bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary fat increases solid tumor growth and metastasis of 4T1 murine mammary carcinoma cells and mortality in obesity-resistant BALB/c mice
Authors: Kim Eun Ji , Choi Mi-Ran , Park Heesook , Kim Minhee , Hong Ji Eun , Lee Jae-Yong , Chun Hyang Sook , Lee Ki Won , Yoon Park Jung Han
Published: August 2011

Introduction

High-fat diets (HFDs) are known to cause obesity and are associated with breast cancer progression and metastasis. Because obesity is associated with breast cancer progression, it is important to determine whether dietary fat per se stimulates breast cancer progression in the absence of obesity. This study investigated whether an HFD increases breast cancer growth and metastasis, as well as mortality, in obesity-resistant BALB/c mice.

Methods

The 4-week-old, female BALB/c mice were fed HFD (60% kcal fat) or control diet (CD, 10% kcal fat) for 16 weeks. Subsequently, 4T1 mammary carcinoma cells were injected into the inguinal mammary fat pads of mice fed continuously on their respective diets. Cell-cycle progression, angiogenesis, and immune cells in tumor tissues, proteases and adhesion molecules in the lungs, and serum cytokine levels were analyzed with immunohistochemistry, Western blotting, and enzyme-linked immunosorbent assay (ELISA). In vitro studies were also conducted to evaluate the effects of cytokines on 4T1 cell viability, migration, and adhesion.

Results

Spleen and gonadal fat-pad weights, tumor weight, the number and volume of tumor nodules in the lung and liver, and tumor-associated mortality were increased in the HFD group, with only slight increases in energy intake and body weight. HF feeding increased macrophage infiltration into adipose tissues, the number of lipid vacuoles and the expression of cyclin-dependent kinase (CDK)2, cyclin D1, cyclin A, Ki67, CD31, CD45, and CD68 in the tumor tissues, and elevated serum levels of complement fragment 5a (C5a), interleukin (IL)-16, macrophage colony-stimulating factor (M-CSF), soluble intercellular adhesion molecule (sICAM)-1, tissue inhibitors of metalloproteinase (TIMP)-1, leptin, and triggering receptor expressed on myeloid cells (TREM)-1. Protein levels of the urokinase-type plasminogen activator, ICAM-1, and vascular cell adhesion molecule-1 were increased, but plasminogen activator inhibitor-1 levels were decreased in the lungs of the HFD group. In vitro assays using 4T1 cells showed that sICAM-1 increased viability; TREM-1, TIMP-1, M-CSF, and sICAM-1 increased migration; and C5a, sICAM-1, IL-16, M-CSF, TIMP-1, and TREM-1 increased adhesion.

Conclusions

Dietary fat increases mammary tumor growth and metastasis, thereby increasing mortality in obesity-resistant mice.
Transcriptome analysis of embryonic mammary cells reveals insights into mammary lineage establishment
Authors: Wansbury Olivia , Mackay Alan , Kogata Naoko , Mitsopoulos Costas , Kendrick Howard , Davidson Kathryn , Ruhrberg Christiana , Reis-Filho Jorge S , Smalley Matthew J , Zvelebil Marketa , Howard Beatrice A
Published: August 2011

Introduction

The mammary primordium forms during embryogenesis as a result of inductive interactions between its constitutive tissues, the mesenchyme and epithelium, and represents the earliest evidence of commitment to the mammary lineage. Previous studies of embryonic mouse mammary epithelium indicated that, by mid-gestation, these cells are determined to a mammary cell fate and that a stem cell population has been delimited. Mammary mesenchyme can induce mammary development from simple epithelium even across species and classes, and can partially restore features of differentiated tissue to mouse mammary tumours in co-culture experiments. Despite these exciting properties, the molecular identity of embryonic mammary cells remains to be fully characterised.

Methods

Here, we define the transcriptome of the mammary primordium and the two distinct cellular compartments that comprise it, the mammary primordial bud epithelium and mammary mesenchyme. Pathway and network analysis was performed and comparisons of embryonic mammary gene expression profiles to those of both postnatal mouse and human mammary epithelial cell sub-populations and stroma were made.

Results

Several of the genes we have detected in our embryonic mammary cell signatures were previously shown to regulate mammary cell fate and development, but we also identified a large number of novel candidates. Additionally, we determined genes that were expressed by both embryonic and postnatal mammary cells, which represent candidate regulators of mammary cell fate, differentiation and progenitor cell function that could signal from mammary lineage inception during embryogenesis through postnatal development. Comparison of embryonic mammary cell signatures with those of human breast cells identified potential regulators of mammary progenitor cell functions conserved across species.

Conclusions

These results provide new insights into genetic regulatory mechanisms of mammary development, particularly identification of novel potential regulators of mammary fate and mesenchymal-epithelial cross-talk. Since cancers may represent diseases of mesenchymal-epithelial communications, we anticipate these results will provide foundations for further studies into the fundamental links between developmental, stem cell and breast cancer biology.
Roscovitine confers tumor suppressive effect on therapy-resistant breast tumor cells
Authors: Nair Binoj C , Vallabhaneni Sreeram , Tekmal Rajeshwar R , Vadlamudi Ratna K
Published: August 2011

Introduction

Current clinical strategies for treating hormonal breast cancer involve the use of anti-estrogens that block estrogen receptor (ER)α functions and aromatase inhibitors that decrease local and systemic estrogen production. Both of these strategies improve outcomes for ERα-positive breast cancer patients, however, development of therapy resistance remains a major clinical problem. Divergent molecular pathways have been described for this resistant phenotype and interestingly, the majority of downstream events in these resistance pathways converge upon the modulation of cell cycle regulatory proteins including aberrant activation of cyclin dependent kinase 2 (CDK2). In this study, we examined whether the CDK inhibitor roscovitine confers a tumor suppressive effect on therapy-resistant breast epithelial cells.

