bluuebunny/crossref_metadata_2025_split huggingface dataset:
Airborne cultivable microflora and microbial transfer in farm buildings and rural dwellings
Authors: Normand Anne-Cécile , Sudre Bertrand , Vacheyrou Mallory , Depner Martin , Wouters Inge M , Noss Ilka , Heederik Dick , Hyvärinen Anne , Genuneit Jon , Braun-Fahrländer Charlotte , von Mutius Erika , Piarroux Renaud ,   the GABRIEL-A Study Group
Published: March 2011

ObjectivesExposure to environments rich in microorganisms such as farms has been shown to protect against the development of childhood asthma and allergies. However, it remains unclear where, and how, farm and other rural children are exposed to microbes. Furthermore, the composition of the microbial flora is poorly characterised. We tested the hypothesis that farm children are exposed indoors to substantial levels of viable microbes originating from animal sheds and barns. We also expected that environmental microbial flora on farms and in farm homes would be more complex than in the homes of rural control children.MethodsDust samples were collected using passive samplers in the bedrooms of the following groups of children in rural Bavaria, Germany: (i) those living on farms (n=144), (ii) those regularly exposed to farm environments but not living on farms (n=149) and (iii) those never visiting farms (n=150). For farm children, additional samples were collected in animal sheds and barns. All samples were subjected to fungal and bacterial culturing.ResultsDetectable levels of microorganisms were more often found in samples taken from farm dwellings than from other homes. Farm dwellings also showed higher microbial levels. Microbial counts of farm dwelling samples correlated with the counts in corresponding animal sheds and barns.ConclusionsMicroorganisms are transported from animal sheds and barns into farm dwellings. Therefore, children living in these environments are exposed when indoors and when visiting animal sheds and barns. Indoor exposure may also contribute to the protective effect of the farm environment.
What has change management in industry got to do with improving patient safety?
Authors: Noble Douglas J , Lemer Claire , Stanton Emma 
Published: March 2011

ABSTRACT

Background
Healthcare is often in a constant state of change - for political, technological, patient related, and scientific reasons. Yet, for a business where change is the norm, too little time is spent thinking theoretically about how change occurs. One area where change is still needed is in patient safety.

Methods
Presented is an analysis of the literature on change to suggest how this may inform patient safety.

Results
No one change approach guarantees success in patient safety. Success very much depends on selecting the best fit change framework and adapting it to local context. Well regarded change models, like that of Kotter, are not well tested within a healthcare context. Those that are, such as Pettigrew, do not specifically address all the issues associated with patient safety. Kotter's phases of change may be applied in a healthcare context to enhance patient safety.

Conclusion
Kotter's model is well studied in non-healthcare contexts and has potential to be adapted for improving patient safety.
Stress and recovery in junior doctors
Authors: Ochsmann Elke , Lang Jessica , Drexler Hans , Schmid Klaus 
Published: March 2011

ABSTRACT

Objective
Junior doctors are thought to experience increased mental strain in comparison to other occupations. The aim of the present study was to analyse selected work related influencing factors of strain and recovery in junior doctors.

Methods
In September 2006, 1494 young doctors were asked to participate in a postal questionnaire study featuring the Recovery Stress Questionnaire (RESTQ) and additional questions on job specific risk factors. Using hierarchical linear regression analyses the answers of 637 participants with less than 1.5 years work experience in patient care were analysed.

Results
Results revealed that overtime work, as well as lack of performance related feedback from supervisors, were consistently related to increased levels of strain among junior doctors. These risk factors were also predominantly related to recovery. In addition, feedback from colleagues was significantly associated with the recovery sub-scales (except with sleep quality).

Conclusions
Overtime work and performance related feedback from supervisors seem to be important work related factors concerning junior doctors’ levels of strain and recovery. In addition, performance feedback from colleagues seems to be a major resource for recovery. The findings have implications regarding work time regulations and the necessity of leadership skill development training regarding feedback talks and fostering a desirable social climate in the healthcare system for the wellbeing of junior doctors.
Preserved or slightly depressed ejection fraction and outcomes after myocardial infarction
Authors: Badheka Apurva O , Rathod Ankit , Bharadwaj Aditya S , Manickam Palaniappan , Kizilbash Mohammad A , Veeranna Vikas , Jacob Sony , Afonso Luis 
Published: March 2011

ABSTRACT

Background
Left ventricular ejection fraction (EF) in post-myocardial infarction (MI) patients is a strong predictor of adverse cardiovascular events. Although resting EF as measured by transthoracic echocardiography (TTE), contrast ventriculography (CNV), and radionuclide angiography (RNA) exhibit high correlation, there is only modest agreement between these modalities. This study sought to explore whether modality of EF assessment influences prognostication of post-MI patients with normal or slightly reduced EF.

