bluuebunny/crossref_metadata_2025 huggingface dataset:
COPING WITH RESETTLEMENT DIFFICULTIES: A QUALITATIVE ANALYSIS OF COPING STRATEGIES USED BY MAINLAND CHINESE IMMIGRANTS IN HONG KONG
Authors: WONG DANIEL FU KEUNG
Published: December 2009

A qualitative study was undertaken to explore the coping strategies used by mainland Chinese immigrants in Hong Kong to handle psychosocial stressors experienced during the resettlement stage of the migration process. It was revealed that coping strategies employed were stage-specific and culture-specific. While problem-solving strategies and compromise were used by immigrants to deal with recurring, daily resettlement difficulties, cognitive strategies of positive comparisons and positive and optimistic thinking were utilised to change the meanings of these difficulties. Acceptance and avoidance strategies were culture-specific, and were useful in reducing the stress associated with the resettlement difficulties encountered. It was also found that strategies such as acceptance, compromise and avoidance might have deleterious effects on the longer-term adjustment of immigrants. Implications for counselling the immigrants were suggested.
UNRELATED ADOPTION IN HONG KONG: PROFILE AND EMERGING ISSUES
Authors: KO GRACE PO-CHEE
Published: December 2009

This is the first systematic study of adoption in Hong Kong. It examines the changing profile of non-relative adoption in 1987 to 1993 as shown by the files of 486 successful non-relative adoption cases that were analysed. Characteristics of the adoptive parents, the birth parents and the adopted children are presented in descriptive statistics and their inter-relationships are pointed out. The findings are discussed in the light of the changing scene of adoption work against the socio-economic-political background of Hong Kong. A series of recommendations, based on the findings of the study, to the Social Welfare Department are made.

这是香港第一个对领养作有系统的研究。本文分析了486个文件夹，并勾划出1987至1993年间非亲属领养在转变中的剪影。

本文更发表了有关领养父母、生父母及被领养儿童的特徵和描述性统计数据，更指出了其间的关系。就研究所得结果，以社会、经济和政治作背景，本文讨论了领养工作在香港的改变，也向社会福利署作出了连串的建议。
SENSOR GRID ARCHITECTURE FOR REMOTE PATIENT HEALTH CARE MONITORING
Authors: LUDWIG SIMONE A.
Published: December 2009

Recent advancement in wireless sensor network technology has completely changed the way the physicians and other health professionals monitor and access patients' health status records in real time, interact with each other, and access the past and present medical records of patients. However, the sensor nodes used in a wireless sensor network to monitor patients' health are resource constraint in nature with limited processing and communication capability. In future, an increase of wireless sensor networks to monitor and analyze patients' health records is envisioned and therefore, the resource constraint nature of wireless sensor networks needs to be addressed. In this paper, an architecture to overcome the limitations of wireless sensor networks is introduced using Grid computing technology. Sensor Grid technology combines these two technologies by extending the Grid computing paradigm to the sensor resources in wireless sensor networks. This paper outlines how the Sensor Grid technology provides a solution for remote patient monitoring to address the resource constraint nature of the sensor devices in a wireless sensor network.
ASSIGNING SEMANTICS TO SENSED HUMAN ACTIONS: A FRAMEWORK AND STEPS TOWARDS AN ABSTRACT MODEL
Authors: LOKE SENG W. , TIVENDALE CHRIS
Published: December 2009

While there have been many applications that rely on sensors for human computer interaction, for monitoring environments, and for smart context-aware applications, many systems are built in an ad hoc manner, and targets specific domains. There will be a growing demand for such applications whether for everyday life or games. This paper reports on work in two directions towards general development strategies for sensor-driven systems: one is an XML programmable framework and the other an abstract relational model for specifying such sensor-based human computer interaction systems (together with the ability to formally define properties of such systems). While we describe a specific implementation and model, the paper advocates high-level programmability, and development via formal abstract specifications, as two important areas of research towards systematic development of sensor-based interaction systems.
PROJECTING AWAY THE CLASS IMBALANCE PROBLEM IN AUTHOR ATTRIBUTION
Authors: GEHRKE GRANT , MARTELL CRAIG , SCHEIN ANDREW , ANAND PRANAV
Published: December 2009

Author identification algorithms attempt to ascribe document to author, with an eye towards diverse application areas including: forensic evidence, authenticating communications, and intelligence gathering. We view author identification as a single label classification problem, where 2000 authors would imply 2000 possible categories to assign to a post. Experiments with a naive Bayes classifier on a blog author identification task demonstrate a remarkable tendency to over-predict the most prolific authors. Literature search confirms that the class imbalance phenomenon is a challenge for author identification as well as other machine learning tasks. We develop a vector projection method to remove this hazard, and achieve a 63% improvement in accuracy over the baseline on the same task. Our method adds no additional asymptotic computational complexity to naive Bayes, and has no free parameters to set. The projection technique will likely prove useful for other natural language tasks exhibiting class imbalance.
Environmental urban geotechnics
Authors: Jefferson I. , Braithwaite P.
Published: December 2009