Methods

Using various in vitro and in vivo assays, we tested the effect of roscovitine on three hormonal therapy-resistant model cells: (a) MCF-7-TamR (acquired tamoxifen resistance model); (b) MCF-7-LTLTca (acquired letrozole resistance model); and (c) MCF-7-HER2 that exhibit tamoxifen resistance (ER-growth factor signaling cross talk model).

Results

Hormonal therapy-resistant cells exhibited aberrant activation of the CDK2 pathway. Roscovitine at a dose of 20 μM significantly inhibited the cell proliferation rate and foci formation potential of all three therapy-resistant cells. The drug treatment substantially increased the proportion of cells in G2/M cell cycle phase with decreased CDK2 activity and promoted low cyclin D1 levels. Interestingly, roscovitine also preferentially down regulated the ERα isoform and ER-coregulators including AIB1 and PELP1. Results from xenograft studies further showed that roscovitine can attenuate growth of therapy-resistant tumors in vivo.

Conclusions

Roscovitine can reduce cell proliferation and survival of hormone therapy-resistant breast cancer cells. Our results support the emerging concept that inhibition of CDK2 activity has the potential to abrogate growth of hormonal therapy-resistant cells.
Electrical impedance tomography measured at two thoracic levels can visualize the ventilation distribution changes at the bedside during a decremental positive end-expiratory lung pressure trial
Authors: Bikker Ido G , Preis Carsten , Egal Mahamud , Bakker Jan , Gommers Diederik
Published: August 2011

Introduction

Computed tomography of the lung has shown that ventilation shifts from dependent to nondependent lung regions. In this study, we investigated whether, at the bedside, electrical impedance tomography (EIT) at the cranial and caudal thoracic levels can be used to visualize changes in ventilation distribution during a decremental positive end-expiratory pressure (PEEP) trial and the relation of these changes to global compliance in mechanically ventilated patients.

Methods

Ventilation distribution was calculated on the basis of EIT results from 12 mechanically ventilated patients after cardiac surgery at a cardiothoracic ICU. Measurements were taken at four PEEP levels (15, 10, 5 and 0 cm H2O) at both the cranial and caudal lung levels, which were divided into four ventral-to-dorsal regions. Regional compliance was calculated using impedance and driving pressure data.

Results

We found that tidal impedance variation divided by tidal volume significantly decreased on caudal EIT slices, whereas this measurement increased on the cranial EIT slices. The dorsal-to-ventral impedance distribution, expressed according to the center of gravity index, decreased during the decremental PEEP trial at both EIT levels. Optimal regional compliance differed at different PEEP levels: 10 and 5 cm H2O at the cranial level and 15 and 10 cm H2O at the caudal level for the dependent and nondependent lung regions, respectively.

Conclusions

At the bedside, EIT measured at two thoracic levels showed different behavior between the caudal and cranial lung levels during a decremental PEEP trial. These results indicate that there is probably no single optimal PEEP level for all lung regions.
Elevated red cell distribution width predicts poor outcome in young patients with community acquired pneumonia
Authors: Braun Eyal , Domany Erel , Kenig Yael , Mazor Yoav , Makhoul Badira F , Azzam Zaher S
Published: August 2011

Introduction

Community acquired pneumonia (CAP) is a major cause of morbidity and mortality. While there is much data about risk factors for severe outcome in the general population, there is less focus on younger group of patients. Therefore, we aimed to detect simple prognostic factors for severe morbidity and mortality in young patients with CAP.

Methods

Patients of 60 years old or younger, who were diagnosed with CAP (defined as pneumonia identified 48 hours or less from hospitalization) between March 1, 2005 and December 31, 2008 were retrospectively analyzed for risk factors for complicated hospitalization and 90-day mortality.

Results

The cohort included 637 patients. 90-day mortality rate was 6.6% and the median length of stay was 5 days. In univariate analysis, male patients and those with co-morbid conditions tended to have complicated disease. In multivariate analysis, variables associated with complicated hospitalization included post chest radiation state, prior neurologic damage, blood urea nitrogen (BUN) > 10.7 mmol/L and red cell distribution width (RDW) > 14.5%; whereas, variables associated with an increased risk of 90-day mortality included age ≥ 51 years, prior neurologic damage, immunosuppression, and the combination of abnormal white blood cells (WBC) and elevated RDW. Complicated hospitalization and mortality rate were significantly higher among patients with increased RDW regardless of the white blood cell count. Elevated RDW was associated with a significant increase in complicated hospitalization and 90-day mortality rates irrespective to hemoglobin levels.

Conclusions

In young patients with CAP, elevated RDW levels are associated with significantly higher rates of mortality and severe morbidity. RDW as a prognostic marker was unrelated with hemoglobin levels.

