bluuebunny/crossref_metadata_2025 huggingface dataset:
New Pipeline Flex device: initial experience and technical nuances
Authors: Pereira Vitor Mendes , Kelly Michael , Vega Pedro , Murias Eduardo , Yilmaz Hasan , Erceg Gorislav , Pellaton Alain , Lovblad Karl-olof , Krings Timo
Published: October 2014

Background

Flow diverter stents (FDS) have been described as a breakthrough in the treatment of intracranial aneurysms. Of the various flow diverter models, the Pipeline device has been the main approved and used device, with established and good long-term results.

Objective

To present the first series of patients treated with its new version, the Pipeline Flex device. This has kept the same device design and configuration but redesigned and completely modified the delivery system.

Methods

In this technical report, we include 10 consecutive patients harboring 12 saccular aneurysms of the anterior circulation. We report the main changes on the system, immediate results, and technical nuances with illustrative cases.

Results

We implanted 12 devices, including 11 Pipeline Flex and one Pipeline device. We used the old version in one case that required a second layer with a short length not available in the Pipeline Flex size range. All attempts at treatment were successful and no device was discharged or removed. Recovery was required or used in half of the cases with good or excellent performance, except in one case that presented with multiple proximal loops and tight curves. We had two transitory events without ischemic lesions on MRI that recovered 1 and 4 h after all patients were discharged home asymptomatic.

Conclusions

Pipeline Flex represents a major advance in FDS technology. The redesigned system has significantly improved the deployment of the Pipeline stent, by enabling the operator to resheath the device. It has the potential to continue revolutionizing the endovascular approach for intracranial aneurysms.
Multimodal angiographic assessment of cerebral arteriovenous malformations: a pilot study
Authors: Blanc Raphaël , Seiler Aude , Robert Thomas , Baharvahdat Humain , Lafarge Maxime , Savatovsky Julien , Hodel Jérôme , Ciccio Gabriele , Chauvet Dorian , Pistocchi Silvia , Bartolini Bruno , Redjem Hocine , Piotin Michel
Published: October 2014

Purpose

We describe our protocol of three-dimensional (3D) Roadmap intracranial navigation and image fusion for analysis of the angioarchitecture and endovascular treatment of brain arteriovenous malformations (AVMs).

Methods

We performed superselective catheterization of brain AVMs feeders under 3D-Roadmap navigation. Angiograms of each catheterized artery on two registered orthogonal views were transferred to the imaging workstations, and dedicated postprocessing imaging software allowed automated multiple overlays of the arterial supply of the AVM superselective acquisitions on the global angiogram in angiographic or 3D views and on coregistered MRI datasets.

Results

11 untreated brain AVMs (4 with hemorrhagic presentation) were explored. The superselective acquisitions were performed under 3D-Roadmap navigation in 74 arteries, for a total of 79 targeted arteries. Imaging analysis was available at table side or postoperatively for discussion of the therapeutic strategy. No complications occurred during superselective catheterization. The accuracy of the coregistration of angiogram and MRI was submillimetric after automated mutual information coregistration, with manual re-registration by the physicians.

Conclusions

Superselective angiograms acquired under 3D-Roadmap navigation can be postprocessed with multiple overlays. The fluoroscopic navigation under 3D-Roadmapping and the coregistration of 3D rotational angiography, selective angiography, and 3D MR datasets appears reliable with millimeter accuracy, and could be implemented in the critical brain AVM embolization setting to allow refined analysis of AVM angioarchitecture.
Periconal arterial anastomotic circle and posterior lumbosacral watershed zone of the spinal cord
Authors: Gailloud Philippe , Gregg Lydia , Galan Peter , Becker Daniel , Pardo Carlos
Published: October 2014

Background

The existence of spinal cord watershed territories was suggested in the 1950s. Segmental infarcts within the junctional territories of adjacent radiculomedullary contributors and isolated spinal gray matter ischemia constitute two well-recognized types of watershed injury. This report describes the existence of another watershed territory related to the particular configuration of the spinal vasculature in the region of the conus medullaris.

Methods

The anatomical bases underlying the concept of a posterior lumbosacral watershed zone are demonstrated with angiographic images obtained in a 16-year-old child. The clinical importance of this watershed zone is illustrated with MRI and angiographic data of three patients with a conus medullaris infarction.

Results

In all three cases of spinal ischemia an intersegmental artery providing a significant radiculomedullary contribution for the lower cord was compromised by a compressive mechanism responsible for decreased spinal cord perfusion (diaphragmatic crus syndrome in two cases, disk herniation in one). The ischemic injury, located at the junction of the anterior and posterior spinal artery territories along the dorsal aspect of the conus medullaris, was consistent with a watershed mechanism. This zone is at risk because of the caudocranial direction of flow within the most caudal segment of the posterior spinal arterial network which, from a functional standpoint, depends on the anterior spinal artery.

