bluuebunny/crossref_metadata_2025 huggingface dataset:
Management-based risk prediction in community-acquired pneumonia by scores and biomarkers
Authors: Kolditz Martin , Ewig Santiago , Höffken Gert
Published: September 2012

Community-acquired pneumonia (CAP) represents a major life-threatening infection, but disease course and outcome is highly variable. Major drivers of prognosis are respiratory failure, sepsis-related organ dysfunction and unstable comorbidities.

Current risk stratification tools have been primarily designed to predict mortality and identify low risk patients potentially suitable for ambulatory management. Detection of patients at high risk for clinical deterioration by current scores remains suboptimal.

Therefore, management-related risk stratification tools designed to predict benefit from early intensified monitoring and treatment strategies in hospitalised CAP are advocated. An approach including early and repeatedly evaluated clinical markers of respiratory failure, sepsis-related organ dysfunction or decompensating comorbidity combined with individual definition of treatment goals is suggested.

Inflammatory biomarkers can add prognostic information. New cardiovascular or stress-related biomarkers like copeptin, midregional proadrenomedullin and cortisol have been repeatedly linked with outcome and disease course in CAP and improved clinical scoring in observational studies. Thus they represent promising tools for individualised risk stratification. A major task in future CAP research will be the evaluation of their additional value in large interventional trials with control groups incorporating strict management guidance by clinical criteria.
Delamanid improves outcomes and reduces mortality in multidrug-resistant tuberculosis
Authors: Skripconoka Vija , Danilovits Manfred , Pehme Lea , Tomson Tarmo , Skenders Girts , Kummik Tiina , Cirule Andra , Leimane Vaira , Kurve Anu , Levina Klavdia , Geiter Lawrence J. , Manissero Davide , Wells Charles D.
Published: September 2012

Multidrug-resistant and extensively drug-resistant tuberculosis (TB) are associated with worse treatment outcomes for patients, including higher mortality, than for drug-sensitive tuberculosis. Delamanid (OPC-67683) is a novel anti-TB medication with demonstrated activity against multidrug-resistant disease.

Patients who participated in the previously reported randomised, placebo-controlled trial of delamanid and the subsequent open-label extension trial were eligible to participate in a 24-month observational study designed to capture treatment outcomes. Treatment outcomes, as assessed by clinicians and defined by the World Health Organization, were categorised as favourable and unfavourable. Delamanid treatment groups were combined for analysis, based on their duration of treatment. In total, for 421 (87.5%) out of 481 patients from the original randomised controlled trial, consent was granted for follow-up assessments.

Favourable outcomes were observed in 143 (74.5%) out of 192 patients who received delamanid for ≥6 months, compared to 126 (55%) out of 229 patients who received delamanid for ≤2 months. Mortality was reduced to 1.0% among those receiving long-term delamanidversusshort-term/no delamanid (8.3%; p<0.001). Treatment benefit was also seen among patients with extensively drug-resistant TB.

This analysis suggests that treatment with delamanid for 6 months in combination with an optimised background regimen can improve outcomes and reduce mortality among patients with both multidrug-resistant and extensively drug-resistant TB.
Dysfunctional breathing in children with asthma: a rare but relevant comorbidity
Authors: de Groot Eric P. , Duiverman Eric J. , Brand Paul L.P.
Published: September 2012

Hyperventilation and other clinical manifestations of dysfunctional breathing have been reported in childhood, but the prevalence is unknown. In adults, dysfunctional breathing may be a relevant comorbidity in asthma. We aimed to determine the prevalence of dysfunctional breathing in children with asthma and its impact on asthma control.

We performed a cross-sectional survey in 203 asthmatic children (aged 5–18 years), using the Nijmegen Questionnaire and the paediatric Asthma Control Questionnaire.

Dysfunctional breathing was found in 11 (5.3%) children; more females (eight (12.9%) out of 62) than males (three (2.1%) out 144, p=0.002). There was a dose–dependent relationship between increasing Nijmegen Questionnaire scores (increased risk of dysfunctional breathing) and poorer asthma control. Poor asthma control was more common in patients with dysfunctional breathing (10 (90.9%) out of 11 children) than in children without (65 (32.3%) out of 192 children; OR 19.3, 95% CI 3.14–430.70; p<0.0001). The median Asthma Control Questionnaire in children with dysfunctional breathing was higher (median (range) 2.00 (1.50–3.17)) than in children without (0.50 (0.17–1.17); p<0.001).

The prevalence of dysfunctional breathing in children and adolescents referred to a hospital-based paediatric asthma clinic for severe or difficult-to-control asthma is 5%. The association between dysfunctional breathing and asthma control suggests that this may be a clinically relevant comorbidity in paediatric asthma.
In vivoprobe-based confocal laser endomicroscopy in amiodarone-related pneumonia
Authors: Salaün Mathieu , Roussel Francis , Bourg-Heckly Geneviève , Vever-Bizet Christine , Dominique Stéphane , Genevois Anne , Jounieaux Vincent , Zalcman Gérard , Bergot Emmanuel , Vergnon Jean-Michel , Thiberville Luc
Published: September 2012

Probe-based confocal laser endomicroscopy (pCLE) allows microscopic imaging of the alveoli during bronchoscopy. The objective of the study was to assess the diagnostic accuracy of pCLE for amiodarone-related pneumonia (AMR-IP).

Alveolar pCLE was performed in 36 nonsmoking patients, including 33 consecutive patients with acute or subacute interstitial lung disease (ILD), of which 17 were undergoing treatment with amiodarone, and three were amiodarone-treated patients without ILD.

