bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrogen‐Bond‐Mediated Asymmetric Catalysis
Authors: Yu Xinhong , Wang Wei
Published: February 2008

The utilization of hydrogen bonding as an activation force has become a powerful tool in asymmetric organocatalysis. Significant advances have been made in the recent past in this emerging field. Due to space constraints, this Focus Review summarizes only the key aspects with an emphasis on catalysis based on chiral ureas and thioureas, diols, and phosphoric acids. The examples provided neatly demonstrate that chiral ureas and thioureas, diols, and phosphoric acids display effective and unique activation modes of catalysis for a broad spectrum of asymmetric organic transformations, including single‐step and multiple‐step cascade reactions. These functionalities, which have the ability to afford efficient H‐bond activation of electrophiles including CO, CN, aziridines, and epoxides, have established their status as “privileged” functional groups in the design of organocatalysts.
Mobile phone electromagnetic radiation activates MAPK signaling and regulates viability in Drosophila
Authors: Lee Kyu‐Sun , Choi Jong‐Soon , Hong Sae‐Yong , Son Tae‐Ho , Yu Kweon
Published: February 2008

Mobile phones are widely used in the modern world. However, biological effects of electromagnetic radiation produced by mobile phones are largely unknown. In this report, we show biological effects of the mobile phone 835 MHz electromagnetic field (EMF) in the Drosophila model system. When flies were exposed to the specific absorption rate (SAR) 1.6 W/kg, which is the proposed exposure limit by the American National Standards Institute (ANSI), more than 90% of the flies were viable even after the 30 h exposure. However, in the SAR 4.0 W/kg strong EMF exposure, viability dropped from the 12 h exposure. These EMF exposures triggered stress response and increased the production of reactive oxygen species. The EMF exposures also activated extracellular signal regulated kinase (ERK) and c‐Jun N‐terminal kinase (JNK) signaling, but not p38 kinase signaling. Interestingly, SAR 1.6 W/kg activated mainly ERK signaling and expression of an anti‐apoptotic gene, whereas SAR 4.0 W/kg strongly activated JNK signaling and expression of apoptotic genes. In addition, SAR 4.0 W/kg amplified the number of apoptotic cells in the fly brain. These findings demonstrate that the exposure limit on electromagnetic radiation proposed by ANSI triggered ERK‐survival signaling but the strong electromagnetic radiation activated JNK‐apoptotic signaling in Drosophila. Bioelectromagnetics 29:371–379, 2008. © 2008 Wiley‐Liss, Inc.
A new view of protein synthesis: Mapping the free energy landscape of the ribosome using single‐molecule FRET
Authors: Munro James B. , Vaiana Andrea , Sanbonmatsu Kevin Y. , Blanchard Scott C.
Published: February 2008

This article reviews the application of single‐molecule fluorescence resonance energy transfer (smFRET) methods to the study of protein synthesis catalyzed by the ribosome. smFRET is a powerful new technique that can be used to investigate dynamic processes within enzymes spanning many orders of magnitude. The application of wide‐field smFRET imaging methods to the study of dynamic processes in the ribosome offers a new perspective on the mechanism of protein synthesis. Using this technique, the structural and kinetic parameters of tRNA motions within wild‐type and specifically mutated ribosome complexes have been obtained that provide valuable new insights into the mechanism and regulation of translation elongation. The results of these studies are discussed in the context of current knowledge of the ribosome mechanism from both structural and biophysical perspectives. © 2008 Wiley Periodicals, Inc. Biopolymers 89: 565–577, 2008.

