Response of Phytoplankton Photophysiology to Varying Environmental Conditions in the Sub-Antarctic and Polar Frontal Zone

Climate-driven changes are expected to alter the hydrography of the Sub-Antarctic Zone (SAZ) and Polar Frontal Zone (PFZ) south of Australia, in which distinct regional environments are believed to be responsible for the differences in phytoplankton biomass in these regions. Here, we report how the dynamic influences of light, iron and temperature, which are responsible for the photophysiological differences between phytoplankton in the SAZ and PFZ, contribute to the biomass differences in these regions. High effective photochemical efficiency of photosystem II (F 0 q/F 0 mw0.4), maximum photosynthesis rate (PB max), light-saturation intensity (Ek), maximum rate of photosynthetic electron transport (1/tPSII), and low photoprotective pigment concentrations observed in the SAZ correspond to high chlorophyll a and iron concentrations. In contrast, phytoplankton in the PFZ exhibits low F 0 q/F 0 m (* 0.2) and high concentrations of photoprotective pigments under low light environment. Strong negative relationships between iron, temperature, and photoprotective pigments demonstrate that cells were producing more photoprotective pigments under low temperature and iron conditions, and are responsible for the low biomass and low productivity measured in the PFZ. As warming and enhanced iron input is expected in this region, this could probably increase phytoplankton photosynthesis in this region. However, complex interactions between the biogeochemical processes (e.g. stratification caused by warming could prevent mixing of nutrients), which control phytoplankton biomass and productivity, remain uncertain

Azithromycin treatment modifies airway and blood gene expression networks in neutrophilic COPD.

Long-term, low-dose azithromycin reduces exacerbation frequency in chronic obstructive pulmonary disease (COPD), yet the mechanism remains unclear. This study characterised genome-wide gene expression changes in patients with neutrophilic COPD following long-term, low-dose azithromycin treatment. Patients with neutrophilic COPD (>61% or >162×104 cells per mL sputum neutrophils) were randomised to receive either azithromycin or placebo for 12 weeks. Sputum and blood were obtained before and after 12 weeks of treatment. Gene expression was defined using microarrays. Networks were analysed using the Search Tool for the Retrieval of Interacting Gene database. In sputum, 403 genes were differentially expressed following azithromycin treatment (171 downregulated and 232 upregulated), and three following placebo treatment (one downregulated and two upregulated) compared to baseline (adjusted p1.5). In blood, 138 genes were differentially expressed with azithromycin (121 downregulated and 17 upregulated), and zero with placebo compared to baseline (adjusted p1.3). Network analysis revealed one key network in both sputum (14 genes) and blood (46 genes), involving interferon-stimulated genes, human leukocyte antigens and genes regulating T-cell responses. Long-term, low-dose azithromycin is associated with downregulation of genes regulating antigen presentation, interferon and T-cell responses, and numerous inflammatory pathways in the airways and blood of neutrophilic COPD patients

Canine distemper virus neutralization activity is low in human serum and it is sensitive to an amino acid substitution in the hemagglutinin protein

© 2015 Elsevier Inc.Serum was analyzed from 146 healthy adult volunteers in eastern Africa to evaluate measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb) prevalence and potency. MV plaque reduction neutralization test (PRNT) results indicated that all sera were positive for MV nAbs. Furthermore, the 50% neutralizing dose (ND50) for the majority of sera corresponded to antibody titers induced by MV vaccination. CDV nAbs titers were low and generally were detected in sera with high MV nAb titers. A mutant CDV was generated that was less sensitive to neutralization by human serum. The mutant virus genome had 10 nucleotide substitutions, which coded for single amino acid substitutions in the fusion (F) and hemagglutinin (H) glycoproteins and two substitutions in the large polymerase (L) protein. The H substitution occurred in a conserved region involved in receptor interactions among morbilliviruses, implying that this region is a target for cross-reactive neutralizing antibodies

