A repeating fast radio burst source in a globular cluster.

Fast radio bursts (FRBs) are flashes of unknown physical origin1. The majority of FRBs have been seen only once, although some are known to generate multiple flashes2,3. Many models invoke magnetically powered neutron stars (magnetars) as the source of the emission4,5. Recently, the discovery6 of another repeater (FRB 20200120E) was announced, in the direction of the nearby galaxy M81, with four potential counterparts at other wavelengths6. Here we report observations that localized the FRB to a globular cluster associated with M81, where it is 2 parsecs away from the optical centre of the cluster. Globular clusters host old stellar populations, challenging FRB models that invoke young magnetars formed in a core-collapse supernova. We propose instead that FRB 20200120E originates from a highly magnetized neutron star formed either through the accretion-induced collapse of a white dwarf, or the merger of compact stars in a binary system7. Compact binaries are efficiently formed inside globular clusters, so a model invoking them could also be responsible for the observed bursts.

Effect of the New Nordic Diet compared with usual care on glucose control in gestational diabetes mellitus: Study protocol for the randomized controlled trial intervention with new Nordic DIet in women with GestatiOnal diabetes mellitus (iNDIGO).

BACKGROUND: Gestational diabetes mellitus (GDM) is a pregnancy complication associated with short- and long-term health consequences for mother and child. First line treatment is diet and exercise but there is a recognized knowledge gap as to what diet treatment is optimal. A healthy Nordic diet has been associated with improved health but no studies in women with GDM exist. The New Nordic Diet (NND) is an initiative with the purpose to develop a healthy Nordic diet including foods with the potential to grow in Nordic countries; including fruit, berries, vegetables, whole-grain cereal products, nuts, fish, and rapeseed oil. The purpose of the intervention with new Nordic DIet in women with GestatiOnal diabetes mellitus (iNDIGO) is to test if the NND compared with usual care improves glucose control in women with GDM. METHODS: The iNDIGO study is a randomized parallel controlled trial where 50 women with GDM will be randomized to either an NND or usual care for 14 days (30-32 weeks of gestation). Participants in the NND group will receive menus and food bags containing foods to be consumed. Primary outcome is glycemic control (time in target) measured using continuous glucose monitoring. Compliance to the dietary intervention will be tested using dietary biomarkers and adherence questionnaires. CONCLUSION: Diet treatment represents first line treatment in GDM but it remains unclear what type of diets are effective. iNDIGO is an efficacy study and will provide evidence as to whether a healthy Nordic diet can improve glucose control in women with GDM. TRIAL REGISTRATION: ClinicalTrials.gov registration Number: NCT04169243. Registered 19 November 2019, https://clinicaltrials.gov/ct2/show/NCT04169243.

Chronic pain after open inguinal hernia repair: expertise-based randomized clinical trial of heavyweight or lightweight mesh.

BACKGROUND: There is a shortage of high-quality studies regarding choice of mesh in open anterior inguinal hernia repair in relation to long-term chronic pain. The authors hypothesized that heavyweight compared with lightweight mesh causes increased postoperative pain. METHODS: An RCT was undertaken between 2007 and 2009 at two sites in Sweden. Men aged 25 years or older with an inguinal hernia evaluated in the outpatient clinic were randomized in an unblinded fashion to heavyweight or lightweight mesh for open anterior inguinal hernia repair. Data on pain affecting daily activities, as measured by the Short-Form Inguinal Pain Questionnaire 9-12 years after surgery, were collected as the primary outcome. Differences between groups were evaluated by generalized odds and numbers needed to treat. RESULTS: A total of 412 patients were randomized; 363 were analysed with 320 questionnaires sent out. A total of 271 questionnaires (84.7 per cent) were returned; of these, 121 and 150 patients were in the heavyweight and lightweight mesh groups respectively. Pain affecting daily activities was more pronounced in patients randomized to heavyweight versus lightweight mesh (generalized odds 1.33, 95 per cent c.i. 1.10 to 1.61). This translated into a number needed to treat of 7.06 (95 per cent c.i. 4.28 to 21.44). Two reoperations for recurrence were noted in the heavyweight mesh group, and one in the lightweight mesh group. CONCLUSION: A large-pore lightweight mesh causes significantly less pain affecting daily activities a decade after open anterior inguinal hernia repair. Registration number: NCT00451893 (http://www.clinicaltrials.gov).

