Measurement of the Nucleon F_{2}

The ratio of the nucleon F_{2} structure functions, F_{2}^{n}/F_{2}^{p}, is determined by the MARATHON experiment from measurements of deep inelastic scattering of electrons from ^{3}H and ^{3}He nuclei. The experiment was performed in the Hall A Facility of Jefferson Lab using two high-resolution spectrometers for electron detection, and a cryogenic target system which included a low-activity tritium cell. The data analysis used a novel technique exploiting the mirror symmetry of the two nuclei, which essentially eliminates many theoretical uncertainties in the extraction of the ratio. The results, which cover the Bjorken scaling variable range 0.19

Probing Few-Body Nuclear Dynamics via

We report the first measurement of the (e,e^{'}p) three-body breakup reaction cross sections in helium-3 (^{3}He) and tritium (^{3}H) at large momentum transfer [⟨Q^{2}⟩≈1.9 (GeV/c)^{2}] and x_{B}>1 kinematics, where the cross section should be sensitive to quasielastic (QE) scattering from single nucleons. The data cover missing momenta 40≤p_{miss}≤500 MeV/c that, in the QE limit with no rescattering, equals the initial momentum of the probed nucleon. The measured cross sections are compared with state-of-the-art ab initio calculations. Overall good agreement, within ±20%, is observed between data and calculations for the full p_{miss} range for ^{3}H and for 100≤p_{miss}≤350 MeV/c for ^{3}He. Including the effects of rescattering of the outgoing nucleon improves agreement with the data at p_{miss}>250 MeV/c and suggests contributions from charge-exchange (SCX) rescattering. The isoscalar sum of ^{3}He plus ^{3}H, which is largely insensitive to SCX, is described by calculations to within the accuracy of the data over the entire p_{miss} range. This validates current models of the ground state of the three-nucleon system up to very high initial nucleon momenta of 500 MeV/c.

Dietary starch promotes hepatic lipogenesis in barramundi (Lates calcarifer).

Barramundi (Lates calcarifer) are a highly valued aquaculture species, and, as obligate carnivores, they have a demonstrated preference for dietary protein over lipid or starch to fuel energetic growth demands. In order to investigate how carnivorous fish regulate nutritional cues, we examined the metabolic effects of feeding two isoenergetic diets that contained different proportions of digestible protein or starch energy. Fish fed a high proportion of dietary starch energy had a higher proportion of liver SFA, but showed no change in plasma glucose levels, and few changes in the expression of genes regulating key hepatic metabolic pathways. Decreased activation of the mammalian target of rapamycin growth signalling cascade was consistent with decreased growth performance values. The fractional synthetic rate (lipogenesis), measured by TAG 2H-enrichment using 2H NMR, was significantly higher in barramundi fed with the starch diet compared with the protein diet (0·6 (se 0·1) v. 0·4 (se 0·1) % per d, respectively). Hepatic TAG-bound glycerol synthetic rates were much higher than other closely related fish such as sea bass, but were not significantly different (starch, 2·8 (se 0·3) v. protein, 3·4 (se 0·3) % per d), highlighting the role of glycerol as a metabolic intermediary and high TAG-FA cycling in barramundi. Overall, dietary starch significantly increased hepatic TAG through increased lipogenesis. Compared with other fish, barramundi possess a unique mechanism to metabolise dietary carbohydrates and this knowledge may define ways to improve performance of advanced formulated feeds.

First Observation of P-odd γ Asymmetry in Polarized Neutron Capture on Hydrogen.

We report the first observation of the parity-violating gamma-ray asymmetry A_{γ}^{np} in neutron-proton capture using polarized cold neutrons incident on a liquid parahydrogen target at the Spallation Neutron Source at Oak Ridge National Laboratory. A_{γ}^{np} isolates the ΔI=1, ^{3}S_{1}→^{3}P_{1} component of the weak nucleon-nucleon interaction, which is dominated by pion exchange and can be directly related to a single coupling constant in either the DDH meson exchange model or pionless effective field theory. We measured A_{γ}^{np}=[-3.0±1.4(stat)±0.2(syst)]×10^{-8}, which implies a DDH weak πNN coupling of h_{π}^{1}=[2.6±1.2(stat)±0.2(syst)]×10^{-7} and a pionless EFT constant of C^{^{3}S_{1}→^{3}P_{1}}/C_{0}=[-7.4±3.5(stat)±0.5(syst)]×10^{-11} MeV^{-1}. We describe the experiment, data analysis, systematic uncertainties, and implications of the result.

Risk factors and clinical outcomes of cytomegalovirus disease occurring more than one year post solid organ transplantation.