Methods and results
The National Heart, Lung, and Blood Institute (NHLBI) limited access dataset of the Prevention of Events with Angiotensin Converting Enzyme Inhibition (PEACE) Trial (1996–2003, n=8290) comparing trandolapril versus placebo was used. The cohort was partitioned into TTE (n=2582), RNA (n=816), and CNV (n=1155) groups based on modality of EF assessment. EF was a significant predictor of cardiovascular mortality (HR 0.97, 95% CI 0.95 to 0.98; p&lt;0.005) and all cause mortality (HR 0.98, 95% CI 0.97 to 0.99; p=0.0002) on multivariate analysis in this population with preserved or mildly depressed EF. Although CNV, TTE, and RNA groups differed significantly in terms of baseline variables, no appreciable differences were noted between RNA (HR 1.13, 95% CI 0.85 to 1.50; ns) and CNV (HR 1.13, 95% CI 0.99 to 1.27; ns) groups, compared with TTE for all cause mortality. Similarly, no significant differences were observed for cardiovascular mortality between RNA (HR 1.23, 95% CI 0.82 to 1.84; p=0.31) and CNV (HR 1.14, 95% CI 0.78 to 1.67, p=0.49) versus TTE.

Conclusion
EF is a significant predictor of all-cause mortality and cardiovascular mortality in patients with preserved or mildly depressed EF. Modalities of EF measurement are interchangeable and do not play a significant role in prognostication in a post-MI population.
Sleep apnoea in severe aortic stenosis
Authors: Prinz Christian , Bitter Thomas , Oldenburg Olaf , Faber Lothar , Horstkotte Dieter , Piper Cornelia 
Published: March 2011

ABSTRACT

Background
There are as yet no data on the prevalence of sleep apnoea in patients with severe aortic stenosis (AS).

Aims
To assess the occurrence, severity and clinical correlates of sleep apnoea in patients with AS.

Methods
During a 4-month period in 2010, 67 patients were consecutively included in this study, 42 of which (19 men; mean±SD age 72±9 years) had severe AS (aortic valve opening area ≤1.0 cm2); all were investigated with cardiorespiratory polygraphy. Sleep apnoea was diagnosed if the apnoea–hypopnoea index (AHI) (median (lower quartile, upper quartile)) was ≥5/h. The control group of 25 patients matched for age, body mass index and sex had angiographic exclusion of coronary artery disease, regular left ventricular ejection fraction, and no valve disease.

Results
Sleep apnoea was found in 30/42 patients with AS (71%; AHI=23/h (14/h, 36/h)). The severity was significantly greater in patients with severe AS than in the control group (AHI=12/h (8/h, 17/h)) (p&lt;0.01). Half of the patients with sleep apnoea had obstructive sleep apnoea (OSA) (AHI=15/h (9/h, 28/h)), and half had central sleep apnoea (CSA) (AHI=25/h (18/h, 45/h)). New York Heart Association classification and severity of sleep apnoea correlated with η=0.5 (η2=0.3). The severity of CSA correlated with pulmonary artery pressure (r=0.7, p&lt;0.01) and pulmonary capillary wedge pressure (r=0.7, p&lt;0.01). Patients with AS and CSA had a lower Pco 2 than those with OSA and those without sleep apnoea (p&lt;0.01).

Conclusions
Sleep apnoea is common in patients with severe AS. The severity of CSA correlates with pulmonary hypertension, which may suggest that myocardial adaptation is exhausting.
Renin–angiotensin system antagonists in the perioperative setting: clinical consequences and recommendations for practice
Authors: Auron Moises , Harte Brian , Kumar Ajay , Michota Franklin 
Published: March 2011

ABSTRACT
There are no existing guidelines supporting the withdrawal or continuation of renin–angiotensin–aldosterone system (RAAS) antagonists in the preoperative setting. RAAS antagonists include ACE inhibitors, angiotensin II receptor subtype 1 blockers and direct renin inhibitors (eg, aliskiren), as well as the aldosterone antagonists. The use of these agents before surgery has been associated with a variable incidence of hypotension during the initial 30 min after induction of anaesthesia; however, these hypotensive episodes have not been conclusively linked to any significant postoperative complications, although recent data suggest an increase in postoperative morbidity and mortality in patients undergoing coronary artery bypass grafting. Further studies are required to be able to demonstrate if the organ-protective benefits of RAAS antagonists justify their continuation in the perioperative setting. Temporary withdrawal of RAAS antagonists in these patients may prevent or attenuate intraoperative hypotension and hypovolaemia. Alternatively, the increase in RAAS activity and blood pressure expected with cessation of RAAS antagonist therapy may impair regional circulation secondary to an increase in systemic vascular resistance. Full discussion of the potential implications of perioperative RAAS antagonist therapy with the surgical team is important, and strategies to ensure careful monitoring and maintenance of adequate intravenous volume before induction of anaesthesia are essential.
High-Throughput Screen Identifies Novel Inhibitors of Cancer Biomarker α-Methylacyl Coenzyme A Racemase (AMACR/P504S)
Authors: Wilson Brice A.P. , Wang Haofan , Nacev Benjamin A. , Mease Ronnie C. , Liu Jun O. , Pomper Martin G. , Isaacs William B. 
Published: March 2011