This paper gives a brief overview of 29 papers that were submitted to the 10th Congress of the International Association for Engineering Geology and the Environment (IAEG) held in Nottingham, UK. The ‘Environmental Urban Geotechnics’ theme was one of 12 sessions featured within the Congress. The contributions within this theme were truly international, reflecting the global contribution that engineering geology and geotechnics make to urban environments and their development. Papers within this theme have been submitted from 14 countries including Algeria, China, the Czech Republic, France, Japan, South Korea, Lithuania, Poland, Russia, Singapore, Saudi Arabia, the UK and the USA. The papers are diverse in nature, covering the many different contributory facets that were encompassed within the theme. These papers, discussed here, have been grouped into sub-themes for convenience, reflecting commonalities in what was a very broad and diverse coverage. Of the papers presented under this theme, eight examined assessment of geohazards ranging from anthropogenic ground hazards in the form of contamination to natural hazards related to specific problematic ground behaviour. Ten papers discussed issues related to analytical or numerical approaches, used to assess a range of ground-related problems including a number of key geohazards that affect the urban environment. A further six papers examined ground improvements, and five papers dealt with what has been called here geostructures, taken for the purposes of this paper as retaining structures and other ground–structure interaction problems. A number of case studies were detailed relating to a wide range of ground conditions, consistent with material commonly found in urban environments. Where appropriate, the information gleaned from the papers has been supplemented with additional material gathered during the question and answer sessions undertaken during the presentations. From this, development of the implicit theme of sustainability common to the vast majority of papers under the environmental urban geotechnics theme has been made.
Challenges for regional infrastructure: acceptable risk, prioritization of repair and vulnerability reduction
Authors: Sharpe L. , Allenby D.
Published: December 2009

This paper discusses three major issues identified from the 29 papers accepted for the session entitled ‘Infrastructure for the City and its Regions', part of the 10th Congress of the International Association of Engineering Geology and the Environment (IAEG). These three issues are of significant importance to the owners and operators of infrastructure worldwide in terms of both the management of existing networks and the planning of future projects. They can be summarized as: (1) risk mitigation with respect to site investigation, feasibility and route selection; (2) the strategic management of existing infrastructure assets; (3) the protection of earthwork assets against future climatic change. Both (2) and (3) are discussed with reference to the UK rail network. The importance of historical records and research reported in the session is highlighted, and the example of strategic management of the largely Victorian railway tunnel network is discussed. Landslides and flooding are seen as the major risks affecting infrastructure earthwork assets in relation to climate change. The way in which risks to assets and public safety are currently assessed, given priority for repair, and managed is explored.
Geology of megacities and urban areas
Authors: Marker B. R.
Published: December 2009

Urban geology is not a discipline, as such, but, rather, involves the deployment of the full range of relevant geoscience techniques to urbanized areas. Geoscience issues relevant to megacities and urban areas are essentially the same as those experienced elsewhere but their effects are often greater. Many, if not all, of the papers presented at the IAEG 2006 Congress were, thus, relevant to a greater or lesser degree, and provide a rich source of varied case studies. This paper reviews some important cross-cutting issues, making particular reference to the contributions to the Congress.
Geological evolution of the NW corner of the Caribbean Plate
Authors: Valls Alvarez Ricardo A.
Published: December 2009

The Caribbean Plate consists of a plateau basalt, formed probably in the Middle Cretaceous, complicated by a continental block, Chortís, several magmatic arcs, strike–slip motions along major fault systems such as the Motagua–Polochic fault zone in Guatemala, the pull-apart basin of the Cayman Trough and subduction zones below Central America and the Lesser Antilles. Five major collisional events have been identified: (i) Late Paleocene–Middle Eocene collision of the Greater Antilles with the Bahamas platform; (ii) Late Cretaceous collision of Chortís with the Maya Block; (iii) emplacement of nappes upon the Venezuelan foreland in the Cenozoic; (iv) collision of the Western Cordillera oceanic complex with the Central Cordillera of Colombia; and (v) Miocene collision of the eastern Costa Rica–Panama arc with the Western Cordillera. All these ‘orogenic events’ show an eastward movement of the Caribbean Plate relative to the Americas. Migration of the Jamaica Block from the Pacific caused obduction of the oldest ophiolites of Huehuetenango at the western end of the Polochic–Río Negro faults in Guatemala. South-southwest migration of the Chortís Block from west of Mexico and northward towards the Maya Block destroyed a trench associated with the Motagua–Jalomáx fault system and caused the Chuacús Orogeny, emplacing Guatemalan ophiolite complexes and metamorphosing the rocks from the Chuacús Series.
Key issues on the post-Mesozoic Southern Caribbean Plate boundary
Authors: Audemard Franck A.
Published: December 2009

A lithospheric-scale, geodynamic model of the Caribbean southern boundary takes into account tectonic and stratigraphic elements previously unconsidered or not well constrained. The Falcón, Bonaire, Blanquilla and Grenada basins are parts of a former single back-arc basin associated with the migrating Mesozoic Caribbean Arc in Late Eocene–Oligocene times. Spreading of the crescent-shaped basin was triggered by declining Caribbean eastward motion in response to increased convergence between the two Americas at around 38–33 Ma. Dextral wrenching along the southern boundary started in western Venezuela at 17–15 Ma and progressed eastward to the El Pilar Fault by 12 Ma. Eastward motion of the Caribbean relative to South America was earlier accommodated by east-progressing, non-partitioned oblique subduction and collision, as illustrated today in eastern Venezuela around the Los Bajos–El Soldado fault system. Extrusion of the Maracaibo and Bonaire blocks towards the NNE started around 5 Ma, thus the dextral Boconó fault is a young feature. Total plate boundary Cenozoic dextral wrenching recorded onshore Venezuela does not exceed 100 km and is more likely to be in the order of 55 km.
The vanishing Carib Halite Formation (Neocomian), Colombia-Venezuela-Trinidad prolific petroleum province
Authors: Higgs Roger
Published: December 2009