A systematic review of working conditions and occupational health among immigrants in Europe and Canada.

BACKGROUND: A systematic attempt to summarize the literature that examines working conditions and occupational health among immigrant in Europe and Canada. METHODS: We established inclusion criteria, searched systematically for articles included in the Medline, Embase and Social Sciences Citation Index databases in the period 2000-2016 and checked the reference lists of all included papers. RESULTS: Eighty-two studies were included in this review; 90% were cross-sectional and 80% were based on self-report. Work injuries were consistently found to be more prevalent among immigrants in studies from different countries and in studies with different designs. The prevalence of perceived discrimination or bullying was found to be consistently higher among immigrant workers than among natives. In general, however, we found that the evidence that immigrant workers are more likely to be exposed to physical or chemical hazards and poor psychosocial working conditions is very limited. A few Scandinavian studies support the idea that occupational factors may partly contribute to the higher risk of sick leave or disability pension observed among immigrants. However, the evidence for working conditions as a potential mediator of the associations between immigrant status and poor general health and mental distress was very limited. CONCLUSION: Some indicators suggest that immigrant workers in Europe and Canada experience poorer working conditions and occupational health than do native workers. However, the ability to draw conclusions is limited by the large gaps in the available data, heterogeneity of immigrant working populations, and the lack of prospectively designed cohort studies.

The circumstellar envelope around the S-type AGB star W Aql. Effects of an eccentric binary orbit.

CONTEXT: Recent observations at subarcsecond resolution, now possible also at submillimeter wavelengths, have shown intricate circumstellar structures around asymptotic giant branch (AGB) stars, mostly attributed to binary interaction. The results presented here are part of a larger project aimed at investigating the effects of a binary companion on the morphology of circumstellar envelopes (CSEs) of AGB stars. AIMS: AGB stars are characterized by intense stellar winds that build CSEs around the stars. Here, the CO(J = 3→2) emission from the CSE of the binary S-type AGB star W Aql has been observed at subarcsecond resolution using ALMA. The aim of this paper is to investigate the wind properties of the AGB star and to analyse how the known companion has shaped the CSE. METHODS: The average mass-loss rate during the creation of the detected CSE is estimated through modelling, using the ALMA brightness distribution and previously published single-dish measurements as observational constraints. The ALMA observations are presented and compared to the results from a 3D smoothed particle hydrodynamics (SPH) binary interaction model with the same properties as the W Aql system and with two different orbital eccentricities. Three-dimensional radiative transfer modelling is performed and the response of the interferometer is modelled and discussed. RESULTS: The estimated average mass-loss rate of W Aql is M = 3.0×10-6 M⊙ yr-1 and agrees with previous results based on single-dish CO line emission observations. The size of the emitting region is consistent with photodissociation models. The inner 10″ of the CSE is asymmetric with arc-like structures at separations of 2-3″ scattered across the denser sections. Further out, weaker spiral structures at greater separations are found, but this is at the limit of the sensitivity and field of view of the ALMA observations. CONCLUSIONS: The CO(J = 3→2) emission is dominated by a smooth component overlayed with two weak arc patterns with different separations. The larger pattern is predicted by the binary interaction model with separations of ~10″ and therefore likely due to the known companion. It is consistent with a binary orbit with low eccentricity. The smaller separation pattern is asymmetric and coincides with the dust distribution, but the separation timescale (200 yrs) is not consistent with any known process of the system. The separation of the known companions of the system is large enough to not have a very strong effect on the circumstellar morphology. The density contrast across the envelope of a binary with an even larger separation will not be easily detectable, even with ALMA, unless the orbit is strongly asymmetric or the AGB star has a much larger mass-loss rate.

From population genomics to conservation and management: a workflow for targeted analysis of markers identified using genome-wide approaches in Atlantic salmon Salmo salar.