Abstract
α-methylacyl coenzyme A racemase (AMACR) is a metabolic enzyme whose overexpression has been shown to be a diagnostic indicator of prostatic adenocarcinoma and other solid tumors. Here, we confirm that attenuation of AMACR expression diminishes the growth of prostate cancer cell lines by using stably expressed short-hairpin RNA constructs. This observation strongly suggests that the AMACR enzyme may be a target for therapeutic inhibition in prostate cancer. To this end, we report here a novel assay capable of screening libraries of diverse small molecules for inhibitors of AMACR activity. This assay facilitated the screening of approximately 5,000 unique compounds and the discovery of 7 distinct chemical entities capable of inhibiting AMACR at low micromolar concentrations. The most potent inhibitor discovered is the seleno-organic compound ebselen oxide [inhibitory concentration (IC50): 0.80 μmol/L]. The parent compound, ebselen (IC50: 2.79 μmol/L), is a covalent inactivator of AMACR (KI(inact): 24 μmol/L). Two of the AMACR inhibitors are selectively toxic to prostate cancer cell lines (LAPC4/LNCaP/PC3) that express AMACR compared to a normal prostate fibroblast cell line (WPMY1) that does not express the protein. This report shows the first high-throughput screen for the discovery of novel AMACR inhibitors, characterizes the first nonsubstrate-based inhibitors, and validates that AMACR is a viable chemotherapeutic target in vitro. Mol Cancer Ther; 10(5); 825–38. ©2011 AACR.
Caspase-3–Dependent Mitotic Checkpoint Inactivation by the Small-Molecule Inducers of Mitotic Slippage SU6656 and Geraldol
Authors: Riffell Jenna L. , Jänicke Reiner U. , Roberge Michel 
Published: March 2011

Abstract
Microtubule-targeting cancer drugs such as paclitaxel block cell-cycle progression at mitosis by prolonged activation of the mitotic checkpoint. Cells can spontaneously escape mitotic arrest and enter interphase without chromosome segregation by a process termed mitotic slippage that involves the degradation of cyclin B1 without mitotic checkpoint inactivation. Inducing mitotic slippage with chemicals causes cells to die after multiple rounds of DNA replication without cell division, which may enhance the antitumor activity of microtubule-targeting drugs. Here, we explore pathways leading to mitotic slippage by using SU6656 and geraldol, two recently identified chemical inducers of mitotic slippage. Mitotic slippage induced by SU6656 or geraldol was blocked by the proteasome inhibitor MG-132 and involved proteasome-dependent degradation of cyclin B1 and the mitotic checkpoint proteins budding uninhibited by benzimidazole related 1 (BubR1) and cell division cycle 20 (Cdc20) in T98G cells. Mitotic slippage and the degradation of BubR1 and Cdc20 were also inhibited by the caspase-3 and -7 inhibitor DEVD-CHO. MCF-7 cells lacking caspase-3 expression could not degrade BubR1 or undergo mitotic slippage in response to SU6656 or geraldol. Introduction of caspase-3 completely restored the ability of MCF-7 cells to degrade BubR1 and undergo mitotic slippage. However, lack of expression of caspase-3 did not affect cell death after exposure to paclitaxel, with or without mitotic slippage induction. The requirement for caspase-3 for chemically induced mitotic slippage reveals a new mechanism for mitotic exit and a link between mitosis and apoptosis that has implications for the outcome of cancer chemotherapy. Mol Cancer Ther; 10(5); 839–49. ©2011 AACR.
Assessing the Activity of Cediranib, a VEGFR-2/3 Tyrosine Kinase Inhibitor, against VEGFR-1 and Members of the Structurally Related PDGFR Family
Authors: Brave Sandra R. , Ratcliffe Kirsty , Wilson Zena , James Neil H. , Ashton Sue , Wainwright Anna , Kendrew Jane , Dudley Philippa , Broadbent Nicola , Sproat Graham , Taylor Sian , Barnes Claire , Silva Jeffrey C. , Farnsworth Charles L. , Hennequin Laurent , Ogilvie Donald J. , Jürgensmeier Juliane M. , Shibuya Masabumi , Wedge Stephen R. , Barry Simon T. 
Published: March 2011

