Comparing hospital and telephone follow-up for patients treated for stage-I endometrial cancer (ENDCAT trial): a randomised, multicentre, non-inferiority trial.

OBJECTIVE: To evaluate the effectiveness of nurse-led telephone follow-up (TFU) for patients with stage-I endometrial cancer. DESIGN: Multicentre, randomised, non-inferiority trial. SETTING: Five centres in the North West of England. SAMPLE: A cohort of 259 women treated for stage-I endometrial cancer attending hospital outpatient clinics for routine follow-up. METHODS: Participants were randomly allocated to receive traditional hospital based follow-up (HFU) or nurse-led TFU. MAIN OUTCOME MEASURES: Primary outcomes were psychological morbidity (State Trait Anxiety Inventory, STAI-S) and patient satisfaction with the information provided. Secondary outcomes included patient satisfaction with service, quality of life, and time to detection of recurrence. RESULTS: The STAI-S scores post-randomisation were similar between groups [mean (SD): TFU 33.0 (11.0); HFU 35.5 (13.0)]. The estimated between-group difference in STAI-S was 0.7 (95% confidence interval, 95% CI -1.9 to 3.3); the confidence interval lies above the non-inferiority limit (-3.5), indicating the non-inferiority of TFU. There was no significant difference between groups in reported satisfaction with information (odds ratio, OR 0.9; 95% CI 0.4-2.1; P = 0.83). Women in the HFU group were more likely to report being kept waiting for their appointment (P = 0.001), that they did not need any information (P = 0.003), and were less likely to report that the nurse knew about their particular case and situation (P = 0.005). CONCLUSIONS: The TFU provides an effective alternative to HFU for patients with stage-I endometrial cancer, with no reported physical or psychological detriment. Patient satisfaction with information was high, with similar levels between groups. TWEETABLE ABSTRACT: ENDCAT trial shows effectiveness of nurse-led telephone follow-up for patients with stage-I endometrial cancer.

Modeling electrochromic poly-dioxythiophene-containing materials through TDDFT.

A DFT/TDDFT model was developed to predict the chemical properties for three colored to nearly transmissive electrochromic polymers synthesized by the John Reynolds's group. Using a functional-basis set pairing of mPW1PBE/cc-PVDZ along with the conductor polarizable calculation model (CPCM), simulated neutral spectra showed a strong correlation to the experimental UV-Vis data where the largest absolute peak maximum difference was 14 nm. Frontier molecular orbitals, electronic transitions, and ground-state geometries of these systems were evaluated to provide further information about the oxidative process the polymers undergo. Here we report the first colorimetric model using this level of theory.

Evaluation of a Diverse, Worldwide Collection of Wild, Cultivated, and Landrace Pepper (Capsicum annuum) for Resistance to Phytophthora Fruit Rot, Genetic Diversity, and Population Structure.

Pepper is the third most important solanaceous crop in the United States and fourth most important worldwide. To identify sources of resistance for commercial breeding, 170 pepper genotypes from five continents and 45 countries were evaluated for Phytophthora fruit rot resistance using two isolates of Phytophthora capsici. Genetic diversity and population structure were assessed on a subset of 157 genotypes using 23 polymorphic simple sequence repeats. Partial resistance and isolate-specific interactions were identified in the population at both 3 and 5 days postinoculation (dpi). Plant introductions (PIs) 640833 and 566811 were the most resistant lines evaluated at 5 dpi to isolates 12889 and OP97, with mean lesion areas less than Criollo de Morelos. Genetic diversity was moderate (0.44) in the population. The program STRUCTURE inferred four genetic clusters with moderate to very great differentiation among clusters. Most lines evaluated were susceptible or moderately susceptible at 5 dpi, and no lines evaluated were completely resistant to Phytophthora fruit rot. Significant population structure was detected when pepper varieties were grouped by predefined categories of disease resistance, continent, and country of origin. Moderately resistant or resistant PIs to both isolates of P. capsici at 5 dpi were in genetic clusters one and two.

Heterogeneity in the risk of Mycobacterium bovis infection in European badger (Meles meles) cubs.

