Temporal variations in quality of acute stroke care and outcomes in London hyperacute stroke units: a mixed-methods study

This is the final version. Available from the NIHR Journals Library via the DOI in this recordBackground Seven-day working in hospitals is a current priority of international health research and policy. Previous research has shown variability in delivering evidence-based clinical interventions across different times of the day and week. We aimed to identify factors influencing such variations in London hyperacute stroke units. Objectives To investigate variations in quality of acute stroke care and outcomes by day and time of admission in London hyperacute stroke units, and to identify factors influencing such variations. Design This was a prospective cohort study using anonymised patient-level data from the Sentinel Stroke National Audit Programme. Factors influencing variations in care and outcomes were studied through interview and observation data. Setting The setting was acute stroke services in London hyperacute stroke units. Participants A total of 7094 patients with a primary diagnosis of stroke took part. We interviewed hyperacute stroke unit staff (n = 76), including doctors, nurses, therapists and administrators, and 31 patients and carers. We also conducted non-participant observations of delivery of care at different times of the day and week (n = 45, ≈102 hours). Intervention Hub-and-spoke model for care of suspected acute stroke patients in London with performance standards was designed to deliver uniform access to high-quality hyperacute stroke unit care across the week. Main outcome measures Indicators of quality of acute stroke care, mortality at 3 days after admission, disability at the end of the inpatient spell and length of stay. Data sources Sentinel Stroke National Audit Programme data for all patients in London hyperacute stroke units with a primary diagnosis of stroke between 1 January and 31 December 2014, and nurse staffing data for all eight London hyperacute stroke units for the same period. Results We found no variation in quality of care by day and time of admission across the week in terms of stroke nursing assessment, brain scanning and thrombolysis in London hyperacute stroke units, nor in 3-day mortality nor disability at hospital discharge. Other quality-of-care measures significantly varied by day and time of admission. Quality of care was better if the nurse in charge was at a higher band and/or there were more nurses on duty. Staff deliver ‘front-door’ interventions consistently by taking on additional responsibilities out of hours, creating continuities between day and night, building trusting relationships and prioritising ‘front-door’ interventions. Limitations We were unable to measure long-term outcomes as our request to the Sentinel Stroke National Audit Programme, the Healthcare Quality Improvement Partnership and NHS Digital for Sentinel Stroke National Audit Programme data linked with patient mortality status was not fulfilled. Conclusions Organisational factors influence 24 hours a day, 7 days a week (24/7), provision of stroke care, creating temporal patterns of provision reflected in patient outcomes, including mortality, length of stay and functional independence. Future work Further research would help to explore 24/7 stroke systems in other contexts. We need a clearer understanding of variations by looking at absolute time intervals, rather than achievement of targets. Research is needed with longer-term mortality and modified Rankin Scale data, and a more meaningful range of outcomes.National Institute for Health Research (NIHR

The Geographic Synchrony of Seasonal Influenza: A Waves across Canada and the United States

BACKGROUND: As observed during the 2009 pandemic, a novel influenza virus can spread globally before the epidemic peaks locally. As consistencies in the relative timing and direction of spread could form the basis for an early alert system, the objectives of this study were to use the case-based reporting system for laboratory confirmed influenza from the Canadian FluWatch surveillance program to identify the geographic scale at which spatial synchrony exists and then to describe the geographic patterns of influenza A virus across Canada and in relationship to activity in the United States (US). METHODOLOGY/PRINCIPAL FINDINGS: Weekly laboratory confirmations for influenza A were obtained from the Canadian FluWatch and the US FluView surveillance programs from 1997/98 to 2006/07. For the six seasons where at least 80% of the specimens were antigenically similar, we identified the epidemic midpoint of the local/regional/provincial epidemics and analyzed trends in the direction of spread. In three out of the six seasons, the epidemic appeared first in Canada. Regional epidemics were more closely synchronized across the US (3-5 weeks) compared to Canada (5-13 weeks), with a slight gradient in timing from the southwest regions in the US to northeast regions of Canada and the US. Cities, as well as rural areas within provinces, usually peaked within a couple of weeks of each other. The anticipated delay in peak activity between large cities and rural areas was not observed. In some mixed influenza A seasons, lack of synchronization sub-provincially was evident. CONCLUSIONS/SIGNIFICANCE: As mixing between regions appears to be too weak to force a consistency in the direction and timing of spread, local laboratory-based surveillance is needed to accurately assess the level of influenza activity in the community. In comparison, mixing between urban communities and adjacent rural areas, and between some communities, may be sufficient to force synchronization

