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Summary: It is unclear if cardiopulmonary resuscitation is an aerosol‐generating procedure and whether this poses a risk of airborne disease transmission to healthcare workers and bystanders. Use of airborne transmission precautions during cardiopulmonary resuscitation may confer rescuer protection but risks patient harm due to delays in commencing treatment. To quantify the risk of respiratory aerosol generation during cardiopulmonary resuscitation in humans, we conducted an aerosol monitoring study during out‐of‐hospital cardiac arrests. Exhaled aerosol was recorded using an optical particle sizer spectrometer connected to the breathing system. Aerosol produced during resuscitation was compared with that produced by control participants under general anaesthesia ventilated with an equivalent respiratory pattern to cardiopulmonary resuscitation. A porcine cardiac arrest model was used to determine the independent contributions of ventilatory breaths, chest compressions and external cardiac defibrillation to aerosol generation. Time‐series analysis of participants with cardiac arrest (n = 18) demonstrated a repeating waveform of respiratory aerosol that mapped to specific components of resuscitation. Very high peak aerosol concentrations were generated during ventilation of participants with cardiac arrest with median (IQR [range]) 17,926 (5546–59,209 [1523–242,648]) particles.l‐1, which were 24‐fold greater than in control participants under general anaesthesia (744 (309–2106 [23–9099]) particles.l‐1, p < 0.001, n = 16). A substantial rise in aerosol also occurred with cardiac defibrillation and chest compressions. In a complimentary porcine model of cardiac arrest, aerosol recordings showed a strikingly similar profile to the human data. Time‐averaged aerosol concentrations during ventilation were approximately 270‐fold higher than before cardiac arrest (19,410 (2307–41,017 [104–136,025]) vs. 72 (41–136 [23–268]) particles.l‐1, p = 0.008). The porcine model also confirmed that both defibrillation and chest compressions generate high concentrations of aerosol independent of, but synergistic with, ventilation. In conclusion, multiple components of cardiopulmonary resuscitation generate high concentrations of respiratory aerosol. We recommend that airborne transmission precautions are warranted in the setting of high‐risk pathogens, until the airway is secured with an airway device and breathing system with a filter. [ABSTRACT FROM AUTHOR]

Midichloria spp. are intracellular bacterial symbionts of ticks. Representatives of this genus colonise mitochondria in the cells of their hosts. To shed light on this unique interaction we evaluated the presence of an intramitochondrial localization for three Midichloria in the respective tick host species and generated eight high‐quality draft genomes and one closed genome, showing that this trait is non‐monophyletic, either due to losses or multiple acquisitions. Comparative genomics supports the first hypothesis, as the genomes of non‐mitochondrial symbionts are reduced subsets of those capable of colonising the organelles. We detect genomic signatures of mitochondrial tropism, including the differential presence of type IV secretion system and flagellum, which could allow the secretion of unique effectors and/or direct interaction with mitochondria. Other genes, including adhesion molecules, proteins involved in actin polymerisation, cell wall and outer membrane proteins, are only present in mitochondrial symbionts. The bacteria could use these to manipulate host structures, including mitochondrial membranes, to fuse with the organelles or manipulate the mitochondrial network. [ABSTRACT FROM AUTHOR]

The Shoemaker, McLean, and Pratt (SMP) buffer pH method has been used historically in Oregon for estimating lime requirement, however concerns regarding hazardous waste disposal have caused increased interest in nonhazardous methods. The objective was to compare nonhazardous lime requirement estimate (LRE) methods to the SMP method for predicting incubation lime requirement (LRi) for Oregon soils. Twenty‐four soils (pH ≤ 5.5) were incubated with seven rates of CaCO3 ranging from 0 to 22.4 Mg ha–1 and incubated for 90 d at 19 °C. Seven different LRE methods were evaluated and regressed against LRi for pH targets of 5.6, 6.0, and 6.4 using linear regression. The Sikora (r2 =.91–.93), modified Mehlich (r2 =.87–.90), and Sikora‐2 (r2 =.82–.93) buffer methods showed potential as alternatives to SMP (r2 =.91–.93) based on accuracy. A multilinear model combining clay content, KCl‐extractable Al, soil organic matter (SOM), extractable Mg, and pH1:2 also effectively predicted LRi (R2 =.97). The Moore–Sikora method (r2 =.89–.93) showed precision issues due to high replication variability. The single addition of Ca(OH)2 method (r2 =.67–.74) was less accurate than other evaluated methods. In conclusion, there were several viable non‐hazardous LRE method alternatives to the SMP buffer method for Oregon soils, based on accuracy and precision. Core Ideas: The SMP, Sikora, Sikora‐2, and modified Mehlich methods accurately estimated lime requirement (LR).A multiparameter model including clay, SOM, Al, Mg, and pH also accurately estimated LR.The Ca(OH)2 and Moore–Sikora methods were relatively poor predictors of LR. [ABSTRACT FROM AUTHOR]

Among 125 inpatients with diabetic foot infections managed by a multidisciplinary foot ulcer unit, knowledge of methicillin‐resistant Staphylococcus aureus colonisation status assisted decision‐making to prescribe appropriately or with‐hold empiric anti‐methicillin‐resistant Staphylococcus aureus therapy. Despite adherence to national guidelines, apparent overuse of anti‐pseudomonal therapy was frequent, providing potential antimicrobial stewardship opportunities. [ABSTRACT FROM AUTHOR]