Conclusions

The posterior thoracolumbar watershed zone of the spinal cord represents an area at increased risk of ischemic injury, particularly in the context of partial flow impairment related to arterial compression mechanisms.
Total spinal anaesthesia following spinal lumbosacral injection of bupivacaine 0.5 per cent in a cat
Authors: Casoni Daniela , Rohrbach Helene , Spadavecchia Claudia
Published: October 2014

A 16‐year‐old castrated male cat underwent general anaesthesia twice within three weeks for perineal urethrostomy and its surgical revision. The cat was affected by compensated hyperthrophic cardiomyopathy. The first anaesthesia was uneventful; in the second anaesthesia a lumbosacral spinal injection of bupivacaine 0.5 per cent was carried out during inhalant anaesthesia. Immediately after completion of injection, respiratory arrest, bilateral mydriasis and cardiovascular collapse occurred. Supportive measures restored normotension and normal cardiac rhythm. Inhalation of isoflurane was immediately interrupted after respiratory arrest. Nevertheless, the cat remained comatose for two hours and it was transferred to the intensive care unit under oxygen supplementation by mask once responsive to visual stimuli. Twenty‐four hours later, neurological exam did not reveal any deficit and the cat recovered completely.
Stratigraphic continuity and fragmentary sedimentation: the success of cyclostratigraphy as part of integrated stratigraphy
Authors: Hilgen Frederik J. , Hinnov Linda A. , Abdul Aziz Hayfaa , Abels Hemmo A. , Batenburg Sietske , Bosmans Joyce H. C. , de Boer Bas , Hüsing Silja K. , Kuiper Klaudia F. , Lourens Lucas J. , Rivera Tiffany , Tuenter Erik , Van de Wal Roderik S. W. , Wotzlaw Jörn-Frederik , Zeeden Christian
Published: October 2014

The Milankovitch theory of climate change is widely accepted, but the registration of the climate changes in the stratigraphic record and their use in building high-resolution astronomically tuned timescales has been disputed due to the complex and fragmentary nature of the stratigraphic record. However, results of time series analysis and consistency with independent magnetobiostratigraphic and/or radio-isotopic age models show that Milankovitch cycles are recorded not only in deep marine and lacustrine successions, but also in ice cores and speleothems, and in eolian and fluvial successions. Integrated stratigraphic studies further provide evidence for continuous sedimentation at Milankovitch time scales (10
4
years up to 10
6
years). This combined approach also shows that strict application of statistical confidence limits in spectral analysis to verify astronomical forcing in climate proxy records is not fully justified and may lead to false negatives. This is in contrast to recent claims that failure to apply strict statistical standards can lead to false positives in the search for periodic signals. Finally, and contrary to the argument that changes in insolation are too small to effect significant climate change, seasonal insolation variations resulting from orbital extremes can be significant (20% and more) and, as shown by climate modelling, generate large climate changes that can be expected to leave a marked imprint in the stratigraphic record. The tuning of long and continuous cyclic successions now underlies the standard geological time scale for much of the Cenozoic and also for extended intervals of the Mesozoic. Such successions have to be taken into account to fully comprehend the (cyclic) nature of the stratigraphic record.
Characterizing and identifying structural domains at rifted continental margins: application to the Bay of Biscay margins and its Western Pyrenean fossil remnants
Authors: Tugend J. , Manatschal G. , Kusznir N. J. , Masini E.
Published: October 2014

We use the Bay of Biscay and Western Pyrenees as a natural laboratory to develop and apply an approach to characterize and identify distinctive rifted margin domains in offshore and onshore settings. The Bay of Biscay and Western Pyrenees offer access to seismically imaged, drilled and exposed parts of one and the same hyperextended rift system. Offshore, we use gravity inversion and flexural backstripping techniques combined with seismic interpretation to provide estimates of accommodation space, crustal thickness and lithosphere thinning. Onshore, we focus on key outcrops of the former rift domain to describe the nature of sediment and basement rocks, and of their interface. This qualitative and quantitative characterization provides diagnostic elements for the identification of five distinct structural domains at magma-poor rifted margins and their fossil analogues (proximal, necking, hyperthinned, exhumed mantle and oceanic domains). This new approach can be used to reconcile offshore and onshore observations, and to aid interpretation when only local observations are available. Onshore remnants can be placed in an offshore rifted-margin context, enabling the prediction of first-order crustal architecture. For the interpretation of offshore seismic reflection sections, geological insights into rift structures and basement nature can be suggested based on onshore analogies.

Supplementary material:

Sensitivity of backstripping results to flexural rigidity is available at
http://www.geolsoc.org.uk/SUP18778
.
Hydrogen gas attenuates embryonic gene expression and prevents left ventricular remodeling induced by intermittent hypoxia in cardiomyopathic hamsters
Authors: Kato Ryuji , Nomura Atsuo , Sakamoto Aiji , Yasuda Yuki , Amatani Koyuha , Nagai Sayuri , Sen Yoko , Ijiri Yoshio , Okada Yoshikatsu , Yamaguchi Takehiro , Izumi Yasukatsu , Yoshiyama Minoru , Tanaka Kazuhiko , Hayashi Tetsuya
Published: October 2014

The prevalence of sleep apnea is very high in patients with heart failure (HF). The aims of this study were to investigate the influence of intermittent hypoxia (IH) on the failing heart and to evaluate the antioxidant effect of hydrogen gas. Normal male Syrian hamsters ( n = 22) and cardiomyopathic (CM) hamsters ( n = 33) were exposed to IH (repeated cycles of 1.5 min of 5% oxygen and 5 min of 21% oxygen for 8 h during the daytime) or normoxia for 14 days. Hydrogen gas (3.05 vol/100 vol) was inhaled by some CM hamsters during hypoxia. IH increased the ratio of early diastolic mitral inflow velocity to mitral annulus velocity (E/e′, 21.8 vs. 16.9) but did not affect the LV ejection fraction (EF) in normal Syrian hamsters. However, IH increased E/e′ (29.4 vs. 21.5) and significantly decreased the EF (37.2 vs. 47.2%) in CM hamsters. IH also increased the cardiomyocyte cross-sectional area (672 vs. 443 μm2) and interstitial fibrosis (29.9 vs. 9.6%), along with elevation of oxidative stress and superoxide production in the left ventricular (LV) myocardium. Furthermore, IH significantly increased the expression of brain natriuretic peptide, β-myosin heavy chain, c- fos, and c- jun mRNA in CM hamsters. Hydrogen gas inhalation significantly decreased both oxidative stress and embryonic gene expression, thus preserving cardiac function in CM hamsters. In conclusion, IH accelerated LV remodeling in CM hamsters, at least partly by increasing oxidative stress in the failing heart. These findings might explain the poor prognosis of patients with HF and sleep apnea.
Multimodal functional and anatomic imaging identifies preclinical microvascular abnormalities in type 1 diabetes mellitus
Authors: Lockhart C. J. , McCann A. J. , Pinnock R. A. , Hamilton P. K. , Harbinson M. T. , McVeigh G. E.
Published: October 2014

