Repeat operations in patients with anal fistula, a retrospective study across England and Wales.

AIM: This article reports the frequency of repeat operations including waiting times within the National Health Service (NHS) of England and Wales. METHODS: Retrospective study on repeat operations for anal fistula (AF) performed between 1st January 2010 and 31st December 2016. Data were extracted from the national registry of data entered into Hospital Episode Statistics (HES). Patient factors (age, sex, self-declared ethnicity) and geographical location were tested for association with repeat operations and time to the second operation. RESULTS: We analysed 36,223 patients that had an operation for AF within 148 NHS trusts. The median follow-up time was 28 months. The majority of patients (67.4%) had only one operation. Eighty-five per cent of them remained under the care of a single consultant. Six per cent of the repeat surgeries occurred in at least three different treatment sites. Young age and female sex were associated with higher rates of repeat operations. Non-declared and Black or Black British ethnicity were associated with fewer operations. The median waiting time between the first and second operations was 27.4 weeks (IQR: 14.7-55.3); between the second and third 28.0 weeks (IQR: 14.7-57.0); between the third and fourth 29.0 weeks. CONCLUSION: This large real world population-based study shows that the majority of patients with AF undergo only one operation. Patients requiring multiple procedures tend to stay under the care of a small number of consultants but waiting times between operations are long. There is a geographical variation in the number of operations and the time between them.

Production of Highly Polarized Positrons Using Polarized Electrons at MeV Energies.

The Polarized Electrons for Polarized Positrons experiment at the injector of the Continuous Electron Beam Accelerator Facility has demonstrated for the first time the efficient transfer of polarization from electrons to positrons produced by the polarized bremsstrahlung radiation induced by a polarized electron beam in a high-Z target. Positron polarization up to 82% have been measured for an initial electron beam momentum of 8.19 MeV/c, limited only by the electron beam polarization. This technique extends polarized positron capabilities from GeV to MeV electron beams, and opens access to polarized positron beam physics to a wide community.

New Measurement of the π0 radiative decay width.

High precision measurements of the differential cross sections for π0 photoproduction at forward angles for two nuclei, 12C and 208Pb, have been performed for incident photon energies of 4.9-5.5 GeV to extract the π0→γγ decay width. The experiment was done at Jefferson Lab using the Hall B photon tagger and a high-resolution multichannel calorimeter. The π0→γγ decay width was extracted by fitting the measured cross sections using recently updated theoretical models for the process. The resulting value for the decay width is Γ(π0→γγ)=7.82±0.14(stat)±0.17(syst) eV. With the 2.8% total uncertainty, this result is a factor of 2.5 more precise than the current Particle Data Group average of this fundamental quantity, and it is consistent with current theoretical predictions.

Feasibility study of hospital antimicrobial stewardship analytics using electronic health records.

BACKGROUND: Hospital antimicrobial stewardship (AMS) programmes are multidisciplinary initiatives to optimize antimicrobial use. Most hospitals depend on time-consuming manual audits to monitor clinicians' prescribing. But much of the information needed could be sourced from electronic health records (EHRs). OBJECTIVES: To develop an informatics methodology to analyse characteristics of hospital AMS practice using routine electronic prescribing and laboratory records. METHODS: Feasibility study using electronic prescribing, laboratory and clinical coding records from adult patients admitted to six specialities at Queen Elizabeth Hospital, Birmingham, UK (September 2017-August 2018). The study involved: (i) a review of AMS standards of care; (ii) their translation into concepts measurable from commonly available EHRs; and (iii) a pilot application in an EHR cohort study (n = 61679 admissions). RESULTS: We developed data modelling methods to characterize antimicrobial use (antimicrobial therapy episode linkage methods, therapy table, therapy changes). Prescriptions were linked into antimicrobial therapy episodes (mean 2.4 prescriptions/episode; mean length of therapy 5.8 days), enabling several actionable findings. For example, 22% of therapy episodes for low-severity community-acquired pneumonia were congruent with prescribing guidelines, with a tendency to use broader-spectrum antibiotics. Analysis of therapy changes revealed IV to oral therapy switching was delayed by an average 3.6 days (95% CI: 3.4-3.7). Microbial cultures were performed prior to treatment initiation in just 22% of antibacterial prescriptions. The proposed methods enabled fine-grained monitoring of AMS practice down to specialities, wards and individual clinical teams by case mix, enabling more meaningful peer comparison. CONCLUSIONS: It is feasible to use hospital EHRs to construct rapid, meaningful measures of prescribing quality with potential to support quality improvement interventions (audit/feedback to prescribers), engagement with front-line clinicians on optimizing prescribing, and AMS impact evaluation studies.

