Actively evolving subglacial conduits and eskers initiate ice shelf channels at an Antarctic grounding line.

Ice-shelf channels are long curvilinear tracts of thin ice found on Antarctic ice shelves. Many of them originate near the grounding line, but their formation mechanisms remain poorly understood. Here we use ice-penetrating radar data from Roi Baudouin Ice Shelf, East Antarctica, to infer that the morphology of several ice-shelf channels is seeded upstream of the grounding line by large basal obstacles indenting the ice from below. We interpret each obstacle as an esker ridge formed from sediments deposited by subglacial water conduits, and calculate that the eskers' size grows towards the grounding line where deposition rates are maximum. Relict features on the shelf indicate that these linked systems of subglacial conduits and ice-shelf channels have been changing over the past few centuries. Because ice-shelf channels are loci where intense melting occurs to thin an ice shelf, these findings expose a novel link between subglacial drainage, sedimentation and ice-shelf stability.

Techniques for automated local activation time annotation and conduction velocity estimation in cardiac mapping.

Measurements of cardiac conduction velocity provide valuable functional and structural insight into the initiation and perpetuation of cardiac arrhythmias, in both a clinical and laboratory context. The interpretation of activation wavefronts and their propagation can identify mechanistic properties of a broad range of electrophysiological pathologies. However, the sparsity, distribution and uncertainty of recorded data make accurate conduction velocity calculation difficult. A wide range of mathematical approaches have been proposed for addressing this challenge, often targeted towards specific data modalities, species or recording environments. Many of these algorithms require identification of activation times from electrogram recordings which themselves may have complex morphology or low signal-to-noise ratio. This paper surveys algorithms designed for identifying local activation times and computing conduction direction and speed. Their suitability for use in different recording contexts and applications is assessed.

Annexin-1-deficient mice exhibit spontaneous airway hyperresponsiveness and exacerbated allergen-specific antibody responses in a mouse model of asthma.

BACKGROUND: Glucocorticoids are the mainstream drugs used in the treatment and control of inflammatory diseases such as asthma. Annexin-1 (ANXA1) is an anti-inflammatory protein which has been described as an endogenous protein responsible for some anti-inflammatory glucocorticoid effects. Previous studies have identified its importance in other immune diseases such as rheumatoid arthritis and cystic fibrosis. ANXA1-deficient ((-/-)) mice are Th2 biased, and ANXA1 N-terminus peptide exhibits anti-inflammatory activity in a rat model of pulmonary inflammation. OBJECTIVE: ANXA1 protein is found in bronchoalveolar lavage fluid from asthmatics. However, the function of ANXA1 in the pathological development of allergy or asthma is unclear. Thus, in this study we intended to examine the effect of ANXA1 deficiency on allergen-specific antibody responses and airway responses to methacholine (Mch). METHODS: ANXA1(-/-) mice were sensitized with ovalbumin (OVA) and challenged with aerosolized OVA. Airway resistance, lung compliance and enhanced pause (PenH) were measured in naïve, sensitized and saline or allergen-challenged wild-type (WT) and ANXA1(-/-) mice. Total and allergen-specific antibodies were measured in the serum. RESULTS: We show that allergen-specific and total IgE, IgG2a and IgG2b levels were significantly higher in ANXA1(-/-) mice. Furthermore, naïve ANXA1(-/-) mice displayed higher airway hypersensitivity to inhaled Mch, and significant differences were also observed in allergen-sensitized and allergen-challenged ANXA1(-/-) mice compared with WT mice. CONCLUSIONS: In conclusion, ANXA1(-/-) mice possess multiple features characteristic to allergic asthma, such as airway hyperresponsiveness and enhanced antibody responses, suggesting that ANXA1 plays a critical regulatory role in the development of asthma. CLINICAL RELEVANCE: We postulate that ANXA1 is an important regulatory factor in the development of allergic disease and dysregulation of its expression can lead to pathological changes which may affect disease progression.

Honeybee venom secretory phospholipase A2 induces leukotriene production but not histamine release from human basophils.

The role of basophils in an anaphylactic response is well recognized but is usually masked by mast cells, which contain similar mediators for the induction of generalized vasodilatation and laryngeal constriction. The rapid onset of systemic anaphylactic symptoms, particularly in insect stings and ingested food, suggest that basophils, a circulating pool of cells containing histamine and other potent mediators such as leukotrienes, may be more involved in systemic anaphylaxis than originally thought. We wished to examine if secretory phospholipase A2, a systemic allergen found in honey bee venom (HBV-sPLA2) may activate basophils directly leading to rapid systemic mediator release. Basophils were isolated from human blood and stimulated with increasing concentrations of HBV-sPLA2. We found that physiological concentrations of HBV-sPLA2 induce rapid leukotriene C4 production from purified human basophils within 5 min, while interleukin (IL)-4 expression and production was induced at later time-points. Histamine release was not induced, signifying that HBV-sPLA2 did not induce generalized degranulation. Surface expression of CD63, CD69 and CD11b were up-regulated following HBV-sPLA2 treatment. Stimulation of basophils with anti-immunoglobulin E (IgE) following treatment with HBV-sPLA2 did not induce more leukotriene release. To investigate the mechanism of leukotriene production, 9-12 octadecadiynioc acid, a cyclooxygenase-1 (COX-1) and 15-lipoxygenase inhibitor, was used and this abrogated leukotriene production. These results indicate that HBV-sPLA2 can directly activate human basophils in vitro to induce leukotriene production.

