Evaluation of a standardised protocol to measure the disease burden of respiratory syncytial virus infection in young children in primary care.

BACKGROUND: A better understanding of the burden of respiratory syncytial virus (RSV) infections in primary care is needed for policymakers to make informed decisions regarding new preventive measures and treatments. The aim of this study was to develop and evaluate a protocol for the standardised measurement of the disease burden of RSV infection in primary care in children aged < 5 years. METHODS: The standardised protocol was evaluated in Italy and the Netherlands during the 2019/20 winter. Children aged < 5 years who consulted their primary care physician, met the WHO acute respiratory infections (ARI) case definition, and had a laboratory confirmed positive test for RSV (RT-PCR) were included. RSV symptoms were collected at the time of swabbing. Health care use, duration of symptoms and socio-economic impact was measured 14 days after swabbing. Health related Quality of life (HRQoL) was measured using the parent-proxy report of the PedsQL™4.0 generic core scales (2-4 years) and PedsQL™4.0 infant scales (0-2 years) 30 days after swabbing. The standardised protocol was evaluated in terms of the feasibility of patient recruitment, data collection procedures and whether parents understood the questions. RESULTS: Children were recruited via a network of paediatricians in Italy and a sentinel influenza surveillance network of general practitioners in the Netherlands. In Italy and the Netherlands, 293 and 152 children were swabbed respectively, 119 and 32 tested RSV positive; for 119 and 12 children the Day-14 questionnaire was completed and for 116 and 11 the Day-30 questionnaire. In Italy, 33% of the children had persistent symptoms after 14 days and in the Netherlands this figure was 67%. Parents had no problems completing questions concerning health care use, duration of symptoms and socio-economic impact, however, they had some difficulties scoring the HRQoL of their young children. CONCLUSION: RSV symptoms are common after 14 days, and therefore, measuring disease burden outcomes like health care use, duration of symptoms, and socio-economic impact is also recommended at Day-30. The standardised protocol is suitable to measure the clinical and socio-economic disease burden of RSV in young children in primary care.

Ageing in corrective services: from the perspective of prison chaplains.

The number of older inmates in New South Wales prisons has increased over the past ten years but it is unclear whether corrective services can cater for the increase. The current study reports the results of a qualitative study about ageing in prison. Eight prison chaplains from four corrective facilities in NSW were interviewed using a semi-structured interview schedule. The results of a thematic analysis revealed four main themes: the system, the services, the environment and the inmate. The themes reveal a system that is not designed to cope with an ageing population. Inmates become resentful of what has happened to them rather than for the damage they have done to somebody else. The system lacks processes and programmes to enable proper rehabilitation. The issues raised by the chaplains in terms of services, the environment and the inmates decrease the possibility that an older inmate will adapt to the environment and successfully age in place.

Waning population immunity prior to a large Q fever epidemic in the south of The Netherlands.

Historical survey data suggest that the seroprevalence of antibodies against Coxiella burnetii in the general population of The Netherlands decreased from more than 40% in 1983 to 2·4% in 2007, just before the start of the large 2007-2010 Q fever epidemic. To assess whether the sharp decline in seroprevalence was real, we performed a cross-sectional study using historical samples. We tested samples using a contemporary commercial indirect immunofluorescence assay. In plasma samples from the south of The Netherlands from 1987, we found an age- and sex-standardized seroprevalence of 14·4% (95% confidence interval 11·2-18·3). This was significantly lower than a 1983 estimate from the same area (62·5%), but significantly higher than 2008 (1·0%) and 2010 (2·3%) estimates from the same area. The study suggests that there was a steady and sharp decline in Q fever seroprevalence in the south of The Netherlands from 1987 to 2008. We assume that seroprevalence has decreased in other parts of The Netherlands as well and seroprevalence surveys in other European countries have shown a similar declining trend. Waning population immunity in The Netherlands may have contributed to the scale of the 2007-2010 Q fever epidemic. For a better understanding of the infection dynamics of Q fever, we advocate an international comparative study of the seroprevalence of C. burnetii.

Unicortical fixation of metacarpal fractures: is it strong enough?

Unicortical fixation has some practical and theoretical advantages over bicortical fixation. Questions have been raised to its adequacy for post-operative mobilization. We hypothesized that fixation using a plate and eight unicortical screws would be as strong as using a plate and four bicortical screws. A total of 40 unicortical and 40 bicortical fixations were compared using a cadaveric metacarpal model. Unicortical fixation was performed using an eight-hole parallel plate and bicortical fixation with a four-hole straight plate. Fixations were tested to failure using four-point bending load. The mean load to failure was 414 N SD 38(SE) for the unicortical group and 296 N SD 29(SE) for the bicortical group. Significant differences between these two constructs were observed. The mean stiffness of the fixation was higher for the bicortical group than the unicortical, although this difference did not reach significance. Unicortical fixation alone is sufficient to enable early post-operative mobilization in a live model.