Structural and functional changes in the microcirculation in type 1 diabetes mellitus predict future end-organ damage and macrovascular events. We explored the utility of novel signal processing techniques to detect and track changes in ocular hemodynamics in patients with this disease. Twenty-four patients with uncomplicated type 1 diabetes mellitus and eighteen age- and sex-matched control subjects were studied. Doppler ultrasound was used to interrogate the carotid and ophthalmic arteries, and digital photography was used to image the retinal vasculature. Frequency analysis algorithms were applied to quantify velocity waveform structure and retinal photographic data at baseline and after inhalation of 100% O2. Frequency data were compared between groups. No significant differences were found in the resistive index between groups at baseline or after inhaled O2. Frequency analysis of Doppler flow velocity waveforms identified significant differences in bands 3–7 between patients and control subjects in data captured from the ophthalmic artery ( P < 0.01 for each band). In response to inhaled O2, changes in frequency band amplitudes were significantly greater in control subjects compared with patients ( P < 0.05). Only control subjects demonstrated a positive correlation ( R = 0.61) between changes in retinal vessel diameter and frequency band amplitudes derived from ophthalmic artery waveform data. The use of multimodal signal processing techniques applied to Doppler flow velocity waveforms and retinal photographic data identified preclinical changes in the ocular microcirculation in patients with uncomplicated diabetes mellitus. An impaired autoregulatory response of the retinal microvasculature may contribute to the future development of retinopathy in such patients.
Resolvin D1 reverses reactivity and Ca2+ sensitivity induced by ET-1, TNF-α, and IL-6 in the human pulmonary artery
Authors: Hiram Roddy , Rizcallah Edmond , Sirois Chantal , Sirois Marco , Morin Caroline , Fortin Samuel , Rousseau Eric
Published: October 2014

Pulmonary hypertension (PH) is a rare and progressive disease characterized by an inflammatory status and vessel wall remodeling, resulting in increased pulmonary artery resistance. During the last decade, treatments have been proposed; most of them target the endothelial pathways that stimulate smooth muscle cell relaxation. However, PH remains associated with significant morbidity. We hypothesized that inflammation plays a crucial role in the severity of the abnormal vasoconstriction in PH. The goal of this study was to assess the effects of resolvin D1 (RvD1), a potent anti-inflammatory agent, on the pharmacological reactivity of human pulmonary arteries (HPAs) via an in vitro model of induced hyperreactivity. The effects of RvD1 and monoacylglyceride compounds were measured on contractile activity and Ca2+ sensitivity developed by HPAs that had been pretreated (or not) under proinflammatory conditions with either 10 ng/ml TNF-α or 10 ng/ml IL-6 or under hyperreactive conditions with 5 nM endothelin-1. The results demonstrated that, compared with controls, 24-h pretreatment with TNF-α, IL-6, or endothelin-1 increased reactivity and Ca2+ sensitivity of HPAs as revealed by agonist challenges with 80 mM KCl, 1 μM serotonin (5-hydroxytryptamine), 30 nM U-46619, and 1 μM phorbol 12,13-dibutyrate. However, 300 nM RvD1 as well as 1 μM monoacylglyceride-docosapentaenoic acid monoglyceride strongly reversed the overresponsiveness induced by both proinflammatory and hyperreactive treatments. In pretreated pulmonary artery smooth muscle cells, Western blot analyses revealed that RvD1 treatment decreased the phosphorylation level of CPI-17 and expression of transmembrane protein member 16A while increasing the detection of G protein-coupled receptor 32. The present data demonstrate that RvD1, a trihydroxylated docosahexaenoic acid derivative, decreases induced overreactivity in HPAs via a reduction in CPI-17 phosphorylation and transmembrane protein member 16A expression.
Thyrotropin-releasing hormone overexpression induces structural changes of the left ventricle in the normal rat heart
Authors: Schuman Mariano L. , Peres Diaz Ludmila S. , Landa Maria S. , Toblli Jorge E. , Cao Gabriel , Alvarez Azucena L. , Finkielman Samuel , Pirola Carlos J. , García Silvia I.
Published: October 2014