Abstract: Background: Accurate diabetes prevalence estimates are important for health service planning and prioritisation. Available data have limitations, suggesting that the contemporary burden of diabetes in Australia is best assessed from multiple sources. Aims: To use systematic active detection of diabetes cases in a postcode‐defined urban area through the Fremantle Diabetes Study Phase II (FDS2) to complement other epidemiological and survey data in estimating the national prevalence of diabetes and its types. Methods: People with known diabetes in a population of 157 000 were identified (n = 4639) from a variety of sources and those providing informed consent (n = 1668 or 36%) were recruited to the FDS2 between 2008 and 2011. All FDS2 participants were assigned a type of diabetes based on clinical and laboratory (including serological and genetic) features. Data from people identified through the FDS2 were used to complement Australian Health Survey and National Diabetes Services Scheme prevalence estimates (the proportions of people well controlled on no pharmacotherapy and registering with the National Diabetes Services Scheme respectively) in combination with Australian Bureau of Statistics data to generate the prevalence of diabetes in Australia. Results: Based on data from multiple sources, 4.8% or 1.1 million Australians had diabetes in 2011–2012, of whom 85.8% had type 2 diabetes, 7.9% type 1 diabetes and 6.3% other types (latent autoimmune diabetes of adults, monogenic diabetes and secondary diabetes). Conclusions: Approximately 1 in 20 Australians has diabetes. Although most have type 2 diabetes, one in seven has other types that may require more specialised diagnosis and/or management. [ABSTRACT FROM AUTHOR]

The Labour Force Survey is used to examine the influence of sector on the UK gender pay gap 1997–2015. The assessment is twofold: first comparing gender pay gaps within sectors and second through identifying the contribution of the concentration of women in the public sector to the overall gender pay gap. The long‐term narrowing of the gender pay gap, which predominately reflects relative improvements in women's productivity‐related characteristics, is found to stall in 2010 within each sector. This is considered in the context of claims that public sector austerity represents a critical turning point in progress toward gender equality at work. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence of monogenic diabetes in an Australian community.Design: Longitudinal observational study of a cohort recruited between 2008 and 2011.Setting: Urban population of 157 000 people (Fremantle, Western Australia).Participants: 1668 (of 4639 people with diabetes) who consented to participation (36.0% participation).Main Outcome Measures: Prevalence of maturity-onset diabetes of the young (MODY) and permanent neonatal diabetes in patients under 35 years of age, from European and non-European ethnic backgrounds, who were at risk of MODY according to United Kingdom risk prediction models, and who were then genotyped for relevant mutations.Results: Twelve of 148 young participants with European ethnic backgrounds (8%) were identified by the risk prediction model as likely to have MODY; four had a glucokinase gene mutation. Thirteen of 45 with non-European ethnic backgrounds (28%) were identified as likely to have MODY, but none had a relevant mutation (DNA unavailable for one patient). Two patients with European ethnic backgrounds (one likely to have MODY) had neonatal diabetes. The estimated MODY prevalence among participants with diagnosed diabetes was 0.24% (95% confidence interval [CI], 0.08-0.66%), an overall population prevalence of 89 cases per million; the prevalence of permanent neonatal diabetes was 0.12% (95% CI, 0.02-0.48%) and the population prevalence 45 cases per million.Conclusions: One in 280 Australians diagnosed with diabetes have a monogenic form; most are of European ethnicity. Diagnosing MODY and neonatal diabetes is important because their management (including family screening) and prognosis can differ significantly from those for types 1 and 2 diabetes. [ABSTRACT FROM AUTHOR]

Background Because published studies have usually involved imprecise assays and selected patients with limited additional data and follow-up, the consequences of a low serum testosterone in diabetes are unclear. This study assessed the prevalence, associates and prognosis of a low testosterone in community-dwelling men with type 2 diabetes. Design Longitudinal observational study. Patients 788 men (mean ± SD age: 65·8 ± 11·3 years) followed for 4·0 ± 1·1 years. Measurements Serum testosterone, SHBG, erectile dysfunction (ED; Sexual Health Inventory for Men score <22), anaemia (haemoglobin <130 g/l), all-cause mortality. Results The mean ± SD total serum testosterone by liquid chromatography/mass spectrometry was 13·1 ± 5·9 nmol/l (30·6% <10 nmol/l). Most men with a total testosterone <10 nmol/l (67·0%) had a normal/low serum LH. Serum testosterone was independently associated with anaemia ( P < 0·001), but not ED ( P = 0·80), in logistic regression models. The optimal cut-point (Youden Index) for anaemia was 9·8 nmol/l (sensitivity 53·6%, specificity 75·4%). During the follow-up, 102 men (12·9%) died. There was a U-shaped relationship between total serum testosterone quintiles and death ( P = 0·003, log rank test). The middle quintile (>11·1 to ≤13·7 nmol/l) had the lowest risk and there was a 78% increased risk for highest (>16·9 nmol/l) vs lowest (≤8·6 nmol/l) quintile in Cox proportional hazards modelling ( P = 0·036). Free serum testosterone and SHBG quintiles were not associated with death. Conclusions These data provide some support for the general conventional serum testosterone <10 nmol/l cut-point in identifying an increased risk of anaemia and the subsequent death in men with type 2 diabetes, but indicate that high-normal levels are also an adverse prognostic indicator. [ABSTRACT FROM AUTHOR]