Trial registration

ClinicalTrials.Gov NCT00845312
Plasma cell-free DNA in patients needing mechanical ventilation
Authors: Okkonen Marjatta , Lakkisto Päivi , Korhonen Anna-Maija , Parviai-nen Ilkka , Reinikainen Matti , Varpula Tero , Pettilä Ville ,   The FINNALI Study Group
Published: August 2011

Introduction

Concentrations of plasma cell-free DNA are increased in various diseases and have shown some prognostic value in many patient groups, including critically ill patients. Pathophysiological processes behind the need for mechanical ventilation and the treatment itself could raise plasma levels of cell-free DNA. We evaluated levels of plasma cell-free DNA and their prognostic value in patients needing mechanical ventilation.

Methods

We studied prospectively 580 mechanically ventilated critically ill patients. Blood samples were taken at study admission (Day 0) and on Day 2. Plasma cell-free DNA concentrations were measured by real-time quantitative PCR assay for the β-globin gene and are expressed as genome equivalents (GE)/ml.

Results

Median (interquartile range, IQR) plasma cell-free DNA concentration was 11,853 GE/ml (5,304 to 24,620 GE/mL) at study admission, and 11,610 GE/mL (6,411 to 21,558 GE/mL) on Day 2. Concentrations at admission were significantly higher in 90-day non-survivors than survivors, 16,936 GE/mL (7,262 to 46,866 GE/mL) versus 10,026 GE/mL (4,870 to 19,820 GE/mL), P < 0.001. In a multivariate logistic regression analysis plasma cell-free DNA concentration over 16,000 GE/ml remained an independent predictor of 90-day mortality (adjusted odds ratio 2.16, 95% confidence interval CI 1.37 to 3.40). Positive likelihood ratio of plasma cell-free DNA at admission for the prediction of 90-day mortality was 1.72 (95% CI 1.40 to 2.11).

Conclusions

Plasma levels of cell-free DNA were significantly higher in non-survivors than survivors. Plasma DNA level at baseline was an independent predictor of 90-day mortality. However, its clinical benefit as a prognostic marker seems to be limited.
Hybrid selection for sequencing pathogen genomes from clinical samples
Authors: Melnikov Alexandre , Galinsky Kevin , Rogov Peter , Fennell Timothy , Van Tyne Daria , Russ Carsten , Daniels Rachel , Barnes Kayla G , Bochicchio James , Ndiaye Daouda , Sene Papa D , Wirth Dyann F , Nusbaum Chad , Volkman Sarah K , Birren Bruce W , Gnirke Andreas , Neafsey Daniel E
Published: August 2011

We have adapted a solution hybrid selection protocol to enrich pathogen DNA in clinical samples dominated by human genetic material. Using mock mixtures of human and Plasmodium falciparum malaria parasite DNA as well as clinical samples from infected patients, we demonstrate an average of approximately 40-fold enrichment of parasite DNA after hybrid selection. This approach will enable efficient genome sequencing of pathogens from clinical samples, as well as sequencing of endosymbiotic organisms such as Wolbachia that live inside diverse metazoan phyla.
Farnesyltransferase inhibitor treatment restores chromosome territory positions and active chromosome dynamics in Hutchinson-Gilford progeria syndrome cells
Authors: Mehta Ishita S , Eskiw Christopher H , Arican Halime D , Kill Ian R , Bridger Joanna M
Published: August 2011

Background

Hutchinson-Gilford progeria syndrome (HGPS) is a premature ageing syndrome that affects children leading to premature death, usually from heart infarction or strokes, making this syndrome similar to normative ageing. HGPS is commonly caused by a mutation in the A-type lamin gene, LMNA (G608G). This leads to the expression of an aberrant truncated lamin A protein, progerin. Progerin cannot be processed as wild-type pre-lamin A and remains farnesylated, leading to its aberrant behavior during interphase and mitosis. Farnesyltransferase inhibitors prevent the accumulation of farnesylated progerin, producing a less toxic protein.

Results

We have found that in proliferating fibroblasts derived from HGPS patients the nuclear location of interphase chromosomes differs from control proliferating cells and mimics that of control quiescent fibroblasts, with smaller chromosomes toward the nuclear interior and larger chromosomes toward the nuclear periphery. For this study we have treated HGPS fibroblasts with farnesyltransferase inhibitors and analyzed the nuclear location of individual chromosome territories. We have found that after exposure to farnesyltransferase inhibitors mis-localized chromosome territories were restored to a nuclear position akin to chromosomes in proliferating control cells. Furthermore, not only has this treatment afforded chromosomes to be repositioned but has also restored the machinery that controls their rapid movement upon serum removal. This machinery contains nuclear myosin 1β, whose distribution is also restored after farnesyltransferase inhibitor treatment of HGPS cells.

Conclusions

This study not only progresses the understanding of genome behavior in HGPS cells but demonstrates that interphase chromosome movement requires processed lamin A.
The value of 3D T1-weighted gradient-echo MR imaging for evaluation of the appendix during pregnancy: preliminary results
Authors: Jang Kyung Mi , Kim Seong Hyun , Choi Dongil , Lee Soon Jin , Rhim Hyunchul , Park Min Jung
Published: August 2011

Background

The use of oral contrast has been essential for the identification of a normal appendix on MR imaging during pregnancy. However, stool could be used as a positive oral contrast as it is characterized by a relatively high signal on T1-weighted imaging, and 3D T1-weighted gradient-echo (T1W-GRE) MR imaging has been used to evaluate 3 mm diameter intestines in fetuses.