BACKGROUND: Cytomegalovirus (CMV) disease typically occurs during the first year after solid organ transplantation, after cessation of antiviral prophylaxis. CMV occurring after the first year is uncommon and not well described. METHODS: We conducted a case-control study to identify potential risk factors and a retrospective cohort study to evaluate 1-month mortality in solid organ transplant (SOT) recipients who developed CMV disease after the first year post transplant, or "very late CMV" (VLCMV), compared with those developing CMV within the first year (CMV Y1), adjusting for demographics, donor and recipient CMV serostatus, immunosuppression, rejection, and co-morbidities. RESULTS: We identified 85 SOT recipients with CMV disease at a single transplant center between January 2006 and October 2008: 23 (27%) had VLCMV and 62 (73%) had CMV Y1. Heart transplantation was independently associated with increased risk (adjusted odd ratio [OR] 4.11; 95% confidence interval [CI] 1.34-12.61; P = 0.01) for VLCMV. Patients with VLCMV had increased 1-month mortality (unadjusted OR 5.39; 95% CI 1.06-27.48; P = 0.02). Mortality was uncommonly attributable to CMV. CONCLUSIONS: CMV disease continues to occur after the first year post solid organ transplantation, particularly in heart transplant recipients, and can be associated with poor outcomes. CMV should be suspected in patients with symptoms or laboratory findings consistent with CMV, even if the patients present >1 year post transplant.

An experience with cardiopulmonary bypass in HIV-infected patients.

Having noted the good clinical status of some HIV patients who were referred for but refused surgery, we undertook surgery with the aim of determining outcome, risk-to-benefit ratio and, if possible, the effect of surgery with cardiopulmonary bypass (CPB) on the progression of their HIV disease. Antiretroviral drugs (ARVD) were not available to these patients. The records of 49 patients, 17 males and 32 females, aged between 17 and 67 years, undergoing surgery with cardiopulmonary bypass over a nine-year period, were reviewed. Forty-eight of these underwent cardiac surgery and one aortic dissection repair. Four HIV-infected patients underwent surgery with good early outcome. Thereafter an absolute CD4 cell count greater than 400/microl (normal 550*1 955/microl) and the absence of the stigmata of AIDS in patients fulfilling the normal criteria for surgery allowed cardiac surgery using CPB. Fifty operations were performed. Three patients with CD4 counts of 37, 868 and 1 245/microl died early, giving a 30-day mortality of 6% for 50 procedures. Six patients with active infective endocarditis (IE) underwent emergency surgery. Three of these, one with a pre- and two with only post-operative counts all below 250/microl, died within three months. Sixteen complications occurred in the remaining 46 patients (34.7%). Pre-operative CD4 cell counts taken in 42 patients averaged 685/microl. Pre- and post-operative counts known in eight showed variations, as did repeated counts in those awaiting surgery. Forty-one patients left hospital in the New York Heart Association (NYHA) class I, five in class II and one in class III. Prior to surgery, the majority (38) were in class III and seven were in class IV. Follow up ranging from two to 70 months averaged 23.1 months. Eight late deaths occurred, three related to AIDS. We found surgery to be worthwhile in selected HIV-infected patients. Early outcome paralleled that in the uninfected, giving a low risk-to-benefit ratio. Emergency surgery in those with active infective endocarditis and marked immune compromise met with high mortality. It is essential in our population to test and stage all patients for HIV. We could not show that CPB accelerated progression to AIDS. This experience and the present availability of ARVDs would enable us to review our selection criteria for surgery.

Pneumonectomy in children.

OBJECTIVES: Surgical literature carries relatively scant information on pneumonectomy in children. We reviewed our experience over 7 years, determined the risk/benefit ratio and compared our experience with reports from the literature. METHODS: The records of children undergoing pneumonectomy, 14 years and younger, over a 7-year period from January 1991 to December 1997, are analysed, the techniques used to determine the need for and extent of surgery are studied, whilst the problems and outcome of surgery in this age group are determined. RESULTS: Fifty-nine children, 40 males, 19 females, aged 6 months to 14 years, average age of 7.5 years, underwent pneumonectomy. A history of pulmonary infection/s and a chest radiograph suggestive of lung destruction were indicators for investigation by bronchography and/or computerized axial tomography of the chest (HRCT scan). This determined the nature and extent of disease and the possibility and extent of surgery required. Bronchus blockers (22), five others in combination with the prone operating position, prone position (six) and a double lumen tube in one, were used to protect the healthy lung at surgery. Spill of pus was recognized once with a bronchus blocker and the prone position used in combination. Six intra-operative complications (10.1%) were recognized: bronchial spill (one) without consequence, conversion of bi-lobectomy to pneumonectomy due to pulmonary artery injury (one), cardiac arrest (with resuscitation, one), bradycardia with hypotension (one), excessive bleeding (one) and intra-pleural spill of debris (one), the last without consequence. Seven post-operative complications (11.8%) occurred: one empyema (sterilized), bleeding one, pulmonary infection two, suspected but unproven broncho-pleural fistulae two, prolonged antibiotics in one, reason unrecorded. One pneumonectomy through an empyema was uncomplicated. The main histological features were bronchiectasis (38), active tuberculosis (eight), end-stage lung (five), collapse and pulmonary haemorrhage (one), lobar emphysema (one). Histology unrecorded (one). No death occurred. All patients left hospital well. CONCLUSIONS: Careful preparation, often including anti-tuberculosis cover, and timing of pneumonectomy are essential. Meticulous anaesthetic and surgical technique and co-operation are critical. Bronchus blockers functioned well but are not without risk. Attention to detail makes pneumonectomy safe in childhood.