This paper examines the impact of the UK Public Sector Pay Review Bodies ( PRBs) on the pay of their remit groups comparing the real weekly earnings of workers using ASHE and LFS data from 1993 to 2007 for 10 occupational subgroups. Using consecutive difference-in-differences we can identify whether the PRBs have had an impact by comparing the differences in pay for different occupations in successive time periods. Our examination of the annual changes in differentials suggest that the PRBs may have had relatively little systematic impact on earnings over and above that observed for comparable individuals working elsewhere in the public sector. [ABSTRACT FROM AUTHOR]

Via propensity score matching (PSM) and Rosenbaum Bounds (RB), this paper reports new evidence on the premiums charged by big 4 and the top 4 mid-tier (mid 4) auditors relative to their smaller counterparts in the private corporate market. The results demonstrate that big 4 and mid 4 premiums are in accord with theoretical predictions on auditor quality differences; and that these premiums are relatively insensitive to potential hidden bias when gauged by the RB method for appraising confounding variables under bounded uncertainty. Given the limitations of conventional methods, PSM is being increasingly adopted in accounting studies to estimate treatment effects. Employing paired and simultaneous multi-sample PSM premium estimates, we provide a comprehensive evaluation and illustration of the RB method, together with the advantages and limitations of PSM, on which RB is predicated, when compared to alternative estimators. We demonstrate that PSM, when coupled with RB, provide novel empirical evidence for premiums estimated across three different matched audit quality tiers, to those estimated in prior studies which employ Heckman methods, to hidden bias equivalents and to the sensitivity of the bounds parameters to the omission of covariates employed in the study. New evidence on premiums across size quartiles, and quantile regression estimates over audit fee percentiles, support the PSM findings. [ABSTRACT FROM AUTHOR]

Background: Surgical site infections (SSIs) contribute to increased morbidity, mortality, and hospitalization costs. A previously unidentified factor that may reduce SSIs is the use of local anesthesia. The objective of this study was to determine if the use of local anesthesia is independently associated with a lower incidence of SSIs compared to nonlocal anesthesia. Methods: Using the American College of Surgeons National Surgical Quality Improvement Program database (2005-2007), we identified all patients undergoing surgical procedures that could be performed using local or general anesthesia, depending on the preference of the surgeon. Logistic regression was used to identify factors independently associated with the use of local anesthesia. Propensity matching was then used to match local and nonlocal anesthesia cases while controlling for patient and operative characteristics. SSI rates were compared using a χ test. Results: Of 111,683 patients, 1928 underwent local anesthesia; and in 109,755 cases the patients were given general anesthesia where a local anesthetic potentially could have used. In the unmatched analysis, patients with local anesthesia had a significantly lower incidence of SSIs than patients with nonlocal anesthesia (0.7 vs. 1.4%, P = 0.013). Similarly, after propensity matching, the incidence of SSIs in patients given local anesthesia was significantly lower than for that of patients given nonlocal anesthesia (0.8 vs. 1.4%, P = 0.043). Conclusions: Use of local anesthesia is independently associated with a lower incidence of SSIs. It may provide a safe, simple approach to reducing the number of SSIs. [ABSTRACT FROM AUTHOR]

A method of inoculating seedlings with the fungus Ramularia collo-cygni, the causal agent of ramularia leaf spot (RLS), an increasingly important problem in barley in Europe and elsewhere, is described. Symptoms of RLS similar to those found in the field were reproduced on seedlings and the fungus was re-isolated from them, fulfilling the third and fourth of Koch's postulates. The method was similar to one used for the related fungus, Mycosphaerella graminicola (anamorph Septoria tritici), a pathogen of wheat. Briefly, plants were sprayed with a suspension of R. collo-cygni mycelium fragments, incubated at 15°C, first in darkness for 48 h then in a 16-h-light/8-h-dark cycle. Disease levels reached saturation when plants were sprayed to runoff with a suspension of 480 cm2 of mycelium, scraped from the entire surface of 7·5 Petri dishes (9 cm diameter) and sieved, in 50 mL water. Growth of seedlings in high light intensity (900  µmol m−2 s−1, 16-h daylength) before inoculation increased disease symptoms, but reduced disease when applied after inoculation. In contrast to M. graminicola, near-ultraviolet light after inoculation reduced symptom development. It is proposed that for the full development of RLS, plants should be grown in a stressful environment before inoculation. Nine barley lines were assessed for their resistance to RLS as seedlings and a subset were tested in field trials with natural infection by R. collo-cygni. There was cultivar-by-isolate interaction in the amount of RLS symptoms on seedlings. RLS levels on adult plants in field plots were correlated with RLS scores on seedlings formed by one isolate but not the other. [ABSTRACT FROM AUTHOR]

