Tropopause level Rossby wave breaking in the Northern Hemisphere: a feature-based validation of the ECHAM5-HAM climate model

Breaking synoptic-scale Rossby waves (RWB) at the tropopause level are central to the daily weather evolution in the extratropics and the subtropics. RWB leads to pronounced meridional transport of heat, moisture, momentum, and chemical constituents. RWB events are manifest as elongated and narrow structures in the tropopause-level potential vorticity (PV) field. A feature-based validation approach is used to assess the representation of Northern Hemisphere RWB in present-day climate simulations carried out with the ECHAM5-HAM climate model at three different resolutions (T42L19, T63L31, and T106L31) against the ERA-40 reanalysis data set. An objective identification algorithm extracts RWB events from the isentropic PV field and allows quantifying the frequency of occurrence of RWB. The biases in the frequency of RWB are then compared to biases in the time mean tropopause-level jet wind speeds. The ECHAM5-HAM model captures the location of the RWB frequency maxima in the Northern Hemisphere at all three resolutions. However, at coarse resolution (T42L19) the overall frequency of RWB, i.e. the frequency averaged over all seasons and the entire hemisphere, is underestimated by 28%.The higher-resolution simulations capture the overall frequency of RWB much better, with a minor difference between T63L31 and T106L31 (frequency errors of −3.5 and 6%, respectively). The number of large-size RWB events is significantly underestimated by the T42L19 experiment and well represented in the T106L31 simulation. On the local scale, however, significant differences to ERA-40 are found in the higher-resolution simulations. These differences are regionally confined and vary with the season. The most striking difference between T106L31 and ERA-40 is that ECHAM5-HAM overestimates the frequency of RWB in the subtropical Atlantic in all seasons except for spring. This bias maximum is accompanied by an equatorward extension of the subtropical westerlies.

Intraobserver and interobserver agreement for results of low-field magnetic resonance imaging in dogs with and without clinical signs of disk-associated wobbler syndrome

OBJECTIVE: To determine interobserver and intraobserver agreement for results of low-field magnetic resonance imaging (MRI) in dogs with and without disk-associated wobbler syndrome (DAWS). DESIGN: Validation study. ANIMALS: 21 dogs with and 23 dogs without clinical signs of DAWS. PROCEDURES: For each dog, MRI of the cervical vertebral column was performed. The MRI studies were presented in a randomized sequence to 4 board-certified radiologists blinded to clinical status. Observers assessed degree of disk degeneration, disk-associated and dorsal compression, alterations in intraspinal signal intensity (ISI), vertebral body abnormalities, and new bone formation and categorized each study as originating from a clinically affected or clinically normal dog. Interobserver agreement was calculated for 44 initial measurements for each observer. Intraobserver agreement was calculated for 11 replicate measurements for each observer. RESULTS: There was good interobserver agreement for ratings of disk degeneration and vertebral body abnormalities and moderate interobserver agreement for ratings of disk-associated compression, dorsal compression, alterations in ISI, new bone formation, and suspected clinical status. There was very good intraobserver agreement for ratings of disk degeneration, disk-associated compression, alterations in ISI, vertebral body abnormalities, and suspected clinical status. There was good intraobserver agreement for ratings of dorsal compression and new bone formation. Two of 21 clinically affected dogs were erroneously categorized as clinically normal, and 4 of 23 clinically normal dogs were erroneously categorized as clinically affected. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that variability exists among observers with regard to results of MRI in dogs with DAWS and that MRI could lead to false-positive and false-negative assessments.