Nine out of 17 patients were diagnosed with high-probability AMR-IP (HP-AMR-IP) by four experts, and three separate observers. Bronchoalveolar lavage findings did not differ between HP-AMR-IP and low-probability AMR-IP (LP-AMR-IP) patients. In HP-AMR-IP patients, pCLE showed large (>20 μm) and strongly fluorescent cells in 32 out of 38 alveolar areas. In contrast, these cells were observed in only two out of 39 areas from LP-AMR-IP patients, in one out of 59 areas from ILD patients not receiving amiodarone and in none of the 10 areas from amiodarone-treated patients without ILD (p<0.001; HP-AMR-IPversusother groups). The presence of at least one alveolar area with large and fluorescent cells had a sensitivity, specificity, negative predictive value and positive predictive value for the diagnosis of AMR-IP of 100%, 88%, 100% and 90%, respectively.

In conclusion, pCLE appears to be a valuable tool for thein vivodiagnosis of AMR-IP in subacute ILD patients.
Sleep clinical record: an aid to rapid and accurate diagnosis of paediatric sleep disordered breathing
Authors: Villa Maria Pia , Paolino Maria Chiara , Castaldo Rosa , Vanacore Nicola , Rizzoli Alessandra , Miano Silvia , Del Pozzo Marco , Montesano Marilisa
Published: September 2012

Overnight polysomnography (PSG) is an expensive procedure which can only be used in a minority of cases, although it remains the gold standard for the diagnosis of sleep disordered breathing (SDB). The objective of this study was to develop a simple, PSG-validated tool to screen SDB, thus reducing the use of PSG.

For every participant we performed PSG and a sleep clinical record was completed. The sleep clinical record consists of three items: physical examination, subjective symptoms and clinical history. The clinical history analyses behavioural and cognitive problems. All three items were used to create a sleep clinical score (SCS).

We studied 279 children, mean±sdage 6.1±3.1 years, 63.8% male; 27.2% with primary snoring and 72.8% with obstructive sleep apnoea (OSA) syndrome. The SCS was higher in the OSA syndrome group compared to the primary snoring group (8.1±9.6versus0.4±0.3, p<0.005), correlated with apnoea/hypopnoea index (p=0.001) and had a sensitivity of 96.05%. Positive and negative likelihood ratios were 2.91 and 0.06, respectively.

SCS may effectively be used to screen patients as candidates for PSG study for suspected OSA syndrome, and to enable those with a mild form of SDB to receive early treatment.
Prevalence and prognosis of COPD in critically ill patients between 1998 and 2008
Authors: Funk Georg-Christian , Bauer Peter , Burghuber Otto Chris , Fazekas Andreas , Hartl Sylvia , Hochrieser Helene , Schmutz Rene , Metnitz Philipp
Published: September 2012

The epidemiology of chronic obstructive pulmonary disease (COPD) in critically ill patients is largely unknown. The aims of the study were: 1) to determine whether COPD, either as the cause of intensive care unit (ICU) admission or as a comorbid condition, is an independent risk factor for increased morbidity and mortality; and 2) to investigate time trends in proportion and outcome of acute respiratory failure in patients with COPD admitted to ICUs.

Prospectively recorded data from 194 453 adults consecutively admitted to 87 Austrian ICUs over a period of 11 years (1998–2008) were retrospectively analysed.

COPD was present in 8.6% of all patients. The risk-adjusted mortality of patients with COPD was higher than in patients without COPD. The presence of COPD was an independent risk factor for increased mortality and was associated with prolonged mechanical ventilation and prolonged weaning. During the course of the 11 years, the proportion of acute respiratory failure due to COPD increased by about two-thirds, and the use of noninvasive ventilation within the COPD cohort more than doubled. Simultaneously, the risk-adjusted mortality of patients with COPD improved.

In critically ill patients, the presence of COPD is increasing and is an independent risk factor for mortality and morbidity.
Combining laser microdissection and RNA-seq to chart the transcriptional landscape of fungal development
Authors: Teichert Ines , Wolff Gabriele , Kück Ulrich , Nowrousian Minou
Published: September 2012

Background

During sexual development, filamentous ascomycetes form complex, three-dimensional fruiting bodies for the protection and dispersal of sexual spores. Fruiting bodies contain a number of cell types not found in vegetative mycelium, and these morphological differences are thought to be mediated by changes in gene expression. However, little is known about the spatial distribution of gene expression in fungal development. Here, we used laser microdissection (LM) and RNA-seq to determine gene expression patterns in young fruiting bodies (protoperithecia) and non-reproductive mycelia of the ascomycete Sordaria macrospora.

Results

Quantitative analysis showed major differences in the gene expression patterns between protoperithecia and total mycelium. Among the genes strongly up-regulated in protoperithecia were the pheromone precursor genes ppg1 and ppg2. The up-regulation was confirmed by fluorescence microscopy of egfp expression under the control of ppg1 regulatory sequences. RNA-seq analysis of protoperithecia from the sterile mutant pro1 showed that many genes that are differentially regulated in these structures are under the genetic control of transcription factor PRO1.