Objective There are conflicting data regarding the relationship between thyroid function and body mass index (BMI) in euthyroid subjects, and it is uncertain whether tobacco smoking modifies this relationship. The objective of this study was to examine the relationships between thyroid function, BMI and smoking in euthyroid subjects. Design Linear regression models were used to examine the relationships between serum free T4, serum TSH, BMI and smoking in a cross-sectional, community-based sample of 1853 euthyroid subjects in Busselton, Western Australia. Results There was a significant negative relationship between free T4 and BMI: after adjustment for age and sex, each 1 pmol/l increase in free T4 was associated with a decrease in BMI of 0·12 kg/m2 (95% CI 0·06, 0·18; P < 0·001). The mean BMI ± SD of subjects in the highest quintile of free T4 concentration was 24·4 ± 3·5 kg/m2, compared with 26·1 ± 3·8 kg/m2 for the lowest quintile. The relationship between free T4 and BMI was statistically significant (adjusted for age and sex) in subjects who had never smoked ( P = 0·001) and former smokers ( P = 0·011), but not in current smokers ( P = 0·77). There was no significant relationship between TSH and BMI: after adjustment for age and sex, each 1 mU/l increase in TSH was associated with an increase in BMI of 0·08 kg/m2 (95% CI –0·16, 0·32; P = 0·53). Conclusions In euthyroid subjects, small differences in free T4 are associated with differences in BMI. This relationship is not present in current smokers. We speculate that this may be relevant to weight changes associated with smoking cessation. [ABSTRACT FROM AUTHOR]

Effective stimulation of NF-κB in T cells following TCR ligation requires the activity of caspase-8. The active caspase-8 complex includes the paracaspase, MALT1, and Bcl-10, which connect to the NF-κB pathway. It has been less clear what regulates the level of caspase-8 activity during T cell activation. A likely candidate is cellular FLIP (c-FLIP), an enzymatically inert caspase-8 homologue. Two alternatively spliced forms of c-FLIP exist, a long form (c-FLIP [ABSTRACT FROM AUTHOR]

The hypothesis that the increased use of the powdery mildew-resistance gene mlo has caused the increase in spotting diseases of barley over the past 20 years was tested in field trials. Near-isogenic lines with alleles of the Mlo gene for susceptibility or resistance to mildew in two parental backgrounds were trialled at four sites in Scotland and two in Ireland that were prone to spotting diseases, over 3 consecutive years. Mildew was controlled by sprays with quinoxyfen. Disease levels were low in the trials, the two most important diseases being scald caused by Rhynchosporium secalis and ramularia leaf spot caused by Ramularia collo-cygni. There were high levels of abiotic spotting. Lines with mutant mlo alleles consistently developed less Rh. secalis and Ra. collo-cygni, but more abiotic spots. This study indicates that the mlo mildew-resistance gene has not alone been responsible for the rise in spotting diseases over the past 20 years. Possible reasons for the rise are discussed, including the interaction of the mlo gene with the environment. [ABSTRACT FROM AUTHOR]

The extent to which the impact of computer skills depends on how computers are used is investigated using British data from an establishment survey, cohort studies and the European E-Living survey. We examine the importance of type of activity and frequency of use in these various data sources. We find that the impact on earnings depends on which cohort of workers is examined and that there are differences over time. The regression results show that the use of computers for internet access and for email is positively significant across all of our data sets, although there are differences in the size of the effects between men and women. [ABSTRACT FROM AUTHOR]

Gender pay differences are not merely a problem for women returning to work and part-time employees, but also for those in full-time, continuous careers. In data from cohort studies, the gender wage gap for full-time workers in their early thirties fell between 1978 and 2000. This equalization reflects improvements in women’s education and experience rather more than a move towards equal treatment. Indeed, had the typical woman full-timer in 2000 been paid at men’s rates she would have actually received higher pay than the typical man. Within one cohort, passing from age 33 to 42, gender inequality increased. This was partly due to differences in the qualifications and experience of the women in employment at those points, but unequal treatment also rose among women employed full time at both ages. [ABSTRACT FROM AUTHOR]

Twenty-four wheat cultivars and breeding lines were screened for isolate-specific resistance to septoria tritici blotch (STB) caused by 12 isolates of Mycosphaerella graminicola. New isolate-specific resistances that could be used in wheat breeding were identified. Major sources of resistance to STB used in world breeding programmes for decades, such as Kavkaz-K4500, Veranopolis, Catbird and TE9111, have several isolate-specific resistances. This suggests that ‘pyramiding’ several resistance genes in one cultivar may be an effective and durable strategy for breeding for resistance to STB in wheat. Several cultivars, including Arina, Milan and Senat, had high levels of partial resistance to most isolates tested as well as isolate-specific resistances. Resistance to isolate IPO323 was common, present in all but one of the major sources of resistance tested. This suggests that resistance to IPO323 may be an indicator of varietal resistance to STB in the field. [ABSTRACT FROM AUTHOR]

A sialylated lacto-N -neotetraose (Sial-lNnT) structural unit was identified and structurally characterized in the lipopolysaccharide (LPS) from the genome-sequenced strain Road (RM118) of the human pathogen Haemophilus influenzae grown in the presence of sialic acid. A combination of molecular genetics, MS and NMR spectroscopy techniques showed that this structural unit extended from the proximal heptose residue of the inner core region of the LPS molecule. The structure of the Sial-lNnT unit was identical to that found in meningococcal LPS, but glycoforms containing truncations of the Sial-lNnT unit, comprising fewer residues than the complete oligosaccharide component, were not detected. The finding of sialylated glycoforms that were either fully extended or absent suggests a novel biosynthetic feature for adding the terminal tetrasaccharide unit of the Sial-lNnT to the glycose acceptor at the proximal inner core heptose. [ABSTRACT FROM AUTHOR]