Genome-wide identification of quantitative trait loci in a cross between Hampshire and Landrace I: carcass traits

We report the identification of quantitative trait loci (QTL) affecting carcass composition, carcass length, fat deposition and lean meat content using a genome scan across 462 animals from a combined intercross and backcross between Hampshire and Landrace pigs. Data were analysed using multiple linear regression fitting additive and dominance effects. This model was compared with a model including a parent-of-origin effect to spot evidence of imprinting. Several precisely defined muscle phenotypes were measured in order to dissect body composition in more detail. Three significant QTL were detected in the study at the 1% genome-wide level, and twelve significant QTL were detected at the 5% genome-wide level. These QTL comprise loci affecting fat deposition and lean meat content on SSC1, 4, 9, 10, 13 and 16, a locus on SSC2 affecting the ratio between weight of meat and bone in back and weight of meat and bone in ham and two loci affecting carcass length on SSC12 and 17. The well-defined phenotypes in this study enabled us to detect QTL for sizes of individual muscles and to obtain information of relevance for the description of the complexity underlying other carcass traits.

Inhibition by interferon-gamma of human mononuclear cell-mediated low density lipoprotein oxidation. Participation of tryptophan metabolism along the kynurenine pathway

In this study we examined the potential inhibition by interferon-gamma (IFN gamma) of the early stages of low density lipoprotein (LDL) oxidation mediated by human peripheral blood mononuclear cells (PBMC) and monocyte-derived macrophages (MDM) in Ham's F-10 medium supplemented with physiological amounts of L-tryptophan (Trp). We assessed LDL oxidation by measuring the consumption of LDL's major antioxidant (i.e., alpha-tocopherol) and targets for oxidation (cholesteryllinoleate and cholesterylarachidonate), together with the accumulation of cholesterylester hydroperoxides and the increase in relative electrophoretic mobility of the lipoprotein particle. Exposure of PBMC or MDM to IFN gamma induced the degradation of extracellular Trp with concomitant accumulation of kynurenine, anthranilic and 3-hydroxyanthranilic acid (3HAA) in the culture medium. Formation of 3HAA, but neither Trp degradation nor formation of kynurenine and anthranilic acid, was inhibited by low amounts of diphenylene iodonium (DPI) in a concentration-dependent manner. In contrast to oxidative Trp metabolism, exposure of human PBMC or MDM to IFN gamma failed to induce degradation of arginine, and nitrite was not detected in the cell supernatant, indicating that nitric oxide synthase was not induced under these conditions. Incubation of LDL in Trp-supplemented F-10 medium resulted in a time-dependent oxidation of the lipoprotein that was accelerated in the presence of PBMC or MDM but inhibited strongly in the presence of both cells and IFN gamma, i.e., when Trp degradation and formation of 3HAA were induced. In contrast, when IFN gamma was added to PBMC or MDM in F-10 medium that was virtually devoid of Trp, inhibition of cell-accelerated LDL oxidation was not observed. Exogenous 3HAA added to PBMC or purified monocytes in the absence of IFN gamma also strongly and in a concentration-dependent manner inhibited LDL oxidation. Selective inhibition of IFN gamma-induced formation of 3HAA by DPI caused reversion of the inhibitory action of this cytokine on both PBMC- and MDM-mediated LDL oxidation. These results show that IFN gamma treatment of human PBMC or MDM in vitro attenuates the extent of LDL oxidation caused by these cells, and indicate that Trp degradation with formation of 3HAA is a major contributing factor to this inhibitory activity.

Pulmonary-artery pressure and exhaled nitric oxide in Bolivian and Caucasian high altitude dwellers

There is evidence that high altitude populations may be better protected from hypoxic pulmonary hypertension than low altitude natives, but the underlying mechanism is incompletely understood. In Tibetans, increased pulmonary respiratory NO synthesis attenuates hypoxic pulmonary hypertension. It has been speculated that this mechanism may represent a generalized high altitude adaptation pattern, but direct evidence for this speculation is lacking. We therefore measured systolic pulmonary-artery pressure (Doppler chocardiography) and exhaled nitric oxide (NO) in 34 healthy, middle-aged Bolivian high altitude natives and in 34 age- and sex-matched, well-acclimatized Caucasian low altitude natives living at high altitude (3600 m). The mean+/-SD systolic right ventricular to right atrial pressure gradient (24.3+/-5.9 vs. 24.7+/-4.9 mmHg) and exhaled NO (19.2+/-7.2 vs. 22.5+/-9.5 ppb) were similar in Bolivians and Caucasians. There was no relationship between pulmonary-artery pressure and respiratory NO in the two groups. These findings provide no evidence that Bolivian high altitude natives are better protected from hypoxic pulmonary hypertension than Caucasian low altitude natives and suggest that attenuation of pulmonary hypertension by increased respiratory NO synthesis may not represent a universal adaptation pattern in highaltitude populations.