Conclusions

We have generated transcriptional profiles of young fungal sexual structures using a combination of LM and RNA-seq. This allowed a high spatial resolution and sensitivity, and yielded a detailed picture of gene expression during development. Our data revealed significant differences in gene expression between protoperithecia and non-reproductive mycelia, and showed that the transcription factor PRO1 is involved in the regulation of many genes expressed specifically in sexual structures. The LM/RNA-seq approach will also be relevant to other eukaryotic systems in which multicellular development is investigated.
Effects of yeast trehalose-6-phosphate synthase 1 on gene expression and carbohydrate contents of potato leaves under drought stress conditions
Authors: Kondrák Mihály , Marincs Ferenc , Antal Ferenc , Juhász Zsófia , Bánfalvi Zsófia
Published: September 2012

Background

The development of drought-tolerant, elite varieties of potato (Solanum tuberosumL.) is a challenging task, which might be achieved by introducing transgenic lines into breeding. We previously demonstrated that strains of the White Lady potato cultivar that express the yeast trehalose-6-phosphate synthase (TPS1) gene exhibit improved drought tolerance.

Results

We investigated the responses of the drought-sensitive potato cultivar White Lady and the drought-tolerantTPS1transgenic variant to prolonged drought stress at both the transcriptional and metabolic levels. Leaf mRNA expression profiles were compared using the POCI microarray, which contains 42,034 potato unigene probes. We identified 379 genes of known function that showed at least a 2-fold change in expression across genotypes, stress levels or the interaction between these factors. Wild-type leaves had twice as many genes with altered expression in response to stress thanTPS1transgenic leaves, but 112 genes were differentially expressed in both strains. We identified 42 transcription factor genes with altered expression, of which four were uniquely up-regulated inTPS1transgenic leaves. The majority of the genes with altered expression that have been implicated in photosynthesis and carbohydrate metabolism were down-regulated in both the wild-type andTPS1transgenic plants. In agreement with this finding, the starch concentration of the stressed leaves was very low. At the metabolic level, the contents of fructose, galactose and glucose were increased and decreased in the wild-type andTPS1transgenic leaves, respectively, while the amounts of proline, inositol and raffinose were highly increased in both the wild-type andTPS1transgenic leaves under drought conditions.

Conclusions

To our knowledge, this study is the most extensive transcriptional and metabolic analysis of a transgenic, drought-tolerant potato line. We identified four genes that were previously reported as drought-responsive in non-transgenic Andean potato cultivars. The substantial increases in proline, inositol and raffinose contents detected in both the wild-type andTPS1transgenic leaves appears to be a general response of potatoes to drought stress. The four transcription factors uniquely up-regulated inTPS1transgenic leaves are good candidates for future functional analyses aimed at understanding the regulation of the 57 genes with differential expression inTPS1transgenic leaves.
Use of health care services and pharmaceutical agents in coeliac disease: a prospective nationwide study
Authors: Ukkola Anniina , Kurppa Kalle , Collin Pekka , Huhtala Heini , Forma Leena , Kekkonen Leila , Mäki Markku , Kaukinen Katri
Published: September 2012

Background

Approximately 1% of the population suffer from coeliac disease. However, the disease is heavily underdiagnosed. Unexplained symptoms may lead to incremented medical consultations and productivity losses. The aim here was to estimate the possible concealed burden of untreated coeliac disease and the effects of a gluten-free diet.

Methods

A nationwide cohort of 700 newly detected adult coeliac patients were prospectively evaluated. Health care service use and sickness absence from work during the year before diagnosis were compared with those in the general population; the data obtained from an earlier study. Additionally, the effect of one year on dietary treatment on the aforementioned parameters and on consumption of pharmaceutical agents was assessed.

Results

Untreated coeliac patients used primary health care services more frequently than the general population. On a gluten-free diet, visits to primary care decreased significantly from a mean 3.6 to 2.3. The consumption of medicines for dyspepsia (from 3.7 to 2.4 pills/month) and painkillers (6.8-5.5 pills/month) and the number of antibiotic courses (0.6-0.5 prescriptions/year) was reduced. There were no changes in hospitalizations, outpatient visits to secondary and tertiary care, use of other medical services, or sickness absence, but the consumption of nutritional supplements increased on treatment.

Conclusions

Coeliac disease was associated with excessive health care service use and consumption of drugs before diagnosis. Dietary treatment resulted in a diminished burden to the health care system and lower use of on-demand medicines and antibiotic treatment. The results support an augmented diagnostic approach to reduce underdiagnosis of coeliac disease.

Trial registration

ClinicalTrials.gov NCT01145287
Nutritional status and clinical outcome of children on continuous renal replacement therapy: a prospective observational study
Authors: Castillo Ana , Santiago Maria J , López-Herce Jesús , Montoro Sandra , López Jorge , Bustinza Amaya , Moral Ramón , Bellón Jose M
Published: September 2012

Background

No studies on continuous renal replacement therapy (CRRT) have analyzed nutritional status in children. The objective of this study was to assess the association between mortality and nutritional status of children receiving CRRT.

Methods

Prospective observational study to analyze the nutritional status of children receiving CRRT and its association with mortality. The variables recorded were age, weight, sex, diagnosis, albumin, creatinine, urea, uric acid, severity of illness scores, CRRT-related complications, duration of admission to the pediatric intensive care unit, and mortality.

