Increasing stair climbing in a train station: effects of contextual variables and visibility

Accumulation of physical activity during daily living is a current public health target that is influenced by the layout of the built environment. This study reports how the layout of the environment may influence responsiveness to an intervention. Pedestrian choices (n = 41 717) between stairs and the adjacent escalators were monitored for seven weeks in a train station (Birmingham, UK). After a 3.5 week baseline period, a stair riser banner intervention to increase stair climbing was installed on two staircases adjacent to escalators and monitoring continued for a further 3.5 weeks. Logistic regression analyses revealed that the visibility of the intervention, defined as the area of visibility in the horizontal plane opposite to the direction of travel (termed the isovist) had a major effect on success of the intervention. Only the largest isovist produced an increase in stair climbing (isovist=77.6 m2, OR = 1.10, CIs 1.02-1.19; isovist=40.7 m2, OR = 0.98, CIs 0.91-1.06; isovist=53.2 m2, OR = 1.00, CIs 0.95-1.06). Additionally, stair climbing was more common during the morning rush hour (OR = 1.56, CIs 1.80-2.59) and at higher levels of pedestrian traffic volume (OR = 1.92, CIs 1.68-2.21). The layout of the intervention site can influence responsiveness to point-of-choice interventions. Changes to the design of train stations may maximize the choice of the stairs at the expense of the escalator by pedestrians leaving the station.

Structure-function analysis of the human TFIIB-related factor II protein reveals an essential role for the C-terminal domain in RNA polymerase III transcription.

The transcription factors TFIIB, Brf1, and Brf2 share related N-terminal zinc ribbon and core domains. TFIIB bridges RNA polymerase II (Pol II) with the promoter-bound preinitiation complex, whereas Brf1 and Brf2 are involved, as part of activities also containing TBP and Bdp1 and referred to here as Brf1-TFIIIB and Brf2-TFIIIB, in the recruitment of Pol III. Brf1-TFIIIB recruits Pol III to type 1 and 2 promoters and Brf2-TFIIIB to type 3 promoters such as the human U6 promoter. Brf1 and Brf2 both have a C-terminal extension absent in TFIIB, but their C-terminal extensions are unrelated. In yeast Brf1, the C-terminal extension interacts with the TBP/TATA box complex and contributes to the recruitment of Bdp1. Here we have tested truncated Brf2, as well as Brf2/TFIIB chimeric proteins for U6 transcription and for assembly of U6 preinitiation complexes. Our results characterize functions of various human Brf2 domains and reveal that the C-terminal domain is required for efficient association of the protein with U6 promoter-bound TBP and SNAP(c), a type 3 promoter-specific transcription factor, and for efficient recruitment of Bdp1. This in turn suggests that the C-terminal extensions in Brf1 and Brf2 are crucial to specific recruitment of Pol III over Pol II.

The DNA-binding domain (DBD) is essential for NR2E3 dimerization and interaction with Crx

Purpose:NR2E3 (PNR) is an orphan nuclear receptor essential for proper photoreceptor determination and differentiation. In humans, mutations in NR2E3 have been associated with the recessively inherited enhanced short wavelength sensitive (S-) cone syndrome (ESCS) and, more recently, with autosomal dominant retinitis pigmentosa (adRP). NR2E3 acts in concert with the transcription factors Crx and Nrl to repress cone-specific genes and activate rod-specific genes. NR2E3 and Crx have been shown to physically interact by their DNA-binding domain (DBD), which may also be implicated in the dimerization process of the nuclear receptor. However, neither NR2E3 homodimerization nor NR2E3/Crx complex formation has been investigated in detail. Methods:In this present work, we analyzed the dimerization of the NR2E3 protein and its interaction with Crx by bioluminescence resonance energy transfer (BRET2) which utilizes Renilla luciferase (hRluc) protein and its substrate DeepBlueC as an energy donor and a mutant green fluorescent protein (GFP2) as the acceptor. We investigated, on whole intact cells, the role of NR2E3 DBD-mutations in dimerization and association with Crx. Results:We clearly showed that NR2E3 formed homodimers in HEK-293T cells. Moreover, all causative NR2E3 mutations present in the DBD of the protein showed an alteration in dimerization, except for the R76Q and the R104W mutants. Interestingly, the adRP-linked G56R mutant was the only DBD-NR2E3 mutant that showed a correct interaction with Crx. Finally, we observed a decrease in rhodospin gene transactivation for all DBD-NR2E3 mutants tested and no potentiation for the adRP-linked G56R mutant. In addition, the p.G56R mutant enhanced the transrepression of M-opsin promoter, while all other DBD-NR2E3 mutants did not repress M-opsin transactivation. Conclusions:A defect, either in the dimer formation or in the interaction of NR2E3 with Crx, leads to abnormal transcriptional activity on rhodopsin and M-opsin promoter and to an atypical retinal development; while the titration of Crx by p.G56R-NR2E3 leads to low levels of rhodopsin and M-opsin expression and may be responsible for the strong adRP phenotype.