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Multiple signaling pathways coordinately mediate reactive oxygen species dependent cardiomyocyte hypertrophy
Authors: Indira K. Adiga , Renuka R. Nair
Published: February 2008

The heart responds to an increased demand arising due to physiological stimuli or pathological insults by hypertrophy of myocytes. Reactive oxygen species (ROS) have recently been identified as the molecular intermediates in the translation of mechanical stimuli to cellular response. Different signal transduction pathways have been implicated with cardiac hypertrophy, prominent among them being, mitogen‐activated protein kinase (MAPK), protein kinase C (PKC) and calcineurin. It remains unclear whether the ROS induced hypertrophy is mediated through one or more of these pathways. This study was taken up with the objective to affirm the role of ROS in the induction of cardiomyocyte hypertrophy and examine the contribution of specific pathways in the mediation of the hypertrophic response. The cellular response to enzyme‐generated reactive oxygen species was examined in cultured cells from newborn rat heart. Pathway specific inhibitors were used to identify the role of each pathway in the mediation of cellular hypertrophy. Cellular hypertrophy in response to hypoxanthine‐xanthine oxidase was prevented by inhibition of any one of the pathways; leading to the inference that oxidative stress induced hypertrophy is mediated by coordinative regulation of the three major pathways. Copyright © 2008 John Wiley & Sons, Ltd.
Analytic Models of Domain‐Averaged Fermi Holes: A New Tool for the Study of the Nature of Chemical Bonds
Authors: Ponec Robert , Cooper David L. , Savin Andreas
Published: February 2008

Simple analytical models are introduced that significantly enhance the ability to understand and rationalise the nature of bonding interactions depicted by domain‐averaged Fermi hole (DAFH) analysis. The examples presented show that besides shedding new light on the role of electron‐sharing in ordinary two‐centre two‐electron (2c–2e) chemical bonds that are well represented by the classical Lewis model, the proposed approach also provides interesting new insights into the nature of bonding interactions that go beyond the traditional Lewis paradigm. This is, for example, the case of 3c–2e multicentre bonding, but a straightforward extension of the approach also reveals for direct metal–metal bonding the existence of a completely new type of bonding interaction that involves the mutual exchange of electrons between the lone pairs on adjacent metal atoms.
A Novel Green Template for the Synthesis of Mesoporous Silica
Authors: Xu Yeping , Xu Shangjie , Emmler Thomas , Roelofs Frank , Boettcher Christoph , Haag Rainer , Buntkowsky Gerd
Published: February 2008

Mesoporous pure silicas and functionalized silica with a narrow pore size distribution centered at 3.8 nm were prepared by a novel template, amphiphilic dendritic polyglycerol. The resulting silica materials were characterized by electron microscopy; nitrogen adsorption; 1H, 13C, and 29Si solid‐state cross‐polarization magic‐angle spinning NMR spectroscopy. It was shown that the template could be completely removed from the pure and functionalized silica in an environmentally friendly way by means of a simple water extraction procedure. Furthermore, it was shown that these materials could be easily functionalized, for example, by employing aminopropyl groups. Thus, a new environmentally friendly pathway to this fascinating class of silica material has been opened.
Photoelectron circular dichroism: Chiral asymmetry in the angular distribution of electrons emitted by (+)‐S‐carvone
Authors: Powis Ivan
Published: February 2008

The technique of photoelectron circular dichroism (PECD) is introduced and illustrated by the presentation of results obtained for the C 1s core ionization of (+)‐S‐carvone enantiomers. Using circularly polarized ionizing radiation, large chiral effects in the angular distribution of photoelectrons emitted from a dilute, randomly oriented gas phase sample can be detected. This effect is predicted in the pure electric dipole approximation and is expected to be quite general. The forward–backward asymmetry regularly exceeds 10%, as demonstrated here for the carbonyl C 1s photoemission of carvone. Calculations are presented that reveal a pronounced dependence of this effect on molecular conformation. In the case of carvone the PECD associated with the C 1s electron localized at the carbonyl group varies with orientation of the isopropenyl tail group at the opposite end of the molecule. Comparisons of calculations with experiment confirm the molecular configuration and permit inferences to be drawn concerning the relative conformer populations in the experimental sample. Chirality, 2008. © 2008 Wiley‐Liss, Inc.
Targeted RNA Interference of Cyclin A2 Mediated by Functionalized Single‐Walled Carbon Nanotubes Induces Proliferation Arrest and Apoptosis in Chronic Myelogenous Leukemia K562 Cells
Authors: Wang Xiaohui , Ren Jinsong , Qu Xiaogang
Published: February 2008