Results

The sample comprised 174 critically ill children on CRRT. The median weight of the patients was 10 kg, 35% were under percentile (P) 3, and 56% had a weight/P50 ratio of less than 0.85. Only two patients were above P95. The mean age for patients under P3 was significantly lower than that of the other patients (p = 0.03). The incidence of weight under P3 was greater in younger children (p = 0.007) and in cardiac patients and in those who had previous chronic renal insufficiency (p = 0.047). The mortality analysis did not include patients with pre-existing renal disease. Mortality was 38.9%. Mortality for patients with weight < P3 was greater than that of children with weight > P3 (51% vs 33%; p = 0.037). In the univariate and multivariate logistic regression analyses, the only factor associated with mortality was protein-energy wasting (malnutrition) (OR, 2.11; 95% CI, 1.067-4.173; p = 0.032).

Conclusions

The frequency of protein-energy wasting in children who require CRRT is high, and the frequency of obesity is low. Protein-energy wasting is more frequent in children with previous end-stage renal disease and heart disease. Underweight children present a higher mortality rate than patients with normal body weight.
Is there an advantage to delivering breast boost in the lateral decubitus position?
Authors: Kannan Neeta , Kabolizadeh Peyman , Kim Hayeon , Houser Christopher , Beriwal Sushil
Published: September 2012

Background

The purpose of this study was to compare the change in depth of target volume and dosimetric parameters between the supine and lateral decubitus positions for breast boost treatment with electron beam therapy.

Methods

We analyzed 45 patients who were treated, between 2009–2010, with whole breast radiation (WBRT) followed by a tumor bed boost in the lateral decubitius position. Tumor bed volume, distance from skin to the maximal depth of the tumor bed, D90 (dose covering 90% of the tumor bed volume), maximal dose, electron energy and doses to heart and lungs were compared. Additional variables of body mass index (BMI) and tumor bed location were also analyzed to see if there was a benefit limited to any subgroup.

Results

Median BMI for the 45 patients treated was 30.6 (20.6-42.4). When comparing the supine scan to the lateral decubitus scan, there was no significant difference in the tumor bed volume (p = 0.116). There was a significant difference between depth to the tumor bed in the supine scan and lateral decubitus scan (p < 0.001). The mean maximum doses and D90 between the two scans were 110.7 (100.0-133.0)% vs 106.1 (95.1-116.9)% (p < 0.05) and 93.9 (81.3-01.0-101.0)% vs. 98.2 (89.1-108.0)% (p = 0.004) respectively. There was no difference in dose delivered to the lungs or heart between the two scans (p = 0.848 and p = 0.992 respectively). On subset analysis, there was a difference in depth to tumor that was seen across all BMI classes, including normal (p ≤ 0.001, overweight (p ≤ 0.001) and obese (p ≤ 0.001). The majority of patients had a tumor in the upper outer quadrant (77.8%) and on subset analysis, there was a significant difference in tumor bed volume (p < 0.01), depth to tumor (p < 0.01), tumor bed coverage [D90] (p < 0.05), maximum dose (p < 0.05) and energy (p < 0.001) for this location.

Conclusions

Delivering a tumor bed boost in the lateral decubitus position reduces the distance to the tumor bed allowing for a lower energy treatment to be used to treat breast cancer. It improves coverage and decreases maximal dose to the target volume, all of which would help reduce skin morbidities and should be considered for patients with upper outer quadrant disease, irrespective of BMI status.
Biomechanical stability of a supra-acetabular pedicle screw Internal Fixation device (INFIX) vs External Fixation and plates for vertically unstable pelvic fractures
Authors: Vigdorchik Jonathan M , Esquivel Amanda O , Jin Xin , Yang King H , Onwudiwe Ndidi A , Vaidya Rahul
Published: September 2012

Background

We have recently developed a subcutaneous anterior pelvic fixation technique (INFIX). This internal fixator permits patients to sit, roll over in bed and lie on their sides without the cumbersome external appliances or their complications. The purpose of this study was to evaluate the biomechanical stability of this novel supraacetabular pedicle screw internal fixation construct (INFIX) and compare it to standard internal fixation and external fixation techniques in a single stance pelvic fracture model.

Methods

Nine synthetic pelves with a simulated anterior posterior compression type III injury were placed into three groups (External Fixator, INFIX and Internal Fixation). Displacement, total axial stiffness, and the stiffness at the pubic symphysis and SI joint were calculated. Displacement and stiffness were compared by ANOVA with a Bonferroni adjustment for multiple comparisons

Results

The mean displacement at the pubic symphysis was 20, 9 and 0.8 mm for external fixation, INFIX and internal fixation, respectively. Plate fixation was significantly stiffer than the INFIX and external Fixator (P = 0.01) at the symphysis pubis. The INFIX device was significantly stiffer than external fixation (P = 0.017) at the symphysis pubis. There was no significant difference in SI joint displacement between any of the groups.

Conclusions

Anterior plate fixation is stiffer than both the INFIX and external fixation in single stance pelvic fracture model. The INFIX was stiffer than external fixation for both overall axial stiffness, and stiffness at the pubic symphysis. Combined with the presumed benefit of minimizing the complications associated with external fixation, the INFIX may be a more preferable option for temporary anterior pelvic fixation in situations where external fixation may have otherwise been used.
Secondhand smoke in combination with ambient air pollution exposure is associated with increasedx CpG methylation and decreased expression of IFN-γ in T effector cells and Foxp3 in T regulatory cells in children
Authors: Kohli Arunima , Garcia Marco A , Miller Rachel L , Maher Christina , Humblet Olivier , Hammond S Katharine , Nadeau Kari
Published: September 2012

Background

Secondhand smoke (SHS) and ambient air pollution (AAP) exposures have been associated with increased prevalence and severity of asthma and DNA modifications of immune cells. In the current study, we examined the association between SHS and AAP with DNA methylation and expression of interferon-gamma (IFN-γ) and forkhead box protein 3 (Foxp3) in T cell populations.