Literature survey reveals evidence of a thick (
c
. 3 km), largely dissolved, Berriasian–Valanginian ‘Carib Halite Formation’, deposited in a Jurassic to Coniacian ‘Carib Graben’ from Colombia through Venezuela to Trinidad. From Campanian time the graben inverted into the (partly metamorphosed) south-verging nappe/thrust-belt of northern South America (Guajira to Trinidad), and later the bivergent Eastern Cordillera and Mérida Andes. Outcropping halite is confined to Colombia. Numerous lines of evidence suggest
buried
halite in Colombia, Venezuela and Trinidad: drowning coastal geomorphology (halite-solution subsidence); subaerial and submarine closed depressions (solution pits); saline springs; mud-volcano-fluid analysis; heat-flow anomalies; gravity anomalies; and thrust-belt structural style. Other data suggest thick (kilometres)
vanished
halite: a Berriasian regional faunal gap; highly organic shales/phyllites (solution residues); intense fracturing (solution collapse); metamorphic-grade discontinuities (solution weld); and Neogene supraorogen basins attributable to buried-halite solution, for example Gulf of Venezuela, Monagas thrust belt, Gulf of Paria and onshore Trinidad. Halite solution by circulating meteoric water is inferred to have begun near 11 Ma, reflecting climate change (wetter) accompanying the onset of the Gulf Stream, induced by collision of the Panamá Arc against Colombia, interrupting deep-sea Caribbean–Pacific interchange. The Carib Halite concept has important implications for exploration in the oil-rich thrust belts of Colombia, Venezuela and Trinidad. There is also potential for new finds of emeralds and other evaporite-associated minerals.
Present-day strain field on the South American slab underneath the Sandwich Plate (Southern Atlantic Ocean): a kinematic model
Authors: Giner-Robles J. L. , Pérez-López R. , Rodríguez-Pascua M. A. , Martínez-Díaz J. J. , González-Casado J. M.
Published: December 2009

This work analyses the present-day principal strain orientation on the downgoing slab of the South America Plate (SAM) beneath the Sandwich Plate (SAND). The strain regime was deduced from the study of 331 earthquake focal mechanism solutions examined by fault population analysis methods. In the slab, the maximum horizontal shortening direction (ey) rotates in trend in a clockwise direction from NE in the north, to SE in the south. Based on this rotation, three different areas were defined according to the prevailing focal mechanism type: (1) the North Zone, with ey oriented N058°E and reverse and strike–slip focal mechanisms; (2) the Central Zone, with only reverse focal mechanisms and ey striking N080°E; and (3) the South Zone, with ey oriented N106°E and reverse and strike–slip focal mechanisms. The strain field in the North Zone of the SAND involves decoupling of the slab at approximately 70 km depth. In contrast, the South Zone edge slab exhibits no decoupling and it exhibits different geometry (hook-like shaped) from the North Zone. Finally, we define the dextral strike–slip component acting at the South Sandwich Fracture Zone (SSFZ), according to focal mechanism solutions and the regional tectonic configuration.
Synchronous 29-19 Ma arc hiatus, exhumation and subduction of forearc in southwestern Mexico
Authors: Keppie J. Duncan , Morán-Zenteno Dante J. , Martiny Barbara , González-Torres Enrique
Published: December 2009

The geology of southwestern Mexico (102–96°W) records several synchronous events in the Late Oligocene–Early Miocene (29–19 Ma): (1) a hiatus in arc magmatism; (2) removal of a wide (
c
. 210 km) Upper Eocene–Lower Oligocene forearc; (3) exhumation of 13–20 km of Upper Eocene–Lower Oligocene arc along the present day coast; and (4) breakup of the Farallon Plate. Events 2 and 3 have traditionally been related to eastward displacement of the Chortís Block from a position off southwestern Mexico between 105°W and 97°W; however at 30 Ma the Chortís Block would have lain east of 95°W. We suggest that the magmatic hiatus was caused by subduction of the forearc, which replaced the mantle wedge by relatively cool crust. Assuming that the subducted block separated along the forearc–arc boundary, a likely zone of weakness due to magmatism, the subducted forearc is estimated to be wedge-shaped varying from zero to
c
. 90 km in thickness; however such a wedge is not apparent in seismic data across central Mexico. Given the 121 km/Ma convergence rate between 20 and 10 Ma and 67 km/Ma since 10 Ma, it is probable that any forearc has been deeply subducted. Potential causes for subduction of the forearc include collision of an oceanic plateau with the trench, and a change in plate kinematics synchronous with breakup of the Farallon Plate and initiation of the Guadalupe–Nazca spreading ridge.
Analogue models of an Early Cenozoic transpressive regime in southern Mexico: implications on the evolution of the Xolapa complex and the North American-Caribbean Plate boundary
Authors: Cerca Mariano , Ferrari Luca , Tolson Gustavo , Corti Giacomo , Bonini Marco , Manetti Piero
Published: December 2009