Effect of ascent protocol on acute mountain sickness and success at Muztagh Ata, 7546 m

Bloch, Konrad E., Alexander J. Turk, Marco Maggiorini, Thomas Hess, Tobias Merz, Martina M. Bosch, Daniel Barthelmes, Urs Hefti, Jacqueline Pichler, Oliver Senn, and Otto D. Schoch. Effect of ascent protocol on acute mountain sickness and success at Muztagh Ata, 7546 m. High Alt. Med. Biol. 10:25-32, 2009.-Data on acclimatization during expedition-style climbing to > 5000 m are scant. We evaluated the hypothesis that minor differences in ascent protocol influence acute mountain sickness (AMS) symptoms and mountaineering success in climbers to Muztagh Ata (7546 m), Western China. We performed a randomized, controlled trial during a high altitude medical research expedition to Muztagh Ata. Thirty-four healthy mountaineers (mean age 45 yr, 7 women) were randomized to follow one of two protocols, ascending within 15 or 19 days to the summit of Muztagh Ata at 7546 m, respectively. The main outcome measures, AMS symptom scores and the number of proceeding climbers, were assessed daily. Mean +/- SD AMS-C scores of 16 climbers randomized to slow ascent were 0.06 +/- 0.18, 0.26 +/- 0.08, 0.41 +/- 0.45, 0.53 +/- 0.77 at camps I (5533 m), II (6265 m), III (6865 m), and the summit (7546 m), respectively. Corresponding values in 18 climbers randomized to fast ascent were significantly higher: 0.17 +/- 0.23, 0.43 +/- 0.75, 0.49 +/- 0.36, and 0.69 +/- 0.54 (p < 0.008, vs. slow ascent in regression analysis accounting for weather-related protocol deviation). Climbers randomized to slow ascent were able to ascend according to the protocol without AMS for significantly more days than climbers randomized to fast ascent (p = 0.04, Kaplan-Meier analysis). More climbers randomized to slow ascent were successful in reaching the highest camp at 6865 m without AMS (odds ratio 9.5; 95% confidence interval 1.02 to 89). In climbers ascending to very high altitudes, differences of a few days in acclimatization have a significant impact on symptom severity, the prevalence of AMS, and mountaineering success. ClinicalTrials.gov Identifier NCT00603122.

Mechanisms and drug therapy of pulmonary hypertension at high altitude

Pulmonary vasoconstriction represents a physiological adaptive mechanism to high altitude. If exaggerated, however, it is associated with important morbidity and mortality. Recent mechanistic studies using short-term acute high altitude exposure have provided insight into the importance of defective vascular endothelial and respiratory epithelial nitric oxide (NO) synthesis, increased endothelin-1 bioavailability, and overactivation of the sympathetic nervous system in causing exaggerated hypoxic pulmonary hypertension in humans. Based on these studies, drugs that increase NO bioavailability, attenuate endothelin-1 induced pulmonary vasoconstriction, or prevent exaggerated sympathetic activation have been shown to be useful for the treatment/prevention of exaggerated pulmonary hypertension during acute short-term high altitude exposure. The mechanisms underpinning chronic pulmonary hypertension in high altitude dwellers are less well understood, but recent evidence suggests that they differ in some aspects from those involved in short-term adaptation to high altitude. These differences have consequences for the choice of the treatment for chronic pulmonary hypertension at high altitude. Finally, recent data indicate that fetal programming of pulmonary vascular dysfunction in offspring of preeclampsia and children generated by assisted reproductive technologies represents a novel and frequent cause of pulmonary hypertension at high altitude. In animal models of fetal programming of hypoxic pulmonary hypertension, epigenetic mechanisms play a role, and targeting of these mechanisms with drugs lowers pulmonary artery pressure. If epigenetic mechanisms also are operational in the fetal programming of pulmonary vascular dysfunction in humans, such drugs may become novel tools for the treatment of hypoxic pulmonary hypertension.