A genotyping assay for the Ion Torrent Ion PGM platform was developed for fast and cost-effective targeted genotyping of key single nucleotide polymorphisms (SNPs) earlier identified using a genome-wide SNP array in Atlantic salmon Salmo salar. The method comprised a simple primer design step for multiplex-polymerase chain reaction (PCR), followed by two rounds of Ion Torrent Ion PGM sequencing to empirically evaluate marker efficiency in large multiplexes and to optimise or exclude them when necessary. Of 282 primer pairs initially tested, 217 were successfully amplified, indicating good amplification success (>75%). These markers included the sdy partial gene product to determine genetic sex, as well as three additional modules comprising SNPs for assessing neutral genetic variation (NSNP = 150), examining functional genetic variation associated with sea age at maturity (NSNP = 5), and for performing genetic subpopulation assignment (NSNP = 61). The assay was primarily developed to monitor long-term genetic changes in S. salar from the Teno River, but modules are likely suitable for application in a wide range of S. salar populations. Furthermore, the fast and versatile assay development pipeline offers a strategy for developing targeted sequencing assays in any species.

Cognitive testing with the Post-Operative Quality of Recovery Scale in pre-surgery cancer patients--a controlled study.

BACKGROUND: Post-Operative Quality of Recovery Scale (PQRS) has been revised to allow for the normal variation in cognitive performance seen in healthy volunteers. This modification could result in exclusion of test subjects because of poor baseline performance. Our aim was to investigate the impact of severe disease and waiting for cancer surgery on PQRS baseline cognitive performance and exclusion rate, and also on variation in cognitive performance at test re-test. METHODS: Sixty-one subjects, 31 women diagnosed with breast cancer and waiting for surgery and 30 healthy women, performed the PQRS cognitive, nociceptive and emotional domains three times in 48 h. Exclusion rate, change in score and the proportion fulfilling 'recovery' criteria at re-tests were assessed. RESULTS: Nine out of 31 patients (29%) and two out of 30 controls (7%) had too low baseline score to be further assessed (P = 0.043). The change in score at re-tests was similar between the groups. Sixty-four per cent and 83% at 20 h and 79% and 86% at 48 h in the patient and control groups respectively fulfilled the 'recovery' criteria (P = 0.45). The 'recovery' for nociceptive and emotional distress was similar between the groups, but anxiety and sadness absolute scores were significantly higher in the patient group. CONCLUSION: Women with breast cancer waiting for surgery expressed a higher level of emotional distress, performed lower at baseline but showed no difference in test re-test variability in cognitive performance according to the PQRS when compared with controls. The considerable exclusion rate among patients waiting for cancer surgery should be acknowledged.

Long-term persistence of a multi-resistant methicillin-susceptible Staphylococcus aureus (MR-MSSA) clone at a university hospital in southeast Sweden, without further transmission within the region.

The objective of this study was to characterise isolates of methicillin-susceptible Staphylococcus aureus (MSSA) with resistance to clindamycin and/or tobramycin in southeast Sweden, including the previously described ECT-R clone (t002) found in Östergötland County, focusing on clonal relatedness, virulence determinants and existence of staphylococcal cassette chromosome (SCC) mec remnants. MSSA isolates with resistance to clindamycin and/or tobramycin were collected from the three county councils in southeast Sweden and investigated with spa typing, polymerase chain reaction (PCR) targeting the SCCmec right extremity junction (MREJ) and DNA microarray technology. The 98 isolates were divided into 40 spa types, and by microarray clustered in 17 multi-locus sequence typing (MLST) clonal complexes (MLST-CCs). All isolates with combined resistance to clindamycin and tobramycin (n = 12) from Östergötland County and two additional isolates (clindamycin-R) were designated as spa type t002, MREJ type ii and were clustered in CC5, together with a representative isolate of the ECT-R clone, indicating the clone's persistence. These isolates also carried several genes encoding exotoxins, Q9XB68-dcs and qacC. Of the isolates in CC15, 83% (25/30) were tobramycin-resistant and were designated spa type t084. Of these, 68% (17/25) were isolated from new-borns in all three counties. The persistence of the ECT-R clone in Östergötland County, although not found in any other county in the region, carrying certain virulence factors that possibly enhance its survival in the hospital environment, highlights the fact that basic hygiene guidelines must be maintained even when MRSA prevalence is low.