Cyclin A2 plays critical role in DNA replication, transcription, and cell cycle regulation. Its overexpression has been detected and related to many types of cancers including leukemia, suggesting that suppression of cyclin A2 would be an attractive strategy to prevent tumor progression. Herein, we apply functionalized single wall carbon nanotubes (f‐SWNTs) to carry small interfering RNA (siRNA) into K562 cells and determine whether inhibition of cyclin A2 would be a potential therapeutic target for chronic myelogenous leukemia. The results show functionalized SWNTs can facilitate the coupling of siRNA specifically targeting human cyclin A2 to form cyclin A2 siRNA–f‐SWNTs complexes. These functionalized SWNTs readily enter K562 cells, resulting in suppression of cyclin A2 expression. We demonstrate that depletion of cyclin A2 in this manner inhibits cell proliferation and promotes apoptosis, and cyclin A2 can serve as a novel therapeutic target. siRNA against cyclin A2 delivered by functionalized single wall carbon nanotubes may be a useful therapeutic strategy for chronic myelogenous leukemia cells. This would provide new insights on additional therapeutic options for chronic myelogenous leukemia beyond chemotherapy in light of increasing multidrug resistance.
Delayed intervention of sporadic renal masses undergoing active surveillance
Authors: Crispen Paul L. , Viterbo Rosalia , Fox Eric B. , Greenberg Richard E. , Chen David Y. T. , Uzzo Robert G.
Published: February 2008

BACKGROUND.

Prompt surgical management remains the standard of care for renal cell carcinoma (RCC). Occasionally, it is necessary to postpone or delay surgical treatment. The authors of this report assessed whether delayed intervention following a period of active surveillance altered minimally invasive or nephron‐sparing treatment plans, increased the risk of stage progression, and/or decreased recurrence‐free survival rates.

METHODS.

The authors searched their institutional kidney cancer database to identify small (≤4 cm in greatest dimension on presentation), enhancing renal masses for which treatment initially was delayed or refused. Clinical, radiographic, and pathologic records were reviewed to determine linear tumor growth kinetics, alterations in treatment plan, stage migration, and cancer‐specific outcomes related to delayed intervention.

RESULTS.

Eighty‐seven sporadic, localized, enhancing renal masses were identified in 82 patients who had management postponed for a median of 14 months (mean, 21 months; range, 6–97 months). Median tumor diameter was 2.0 cm on presentation. Treatment in 60 of 87 tumors (69%) was delayed for ≥12 months, and treatment was delayed for ≥24 months in 29 of 87 tumors (33%). Overall, 66 of 87 tumors (76%) underwent nephron‐sparing approaches. In addition, 52 of 87 tumors (60%) were treated in a minimally invasive fashion. Pathology confirmed RCC in 73 of 87 treated tumors (84%). Fourteen of 54 tumors (26%) that were treated by surgical extirpation were high‐risk tumors, and 3 of 54 tumors (6%) were upstaged on pathologic review.

CONCLUSIONS.

The majority of small, sporadic, clinically localized renal tumors demonstrated slow interval growth. The management of these lesions may be delayed cautiously without limiting or complicating the available treatment options or incurring a high risk of disease progression. Cancer 2008. © 2008 American Cancer Society.
Cancer vaccines: Clinical development challenges and proposed regulatory approaches for patient access to promising treatments
Authors: Stebbing Justin , Wood Christopher , Atkins Michael , Bukowski Ronald , Litwin Stephen , Bower Mark , Parsa Andrew , Levitsky Hyam
Published: February 2008