Thyrotropin-releasing hormone (TRH) hyperactivity has been observed in the left ventricle of spontaneously hypertensive rats. Its long-term inhibition suppresses the development of hypertrophy, specifically preventing fibrosis. The presence of diverse systemic abnormalities in spontaneously hypertensive rat hearts has raised the question of whether specific TRH overexpression might be capable of inducing structural changes in favor of the hypertrophic phenotype in normal rat hearts. We produced TRH overexpression in normal rats by injecting into their left ventricular wall a plasmid driving expression of the preproTRH gene (PCMV-TRH). TRH content and expression of preproTRH, collagen type III, brain natriuretic peptide, β-myosin heavy chain, Bax-to-Bcl-2 ratio, and caspase-3 were measured. The overexpression maneuver was a success, as we found a significant increase in both tripeptide and preproTRH mRNA levels in the PCMV-TRH group compared with the control group. Immunohistochemical staining against TRH showed markedly positive brown signals only in the PCMV-TRH group. TRH overexpression induced a significant increase in fibrosis, evident in the increase of collagen type III expression accompanied by a significant increase in extracellular matrix expansion. We found a significant increase in brain natriuretic peptide and β-myosin heavy chain expression (recognized markers of hypertrophy). Moreover, TRH overexpression induced a slight but significant increase in myocyte diameter, indicating the onset of cell hypertrophy. We confirmed the data “in vitro” using primary cardiac cell cultures (fibroblasts and myocytes). In conclusion, these results show that a specific TRH increase in the left ventricle induced structural changes in the normal heart, thus making the cardiac TRH system a promising therapeutic target.
Compound heterozygosity deteriorates phenotypes of hypertrophic cardiomyopathy with founderMYBPC3mutation: evidence from patients and zebrafish models
Authors: Hodatsu Akihiko , Konno Tetsuo , Hayashi Kenshi , Funada Akira , Fujita Takashi , Nagata Yoji , Fujino Noboru , Kawashiri Masa-aki , Yamagishi Masakazu
Published: October 2014

Although most founder mutation carriers of hypertrophic cardiomyopathy (HCM), such as the cardiac myosin-binding protein C gene ( MYBPC3), arose from a common ancestor exhibit favorable clinical phenotypes, there still remain small fractions of these carriers associated with increased cardiovascular events. However, few data exist regarding the defining factors that modify phenotypes of these patients, particularly in terms of multiple gene mutations. Therefore, we assessed genotype-phenotype correlations and investigated factors that contribute to phenotypic diversities of mutation carriers from 488 unrelated HCM probands. A prevalent founder mutation (Val762Asp) in MYBPC3 was identified in 33 subjects from 19 families. Among them, 28 carriers harbored an isolated Val762Asp mutation and exhibited a late onset of overt HCM compared with other MYBPC3 mutation carriers (62.8 ± 3.0 vs 50.1 ± 2.6 yr, P < 0.05). In contrast, the remaining five carriers had additional sarcomere gene mutations (3 carriers in MYBPC3 and 2 carriers in the cardiac troponin T gene). Of these five carriers, two carriers showed early disease onset and one carrier exhibited end-stage HCM. These phenotypes were recapitulated in zebrafish models; injection of MYBPC3 Val762Asp alone did not alter ventricular size or function, but ventricular dimension was significantly increased when MYBPC3 Val762Asp mRNA was coinjected with MYBPC3 Arg820Gln mRNA. These results demonstrate that MYBPC3 Val762Asp may be associated with unfavorable HCM phenotypes in some cases when combined with another MYBPC3 mutation.
Carl Wilhelm Scheele, the discoverer of oxygen, and a very productive chemist
Authors: West John B.
Published: October 2014

Carl Wilhelm Scheele (1742–1786) has an important place in the history of the discovery of respiratory gases because he was undoubtedly the first person to prepare oxygen and describe some of its properties. Despite this, his contributions have often been overshadowed by those of Joseph Priestley and Antoine Lavoisier, who also played critical roles in preparing the gas and understanding its nature. Sadly, Scheele was slow to publish his discovery and therefore Priestley is rightly recognized as the first person to report the preparation of oxygen. This being said, the thinking of both Scheele and Priestley was dominated by the phlogiston theory, and it was left to Lavoisier to elucidate the true nature of oxygen. In addition to his work on oxygen, Scheele was enormously productive in other areas of chemistry. Arguably he discovered seven new elements and many other compounds. However, he kept a low profile during his life as a pharmacist, and he did not have strong links with contemporary prestigious institutions such as the Royal Society in England or the French Académie des Sciences. He was elected to the Royal Swedish Academy of Science but only attended one meeting. Partly as a result, he remains a somewhat nebulous figure despite the critical contribution he made to the history of respiratory gases and his extensive researches in other areas of chemistry. His death at the age of 43 may have been hastened by his habit of tasting the chemicals that he worked on.
Distinct Luminal-Type Mammary Carcinomas Arise from Orthotopic Trp53-Null Mammary Transplantation of Juvenile versus Adult Mice
Authors: Nguyen David H. , Ouyang Haoxu , Mao Jian-Hua , Hlatky Lynn , Barcellos-Hoff Mary Helen
Published: October 2014

Age and physiologic status, such as menopause, are risk factors for breast cancer. Less clear is what factors influence the diversity of breast cancer. In this study, we investigated the effect of host age on the distribution of tumor subtypes in mouse mammary chimera consisting of wild-type hosts and Trp53 nullizygous epithelium, which undergoes a high rate of neoplastic transformation. Wild-type mammary glands cleared of endogenous epithelium at 3 weeks of age were subsequently transplanted during puberty (5 weeks) or at maturation (10 weeks) with syngeneic Trp53-null mammary tissue fragments and monitored for one year. Tumors arose sooner from adult hosts (AH) compared with juvenile hosts (JH). However, compared with AH tumors, JH tumors grew several times faster, were more perfused, exhibited a two-fold higher mitotic index, and were more highly positive for insulin-like growth factor receptor phosphorylation. Most tumors in each setting were estrogen receptor (ER)-positive (80% JH vs. 70% AH), but JH tumors were significantly more ER-immunoreactive (P = 0.0001) than AH tumors. A differential expression signature (JvA) of juvenile versus adult tumors revealed a luminal transcriptional program. Centroids of the human homologs of JvA genes showed that JH tumors were more like luminal A tumors and AH tumors were more like luminal B tumors. Hierarchical clustering with the JvA human ortholog gene list segregated luminal A and luminal B breast cancers across datasets. These data support the notion that age-associated host physiology greatly influences the intrinsic subtype of breast cancer. Cancer Res; 74(23); 7149–58. ©2014 AACR.
Suppression of Deacetylase SIRT1 Mediates Tumor-Suppressive NOTCH Response and Offers a Novel Treatment Option in Metastatic Ewing Sarcoma
Authors: Ban Jozef , Aryee Dave N.T. , Fourtouna Argyro , van der Ent Wietske , Kauer Max , Niedan Stephan , Machado Isidro , Rodriguez-Galindo Carlos , Tirado Oscar M. , Schwentner Raphaela , Picci Piero , Flanagan Adrienne M. , Berg Verena , Strauss Sandra J. , Scotlandi Katia , Lawlor Elizabeth R. , Snaar-Jagalska Ewa , Llombart-Bosch Antonio , Kovar Heinrich
Published: October 2014