Efficacy and cost-effectiveness of bronchial arterial embolisation in the treatment of major haemoptysis.

OBJECTIVE: To determine the efficacy and cost-effectiveness of bronchial artery embolisation (BAE) in the treatment of major and massive haemoptysis in HIV-positive and negative patients with pulmonary inflammatory disease. METHODS: A retrospective review of patients admitted over a period of 24 months to Wentworth Hospital with major haemoptysis treated using BAE. RESULTS: Eighty-seven patients were treated (77 males, 10 females). Bilateral disease was present in 50 patients (57%). Thirty-two patients were HIV-positive (37%). Embolisation was successfully performed in 77 patients (88.5%), and failed for technical reasons in 10 patients (11.5%). There was only one procedural complication. Fifty-seven patients had a successful outcome, with cessation of haemoptysis within 24 hours (66.5%). Haemoptysis continued in 30 patients (34%) (20 patients embolised and the 10 patients who had failed procedures). Fourteen of these patients (16%) required lobectomy or pneumonectomy as an emergency procedure. Five patients (5.7%) died from respiratory failure or pulmonary haemorrhage. Twenty-four HIV-positive patients were successfully embolised. Costing of BAE, including a 2-day ICU and 3-day ward stay, was R6,720; together with surgical resection the cost was R14,170. CONCLUSIONS: BAE is an effective treatment for major and/or massive haemoptysis in patients with pulmonary inflammatory disease who are not surgical candidates. Patients who are HIV-positive are able to tolerate the procedure well.

The homeostatic rôle of bronchoconstriction.

This article argues in favour of the hypothesis that the homeostatic rôles of bronchoconstriction are to retract the airway tree during expiration, and to assist in the expulsion of mucus from peripheral airways by increasing the velocity of outgoing air. In asthma, this function may be dangerously exaggerated because of the presence of unusually viscous airway secretions and the remodelling of airway walls.

Pneumonectomy for inflammatory lung disease.

OBJECTIVE: Recent surgical literature has highlighted the dangers of pneumonectomy for inflammatory lung disease; therefore the assessment of the risk/benefit ratio of our departmental policy. METHODS: Patients undergoing pneumonectomy for inflammatory lung disease during two 2-year periods, 1991-1992 and 1996-1997 inclusive, were retrospectively analyzed. Clinical indications for investigation and surgery, and radiographic findings were determined. Some comparisons between the two periods were drawn. Rates of morbidity and mortality were the principle outcome measures. RESULTS: One hundred and fifty-five patients, 116 males, 39 females, with an average age of 30.2 years ranging from 1-68 years, underwent pneumonectomy for ongoing features of productive cough, haemoptysis (two emergencies) and chronic empyema all with either bronchographic or computed tomography (CT) evidence of destroyed lung. One hundred and fourteen (72%) had or had had tuberculosis at time of surgery. Histology showed bronchiectasis in 53 (34%), end-stage disease in 49 (31.6%) and active tuberculosis in 48 (30.9%). Over 90% of the patients were free of disease at discharge. Mortality was two (1.2%). Morbidity (23%) included post-pneumonectomy empyema 23 (14.8%), bleeding three (1.9%), broncho-pleural fistula three (1.9%), with wound sepsis in one (0.6%) and thoracic duct injury in one (0.6%). Three groups were identified, (1) pneumonectomy through empyema - a risk group, (2) pneumonectomy in active tuberculosis and (3) pneumonectomy in children. Twenty-three post-pneumonectomy empyemas (PPE) occurred with 21 of these following pneumonectomies through empyema (PTE), six PPEs followed 27 PTEs for active tuberculosis. Fourteen of the 21 empyemas following pneumonectomy through empyema were initially sterilized. Finally 15/23 (65%) of all PPEs were sterilized. Pneumonectomy in active tuberculosis did not carry the mortality or morbidity experienced by others. Pneumonectomy in children was remarkably uncomplicated, with one PPE occurring. CONCLUSIONS: This ongoing study shows pneumonectomy for inflammatory lung to be safe, with good results. Tuberculosis, being so common, adequate pre-operative and operative cover with anti-tuberculosis drugs may enhance results.

