROUND: Genotyping of Pseudomonas aeruginosa (P.a) is used for surveillance at our CF clinic. METHODS: P.a from 1999 to 2012 were analysed, using pulsed-field gel electrophoresis (PFGE) and multiple-locus variable number of tandem repeats analysis (MLVA). RESULTS: Among 232 isolates from 104 patients, we identified 78 unique strains, of which 56 were isolated from individual patients. The B-clone was isolated from 13 patients and the camp transmission clone J-strains from 8 patients at the start of the study. There was no indication of transmission within the clinic. PFGE and MLVA clone identification was in 91% agreement. For patients who provided more than 2 P.a isolates, similar strains were identified over time for 45/49 chronically- and for 6/16 intermittently-colonized patients despite, periods of no detectable P.a after eradication therapy. CONCLUSIONS: Analyses revealed high genotypic diversity, acceptable outcome of eradication therapy and no indication of cross-infection at the CF centre.

Studies of DNA and chromosome damage in skin fibroblasts and blood lymphocytes from psoriasis patients treated with 8-methoxypsoralen and UVA irradiation.

Exposure of human lymphocytes and skin fibroblasts in vitro to a single, clinically used dose of PUVA, i.e., 0.1 micrograms/ml of 8-methoxypsoralen (8-MOP) plus 0.9-4 J/cm2 of longwave ultraviolet radiation (UVA), lead to the formation of DNA damage as determined by alkaline elution, and to chromosome aberrations and sister chromatid exchanges (SCE). When lymphocyte-enriched plasma was obtained from psoriasis patients 2 h after oral intake of 8-MOP and then UVA irradiated (1.8-3.6 J/cm2) in vitro, an increased frequency of chromosome aberrations and SCE was observed. Normal levels of chromosome aberrations and SCE were found in lymphocytes of psoriasis patients after 3-30 weeks of PUVA treatment in vivo. A small but statistically significant increase in the SCE frequency was observed in the lymphocytes of psoriasis patients treated for 1-6 years with PUVA (mean 18.0 SCE/cell) as compared with before PUVA (mean 15.8, p less than 0.05). Skin fibroblasts of psoriasis patients analyzed 5 years after the start of PUVA treatment showed a normal number of SCE but a high fraction of filter-retained DNA in the alkaline elution assay, suggesting the presence of cross-linked DNA.

Studies of acute effects of insulin-like growth factors I and II in human fat cells.

The acute metabolic effects and receptor binding of insulin-like growth factors (IGFs) I and II were studied in human adipose tissue. The IGFs inhibited fat cell glycerol release and stimulated adipocyte 3-O-methylglucose transport and adipose tissue glucose oxidation as effectively as did insulin, but the biological potencies of the IGFs, on a molar basis, were 600-1000 times less than that of insulin. The insulin dose-response curve for antilipolysis gradually shifted to the left in the presence of submaximally and maximally effective IGF-I concentrations, whereas no additive response was found when fat cells were incubated with maximally effective concentrations of insulin and the IGFs. Adipocyte [125I]IGF-I and -II binding was low and was not inhibited by excess unlabeled IGF. In contrast, IGF-I inhibited [125I]insulin binding with a molar potency 1600 times lower than that of native insulin. In adipose tissue segments obtained from patients with untreated noninsulin-dependent diabetes mellitus, IGF-I and insulin inhibited glycerol release in a normal way. Conversely, neither insulin nor IGF-I increased the rate of glucose oxidation significantly above the nonhormone-stimulated level. We conclude that human fat cells lack specific cell surface IGF-binding sites. However, the IGFs definitely produce acute insulin-like effects in the human adipocyte, which seems to be mediated via the insulin receptor.

Adjuvant postoperative radiotherapy and chemotherapy in rectal carcinoma: a review of the Gastrointestinal Tumor Study Group experience.

The Gastrointestinal Tumor Study Group (GITSG) protocol GI-7175 randomized 227 patients between 1975 and 1980 following complete surgical resection of stages B2 and C rectal adenocarcinoma to four treatment arms: (1) no adjuvant therapy, (2) chemotherapy only, (3) radiotherapy only, and (4) radiotherapy and chemotherapy (combined modality). The results of the study showed an advantage for combined modality treatment over no adjuvant therapy for time to recurrence (p = 0.005) and for survival (p = 0.01). Severe acute toxicity was frequent in the combined modality arm (61%) but late effects, including radiation enteritis, have been infrequent. We conclude that postoperative adjuvant therapy is indicated in certain stages of rectal carcinoma and that the present state of knowledge suggests combined modality therapy.

Effect of nicotine on human fetal blood flow.

Immediate maternal and fetal cardiovascular responses to different doses of nicotine and carbon monoxide were studied in 24 pregnant smokers. A noninvasive pulsed Doppler ultrasound technique was used for measuring fetal blood flow in the descending thoracic aorta, the intra-abdominal part of the umbilical vein, and in the umbilical artery. Maternal plasma concentrations of nicotine, carbon monoxide, and catecholamines were measured. Maternal heart rate, blood pressure, fetal heart rate, and fetal aortic and umbilical vein blood flow increased, while pulsatility indices of the fetal aortic and umbilical artery blood velocity waveforms decreased, with increasing maternal nicotine levels; all were unaffected by carbon monoxide. Catecholamine levels remained unaffected. These results seem to confirm that the maternal nicotine intake due to smoking has an immediate, dose-dependent effect on fetal blood flow.

Blood flow in the fetal descending aorta.

Doppler estimation of the blood flow in the descending aorta of the fetus and waveform analysis of the maximum aortic velocity provide valuable information on fetal circulation. When estimating fetal aortic flow, it is important to consider possible sources of error; even when recording the maximum aortic velocity for waveform analysis, to obtain reproducible results it is important to use a low high-pass filter, a well-defined angle of insonation, and a standardized site of measurement and to avoid periods of fetal breathing and activity. In normal pregnancy the time-averaged mean velocity in the descending aorta is stable throughout the third trimester. The weight-related flow is stable until 37 weeks, after which it falls slightly. The placental proportion of the flow in the thoracic descending aorta decreases toward term. In the aorta of normal fetuses there is positive flow throughout the whole heart cycle, which is due to the low vascular resistance in the placental circulation. The waveform of the aortic velocity can be characterized by the PI, which is stable during the last trimester of gestation. Caution is required when interpreting changes in the aortic PI, as it is not only affected by the peripheral resistance but also by the heart performance. Furthermore, PI is related to fetal heart rate. Near term different values of PI are found in different fetal behavioral states. In fetuses with retarded growth and in fetuses at distress, characteristic changes of the aortic velocity waveform have been reported by several researchers: the end-diastolic velocity diminishes and disappears, and in extreme cases a brief reversal of flow in diastole was observed. Consequently, the PI increases in such cases. The absence of the end-diastolic aortic velocity can easily be determined and is the best indicator of fetal status: in fetuses with absent end-diastolic velocity the incidence of perinatal mortality and morbidity is significantly higher than in fetuses with positive flow throughout the cycle. In pregnancies with hypertension or diabetes mellitus, normal aortic flow has been reported, as long as the fetuses were not growth retarded. In cases of severe Rh-isoimmunization, the mean aortic velocity correlates with fetal hematocrit. In hypoxic fetuses the mean velocity was reported to correlate with the degree of hypoxia, hypercarbia, and acidosis.(ABSTRACT TRUNCATED AT 400 WORDS)