Methods

Subjects 7–18 years old were recruited from Fresno (high AAP; n = 62) and Stanford, CA (low AAP; n = 40) and divided into SHS-exposed (Fresno: n = 31, Stanford: n = 6) and non-SHS-exposed (nSHS; Fresno: n = 31, Stanford: n = 34) groups. T cells purified from peripheral blood were assessed for levels of DNA methylation and expression of IFN-γ (in effector T cells) or Foxp3 (in regulatory T cells).

Results

Analysis showed a significant increase in mean % CpG methylation of IFN-γ and Foxp3 associated with SHS exposure (IFN-γ: FSHS 62.10%, FnSHS 41.29%, p < 0.05; SSHS 46.67%, SnSHS 24.85%, p < 0.05; Foxp3: FSHS 74.60%, FnSHS 54.44%, p < 0.05; SSHS 62.40%, SnSHS 18.41%, p < 0.05) and a significant decrease in mean transcription levels of both genes (IFN-γ: FSHS 0.75, FnSHS 1.52, p < 0.05; SHS 2.25, nSHS 3.53, p < 0.05; Foxp3: FSHS 0.75, FnSHS 3.29, p < 0.05; SSHS 4.8, SnSHS 7.2, p < 0.05). AAP was also associated with hypermethylation (IFN-γ: FSHS vs. SSHS, p < 0.05; FnSHS vs. SnSHS, p < 0.05; Foxp3: FSHS vs. SSHS, p < 0.05; FnSHS vs. SnSHS, p < 0.05) and decreased transcription of both genes (IFN-γ: FSHS vs. SSHS, p < 0.05; FnSHS vs. SnSHS, p < 0.05; Foxp3: FSHS vs. SSHS, p < 0.05; FnSHS vs. SnSHS, p < 0.05). Average methylation between AAP- and SHS-only exposures was not significantly different (IFN-γ: p = 0.15; Foxp3: p = 0.27), nor was Foxp3 expression (p = 0.08); IFN-γ expression was significantly decreased in AAP-only subjects (p < 0.05).

Conclusions

Exposures to SHS and AAP are associated with significant hypermethylation and decreased expression of IFN-γ in Teffs and Foxp3 in Tregs. Relative contributions of each exposure to DNA modification and asthma pathogenesis warrant further investigation.
68Ga-DOTATATE PET/CT for the detection of inflammation of large arteries: correlation with18F-FDG, calcium burden and risk factors
Authors: Li Xiang , Samnick Samuel , Lapa Constantin , Israel Ina , Buck Andreas K , Kreissl Michael C , Bauer Wolfgang
Published: September 2012

Background

Ga-[1,4,7,10-tetraazacyclododecane-N,N′,N″,N′″- tetraacetic acid]-d-Phe1,Tyr3-octreotate (DOTATATE) positron emission tomography (PET) is commonly used for the visualization of somatostatin receptor (SSTR)-positive neuroendocrine tumors. SSTR is also known to be expressed on macrophages, which play a major role in inflammatory processes in the walls of coronary arteries and large vessels. Therefore, imaging SSTR expression has the potential to visualize vulnerable plaques. We assessed 68Ga-DOTATATE accumulation in large vessels in comparison to 18F-2-fluorodeoxyglucose (FDG) uptake, calcified plaques (CPs), and cardiovascular risk factors.

Methods

Sixteen consecutive patients with neuroendocrine tumors or thyroid cancer underwent both 68Ga-DOTATATE and 18F-FDG PET/CT for staging or restaging purposes. Detailed clinical data, including common cardiovascular risk factors, were recorded. For a separate assessment, they were divided into a high-risk and a low-risk group. In each patient, we calculated the maximum target-to-background ratio (TBR) of eight arterial segments. The correlation of the TBRmean of both tracers with risk factors including plaque burden was assessed.

Results

The mean TBR of 68Ga-DOTATATE in all large arteries correlated significantly with the presence of CPs (r = 0.52; p < 0.05), hypertension (r = 0.60; p < 0.05), age (r = 0.56; p < 0.05), and uptake of 18F-FDG (r = 0.64; p < 0.01). There was one significant correlation between 18F-FDG uptake and hypertension (0.58; p < 0.05). Out of the 37 sites with the highest focal 68Ga-DOTATATE uptake, 16 (43.2%) also had focal 18F-FDG uptake. Of 39 sites with the highest 18F-FDG uptake, only 11 (28.2%) had a colocalized 68Ga-DOTATATE accumulation.

Conclusions

In this series of cancer patients, we found a stronger association of increased 68Ga-DOTATATE uptake with known risk factors of cardiovascular disease as compared to 18F-FDG, suggesting a potential role for plaque imaging in large arteries. Strikingly, we found that focal uptake of 68Ga-DOTATATE and 18F-FDG does not colocalize in a significant number of lesions.
Fracture mapping using seismic amplitude variation with offset and azimuth analysis at the Weyburn CO2 storage site
Authors: Duxbury Alexander , White Don , Samson Claire , Hall Stephen A. , Wookey James , Kendall J.-Michael
Published: September 2012