The behaviour of certain infected individuals within socially structured populations can have a disproportionately large effect on the spatio-temporal distribution of infection. Endemic infection with Mycobacterium bovis in European badgers (Meles meles) in Great Britain and Ireland is an important source of bovine tuberculosis in cattle. Here we quantify the risk of infection in badger cubs in a high-density wild badger population, in relation to the infection status of resident adults. Over a 24-year period, we observed variation in the risk of cub infection, with those born into groups with resident infectious breeding females being over four times as likely to be detected excreting M. bovis than cubs from groups where there was no evidence of infection in adults. We discuss how our findings relate to the persistence of infection at both social group and population level, and the potential implications for disease control strategies.

Long-term temporal trends and estimated transmission rates for Mycobacterium bovis infection in an undisturbed high-density badger (Meles meles) population.

We describe epidemiological trends in Mycobacterium bovis infection in an undisturbed wild badger (Meles meles) population. Data were derived from the capture, clinical sampling and serological testing of 1803 badgers over 9945 capture events spanning 24 years. Incidence and prevalence increased over time, exhibiting no simple relationship with host density. Potential explanations are presented for a marked increase in the frequency of positive serological test results. Transmission rates (R0) estimated from empirical data were consistent with modelled estimates and robust to changes in test sensitivity and the spatial extent of the population at risk. The risk of a positive culture or serological test result increased with badger age, and varied seasonally. Evidence consistent with progressive disease was found in cubs. This study demonstrates the value of long-term data and the repeated application of imperfect diagnostic tests as indices of infection to reveal epidemiological trends in M. bovis infection in badgers.

Short- and long-term outcomes of polyethylene band attenuation of congenital extrahepatic portosystemic shunts in dogs: 60 cases (2010-2020).

OBJECTIVES: To report the short- and long-term outcomes following attenuation of congenital extrahepatic portosystemic shunts in dogs using a novel polyethylene band. MATERIALS AND METHODS: Records were retrospectively reviewed for dogs that underwent congenital extrahepatic portosystemic shunt attenuation by a polyethylene banding technique, at a single institution between 2010 and 2020. Short-term outcome data were collected from peri-operative clinical records with follow-up examinations, scheduled at 6 and 18 weeks post-operatively, and post-operative imaging when performed. Long-term follow-up was collected by validated owner questionnaire, telephone interview or medical records. Long-term outcomes were categorised by "excellent", "good" or "poor". RESULTS: Sixty dogs were included. Post-operative complications occurred in 10 of 60 dogs (16.7%), four major and six minor, with a peri-operative mortality of 6.7%. Persistent shunting was identified in nine of 53 dogs (17%) available for follow-up examination and four dogs underwent a revision surgery. Long-term follow-up was available for 44 dogs at a median of 75 months post-operatively (range 7 to 128). Long-term outcomes were "excellent" (26) or "good" (8) in 81.8% of dogs and "poor" (8) in 18.2%. At the time of follow-up, 30 of 44 (68.2%) dogs were not receiving any medical treatment and 27 of 28 (96.4%) questionnaire respondents were satisfied with the response to surgery. CLINICAL SIGNIFICANCE: Polyethylene band attenuation of congenital extrahepatic portosystemic shunts provides comparable outcomes to cellophane. The material used in this study is widely available and consistent while being pre-sterilised and pre-folded makes it easy to use.

Does carbetocin for prevention of postpartum haemorrhage at caesarean section provide clinical or financial benefit compared with oxytocin?

Postpartum haemorrhage is a major cause of maternal morbidity and mortality worldwide. A recent Cochrane review of carbetocin (long-acting oxytocin analogue) concluded that its use decreased additional uterotonic requirements, however, no included studies compared its use against intravenous bolus oxytocin. The majority of studies of carbetocin have considered its use in vaginal delivery; no studies have examined the economic implications of its use. This study describes a clinical and financial evaluation undertaken at a United Kingdom District General Hospital surrounding the introduction of carbetocin for prophylaxis against postpartum haemorrhage at caesarean deliveries. A range of clinical outcomes were observed including frequency of postpartum haemorrhage, estimated blood loss, transfusion requirements, change in haemoglobin or haemodynamics, use of additional uterotonics and perioperative recovery. Finally, a composite financial analysis was performed. No clinically significant benefit was found, however associated costs increased by £18.52/patient.