Queering identity : becoming queer in the work of Cassils

This chapter explores the work of genderqueer artist Cassils in order to address the question of what it is to be human from a queer perspective. The challenges from queer and postmodern scholarship to the “identity politics” so central to earlier activist and academic agendas have been well documented. Yet, notwithstanding these valid critiques, identity remains a powerful organizing concept in contemporary experience. These contradictory stances on identity serve as a prompt for thinking about what queer brings to our understandings of being human now and in the near future

A high-throughput de novo sequencing approach for shotgun proteomics using high-resolution tandem mass spectrometry

<p>Abstract</p> <p>Background</p> <p>High-resolution tandem mass spectra can now be readily acquired with hybrid instruments, such as LTQ-Orbitrap and LTQ-FT, in high-throughput shotgun proteomics workflows. The improved spectral quality enables more accurate <it>de novo </it>sequencing for identification of post-translational modifications and amino acid polymorphisms.</p> <p>Results</p> <p>In this study, a new <it>de novo </it>sequencing algorithm, called Vonode, has been developed specifically for analysis of such high-resolution tandem mass spectra. To fully exploit the high mass accuracy of these spectra, a unique scoring system is proposed to evaluate sequence tags based primarily on mass accuracy information of fragment ions. Consensus sequence tags were inferred for 11,422 spectra with an average peptide length of 5.5 residues from a total of 40,297 input spectra acquired in a 24-hour proteomics measurement of <it>Rhodopseudomonas palustris</it>. The accuracy of inferred consensus sequence tags was 84%. According to our comparison, the performance of Vonode was shown to be superior to the PepNovo v2.0 algorithm, in terms of the number of <it>de novo </it>sequenced spectra and the sequencing accuracy.</p> <p>Conclusions</p> <p>Here, we improved <it>de novo </it>sequencing performance by developing a new algorithm specifically for high-resolution tandem mass spectral data. The Vonode algorithm is freely available for download at <url>http://compbio.ornl.gov/Vonode</url>.</p

Challenges in the management of a patient with Cowden syndrome: case report and literature review

We would like to present a patient with a classical phenotype of a rare disorder - Cowden syndrome, its diagnostics and management challenges. A breast surgeon has to be aware of this rare condition when treating a patient with breast manifestations of Cowden syndrome and has to refer the patient to a clinical geneticist for further evaluation. Sequencing of the PTEN gene showed the Asp24Gly mutation. According to the latest literature data, the lifetime risk of breast cancer for Cowden syndrome patients is 81% and surgery is a justified option to reduce the risk of breast cancer. Bilateral risk-reducing mastectomy with immediate reconstruction was performed to eliminate further risk of breast cancer. 3 years after the risk-reducing breast surgery the patient is satisfied with the outcome. This is to our best knowledge the first reported Cowden syndrome case with follow-up data after risk-reducing measures have been taken

Tandem mass spectrometry data quality assessment by self-convolution

<p>Abstract</p> <p>Background</p> <p>Many algorithms have been developed for deciphering the tandem mass spectrometry (MS) data sets. They can be essentially clustered into two classes. The first performs searches on theoretical mass spectrum database, while the second based itself on <it>de novo </it>sequencing from raw mass spectrometry data. It was noted that the quality of mass spectra affects significantly the protein identification processes in both instances. This prompted the authors to explore ways to measure the quality of MS data sets before subjecting them to the protein identification algorithms, thus allowing for more meaningful searches and increased confidence level of proteins identified.</p> <p>Results</p> <p>The proposed method measures the qualities of MS data sets based on the symmetric property of b- and y-ion peaks present in a MS spectrum. Self-convolution on MS data and its time-reversal copy was employed. Due to the symmetric nature of b-ions and y-ions peaks, the self-convolution result of a good spectrum would produce a highest mid point intensity peak. To reduce processing time, self-convolution was achieved using Fast Fourier Transform and its inverse transform, followed by the removal of the "DC" (Direct Current) component and the normalisation of the data set. The quality score was defined as the ratio of the intensity at the mid point to the remaining peaks of the convolution result. The method was validated using both theoretical mass spectra, with various permutations, and several real MS data sets. The results were encouraging, revealing a high percentage of positive prediction rates for spectra with good quality scores.</p> <p>Conclusion</p> <p>We have demonstrated in this work a method for determining the quality of tandem MS data set. By pre-determining the quality of tandem MS data before subjecting them to protein identification algorithms, spurious protein predictions due to poor tandem MS data are avoided, giving scientists greater confidence in the predicted results. We conclude that the algorithm performs well and could potentially be used as a pre-processing for all mass spectrometry based protein identification tools.</p