A parametric level-set method for partially discrete tomography

This paper introduces a parametric level-set method for tomographic reconstruction of partially discrete images. Such images consist of a continuously varying background and an anomaly with a constant (known) grey-value. We represent the geometry of the anomaly using a level-set function, which we represent using radial basis functions. We pose the reconstruction problem as a bi-level optimization problem in terms of the background and coefficients for the level-set function. To constrain the background reconstruction we impose smoothness through Tikhonov regularization. The bi-level optimization problem is solved in an alternating fashion; in each iteration we first reconstruct the background and consequently update the level-set function. We test our method on numerical phantoms and show that we can successfully reconstruct the geometry of the anomaly, even from limited data. On these phantoms, our method outperforms Total Variation reconstruction, DART and P-DART.Comment: Paper submitted to 20th International Conference on Discrete Geometry for Computer Imager

Learning the subtle dance: the experience of therapists who deliver mentalisation-based therapy for borderline personality disorder

Objectives: This study aimed to understand therapists’ lived experiences of delivering mentalisation-based therapy (MBT), including their experiences of service user change. / Method: One-to-one semi-structured interviews or focus groups were conducted with 14 MBT therapists and analysed using interpretative phenomenological analysis (IPA). / Results: Four superordinate themes were identified: 1) experiencing the challenges and complexities of being with service users during MBT; 2) being on a journey of discovery and change; 3) being an MBT therapist: a new way of working and developing a new therapeutic identity; and 4) being a therapist in the group: seeing it all come together / Conclusion: Our findings highlight the complexity, challenges and individualised experience of working therapeutically with service users with a diagnosis of BPD. The study provides a perspective of service use change that is enriched by idiosyncrasies within the therapeutic encounter. We conclude with a consideration of implications for MBT research and clinical practice

Increased homozygosity in the first Hispanic patient with plantar lipomatosis, unusual facies, and developmental delay (Pierpont syndrome): a case report

BACKGROUND: Pierpont syndrome was first described in 1998 with key characteristics including developmental delay, dysmorphic facial features, fat pads on hands and feet, and feeding difficulties. To date the mechanism of inheritance is unknown. Nine out of ten previously described patients with Pierpont syndrome were boys. This is the first report of a case of a non-white patient with Pierpont syndrome and she is the second female patient to be described as having Pierpont syndrome. CASE PRESENTATION: Our patient is a 16-month-old Hispanic girl with extreme developmental delay, microcephaly, large ears, short and thick upper lip, broad philtrum, widely spaced teeth, constipation, dysphagia, fat pads on feet and hands, autistic behavior and seizure-like episodes. She had a normal karyotype (46,XX), and array testing showed greater than 8 % homozygosity with otherwise normal results. Genes within these areas of homozygosity may provide clues to an etiology and suggest autosomal recessive inheritance. This case report highlights the possibility of ethnic variations in this syndrome’s presentation, which may have ramifications in uncovering the pathogenesis as well as expanding the phenotype. CONCLUSION: Pierpont syndrome should be considered in the evaluation of children with the described features, regardless of their gender and ethnicity

Safety, tolerability, and impact on allergic inflammation of autologous E.coli autovaccine in the treatment of house dust mite asthma - a prospective open clinical trial