Transitions between phyllotactic lattice states in curved geometries.

Phyllotaxis, the regular arrangement of leaves or other lateral organs in plants including pineapples, sunflowers and some cacti, has attracted scientific interest for centuries. More recently there has been interest in phyllotaxis within physical systems, especially for cylindrical geometry. In this letter, we expand from a cylindrical geometry and investigate transitions between phyllotactic states of soft vortex matter confined to a conical frustum. We show that the ground states of this system are consistent with previous results for cylindrical confinement and discuss the resulting defect structures at the transitions. We then eliminate these defects from the system by introducing a density gradient to create a configuration in a single state. The nature of the density gradient limits this approach to a small parameter range on the conical system. We therefore seek a new surface, the horn, for which a defect-free state can be maintained for a larger range of parameters.

Sevenless: a cell-specific homeotic mutation of the Drosophila eye.

Each ommatidium in the compound eye of the Drosophila mutant sevenless lacks photoreceptor number seven (R7) from the normal ommatidial complement of eight photoreceptors. A comparison of mutant and normal development reveals that this deficit is caused by the cell-specific transformation of the cell normally fated to produce R7 into a lens-secreting accessory cell, a cone cell.

Dorsal-ventral signaling in the Drosophila eye.

The development of the Drosophila eye has served as a model system for investigations of tissue patterning and cell-cell communication; however, early eye development has not been well understood. The results presented here indicate that specialized cells are established along the dorsal-ventral midline of the developing eye by Notch-mediated signaling between dorsal and ventral cells, and that Notch activation at the midline plays an essential role both in promoting the growth of the eye primordia and in regulating eye patterning. These observations imply that the developmental homology between Drosophila wings and vertebrate limbs extends to Drosophila eyes.

Prevalence, distribution and pathological significance of the bile fluke Pseudamphistomum truncatum in Eurasian otters (Lutra lutra) in Great Britain.

Postmortem examinations on 160 otters found dead in Great Britain from 2005 to 2007 showed a high prevalence of infection with the bile fluke Pseudamphistomum truncatum in otters from Somerset and Dorset but no infection in otters from other areas, including Cornwall, the western half of Devon, north-east England and Scotland. Cases were also recorded for the first time in Gloucestershire and East Anglia. Eighteen of the 28 infected otters were male and no cubs were infected, but there was no significant correlation between infection status and sex or age. There was a strong positive correlation between bile fluke infection and gall bladder pathology. Thirty otters had thickened gall bladders resulting from hyperplasia of the epithelial and smooth muscle layers, fibrosis and infiltration by inflammatory cells and 19 of these were infected. No flukes were detected in the other 11 otters with abnormal gall bladders, possibly as a result of a successful immune response. The majority of otters with thickened gall bladders were in good physical condition but a positive association was not confirmed statistically. Fluke infection was also detected in nine of the 130 otters with apparently normal gall bladders. Liver pathology ranged from mild bile duct hyperplasia and periportal fibrosis to severe sclerosing cholangitis, hepatocyte necrosis and bile stasis. No otters were found to have died as a result of fluke infection, but there was a negative association, approaching significance, between infection and body condition.

Titrated low-dose vaginal and/or oral misoprostol to induce labour for prelabour membrane rupture: a randomised trial.