Cognitive recovery after ambulatory anaesthesia based on desflurane or propofol: a prospective randomised study.

BACKGROUND: The impact of anaesthetic agents on cognitive recovery during the first post-operative week in a middle-aged population undergoing general anaesthesia is insufficiently studied. We hypothesised that patients receiving anaesthesia based on desflurane would have a quicker recovery and regain cognitive capacity faster than patients receiving anaesthesia based on propofol. METHODS: We performed a prospective, randomised, single-blinded study comparing the effects of desflurane and propofol as primary anaesthetic agents on cognitive recovery in 59 American Society of Anesthesiologists Physical Status Classification System I-II women undergoing breast surgery. Cognitive recovery was evaluated using the Cognitive Failure Questionnaire and a modified version of the Post-operative Quality of Recovery Scale. RESULTS: Post-operative cognitive recovery according to Cognitive Failure Questionnaire was 65% and 66% at 72 h, and 71% and 72% at 1 week for the desflurane and the propofol groups, respectively. Recovery according to Post-operative Quality of Recovery Scale was 52% and 50% at 2 h, increasing to 71% and 87% at 48 h for the desflurane and the propofol groups, respectively. At the final point of measurement (Cognitive Failure Questionnaire 1 week, Post-operative Quality of Recovery Scale 48 h), many of the patients had still not reached their baseline cognitive performance. There was no difference in overall cognitive recovery between the desflurane and propofol groups. CONCLUSION: Cognitive recovery was not complete 1 week after surgery in any of the groups. There was no difference in the rate of cognitive recovery in middle-aged patients receiving desflurane or propofol anaesthesia during ambulatory breast surgery.

Post-operative Quality of Recovery Scale: the impact of assessment method on cognitive recovery.

BACKGROUND: We measured cognitive performance and recovery with the Post-operative Quality of Recovery Scale (PQRS) at 30 and 90 min after elective ambulatory or short-stay surgery under general anaesthesia. The aim was to study the impact of the assessment algorithm, comparing the original and modified more liberal score assessment. METHOD: One hundred and ten ASA 1-2 patients scheduled for elective surgery in general anaesthesia responded to the five cognitive performance questions in the PQRS; pre-operatively, 30 and 90 min after end of anaesthesia. Assessment of cognitive recovered was performed according to the original and modified definition which includes a tolerance factor to account for performance variability. RESULTS: Cognitive recovery improved from 30 to 90 min. The modified score assessment decreased number of patients that were evaluated low because it excluded initial low scoring subjects and also dramatically increased number of patients assessed as cognitively recovered; original 9% at 30 min and 28% at 90 min vs. 54% at 30 min and 81% at 90 min, P < 0.001. There were no other significant differences identified when using either the original or modified scoring method for age > 50 years, orthopaedic vs. abdominal surgery, premedication or gender. CONCLUSIONS: The modified definition which includes a tolerance factor to account for performance variability has dramatic effects in increasing the number of patients assessed as recovered. It is from the present study not possible to comment on whether the more liberal assessment provides more or less accurate description of cognitive performance.

Unexpectedly large mass loss during the thermal pulse cycle of the red giant star R Sculptoris.

The asymptotic-giant-branch star R Sculptoris is surrounded by a detached shell of dust and gas. The shell originates from a thermal pulse during which the star underwent a brief period of increased mass loss. It has hitherto been impossible to constrain observationally the timescales and mass-loss properties during and after a thermal pulse--parameters that determine the lifetime of the asymptotic giant branch and the amount of elements returned by the star. Here we report observations of CO emission from the circumstellar envelope and shell around R Sculptoris with an angular resolution of 1.3″. What was previously thought to be only a thin, spherical shell with a clumpy structure is revealed to also contain a spiral structure. Spiral structures associated with circumstellar envelopes have been previously seen, leading to the conclusion that the systems must be binaries. Combining the observational data with hydrodynamic simulations, we conclude that R Sculptoris is a binary system that underwent a thermal pulse about 1,800 years ago, lasting approximately 200 years. About 3 × 10(-3) solar masses of material were ejected at a velocity of 14.3 km s(-1) and at a rate around 30 times higher than the pre-pulse mass-loss rate. This shows that about three times more mass was returned to the interstellar medium during and immediately after the pulse than previously thought.