Background: Asthma is increasing worldwide and results from a complex immunological interaction between genetic susceptibility and environmental factors. Autovaccination with E. coli induces a strong TH-1 immune response, thus offering an option for the treatment of allergic diseases. Methods: Prospective open trial on safety, tolerability, and impact on allergic inflammation of an autologous E.coli autovaccine in intermittent or mild persistent house dust mite asthma. Determination of exhaled nitric monoxide (eNO) before and after bronchial mite challenge initially and after nine months of autovaccination. Results: Median eNO increase after autovaccination was significantly smaller (from 27.3 to 33.8 ppb; p=0.334) compared to initial values (from 32.6 to 42.2 ppb; p=0.046) (p=0.034). In nine subjects and a total of 306 injections, we observed 101 episodes of local erythema (33.3%; median of maximal diameter 2.5 cm), 95 episodes of local swelling (31.1%; median of maximal diameter 3 cm), and 27 episodes of local pain (8.8%). Four subjects reported itching at the injection site with a total of 30 episodes (9.8%). We observed no serious adverse events. All organ functions (inclusive electrocardiogramm) and laboratory testing of the blood (clinical chemistry, hematology) and the urine (screening test, B-microglobuline) were within normal limits. Vital signs undulated within the physiological variability. Conclusion: The administration of autologous autovacine for the treatment of house dust mite asthma resulted in a reduction of the eNO increase upon bronchial mite challenge. In nine subjects and 306 injections, only a few mild local reactions and no systemic severe adverse events were observed. EudraCT Nr. 2005-005534-12 ClinicalTrials.gov ID NCT0067720

Human TRPC5 structures reveal interaction of a xanthine-based TRPC1/4/5 inhibitor with a conserved lipid binding site

TRPC1/4/5 channels are non-specific cation channels implicated in a wide variety of diseases, and TRPC1/4/5 inhibitors have recently entered clinical trials. However, fundamental and translational studies require a better understanding of TRPC1/4/5 channel regulation by endogenous and exogenous factors. Although several potent and selective TRPC1/4/5 modulators have been reported, the paucity of mechanistic insights into their modes-of-action remains a barrier to the development of new chemical probes and drug candidates. Xanthine-based modulators include the most potent and selective TRPC1/4/5 inhibitors described to date, as well as TRPC5 activators. Our previous studies suggest that xanthines interact with a, so far, elusive pocket of TRPC1/4/5 channels that is essential to channel gating. Here we report the structure of a small-molecule-bound TRPC1/4/5 channel—human TRPC5 in complex with the xanthine Pico145—to 3.0 Å. We found that Pico145 binds to a conserved lipid binding site of TRPC5, where it displaces a bound phospholipid. Our findings explain the mode-of-action of xanthine-based TRPC1/4/5 modulators, and suggest a structural basis for TRPC1/4/5 modulation by endogenous factors such as (phospho)lipids and Zn2+ ions. These studies lay the foundations for the structure-based design of new generations of TRPC1/4/5 modulators

A review of RCTs in four medical journals to assess the use of imputation to overcome missing data in quality of life outcomes

Background: Randomised controlled trials (RCTs) are perceived as the gold-standard method for evaluating healthcare interventions, and increasingly include quality of life (QoL) measures. The observed results are susceptible to bias if a substantial proportion of outcome data are missing. The review aimed to determine whether imputation was used to deal with missing QoL outcomes. Methods: A random selection of 285 RCTs published during 2005/6 in the British Medical Journal, Lancet, New England Journal of Medicine and Journal of American Medical Association were identified. Results: QoL outcomes were reported in 61 (21%) trials. Six (10%) reported having no missing data, 20 (33%) reported ≤ 10% missing, eleven (18%) 11%–20% missing, and eleven (18%) reported >20% missing. Missingness was unclear in 13 (21%). Missing data were imputed in 19 (31%) of the 61 trials. Imputation was part of the primary analysis in 13 trials, but a sensitivity analysis in six. Last value carried forward was used in 12 trials and multiple imputation in two. Following imputation, the most common analysis method was analysis of covariance (10 trials). Conclusion: The majority of studies did not impute missing data and carried out a complete-case analysis. For those studies that did impute missing data, researchers tended to prefer simpler methods of imputation, despite more sophisticated methods being available.The Health Services Research Unit is funded by the Chief Scientist Office of the Scottish Government Health Directorate. Shona Fielding is also currently funded by the Chief Scientist Office on a Research Training Fellowship (CZF/1/31)

A review of RCTs in four medical journals to assess the use of imputation to overcome missing data in quality of life outcomes

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