Summary We have identified a gene, lpt-3 , that is required for the addition of phosphoethanolamine to the 3-position (PEtn-3) on the β -chain heptose (HepII) of the inner core lipopolysaccharide (LPS) of Neisseria meningitidis (Nm ). The presence of this PEtn-3 substituent is characteristic of the LPS of a majority (≈ 70%) of hypervirulent Nm strains, irrespective of capsular serogroup, and is required for the binding of a previously described monoclonal antibody (mAb B5) to a surface-accessible epitope. All strains of Nm that have PEtn-3 possess the lpt-3 gene. In some lpt-3 -containing strains, the 3-position on HepII is preferentially substituted by glucose instead of PEtn, the result of lgtG phase variation mediated by slippage of a homopolymeric tract of cytidines. Inactivation of lpt-3 resulted in loss of PEtn-3, lack of reactivity with mAb B5 and conferred relative resistance to bactericidal killing and opsonophagocytosis by mAb B5 in vitro . Thus, the identification of lpt-3 has facilitated rigorous genetic, structural and immunobiological definition of an immunodominant epitope that is a candidate immunogen for inclusion in an LPS-based vaccine to protect against invasive meningococcal disease. [ABSTRACT FROM AUTHOR]

Examines the longer run effects of youth training using the Youth Cohort Study Cohort III. Identification of the problem of attrition; Effects of the estimation of the earnings and employment equations on the effects of training; Observation of significant returns to quality training.

We have identified a gene for the addition of N-acetylneuraminic acid (Neu5Ac) in an α-2,3-linkage to a lactosyl acceptor moiety of the lipopolysaccharide (LPS) of the human pathogen Haemophilus influenzae. The gene is one that was identified previously as a phase-variable gene known as lic3A. Extracts of H. influenzae, as well as recombinant Escherichia coli strains producing Lic3A, demonstrate sialyltransferase activity in assays using synthetic fluorescent acceptors with a terminal galactosyl, lactosyl or N-acetyl-lactosaminyl moiety. In the RM118 strain of H. influenzae, Lic3A activity is modulated by the action of another phase-variable glycosyltransferase, LgtC, which competes for the same lactosyl acceptor moiety. Structural analysis of LPS from a RM118:lgtC mutant and the non-typeable strain 486 using mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy confirmed that the major sialylated species has a sialyl-α-(2–3)-lactosyl extension off the distal heptose. This sialylated glycoform was absent in strains containing a lic3A gene disruption. Low amounts of sialylated higher molecular mass glycoforms were present in RM118:lgtC lic3A, indicating the presence of a second sialyltransferase. Lic3A mutants of H. influenzae strains show reduced resistance to the killing effects of normal human serum. Lic3A, encoding an α-2,3-sialyltransferase activity, is the first reported phase-variable sialyltransferase gene. [ABSTRACT FROM AUTHOR]

A survey of Haemophilus influenzae strains indicated that around one-third of capsular strains and over two-thirds of non-typeable strains included sialic acid in their lipopolysaccharides (LPS). Mutation of the CMP-Neu5Ac synthetase gene (siaB ) resulted in a sialylation-deficient phenotype. Isogenic pairs, wild type and siaB mutant of two non-typeable strains were used to demonstrate that sialic acid influences resistance to the killing effect of normal human serum but has little effect on attachment to, or invasion of, cultured human epithelial cells or neutrophils. We determine for the first time the site of attachment of sialic acid in the LPS of a non-typeable strain and report that a small proportion of glycoforms include two sialic acid residues in a disaccharide unit. [ABSTRACT FROM AUTHOR]

The article discusses the effects of monopolies in a partial monopoly model. Its purpose is to make a solution to the partial monopoly model which will allow one to make calculations of the effects of monopolies on the allotment of resources. The model being considered consists of a product and a labour market. Labour is the only variable input considered in the production process, whereas firms acted as price takers in the labour market. Four types of the model are tested which are described in the paper. The comparison of the output of the different models show the substance of the study.

