Flow-directed PCA for monitoring networks.

Measurements recorded over monitoring networks often possess spatial and temporal correlation inducing redundancies in the information provided. For river water quality monitoring in particular, flow-connected sites may likely provide similar information. This paper proposes a novel approach to principal components analysis to investigate reducing dimensionality for spatiotemporal flow-connected network data in order to identify common spatiotemporal patterns. The method is illustrated using monthly observations of total oxidized nitrogen for the Trent catchment area in England. Common patterns are revealed that are hidden when the river network structure and temporal correlation are not accounted for. Such patterns provide valuable information for the design of future sampling strategies.

Nut allergy prevalence and differences between Asian-born children and Australian-born children of Asian descent: a state-wide survey of children at primary school entry in Victoria, Australia.

BACKGROUND: Asian infants born in Australia are three times more likely to develop nut allergy than non-Asian infants, and rates of challenge-proven food allergy in infants have been found to be unexpectedly high in metropolitan Melbourne. To further investigate the risk factors for nut allergy, we assessed the whole-of-state prevalence distribution of parent-reported nut allergy in 5-year-old children entering school. METHODS: Using the 2010 School Entrant Health Questionnaire administered to all 5-year-old children in Victoria, Australia, we assessed the prevalence of parent-reported nut allergy (tree nut and peanut) and whether this was altered by region of residence, socio-economic status, country of birth or history of migration. Prevalence was calculated as observed proportion with 95% confidence intervals (CI). Risk factors were evaluated using multivariable logistic regression and adjusted for appropriate confounders. RESULTS: Parent-reported nut allergy prevalence was 3.1% (95% CI 2.9-3.2) amongst a cohort of nearly 60 000 children. It was more common amongst children of mothers with higher education and socio-economic index and less prevalent amongst children in regional Victoria than in Melbourne. While children born in Australia to Asian-born mothers (aOR 2.67, 95% CI 2.28-3.27) were more likely to have nut allergy than non-Asian children, children born in Asia who subsequently migrated to Australia were at decreased risk of nut allergy (aOR 0.1, 95% CI 0.03-0.31). CONCLUSION: Migration from Asia after the early infant period appears protective for the development of nut allergy. Additionally, rural regions have lower rates of nut allergy than urban areas.

Evolving practice: X-linked agammaglobulinemia and lung transplantation.

X-linked agammaglobulinemia (XLA) is a rare primary humoral immunodeficiency syndrome characterized by agammaglobulinemia, recurrent infections and bronchiectasis. Despite the association with end-stage bronchiectasis, the literature on XLA and lung transplantation is extremely limited. We report a series of 6 XLA patients with bronchiectasis who underwent lung transplantation. Short-term outcomes were excellent however long-term outcomes were disappointing with a high incidence of pulmonary sepsis and chronic lung allograft dysfunction (CLAD).

Characterisation of an OCS-dependent severe asthma population treated with mepolizumab.

UNLABELLED: A subpopulation of patients with asthma treated with maximal inhaled treatments is unable to maintain asthma control and requires additional therapy with oral corticosteroids (OCS); a subset of this population continues to have frequent exacerbations. Alternate treatment options are needed as daily use of OCS is associated with significant systemic adverse effects that affect many body systems and have a direct association with the dose and duration of OCS use. We compared the population demographics, medical conditions and efficacy responses of the OCS-dependent group from the DREAM study of mepolizumab with the group not managed with daily OCS. TRIAL REGISTRATION NUMBER: NCT01000506.

Awake intubation and awake prone positioning of a morbidly obese patient for lumbar spine surgery.

We describe the awake fibreoptic intubation followed by awake prone positioning of a woman weighing 180 kg with body mass index of 62 kg.m(-2) requiring emergency lumbar discectomy for cauda equina syndrome. This approach was taken to overcome difficulties in transfering an anaesthetised patient on to the operating table. Following topical anaesthesia with lidocaine and low-dose remifentanil infusion, oral intubation was performed using a split oral airway to guide the fibrescope. The patient positioned herself on the Jackson operating table, following which general anaesthesia was induced. This technique optimised protection of the patient's eyes and other pressure areas while preventing undue cardiorespiratory compromise. The patient tolerated the procedure well, and later confirmed that she would consent to undergoing the same procedure again if further surgery became necessary.