Airway subepithelial fibrosis in a murine model of atopic asthma: suppression by dexamethasone or anti-interleukin-5 antibody.

Fibrosis in the reticular layer beneath the epithelial basement membrane is a feature of airway remodeling in human asthma. We previously reported the presence of subepithelial fibrosis (SEF) in a disease model of atopic asthma in which mice were sensitized and intratracheally challenged with ovalbumin (OVA) (Blyth and colleagues, Am. J. Respir. Cell Mol. Biol. 1996;14:425-438). Here, we describe further studies to quantify the degree of SEF after its induction by repeated exposure of the airways to allergen. The amount of subepithelial reticulin in the airways of animals challenged three times with 80 microg OVA was typically increased 1. 4-fold. The increased amount of reticulin showed no reduction after a 50-d period after the third allergen challenge. A reduction in SEF was achieved by daily treatment with dexamethasone (DEX) for 8 d during the allergen challenge period, or by treatment with anti-interleukin-5 antibody (TRFK5) at the time of allergen challenge. Postchallenge treatment with DEX for 15 d resulted in significant resolution of previously established SEF. Severe nonallergic inflammation during repeated exposure of airways to lipopolysaccharide did not induce SEF. The results indicate that development of SEF is associated with eosinophil infiltration into airways, and may occur only when the inflammatory stimulus is allergic in nature.

Optical biosensing of nitric oxide using the metalloprotein cytochrome c'.

The metalloprotein cytochrome c' was extracted and purified from the bacterium Paracoccus denitrificans in order to develop a specific biosensing system for nitric oxide (NO). The metalloprotein was encapsulated in a porous silicate sol-gel glass to enable spectroscopic changes in the haem centre as a function of NO ligation to be quantified using absorption measurements. Spectroscopic evidence suggested that, between 2 and 4 d after encapsulation, the cytochrome c' protein changed conformation in the locality of the haem moiety, possibly from a five to a six coordinate haem centre. Such conformational changes were also observed when the cytochrome c' was stored in solution, although over a 2-3 month period. The conformational changes occurring in the protein altered the spectral characteristics of the reduced, oxidised and nitrosyl complex of the cytochrome c' and appear to change the binding affinity of the protein towards NO. However, the encapsulated (reconformed) cytochrome c' was shown to retain its selectivity towards NO with good reproducibility (seven consecutive measurements of NO produced an intensity value with a relative standard deviation of 0.28%). An NO calibration curve, using the in situ release of NO from the donor diethylamine NONOate, was obtained for the encapsulated cytochrome c' with an approximate working range of 10-400 mumol l-1.

Pulmonary angiography and embolization for severe hemoptysis due to cavitary pulmonary tuberculosis.

PURPOSE: To identify the role of pulmonary angiography in the diagnosis and treatment of severe hemoptysis due to cavitary pulmonary tuberculosis. METHODS: Selective pulmonary angiography was performed on eight patients with severe hemoptysis uncontrolled by previous bronchial and systemic arterial embolization. RESULTS: Three (38%) patients had Rasmussen aneurysms, which were successfully embolized with steel coils. Five patients demonstrated pulmonary arterial hypoperfusion in the diseased lung. CONCLUSIONS: We recommend pulmonary angiography in cavitary tuberculous patients with severe hemoptysis who do not respond to systemic arterial embolization. Rasmussen aneurysms are effectively treated by steel coil occlusion.

Induction, duration, and resolution of airway goblet cell hyperplasia in a murine model of atopic asthma: effect of concurrent infection with respiratory syncytial virus and response to dexamethasone.