Genetic Selection of Low Fertile Onchocerca volvulus by Ivermectin Treatment

Onchocerca volvulus is the causative agent of onchocerciasis, or “river blindness”. Ivermectin has been used for mass treatment of onchocerciasis for up to 18 years, and recently there have been reports of poor parasitological responses to the drug and evidence of drug resistance. Drug resistance has a genetic basis. In this study, genetic changes in β-tubulin, a gene associated with ivermectin resistance in nematodes, were seen in parasites obtained from the patients exposed to repeated ivermectin treatment compared with parasites obtained from the same patients before any exposure to ivermectin. Furthermore, the extent of the genetic changes was dependent on the level of ivermectin treatment exposure. This genetic selection was associated with a lower reproductive rate in the female parasites. The data indicates that this genetic selection is for a population of O. volvulus that is more tolerant to ivermectin. This selection could have implications for the development of ivermectin resistance in O. volvulus and for the ongoing onchocerciasis control programmes. Monitoring for the possible development and spread of ivermectin resistance, as part of the control programmes, should be implemented so that any foci of resistant parasites can be treated by alternative control measures

Polymorphisms in the glucocerebrosidase gene and pseudogene urge caution in clinical analysis of Gaucher disease allele c.1448T>C (L444P)

BACKGROUND: Gaucher disease is a potentially severe lysosomal storage disorder caused by mutations in the human glucocerebrosidase gene (GBA). We have developed a multiplexed genetic assay for eight diseases prevalent in the Ashkenazi population: Tay-Sachs, Gaucher type I, Niemann-Pick types A and B, mucolipidosis type IV, familial dysautonomia, Canavan, Bloom syndrome, and Fanconi anemia type C. This assay includes an allelic determination for GBA allele c.1448T>C (L444P). The goal of this study was to clinically evaluate this assay. METHODS: Biotinylated, multiplex PCR products were directly hybridized to capture probes immobilized on fluorescently addressed microspheres. After incubation with streptavidin-conjugated fluorophore, the reactions were analyzed by Luminex IS100. Clinical evaluations were conducted using de-identified patient DNA samples. RESULTS: We evaluated a multiplexed suspension array assay that includes wild-type and mutant genetic determinations for Gaucher disease allele c.1448T>C. Two percent of samples reported to be wild-type by conventional methods were observed to be c.1448T>C heterozygous using our assay. Sequence analysis suggested that this phenomenon was due to co-amplification of the functional gene and a paralogous pseudogene (ΨGBA) due to a polymorphism in the primer-binding site of the latter. Primers for the amplification of this allele were then repositioned to span an upstream deletion in the pseudogene, yielding a much longer amplicon. Although it is widely reported that long amplicons negatively impact amplification or detection efficiency in recently adopted multiplex techniques, this assay design functioned properly and resolved the occurrence of false heterozygosity. CONCLUSION: Although previously available sequence information suggested GBA gene/pseudogene discrimination capabilities with a short amplified product, we identified common single-nucleotide polymorphisms in the pseudogene that required amplification of a larger region for effective discrimination

Effectiveness of flow obstructions in enhancing electro-osmotic flow

In this paper the influence of obstructions on micro-channel electroosmotic flow is investigated for the first time. To carry out such a study, regular obstructions are introduced into micro-channels and flow rates are numerically calculated. The effect of channel width on flow rates is analysed on both free and obstructed channels. The solid material considered for channel walls and obstructions is silicon and the electrolyte is de-ionised water. The parameters studied include channel width, obstruction size and effective porosity of the channel. The effective porosity is varied between 0.4 and 0.8 depending on other chosen parameters. The results clearly demonstrate that, under the analysed conditions, introduction of obstructions into channels wider than100 micro meters enhances the flow rate induced by electro-osmosis