Field reversed configuration confinement enhancement through edge biasing and neutral beam injection.

Field reversed configurations (FRCs) with high confinement are obtained in the C-2 device by combining plasma gun edge biasing and neutral beam injection. The plasma gun creates an inward radial electric field that counters the usual FRC spin-up. The n = 2 rotational instability is stabilized without applying quadrupole magnetic fields. The FRCs are nearly axisymmetric, which enables fast ion confinement. The plasma gun also produces E × B shear in the FRC edge layer, which may explain the observed improved particle transport. The FRC confinement times are improved by factors 2 to 4, and the plasma lifetimes are extended from 1 to up to 4 ms.

Palliative care for patients with chronic obstructive pulmonary disease: exploring the landscape.

Patients with chronic obstructive pulmonary disease experience a substantial symptom burden, high levels of psychosocial need and significant mortality. This epidemiological study reveals that the majority of patients are cared for in the public hospital system (64%) and generally die in hospital (72%) with a number of identifiable predictors of 6-month mortality. Our results suggest that palliative care services need to be redirected from a community-based admission focus to a model that is responsive to emergency and acute care hospital systems.

Negotiating hope with chronic obstructive pulmonary disease patients: a qualitative study of patients and healthcare professionals.

BACKGROUND: The information needs of patients with chronic obstructive pulmonary disease (COPD) towards the end of life are poorly understood. AIM: This study explored the views of patients with COPD and healthcare professionals, focusing upon information needs and treatment preferences. METHOD: In-depth, semi-structured interviews were held with patients with COPD following admission to hospital with respiratory failure, and focus groups held with healthcare professionals from hospital and community settings. RESULTS: Ten patients were interviewed, who had a median 4 previous hospital admissions, and had smoked for median 47 years. Five focus groups were held with 31 healthcare professionals (18 nurses, 7 doctors, 6 allied health). The theme underpinning all discussions was of tension between maintaining hope and negotiating the reality of the illness and its consequences. Within this theme, patients tended to be optimistic, viewed acute exacerbations as separate from their underlying chronic illness, and were keen for intensive treatments, including intubation if acutely unwell. They had little understanding of the complexities of decision-making around treatment escalation. Both patients and health workers believed that information around end of life should be offered routinely, but delivered in a manner that recognises and maintains a form of hope. CONCLUSION: Patients and healthcare professionals believe information around illness course, future goals and treatment is important to care. An expanded view of hope may assist when providing such information, including when discussing goals of care in the setting of advanced illness.

Transportin mediates nuclear entry of DNA in vertebrate systems.

Delivery of DNA to the cell nucleus is an essential step in many types of viral infection, transfection, gene transfer by the plant pathogen Agrobacterium tumefaciens and in strategies for gene therapy. Thus, the mechanism by which DNA crosses the nuclear pore complex (NPC) is of great interest. Using nuclei reconstituted in vitro in Xenopus egg extracts, we previously studied DNA passage through the nuclear pores using a single-molecule approach based on optical tweezers. Fluorescently labeled DNA molecules were also seen to accumulate within nuclei. Here we find that this import of DNA relies on a soluble protein receptor of the importin family. To identify this receptor, we used different pathway-specific cargoes in competition studies as well as pathway-specific dominant negative inhibitors derived from the nucleoporin Nup153. We found that inhibition of the receptor transportin suppresses DNA import. In contrast, inhibition of importin beta has little effect on the nuclear accumulation of DNA. The dependence on transportin was fully confirmed in assays using permeabilized HeLa cells and a mammalian cell extract. We conclude that the nuclear import of DNA observed in these different vertebrate systems is largely mediated by the receptor transportin. We further report that histones, a known cargo of transportin, can act as an adaptor for the binding of transportin to DNA.

Staff experiences of a reablement approach to care for older people in a regional Australian community: A qualitative study.