Adherence of capsulate Neisseria meningitidis to endothelial and epithelial cells is facilitated in variants that express pill. Whereas piliated variants of N. meningitidis strain C311 adhered to endothelial cells in large numbers (>150 bacteria/cell), derivatives containing specific mutations that disrupt pilE encoding the pilin subunit were both non-piliated and failed to adhere to endothelial cells (<1 bacterium/ cell). In addition, meningococcal pill recognized human endothelial and epithelial cells but not cells originating from other animals. Variants of strain C311 were obtained that expressed pilins of reduced apparent Mr and exhibited a marked increase in adherence to epithelial cells. Structural analysis of pilins from two hyper-adherent variants and the parent strain were carried out by DNA sequencing of their pilE genes. Deduced molecular weights of pilins were considerably lower compared with their apparent Mr values on SDS-PAGE. Hyper-adherent pilins shared unique changes in sequence including substitution of Asn-113 for Asp-113 and changes from Asn-Asp-Thr-Asp to Thr-Asp-Ala-Lys at residues 127-130 in mature pitin. Asn residues 113 and 127 of 'parental' pilin both form part of the typical eukaryotic N-glycosylation motif Asn-X-Ser/Thr and could potentially be glycosylated post-translationalty. The presence of carbohydrate on pilin was demonstrated and when pilins were deglycosylated, their migration on SDS-PAGE increased, supporting the notion that variable glycosylation accounts for discrepancies in apparent and deduced molecular weights. Functionally distinct pilins produced by two fully piliated variants of a second strain (MC58) differed only in that the putative glycosylation motif Asn-60-Asn-61-Thr-62 in an adherent variant was replaced with Asp-60-Asn-61-Ser-62 in a non-adherent variant. Fully adherent backswitchers obtained from the non-adherent... [ABSTRACT FROM AUTHOR]

Neisseria meningitidis (Nm) isolates from disease or during carriage express, on their outer membranes, one or more of a family of closely related proteins designated Opa proteins. In this study, we have examined the potential roles of Nm Opa proteins in bacterial attachment and invasion of endothelial as well as epithelial cells and compared the influence of Opa proteins with that of Opc protein, which has been previously shown to increase bacterial interactions with eukaryotic cells. Several variants expressing different Opa proteins (A, B, D) or Opt were selected from a culture of capsule-deficient non-piliated bacteria of strain C751. Although the Opa proteins increased bacterial attachment and invasion of endothelial cells, Opc was the most effective protein in increasing bacterial interactions with these cells. In contrast, attachment to several human epithelial cells was facilitated at least as much by OpaB as Opc protein. OpaA was largely without effect whereas OpaD conferred intermediate attachment. OpaB also increased invasion of epithelial cells; more bacteria were internalized by Chang conjunctival cells compared with Hep-2 larynx carcinoma or A549 lung carcinoma cells. Monoclonal antibody reacting with OpaB inhibited bacterial interactions with the host cells. Opa-mediated interactions were also eliminated or significantly reduced in variants expressing capsule or those with sialylated lipopolysaccharide. These data are consistent with the notion that environmental factors controlling capsule and lipopolysaccharide phenotype may modulate bacterial interactions mediated by these OM proteins. In permissive microenvironments, some Opa proteins may be important in bacterial colonization and translocation in addition to Opc. The data also support the notion that Nm Opa may confer tissue tropism. [ABSTRACT FROM AUTHOR]

Whereas capsulate strains of Neisseria meningitidis are dependent on pili for adhesion to human endothelial and epithelial cells, strains which lacked assembled pili and were partially capsule-deficient adhered to and invaded human endothelial and epithelial cells If they expressed the Opc protein. Bacteria expressing low or undetectable levels of Opc protein tailed to adhere to or invade eukaryotic cells. In addition, the presence of OpaAC751 protein on the surface of bacteria did not increase bacterial interactions with host cells. Association of Opc-express ing bacteria was inhibited by antibodies against Opc. Invasion was dependent on the host-cell cytoskeletal activity and was inhibited by cytochalasin D. In some cells, infected at the apical surface, bacteria emerging from basal surface were detected by electron microscopy. Opc is found in diverse meningococci and may represent a common virulence factor which facilitates adherence and invasion by these bacteria. [ABSTRACT FROM AUTHOR]

Social factor differences between respondents with and without courtship violence experience and between male offenders and female victims were explored. Data from the Seven College Survey revealed that those with courtship violence experience (victims and offenders) exhibit relatively "problematic" social profiles. Especially significant were race, religion, .social s tress, isolation, disrupted home, distant-harsh parenting, early dating, and school, employment, and alcohol problems. Offenders differed from victims in closeness to male parents and frequency of church attendance. Implications for relevance of the theory of patriarchy to courtship, and for parent education and the counseling professions are discussed. [ABSTRACT FROM AUTHOR]

Using data from a seven college sample of students, gender differences in three dimensions of courtship violence victimization (acts, meanings, and events) are explored. Females were principle victims by both male and female report. Rates of commission of acts and initiation of violence were similar across gender, although females sustained more higher level violence. Male reports of motives were largely culpability reducing. Females reported many more sexual assaults, and physical and emotional injury than males. Males did not perceive families as sustaining greater harm. Implications of the results for practitioners, particularly for understanding "batterer denial" are discussed. [ABSTRACT FROM AUTHOR]

Recent studies have found violence to be a common feature of premarital dating and courtship. The association of life events stress with courtship violence is examined via a questionnaire of the experiences of a sample of college undergraduates. Life event stress was found to be unrelated to involvement in courtship violence among women. For men, only culturally undesirable events were associated with increased courtship violence. An increasing rate of culturally desirable events was associated with decreased courtship violence, and undesirable health related events had no significant effect. [ABSTRACT FROM AUTHOR]

Recent concern with family violence has focused on child abuse and wife battering, while other forms have been relatively neglected. A need to recognize and focus on violence that occurs during the dating and courtship period is suggested. Descriptive information on the extent and nature of courtship violence found in a sample of college students is reported. The significance of the figures, the "idealized" nature of both popular and professional accounts of the dating and courtship period, and the need for further work in this area are discussed. [ABSTRACT FROM AUTHOR]