Probing quark-gluon interactions with transverse polarized scattering.

We have extracted QCD matrix elements from our data on doubly polarized inelastic scattering of electrons on nuclei. We find the higher twist matrix element d˜2, which arises strictly from quark-gluon interactions, to be unambiguously nonzero. The data also reveal an isospin dependence of higher twist effects if we assume that the Burkhardt-Cottingham sum rule is valid. The fundamental Bjorken sum rule obtained from the a0 matrix element is satisfied at our low momentum transfer.

Mortality related to primary bariatric surgery in England.

BACKGROUND: Bariatric surgery is an accepted treatment option for severe obesity. Previous analysis of the independently collected Hospital Episode Statistics (HES) data for outcomes after bariatric surgery demonstrated a 30-day postoperative mortality rate of 0·3 per cent in the English National Health Service (NHS). However, there have been no published mortality data for bariatric procedures performed since 2008. This study aimed to assess mortality related to bariatric surgery in England from 2009. METHODS: HES data were used to identify all patients who had primary bariatric surgery from 2009 to 2016. Clinical codes were used selectively to identify all primary bariatric procedures but exclude revision or conversion procedures and operations for malignant or other benign disease. The primary outcome measures were HES in-hospital and Office for National Statistics (ONS) 30-day mortality after discharge. RESULTS: A total of 41 241 primary bariatric procedures were carried out in the NHS between 2009 and 2016, with 29 in-hospital deaths (0·07 per cent). The 30-day mortality rate after discharge was 0·08 per cent (32 of 41 241). Both the in-hospital and 30-day mortality rates after discharge demonstrated a downward trend over the study period. CONCLUSION: Overall in-hospital and 30-day mortality rates remain very low after primary bariatric surgery. An increased uptake of bariatric surgery within the English NHS has been safe.

Cloning and functional characterization of a novel human CC chemokine that binds to the CCR3 receptor and activates human eosinophils.

Eotaxin has been found to bind exclusively to a single chemokine receptor, CCR3. Using expression sequence tag screening of an activated monocyte library, a second chemokine has been identified; it was expressed and purified from a Drosophila cell culture system and appears to only activate CCR3. Eotaxin-2, MPIF-2, or CKbeta-6, is a human CC chemokine with low amino acid sequence identity to other chemokines. Eotaxin-2 promotes chemotaxis and Ca2+ mobilization in human eosinophils but not in neutrophils or monocytes. Cross-desensitization calcium mobilization experiments using purified eosinophils indicate that eotaxin and MCP-4, but not RANTES, MIP-1alpha, or MCP-3, can completely cross-desensitize the calcium response to eotaxin-2 on these cells, indicating that eotaxin-2 shares the same receptor used by eotaxin and MCP-4. Eotaxin-2 was the most potent eosinophil chemoattractant of all the chemokines tested. Eotaxin-2 also displaced 125I-eotaxin bound to the cloned CCR3 stably expressed in CHO cells (CHO-CCR3) and to freshly isolated human eosinophils with affinities similar to eotaxin and MCP-4. 125I-Eotaxin-2 binds with high affinity to eosinophils and both eotaxin and cold eotaxin-2 displace the ligand with equal affinity. Eotaxin and eotaxin-2 promote a Ca2+ transient in RBL-2H3 cells stably transfected with CCR3 (RBL-2H3-CCR3) and both ligands cross-desensitized the response of the other but not the response to LTD4. The data indicate that eotaxin-2 is a potent eosinophil chemotactic chemokine exerting its activity solely through the CCR3 receptor.

Creation of oral care flavours to deliver breath-freshening benefits.

OBJECTIVE: Oral care products deliver breath freshening primarily via mechano-chemical cleaning or by antimicrobial active systems. Dental flavours provide taste benefits, and freshen breath mainly by sensorial masking. We aimed to determine whether flavours could deliver breath freshening in products by inhibiting bacterial volatile sulphide compound (VSC) production. SUBJECTS AND METHODS: Flavour materials were screened for inhibition of hydrogen sulphide formation by Klebsiella pneumoniae in vitro, grouped by efficacy, and data provided to flavourists. Flavours were formulated to maximize the content of VSC-effective ingredients and re-screened to confirm performance. Extensive, iterative testing of flavours identified reliable creative rules to deliver efficient inhibition of H2S generation. Breath-freshening flavours in whole products were then tested in-house in a 'breath freshness panel'. MAIN OUTCOME MEASURES: Malodour of panellists (not preselected for malodour score) was scored before and after product use, on the 'Rosenberg' 0-5 scale, together with residual flavour score, by extensively trained judges. Products were tested in double-blind, crossover studies, and results analysed using ANOVA. RESULTS AND CONCLUSIONS: Products flavoured using these rules delivered significantly greater breath freshening at 2 h than control products, and equivalent benefits to products containing 0.1% (w/w) triclosan or 0.2% (w/w) zinc sulphate.