Cap rock integrity is an essential characteristic of any reservoir to be used for long-term [Formula: see text] storage. Seismic AVOA (amplitude variation with offset and azimuth) techniques have been applied to map HTI anisotropy near the cap rock of the Weyburn field in southeast Saskatchewan, Canada, with the purpose of identifying potential fracture zones that may compromise seal integrity. This analysis, supported by modeling, observes the top of the regional seal (Watrous Formation) to have low levels of HTI anisotropy, whereas the reservoir cap rock (composite Midale Evaporite and Ratcliffe Beds) contains isolated areas of high intensity anisotropy, which may be fracture-related. Properties of the fracture fill and hydraulic conductivity within the inferred fracture zones are not constrained using this technique. The predominant orientations of the observed anisotropy are parallel and normal to the direction of maximum horizontal stress (northeast–southwest) and agree closely with previous fracture studies on core samples from the reservoir. Anisotropy anomalies are observed to correlate spatially with salt dissolution structures in the cap rock and overlying horizons as interpreted from 3D seismic cross sections.
AVO inversion and poroelasticity with P- and S-wave moduli
Authors: Zong Zhaoyun , Yin Xingyao , Wu Guochen
Published: September 2012

The fluid term in the Biot-Gassmann equation plays an important role in reservoir fluid discrimination. The density term imbedded in the fluid term, however, is difficult to estimate because it is less sensitive to seismic amplitude variations. We combined poroelasticity theory, amplitude variation with offset (AVO) inversion, and identification of P- and S-wave moduli to present a stable and physically meaningful method to estimate the fluid term, with no need for density information from prestack seismic data. We used poroelasticity theory to express the fluid term as a function of P- and S-wave moduli. The use of P- and S-wave moduli made the derivation physically meaningful and natural. Then we derived an AVO approximation in terms of these moduli, which can then be directly inverted from seismic data. Furthermore, this practical and robust AVO-inversion technique was developed in a Bayesian framework. The objective was to obtain the maximum a posteriori solution for the P-wave modulus, S-wave modulus, and density. Gaussian and Cauchy distributions were used for the likelihood and a priori probability distributions, respectively. The introduction of a low-frequency constraint and statistical probability information to the objective function rendered the inversion more stable and less sensitive to the initial model. Tests on synthetic data showed that all the parameters can be estimated well when no noise is present and the estimated P- and S-wave moduli were still reasonable with moderate noise and rather smooth initial model parameters. A test on a real data set showed that the estimated fluid term was in good agreement with the results of drilling.
Reservoir characterization based on seismic spectral variations
Authors: Wang Yanghua
Published: September 2012

The seismic frequency spectrum provides a useful source of information for reservoir characterization. For a seismic profile presented in the time-space domain, a vector of the frequency spectrum can be generated at every sampling point. Because the spectrum vectors at different time-space locations have different variation features, I attempt for the first time to exploit the variation pattern of the frequency spectrum for reservoir characterization, and test this innovative technology in prediction of coalbed methane (CBM) reservoirs. The prediction process implicitly takes account of the CBM reservoir factors (such as viscosity, elasticity, cleat system, wave interference within a coal seam, etc.) that affect the frequency spectrum, but strong amplitudes in seismic reflections do not necessarily show any influence in clustering analysis of spectral variation patterns. By calibrating these variation patterns quantitatively with CBM productions in well locations, we are able to characterize the spatial distribution of potential reservoirs.
Association Between Circulating Tumor Cells and Prognosis in Patients With Stage III Melanoma With Sentinel Lymph Node Metastasis in a Phase III International Multicenter Trial
Authors: Hoshimoto Sojun , Shingai Tatsushi , Morton Donald L. , Kuo Christine , Faries Mark B. , Chong Kelly , Elashoff David , Wang He-Jing , Elashoff Robert M. , Hoon Dave S.B.
Published: September 2012

Purpose

The outcomes of patients with melanoma who have sentinel lymph node (SLN) metastases can be highly variable, which has precluded establishment of consensus regarding treatment of the group. The detection of high-risk patients from this clinical setting may be helpful for determination of both prognosis and management. We report the utility of multimarker reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) detection of circulating tumor cells (CTCs) in patients with melanoma diagnosed with SLN metastases in a phase III, international, multicenter clinical trial.

Patients and Methods

Blood specimens were collected from patients with melanoma (n = 331) who were clinically disease-free after complete lymphadenectomy (CLND) before entering onto a randomized adjuvant melanoma vaccine plus bacillus Calmette-Guérin (BCG) versus BCG placebo trial from 30 melanoma centers (United States and international). Blood was assessed using a verified multimarker RT-qPCR assay (MART-1, MAGE-A3, and GalNAc-T) of melanoma-associated proteins. Cox regression analyses were used to evaluate the prognostic significance of CTC status for disease recurrence and melanoma-specific survival (MSS).

Results

Individual CTC biomarker detection ranged from 13.4% to 17.5%. There was no association of CTC status (zero to one positive biomarkers v two or more positive biomarkers) with known clinical or pathologic prognostic variables. However, two or more positive biomarkers was significantly associated with worse distant metastasis disease-free survival (hazard ratio [HR] = 2.13, P = .009) and reduced recurrence-free survival (HR = 1.70, P = .046) and MSS (HR = 1.88, P = .043) in a multivariable analysis.