We present analogue models that illustrate the tectonic evolution of the continental margin of southwestern Mexico and the Early Cenozoic deformation of the Xolapa complex. Together with geological data they suggest that oblique convergence caused distributed deformation and mountain building near the present-day margin of southern Mexico in a general left-lateral transpressional regime. A similar deformation is also observed north of the Xolapa complex in Maastrichtian to Paleocene sedimentary and volcanic rock units. Since post-Oligocene exhumation of middle crust does not significantly affect Late Eocene to Oligocene volcanic rocks, we infer that the evolution of the transform margin led to the formation of discrete boundaries that eventually decoupled exhumed mid-lower crust from the onshore upper-crust sequences since the Late Eocene.
A seismotectonic model for the Chortís Block
Authors: Guzmán-Speziale Marco
Published: December 2009

I propose a new seismotectonic model for the Chortís Block, at the northwestern corner of the Caribbean Plate. Shallow seismicity in the area clearly shows three zones of deformation: one along the North America–Caribbean Plate boundary and another along the Central America volcanic arc, and one in the area of the grabens of northern Central America. Analysis of Centroid moment–tensor solutions for shallow earthquakes in these three area show that
T
or tension axes are horizontal and trend away from the corner, and that
P
or compression axes for the plate boundary and the volcanic arc are also horizontal and trending towards the corner. Calculation of seismic moment release per unit volume reveals similar values for the volcanic arc and the plate boundary. The state of stress and similarity in seismic moment release suggest that the Chortís Block is being extruded towards the ESE. This is probably due to compression of the large North America and Cocos Plates that surround it.
RAGE supports parathyroid hormone-induced gains in femoral trabecular bone
Authors: Philip Binu K. , Childress Paul J. , Robling Alexander G. , Heller Aaron , Nawroth Peter P. , Bierhaus Angelika , Bidwell Joseph P.
Published: December 2009

Parathyroid hormone (PTH) restores bone mass to the osteopenic skeleton, but significant questions remain as to the underlying mechanisms. The receptor for advanced glycation end products (RAGE) is a multiligand receptor of the immunoglobulin superfamily; however, recent studies indicate a role in bone physiology. We investigated the significance of RAGE to hormone-induced increases in bone by treating 10-wk-old female Rage-knockout (KO) and wild-type (WT) mice with human PTH-(1–34) at 30 μg·kg−1·day−1 or vehicle control, 7 days/wk, for 7 wk. PTH produced equivalent relative gains in bone mineral density (BMD) and bone mineral content (BMC) throughout the skeleton in both genotypes. PTH-mediated relative increases in cortical area of the midshaft femur were not compromised in the null mice. However, the hormone-induced gain in femoral cancellous bone was significantly attenuated in Rage-KO mice. The loss of RAGE impaired PTH-mediated increases in femoral cancellous bone volume, connectivity density, and trabecular number but did not impact increases in trabecular thickness or decreases in trabecular spacing. Disabling RAGE reduced femoral expression of bone formation genes, but their relative PTH-responsiveness was not impaired. Neutralizing RAGE did not attenuate vertebral cancellous bone response to hormone. Rage-null mice exhibited an attenuated accrual rate of bone mass, with the exception of the spine, and an enhanced accrual rate of fat mass. We conclude that RAGE is necessary for key aspects of the skeleton's response to anabolic PTH. Specifically, RAGE is required for hormone-mediated improvement of femoral trabecular architecture but not intrinsically necessary for increasing cortical thickness.
Responses of Amygdala Neurons to Positive Reward-Predicting Stimuli Depend on Background Reward (Contingency) Rather Than Stimulus-Reward Pairing (Contiguity)
Authors: Bermudez Maria A. , Schultz Wolfram
Published: December 2009

Prediction about outcomes constitutes a basic mechanism underlying informed economic decision making. A stimulus constitutes a reward predictor when it provides more information about the reward than the environmental background. Reward prediction can be manipulated in two ways, by varying the reward paired with the stimulus, as done traditionally in neurophysiological studies, and by varying the background reward while holding stimulus-reward pairing constant. Neuronal mechanisms involved in reward prediction should also be sensitive to changes in background reward independently of stimulus-reward pairing. We tested this assumption on a major brain structure involved in reward processing, the central and basolateral amygdala. In a 2 × 2 design, we examined the influence of rewarded and unrewarded backgrounds on neuronal responses to rewarded and unrewarded visual stimuli. Indeed, responses to the unchanged rewarded stimulus depended crucially on background reward in a population of amygdala neurons. Elevating background reward to the level of the rewarded stimulus extinguished these responses, and lowering background reward again reinstated the responses without changes in stimulus-reward pairing. None of these neurons responded specifically to an inhibitory stimulus predicting less reward compared with background (negative contingency). A smaller group of amygdala neurons maintained stimulus responses irrespective of background reward, possibly reflecting stimulus-reward pairing or visual sensory processes without reward prediction. Thus in being sensitive to background reward, the responses of a population of amygdala neurons to phasic stimuli appeared to follow the full criteria for excitatory reward prediction (positive contingency) rather than reflecting simple stimulus-reward pairing (contiguity).
Temporal Dynamics of 2D Motion Integration for Ocular Following in Macaque Monkeys
Authors: Barthélemy Fréderic V. , Fleuriet Jérome , Masson Guillaume S.
Published: December 2009