The developmental receptor NOTCH plays an important role in various human cancers as a consequence of oncogenic mutations. Here we describe a novel mechanism of NOTCH-induced tumor suppression involving modulation of the deacetylase SIRT1, providing a rationale for the use of SIRT1 inhibitors to treat cancers where this mechanism is inactivated because of SIRT1 overexpression. In Ewing sarcoma cells, NOTCH signaling is abrogated by the driver oncogene EWS-FLI1. Restoration of NOTCH signaling caused growth arrest due to activation of the NOTCH effector HEY1, directly suppressing SIRT1 and thereby activating p53. This mechanism of tumor suppression was validated in Ewing sarcoma cells, B-cell tumors, and human keratinocytes where NOTCH dysregulation has been implicated pathogenically. Notably, the SIRT1/2 inhibitor Tenovin-6 killed Ewing sarcoma cells in vitro and prohibited tumor growth and spread in an established xenograft model in zebrafish. Using immunohistochemistry to analyze primary tissue specimens, we found that high SIRT1 expression was associated with Ewing sarcoma metastasis and poor prognosis. Our findings suggest a mechanistic rationale for the use of SIRT1 inhibitors being developed to treat metastatic disease in patients with Ewing sarcoma. Cancer Res; 74(22); 6578–88. ©2014 AACR.
Alcohol Consumption in Relation to Plasma Sex Hormones, Prolactin, and Sex Hormone–Binding Globulin in Premenopausal Women
Authors: Hirko Kelly A. , Spiegelman Donna , Willett Walter C. , Hankinson Susan E. , Eliassen A. Heather
Published: October 2014

Background: Alcohol consumption is a consistent risk factor for breast cancer, and evidence suggests premenopausal plasma hormones are associated with breast cancer.

Methods: Plasma concentrations of estradiol, estrone, estrone sulfate, testosterone, androstenedione, progesterone, prolactin, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), and sex hormone–binding globulin (SHBG) were measured in samples collected in 1996–99. Average alcohol intake was calculated from semiquantitative food frequency questionnaires collected in 1995 and 1999. We used generalized linear models to calculate geometric mean hormone concentrations across alcohol categories and the percentage difference for the highest versus lowest category.

Results: Comparing women who consumed >20 g/d with nondrinkers, levels were 25.7% higher for luteal estrone (geometric mean, 106 vs. 84.5 pg/mL; Ptrend = 0.001), 27.2% higher for luteal estradiol (182 vs. 143 pg/mL; Ptrend = 0.006), and 16.8% higher for SHBG (85.6 vs. 73.3 nmol/L; Ptrend = 0.03); concentrations of free testosterone were 17.9% lower (0.16 vs. 0.20 ng/dL; Ptrend = 0.002). Women consuming >10 g/d compared with nondrinkers had 26.5% higher concentrations of follicular estrone sulfate (950 vs. 751 pg/mL; Ptrend = 0.04). We did not observe significant associations between alcohol and the other sex hormones evaluated. Significant positive associations were observed with beer intake, but not other alcohol types, for DHEA (Pinteraction = 0.003) and androstenedione (Pinteraction = 0.006).

Conclusion: Alcohol consumption was significantly positively associated with plasma luteal estrogen concentrations, but not with androgen levels, nor estrone or estradiol measured in the follicular phase.

Impact: Differences in premenopausal estrogen levels may contribute to the association between alcohol and breast cancer. Cancer Epidemiol Biomarkers Prev; 23(12); 2943–53. ©2014 AACR.
NK Cell Genotype and Phenotype at Diagnosis of Acute Lymphoblastic Leukemia Correlate with Postinduction Residual Disease
Authors: Sullivan Erin M. , Jeha Sima , Kang Guolian , Cheng Cheng , Rooney Barbara , Holladay Martha , Bari Rafijul , Schell Sarah , Tuggle MaCal , Pui Ching-Hon , Leung Wing
Published: October 2014

Purpose: Not all natural killer (NK) cells are equally cytotoxic against leukemia because of differences in receptor gene content and surface expression. We correlated NK cell genotype and phenotype at diagnosis of childhood acute lymphoblastic leukemia (ALL) with minimal residual disease (MRD) after induction chemotherapy.

Experimental Design: The NK cells and leukemia blasts of 244 patients were analyzed at diagnosis by killer-cell immunoglobulin-like receptor (KIR) typing and immunophenotyping. The results were correlated statistically with postinduction MRD status.