OBJECTIVE: To evaluate the clinical effectiveness and safety of titrated low-dose misoprostol for induction of labour (IOL) in the presence of prelabour rupture of membranes (PROM). DESIGN: Randomised controlled trial. SETTING: Maternity units in the UK (9) and Egypt (1). POPULATION: Women >34 weeks of gestation with PROM, singleton viable fetus and no previous caesarean section. METHODS: Subjects randomised to IOL with a titrated low-dose misoprostol regimen (oral except if unfavourable cervix, where initial dose vaginal) or a standard induction method, namely vaginal dinoprostone followed by intravenous oxytocin if the cervix was unfavourable or intravenous oxytocin alone if the cervix was favourable. MAIN OUTCOME MEASURES: Primary outcome measures were caesarean section and failure to achieve vaginal delivery within 24 hours. Analysis was by intention to treat. RESULTS: The trial did not achieve the planned sample size of 1890 due to failure in obtaining external funding. Seven hundred and fifty-eight women were randomised (375 misoprostol and 383 standard). There were less caesarean section (14 versus 18%, relative risk [RR] 0.79; 95% CI 0.57-1.09) and less women who failed to achieve vaginal delivery within 24 hours in the misoprostol group (24 versus 31%, RR 0.79; 95% CI 0.63-1.00), but the differences were not statistically significant. Subgroup analysis showed that with unfavourable cervix, misoprostol may be more effective than vaginal dinoprostone. There was no difference in hyperstimulation syndrome. There were more maternal adverse effects with misoprostol, but no significant differences in maternal and neonatal complications. CONCLUSIONS: Titrated low-dose misoprostol may be a reasonable alternative for IOL in the presence of PROM, particularly in women with an unfavourable cervix. Safety and rare serious adverse events could not be evaluated in a trial of this size.

Angiostrongylus vasorum and Eucoleus aerophilus in foxes (Vulpes vulpes) in Great Britain.

The nematode parasite Angiostrongylus vasorum is a source of increasing concern in several parts of the world, where it causes significant disease in dogs. Wild canids, especially foxes, are likely to have a role in the epidemiology of canine infection, and the parasite could also affect fox health and population dynamics. The heart and pulmonary vasculature of 546 foxes culled mostly by gamekeepers in Great Britain in 2005-2006 were examined by dissection and a modified flushing technique. Forty foxes were found to be infected, giving an overall prevalence in the UK fox population of 7.3% (5.3-9.9). Prevalence varied widely between regions, from 0% (0-3) in Scotland and northern England to 23% (16-32) in south-east England. This closely matches the perceived incidence of disease in dogs, which is commonly diagnosed in the south-east but rarely in the north. In the Midlands, where disease has recently appeared in dogs, prevalence in foxes was 4.8% (2-11). Close geographical overlap of parasite distribution in foxes and dogs does not necessarily indicate an important wildlife reservoir of infection, but does suggest that A. vasorum might be spreading northwards. The hearts of infected foxes had thicker right ventricles than those of uninfected foxes, suggesting that the parasite could affect fox health and fitness. Burdens ranged from 1 to 59 adult nematodes. Sex, age and body condition were not significantly associated with infection. Eucoleus aerophilus and Crenosoma vulpis, nematode parasites of the respiratory system, were found in 213 and 11 foxes respectively, with slightly higher prevalence of E. aerophilus in the south and east. No specimens of the heartworm Dirofilaria immitis were found, giving an upper 95% confidence interval for prevalence of 0.84%.

Naturally processed and presented epitopes of the islet cell autoantigen IA-2 eluted from HLA-DR4.

During immune responses, antigen-presenting cells (APCs) process antigens and present peptide epitopes complexed with human leukocyte antigen (HLA) molecules. CD4 cells recognize these naturally processed and presented epitopes (NPPEs) bound to HLA class II molecules. Epitope identification is important for developing diagnostic and therapeutic tools for immune-mediated diseases and providing insight into their etiology, but current approaches overlook effects of natural processing on epitope selection. We have developed a technique to identify NPPEs using mass spectrometry (MS) after antigen is targeted onto APCs using a lectin-based antigen delivery system (ADS). We applied the technique to identify NPPEs of the intracellular domain of the type 1 diabetes mellitus-associated (type 1 DM-associated) autoantigen insulinoma-associated-2 (IA-2ic), presented by HLA-DR4 (0401). IA-2ic-derived NPPEs eluted from HLA-DR4 constitute 6 sets of peptides nested around distinct core regions. Synthetic peptides based on these regions bind HLA-DR4 and elicit primary T-cell proliferation frequently in HLA-DR4-positive type 1 DM patients, but rarely in non-HLA-DR4 patients, and in none of the HLA-DR4 nondiabetic controls we tested. This flexible, direct approach identifies an HLA allele-specific map of NPPEs for any antigen, presented by any HLA class II molecule. This method should enable a greater understanding of epitope selection and lead to the generation of sensitive and specific reagents for detecting autoreactive T cells.