Using COS (African green monkey kidney) cells transfected with cDNAs encoding human cell surface molecules, we have identified human cellular receptors for meningococcal virulence-associated Opa proteins, which are expressed by the majority of disease and carrier isolates. These receptors belong to the immunoglobulin superfamily of adhesion molecules and are expressed on epithelial, endothelial and phagocytic cells. Using soluble chimeric receptor molecules, we have demonstrated that meningococcal Opa proteins bind to the N-terminal domain of biliary glycoproteins (classified as BGP or CD66a) that belong to the CEA (CD66) family. Moreover, the Opa proteins of the related pathogen Neisseria gonorrhoeae, responsible for urogenital infections, also interact with this receptor, making CD66a a common target for pathogenic neisseriae. Over 95% of Opa-expressing clinical and mucosal isolates of meningococci and gonococci were shown to bind to the CD66 N-domain, demonstrating the presence of a conserved receptor-binding function in the majority of neisserial Opa proteins. [ABSTRACT FROM AUTHOR]

Opa protein-expressing pathogenic neisseriae interact with CD66a-transfected COS (African green monkey kidney) and CHO (Chinese hamster ovary) cells. CD66a (BGP) is a member of carcinoembryonic antigen (CEA, CD66) family. The interactions occur at the N-terminal domain of CD66a, a region that is highly conserved between members of the CEA subgroup of the CD66 family. In this study, we have investigated the roles of CD66 expressed on human epithelial cells and polymorphonuclear phagocytes (PMNs) in adhesion mediated via Opa proteins. Using human colonic (HT29) and lung (A549) epithelial cell lines known to express CD66 molecules, we show that these receptors are used by meningococci. A monoclonal antibody, YTH71.3, against the N-terminal domain of CD66, but not 3B10 directed against domains, A1/B1, inhibited meningococcal adhesion to host cells. When acapsulate bacteria expressing Opa proteins were used, large numbers of bacteria adhered to HT29 and A549 cells. In addition, both CD66a-transfected CHO cells and human epithelial cells were invaded by Opa-expressing meningococci, suggesting that epithelial cell invasion may occur via Opa-CD66 interactions. In previous studies we have shown that serogroup A strain C751 expresses three Opa proteins, all of which mediate non-opsonic interactions with neutrophils. We have examined the mechanisms of these interactions using antibodies and soluble chimeric receptors. The results indicate that the nature of their interactions with purified CD66a molecules and with CD66 on neutrophils is alike and that these interactions occur at the N-terminal domain of CD66. Thus, the Opa family of neisserial ligands may interact with several members of the CD66 family via their largely conserved N-terminal domains. [ABSTRACT FROM AUTHOR]

The interplay between four surface-expressed virulence factors of Neisseria meningitidis (pili, Opc, capsule and lipopolysaccharide (LPS)) in host cell adhesion and invasion was examined using derivatives of a serogroup B strain, MC58, created by mutation (capsule, Opc) and selection of variants. To examine the role of Opc and of additional expression of pili, bacteria lacking the expression of Opa proteins were used. The effects of different LPS structures were examined in variants expressing either sialylated (L3 immunotype) or truncated non-sialylated (L8 immunotype) LPS. Studies showed that (i) pili were essential for meningococcal interactions with host cells in both capsulate and acapsulate bacteria with the sialylated L3 LPS immunotype, (ii) the Opc-mediated invasion of host cells by piliated and non-piliated bacteria was observed only in acapsulate organisms with L8 LPS immunotype, and (iii) expression of pili in Opc-expressing bacteria resulted in increased invasion. Investigations on the mechanisms of cellular invasion indicated that the Opc-mediated invasion was dependent on the presence of serum in the incubation medium and was mediated by serum proteins with arginine--glycine--aspartic acid (RGD) sequence. Cellular invasion in piliated Opc+ phenotype also required bridging molecules containing the RGD recognition sequence and appeared to involve the integrin αvβ3 as a target receptor on endothelial cells. These studies extend the previous observations on variants of a serogroup A strain (C751) and show that Opc mediates cellular invasion in distinct meningococcal strains and provide confirmation of its mechanism of action. This is the first investigation that evaluates, using derivatives of a single strain, the interplay between four meningococcal surface virulence factors in host cell invasion. [ABSTRACT FROM AUTHOR]

Neisseria meningitidis pili are filamentous protein structures that are essential adhesins in capsulate bacteria. Pili of adhesion variants of meningococcal strain C311 contain glycosyl residues on pilin (PilE), their major structural subunit. Despite the presence of three potential N-linked glycosylation sites, none appears to be occupied in these pilins. Instead, a novel O-linked trisaccharide substituent, not previously found as a constituent of glycoproteins, is present within a peptide spanning amino acid residues 45 to 73 of the PilE molecule. This structure contains a terminal 1-4-linked digalactose moiety covalently linked to a 2,4-diacetamido-2,4,6-trideoxyhexose sugar which is directly attached to pilin. Pilins derived from galactose epimerase (galE) mutants lack the digalactosyl moiety, but retain the diacetamidotrideoxyhexose substitution. Both parental (#3) pilins and those derived from a hyper-adherent variant (#16) contained identical sugar substitutions in this region of pilin, and galE mutants of #3 were similar to the parental phenotype in their adherence to host cells. These studies have confirmed our previous observations that meningococcal pili are glycosylated and provided the first structural evidence for the presence of covalently linked carbohydrate on pili. In addition, they have revealed a completely novel protein/saccharide linkage. [ABSTRACT FROM AUTHOR]