Conclusion

CTC biomarker status is a prognostic factor for recurrence-free survival, distant metastasis disease-free survival, and MSS after CLND in patients with SLN metastasis. This multimarker RT-qPCR analysis may therefore be useful in discriminating patients who may benefit from aggressive adjuvant therapy or stratifying patients for adjuvant clinical trials.
Parenthood in Survivors of Hodgkin Lymphoma: An EORTC-GELA General Population Case-Control Study
Authors: van der Kaaij Marleen A.E. , Heutte Natacha , Meijnders Paul , Abeilard-Lemoisson Edwige , Spina Michele , Moser Lotte C. , Allgeier Anouk , Meulemans Bart , Dubois Brice , Simons Arnold H.M. , Lugtenburg Pieternella J. , Aleman Berthe M.P. , Noordijk Evert M. , Fermé Christophe , Thomas José , Stamatoullas Aspasia , Fruchart Christophe , Brice Pauline , Gaillard Isabelle , Doorduijn Jeanette K. , Sebban Catherine , Smit Wilma G.J.M. , Bologna Serge , Roesink Judith M. , Ong Francisca , André Marc P.E. , Raemaekers John M.M. , Henry-Amar Michel , Kluin-Nelemans Hanneke C.
Published: September 2012

Purpose

We investigated the impact of Hodgkin lymphoma (HL) on parenthood, including factors influencing parenthood probability, by comparing long-term HL survivors with matched general population controls.

Patients and Methods

A Life Situation Questionnaire was sent to 3,604 survivors treated from 1964 to 2004 in successive clinical trials. Responders were matched with controls (1:3 or 4) for sex, country, education, and year of birth (10-year groups). Controls were given an artificial date of start of treatment equal to that of their matched case. The main end point was presence of biologic children after treatment, which was evaluated by using conditional logistic regression analysis. Logistic regression analysis was used to analyze factors influencing spontaneous post-treatment parenthood.

Results

In all, 1,654 French and Dutch survivors were matched with 6,414 controls. Median follow-up was 14 years (range, 5 to 44 years). After treatment, the odds ratio (OR) for having children was 0.77 (95% CI, 0.68 to 0.87; P < .001) for survivors compared with controls. Of 898 survivors who were childless before treatment, 46.7% achieved post-treatment parenthood compared with 49.3% of 3,196 childless controls (OR, 0.87; P = .08). Among 756 survivors with children before treatment, 12.4% became parents after HL treatment compared with 22.2% of 3,218 controls with children before treatment (OR, 0.49; P < .001). Treatment with alkylating agents, second-line therapy, and age older than 35 years at treatment appeared to reduce the chances of spontaneous post-treatment parenthood.

Conclusion

Survivors of HL had slightly but significantly fewer children after treatment than matched general population controls. The difference concerned only survivors who had children before treatment and appears to have more personal than biologic reasons. The chance of successful post-treatment parenthood was 76%.
Noninitiation of Adjuvant Chemotherapy in Women With Localized Breast Cancer: The Breast Cancer Quality of Care Study
Authors: Neugut Alfred I. , Hillyer Grace Clarke , Kushi Lawrence H. , Lamerato Lois , Leoce Nicole , Nathanson S. David , Ambrosone Christine B. , Bovbjerg Dana H. , Mandelblatt Jeanne S. , Magai Carol , Tsai Wei Yann , Jacobson Judith S. , Hershman Dawn L.
Published: September 2012

Purpose

For some women, adjuvant chemotherapy for nonmetastatic breast cancer decreases recurrences and increases survival; however, patient-physician decisions regarding chemotherapy receipt can be influenced by medical and nonmedical factors.

Patients and Methods

We used a prospective cohort design and multivariate modeling to investigate factors related to noninitiation of chemotherapy among women with newly diagnosed breast cancer recruited from three US sites. We interviewed patients at baseline and during treatment on sociodemographic, tumor, and treatment decision-making factors. Patients were categorized according to National Comprehensive Cancer Network guidelines as those for whom chemotherapy was definitely indicated, clinically discretionary, or discretionary based on age greater than 70 years.

Results

Of 1,145 patients recruited, chemotherapy was clinically indicated for 392 patients, clinically discretionary for 459 patients, discretionary because of age for 169 patients, and not indicated for 93 patients; data were insufficient for 32 patients. Chemotherapy rates were 90% for those in whom chemotherapy was clinically indicated, 36% for those in whom it was discretionary because of clinical factors, and 19% for those in whom it was discretionary based on age greater than 70 years. Nonreceipt of chemotherapy was associated with older age, more negative beliefs about treatment efficacy, less positive beliefs about chemotherapy, and more concern about adverse effects. In the two discretionary groups, clinical predictors of worse outcome (greater tumor size, positive nodes, worse grade, and estrogen receptor– and progesterone receptor–negative status) were associated with increased chemotherapy initiation.

Conclusion

Utilization of adjuvant chemotherapy was most common among patients who, based on clinical criteria, would most likely benefit from it, patients with more positive than negative beliefs regarding treatment efficacy, and patients with few concerns about adverse effects.
Overexpression of Cyclin D3 Improves Decidualization Defects in Hoxa-10−/− Mice
Authors: Sroga Julie M. , Gao Fei , Ma Xinghong , Das Sanjoy K.
Published: September 2012