Purpose

To evaluate the added value of 3D T1W-GRE MR imaging in combination with T2-weighted imaging (T2WI) compared to T2WI alone for evaluating the appendix during pregnancy.

Material and Methods

Eighteen consecutive pregnant patients who were clinically suspected of having acute appendicitis underwent appendix MR imaging which included T2WI with or without spectral presaturation attenuated inversion-recovery (SPAIR) fat suppression, and 3D T1W-GRE with SPAIR fat suppression. Two radiologists reviewed the two image sets (the T2WI set and the combined set of T2WI and 3D T1W-GRE images). Pathologic and clinical results served as the reference standard. The differences in the degree of visibility of the appendix and confidence scale for diagnosing acute appendicitis between two image sets were compared by using the paired Wilcoxon signed rank test.

Results

For both reviewers, the degree of visibility of the appendix using the combined T2WI and 3D T1W-GRE images was significantly higher than using T2WI alone ( P < 0.01), and the confidence levels for acute appendicitis using combined T2WI and 3D T1W-GRE images were significantly different from those using T2WI alone ( P < 0.01). In the 13 patients with a normal appendix, both reviewers showed improved confidence levels for appendicitis using combined T2WI and 3D T1W-GRE images than T2WI alone.

Conclusion

Adding 3D T1W-GRE images to T2WI is helpful for identification of the appendix, as compared to T2WI alone in pregnant women without ingestion of oral contrast material. This may improve diagnostic confidence for acute appendicitis in pregnant patients.
Preoperative evaluation of neurovascular relationship by using contrast-enhanced and unenhanced 3D time-of-flight MR angiography in patients with trigeminal neuralgia
Authors: Zhou Qin , Liu Zhiling , Li Chuanfu , Qu Chuncheng , Ni Shilei , Zeng Qingshi
Published: August 2011

Background

Microvascular decompression is an etiological strategy for the therapy of trigeminal neuralgia (TN). Preoperative identification of neurovascular compression, therefore, could have an impact on the determination of appropriate treatment for TN.

Purpose

To evaluate the value of contrast-enhanced and unenhanced three-dimensional (3D) time-of-flight (TOF) MR angiography in the visualization of neurovascular relationship in patients with TN.

Material and Methods

Thirty-seven patients with unilateral TN underwent unenhanced and contrast-enhanced 3D TOF MR angiography with a 3.0-T MR system. Images were reviewed by a radiologist blinded to clinical details. Vascular contact with the trigeminal nerve was identified, and the nature of the involved vessels (artery or vein) was determined. All patients underwent microvascular decompression.

Results

In 37 patients with TN, contrast-enhanced 3D TOF MR angiography identified surgically verified neurovascular contact in 35 of 36 symptomatic nerves, and there was no false-positive. Based on surgical findings, the sensitivity of MR imaging was 97.2% and specificity 100%. The nature of the offending vessel was correctly identified in 94.4% of the patients by using the combination of contrast-enhanced and unenhanced MR angiography.

Conclusion

Contrast-enhanced 3D TOF MR angiography is useful in the detection of vascular contact with the trigeminal nerve in patients with TN, and this MR imaging in combination with unenhanced MR angiography could help in the identification of the nature of the responsible vessels.
Variation of fee-for-service specialist direct care work effort with patient overall illness burden
Authors: Goodman Robert
Published: August 2011

Objective

To explore whether a common industry measure of overall patient illness burden, used to assess the total costs of members in a health plan, would be suitable to describe variation in a summary metric of utilization that assesses specialist physician direct patient care services not grouped into clinical episodes, but with exclusion criteria applied to reduce any bias in the data.

Data sources/study setting

Calendar year 2006 administrative data on 153,557 commercial members enrolled in a non-profit single-state statewide Health Maintenance Organization (HMO) and treated by 4356 specialists in 11 specialties. The health plan's global referral process and specialist fee-for-service reimbursement likely makes these results applicable to the non-managed care setting, as once a global referral was authorized there was no required intervention by the HMO or referring primary care provider for the majority of any subsequent specialist direct clinical care.

Study design

Specialty-specific correlations and ordinary least-squares regression models to assess variations in specialist direct patient care work effort with patient overall illness burden, after the application of exclusion criteria to reduce potential bias in the data.

Principle findings

Statistically significant positive correlations exist between specialist direct patient care work effort and patient overall illness burden for all studied specialties. Regression models revealed a generally monotonic increasing relationship between illness burden categories and aggregate specialist direct patient care work effort. Almost all regression model differences from the reference category across specialties are statistically significant ( P ≤ 0.012). Assessment of additional results demonstrates the relationship has more substantive significance in some specialties and less in others. The most substantive relationships in this study were found in the specialties of orthopaedic surgery, general surgery and interventional cardiology.

