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.

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.

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.

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.

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.

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.

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.

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

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.

Measurement of the electric form factor of the neutron through d-->(e-->,e(')n)p at Q2 = 0.5 (GeV/c)(2).

We report the first measurement using a solid polarized target of the neutron electric form factor G(n)(E) via d-->(e-->,e(')n)p. G(n)(E) was determined from the beam-target asymmetry in the scattering of longitudinally polarized electrons from polarized deuterated ammonia ( 15ND3). The measurement was performed in Hall C at Thomas Jefferson National Accelerator Facility in quasifree kinematics with the target polarization perpendicular to the momentum transfer. The electrons were detected in a magnetic spectrometer in coincidence with neutrons in a large solid angle segmented detector. We find G(n)(E) = 0.04632+/-0.00616(stat)+/-0.00341(syst) at Q2 = 0.495 (GeV/c)(2).

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.

Expression, purification, and crystallization of the Escherichia coli selenomethionyl beta-ketoacyl-acyl carrier protein synthase III.

Bacterial beta-ketoacyl-acyl carrier protein (ACP) synthase III (KAS III, also called FabH) catalyzes the condensation and transacylation of acetyl-CoA with malonyl-ACP. In order to understand the mode of enzyme/substrate interaction and design small molecule inhibitors, we have expressed, purified, and crystallized a selenomethionyl-derivative of E. coli KAS III. Several lines of evidence confirmed that purified selenomethionyl KAS III was homogenous, stably folded, and enzymatically active. Dynamic light scattering, size exclusion chromatography, and mass spectrometry results indicated that selenomethionyl KAS III is a noncovalent homodimer. Diffraction quality crystals of selenomethionyl KAS III/acetyl-CoA complex, which grew overnight to a size of 0.2 mm(3), belonged to the tetragonal space group P4(1)2(1)2.

Identification of unique truncated KC/GRO beta chemokines with potent hematopoietic and anti-infective activities.

SK&F 107647, a previously described synthetic immunomodulatory peptide, indirectly stimulates bone marrow progenitor cells and phagocytic cells, and enhances host defense effector mechanisms in bacterial and fungal infection models in vivo. In vitro, SK&F 107647 induces the production of a soluble mediator that augments colony forming cell (CFU-GM) formation in the presence of CSFs. In this paper we purified and sequenced the stromal cell-derived hematopoietic synergistic factors (HSF) secreted from both murine and human cell lines stimulated with SK&F 107647. Murine HSF is an N-terminal 4-aa truncated form of the CXC chemokine, KC, while human HSF was identified as an N-terminal 4-aa truncated form of the CXC chemokine, GRO beta. In comparison to their full-length forms, truncated KC and truncated GRO beta were 10 million times more potent as synergistic growth stimulants for CFU-GM. Enhanced potency of these novel truncated chemokines relative to their full-length forms was also demonstrated in respiratory burst assays, CD11b Ag expression, and intracellular killing of the opportunistic pathogen, Candida albicans. Administration of truncated KC significantly enhanced survival of mice lethally infected with C. albicans. The results reported herein delineate the biological mechanism of action of SK&F 107647, which functions via the induction of unique specific truncated forms of the chemokines KC and GRO beta. To our knowledge, this represents the first example where any form of KC or GRO beta were purified from marrow stromal cells. Additionally, this is the first demonstration of in vivo efficacy of a CXC chemokine in an animal infectious fungal disease model.

Human urotensin-II is a potent vasoconstrictor and agonist for the orphan receptor GPR14.

Urotensin-II (U-II) is a vasoactive 'somatostatin-like' cyclic peptide which was originally isolated from fish spinal cords, and which has recently been cloned from man. Here we describe the identification of an orphan human G-protein-coupled receptor homologous to rat GPR14 and expressed predominantly in cardiovascular tissue, which functions as a U-II receptor. Goby and human U-II bind to recombinant human GPR14 with high affinity, and the binding is functionally coupled to calcium mobilization. Human U-II is found within both vascular and cardiac tissue (including coronary atheroma) and effectively constricts isolated arteries from non-human primates. The potency of vasoconstriction of U-II is an order of magnitude greater than that of endothelin-1, making human U-II the most potent mammalian vasoconstrictor identified so far. In vivo, human U-II markedly increases total peripheral resistance in anaesthetized non-human primates, a response associated with profound cardiac contractile dysfunction. Furthermore, as U-II immunoreactivity is also found within central nervous system and endocrine tissues, it may have additional activities.

Analysis of prosthetic femoral heads retrieved at autopsy.

This study examined 24 prosthetic femoral heads retrieved at autopsy from patients with clinically and radiographically successful arthroplasties. Four alumina ceramic and 20 cobalt chrome heads in service for an average of 8.5 years were examined with a contact and a laser stylus profilometer. The authors documented general increases in surface roughness of the cobalt chrome and ceramic femoral heads attributable to in vivo articulation and also observed wear polishing around the apical region of the cobalt chrome heads. The roughness of the prosthetic femoral heads was compared with the polyethylene wear in the matching liners. No relationship was found between femoral head roughness values and polyethylene wear or component duration in situ. The only variable related to the pattern of head roughness and polyethylene wear was the presence of embedded particle debris in the polyethylene liner. Roughness parameters for cobalt chrome heads without embedded debris in the polyethylene liner were fairly uniform around the head. Roughness values, which were higher for heads associated with debris, had a decreasing gradient of surface roughness from the equator to the apex. In addition, the polyethylene wear rate for cups with embedded particle debris in the liner was significantly greater than the wear rate for cups without embedded debris. This study also showed a strong correlation between surface roughness values measured with the contact profilometer and values measured with the noncontact laser profilometer. However, laser profilometer values were four to six times higher, indicating that roughness parameters measured by the two different profilometers cannot be compared directly. Findings of this study point consistently to the influence of third body wear particles on prosthetic femoral head roughness and polyethylene wear. These results stress the importance of minimizing all foreign body debris in maintaining a well functioning articular couple.

Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior.

The hypothalamus plays a central role in the integrated control of feeding and energy homeostasis. We have identified two novel neuropeptides, both derived from the same precursor by proteolytic processing, that bind and activate two closely related (previously) orphan G protein-coupled receptors. These peptides, termed orexin-A and -B, have no significant structural similarities to known families of regulatory peptides. prepro-orexin mRNA and immunoreactive orexin-A are localized in neurons within and around the lateral and posterior hypothalamus in the adult rat brain. When administered centrally to rats, these peptides stimulate food consumption. prepro-orexin mRNA level is up-regulated upon fasting, suggesting a physiological role for the peptides as mediators in the central feedback mechanism that regulates feeding behavior.