Uterine decidualization, a crucial process for implantation, is a tightly regulated process encompassing proliferation, differentiation, and polyploidization of uterine stromal cells. Hoxa (Homeobox A)-10, a homeobox transcription factor, is highly expressed in decidualizing stromal cells. Targeted gene deletion experiments have demonstrated marked infertility resulting from severely compromised decidualization in Hoxa-10−/− mice. However, the underlying mechanism by which Hoxa-10 regulates stromal cell differentiation remains poorly understood. Cyclin D3, a G1 phase cell-cycle regulatory protein involved in stromal cell proliferation and decidualization, is significantly reduced in Hoxa-10−/− mice. The expression of cyclin D3 in the pregnant mouse uterus parallels stromal cell decidualization. Here, we show that adenovirus-driven cyclin D3 replacement in Hoxa-10−/− mice improves stromal cell decidualization. To address our question of whether cyclin D3 replacement in Hoxa-10−/− mice can improve decidualization, both in vitro and in vivo studies were completed after the addition of cyclin D3 or empty (control) viral vectors. Immunostaining demonstrated increased proliferation and decidualization in both in vitro and in vivo studies, and in situ hybridization confirmed increased expression of decidualization markers in vivo. Placentation was demonstrated as well in vivo in the cyclin D3-replaced animals. However, fertility was not restored in Hoxa-10−/− mice after d 10 of pregnancy. Finally, we identified several downstream targets of cyclin D3 during decidualization in vitro via proteomics experiments, and these were confirmed using in situ hybridization in vivo. Collectively, these results demonstrate that cyclin D3 expression influences a host of genes involved in decidualization and can improve decidualization in Hoxa-10−/− mice.
Effect of okadaic acid on cultured clam heart cells: involvement of MAPkinase pathways
Authors: Hanana Houda , Talarmin Hélène , Pennec Jean-Pierre , Droguet Mickael , Morel Julie , Dorange Germaine
Published: September 2012

Okadaic acid (OA) is one of the main diarrhetic shellfish poisoning toxins and a potent inhibitor of protein phosphatases 1 and 2A. The downstream signal transduction pathways following the protein phosphatase inhibition are still unknown and the results of most of the previous studies are often conflicting. The aim of the present study was to evaluate the effects of OA on heart clam cells and to analyse its possible mechanisms of action by investigating the signal transduction pathways involved in OA cytotoxicity. We showed that OA at 1 µM after 24 h of treatment induces disorganization of the actin cytoskeleton, rounding and detachment of fibroblastic cells. Moreover, treatment of heart cells revealed a sequential activation of MAPK proteins depending on the OA concentration. We suggest that the duration of p38 and JNK activation is a critical factor in determining cell apoptosis in clam cardiomyocytes. In the opposite, ERK activation could be involved in cell survival. The cell death induced by OA is a MAPK modulated pathway, mediated by caspase 3-dependent mechanism. OA was found to induce no significant effect on spontaneous beating rate or inward L-type calcium current in clam cardiomyocytes, suggesting that PP1 was not inhibited even by the highest dose of OA.
The anti-motility signaling mechanism of TGFβ3 that controls cell traffic during skin wound healing
Authors: Han Arum , Bandyopadhyay Balaji , Jayaprakash Priyamvada , Lua Ingrid , Sahu Divya , Chen Mei , Woodley David T. , Li Wei
Published: September 2012

When skin is wounded, migration of epidermal keratinocytes at the wound edge initiates within hours, whereas migration of dermal fibroblasts toward the wounded area remains undetectable until several days later. This “cell type traffic” regulation ensures proper healing of the wound, as disruptions of the regulation could either cause delay of wound healing or result in hypertrophic scars. TGFβ3 is the critical traffic controller that selectively halts migration of the dermal, but not epidermal, cells to ensure completion of wound re-epithelialization prior to wound remodeling. However, the mechanism of TGFβ3's anti-motility signaling has never been investigated. We report here that activated TβRII transmits the anti-motility signal of TGFβ3 in full to TβRI, since expression of the constitutively activated TβRI-TD mutant was sufficient to replace TGFβ3 to block PDGF-bb-induced dermal fibroblast migration. Second, the three components of R-Smad complex are all required. Individual downregulation of Smad2, Smad3 or Smad4 prevented TGFβ3 from inhibiting dermal fibroblast migration. Third, Protein Kinase Array allowed us to identify the protein kinase A (PKA) as a specific downstream effector of R-Smads in dermal fibroblasts. Activation of PKA alone blocked PDGF-bb-induced dermal fibroblast migration, just like TGFβ3. Downregulation of PKA's catalytic subunit nullified the anti-motility signaling of TGFβ3. This is the first report on anti-motility signaling mechanism by TGFβ family cytokines. Significance of this finding is not only limited to wound healing but also to other human disorders, such as heart attack and cancer, where the diseased cells have often managed to avoid the anti-motility effect of TGFβ.
A Nestin-cre transgenic mouse is insufficient for recombination in early embryonic neural progenitors
Authors: Liang Huixuan , Hippenmeyer Simon , Ghashghaei H. Troy
Published: September 2012

Nestin-cre transgenic mice have been widely used to direct recombination to neural stem cells (NSCs) and intermediate neural progenitor cells (NPCs). Here we report that a readily utilized, and the only commercially available, Nestin-cre line is insufficient for directing recombination in early embryonic NSCs and NPCs. Analysis of recombination efficiency in multiple cre-dependent reporters and a genetic mosaic line revealed consistent temporal and spatial patterns of recombination in NSCs and NPCs. For comparison we utilized a knock-in Emx1cre line and found robust recombination in NSCs and NPCs in ventricular and subventricular zones of the cerebral cortices as early as embryonic day 12.5. In addition we found that the rate of Nestin-cre driven recombination only reaches sufficiently high levels in NSCs and NPCs during late embryonic and early postnatal periods. These findings are important when commercially available cre lines are considered for directing recombination to embryonic NSCs and NPCs.