Results: The odds of being MRD positive in patients with KIR telomeric (Tel)-A/B genotype were 2.85 times the odds in those with Tel-A/A genotype (P = 0.035). MRD-positive patients were more likely to have KIR2DL5A (P = 0.006) and expressed less activating receptor NKp46 and FASL on their NK cells (P = 0.0074 and P = 0.029, respectively). The odds of being MRD positive increased by 2.01-fold for every percentage increase in NK cells expressing KIR2DL1 in the presence of HLA-C2 ligand (P = 0.034). The quantity of granzyme B inhibitor PI-9 in the leukemia blasts was greater in patients who were MRD positive (P = 0.038). Collectively, five NK cell–related factors (Tel-B–associated KIR2DL5A, NKp46, FASL, granzyme B, and PI-9) are strongly associated with MRD positivity at the end of induction with 100% sensitivity and 80% specificity.

Conclusions: Our data support the hypothesis that NK cells with a strong effector phenotype in the setting of decreased leukemia resistance are associated with better leukemia control. Clin Cancer Res; 20(23); 5986–94. ©2014 AACR.
WHSC1 Promotes Oncogenesis through Regulation of NIMA-Related Kinase-7 in Squamous Cell Carcinoma of the Head and Neck
Authors: Saloura Vassiliki , Cho Hyun-Soo , Kiyotani Kazuma , Alachkar Houda , Zuo Zhixiang , Nakakido Makoto , Tsunoda Tatsuhiko , Seiwert Tanguy , Lingen Mark , Licht Jonathan , Nakamura Yusuke , Hamamoto Ryuji
Published: October 2014

Squamous cell carcinoma of the head and neck (SCCHN) is a relatively common malignancy with suboptimal long-term prognosis, thus new treatment strategies are urgently needed. Over the last decade, histone methyltransferases (HMT) have been recognized as promising targets for cancer therapy, but their mechanism of action in most solid tumors, including SCCHN, remains to be elucidated. This study investigated the role of Wolf–Hirschhorn syndrome candidate 1 (WHSC1), an NSD family HMT, in SCCHN. Immunohistochemical analysis of locoregionally advanced SCCHN, dysplastic, and normal epithelial tissue specimens revealed that WHSC1 expression and dimethylation of histone H3 lysine 36 (H3K36me2) were significantly higher in SCCHN tissues than in normal epithelium. Both WHSC1 expression and H3K36me2 levels were significantly correlated with histologic grade. WHSC1 knockdown in multiple SCCHN cell lines resulted in significant growth suppression, induction of apoptosis, and delay of the cell-cycle progression. Immunoblot and immunocytochemical analyses in SCCHN cells demonstrated that WHSC1 induced H3K36me2 and H3K36me3. Microarray expression profile analysis revealed NIMA-related kinase-7 (NEK7) to be a downstream target gene of WHSC1, and chromatin immunoprecipitation (ChIP) assays showed that NEK7 was directly regulated by WHSC1 through H3K36me2. Furthermore, similar to WHSC1, NEK7 knockdown significantly reduced cell-cycle progression, indicating that NEK7 is a key player in the molecular pathway regulated by WHSC1.

Implications: WHSC1 possesses oncogenic functions in SCCHN and represents a potential molecular target for the treatment of SCCHN. Mol Cancer Res; 13(2); 293–304. ©2014 AACR.
Methylation Analysis of the FAM19A4 Gene in Cervical Scrapes Is Highly Efficient in Detecting Cervical Carcinomas and Advanced CIN2/3 Lesions
Authors: De Strooper Lise M.A. , Meijer Chris J.L.M. , Berkhof Johannes , Hesselink Albertus T. , Snijders Peter J.F. , Steenbergen Renske D.M. , Heideman Daniëlle A.M.
Published: October 2014

Primary testing for human papillomavirus (HPV) in cervical screening requires triage to differentiate women with transient infection from those with persistent infection who require more intensive management given their risk for cervical (pre)cancer. In this study, the clinical performance of a novel methylation marker FAM19A4 for the triage of high-risk (hr)HPV-positive women was evaluated. Using a training-validation set approach, we analyzed a FAM19A4 quantitative methylation-specific PCR (qMSP). The training set comprised hrHPV-positive cervical scrapes of 43 women with cervical intraepithelial neoplasia grade 3 or worse (CIN3+) and 135 women with ≤CIN1. The validation set comprised hrHPV-positive cervical scrapes of 52 women with CIN2+, including 33 CIN3+, 19 CIN2, and 166 women with ≤CIN1. The methylation threshold of FAM19A4 qMSP that gave rise to CIN3+ specificity of 70% in the training set was applied in the validation set. This resulted in CIN3+ sensitivity of 75.8% [95% confidence interval (CI), 61.1–90.4] at 67.0% (95% CI, 60.3–73.8) specificity. Next, the validated qMSP was applied to an independent series of hrHPV-positive cervical scrapes of 22 women with cervical cancer, 29 with advanced CIN2/3 [i.e., women with a known preceding hrHPV infection (PHI) lasting ≥5 years as proxy of longer duration of lesion existence], and 19 with early CIN2/3 (i.e., PHI <5 years). All carcinomas (22/22) and advanced CIN2/3 lesions (29/29) were FAM19A4 methylation–positive, compared with 42.1% (8/19; 95% CI, 19.9–64.3) of early CIN2/3 lesions. In conclusion, FAM19A4 is an attractive triage marker for hrHPV-positive women, with a high reassurance for the detection of cervical carcinoma and advanced CIN2/3 lesions. Cancer Prev Res; 7(12); 1251–7. ©2014 AACR.
Ischemic Electrocardiographic Abnormalities and Prognosis in Decompensated Heart Failure
Authors: Greig Douglas , Austin Peter C. , Zhou Limei , Tu Jack V. , Pang Peter S. , Ross Heather J. , Lee Douglas S.
Published: October 2014

Background—

Identification of coronary ischemia may enable targeted diagnostic and therapeutic strategies for acute heart failure. We determined the risk of 30-day mortality associated with ischemic ECG abnormalities in patients with acute heart failure.