Association between hospice care and psychological outcomes in Alzheimer's spousal caregivers.

CONTEXT Dementia care giving can lead to increased stress, physical and psychosocial morbidity, and mortality. Anecdotal evidence suggests that hospice care provided to people with dementia and their caregivers may buffer caregivers from some of the adverse outcomes associated with family caregiving in Alzheimer's Disease (AD). OBJECTIVES This pilot study examined psychological and physical outcomes among 32 spousal caregivers of patients with AD. It was hypothesized that caregivers who utilized hospice services would demonstrate better outcomes after the death of their spouse than caregivers who did not utilize hospice. METHODS The charts of all spousal caregivers enrolled in a larger longitudinal study from 2001 to 2006 (N=120) were reviewed, and participants whose spouse had died were identified. Of these, those who received hospice care (n=10) were compared to those who did not (n=22) for various physiological and psychological measures of stress, both before and after the death of the care recipient. An Analysis of Covariance (ANCOVA), with postdeath scores as the dependent variable and pre-death scores as covariates, was used for all variables. RESULTS Significant group differences were found in postdeath depressive symptoms (HAM-D; F(1,29)=6.10, p<0.05) and anxiety symptoms (HAM-A; F(1,29)=5.71, p<0.05). Most psychological outcome variables demonstrated moderate effect sizes with a Cohen's d of>0.5 between groups. CONCLUSIONS These data suggest that hospice enrollment may ameliorate the detrimental psychological effects in caregivers who have lost a spouse with Alzheimer's Disease. Based on these pilot data, further prospective investigation is warranted.

Shoot meristem maintenance is controlled by a GRAS-gene mediated signal from differentiating cells

Plant shoot development depends on the perpetuation of a group of undifferentiated cells in the shoot apical meristem (SAM). In the Petunia mutant hairy meristem (ham), shoot meristems differentiate postembryonically as continuations of the subtending stem. HAM encodes a putative transcription factor of the GRAS family, which acts non-cell-autonomously from L3-derived tissue of lateral organ primordia and stem provasculature. HAM acts in parallel with TERMINATOR (PhWUSCHEL) and is required for continued cellular response to TERMINATOR and SHOOTMERISTEMLESS (PhSTM). This reveals a novel mechanism by which signals from differentiating tissues extrinsically control stem cell fate in the shoot apex.

Oxidative Stress in Hypobaric Hypoxia and Influence on Vessel-Tone Modifying Mediators