Conclusions

For many specialties, specialists do vary physician direct patient care utilization with patient overall illness burden. Accounting for patient overall health status is important to fairly compare specialists of certain specialties on utilization for health plan specialist network management. Additional study is required to evaluate health plan application of this methodology.
Uninformative Advertising as an Invitation to Search
Authors: Mayzlin Dina , Shin Jiwoong
Published: August 2011

What the firm should say in an advertising message, the choice of content, is a critical managerial decision. Here, we focus on a particular aspect of the advertising content choice: an attribute-focused appeal versus an appeal with no direct information on product attributes. We make two assumptions that capture the reality of the advertising context. First, we assume that the bandwidth of advertising is limited: a firm can only communicate about a limited number of attributes. Second, we assume that consumers are active: they can choose to engage in a costly search to obtain additional product-related information. In this setting, we show that there exists an equilibrium where the high-quality firm chooses to produce messages devoid of any attribute information in order to invite the consumer to engage in search, which is likely to uncover positive information about the product. Whereas most of the previous literature has focused on the decision to advertise as a signal of quality, we show that message content, coupled with consumer search, can also serve as a credible signal of quality. In an extension, we show that our results are robust to endogenizing the firm's decision on the amount of advertising spending.
Association of Cognitive Impairment with Combinations of Vitamin B12–Related Parameters
Authors: Lildballe Dorte L , Fedosov Sergey , Sherliker Paul , Hin Harold , Clarke Robert , Nexo Ebba
Published: August 2011

BACKGROUND

Low vitamin B12 concentrations have been associated with higher risks of cognitive impairment, but whether these associations are causal is uncertain. The associations of cognitive impairment with combinations of vitamin B12, holotranscobalamin, methylmalonic acid, and total homocysteine, and with the vitamin B12 transport proteins transcobalamin and haptocorrin, have not been previously studied.

METHODS

We performed a population-based cross-sectional study of 839 people 75 years old or older. We examined the association of cognitive function as measured by mini–mental state examination scores, with markers of vitamin B12 status. Spearman correlations as well as multivariate-adjusted odds ratios and 95% CIs for cognitive impairment were calculated for extreme thirds of serum concentrations of vitamin B12, holotranscobalamin, methylmalonic acid, total homocysteine, combination of these markers in a wellness score, heaptocorrin, and transcobalamin for all data and with B12 analogs in a nested case-control study.

RESULTS

Cognitive impairment was significantly associated with low vitamin B12 [odds ratio 2.3 (95% CI 1.2–4.5)]; low holotranscobalamin [4.1 (2.0–8.7)], high methylmalonic acid [3.5 (1.8–7.1)], high homocysteine [4.8 (2.3–10.0)] and low wellness score [5.1 (2.61–10.46)]. After correction for relevant covariates, cognitive impairment remained significantly associated with high homocysteine [4.85 (2.24–10.53)] and with a low wellness score [5.60 (2.61–12.01)] but not with transcobalamin, haptocorrin, or analogs on haptocorrin.

CONCLUSIONS

Cognitive impairment was associated with the combined effects of the 4 biomarkers of vitamin B12 deficiency when included in a wellness score but was not associated with binding proteins or analogs on haptocorrin.
Determination of Hemolysis Thresholds by the Use of Data Loggers in Pneumatic Tube Systems
Authors: Streichert Thomas , Otto Benjamin , Schnabel Claudia , Nordholt Gerhard , Haddad Munif , Maric Mario , Petersmann Astrid , Jung Roman , Wagener Christoph
Published: August 2011

BACKGROUND

Pneumatic tube systems (PTSs) for the transport of blood samples are regaining popularity in medical centers after earlier reports that their use could introduce preanalytical distortions such as hemolysis and changes in blood gases.

METHODS

We drew duplicate blood samples from 30 volunteers. One sample was hand transported, and the other sample was transported through a PTS together with a mini–data logger that provided continuous measurements of temperature, humidity, pressure, and acceleration. After transport the samples were analyzed at the same time. We looked for possible relationships of the transport method and the parameters measured by the data loggers with differences in hematological parameters, standard clinical chemistry analyses, blood coagulation, erythrocyte sedimentation rate, and blood gas analysis.

RESULTS

There were no significant differences in temperature, humidity, and pressure between the methods of transport, but we observed significant differences in 3-axis accelerations. The combined effect of these forces could be described by the right-tailed area under the vector sum acceleration distribution. Our data show that this area correlated with PTS speed and that PTS speed and the area under the curve exhibited a direct relation to the degree of hemolysis.

CONCLUSIONS

Assessment of 3-axis acceleration by use of data loggers can be used to identify preanalytical deviations that result from the transportation of blood samples in PTSs. Our approach could be used for the evaluation and regular control of PTSs without the need for repeated blood drawing and laboratory analyses.
Identification of Recent Cannabis Use: Whole-Blood and Plasma Free and Glucuronidated Cannabinoid Pharmacokinetics following Controlled Smoked Cannabis Administration
Authors: Schwope David M , Karschner Erin L , Gorelick David A , Huestis Marilyn A
Published: August 2011

BACKGROUND

Δ9-Tetrahydrocannabinol (THC) is the most frequently observed illicit drug in investigations of accidents and driving under the influence of drugs. THC-glucuronide has been suggested as a marker of recent cannabis use, but there are no blood data following controlled THC administration to test this hypothesis. Furthermore, there are no studies directly examining whole-blood cannabinoid pharmacokinetics, although this matrix is often the only available specimen.

METHODS

Participants (9 men, 1 woman) resided on a closed research unit and smoked one 6.8% THC cannabis cigarette ad libitum. We quantified THC, 11-hydroxy-THC (11-OH-THC), 11-nor-9-carboxy-THC (THCCOOH), cannabidiol (CBD), cannabinol (CBN), THC-glucuronide and THCCOOH-glucuronide directly in whole blood and plasma by liquid chromatography/tandem mass spectrometry within 24 h of collection to obviate stability issues.