Detection and characterisation of SCCmec remnants in multiresistant methicillin-susceptible Staphylococcus aureus causing a clonal outbreak in a Swedish county.

The purpose of this study was to investigate if multiresistant methicillin-susceptible Staphylococcus aureus (MR-MSSA) causing a clonal outbreak in Östergötland County, Sweden, were derived from methicillin-resistant S. aureus (MRSA) by carrying remnants of SCCmec, and, if so, to characterise this element. A total of 54 MSSA isolates with concomitant resistance to erythromycin, clindamycin and tobramycin from 49 patients (91% clonally related, spa type t002) were investigated with the BD GeneOhm MRSA assay and real-time polymerase chain reaction (PCR) targeting the SCCmec integration site/SCCmec right extremity junction. DNA sequencing of one isolate representing the MR-MSSA outbreak clone was performed by massive parallel 454 pyrosequencing. All isolates that were part of the clonal outbreak carried SCCmec remnants. The DNA sequencing revealed the carriage of a pseudo-SCC element 12 kb in size, with a genomic organisation identical to an SCCmec type ΙΙ element, except for a 41-kb gap. This study demonstrates the presence of a pseudo-SCC element resembling SCCmec type II among MR-MSSA, suggesting possible derivation from MRSA. The presence of SCCmec remnants should always be considered when SCCmec typing is used for MRSA detection, and may not be suitable in locations with a high prevalence of MR-MSSA, since this might give a high number of false-positive results.

No induction of thiopurine methyltransferase during thiopurine treatment in inflammatory bowel disease.

The aim of this study was to follow, during standardized initiation of thiopurine treatment, thiopurine methyltransferase (TPMT) gene expression and enzyme activity and thiopurine metabolite concentrations, and to study the role of TPMT and ITPA 94C > A polymorphisms for the development of adverse drug reactions. Sixty patients with ulcerative colitis or Crohn's disease were included in this open and prospective multi-center study. Thiopurine naïve patients were prescribed azathioprine (AZA), patients previously intolerant to AZA received 6-mercaptopurine (6-MP). The patients followed a predetermined dose escalation schedule, reaching target dose at Week 3; 2.5 and 1.25 mg/kg body weight for AZA and 6-MP, respectively. The patients were followed every week during Weeks 1-8 from baseline and then every 4 weeks until 20 weeks. TPMT activity and thiopurine metabolites were determined in erythrocytes, TPMT and ITPA genotypes, and TPMT gene expression were determined in whole blood. One homozygous TPMT-deficient patient was excluded. Five non compliant patients were withdrawn during the first weeks. Twenty-seven patients completed the study per protocol; 27 patients were withdrawn because of adverse events. Sixty-seven percent of the withdrawn patients tolerated thiopurines at a lower dose at Week 20. There was no difference in baseline TPMT enzyme activity between individuals completing the study and those withdrawn for adverse events (p = 0.45). A significant decrease in TPMT gene expression (TPMT/huCYC ratio, p = 0.02) was found, however TPMT enzyme activity did not change. TPMT heterozygous individuals had a lower probability of remaining in the study on the predetermined dose (p = 0.039). The ITPA 94C > A polymorphism was not predictive of adverse events (p = 0.35).

Impaired transport as a mechanism of resistance to thiopurines in human T-lymphoblastic leukemia cells.

In order to better understand the mechanisms of resistance to thiopurines, we studied two sublines of the MOLT4 T-lymphoblastic leukemia cell line, resistant to 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG). We found that the underlying mechanism of resistance in both resistant cell lines was a markedly reduction in initial transport of 6-MP (3- and 5-fold, respectively, in 6-MP- and 6-TG-resistant cells). No significant alteration of activities of hypoxanthine-guanine phosphoribosyl transferase, thiopurine methyltransferase or inosine monophosphate dehydrogenase, the key enzymes involved in the metabolism of thiopurines was detected. We conclude that defected initial transport of thiopurines by cells may very well explain their resistance to these drugs.

