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Model study of tropospheric trace species distributions during PEM-West A
A three-dimensional mesoscale transport/photochemical model is used to study the transport and photochemical transformation of trace species over eastern Asia and western Pacific for the period from September 20 to October 6, 1991, of the Pacific Exploratory Mission-West A experiment. The influence of emissions from the continental boundary layer that was evident in the observed trace species distributions in the lower troposphere over the ocean is well simulated by the model. In the upper troposphere, species such as O3, NOy (total reactive nitrogen species), and SO2 which have a significant source in the stratosphere are also simulated well in the model, suggesting that the upper tropospheric abundances of these species are strongly influenced by stratospheric fluxes and upper tropospheric sources. In the case of SO2 the stratospheric flux is identified to be mostly from the Mount Pinatubo eruption. Concentrations in the upper troposphere for species such as CO and hydrocarbons, which are emitted in the continental boundary layer and have a sink in the troposphere, are significantly underestimated by the model. Two factors have been identified to contribute significantly to the underestimate: one is emissions upwind of the model domain (eastern Asia and western Pacific); the other is that vertical transport is underestimated in the model. Model results are also grouped by back trajectories to study the contrast between compositions of marine and continental air masses. The model-calculated altitude profiles of trace species in continental and marine air masses are found to be qualitatively consistent with observations. However, the difference in the median values of trace species between continental air and marine air is about twice as large for the observed values as for model results. This suggests that the model underestimates the outflow fluxes of trace species from the Asian continent and the Pacific rim countries to the ocean. Observed altitude profiles for species like CO and hydrocarbons show a negative gradient in continental air and a positive gradient in marine air. A mechanism which may be responsible for the altitude gradients is proposed
Influenza epidemiology, vaccine coverage and vaccine effectiveness in children admitted to sentinel Australian hospitals in 2014: The influenza complications alert network (FluCAN)
The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance programme operating in all states and territories in Australia. We summarise the epidemiology of children hospitalised with laboratory-confirmed influenza in 2014 and reports on the effectiveness of inactivated trivalent inactivated vaccine (TIV) in children. In this observational study, cases were defined as children admitted with acute respiratory illness (ARI) with influenza confirmed by PCR. Controls were hospitalised children with ARI testing negative for influenza. Vaccine effectiveness (VE) was estimated as 1 minus the odds ratio of vaccination in influenza positive cases compared with test-negative controls using conditional logistic regression models. From April until October 2014, 402 children were admitted with PCR-confirmed influenza. Of these, 28% were aged < 1 year, 16% were Indigenous, and 39% had underlying conditions predisposing to severe influenza. Influenza A was detected in 90% of cases of influenza; influenza A(H1N1)pdm09 was the most frequent subtype (109/141 of subtyped cases) followed by A(H3N2) (32/141). Only 15% of children with influenza received antiviral therapy. The adjusted VE of one or more doses of TIV for preventing hospitalised influenza was estimated at 55.5% (95% confidence intervals (CI): 11.6–77.6%). Effectiveness against influenza A(H1N1)pdm09 was high (91.6%, 95% CI: 36.0–98.9%) yet appeared poor against H3N2. In summary, the 2014 southern hemisphere TIV was moderately effective against severe influenza in children. Significant VE was observed against influenza A(H1N1)pdm0
Criteria for the use of omics-based predictors in clinical trials.
The US National Cancer Institute (NCI), in collaboration with scientists representing multiple areas of expertise relevant to 'omics'-based test development, has developed a checklist of criteria that can be used to determine the readiness of omics-based tests for guiding patient care in clinical trials. The checklist criteria cover issues relating to specimens, assays, mathematical modelling, clinical trial design, and ethical, legal and regulatory aspects. Funding bodies and journals are encouraged to consider the checklist, which they may find useful for assessing study quality and evidence strength. The checklist will be used to evaluate proposals for NCI-sponsored clinical trials in which omics tests will be used to guide therapy
Breast MRI and tumour biology predict axillary lymph node response to neoadjuvant chemotherapy for breast cancer
Weaning from Mechanical Ventilation
For most patients who require mechanical ventilation weaning and extubation is simple. In these patients a variety of strategies can be successful. In addition, sim ple criteria may predict when the patient is ready for extubation. For the small group of patients who require prolonged mechanical ventilation, however, contro versy exists about how best to remove ventilator sup port by weaning, and available data are sparse. Much of the controversy has centered on T-piece weaning ver sus intermittent mandatory ventilation. To date no con trolled study has demonstrated the superiority of either intermittent mandatory ventilation or T-piece weaning in difficult-to-wean patients. In the evolution of this con troversy, concern has developed over the potential for increased inspiratory work and expiratory resistance that may be associated with certain intermittent manda tory ventilation systems. The possibility that significant inspiratory work may occur during assist-control venti lation has also been demonstrated. Respiratory muscle weakness and fatigue is likely important in failure to wean. Other possible causes are failure of the cardiovas cular system and impaired ability of the lung to carry out gas exchange. In this article we first examine criteria and techniques for weaning short-term ventilator pa tients. We then examine criteria to begin the weaning process in prolonged ventilation patients, potential causes of failure to wean, and techniques that can be used to remove ventilator support from patients who are difficult to wean. Much literature has been devoted to techniques and criteria for weaning and extubation of patients from mechanical ventilation. For most patients who require ventilatory support, weaning and extuba tion can be easily accomplished by a variety of tech niques [1-4]. At one referral center 77.2% of all surviving patients were weaned from the ventilator within 72 hours of the onset of mechanical ventila tion, and 91% were weaned within 7 days [1]. Less than 10% of ventilated patients potentially posed problems in weaning from mechanical ventilation. Similarly, at a community hospital, few surviving patients required prolonged ventilatory support [2]. In easy-to-wean patients, Sahn and Lakshminarayan [5] described simple criteria that are predictive of successful discontinuation of ventilator support. For the small group of patients who require pro longed mechanical ventilation, however, minimal data are available. In these patients criteria to deter mine weaning ability or which measurements to follow are not clearly defined. Furthermore, no controlled trials are available to compare the differ ent weaning techniques proposed. In this article we first address routine weaning of the patient who has not required prolonged ventilator support. We then examine the difficult-to-wean patient and dis cuss criteria to begin the weaning process, poten tial causes of failure to wean, and available weaning techniques.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68923/2/10.1177_088506668800300207.pd
'Reaching the hard to reach' - lessons learned from the VCS (voluntary and community Sector). A qualitative study.