Abstract
Cediranib is a potent inhibitor of the VEGF receptor (VEGFR)-2 and VEGFR-3 tyrosine kinases. This study assessed the activity of cediranib against the VEGFR-1 tyrosine kinase and the platelet-derived growth factor receptor (PDGFR)-associated kinases c-Kit, PDGFR-α, and PDGFR-β. Cediranib inhibited VEGF-A–stimulated VEGFR-1 activation in AG1-G1-Flt1 cells (IC50 = 1.2 nmol/L). VEGF-A induced greatest phosphorylation of VEGFR-1 at tyrosine residues Y1048 and Y1053; this was reversed by cediranib. Potency against VEGFR-1 was comparable with that previously observed versus VEGFR-2 and VEGFR-3. Cediranib also showed significant activity against wild-type c-Kit in cellular phosphorylation assays (IC50 = 1–3 nmol/L) and in a stem cell factor–induced proliferation assay (IC50 = 13 nmol/L). Furthermore, phosphorylation of wild-type c-Kit in NCI-H526 tumor xenografts was reduced markedly following oral administration of cediranib (≥1.5 mg/kg/d) to tumor-bearing nude mice. The activity of cediranib against PDGFR-β and PDGFR-α was studied in tumor cell lines, vascular smooth muscle cells (VSMC), and a fibroblast line using PDGF-AA and PDGF-BB ligands. Both receptor phosphorylation (IC50 = 12–32 nmol/L) and PDGF-BB–stimulated cellular proliferation (IC50 = 32 nmol/L in human VSMCs; 64 nmol/L in osteosarcoma cells) were inhibited. In vivo, ligand-induced PDGFR-β phosphorylation in murine lung tissue was inhibited by 55% following treatment with cediranib at 6 mg/kg but not at 3 mg/kg or less. In contrast, in C6 rat glial tumor xenografts in mice, ligand-induced phosphorylation of both PDGFR-α and PDGFR-β was reduced by 46% to 61% with 0.75 mg/kg cediranib. Additional selectivity was showed versus Flt-3, CSF-1R, EGFR, FGFR1, and FGFR4. Collectively, these data indicate that cediranib is a potent pan-VEGFR kinase inhibitor with similar activity against c-Kit but is significantly less potent than PDGFR-α and PDGFR-β. Mol Cancer Ther; 10(5); 861–73. ©2011 AACR.
Association of Vascular Risk Factors With Cervical Artery Dissection and Ischemic Stroke in Young Adults
Authors: Debette Stéphanie , Metso Tiina , Pezzini Alessandro , Abboud Shérine , Metso Antti , Leys Didier , Bersano Anna , Louillet Fabien , Caso Valeria , Lamy Chantal , Medeiros Elisabeth , Samson Yves , Grond-Ginsbach Caspar , Engelter Stefan T. , Thijs Vincent , Beretta Simone , Béjot Yannick , Sessa Maria , Lorenza Muiesan Maria , Amouyel Philippe , Castellano Maurizio , Arveiler Dominique , Tatlisumak Turgut , Dallongeville Jean 
Published: March 2011

Background—
Little is known about the risk factors for cervical artery dissection (CEAD), a major cause of ischemic stroke (IS) in young adults. Hypertension, diabetes mellitus, smoking, hypercholesterolemia, and obesity are important risk factors for IS. However, their specific role in CEAD is poorly investigated. Our aim was to compare the prevalence of vascular risk factors in CEAD patients versus referents and patients who suffered an IS of a cause other than CEAD (non-CEAD IS) in the multicenter Cervical Artery Dissection and Ischemic Stroke Patients (CADISP) study.