Compression force-depth relationship during out-of-hospital cardiopulmonary resuscitation.

BACKGROUND: Recent clinical studies reporting the high frequency of inadequate chest compression depth (<38 mm) during CPR, have prompted the question if adult human chest characteristics render it difficult to attain the recommended compression depth in certain patients. MATERIAL AND METHODS: Using a specially designed monitor/defibrillator equipped with a sternal pad fitted with an accelerometer and a pressure sensor, compression force and depth was measured during CPR in 91 adult out-of-hospital cardiac arrest patients. RESULTS: There was a strong non-linear relationship between the force of compression and depth achieved. Mean applied force for all patients was 30.3+/-8.2 kg and mean absolute compression depth 42+/-8 mm. For 87 of 91 patients 38 mm compression depth was obtained with less than 50 kg. Stiffer chests were compressed more forcefully than softer chests (p<0.001), but softer chests were compressed more deeply than stiffer chests (p=0.001). The force needed to reach 38 mm compression depth (F38) and mean compression force were higher for males than for females: 29.8+/-14.5 kg versus 22.5+/-10.2 kg (p<0.02), and 32.0+/-8.3 kg versus 27.0+/-7.0 kg (p<0.01), respectively. There was no significant variation in F38 or compression depth with age, but a significant 1.5 kg mean decrease in applied force for each 10 years increase in age (p<0.05). Chest stiffness decreased significantly (p<0.0001) with an increasing number of compressions performed. Average residual force during decompression was 1.7+/-1.0 kg, corresponding to an average residual depth of 3+/-2 mm. CONCLUSION: In most out-of-hospital cardiac arrest victims adequate chest compression depth can be achieved by a force<50 kg, indicating that an average sized and fit rescuer should be able to perform effective CPR in most adult patients.

Analysis of transcription complexes and effects of ligands by microelectrospray ionization mass spectrometry.

The human vitamin D receptor (VDR) and retinoid X receptor-alpha (RXRalpha) modulate gene activity by forming homodimeric or heterodimeric complexes with specific DNA sequences and interaction with other elements of the transcriptional apparatus in the presence of their known endogenous ligands 1alpha,25-dihydroxyvitamin D3 (1, 25-[OH]2D3) and 9-cis-retinoic acid (9-c-RA). We used rapid buffer exchange gel filtration in conjunction with microelectrospray ionization mass spectrometry (microESI-MS) to study the binding of these receptors to the osteopontin vitamin D response element (OP VDRE). In the absence of DNA, both VDR and RXRalpha existed primarily as monomers, but in the presence of OP VDRE, homodimeric RXRalpha and heterodimeric RXRalpha-VDR complexes were shown to bind OP VDRE. Addition of 9-c-RA increased RXRalpha homodimer-OP VDRE complexes, and addition of 1,25-(OH) 2D3 resulted in formation of 1, 25-(OH)2D 3-VDR-RXRalpha-OP VDRE complexes. Addition of low-affinity binding ligands had no detectable effect on the VDR-RXRalpha-OP VDRE transcription complex. These results demonstrate the utility of microESI-MS in analyzing multimeric, high-molecular-weight protein-protein and protein-DNA complexes, and the effects of ligands on these transcriptional complexes.

Metal mediated sterol receptor-DNA complex association and dissociation determined by electrospray ionization mass spectrometry.

The vitamin D receptor (VDR) binds to specific DNA sequences termed vitamin D response elements (VDREs) thereby enhancing or repressing transcription. We have used electrospray ionization mass spectrometry to examine the interaction between the DNA-binding domain of the vitamin D receptor (VDR DBD) with a double-stranded DNA (dsDNA) sequence containing the VDRE from the mouse osteopontin gene. The VDR DBD was shown to bind to the appropriate DNA sequence only when bound to 2 moles of zinc (Zn2+) or cadmium (Cd2+) per mole of protein. Additional binding of Zn2+ or Cd2+ by the protein caused the protein to dissociate from the dsDNA. These results show that the VDR DBD/DNA metal-dependent association occurs when the receptor is occupied by 2 moles of Zn2+ per mole of protein and that further binding of Zn2+ to the protein causes dissociation of the complex.