Adverse events leading to modification of therapy in a large cohort of patients with inflammatory bowel disease.

BACKGROUND: Adverse events leading to discontinuation or dose reduction of thiopurine therapy occur in 9-28% of patients with inflammatory bowel disease. AIMS: To evaluate the influence of thiopurine methyltransferase status and thiopurine metabolites in a large patient population for the risk of developing adverse event. METHODS: Three hundred and sixty-four patients with inflammatory bowel disease and present or previous thiopurine therapy were identified from a local database. RESULTS: The adverse event observed in 124 patients (34%) were more common in adults than children (40% vs. 15%; P < 0.001) and in low to intermediate (

Pharmacogenetics during standardised initiation of thiopurine treatment in inflammatory bowel disease.

BACKGROUND: Firm recommendations about the way thiopurine drugs are introduced and the use of thiopurine methyltransferase (TPMT) and metabolite measurements during treatment in inflammatory bowel disease (IBD) are lacking. AIM: To evaluate pharmacokinetics and tolerance after initiation of thiopurine treatment with a fixed dosing schedule in patients with IBD. PATIENTS: 60 consecutive patients with Crohn's disease (n = 33) or ulcerative colitis (n = 27) were included in a 20 week open, prospective study. METHODS: Thiopurine treatment was introduced using a predefined dose escalation schedule, reaching a daily target dose at week 3 of 2.5 mg azathioprine or 1.25 mg 6-mercaptopurine per kg body weight. TPMT and ITPA genotypes, TPMT activity, TPMT gene expression, and thiopurine metabolites were determined. Clinical outcome and occurrence of adverse events were monitored. RESULTS: 27 patients completed the study per protocol, while 33 were withdrawn (early protocol violation (n = 5), TPMT deficiency (n = 1), thiopurine related adverse events (n = 27)); 67% of patients with adverse events tolerated long term treatment on a lower dose (median 1.32 mg azathioprine/kg body weight). TPMT activity did not change during the 20 week course of the study but a significant decrease in TPMT gene expression was found (TPMT/huCYC ratio; p = 0.02). Patients with meTIMP concentrations >11,450 pmol/8 x 10(8) red blood cells during steady state at week 5 had an increased risk of developing myelotoxicity (odds ratio = 45.0; p = 0.015). CONCLUSIONS: After initiation of thiopurine treatment using a fixed dosing schedule, no general induction of TPMT enzyme activity occurred, though TPMT gene expression decreased. The development of different types of toxicity was unpredictable, but we found that measurement of meTIMP early in the steady state phase helped to identify patients at risk of developing myelotoxicity.

Gastric emptying and duodeno-gastro-oesophageal reflux in gastro-oesophageal reflux disease.

BACKGROUND: Previous studies present conflicting results regarding relationship between gastric emptying and gastro-oesophageal reflux disease. Reflux of duodenal content to oesophagus is generally considered to be associated with more severe disease. AIM: To assess presence of a gastric emptying disorder in persons with reflux of duodenal contents to oesophagus and to identify any correlation with gastric emptying and oesophageal motility. METHODOLOGY: A total of 15 subjects with (B+) and 15 subjects without (B-) bile reflux to oesophagus determined by 24-hour bilirubin monitoring were studied with scintigraphic solid gastric emptying and 24-hour oesophageal manometry. RESULTS: There was no difference in lag phase [median 23.7 (range 10.8-44.0) vs 24.6 (8.1-40.1) min], half emptying time [74.6 (48.0-93.6) vs 82.8 (54.4-153.9) min] or emptying rate [0.89 (0.59-1.34) vs 0.83 (0.36-1. 15)%/min] for B- and B+ subjects, respectively. In addition, there was no difference in emptying rate of gastric fundus between B- and B+ subjects. Subjects with bile reflux had less effective oesophageal contractions of oesophageal body [9.4(3.3-37)%] compared to subjects without bile reflux [32(19-47)%, p = 0.002]. However, there was no correlation between oesophageal motility and gastric emptying. CONCLUSION: Results suggest that a gastric emptying disorder is a less likely contributing cause of bile reflux to the oesophagus, but bile reflux is associated with less effective oesophageal motility.