RESULTS

Median whole blood (plasma) observed maximum concentrations (Cmax) were 50 (76), 6.4 (10), 41 (67), 1.3 (2.0), 2.4 (3.6), 89 (190), and 0.7 (1.4) μg/L 0.25 h after starting smoking for THC, 11-OH- THC, THCCOOH, CBD, CBN, and THCCOOH-glucuronide, respectively, and 0.5 h for THC-glucuronide. At observed Cmax, whole-blood (plasma) detection rates were 60% (80%), 80% (90%), and 50% (80%) for CBD, CBN, and THC-glucuronide, respectively. CBD and CBN were not detectable after 1 h in either matrix (LOQ 1.0 μg/L).

CONCLUSIONS

Human whole-blood cannabinoid data following cannabis smoking will assist whole blood and plasma cannabinoid interpretation, while furthering identification of recent cannabis intake.
Informationsinfrastrukturen gestern, heute, morgen. Anmerkungen zu Empfehlungen des Wissenschaftsrates
Authors: Dugall Berndt
Published: August 2011

Mit den „Empfehlungen zu Forschungsinfrastrukturen“ hat der Wissenschaftsrat im Frühjahr 2011 umfängliche Hinweise und Vorschläge zur Neuordnung insbesondere der Informationsinfrastrukturen in Deutschland unterbreitet. Dabei spielen die gravierenden Veränderungen der letzten Jahre in diesem Bereich eine wesentliche Rolle. In dem vorliegenden Beitrag werden die Vorschläge und Thesen auf der Basis der Entwicklung und Herausbildung von Informationsinfrastrukturen in den letzten 50 Jahren in Deutschland unter besonderer Berücksichtigung der jeweils dazu ergangenen früheren Empfehlungen des Wissenschaftsrats diskutiert.
Uniqueness of lattice packings and coverings of extreme density
Authors: Gruber Peter M.
Published: August 2011

For d = 2, 3 a generic convex body in has a unique lattice packing and for d ≥ 4 at most a(d) lattice packings of maximum density, where a(d) ≥ 1 is a constant. If in a certain connectedness property holds, one may take a(d) = 1. Dually, for d = 2 a generic convex body has a unique lattice covering of minimum density and for d ≥ 3 there is a constant b(d) ≥ 1 such that it has at most b(d) such coverings.
Impact of New Chemotherapeutic and Targeted Agents on Survival in Stage IV Non-Small Cell Lung Cancer
Authors: Yu Joanne L. , Simmons Christine , Victor J. Charles , Han Dolly , Hogeveen Sophie , Leighl Natasha , Verma Sunil
Published: August 2011

Purpose.

Significant advances in the systemic management of metastatic non-small cell lung cancer (NSCLC) have occurred over the past decade, with options now including multiple lines of chemotherapy, epidermal growth factor receptor inhibitors, and antiangiogenic agents. Improvements in overall survival have been demonstrated in randomized controlled trials comparing these newer agents with best supportive care or standard therapy. This study examined uptake of these therapies in general practice and their impact on survival.

Methods.

This retrospective cohort study compared demographic, treatment, and survival data among 987 patients diagnosed with stage IV NSCLC at two institutions in 1998, 2003, and 2008. Cohorts were selected based on intervals when doublet chemotherapy, second-line chemotherapy, and targeted agents were incorporated into the standard treatment regimen.

Results.

The proportion of patients receiving systemic therapy increased over time (20% in 1998, 42% in 2008). Overall survival improved significantly across cohorts (p < .001), with 2-year survival rates of 0.3% in 1998, 4% in 2003, and 15% in 2008. In a multivariate survival analysis, the 2003 and 2008 cohorts were independently associated with longer survival, as was the use of one or more lines of systemic therapy. Elderly patients (aged ≥70 years) were also more likely to receive systemic therapy over time, with longer overall survival (p < .001).

Conclusion.

Over the past decade, there has been an increasing use of systemic therapy in stage IV NSCLC patients, including the elderly. This has been associated with significantly longer overall survival.
Prognostic Role of Vitamin D Status and Efficacy of Vitamin D Supplementation in Cancer Patients: A Systematic Review
Authors: Buttigliero Consuelo , Monagheddu Chiara , Petroni Paola , Saini Andrea , Dogliotti Luigi , Ciccone Giovannino , Berruti Alfredo
Published: August 2011

Background.

Whether or not hypovitaminosis D can influence the prognosis of cancer patients and whether or not vitamin D (vitD) supplementation improves outcome remain controversial.

Design.

Studies evaluating the prognostic role of vitD and vitD receptor (VDR) in cancer patients and trials evaluating the efficacy of vitD administration on patient outcome were identified by a search of MEDLINE, EMBASE, ISI Web of Knowledge, and the Cochrane Library through June 2010.

Results.