Proposal of three thermodynamic variables to discriminate between storms associated with hail and storms with intense rainfall in Catalonia (Proposta de tres variables termodinàmiques per discriminar entre tempestes amb pedregades i tempestes amb pluges intenses)

Between late spring and early fall, the development of storms is common in Catalonia. Despite the fact that they usually produce heavy showers of short duration, they can also involve severe weather with ice pellets or hail. While the latter usually affect inland regions, and there are numerous publications on these cases; the analysis of events affecting the coast and causing damage to public and private properties is not so well developed. The aim of this study is to provide additional thermodynamic indicators that help differentiate storms with hail from storms without hail, considering cases that have affected various regions of Catalonia, mainly coastal areas. The aim is to give more information to improve prognosis and the ability to detail information in these situations. The procedure developed involved the study of several episodes of heavy rainfall and hail that hit Catalonia during the 2003-2009 period, mainly in the province of Girona, and validated the proposal during the campaign of late summer and fall of 2009, as well as 2012. For each case, several variables related to temperature, humidity and wind were analyzed at different levels of the atmosphere, while the information provided by the radio sounding in Barcelona was also taken into account. From this study, it can be concluded that the temperature difference between 500 hPa and 850 hPa, the humidity in the lower layers of the atmosphere and the LI index are good indicators for the detection of storms with associated hail.

Introduction of snow and geomorphic disturbance variables into predictive models of alpine plant distribution in the Western Swiss Alps

Indirect topographic variables have been used successfully as surrogates for disturbance processes in plant species distribution models (SDM) in mountain environments. However, no SDM studies have directly tested the performance of disturbance variables. In this study, we developed two disturbance variables: a geomorphic index (GEO) and an index of snow redistribution by wind (SNOW). These were developed in order to assess how they improved both the fit and predictive power of presenceabsence SDM based on commonly used topoclimatic (TC) variables for 91 plants in the Western Swiss Alps. The individual contribution of the disturbance variables was compared to TC variables. Maps of models were prepared to spatially test the effect of disturbance variables. On average, disturbance variables significantly improved the fit but not the predictive power of the TC models and their individual contribution was weak (5.6% for GEO and 3.3% for SNOW). However their maximum individual contribution was important (24.7% and 20.7%). Finally, maps including disturbance variables (i) were significantly divergent from TC models in terms of predicted suitable surfaces and connectivity between potential habitats, and (ii) were interpreted as more ecologically relevant. Disturbance variables did not improve the transferability of models at the local scale in a complex mountain system, and the performance and contribution of these variables were highly species-specific. However, improved spatial projections and change in connectivity are important issues when preparing projections under climate change because the future range size of the species will determine the sensitivity to changing conditions.

Effect of an ectoparasite on reproduction in great tits.

1. The effect of a haematophageous ectoparasite, the hen flea, on quality an number of offspring was experimentally investigated in the great tit. The experiment consisted of a controlled infestation of a random sample of nests with the parasitic flea and of a regular treatment of control nests with Microwaves in order to eliminate the naturally occurring fleas. 2. To assess the effects of fleas on variables related to offspring number, we considered the number of hatchlings and fledglings, the mortality between hatching and fledging, and the hatching and fledging success. For assessment of offspring quality, we measured body mass, tarsus and wing length, and calculated the nutritional condition of, nestlings as the ratio of body mass to tarsus length. A physiological variable, the haematocrit level, was also measured. 3. Hatching success and hatchling numbers did not differ between the two experimental groups. Offspring mortality between hatching and fledging was significantly higher in the infested broods (xBAR = 0.22 chicks dead per day) than in the parasite-free broods (xBAR = 0.07 dead per day). Fledging success was 83% in the parasite-free broods, but only 53% in the infested ones. The number of fledglings in infested broods (xBAR = 3.7 fledglings +/-2.1 SD) was significantly lower than in the parasite-free (xBAR = 4.9 +/- 1.1 SD) broods. 4. Body mass of chicks in the infested broods was significantly smaller than in the parasite-free broods both 14 days and 17 days after hatching. The chicks in the infested broods reached a significantly smaller tarsus length than the ones in the parasite-free broods. Close to fledging, the nutritional condition of chicks was significantly lower in infested broods. Haematocrit levels were significantly lower in the infested broods. 5. Brood size correlated differently with body mass and condition of chicks in infested and parasite-free nests. In parasite-free broods both body mass and condition of chicks at age 17 days, i.e. close to fledging, were significantly higher in small broods than in large ones. However, in the infested broods chicks were of the same body mass and condition in large as in small broods. Therefore, in parasite-free broods fitness can potentially be gained through offspring quality or number or both, whereas in infested broods it can be gained through offspring quantity only. In other words, a trade-off between quality and number of offspring is feasible only in the absence of the parasitic hen flea. 6. These results emphasize the need to study the effects of ectoparasites on ecological, behavioural and evolutionary traits of their bird hosts. A knowledge of these effects is essential for the understanding of population dynamics, behaviour and life-history traits of the hosts.