Rapid Optimization of Engineered Metabolic Pathways with Serine Integrase Recombinational Assembly (SIRA).

Metabolic pathway engineering in microbial hosts for heterologous biosynthesis of commodity compounds and fine chemicals offers a cheaper, greener, and more reliable method of production than does chemical synthesis. However, engineering metabolic pathways within a microbe is a complicated process: levels of gene expression, protein stability, enzyme activity, and metabolic flux must be balanced for high productivity without compromising host cell viability. A major rate-limiting step in engineering microbes for optimum biosynthesis of a target compound is DNA assembly, as current methods can be cumbersome and costly. Serine integrase recombinational assembly (SIRA) is a rapid DNA assembly method that utilizes serine integrases, and is particularly applicable to rapid optimization of engineered metabolic pathways. Using six pairs of orthogonal attP and attB sites with different central dinucleotide sequences that follow SIRA design principles, we have demonstrated that ΦC31 integrase can be used to (1) insert a single piece of DNA into a substrate plasmid; (2) assemble three, four, and five DNA parts encoding the enzymes for functional metabolic pathways in a one-pot reaction; (3) generate combinatorial libraries of metabolic pathway constructs with varied ribosome binding site strengths or gene orders in a one-pot reaction; and (4) replace and add DNA parts within a construct through targeted postassembly modification. We explain the mechanism of SIRA and the principles behind designing a SIRA reaction. We also provide protocols for making SIRA reaction components and practical methods for applying SIRA to rapid optimization of metabolic pathways.

A national measles epidemic in Switzerland in 1997 : consequences for the elimination of measles by the year 2007.

Clinical cases of measles have been reported to the Swiss Sentinel Surveillance Network (Sentinella) since June 1986 and measles infections have been monitored by the national laboratory notification system since January 1988. These two surveillance syste

Asthma trends in Switzerland: the Swiss Sentinel Surveillance Network, 1988-1996.

The setting up of the Swiss Sentinel Surveillance Network (SSSN) in 1986 has provided an excellent opportunity to study the distribution and determinants of asthma. The system provides morbidity data, which are representative of family practices in primar

[Effects of the 1987 revision of the definition for an AIDS case in Switzerland]. / Effekte der Revision der Aids-Falldefinition von 1987 in der Schweiz.

AIDS cases diagnosed in Switzerland after the revision of 1987 and reported to the Swiss Federal Office of Public Health until 31.12.1992 were categorised according to whether they conformed to the diagnostic criteria valid before the revision (= "pre-87"-group) or only to the new criteria introduced with the revision (= "post-87"-group). Compared to the "pre-87"-group, the proportion of injecting drug users was higher, the proportion of homosexual men was lower, the patients were younger and Pneumocystis carinii pneumonia (PCP) and Kaposi-sarcoma were diagnosed less frequently in the "post-87"-group. The revision of the AIDS case-definition affected the proportion of Aids-diagnoses with PCP over time. It improved the surveillance of AIDS morbidity in Switzerland but its effects must be distinguished from true phenomena of the AIDS-epidemic.

The complete paediatrician: attributes of good practice.

The attributes which the author considers help to make up good paediatric practice are discussed. Some of the problems associated with their achievement are examined. All of these ingredients can never be possessed by any one of us though each of us should have them as our aim. Their full spectrum, to be evident in practice, needs us to be members of a team.

Ward sisters' views of the effect of NHS changes.

The role of the ward sister or charge nurse has long been acknowledged as being central to the provision of high-quality patient care. Health service reforms since the 1980s have led to greater managerial responsibility for ward sisters and charge nurses, who are often now known as ward managers. This paper reports on a study carried out in one hospital which described how 15 charge nurses and ward sisters saw their roles in the light of recent changes. While the informants spoke of areas of their jobs with which they were satisfied, such as control over financial resources, there were also areas of concern. These included the pace of change and the sense of isolation that they experienced. The ward sister's responses are described and recommendations for practice outlined.

Single-chain factor XII exhibits activity when complexed to polyphosphate.