An abundantly secreted glycoprotein from Drosophila melanogaster is related to mammalian secretory proteins produced in rheumatoid tissues and by activated macrophages.

An abundantly secreted 47-kDa glycoprotein, DS47, was purified from Drosophila melanogaster (Dm) Schneider line-2 cells, a line exhibiting macrophage-like properties. DS47 is also secreted from several Dm cell lines resembling S2 but not from lines that are morphologically distinct. A cDNA cline was isolated from an S2 cell cDNA library using oligodeoxyribonucleotide probes based on the DS47 amino acid (aa) sequence and found to encode a novel secretory glycoprotein of 452 aa. Analysis of DS47 protein production and mRNA expression during fly development indicates that both are present throughout the entire Dm life cycle, suggesting that DS47 may be important at all developmental stages. In larvae, the DS47 message is made in the fat body and by hemocytes, and secreted into the hemolymph. DS47 is related to a human cartilage glycoprotein, HC gp-39, that is secreted from cell types associated with the arthritic joint, such as synovial cells and activated macrophages. Interestingly, the HC gp-39 message is most readily detected in the human liver, an organ that is somewhat analogous to the Dm fat body. DS47 also shares homology to a mouse secretory glycoprotein, YM-1, identified in activated macrophages. These homologies extend to the chitinase gene family and include a conserved cysteine aa motif, as well as two blocks of aa within the enzymatic active site, although neither DS-47 nor HC gp-39 exhibit chitinase activity. Potential functions of this conserved protein family are discussed.

Examination of micro-tip reversed-phase liquid chromatographic extraction of peptide pools for mass spectrometric analysis.

Mass spectrometry occupies a central position in most current protein identification schemes. So-called 'mass fingerprinting' techniques rely on composite mass patterns of proteolytic fragments, or dissociation products thereof, to query databases. Keys to successful analysis of ever smaller amounts are sensitivity and complete spectral information, both of which depend for a large part on proper sample preparation. Clean-up and concentration of peptide mixtures over eppendorf gel loading tips filled with chromatographic media (i.e. 'micro-tips') are believed to be quite useful in this regard. We have studied quantitative and qualitative aspects of polypeptide extraction using these small manual devices. Optimization of sample volume and additives, micro-tip bed volume, and eluent composition and volume, all contribute to effective recovery (approximately 65-70%, on average). Improper digest conditions can, in fact, lead to far bigger losses, suggesting the need for at least trace amounts of Zwittergent 3-16. Of particular interest is our finding that partial fractionation, obtained by two-step micro-tip elution, generally results in more and better signals during subsequent mass analysis. Thus, by using optimized micro-tips, in combination with adequate sample handling and instrumentation, direct mass spectrometric identification can be routinely and successfully done in any resource facility type setting.

Observations of lameness, hoof conformation and development of lesions in dairy cattle over four lactations.

Lameness and lesions in the claws of 31 autumn-calving Holstein Friesian dairy cows were recorded from before their first-calving until their fifth lactation. The animals were managed by the same herdsman and housed adjacently in the same building in one of two herds grazed either on clover-rich pastures (herd 1) or on conventional ryegrass (herd 2). All four hooves were examined routinely four times during each lactation, and claw lesions were scored for severity and drawn on hoof maps. Heel erosion and infectious skin conditions of the hoof were also recorded, and hoof conformation, hardness, and growth and wear were measured. The animals' locomotion was scored weekly throughout the winter housing period and any observed to be lame were examined to determine the cause. The development of lesions was modelled by using hierarchic smoothing splines. There was no significant effect of herd except on the prevalence of lameness in lactation 2 when the incidence of (inter)digital dermatitis was higher in herd 2. Lesion and locomotion scores were significantly higher by lactation 4 (P<0.05). There were significant effects (P<0.05) of weeks postcalving on lesion formation, claw conformation, and heel erosion.

Occurrence and characteristics of fastidious Campylobacteraceae species in porcine samples.