Variation in biomass related variables of reed canary grass

Selostus: Ruokohelven biomassan tuotantoon vaikuttavien ominaisuuksien vaihtelu

Lack of extended venous thromboembolism prophylaxis in high-risk patients undergoing major orthopaedic or major cancer surgery. Electronic Assessment of VTE Prophylaxis in High-Risk Surgical Patients at Discharge from Swiss Hospitals (ESSENTIAL).

Extended pharmacological venous thromboembolism (VTE) prophylaxis beyond discharge is recommended for patients undergoing high-risk surgery. We prospectively investigated prophylaxis in 1,046 consecutive patients undergoing major orthopaedic (70%) or major cancer surgery (30%) in 14 Swiss hospitals. Appropriate in-hospital prophylaxis was used in 1,003 (96%) patients. At discharge, 638 (61%) patients received prescription for extended pharmacological prophylaxis: 564 (77%) after orthopaedic surgery, and 74 (23%) after cancer surgery (p < 0.001). Patients with knee replacement (94%), hip replacement (81%), major trauma (80%), and curative arthroscopy (73%) had the highest prescription rates for extended VTE prophylaxis; the lowest rates were found in patients undergoing major surgery for thoracic (7%), gastrointestinal (19%), and hepatobiliary (33%) cancer. The median duration of prescribed extended prophylaxis was longer in patients with orthopaedic surgery (32 days, interquartile range 14-40 days) than in patients with cancer surgery (23 days, interquartile range 11-30 days; p<0.001). Among the 278 patients with an extended prophylaxis order after hip replacement, knee replacement, or hip fracture surgery, 120 (43%) received a prescription for at least 35 days, and among the 74 patients with an extended prophylaxis order after major cancer surgery, 20 (27%) received a prescription for at least 28 days. In conclusion, approximately one quarter of the patients with major orthopaedic surgery and more than three quarters of the patients with major cancer surgery did not receive prescription for extended VTE prophylaxis. Future effort should focus on the improvement of extended VTE prophylaxis, particularly in patients undergoing major cancer surgery.

The Glucocorticoid-induced leucine zipper (GILZ) Is essential for spermatogonial survival and spermatogenesis.

Spermatogenesis relies on the precise regulation of the self-renewal and differentiation of spermatogonia to provide a continuous supply of differentiating germ cells. The understanding of the cellular pathways regulating this equilibrium remains unfortunately incomplete. This investigation aimed to elucidate the testicular and ovarian functions of the glucocorticoid-induced leucine zipper protein (GILZ) encoded by the X-linked Tsc22d3 (Gilz) gene. We found that GILZ is specifically expressed in the cytoplasm of proliferating spermatogonia and preleptotene spermatocytes. While Gilz mutant female mice were fully fertile, constitutive or male germ cell-specific ablation of Gilz led to sterility due to a complete absence of post-meiotic germ cells and mature spermatozoa. Alterations were observed as early as postnatal day 5 during the first spermatogenic wave and included extensive apoptosis at the spermatogonial level and meiotic arrest in the mid-late zygotene stage. Overall, these data emphasize the essential role played by GILZ in mediating spermatogonial survival and spermatogenesis.

Mineralocorticoid receptor is essential for corticosteroid-induced up-regulation of L-type calcium currents in cultured neonatal cardiomyocytes.

Despite the fact that mineralocorticoid receptor (MR) antagonist drugs such as spironolactone and eplerenone reduce the mortality in heart failure patients, there is, thus far, no unambiguous demonstration of a functional role of MR in cardiac cells. The aim of this work was to investigate the activation pathway(s) mediating corticosteroid-induced up-regulation of cardiac calcium current (ICa). In this study, using neonatal cardiomyocytes from MR or glucocorticoid receptor (GR) knockout (KO) mice, we show that MR is essential for corticosteroid-induced up-regulation of ICa. This study provides the first direct and unequivocal evidence for MR function in the heart.