Reablement is described as a person-centred, goal-directed intervention with a view to regain, maintain or improve the independence of older clients. Although evidence to support the use of reablement as a multidisciplinary, home-based intervention for community-dwelling older adults is increasing, there is limited knowledge about what it means for care staff who provide client-based services. This study, which was nested in a larger program evaluation, used a descriptive qualitative approach to explore direct care staff and care coordinator experiences of translating a reablement training program into practice for older people in a regional Australian community. Two months after the training program four focus groups were conducted with 13 care coordinators to assimilate staff experiences with development of care plans, systems, processes and practices of reablement. In addition, four direct care staff took part in individual interviews, which centred on eliciting their experience using the reablement approach with clients. Results from the care coordinator focus groups and the direct care staff interviews highlight the importance of reablement staff training and the involvement of staff in the development and delivery of a reablement approach to client-centred care. A number of organisational and client-centred challenges such as communication, functional partnerships, staff education and resourcing are also uncovered in this research into the development of a reablement-focused care service in a regional setting. Overall there is support for the dominating discourse around healthy ageing and the policy approach of ageing in place to support wellness.

Dynamic formation of a hot field reversed configuration with improved confinement by supersonic merging of two colliding high-ß compact toroids.

A hot stable field-reversed configuration (FRC) has been produced in the C-2 experiment by colliding and merging two high-ß plasmoids preformed by the dynamic version of field-reversed θ-pinch technology. The merging process exhibits the highest poloidal flux amplification obtained in a magnetic confinement system (over tenfold increase). Most of the kinetic energy is converted into thermal energy with total temperature (T{i}+T{e}) exceeding 0.5 keV. The final FRC state exhibits a record FRC lifetime with flux confinement approaching classical values. These findings should have significant implications for fusion research and the physics of magnetic reconnection.

Exportins can inhibit major mitotic assembly events in vitro: membrane fusion, nuclear pore formation, and spindle assembly.

XENOPUS: egg extracts are a powerful in vitro tool for studying complex biological processes, including nuclear reconstitution, nuclear membrane and pore assembly, and spindle assembly. Extracts have been further used to demonstrate a moonlighting regulatory role for nuclear import receptors or importins on these cell cycle assembly events. Here we show that exportins can also play a role in these events. Addition of Crm1, Exportin-t, or Exportin-5 decreased nuclear pore assembly in vitro. RanQ69L-GTP, a constitutively active form of RanGTP, ameliorated inhibition. Both Crm1 and Exportin-t inhibited fusion of nuclear membranes, again counteracted by RanQ69L-GTP. In mitotic extracts, Crm1 and Exportin-t negatively impacted spindle assembly. Pulldowns from the extracts using Crm1- or Exportin-t-beads revealed nucleoporins known to be essential for both nuclear pore and spindle assembly, with RanQ69L-GTP decreasing a subset of these target interactions. This study suggests a model where exportins, like importins, can regulate major mitotic assembly events.

Streamflow greatly reduced by converting deciduous hardwood stands to pine.

Fifteen years after two experimental watersheds in the southern Appalachians had been converted from a mature deciduous hardwood cover to white pine, annual streamflow was reduced about 20 centimeters (20 percent) below that expected for the hardwood cover. Streamflow was reduced during every month, with the largest monthly reductions (1.5 to 3.5 centimeters) occurring in the dormant and early growing seasons.

Two mammalian genes transcribed from opposite strands of the same DNA locus.

This report describes the characterization of a genomic locus in the rat that encodes overlapping genes occupying both strands of the same piece of DNA. One gene (strand) encodes gonadotropin-releasing hormone (GnRH). A second gene, SH, is transcribed from the other DNA strand to produce RNA of undefined function. The RNAs transcribed from each DNA strand are spliced and polyadenylated, and share significant exon domains. GnRH is expressed in the central nervous system while SH transcripts are present in the heart. Thus, the genome of a mammalian organism encodes two distinct genes by using both strands of the same DNA.

Expression of a cloned rat brain potassium channel in Xenopus oocytes.