Umbilical cord plasma concentrations of free morphine following single-dose diamorphine analgesia and their relationship to dose-delivery time interval, Apgar scores and neonatal respiration.

OBJECTIVE: To find the effect of dose-delivery interval on cord-blood levels of diamorphine metabolites and its effect on Apgar sores and neonatal respiration. STUDY DESIGN: Pilot study conducted in labour ward of a district general hospital. One hundred women who had normal delivery and received single dose of 7.5mg of intramuscular injection of diamorphine in labour were recruited in the study. A 2.0 ml sample of umbilical venous blood was collected from the placenta after delivery of the baby. The sample was analysed using RIA method to measure free morphine. Details about the labour and baby's condition at birth were recorded. RESULTS: The concentration of free morphine in the umbilical venous blood was significantly associated with the dose-delivery interval (coefficient (95% CI)=1.08(0.99-1.18), p<0.001). Twenty neonates had low Apgar score (< or =7) at 1 min. The odds of such a low score were raised with higher log free morphine in the cord venous plasma, but not statistically significantly (OR (95% CI)=5.3 (0.84-34), p=0.08). Fourteen neonates required resuscitation. The odds of requiring resuscitation were significantly raised with higher log free morphine: OR (95% CI)=9.3 (1.0-86), p=0.05. CONCLUSION: Concentration of free morphine in the umbilical venous blood after delivery was significantly associated with the dose-delivery interval and this had significant effect on the need for resuscitation.

First Report of Race 8 of Downy Mildew, Caused by Peronospora farinosa f. sp. spinaciae, of Spinach in the United States.

Downy mildew, caused by Peronospora farinosa f. sp. spinaciae, is the most economically important disease of spinach (Spinacia oleracea) in the United States and the European Union. In the United States, 23,000 ha of spinach, with a crop value of approximately $170 million, were grown during 2005 (1; http://www.nass.usda.gov/index.asp ). Additionally, per capita, fresh-market spinach consumption has increased 214% in the past decade (1; http://www.nass.usda.gov/index.asp ). Increased demand for fresh-market spinach has led to changes in spinach production practices such as higher planting densities and year-round production. There are currently 10 described races (races 1 to 10) of P. farinosa f. sp. spinaciae. Race 8 was recovered from the Netherlands in 2004 (B. M. Irish, J. Correll, S. T. Koike, and T. Morelock. Plant Dis. [In press]), but has not been previously identified in the United States. In February 2007, several commercial fresh-market spinach fields in central Arizona were severely affected with downy mildew. Symptoms consisted of bright yellow leaf lesions ranging in size from 1 to 3 cm in diameter that supported dense purple sporulation of the pathogen on the corresponding abaxial leaf surface. Affected fields were primarily planted with spinach cv. Parrot, which is reported to be resistant to races 1 to 7 and 9. As much as 32 ha were affected and disease incidence reached as high as 25 to 30%. An isolate (PAR1) of the pathogen was obtained and used to inoculate a standard set of 10 differential spinach cultivars for race identification as previously described (B. M. Irish, J. Correll, S. T. Koike, and T. Morelock. Plant Dis. [In press]). Briefly, a spore suspension (1 × 105 sporangia per ml) was misted onto test plants; plants were then incubated in a dew chamber (20°C, 100% relative humidity) for 24 h and maintained in a greenhouse. Inoculation tests were conducted at least twice at each of two different locations (Arkansas and California), with each test including two replications of 15 plants per differential cultivar. The selective development of downy mildew on specific differentials indicated that the isolate was race 8 (B. M. Irish, J. Correll, S. T. Koike, and T. Morelock. Plant Dis. [In press]). To our knowledge, this is the first report of race 8 in the United States. Since there are a number of commercial spinach cultivars available with resistance to race 8, the economic impact of this race in the United States is expected to be low if resistant cultivars are grown (B. M. Irish, J. Correll, S. T. Koike, and T. Morelock. Plant Dis. [In press]). Reference: (1) R. N. Acharya and I. Molina. NFAPP Newsl. Second Quarter, 2005.