Methods and Results—

Among 8772 patients (53.4% women, median 78 years [Q1, Q3: 68,84]) presenting with acute heart failure to 86 hospital emergency departments in Ontario, Canada, Q-waves, T-wave inversion, or ST-depression were present in 51.8% of subjects. However, presence of ST-depression was the only finding associated with 30-day mortality with adjusted odds ratio 1.24 (95% confidence interval [CI], 1.02–1.50). Using continuous net reclassification improvement, addition of ST-depression to the Emergency Heart failure Mortality Risk Grade model reclassified 16.9% of patients overall, and 29.3% of those with a history of ischemic heart disease (both
P
<0.001). By adding ST-depression to the model, the Emergency Heart failure Mortality Risk Grade was extended to predict 30-day death with high discrimination (
c
-statistic 0.801), with 0.57% mortality rate in the lowest risk decile. Adjusted odds ratios for 30-day mortality were 2.81 (95% CI, 1.48–5.31;
P
=0.002) in quintile 2, 7.41 (95% CI, 4.13–13.30;
P
<0.001) in quintile 3, and 14.47 (95% CI, 8.20–25.54;
P
<0.001) in quintile 4 compared with the lowest risk quintile. When the highest risk quintile was subdivided into 2 equally sized risk strata (deciles 9 and 10), the adjusted odds ratios for 30-day mortality were 27.20 (95% CI, 15.33–48.27;
P
<0.001) in decile 9 and 58.96 (95% CI, 33.54–103.65;
P
<0.001) in highest risk decile 10.

Conclusions—

Presence of ST-depression on the ECG reclassified risk of 30-day mortality in patients with acute heart failure, identifying both high- and low-risk subsets.
Cardiac Remodeling in Response to 1 Year of Intensive Endurance Training
Authors: Arbab-Zadeh Armin , Perhonen Merja , Howden Erin , Peshock Ronald M. , Zhang Rong , Adams-Huet Beverly , Haykowsky Mark J. , Levine Benjamin D.
Published: October 2014

Background—

It is unclear whether, and to what extent, the striking cardiac morphological manifestations of endurance athletes are a result of exercise training or a genetically determined characteristic of talented athletes. We hypothesized that prolonged and intensive endurance training in previously sedentary healthy young individuals could induce cardiac remodeling similar to that observed cross-sectionally in elite endurance athletes.

Methods and Results—

Twelve previously sedentary subjects (aged 29±6 years; 7 men and 5 women) trained progressively and intensively for 12 months such that they could compete in a marathon. Magnetic resonance images for assessment of right and left ventricular mass and volumes were obtained at baseline and after 3, 6, 9, and 12 months of training. Maximum oxygen uptake (

max) and cardiac output at rest and during exercise (C
2
H
2
rebreathing) were measured at the same time periods. Pulmonary artery catheterization was performed before and after 1 year of training, and pressure-volume and Starling curves were constructed during decreases (lower body negative pressure) and increases (saline infusion) in cardiac volume. Mean

max rose from 40.3±1.6 to 48.7±2.5 mL/kg per minute after 1 year (
P
<0.00001), associated with an increase in both maximal cardiac output and stroke volume. Left and right ventricular mass increased progressively with training duration and intensity and reached levels similar to those observed in elite endurance athletes. In contrast, left ventricular volume did not change significantly until 6 months of training, although right ventricular volume increased progressively from the outset; Starling and pressure-volume curves approached but did not match those of elite athletes.

Conclusions—

One year of prolonged and intensive endurance training leads to cardiac morphological adaptations in previously sedentary young subjects similar to those observed in elite endurance athletes; however, it is not sufficient to achieve similar levels of cardiac compliance and performance. Contrary to conventional thinking, the left ventricle responds to exercise with initial concentric but not eccentric remodeling during the first 6 to 9 months after commencement of endurance training depending on the duration and intensity of exercise. Thereafter, the left ventricle dilates and restores the baseline mass-to-volume ratio. In contrast, the right ventricle responds to endurance training with eccentric remodeling at all levels of training.
A Practical Approach to Building Resilience in America’s Communities
Authors: White Robin K. , Edwards Warren C. , Farrar Ann , Plodinec M. John
Published: October 2014

The Community and Regional Resilience Institute has conducted a number of projects and case studies examining the nature and characteristics of community resilience in order to identify processes, tools, and resources that could assist communities in strengthening their resilient capacities. This article begins by describing a theoretical framework for community resilience developed from literature review and community practice. The authors review the Community and Regional Resilience Institute’s practical work to assist selected communities in understanding and improving their resilience through two rounds of case studies and provide summaries of community outcomes and implications of the community work. The article also briefly describes the collaborative development process used to build a web-enabled system of tools, resources, and resilience knowledge that can be used by all communities to build and strengthen resilience. Finally, the article presents key observations arising from the community and collaborative development work and discusses their implications for other communities desiring to improve their resilience.
Purpose and Meaning in Career Development Applications
Authors: Dik Bryan J. , Duffy Ryan D. , Allan Blake A. , O’Donnell Maeve B. , Shim Yerin , Steger Michael F.
Published: October 2014

Purpose and meaning in career development is a rapidly growing, cross-disciplinary area of research and practice in which counseling and vocational psychology aligns with positive psychology to yield promising applications to career counseling. We provide a brief overview of theory related to purpose and meaning in work, then review six specific areas of application: strengths, positive emotions and flow, gratitude, work hope, job crafting, and perceiving and living a calling. The links of these applications to theory and research are emphasized, and recommendations are offered for how counseling and vocational psychologists might leverage these applications in their work with clients engaged in the career development process.
Sideways Camera Rotations of 90° and 135° Result in Poorer Performance of Laparoscopic Tasks for Novices
Authors: Klein Martina I. , Wheeler Noah J. , Craig Curtis
Published: October 2014

Objective:

The aim of this study was to determine the impact of sideways visuomotor rotations between 0° and 180° on novice performance in a laparoscopic simulator.