This study investigated the prevalence and characteristics of Campylobacteraceae including a range of fastidious species in porcine samples. Over a thirteen month period caecal contents (n=402) and pork carcass swabs (n=401) were collected from three pork abattoirs and pork products (n=399) were purchased at point of sale in the Republic of Ireland. Campylobacteraceae isolates were recovered by enrichment, membrane filtration and incubation in antibiotic free media under a modified atmosphere (3% O2, 5% H2, 10% CO2 and 82% N2). Campylobacteraceae isolates were identified as either genus Campylobacter or Arcobacter and then selected species were identified by Polymerase Chain Reaction (PCR). Campylobacteraceae were isolated from 103 (26%) caecal samples, 42 (10%) carcass swabs, and 59 (15%) pork products. Campylobacter coli was the most commonly isolated species found in (37%) all sample types but many fastidious species were also isolated including Campylobacter concisus (10%), Arcobacter butzleri (8%), Campylobacter helveticus (8%), Campylobacter mucosalis (6%), Arcobacter cryaerophilus (3%), Campylobacter fetus subsp. fetus (1%), Campylobacter jejuni subsp. jejuni (1%), Campylobacter lari (0.5%), Campylobacter curvus (0.5%) and Arcobacter skirrowii (0.5%). Among all isolates, 83% contained cadF and 98% flaA. In this study 35% of porcine C. coli were resistant to ciprofloxacin but none of the fastidious species demonstrated any resistance to this drug. The level of resistance to erythromycin was very high (up to 100%) in C. concisus and C. helveticus and this is a real concern as this is the current empiric drug of choice for treatment of severe gastroenteritic Campylobacter infections. The study shows that there is a much wider range of fastidious Campylobacteraceae present in porcine samples than previously assumed with C. concisus the second most common species isolated. The majority of fastidious Campylobacteraceae isolates obtained contained virulence genes and antibiotic resistance indicating potential public health significance.

Proton spin structure in the resonance region.

We have examined the spin structure of the proton in the region of the nucleon resonances (1.085 GeV

Overcoming cultural barriers to change.

This article is a case study which focuses on organisational and cultural change associated with the incorporation of a college which provided pre- and post-registration nursing and midwifery education into a much larger institution within the university sector. Among the issues addressed is whether transformational change, such as that represented by incorporation or merger, can be used by managers to successfully refashion the culture of the organisation, making more effective than traditional or discipline-based management structures. It examines the barriers to change and the various considerations that arose in determining the fit of managerial styles and assesses the outcomes of the process of change.

Beyond night float? The impact of call structure on internal medicine residents.

Limitation of resident working hours has been a critical issue for training programs in recent years. At Providence Medical Center, residents and faculty collaborated in developing goals, implementation strategies, and an evaluation process for a new ward float system. The goals of the float system were to reduce fatigue, facilitate education, maintain continuity of care, and minimize the negative impact of training on residents' personal lives. Evaluation revealed: 1) 74% of the residents preferred Providence Medical Center float system (PMCF) to either night float (NF) (13%) or standard every-fourth-night call (EFNC) (13%); and 2) PMCF was perceived to ensure quality patient care to a greater degree than was NF, to better facilitate resident education than was NF, and to have a less negative impact on personal lives than was EFNC.

Monomeric isomers of human interleukin 5 show that 1:1 receptor recruitment is sufficient for function.

The normally dimeric human interleukin 5 (IL-5) was re-engineered into two monomeric isomer forms to investigate mechanistic features of receptor recognition. One form, denoted GM1-IL-5, is a CD-loop expanded form, in which an 8-residue linker designed for flexibility was inserted between residues 85 and 86. The second, denoted DABC-IL-5, is a circularly permuted form of human IL-5 in which a chain discontinuity was introduced in the CD loop and the two consequent chain fragments were joined at the normal N and C termini by a di-glycyl linker. Both IL-5 isomers folded into stable monomers in solution as shown by sedimentation equilibrium and CD and formed an intrachain disulfide bond predicted from the structure of wild type IL-5. From titration microcalorimetry and optical biosensor analyses, both monomers were shown to interact with the IL-5 receptor alpha chain with 1:1 stoichiometry and affinities 30- to 40-fold weaker than for the dimeric wild type protein. And both monomers stimulated cell proliferation of human IL-5 receptor positive cells with a concentration dependence close to that of wild type. The data show that both monomeric and dimeric forms of IL-5 function through similar 1:1 receptor alpha chain recruitment processes and that it is the helical packing of the monomeric four-helix bundle unit in IL-5, rather than the helical connectivity itself, that appears to play the major role in presenting structural epitopes to trigger functional receptor activation.