Methods and Results—

The study sample comprised 690 CEAD patients (mean age, 44.2±9.9 years; 43.9% women), 556 patients with a non-CEAD IS (44.7±10.5 years; 39.9% women), and 1170 referents (45.9±8.1 years; 44.1% women). We compared the prevalence of hypertension, diabetes mellitus, hypercholesterolemia, smoking, and obesity (body mass index ≥30 kg/m
2
) or overweightness (body mass index ≥25 kg/m
2
and <30 kg/m
2
) between the 3 groups using a multinomial logistic regression adjusted for country of inclusion, age, and gender. Compared with referents, CEAD patients had a lower prevalence of hypercholesterolemia (odds ratio 0.55; 95% confidence interval, 0.42 to 0.71;
P
<0.0001), obesity (odds ratio 0.37; 95% confidence interval, 0.26 to 0.52;
P
<0.0001), and overweightness (odds ratio 0.70; 95% confidence interval, 0.57 to 0.88;
P
=0.002) but were more frequently hypertensive (odds ratio 1.67; 95% confidence interval, 1.32 to 2.1;
P
<0.0001). All vascular risk factors were less frequent in CEAD patients compared with young patients with a non-CEAD IS. The latter were more frequently hypertensive, diabetic, and current smokers compared with referents.

Conclusion—
These results, from the largest series to date, suggest that hypertension, although less prevalent than in patients with a non-CEAD IS, could be a risk factor of CEAD, whereas hypercholesterolemia, obesity, and overweightness are inversely associated with CEAD.
Mitral Regurgitation After Anteroapical Myocardial Infarction
Authors: Yosefy Chaim , Beeri Ronen , Guerrero J. Luis , Vaturi Mordehay , Scherrer-Crosbie Marielle , Handschumacher Mark D. , Levine Robert A. 
Published: March 2011

Background—
Mitral regurgitation (MR) generally accompanies inferobasal myocardial infarction (MI), with leaflet tethering by displaced papillary muscles. Mitral regurgitation is also reported with anteroapical MI without global dilatation or inferior wall motion abnormalities. We hypothesized that anteroapical MI extending to the inferior apex displaces the papillary muscles, tethering the mitral leaflets to cause MR.

Methods and Results—

In the retrospective part of the study, consecutive anteroapical MI patients were studied. Moderate-severe MR occurred in 9% of 234 patients with only anteroapical MI versus 17% of 242 with inferoapical extension (
P
<0.001). Ejection fraction was only mildly different (41±4% versus 46±5%;
P
<0.01). In the human mechanistic portion of the study, 60 anteroapical MI patients (20 with only 2 apical segments involved and 40 with involvement of all 4 apical segments; 20 with MR and 20 without MR) were compared with 20 normal controls. Those with MR (≥moderate) had higher systolic papillary muscle–to-annulus tethering length (
P
<0.01). Mitral regurgitation grade correlated most strongly with tethering length (
r
=0.70) and its diminished systolic shortening (
r
=−0.65). In the animal study, 9 sheep with left anterior descending coronary artery ligation were analyzed. Four sheep that developed MR had inferoapical MI extension with tethering length increasing over 1.5 months (2.1±0.4 to 2.9±0.4 cm,
P
<0.001) versus no significant increase in 5 sheep without MR (2.0±0.4 to 2.1±0.3 cm,
P
not statistically significant). In MR sheep, the normal decrease in tethering length from diastole to systole was eliminated (
P
<0.01).

Conclusions—
Anteroapical MI with inferoapical extension can mechanically displace papillary muscles, causing MR despite the absence of basal and midinferior wall motion abnormalities. This suggests the possibility of repositioning treatments for this condition.
A Spatiotemporal Analysis of Historical Droughts in Korea
Authors: Kim Do-Woo , Byun Hi-Ryong , Choi Ki-Seon , Oh Su-Bin 
Published: March 2011

AbstractThe climatological characteristics of drought in South Korea were investigated using daily precipitation data for 1777–2008. The effective drought index was used to quantify the drought intensity. As a result, five characteristics were discovered. First, South Korea can be divided into four drought subregions (the central, southern, and east coastal regions and Jeju Island) using hierarchical cluster analysis. Second, a map for long-term drought conditions in the four subregions is created that allows identification of the spatiotemporal distribution of droughts for the 231 yr at a glance. Third, droughts in South Korea have time scales that depend on the onset season. Spring (March–May) droughts tend to be short (≤200 days) because the summer (June–September) rainy season follows. Summer droughts tend to be long (>200 days) because the dry season (October–February) follows. In the dry season, droughts tend to be sustained or become severe rather than being initiated or relieved. Fourth, 5-, 14-, 34-, and 115-yr drought cycles were identified by spectral analysis. The 5-yr cycle was dominant in all of the regions, the 14-yr cycle was observed over the southern and east coastal regions, and the 34-yr cycle was observed over the central region. Fifth, the most extreme drought occurred in 1897–1903 (return period: 233 yr) and was associated with the 115-yr drought cycle. After this drought, severe droughts (return period of >10 yr) occurred in 1927–30, 1938–40, 1942–45, 1951–52, 1967–69, and 1994–96; they were caused by the consecutive shortage of summer rainfall for two or more years.