We recently described a murine model of atopic asthma in which a marked, extensive hyperplasia of airway goblet cells is induced by repeated challenge of ovalbumin (OA)-sensitized mice with intratracheally administered allergen (Am. J. Respir. Cell Mol. Biol. 1996;14:425-438). We report here the time course of the duration of this feature and of its spontaneous resolution in the absence of further allergen exposure. Induction of severe neutrophilic inflammation in the airways by repeated intratracheal administration of lipopolysaccharide failed to induce goblet cell hyperplasia (GCH) to as great a degree as that induced by allergen, suggesting that nonallergic inflammation is a relatively poor inducer of this phenotype change in mice. When a "subclinical" infection of the lungs with the human A2 strain of respiratory syncytial virus was superimposed on the model of atopic asthma, recruitment of monocytes and lymphocytes to the airways was enhanced and a discharge of goblet cell mucin contents was observed. This may partly explain the respiratory difficulty that typifies virally induced exacerbations of asthma in humans. Daily systemic treatment of sensitized mice with dexamethasone during the period of allergen challenge produced a dose-related suppression of developing GCH, while similar treatment during the period following the establishment of extensive hyperplasia induced an accelerated resolution toward a normal epithelial phenotype. These results confirm and extend the relevance of this model as a representation of the human disease.

Calcium biosensing with a sol-gel immobilized photoprotein.

Aequorin, the bioluminescent protein found in the jellyfish Aequorea sp., has been immobilized in a porous sol-gel glass environment. The luminescence from this protein is specifically triggered by the presence of calcium ions, thus offering exciting possibilities for the development of an optical biosensor for this cationic species. The luminescence emission spectrum has been measured from the aequorin protein after interaction with calcium ions. The intensity of the luminescence, measured at the peak maximum of 470 nm, for the encapsulated protein has been calibrated against calcium ion concentration. The characterization of the protein within the sol-gel matrix has been reported together with biosensing experiments using human sera and milk samples. The results suggest that the sol-gel encapsulated aequorin protein offers potential as a one shot bioluminescence based biosensor for the determination of calcium ions in such complex matrices.

Lung inflammation and epithelial changes in a murine model of atopic asthma.

A murine model of allergen-induced airway inflammation and epithelial phenotypic change, and the time-courses of these events, are described. Mice were sensitized to ovalbumin using an adjuvant-free protocol, and challenged by multiple intratracheal instillations of ovalbumin by a non-surgical technique. Many of the characteristic features of human atopic asthma were seen in the mice. A marked eosinophilic infiltration of lung tissue and airways followed allergen challenge, and its severity increased with each challenge, as did the number of eosinophils in the blood. Lymphocytes, neutrophils, and monocytes also invaded the lungs. Airway macrophages showed signs of activation, their appearance resembling those recovered from antigen-challenged human asthmatic airways. The airway epithelium was thickened and displayed a marked goblet cell hyperplasia in terminal bronchioles and larger airways. After repeated challenges, the reticular layer beneath the basement membrane of the airway epithelium showed fibrosis, reproducing a commonly observed histologic feature of human asthma. Goblet cell hyperplasia began to appear before eosinophils or lymphocytes had migrated across the airway epithelium, and persisted for at least 11 days after the third intratracheal challenge with ovalbumin, despite the number of inflammatory cells in the lungs and airways having decreased to near-normal levels by 4 days. Plugs of mucus occluded some of the airways. These results indicate that some of the phenotypic changes in airway epithelium that follow an allergic response in the lung can be initiated before the migration of eosinophils or lymphocytes across the epithelial layer.

Satisfaction and continuity of care: staff views of care in a midwife-managed delivery unit.

OBJECTIVE: to examine whether there are differences in the midwife's role in, and satisfaction with, intrapartum care and delivery of women at low obstetric risk in a midwife-managed delivery unit compared to a consultant-led labour ward. DESIGN: a pragmatic randomised controlled trial. Subjects were randomised in a 2:1 ratio between the midwives' unit and the labour ward. SETTING: Aberdeen Maternity Hospital, Grampian, UK. SUBJECTS: midwives within the delivery suite who cared for the 2844 women at low obstetric risk receiving care in a pragmatic randomised controlled trial of the two delivery areas. PRIMARY OUTCOME MEASURES: continuity of carer and midwife satisfaction. FINDINGS: midwives looking after women in the midwives' unit group were significantly more likely to be of a higher grade, more qualified and have a longer length of experience than those in the labour ward group. There was greater continuity of carer both during labour and after delivery in the midwives' unit group. Despite a small but statistically significant difference in overall satisfaction between the groups, area of 'booking' or area of delivery were not important in predicting midwife satisfaction. Autonomy and continuity of carer were the best predictors of midwife satisfaction. CONCLUSIONS: midwife-managed intrapartum care increases continuity of carer and, therefore, midwife satisfaction. Extending this outside the delivery suite requires a system of care that is acceptable to midwives as well as women. Such systems will depend to a large extent on geography, consumer demand and availability of resources. However, midwife satisfaction should also be considered. In order to do this further research is required to fully evaluate the effect these systems have on the midwives working in them.