Several recent studies have shown that extracting pattern motion direction is a dynamical process where edge motion is first extracted and pattern-related information is encoded with a small time lag by MT neurons. A similar dynamics was found for human reflexive or voluntary tracking. Here, we bring an essential, but still missing, piece of information by documenting macaque ocular following responses to gratings, unikinetic plaids, and barber-poles. We found that ocular tracking was always initiated first in the grating motion direction with ultra-short latencies (∼55 ms). A second component was driven only 10–15 ms later, rotating tracking toward pattern motion direction. At the end the open-loop period, tracking direction was aligned with pattern motion direction (plaids) or the average of the line-ending motion directions (barber-poles). We characterized the dependency on contrast of each component. Both timing and direction of ocular following were quantitatively very consistent with the dynamics of neuronal responses reported by others. Overall, we found a remarkable consistency between neuronal dynamics and monkey behavior, advocating for a direct link between the neuronal solution of the aperture problem and primate perception and action.
Are elite endurance athletes genetically predisposed to lower disease risk?
Authors: Gómez-Gallego Félix , Ruiz Jonatan R. , Buxens Amaya , Altmäe Signe , Artieda Marta , Santiago Catalina , González-Freire Marta , Verde Zoraida , Arteta David , Martínez Antonio , Tejedor Diego , Lao José I. , Arenas Joaquin , Lucia Alejandro
Published: December 2009

We compared a polygenic profile that combined 33 disease risk-related mutations and polymorphisms among nonathletic healthy control subjects and elite endurance athletes. The study sample comprised 100 healthy Spanish male nonathletic (sedentary) control subjects and 100 male elite endurance athletes. We analyzed 33 disease risk-related mutations and polymorphisms. We computed a health-related total genotype score (TGS, 0–100) from the accumulated combination of the 33 variants. We did not observe significant differences in genotype or allele distributions among groups, except for the rs4994 polymorphism ( P < 0.001). The computed health-related TGS was similar among groups (23.8 ± 1.0 vs. 24.2 ± 0.8 in control subjects and athletes, respectively; P = 0.553). Similar results were obtained when computing specific TGSs for each main disease category (cardiovascular disease and cancer). We observed no evidence that male elite endurance athletes are genetically predisposed to have lower disease risk than matched nonathletic control subjects.
Myeloid-Derived Suppressor Cells Inhibit T-Cell Activation by Depleting Cystine and Cysteine
Authors: Srivastava Minu K. , Sinha Pratima , Clements Virginia K. , Rodriguez Paulo , Ostrand-Rosenberg Suzanne
Published: December 2009

Myeloid-derived suppressor cells (MDSC) are present in most cancer patients and are potent inhibitors of T-cell–mediated antitumor immunity. Their inhibitory activity is attributed to production of arginase, reactive oxygen species, inducible nitric oxide synthase, and interleukin-10. Here we show that MDSCs also block T-cell activation by sequestering cystine and limiting the availability of cysteine. Cysteine is an essential amino acid for T-cell activation because T cells lack cystathionase, which converts methionine to cysteine, and because they do not have an intact xc− transporter and therefore cannot import cystine and reduce it intracellularly to cysteine. T cells depend on antigen-presenting cells (APC), such as macrophages and dendritic cells, to export cysteine, which is imported by T cells via their ASC neutral amino acid transporter. MDSCs express the xc− transporter and import cystine; however, they do not express the ASC transporter and do not export cysteine. MDSCs compete with APC for extracellular cystine, and in the presence of MDSCs, APC release of cysteine is reduced, thereby limiting the extracellular pool of cysteine. In summary, MDSCs consume cystine and do not return cysteine to their microenvironment, thereby depriving T cells of the cysteine they require for activation and function. Cancer Res; 70(1); 68–77
Mining Tissue Microarray Data to Uncover Combinations of Biomarker Expression Patterns that Improve Intermediate Staging and Grading of Clear Cell Renal Cell Cancer
Authors: Dahinden Corinne , Ingold Barbara , Wild Peter , Boysen Gunther , Luu Van-Duc , Montani Matteo , Kristiansen Glen , Sulser Tullio , Bühlmann Peter , Moch Holger , Schraml Peter
Published: December 2009

Purpose: Tumor stage and nuclear grade are the most important prognostic parameters of clear cell renal cell carcinoma (ccRCC). The progression risk of ccRCC remains difficult to predict particularly for tumors with organ-confined stage and intermediate differentiation grade. Elucidating molecular pathways deregulated in ccRCC may point to novel prognostic parameters that facilitate planning of therapeutic approaches.

Experimental Design: Using tissue microarrays, expression patterns of 15 different proteins were evaluated in over 800 ccRCC patients to analyze pathways reported to be physiologically controlled by the tumor suppressors von Hippel-Lindau protein and phosphatase and tensin homologue (PTEN). Tumor staging and grading were improved by performing variable selection using Cox regression and a recursive bootstrap elimination scheme.

Results: Patients with pT2 and pT3 tumors that were p27 and CAIX positive had a better outcome than those with all remaining marker combinations. A prolonged survival among patients with intermediate grade (grade 2) correlated with both nuclear p27 and cytoplasmic PTEN expression, as well as with inactive, nonphosphorylated ribosomal protein S6. By applying graphical log-linear modeling for over 700 ccRCC for which the molecular parameters were available, only a weak conditional dependence existed between the expression of p27, PTEN, CAIX, and p-S6, suggesting that the dysregulation of several independent pathways are crucial for tumor progression.