Twenty-five studies were included. A negative prognostic role for low serum vitD level was observed in five cohort studies including patients with breast cancer (one study), colon cancer (two studies), prostate cancer (one study), and melanoma (one study), but not in two studies on non-small cell lung cancer and one study on breast cancer. Three of four studies showed that VDR+ tumors carry a better prognosis than VDR− tumors, whereas VDR polymorphisms were significantly associated with prognosis in five of 10 studies. A significant interaction between serum vitD level and VDR polymorphism was observed in one study. Three randomized trials involving advanced prostate cancer patients explored the prognostic role of vitD supplementation. A meta-analysis of these trials showed no effect on survival (pooled risk ratio, 1.07; 95% confidence interval, CI, 0.93–1.23), with strong heterogeneity among studies.

Conclusion.

Hypovitaminosis D seems to be associated with a worse prognosis in some cancers, but vitD supplementation failed to demonstrate a benefit in prostate cancer patients. The currently available evidence is insufficient to recommend vitD supplementation in cancer patients in clinical practice.
If I Am in the Mood, I Enjoy It: An Exploration of Cancer-Related Fatigue and Sexual Functioning in Women with Breast Cancer
Authors: Webber Kate , Mok Kelly , Bennett Barbara , Lloyd Andrew R. , Friedlander Michael , Juraskova Ilona , Goldstein David ,   FolCan study group
Published: August 2011

Learning Objectives

After completing this course, the reader will be able to: Explain the relationship between cancer-related fatigue and sexual function.Identify the presence of mood disorder as a key determinant of sexual problems after adjuvant breast cancer therapy.

This article is available for continuing medical education credit at CME.TheOncologist.com

Background.

We recently reported that cancer-related fatigue (CRF) after adjuvant breast cancer therapy was prevalent and disabling, but largely self-limiting within 12 months. The current paper describes sexual functioning (SF) and its relationship to CRF, mood disorder, and quality of life (QOL) over the first year after completion of adjuvant therapy.

Methods.

Women were recruited after surgery, but prior to commencing adjuvant treatment, for early-stage breast cancer. Self-reported validated questionnaires assessed SF, CRF, mood, menopausal symptoms, disability, and QOL at baseline, completion of therapy, and at 6 months and 12 months after treatment.

Results.

Of the 218 participants, 92 (42%) completed the SF measure (mean age, 50 years). They were significantly younger, more likely to be partnered, and less likely to be postmenopausal than nonresponders. At baseline, 40% reported problems with sexual interest and 60% reported problems with physical sexual function. SF scores declined across all domains at the end of treatment, then improved but remained below baseline at 12 months, with a significant temporal effect in the physical SF subscale and a trend for overall satisfaction. There were significant correlations between the SF and QOL domains (physical and emotional health, social functioning, and general health) as well as overall QOL. The presence of mood disorder, but not fatigue, demographic, or treatment variables, independently predicted worse overall sexual satisfaction.

Conclusions.

Sexual dysfunction is common after breast cancer therapy and impacts QOL. Interventions should include identification and treatment of concomitant mood disorder.
Disproportionate Proximity to Environmental Health Hazards: Methods, Models, and Measurement
Authors: Chakraborty Jayajit , Maantay Juliana A. , Brender Jean D.
Published: August 2011

We sought to provide a historical overview of methods, models, and data used in the environmental justice (EJ) research literature to measure proximity to environmental hazards and potential exposure to their adverse health effects. We explored how the assessment of disproportionate proximity and exposure has evolved from comparing the prevalence of minority or low-income residents in geographic entities hosting pollution sources and discrete buffer zones to more refined techniques that use continuous distances, pollutant fate-and-transport models, and estimates of health risk from toxic exposure.

We also reviewed analytical techniques used to determine the characteristics of people residing in areas potentially exposed to environmental hazards and emerging geostatistical techniques that are more appropriate for EJ analysis than conventional statistical methods.

We concluded by providing several recommendations regarding future research and data needs for EJ assessment that would lead to more reliable results and policy solutions.
Moving Environmental Justice Indoors: Understanding Structural Influences on Residential Exposure Patterns in Low-Income Communities
Authors: Adamkiewicz Gary , Zota Ami R. , Fabian M. Patricia , Chahine Teresa , Julien Rhona , Spengler John D. , Levy Jonathan I.
Published: August 2011

Objectives. The indoor environment has not been fully incorporated into the environmental justice dialogue. To inform strategies to reduce disparities, we developed a framework to identify the individual and place-based drivers of indoor environment quality.

Methods. We reviewed empirical evidence of socioeconomic disparities in indoor exposures and key determinants of these exposures for air pollutants, lead, allergens, and semivolatile organic compounds. We also used an indoor air quality model applied to multifamily housing to illustrate how nitrogen dioxide (NO2) and fine particulate matter (PM2.5) vary as a function of factors known to be influenced by socioeconomic status.

Results. Indoor concentrations of multiple pollutants are elevated in low-socioeconomic status households. Differences in these exposures are driven by the combined influences of indoor sources, outdoor sources, physical structures, and residential activity patterns. Simulation models confirmed indoor sources’ importance in determining indoor NO2 and PM2.5 exposures and showed the influence of household-specific determinants.

Conclusions. Both theoretical models and empirical evidence emphasized that disparities in indoor environmental exposure can be significant. Understanding key determinants of multiple indoor exposures can aid in developing policies to reduce these disparities.
Risk-Based Targeting: Identifying Disproportionalities in the Sources and Effects of Industrial Pollution
Authors: Collins Mary B.
Published: August 2011

Objectives. I assessed the distribution of relative health risk from industrial air pollution in Milwaukee, Wisconsin, and the extent to which risk was disproportionately attributable to a minority of facilities.