Multiple forms of PilC were found in Neisseria meningitidis (Nm) strains isolated from the oropharynx, blood or cerebrospinal fluid expressing either Class I or Class II pili. PilC expression was observed less frequently in case as opposed to carrier isolates. Moreover, PilC and pili were not always co-expressed. Several heavily piliated strains had no detectable PilC protein as determined by Western blotting using an antiserum previously used to detect such proteins in adhesive variants (Nassif et al., 1994). Serogroup 6 strain MC58 produced large numbers of pili, but expressed barely detectable amounts of PilC. A clonal variant of this strain with increased expression of PilC concurrently exhibited increased adherence to Chang conjunctival epithelial cells and human umbilical vein endothelial cells (Huvecs), but with more rapid binding to the former. No alteration in pilin sequence occurred in this variant, suggesting the involvement of PilC in increased adhesion. A Pil- backswitcher isolated from the hyper-adherent variant was PilC+ but was non-adherent, indicating that any PilC adherence function requires pilus expression. Parental variant (low PilC) produced pili in bundles that were easily detached from the bacterial surface and were frequently associated with Huvec surfaces after bacteria had been sheared off, but pili infrequently replaced bacteria during infection with the PilC-expressing variant. The hyper-adherent variant, which appeared to produce morphologically distinct pilus bundles, was able to withstand considerable shearing force and remained firmly attached to Huvecs. This raises the possibility that the observed hyper-adherence may arise from better anchorage of pili to the bacterial surface in addition to increased adhesion to some host cell surfaces. [ABSTRACT FROM AUTHOR]

Interactions of Opc-expressing Neisseria menlngitldfs with polarized and non-polarized human umbilical vein endothelial cells (Huvecs) were investigated. Meta-boiic Inhibitors and cytochalasin D treatment showed that host cellular and cytoskeletal functions were important for Opc-expressing bacteria association with Huvecs at the apical surface, in addition, this interaction required the presence of serum in the Incubation medium whilst association with non-polarized cells did not require serum. Pre-exposure of Opc-expressing bacteria to serum was sufficient to increase the number of bacteria) interactions at the apical surface; B306, a monoclonal antibody (mAb) against Opc, inhibited these interactions, suggesting that OPEC binds to serum factor(s) and this in turn increases adherence to Huvecs. The receptors involved in this 'sandwich' adherence belong to the integrin family since the interaction was Inhibited by peptides containing the amino acid sequence arginine-glycine-aspartic acid (RGD) and the tetra-peptide RGDS (but not the peptide RGES) was inhibitory. Non-polarized cells appeared to expose receptors/sites that bound to Opc-expressing bacteria directly, did not require serum factors and were not inhibited by RGD-containing peptides. Serum-dependent interactions of Opc-expressing bacteria to apical surface was inhibited significantly by several mAbs against avp3 integrins. Some mAbs against a5 and pi caused partial inhibition; antibodies that did not biock the function of p1 integrins or the mAbs against u2 integrins were not inhibitory to bacterial interactions with Huvecs. Purified vitronectin supported adherence of Opc-expressing bacteria to Huvecs but not of Opc bacteria. These interactions were inhibited by mAb B306 against Opc, by RGDS peptides as well as by blocking antibodies directed against avp3 but not antibodies against other integrins. These data suggest that a sequence of molecular events resulting in trimolecular complexes at... [ABSTRACT FROM AUTHOR]

An econometric model of the self employment decision is estimated for a large sample of UK graduates. Although the earnings distributions suggest that there are incentives to be self employed, the difference in the predicted earnings that an individual receives in the self employed and employed sectors is not a significant influence on the choice of sector and the decision depends on personal and social factors. Policies based on changing the pecuniary returns may not encourage the growth of self employment among graduates. The econometric results also suggest that the self employed are a nonrandom subset of the graduate workforce. [ABSTRACT FROM AUTHOR]

There exists a considerable body of opinion subscribing to the view that workers' militancy plays a major role in the genesis of inflation. Concomitant with this view is the search for a suitable index of union militancy. This search has necessarily been concentrated on measures of union activity and several activity measures have been put forward as measures of union militancy. The aim of this article is to analyse the relationships between the most commonly used proxies for union aggressiveness and to see whether it is possible to separate some common measure of "militancy" or "activity" from the alternative measures proposed. It is argued that all the commonly used proxy variables should be analysed simultaneously because it is unlikely that a single variable can capture all the effects of workers' pushfulness. This involves a multivariate approach which recognizes the interdependence between the various measures rather than treating each one as an alternative independent measure. The general conclusion is therefore that a single variable will not capture all the different variations in union activity, let alone militancy.

Assesses the wage effect of the Youth Training Scheme (YTS). Estimation of separate earnings equations for each type of training; Comparison with predicted earnings of typical individuals; Wage differences between the sexes.