Conclusions: The use of recursive bootstrap elimination, as well as graphical log-linear modeling for comprehensive tissue microarray (TMA) data analysis allows the unraveling of complex molecular contexts and may improve predictive evaluations for patients with advanced renal cancer. Clin Cancer Res; 16(1); 88–98
SPARC Is Associated with Gastric Cancer Progression and Poor Survival of Patients
Authors: Zhao Zhong-Sheng , Wang Yuan-Yu , Chu Yong-Quan , Ye Zai-Yuan , Tao Hou-Quan
Published: December 2009

Purpose: The present study investigated the clinical significance of secreted protein, acidic and rich in cysteine (SPARC), in the development and progression of gastric cancer.

Experimental Design: Immunohistochemistry was used to analyze SPARC, integrin β1, and matrix metalloproteinase (MMP)-2 expression in 436 clinicopathologically characterized gastric cancer cases.

Results: SPARC, integrin β1, and MMP-2 protein levels were upregulated in gastric cancer lesions compared with adjacent noncancerous tissues. SPARC protein was detected in 334 of 436 human gastric cancer cases and was highly expressed in 239 tumors. We also found a positive correlation between expression of SPARC and MMP2, and SPARC and integrin β1. In stages I, II, and III, the 5-year survival rate of patients with a high expression of SPARC was significantly lower than those in patients with low expression. In stage IV, SPARC expression did not correlate with the 5-year survival rate. Further multivariate analysis suggested that the depth of invasion; lymph node and distant metastasis; tumor-node-metastasis stage; and upregulation of SPARC, MMP-2, and integrin β1, were independent prognostic indicators for the disease.

Conclusions: Our study provided a basis for the development of a novel biomarker for diagnosis and prognosis of gastric cancer. Expression of SPARC in gastric cancer is significantly associated with lymph node and distant metastasis, high MMP2 expression, high intergrin β1 expression, and poor prognosis. SPARC, intergrin β1, and MMP-2 protein could be useful markers to predict tumor progression. Clin Cancer Res; 16(1); 260–8
Vorinostat Enhances the Activity of Temsirolimus in Renal Cell Carcinoma Through Suppression of Survivin Levels
Authors: Mahalingam Devalingam , Medina Ernest C. , Esquivel Juan A. , Espitia Claudia M. , Smith Sabrina , Oberheu Kelli , Swords Ronan , Kelly Kevin R. , Mita Monica M. , Mita Alain C. , Carew Jennifer S. , Giles Francis J. , Nawrocki Steffan T.
Published: December 2009

Purpose: The mammalian target of rapamycin (mTOR) inhibitor temsirolimus has exhibited promising anticancer activity for the treatment of renal cell cancers (RCC). Survivin expression has been implicated in drug resistance and reducing its levels with the histone deacetylase (HDAC) inhibitor vorinostat may enhance the anticancer activity of temsirolimus.

Experimental Design: The sensitivity of RCC cell lines to the combination of temsirolimus and vorinostat was determined by measuring cell viability, clonogenic survival, and apoptosis. The effects of this combination on survivin levels were determined in vitro and in vivo. Survivin expression was silenced using small interfering RNA to evaluate its role in determining sensitivity to temsirolimus and vorinostat. The effect of the combination on angiogenesis was also determined in RCC xenograft models.

Results: Vorinostat synergistically improved the anticancer activity of temsirolimus in a panel of RCC cell lines in vitro and in two xenograft models in vivo. While each single agent led to a modest decrease in survivin levels, the combination dramatically reduced its expression, which correlated with an induction of apoptosis. Silencing survivin levels induced apoptosis and significantly improved the efficacy of temsirolimus and vorinostat. In addition, the temsirolimus/vorinostat combination led to a strong reduction in angiogenesis.

Conclusions: Vorinostat augmented the anticancer activity of temsirolimus in both in vitro and in vivo models of RCC. The effectiveness of the combination was due to a decrease in survivin levels and corresponding induction of apoptosis, and enhanced inhibition of angiogenesis. Targeting survivin may be a promising therapeutic strategy to improve RCC therapy. Clin Cancer Res; 16(1); 141–53
Aldehyde Dehydrogenase 1–Positive Cancer Stem Cells Mediate Metastasis and Poor Clinical Outcome in Inflammatory Breast Cancer
Authors: Charafe-Jauffret Emmanuelle , Ginestier Christophe , Iovino Flora , Tarpin Carole , Diebel Mark , Esterni Benjamin , Houvenaeghel Gilles , Extra Jean-Marc , Bertucci François , Jacquemier Jocelyne , Xerri Luc , Dontu Gabriela , Stassi Giorgio , Xiao Yi , Barsky Sanford H. , Birnbaum Daniel , Viens Patrice , Wicha Max S.
Published: December 2009

Purpose: To examine the role of cancer stem cells (CSC) in mediating metastasis in inflammatory breast cancer (IBC) and the association of these cells with patient outcome in this aggressive type of breast cancer.

Experimental Design: CSCs were isolated from SUM149 and MARY-X, an IBC cell line and primary xenograft, by virtue of increased aldehyde dehydrogenase (ALDH) activity as assessed by the ALDEFLUOR assay. Invasion and metastasis of CSC populations were assessed by in vitro and mouse xenograft assays. Expression of ALDH1 was determined on a retrospective series of 109 IBC patients and this was correlated with histoclinical data. All statistical tests were two sided. Log-rank tests using Kaplan-Meier analysis were used to determine the correlation of ALDH1 expression with development of metastasis and patient outcome.