The challenges of late‐stage development increasingly are becoming clear as the clinical development of therapeutic cancer vaccines continues to progress. Preclinical and clinical research had indicated that cancer vaccines exert optimal benefit in earlier stage disease or in adjuvant/minimal residual disease (MRD) settings. However, clinical trials in these settings can be prohibitively slow from a development perspective because of the better prognosis of the patient population and the current lack of early surrogate markers of efficacy. Therefore, the ‘optimal’ patient population (the patient group in which the greatest benefit is demonstrated) for any given vaccine studied in this setting generally must be identified first through the conduct of a large randomized trial for each indication, then confirmed in a second large randomized trial. On the basis of the current regulatory paradigm, a late‐stage development program for a cancer vaccine in the earlier stage disease or adjuvant/MRD setting easily could extend past 10 years. The tight funding environment and constant evolution in medical practice, which can make replication of results from the first trial infeasible over such a long timeline, pose additional challenges. In this report, the authors discuss 3 potential regulatory solutions to better enable the development and commercialization of therapeutic cancer vaccines: a U.S. Food and Drug Administration‐proposed cost‐recovery program, conditional marketing authorization, and a new development paradigm. All of these solutions aim to balance a complex equation of biologic rationale, weight of the evidence for efficacy and safety, regulatory expectations, and cost and timeline of clinical development. Cancer 2008. © 2008 American Cancer Society.
In‐hospital complications of autologous hematopoietic stem cell transplantation for lymphoid malignancies
Authors: Jones Jeffrey A. , Qazilbash Muzaffar H. , Shih Ya‐Chen T. , Cantor Scott B. , Cooksley Catherine D. , Elting Linda S.
Published: February 2008

BACKGROUND.

Autologous hematopoietic stem cell transplantation (auto HSCT) is standard of care therapy for multiple myeloma and Hodgkin and non‐Hodgkin lymphomas in front‐line and salvage settings, respectively. Complications remain common, but population‐based estimates of their frequency and relative contribution to cost are not available.

METHODS.

A retrospective cohort comprised of 8891 patients with multiple myeloma and lymphoma admitted to US hospitals for auto HSCT over a 2‐year period (2000‐2001) was extracted from the Nationwide Inpatient Sample (NIS). Patient characteristics, vital status, and total hospital charges were obtained directly from the NIS. Transplant characteristics and outcomes were identified by ICD‐9‐CM codes. Mean hospital charges were examined by outcome and transformed into cost by using Medicare cost‐to‐charge ratios. Factors associated with hospital cost, length of stay, and in‐hospital mortality were explored by using multivariate regression.

RESULTS.

The mean hospital cost for auto HSCT during this period was $51,312. Significant complications were documented for >50% of admissions. Infectious complications (∼ 60%) and stomatitis (∼ 40%) were the most frequent, and both were associated with increased hospital costs (range, $15,000 to $50,000). In‐hospital mortality was rare (<5%) but was associated with markedly increased cost when it occurred. Pretransplant conditioning with total body irradiation was strongly associated with infectious complications, higher cost, and death.

CONCLUSIONS.

Adverse events are both common and costly after auto HSCT. Strategies to minimize complications could significantly reduce not only morbidity and mortality but also the cost of the procedure. Administrative data can be profitably exploited to investigate outcomes in this population. Cancer 2008. © 2008 American Cancer Society.
Pneumonectomy after chemoradiation
Authors: Allen Aaron M. , Mentzer Steven J. , Yeap Beow Y. , Soto Ricardo , Baldini Elizabeth H. , Rabin Michael S. , Sugarbaker David J. , Bueno Raphael
Published: February 2008

BACKGROUND.

The current study was conducted to examine the outcomes of pneumonectomy after induction chemoradiotherapy in patients with locally advanced nonsmall cell lung cancer (NSCLC).

METHODS.

All patients undergoing pneumonectomy after induction therapy at the Brigham and Women's Hospital were retrospectively evaluated for 30‐day and 100‐day mortality and treatment‐related complications with Institutional Review Board approval. Multivariate and univariate analyses for clinical factors correlating with toxicity and/or survival were calculated.

RESULTS.

Between 1995 and 2005, 73 patients underwent pneumonectomy for NSCLC after induction therapy. All patients received radiation (median dose of 54 gray [Gy]) and 69 patients (95%) received concurrent chemotherapy. The median age was 62 years and 43 patients (59%) were male; Thirty‐seven patients (51%) had American Joint Committee on Cancer stage IIIA NSCLC, 27 (37%) had stage IIIB, 6 had stage IIB, and 4 had stage IV NSCLC because of a resected solitary brain metastasis. A majority (44; 60%) of patients received the combination of carboplatin and paclitaxel, whereas 15 (21%) received the combination of cisplatin and etoposide. Forty‐five patients (62%) underwent left pneumonectomy. With a median follow‐up of 28 months, the 1‐year and 2‐year overall survival rates were 70% and 49%, respectively. The 30‐day and 100‐day mortality rates were 6% and 10%, respectively. Only 4 of 73 patients (6%) died of acute respiratory distress syndrome. The rate of nonfatal treatment‐related morbidity was 11%. On univariate analysis, right‐sided pneumonectomy was associated with a higher risk of treatment‐related mortality (P= .099).