Transcriptional feedback loop regulation, function, and ontogeny in Drosophila.

The Drosophila circadian oscillator is composed of interlocked period/timeless (per/tim) and Clock (Clk) transcriptional feedback loops. These feedback loops drive rhythmic transcription having peaks at dawn and dusk during the daily cycle and function in the brain and a variety of peripheral tissues. To understand how the circadian oscillator keeps time and controls metabolic, physiological, and behavioral rhythms, we must determine how these feedback loops regulate rhythmic transcription, determine the relative importance of the per/tim and Clk feedback loops with regard to circadian oscillator function, and determine how these feedback loops come to be expressed in only certain tissues. Substantial insight into each of these issues has been gained from experiments performed in our lab and others and is summarized here.

Relationship between adequacy of dialysis and nutritional status, and their impact on patient survival on CAPD in Hong Kong.

OBJECTIVE: Superior patient survival on continuous ambulatory peritoneal dialysis (CAPD) with 3 x 2-L exchanges has been reported from Hong Kong. This study examined the relationship between indices of dialysis adequacy and nutrition and patient survival on CAPD in Hong Kong. DESIGN: A cross-sectional study on prevalent CAPD patients. Patients were assessed for indices of dialysis adequacy and nutritional status with a composite nutritional index (CNI). Patients were then followed for 24 months. Survival data were analyzed according to adequacy indices and nutritional status. SETTING: All prevalent CAPD patients in nine dialysis centers in Hong Kong as of 1 April 1996. MAIN OUTCOME MEASURE: Mortality. RESULTS: 937 patients were assessed: 68.2% were using 3 x 2-L exchanges per day; mean age was 54.6 +/- 13 years. Mean total Kt/V was 1.83 +/- 0.42 and total creatinine clearance was 55.6 +/- 19.5 L/week/1.73 m2. 19% of patients were moderately to severely malnourished according to the CNI. There was no significant correlation between indices of adequacy and serum albumin or CNI. The 1- and 2-year patient survival from the time of assessment was 90.9% and 79.8%. There was a trend toward better survival in patients with Kt/V greater than 2.0, but it was not statistically significant. Peritoneal Kt/V did not impact survival in anuric patients. Malnourished patients had poorer survival than patients who were better nourished (p = 0.0259). After adjusting for age and diabetes, CNI was predictive of mortality but Kt/V and creatinine clearance were not. CONCLUSIONS: This study demonstrates the importance of nutritional status over adequacy indices in predicting patient survival. There was a lack of correlation between nutritional status and conventional indices of dialysis adequacy.

Modifying psychotropic drug prescription patterns: a follow-up survey.

Cross-sectional surveys of prescription patterns of psychotropic drugs provide a quick, global estimation of the appropriateness of psychopharmacotherapy. Recurrent inadequacies in prescribing for psychiatric patients include polypharmacy, high doses of antipsychotics (APS), the use of multiple APS simultaneously, and the administration of these drugs in multiple divided doses. Faulty prescribing patterns are difficult to amend. Following a survey in a rehabilitation facility for chronic psychiatric patients, a systematic education program and other measures were introduced to improve prescribing habits. Two years later the survey was repeated. Significant improvements were detected in the following areas: reductions in the doses of APS and antiparkinsonian (AP) drugs, reductions in the number of patients placed on these drugs, and reductions in the percentage of patients receiving multiple antipsychotics simultaneously. Despite these reductions in doses of psychotropic agents, patients' rehabilitative potential was not compromised.

A survey of antipsychotic treatment for schizophrenia in Hong Kong.

OBJECTIVE: To obtain information on prescription pattern of antipsychotic drugs for schizophrenic in-patients treated in public hospitals in Hong Kong. Four main areas of antipsychotic treatment are reported in this paper: (1) doses of antipsychotic drugs, (2) the practice of giving multiple antipsychotic agents simultaneously, (3) use of antipsychotics in divided daily doses and (4) co-administration of antipsychotic and antiparkinson drugs. METHODS: A cross-sectional survey of prescriptions of antipsychotic medication for a representative sample of 957 schizophrenic in-patients was conducted on a randomly chosen census day. Questionnaire items included basic demographic and clinical data, as well as inventory for all medications received by patients on census day. RESULTS: The mean antipsychotic dose was 854 +/- 759 (median: 600; range) 0-4450) mg CPZeq. Over two-third of the patients were given more than drug concurrently while less than 20% received the medication in multiple divided doses. Antiparkinson drugs were prescribed with antipsychotic medication in 69.61%, of the subjects. There were few differences between acute and chronic patients with respect to their respective prescription patterns. CONCLUSIONS: Antipsychotic treatment of schizophrenic inpatients in Hong Kong is largely in accord with international standards. Problematic areas identified for closer scrutiny include the concurrent use of more than one antipsychotic drug for both acute and chronic patients, and the higher than recommended doses for antipsychotic drugs and frequent use of antiparkinson medication for chronic patients. Dissemination of these results, accompanied by continuing medical education about psychopharmacology, are planned to further improve the quality of treatment for schizophrenic patients.