Results: Both in vitro and xenograft assays showed that invasion and metastasis in IBC are mediated by a cellular component that displays ALDH activity. Furthermore, expression of ALDH1 in IBC was an independent predictive factor for early metastasis and decreased survival in this patient population.

Conclusions: These results suggest that the metastatic, aggressive behavior of IBC may be mediated by a CSC component that displays ALDH enzymatic activity. ALDH1 expression represents the first independent prognostic marker to predict metastasis and poor patient outcome in IBC. The results illustrate how stem cell research can translate into clinical practice in the IBC field. Clin Cancer Res; 16(1); 45–55
Immunotherapy of Malignant Disease with Tumor Antigen–Specific Monoclonal Antibodies
Authors: Campoli Michael , Ferris Robert , Ferrone Soldano , Wang Xinhui
Published: December 2009

A few tumor antigen (TA)–specific monoclonal antibodies (mAb) have been approved by the Food and Drug Administration for the treatment of several major malignant diseases and are commercially available. Once in the clinic, mAbs have an average success rate of ∼30% and are well tolerated. These results have changed the face of cancer therapy, bringing us closer to more specific and more effective biological therapy of cancer. The challenge facing tumor immunologists at present is represented by the identification of the mechanism(s) underlying the patients' differential clinical response to mAb-based immunotherapy. This information is expected to lead to the development of criteria to select patients to be treated with mAb-based immunotherapy. In the past, in vitro and in vivo evidence has shown that TA-specific mAbs can mediate their therapeutic effect by inducing tumor cell apoptosis, inhibiting the targeted antigen function, blocking tumor cell signaling, and/or mediating complement- or cell-dependent lysis of tumor cells. More recent evidence suggests that TA-specific mAb can induce TA-specific cytotoxic T-cell responses by enhancing TA uptake by dendritic cells and cross-priming of T cells. In this review, we briefly summarize the TA-specific mAbs that have received Food and Drug Administration approval. Next, we review the potential mechanisms underlying the therapeutic efficacy of TA-specific mAbs with emphasis on the induction of TA-specific cellular immune responses and their potential to contribute to the clinical efficacy of TA-specific mAb-based immunotherapy. Lastly, we discuss the potential negative effect of immune escape mechanisms on the clinical efficacy of TA-specific mAb-based immunotherapy. Clin Cancer Res; 16(1); 11–20
Undifferentiated Histology after Endoscopic Resection May Predict Synchronous and Metachronous Occurrence of Early Gastric Cancer
Authors: Seo Ju Hee , Park Jun Chul , Kim Yu Jin , Shin Sung Kwan , Lee Yong Chan , Lee Sang Kil
Published: December 2009

Background: Endoscopic resection (endoscopic mucosal resection, EMR, and endoscopic submucosal dissection, ESD) has been accepted worldwide as a less invasive standard treatment for early gastric cancer (EGC). However, the risk of synchronous and metachronous gastric cancer developing in the post-endoscopic resection patient has become a major problem. We investigated the incidence and characteristics of synchronous and metachronous multiple gastric cancers in a retrospective study of patients with EGC after endoscopic resection. Patients and Methods: We studied the clinicopathological features of 235 patients with EGC who had undergone endoscopic resection and were periodically followed up using endoscopic examinations (181 with a single lesion, 34 synchronous multiple lesions, and 20 metachronous multiple lesions). Results: The overall incidence of synchronous and metachronous multiple gastric cancer was 14.5 and 8.5%, respectively, during a follow-up of 12–77 (median 26.5) months. Undifferentiated histology of the primary lesion was related to the occurrence of synchronous gastric cancer (p < 0.001). Undifferentiated histology and upper location of the primary lesion were correlated with the occurrence of metachronous gastric cancer (p = 0.002, 0.001). Most synchronous and metachronous lesions were well to moderately differentiated (82.4 and 80.0%); however, the proportion with undifferentiated histology (including poorly differentiated carcinoma and signet ring cell carcinoma) in synchronous and metachronous gastric cancer was significantly higher than in single gastric cancer (p = 0.008). Conclusions: Undifferentiated histology of EGC may predict the occurrence of synchronous and metachronous lesions after endoscopic resection.
Timing of Birth and Risk of Multiple Sclerosis in the Scottish Population
Authors: Bayes Hannah K. , Weir Christopher J. , O’Leary Colin
Published: December 2009

Development of multiple sclerosis (MS) is believed to result from interplay of genes and environmental factors, which may be anticipated to act in a seasonal manner. Scotland has the highest prevalence of MS in the world. We aimed to determine if risk of multiple sclerosis is associated with season of birth in the Scottish population. Data for MS patients within the West of Scotland (n = 1,309) was obtained. Birth rates of MS patients were compared with national (n = 6,198,352) and regional (n = 664,447) controls. Excess MS births occur in the spring months, with 22% more than expected (401 observed vs. 328 expected, p < 0.0001). Peak month in both sexes was April. Fewer MS births occurred in autumn, with 16% fewer births compared with regional controls (275 observed vs. 328 expected, p = 0.01). Our study, the largest in the Scottish population, demonstrates season of birth and risk of MS are associated. Elucidating potential environmental factor(s) accounting for such an association remains a challenge.
Relationship between Cerebral Hypoxic Tissue Volume and Prognosis after Stroke
Authors: Wang Yi-Dong , Li Xiang-Pen , Li Mei , Liu Sheng , Lu Xian-Ping , Peng Ying , Huang Ru-Xun
Published: December 2009