Methods. I spatially linked data on airborne emissions, health risk, and sociodemographics by census tract, coupling disproportionality measurements from 2 perspectives: the health risk borne by communities and the harms produced by individual polluters.

Results. Of Milwaukee's 307 census tracts, 90 warranted the highest environmental justice concern. Striking variations in risk production existed between industrial polluters. Of 299 facilities with reported emissions, 30 (10%) contributed 90% of all health risk.

Conclusions. This research adds to an emerging body of work connecting environmental health risk, environmental justice, and corporate responsibility. Findings support the hypothesis that relatively few heavy polluters create most environmental health risk. Environmental policy often devotes insufficient attention to such outliers, in part because of the questionable assumption that pollution is economically necessary for jobs or essential products. Increased emphasis on risk-based targeting of the worst polluters could significantly improve environmental quality and health in overburdened communities.
Skewed Riskscapes and Gentrified Inequities: Environmental Exposure Disparities in Seattle, Washington
Authors: Abel Troy D. , White Jonah
Published: August 2011

Objectives. Few studies have considered the sociohistorical intersection of environmental injustice and gentrification; a gap addressed by this case study of Seattle, Washington. This study explored the advantages of integrating air toxic risk screening with gentrification research to enhance proximity and health equity analysis methodologies. It was hypothesized that Seattle's industrial air toxic exposure risk was unevenly dispersed, that gentrification stratified the city's neighborhoods, and that the inequities of both converged.

Methods. Spatial characterizations of air toxic pollution risk exposures from 1990 to 2007 were combined with longitudinal cluster analysis of census block groups in Seattle, Washington, from 1990 to 2000.

Results. A cluster of air toxic exposure inequality and socioeconomic inequity converged in 1 area of south central Seattle. Minority and working class residents were more concentrated in the same neighborhoods near Seattle's worst industrial pollution risks.

Conclusions. Not all pollution was distributed equally in a dynamic urban landscape. Using techniques to examine skewed riskscapes and socioeconomic urban geographies provided a foundation for future research on the connections among environmental health hazard sources, socially vulnerable neighborhoods, and health inequity.
Data Sources for an Environmental Quality Index: Availability, Quality, and Utility
Authors: Lobdell Danelle T. , Jagai Jyotsna S. , Rappazzo Kristen , Messer Lynne C.
Published: August 2011

Objectives. An environmental quality index (EQI) for all counties in the United States is under development to explore the relationship between environmental insults and human health. The EQI is potentially useful for investigators researching health disparities to account for other concurrent environmental conditions. This article focused on the identification and assessment of data sources used in developing the EQI. Data source strengths, limitations, and utility were addressed.

Methods. Five domains were identified that contribute to environmental quality: air, water, land, built, and sociodemographic environments. An inventory of possible data sources was created. Data sources were evaluated for appropriate spatial and temporal coverage and data quality.

Results. The overall data inventory identified multiple data sources for each domain. From the inventory (187 sources, 617 records), the air, water, land, built environment, and sociodemographic domains retained 2, 9, 7, 4, and 2 data sources for inclusion in the EQI, respectively. However, differences in data quality, geographic coverage, and data availability existed between the domains.

Conclusions. The data sources identified for use in the EQI may be useful to researchers, advocates, and communities to explore specific environmental quality questions.
Reformulating Lead-Based Paint as a Problem in Canada
Authors: O'Grady Kelly , Perron Amélie
Published: August 2011

Leaded gasoline was officially removed from the Canadian market in December 1990. The removal of a major lead source and the subsequent decline in children's blood lead levels marked an important transition point and sparked the emergence of new discourse on lead in Canada. Today, childhood lead poisoning is viewed as a problem of the past or a problem of the United States. Sparse Canadian surveillance data supported this view. Moreover, tensions among federal agencies evolved into a power struggle, with Health Canada ultimately becoming the dominant authority, thereby relegating important research initiatives to obscurity and also shaping a vastly weaker regulatory response to lead than occurred in the United States.
Creating an Environmental Justice Framework for Policy Change in Childhood Asthma: A Grassroots to Treetops Approach
Authors: Kreger Mary , Sargent Katherine , Arons Abigail , Standish Marion , Brindis Claire D.
Published: August 2011

Objectives. The Community Action to Fight Asthma Initiative, a network of coalitions and technical assistance providers in California, employed an environmental justice approach to reduce risk factors for asthma in school-aged children. Policy advocacy focused on housing, schools, and outdoor air quality. Technical assistance partners from environmental science, policy advocacy, asthma prevention, and media assisted in advocacy. An evaluation team assessed progress and outcomes.

Methods. A theory of change and corresponding logic model were used to document coalition development and successes. Site visits, surveys, policymaker interviews, and participation in meetings documented the processes and outcomes. Quantitative and qualitative data were analyzed to assess strategies, successes, and challenges.

Results. Coalitions, working with community residents and technical assistance experts, successfully advocated for policies to reduce children's exposures to environmental triggers, particularly in low-income communities and communities of color. Policies were implemented at various levels.

Conclusions. Environmental justice approaches to policy advocacy could be an effective strategy to address inequities across communities. Strong technical assistance, close community involvement, and multilevel strategies were all essential to effective policies to reduce environmental inequities.