Determinants of the essential one-carbon metabolism metabolites, homocysteine, S-adenosylmethionine, S-adenosylhomocysteine and folate, in cerebrospinal fluid.

BACKGROUND: Disturbances in the levels of one-carbon (1C) metabolism metabolites have been associated with a wide variety of neuropsychiatric diseases. Cerebrospinal fluid (CSF) levels of homocysteine (Hcy) and the other 1C metabolites, nor their interrelatedness and putative determinants, have been studied extensively in a healthy population. METHODS: Plasma and CSF samples from 100 individuals free from neuropsychiatric diseases were analyzed (55 male, 45 female; age 50±17 years). In blood, we measured plasma Hcy, serum folate and serum vitamin B12. In CSF, we measured total Hcy, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) and 5-methyltetrahydrofolate (5-methylTHF). Highly selective analytical methods like liquid chromatography combined with either mass spectrometry or fluorescence detection were used. RESULTS: CSF Hcy was inversely correlated with CSF 5-methylTHF and positively with plasma Hcy, independent of serum folate status. CSF SAH correlated with age, lower CSF 5-methylTHF and higher CSF Hcy. CSF 5-methylTHF showed independent negative correlations with age and positive correlations with serum folate. CSF SAM did not correlate with any of the 1C metabolites. CONCLUSIONS: Aging is characterized by a reduction in CSF 5-methylTHF levels and increased CSF levels of the potentially neurotoxic transmethylation inhibitor SAH. CSF 5-methylTHF, which is itself determined in part by systemic folate status, is a powerful independent determinant of CSF levels of Hcy and SAH.

Callings in career: A typological approach to essential and optional components

A sense of calling in career is supposed to have positive implications for individuals and organizations but current theoretical development is plagued with incongruent conceptualizations of what does or does not constitute a calling. The present study used cluster analysis to identify essential and optional components of a presence of calling among 407 German undergraduate students from different majors. Three types of calling merged: "negative career self-centered", "pro-social religious", and "positive varied work orientation". All types could be described as vocational identity achieved (high commitment/high self-exploration), high in career confidence and career engagement. Not defining characteristics were centrality of work or religion, endorsement of specific work values, or positivity of core self-evaluations. The results suggest that callings entail intense self-exploration and might be beneficial because they correspond with identity achievement and promote career confidence and engagement while not necessarily having pro-social orientations. Suggestions for future research, theory and practice are suggested.

An essential role for transmembrane TNF in the resolution of the inflammatory lesion induced by Leishmania major infection.

TNF is an essential player in infections with Leishmania major, contributing to the control of the inflammatory lesion and, to a lesser degree, to parasite killing. However, the relative contribution of the soluble and transmembrane forms of TNF in these processes is unknown. To investigate the role of transmembrane TNF (mTNF) in the control of L. major infections, mTNF-knock-in (mTNF(Delta/Delta)) mice, which express functional mTNF but do not release soluble TNF, were infected with L. major, and the development of the inflammatory lesion and the immune response was compared to that occurring in L. major-infected TNF(-/-) and wild-type mice. mTNF(Delta/Delta) mice controlled the infection and resolved their inflammatory lesion as well as wild-type mice, a process associated with the early clearance of neutrophils at the site of parasite infection. In contrast, L. major-infected TNF(-/-) mice developed non-healing lesions, characterized by an elevated presence of neutrophils at the site of infection and partial control of parasite number within the lesions. Altogether, the results presented here demonstrate that mTNF, in absence of soluble TNF, is sufficient to control infection due to L. major, enabling the regulation of inflammation, and the optimal killing of Leishmania parasites at the site of infection.

Summer ozone cycles in the Lisbon metropolitan area and its relation to some meteorological variables

The aim of this work is to study the tropospheric ozone concentrations and daily peak cycles in the Lisbon MetropolitanArea (LMA) during the summer season (June, July and August, JJA) covering the 4-yr study period 2002-2005. Theresults show that all the stations have the same pattern: a minimum in the early morning followed by an increase at 1000UTC reaching to a peak at 1300-1400 UTC, dropped again to minimum values 1800 UTC but with different concentrationsdue to regional and local wind circulations and complex dynamic interactions. We identified in Lisbon city the ozone “weekendeffect”. Finally, we studied an episode of very high levels of tropospheric ozone and related daily ozone concentrationswith some meteorological variables.