Background/Aims: Between 50 and 70% of stroke survivors suffer from severe disabilities such as paralysis and aphasia. Poor stroke outcome is a reflection of our incomplete understanding of the underlying mechanisms, and hence the capacity to implement appropriate treatment(s). We evaluated hypoxic tissue after stroke and patient condition severity and prognosis. Methods: Hypoxic tissue volume was quantified within 14 days after stroke. Patients were classified as hypoxic positive or negative. Patients were evaluated at imaging and 21 days later. Prognosis was assessed at 30 and 90 days. Results: Significant improvement was shown in hypoxia-positive (vs. hypoxia-negative) patients (p < 0.05). There were significant positive relationships between the volume of hypoxic tissue and the improvement in specialized test scores at 90 days (p < 0.05 for both). Presence of hypoxic tissue within 14 days after cerebral stroke was related to recovery at 3 weeks and prognosis at 90 days. Conclusions: The assessment of hypoxic tissue volume after stroke may be useful in predicting patient recovery.
Functional Characterization of Calcium-Signaling Pathways of Human Skin-Derived Mesenchymal Stem Cells
Authors: Orciani M. , Mariggiò M.A. , Morabito C. , Di Benedetto G. , Di Primio R.
Published: December 2009

Background: Mesenchymal stem cells (MSCs) derived from adult human tissues are able to differentiate into various specialized cell types. In research, they can therefore be used like embryonic cells but without the ethical restrictions. Among the various human tissues, skin as a source is characterized by great accessibility and availability using noninvasive procedures and is without the risk of oncogenesis after transplantation. The recent isolation of MSCs has shown the lack of knowledge regarding their specific features, including the calcium-signaling pathways. Methods: In this study, we isolated MSCs from human skin biopsies (S-MSCs) and characterized them phenotypically and their calcium-signaling pathways by the means of Ca2+ imaging and video microscopic experiments. Results: The cytofluorimetric analysis of the expression of surface markers on S-MSCs revealed that they express the normal pattern present on MSCs. Interestingly, these cells appeared to be successfully cryopreserved at early passages. Calcium imaging on single S-MSCs shows that these cells did not display significant spontaneous activity or a response to a depolarizing agent. However, ATP or acetylcholine-induced intracellular calcium increase via ionotropic or metabotropic receptors, respectively. Conclusion: The results presented here reveal that S-MSCs show morphological and functional features that make them useful as an in vitro model to study cell differentiation.
Cardiac Surgery in Nonagenarians: Single-Centre Series and Review
Authors: Guilfoyle Mathew R. , Drain Andrew J. , Khan Asmatullah , Ferguson Jonathan , Large Stephen R. , Nashef Samer A.M.
Published: December 2009

Background: Cardiac surgery is widely believed to be an excessively high-risk intervention for very elderly patients with coronary artery or valvular disease. However, as life expectancy and the prospect of sustained quality of life into older age increase, this assumption should be challenged so that surgery is not denied to patients who may derive significant symptomatic benefit with acceptable levels of operative risk. Objective: To evaluate outcomes from cardiac surgery in nonagenarian patients. Design: Analysis of prospectively collected single-centre data and review of outcomes reported in the literature. Results: Twenty-three patients (13 males) aged 90 years or more underwent open cardiac surgery between 1998 and 2007. Four patients died within 30 days of surgery (surgical mortality 17.4%) and all-cause in-hospital morbidity was 74%. Actuarial survival at 1 and 5 years was estimated at 72 and 54%, respectively. Comparison of patients’ survival against age-matched life tables for the English population found a standardised mortality ratio of 0.57 (95% CI: 0.24–0.99; one-sample log-rank test χ2 = 3.93; p < 0.05) representing a significant survival benefit associated with surgery. The majority of patients reported symptomatic improvement reflected by significant decreases in angina and dyspnoea scores. Six single-centre series of nonagenarians and 3 reviews from national databases in the US and UK were identified in the literature. Pooled surgical mortality was 12.7% (95% CI: 8.7–17.3%) with no significant heterogeneity (χ2 = 4.12; p = 0.77; I2 = 0). Conclusion: Cardiac surgery in the elderly carries higher operative risk than in younger patients. However, in selected nonagenarians, surgery can be performed with acceptable morbidity and early mortality, and patients gain significant symptomatic relief and survival benefit.
Achievement Orientations and Strategies
Authors: Nalkur Priya G.
Published: December 2009

Cultures of achievement among street children ( n = 60), former street children ( n = 63), and school-going children ( n = 60), all of whom share the Kilimanjaro culture of Tanzania, are compared. The Thematic Apperception Test, a projective test known to evoke achievement concerns and originally designed for clinical psycho-diagnoses, was used to generate narratives for thematic analyses. The approach is child centered, allowing children to be imaginative under low-stress conditions. Analysis showed that each subculture had a unique achievement orientation and strategy. Among street children, emerging themes of heroic achievement orientation were tempered with paralytic strategies through which goals could not be realized. Former street children’s emergent themes emphasized the presence of beneficial friendships and thus supportive achievement orientation, while strategy themes included exercising choices. School-going children showed deserved achievement orientation in which hard work leads to rewards and control strategy leads to both successful and detrimental outcomes. Themes demonstrate the relative ways in which children adapt to the “difficult life” that has become a common characterization of life in Kilimanjaro.