Background:

The laparoscopic surgical environment often involves visuomotor rotations because the laparoscope may be placed to the surgeon’s side. Basic research by Cunningham indicated that visuomotor rotations between 90° and 135° result in peak performance decrements. Research by Ames and colleagues failed to replicate Cunningham’s results in the laparoscopic environment, possibly due to (a) confounds from carryover effects or (b) use of an alternative laparoscopic training task rather than the straight-line pointing task used by Cunningham. Two experiments were conducted to determine if Cunningham’s results generalize to the laparoscopic environment when controlling for carryover effects for a three-dimensional “straight-line” pointing task (Experiment 1) and a laparoscopic training task (Experiment 2).

Method:

In Experiments 1 and 2, participants were assigned to one of five visuomotor rotations: 0°, 45°, 90°, 135°, or 180°. Utilizing a laparoscopic simulator, participants performed either a three-dimensional pointing task (Experiment 1) or a peg transfer task (Experiment 2).

Results:

In both experiments, visuomotor rotations of 90° or 135° resulted in the poorest performance.

Conclusion:

When controlling for carryover effects, Cunningham’s results generalize to novices’ performance of a pointing and a peg transfer task in the laparoscopic environment.

Applications:

The results indicate that 90° and 135° sideways laparoscope placements may result in worse performance for novices in the laparoscopic environment, indicating potentially longer learning curves for these conditions in the laparoscopic as well as other teleoperation environments.
Fabrication of three-dimensional functionally graded materials using controlled polycaprolactone powder characteristics and laser material processing
Authors: Lee Pil-Ho , Cho Kyounga , Lee Sang Won , Kim Il Won , Park Seungho , Ko Jeonghan , Chung Haseung
Published: October 2014

The functionally graded material is characterized by its gradual change in material compositions and properties over the volume of a component to optimize its functional value. To fabricate functionally graded material parts by additive laser material processing, appropriate powders are critical in term of their size, shape, and mechanical properties. This paper presents new methods to mass produce polycaprolactone powders, a type of biodegradable polymer, with deliberately modified properties as well as to fabricate functionally graded material parts using the modified powders by laser material processing. To modify the properties of the biodegradable polymer powder, this research used two different approaches: recrystallization and spraying. The two different modification methods enabled the significant change of the polycaprolactone powders’ molecular weight that strongly affects mechanical properties. This controlled molecular weight change enabled the gradual variation of the mechanical properties in functionally graded material. By the two different modification methods, the raw materials with irregular shape and size were changed into powders with a round shape and similar sizes, so that they became more suitable for the laser material processing. We verified the modified powder properties such as the size distribution, shape, crystallinity degree, thermophysical properties, and molecular weight by using a variety of methods. The modified polycaprolactone powders with varying mixture ratios were sintered by Nd:YLF laser irradiation with 349-nm wavelength, and the different mechanical properties were verified by micro-tensile tests. As an application of functionally graded material, a biomedical trigger capsule was fabricated and its performance evaluation demonstrated the desired results according to three-dimensional functionally graded material design.
Reduction of water absorption capacity of cellulose fibres for its application in cementitious materials
Authors: Sang Yizhou , Zhao Joe R
Published: October 2014

Although some natural fibres have been used in cementitious materials, the performance of cement with natural fibres has been found to be less satisfactory. The strength loss is partially attributed to the water absorbed by the fibres. In order to alleviate this problem, cellulose fibres were chemically modified to reduce its water adsorption capacity. Results show that calcium hydroxide pretreatment reduces the water adsorption capacity to some extent. Fine grinding treatment further reduced water adsorption. The lowest water adsorption was achieved by cuprammonium solution pretreatment. Theoretical calculation of the hydroxyl groups demonstrates the water adsorbed by crystalline region is almost negligible.
The mechanical and fire safety properties of bamboo fiber reinforced polylactide biocomposites fabricated by injection molding
Authors: Young Wen-Bin , Tsao Yu-Chi
Published: October 2014

Bamboo fiber was considered a good candidate for the reinforcement of green composites. The applications of bamboo fibers as reinforcements in fabric or structural forms to constitute composites have been widely investigated. This study conducted the process from the bamboo strips to the fibers that were compounded with the polylactide to form the composite pellets for the following injection molding process. Alkali treatment of bamboo fiber at 100℃ for 12 h could properly delignify the bamboo fiber strips, resulting in required bamboo fibers. After compounded with polylactide in a banbury mixer to form composite pellets, the injection molding process was used to make composites with improved mechanical properties, including the tensile strength, tensile modulus, flexural strength, flexural modulus, and impact strength. The reinforced effect of the bamboo fiber on polylactide was quite apparent in our experiments. A simple rule of mixture was used to approximate the tensile strength and modulus of the bamboo fiber/polylactide composite. The fire safety improvement of the biocomposite was also investigated by adding fire retardant.
Vitamin B12 deficiency causing night sweats
Authors: Rehman HU
Published: October 2014

Vitamin B12 deficiency is common. It is known to cause a wide spectrum of neurological syndromes, including autonomic dysfunction. Three cases are discussed here in which drenching night sweats were thought to be caused by vitamin B12 deficiency. All three responded dramatically to vitamin B12 therapy.