Potassium channels are ubiquitous membrane proteins with essential roles in nervous tissue, but little is known about the relation between their function and their molecular structure. A complementary DNA library was made from rat hippocampus, and a complementary DNA clone (RBK-1) was isolated. The predicted sequence of the 495-amino acid protein is homologous to potassium channel proteins encoded by the Shaker locus of Drosophila and differs by only three amino acids from the expected product of a mouse clone MBK-1. Messenger RNA transcribed from RBK-1 in vitro directed the expression of potassium channels when it was injected into Xenopus oocytes. The potassium current through the expressed channels resembles both the transient (or A) and the delayed rectifier currents reported in mammalian neurons and is sensitive to both 4-aminopyridine and tetraethylammonium.

The Nup107-160 nucleoporin complex is required for correct bipolar spindle assembly.

The Nup107-160 complex is a critical subunit of the nuclear pore. This complex localizes to kinetochores in mitotic mammalian cells, where its function is unknown. To examine Nup107-160 complex recruitment to kinetochores, we stained human cells with antisera to four complex components. Each antibody stained not only kinetochores but also prometaphase spindle poles and proximal spindle fibers, mirroring the dual prometaphase localization of the spindle checkpoint proteins Mad1, Mad2, Bub3, and Cdc20. Indeed, expanded crescents of the Nup107-160 complex encircled unattached kinetochores, similar to the hyperaccumulation observed of dynamic outer kinetochore checkpoint proteins and motors at unattached kinetochores. In mitotic Xenopus egg extracts, the Nup107-160 complex localized throughout reconstituted spindles. When the Nup107-160 complex was depleted from extracts, the spindle checkpoint remained intact, but spindle assembly was rendered strikingly defective. Microtubule nucleation around sperm centrosomes seemed normal, but the microtubules quickly disassembled, leaving largely unattached sperm chromatin. Notably, Ran-GTP caused normal assembly of microtubule asters in depleted extracts, indicating that this defect was upstream of Ran or independent of it. We conclude that the Nup107-160 complex is dynamic in mitosis and that it promotes spindle assembly in a manner that is distinct from its functions at interphase nuclear pores.

Neuronal adaptation to amphetamine and dopamine: molecular mechanisms of prodynorphin gene regulation in rat striatum.

Induction of prodynorphin gene expression by psychostimulant drugs may represent a compensatory adaptation to excessive dopamine stimulation and may contribute to the aversive aspects of withdrawal. We therefore investigated the molecular mechanisms by which dopamine psychostimulant drugs induce prodynorphin gene expression in vivo and in rat primary striatal cultures. We demonstrate that three recently described cAMP response elements (CREs), rather than a previously reported noncanonical AP-1 site, are critical for dopamine induction of the prodynorphin gene in striatal neurons. CRE-binding protein (CREB) binds to these CREs in striatal cell extracts and is phosphorylated on Ser-133 after dopamine stimulation in a D1 dopamine receptor-dependent manner. Surprisingly, following chronic administration of amphetamine, levels of phosphorylated CREB are increased above basal in rat striatum in vivo, whereas c-fos mRNA is suppressed below basal levels. D1 receptor-mediated CREB phosphorylation appears to mediate adaptations to psychostimulant drugs in the striatum.

Heteropolymeric potassium channels expressed in Xenopus oocytes from cloned subunits.

Voltage-dependent potassium currents were measured in Xenopus oocytes previously injected with RNAs generated in vitro from each of three cloned cDNAs (RBK1, RBK2, and RGK5). The currents differed in their sensitivities to blockade by tetraethylammonium (TEA; respective KDs 0.3, greater than 100, and 10 mM) and in their inactivation during a depolarizing pulse. Injections of RNA combinations (RBK1/RBK2 and RBK1/RGK5) caused currents that had TEA sensitivities different from those expected from the sum, in any proportion, of the two native channels. It is concluded that novel potassium channels are formed by the oocytes injected with two RNAs, presumably by heteropolymerization of subunits; such heteropolymerization would contribute functional diversity to voltage-dependent potassium channels in addition to that provided by a large gene family.