Diagnostic performance of duplex ultrasonography in the detection of high grade internal carotid artery stenosis.

OBJECTIVES: to establish on a national basis whether the diagnostic accuracy of carotid duplex justifies carotid surgery without preoperative angiography. DESIGN: prospective national multicentre study with 10 participating university and county hospitals. MATERIAL AND METHODS: one hundred and thirty-four patients, aged 69+/-9 years, were subjected to routine carotid duplex ultrasonography and angiography. The influence of relevant factors on the relation between ultrasonographic and angiographic variables was evaluated using multiple regression analysis. The capacity of carotid ultrasonography to detect internal carotid artery (ICA) stenosis > or =80% was assessed by receiver operating characteristic analysis. RESULTS: the correlation between peak systolic velocity in ICA (PSV(ICA)) and the angiographic degree of stenosis was strong and significantly influenced only by the applied Doppler angle. Accordingly, the optimal PSV(ICA) cutpoint values for the diagnosis of ICA stenosis > or =80% (ECST method) differed substantially (2.1 and 3.2 m/s) between the two considered angle ranges (0-49 degrees and 50-62 degrees ), the ability to identify high grade ICA stenosis being significantly better at small Doppler angles (0-49 degrees ). CONCLUSION: ultrasonographic duplex technique identifies high grade ICA stenosis with a high degree of accuracy, which can be further improved by the application of small Doppler angles and the use of angle range specific PSV(ICA) cut-off points.

Specific metal-ion binding sites in a model of the P4-P6 triple-helical domain of a group I intron.

Divalent metal ions play a crucial role in RNA structure and catalysis. Phosphorothioate substitution and manganese rescue experiments can reveal phosphate oxygens interacting specifically with magnesium ions essential for structure and/or activity. In this study, phosphorothioate interference experiments in combination with structural sensitive circular dichroism spectroscopy have been used to probe molecular interactions underlying an important RNA structural motif. We have studied a synthetic model of the P4-P6 triple-helical domain in the bacteriophage T4 nrdB group I intron, which has a core sequence analogous to the Tetrahymena ribozyme. Rp and Sp sulfur substitutions were introduced into two adjacent nucleotides positioned at the 3' end of helix P6 (U452) and in the joining region J6/7 (U453). The effects of sulfur substitution on triple helix formation in the presence of different ratios of magnesium and manganese were studied by the use of difference circular dichroism spectroscopy. The results show that the pro-Sp oxygen of U452 acts as a ligand for a structurally important magnesium ion, whereas no such effect is seen for the pro-Rp oxygen of U452. The importance of the pro-Rp and pro-Sp oxygens of U453 is less clear, because addition of manganese could not significantly restore the triple-helical interactions within the isolated substituted model systems. The interpretation is that U453 is so sensitive to structural disturbance that any change at this position hinders the proper formation of the triple helix.

Rapid subcutaneous IgG replacement therapy at home for pregnant immunodeficient women.

The use of slow or rapid, subcutaneous, IgG (SCIG) infusions in pregnant women with primary antibody deficiencies has been described earlier, though only in single-case reports. In this study, we have evaluated the effect of rapid, SCIG infusions during 11 pregnancies in nine women [six women with common variable immunodeficiency (CVID), two with IgG-subclass deficiencies, and one with combined IgA and IgG2 deficiency]. The weekly infusions were given by the women themselves at a dose of 100 mg/kg/week throughout the pregnancy. No adverse systemic reactions or pronounced, local tissue reactions were recorded during or after the more than 400 infusions. The 11 babies were healthy and were born after 38-42 weeks of uneventful gestation. The concentrations of maternal S-IgG at the time of delivery in the four women with CVID ranged from 6.0 to 8.3 g/L, with cord/maternal S-IgG ratios of 1.0-1.5. The IgG subclasses were transferred to the infants. The SCIG home-therapy regime was greatly appreciated by the women.