Background The notion 'hard to reach' is a contested and ambiguous term that is commonly used within the spheres of social care and health, especially in discourse around health and social inequalities. There is a need to address health inequalities and to engage in services the marginalized and socially excluded sectors of society. Methods This paper describes a pilot study involving interviews with representatives from eight Voluntary and Community Sector (VCS) organisations . The purpose of the study was to explore the notion of 'hard to reach' and perceptions of the barriers and facilitators to accessing services for 'hard to reach' groups from a voluntary and community sector perspective. Results The 'hard to reach' may include drug users, people living with HIV, people from sexual minority communities, asylum seekers, refugees, people from black and ethnic minority communities, and homeless people although defining the notion of the 'hard to reach' is not straight forward. It may be that certain groups resist engaging in treatment services and are deemed hard to reach by a particular service or from a societal stance. There are a number of potential barriers for people who may try and access services, including people having bad experiences in the past; location and opening times of services and how services are funded and managed. A number of areas of commonality are found in terms of how access to services for 'hard to reach' individuals and groups could be improved including: respectful treatment of service users, establishing trust with service users, offering service flexibility, partnership working with other organisations and harnessing service user involvement.
Conclusions: If health services are to engage with groups that are deemed 'hard to reach' and marginalised from mainstream health services, the experiences and practices for engagement from within the VCS may serve as useful lessons for service improvement for statutory health services
CF2 Represses Actin 88F Gene Expression and Maintains Filament Balance during Indirect Flight Muscle Development in Drosophila
The zinc finger protein CF2 is a characterized activator of muscle structural genes in the body wall muscles of the Drosophila larva. To investigate the function of CF2 in the indirect flight muscle (IFM), we examined the phenotypes of flies bearing five homozygous viable mutations. The gross structure of the IFM was not affected, but the stronger hypomorphic alleles caused an increase of up to 1.5X in the diameter of the myofibrils. This size increase did not cause any disruption of the hexameric arrangement of thick and thin filaments. RT-PCR analysis revealed an increase in the transcription of several structural genes. Ectopic overexpression of CF2 in the developing IFM disrupts muscle formation. While our results indicate a role for CF2 as a direct negative regulator of the thin filament protein gene Actin 88F (Act88F), effects on levels of transcripts of myosin heavy chain (mhc) appear to be indirect. This role is in direct contrast to that described in the larval muscles, where CF2 activates structural gene expression. The variation in myofibril phenotypes of CF2 mutants suggest the CF2 may have separate functions in fine-tuning expression of structural genes to insure proper filament stoichiometry, and monitoring and/or controlling the final myofibril size
Prediction of peptide and protein propensity for amyloid formation
Understanding which peptides and proteins have the potential to undergo amyloid formation and what driving forces are responsible for amyloid-like fiber formation and stabilization remains limited. This is mainly because proteins that can undergo structural changes, which lead to amyloid formation, are quite diverse and share no obvious sequence or structural homology, despite the structural similarity found in the fibrils. To address these issues, a novel approach based on recursive feature selection and feed-forward neural networks was undertaken to identify key features highly correlated with the self-assembly problem. This approach allowed the identification of seven physicochemical and biochemical properties of the amino acids highly associated with the self-assembly of peptides and proteins into amyloid-like fibrils (normalized frequency of β-sheet, normalized frequency of β-sheet from LG, weights for β-sheet at the window position of 1, isoelectric point, atom-based hydrophobic moment, helix termination parameter at position j+1 and ΔGº values for peptides extrapolated in 0 M urea). Moreover, these features enabled the development of a new predictor (available at http://cran.r-project.org/web/packages/appnn/index.html) capable of accurately and reliably predicting the amyloidogenic propensity from the polypeptide sequence alone with a prediction accuracy of 84.9 % against an external validation dataset of sequences with experimental in vitro, evidence of amyloid formation
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