Increased pulmonary artery pressure is a well-known phenomenon of hypoxia and is seen in patients with chronic pulmonary diseases, and also in mountaineers on high altitude expedition. Different mediators are known to regulate pulmonary artery vessel tone. However, exact mechanisms are not fully understood and a multimodal process consisting of a whole panel of mediators is supposed to cause pulmonary artery vasoconstriction. We hypothesized that increased hypoxemia is associated with an increase in vasoconstrictive mediators and decrease of vasodilatators leading to a vasoconstrictive net effect. Furthermore, we suggested oxidative stress being partly involved in changement of these parameters. Oxygen saturation (Sao2) and clinical parameters were assessed in 34 volunteers before and during a Swiss research expedition to Mount Muztagh Ata (7549 m) in Western China. Blood samples were taken at four different sites up to an altitude of 6865 m. A mass spectrometry-based targeted metabolomic platform was used to detect multiple parameters, and revealed functional impairment of enzymes that require oxidation-sensitive cofactors. Specifically, the tetrahydrobiopterin (BH4)-dependent enzyme nitric oxide synthase (NOS) showed significantly lower activities (citrulline-to-arginine ratio decreased from baseline median 0.21 to 0.14 at 6265 m), indicating lower NO availability resulting in less vasodilatative activity. Correspondingly, an increase in systemic oxidative stress was found with a significant increase of the percentage of methionine sulfoxide from a median 6% under normoxic condition to a median level of 30% (p<0.001) in camp 1 at 5533 m. Furthermore, significant increase in vasoconstrictive mediators (e.g., tryptophan, serotonin, and peroxidation-sensitive lipids) were found. During ascent up to 6865 m, significant altitude-dependent changes in multiple vessel-tone modifying mediators with excess in vasoconstrictive metabolites could be demonstrated. These changes, as well as highly significant increase in systemic oxidative stress, may be predictive for increase in acute mountain sickness score and changes in Sao2.

Measuring depression with a well-being index: Further evidence for the validity of the WHO Well-Being Index (WHO-5) as a measure of the severity of depression

BACKGROUND: In recent years, the WHO Wellbeing Index (WHO-5) has been used as a screening measure for depression. Nevertheless, research on the validity of this measure in the context of clinical depression is sparse. QUESTIONS: The aim of the present study was to investigate the measurement invariance of the WHO-5 across depressed and non-depressed individuals, as well as the shape and specificity of its relationship to measures of depression severity. METHOD: Of the 414 subjects who completed the WHO-5 and the Beck Depression Inventory-II (BDI-II), 207 had a diagnosis of a major depressive episode (MDE). A subsample also completed the Beck Anxiety Inventory (BAI) and was assessed by clinicians using the Hamilton Depression Rating Scale (HAM-D) and the Hamilton Anxiety Rating Scale (HAM-A). RESULTS: The WHO-5 demonstrated strong measurement invariance regarding the presence or absence of a current MDE. The WHO-5 showed a very high negative association with self- and observer-rated measures of depressive symptoms, especially in the range of mild to moderate symptoms. These associations were still substantial after controlling for measures of anxiety symptoms. LIMITATIONS: In addition to a diagnostic interview, only one measure for self- and observer-rated symptoms of depression was used. Furthermore, the observer-rated measure was only assessed in one subsample that exhibited a somewhat restricted range of depression severity. CONCLUSION: Although this index was originally designed as a measure of well-being, the results support the use of the WHO-5 in the context of depression research.

The influence of absorbed solar radiation by Saharan dust on hurricane genesis

To date, the radiative impact of dust and the Sahar an air layer (SAL) on North Atlantic hurricane activity is not yet known. According to previous studies, dust stabilizes the atmosphere due to absorption of solar radiation but thus shifts convection to regions more conducive for hurricane genesis. Here we analyze differences in hurricane genesis and frequency from ensemble sensitivity simulations with radiatively active and inactive dust in the aerosol-climate model ECHAM6-HAM. We investigate dust burden and other hurricane-related variables and determine their influence on disturbances which develop into hurricanes (developing disturbances, DDs) and those which do not (nondeveloping disturbances, NDDs). Dust and the SAL are found to potentially have both inhibiting and supporting influences on background conditions for hurricane genesis. A slight southward shift of DDs is determined when dust is active as well as a significant warming of the SAL, which leads to a strengthening of the vertical circulation associated with the SAL. The dust burden of DDs is smaller in active dust simulations compared to DDs in simulations with inactive dust, while NDDs contain more dust in active dust simulations. However, no significant influence of radiatively active dust on other variables in DDs and NDDs is found. Furthermore, no substantial change in the DD and NDD frequency due to the radiative effects of dust can be detected.