BACKGROUND: The mechanism underpinning factor XII autoactivation was originally characterized with non-physiological surfaces, such as dextran sulfate (DS), ellagic acid, and kaolin. Several 'natural' anionic activating surfaces, such as platelet polyphosphate (polyP), have now been identified. OBJECTIVE: To analyze the autoactivation of FXII by polyP of a similar length to that found in platelets (polyP70 ). METHODS AND RESULTS: PolyP70 showed similar efficacy to DS in stimulating autoactivation of FXII, as detected with amidolytic substrate. Western blotting revealed different forms of FXII with the two activating surfaces: two-chain αFXIIa was formed with DS, whereas single-chain FXII (scFXII; 80 kDa) was formed with polyP70 . Dissociation of scFXII from polyP70 abrogated amidolytic activity, suggesting reversible exposure of the active site. Activity of scFXII-polyP70 was enhanced by Zn(2+) and was sensitive to NaCl concentration. A bell-shaped concentration response to polyP70 was evident, as is typical of surface-mediated reactions. Reaction of scFXII-polyP70 with various concentrations of S2302 generated a sigmoidal curve, in contrast to a hyperbolic curve for αFXIIa, from which a Hill coefficient of 3.67 was derived, indicative of positive cooperative binding. scFXII-polyP70 was more sensitive to inhibition by H-d-Pro-Phe-Arg-chloromethylketone and corn trypsin inhibitor than αFXIIa, but inhibition profiles for C1-inhibitor were similar. Active scFXII-polyP70 was also able to cleave its physiological targets FXI and prekallikrein to their active forms. CONCLUSIONS: Autoactivation of FXII by polyP, of the size found in platelets, proceeds via an active single-chain intermediate. scFXII-polyP70 shows activity towards physiological substrates, and may represent the primary event in initiating contact activation in vivo.

Accurately costing unilateral delayed DIEP flap breast reconstruction.

INTRODUCTION: Free tissue transfer for breast reconstruction is widely practiced in the UK and its availability forms part of the NICE guidelines in treating breast cancer. Free flap reconstruction scores highly on patient reported outcome measures for both immediate and delayed procedures. However there are significant resource implications and a concern that the financial burden is not adequately met by the fixed price tariff system (Payment by Results). This study aims to compare the cost of treatment with both local financial estimates and reimbursement. METHOD: We conducted a prospective costing analysis for 10 consecutive delayed unilateral DIEP breast reconstructions from August 2011 by a single surgeon in Frenchay Hospital, Bristol. Comparison was made to both the hospital's costing estimates and the Health Resource Group (HRG) tariffs received for 27 similar cases performed by the same surgeon in the 2010-11 financial year. RESULTS: The mean treatment cost for performing a delayed unilateral DIEP procedure was £7628 (±£754 Standard Deviation). This compared to an estimate from the financial department of £8072±(£1683 SD). These values were not significantly different (p=0.27). The HRG tariff was £8792 (±£423 SD). There was an average net income of £720 per case. Personnel in theatre represented the largest cost area at an average of 73% of total cost. CONCLUSIONS: This study highlights that the costs of this procedure have been estimated accurately by the financial department and that the current HRG code provides adequate reimbursement. The new HRG code for 2012-13, HRG JA14z, provides significantly less reimbursement at £7012 and measures need to be taken to address this. This study has identified that personnel costs are the greatest contributor to overall cost and allowed us to recognise and implement changes to improve efficiency.

Repression of cancer cell senescence by PKCι.

Senescence is an irreversible growth arrest phenotype adopted by cells that has a key role in protecting organisms from cancer. There is now considerable interest in therapeutic strategies that reactivate this process to control the growth of cancer cells. Protein kinase-Cι (PKCι) is a member of the atypical PKC family and an important downstream mediator in the phosphoinositide-3-kinase (PI-3-kinase) pathway. PKCι expression was found to be upregulated in a subset of breast cancers and breast cancer cell lines. Activation of the PI-3-kinase pathway by introduction of mutant, oncogenic PIK3CA into breast mammary epithelial cells increased both the expression and activation of PKCι. In breast cancer cells lines overexpressing PKCι, depletion of PKCι increased the number of senescent cells, as assessed by senescence-associated ß-galactosidase, morphology and bromodeoxyuridine incorporation. This phenomenon was not restricted to breast cancer cells, as it was also seen in glioblastoma cells in which PKCι is activated by loss of PTEN. Senescence occurred in the absence of a detectable DNA-damage response, was dependent on p21 and was enhanced by the aurora kinase inhibitor VX-680, suggesting that senescence is triggered by defects in mitosis. Depletion of PKCι had no effect on senescence in normal mammary epithelial cell lines. We conclude that PKCι is overexpressed in a subset of cancers where it functions to suppress premature senescence. This function appears to be restricted to cancer cells and inhibition of PKCι may therefore be an effective way to selectively activate premature senescence in cancer cells.