CONCLUSIONS.

With an acceptable mortality rate, a single‐institutional series demonstrated that trimodality therapy including pneumonectomy can be safely accomplished in patients with advanced NSCLC. Cancer 2008. © 2008 American Cancer Society.
Safety and efficacy of arsenic trioxide for patients with advanced metastatic melanoma
Authors: Tarhini Ahmad A. , Kirkwood John M. , Tawbi Hussein , Gooding William E. , Islam Mohammed F. , Agarwala Sanjiv S.
Published: February 2008

BACKGROUND.

Arsenic trioxide (ATO) cytotoxicity and apoptosis induction has been demonstrated with numerous cancer cell lines, including human melanoma.

METHODS.

A second‐line, phase 2, single‐arm study of ATO was conducted in patients with inoperable American Joint Committee on Cancer (AJCC) stage IV melanoma. One cycle consisted of a loading dose of 0.32 mg/kg/day for 4 days in Week 1, followed by 0.25 mg/kg/day twice per week for 6 weeks, followed by 1 week of rest, at which time response assessment was performed.

RESULTS.

Twenty‐one patients (median age, 63.8 years) were accrued. All had stage IV melanoma including M1a (2 patients), M1b (6 patients), and M1c (13 patients) disease. One patient had metastatic choroidal melanoma and 20 patients had cutaneous melanoma. Twenty patients had received prior therapy. Possible treatment‐related grade 3 of 4 toxicities (using the National Cancer Institute Common Toxicity Criteria) included 1 case of idiopathic thrombocytopenic purpura and 1 case of elevated lactate dehydrogenase. Four patients did not complete the first cycle of therapy and were not evaluable for response. Among 17 evaluable patients, 1 patient (6%; 95% confidence interval [95% CI], 0–29%) achieved a partial response lasting 7 months, and 10 patients (59%) had disease stabilization after at least 1 cycle, but all eventually developed disease progression. The median time to disease progression was 17 weeks (95% CI, 11–38 weeks) and the median survival was 13 months (95% CI, 12–26 months).

CONCLUSIONS.

ATO as tested in the current trial was found to be well tolerated and had limited activity in patients with metastatic melanoma. The application of this agent in combination with either chemotherapy or agents that target recognized critical signaling and antiapoptotic pathways of melanoma has not yet been performed. Cancer 2008. © 2008 American Cancer Society.
Natural killer cell neoplasms
Authors: Liang Xiayuan , Graham Douglas K.
Published: February 2008

Natural killer (NK) cell tumors are an uncommon and heterogeneous group of disorders. The World Health Organization (WHO) classified mature NK cell neoplasms into 2 types: 1) extranodal NK cell lymphoma, nasal type and 2) aggressive NK cell leukemia. The mature NK cell tumors are prevalent in Asia and Central and South America. These tumors show polymorphic neoplastic infiltrate with angioinvasion and/or angiodestruction, cytoplasmic azurophilic granules, CD2‐positive (CD2+)/CD3‐negative (CD3−)/cCD3ε+/CD56+ phenotype, and strong association with Epstein‐Barr virus (EBV). Loss of chromosomes 6q, 11q, 13q, and 17p are recurrent aberrations. Although blastic NK cell lymphoma, currently referred to as CD4+/CD56+ hematodermic neoplasm, also was included in the NK cell lymphoma category in the WHO classification scheme, existing evidence indicates a plasmacytoid dendritic cell derivation as opposed to an NK cell origin. Recently, rare cases of CD56+ immature lymphoid tumors have been reported in the literature. These tumors are characterized by blastic appearance, CD3−/CD4−/CD56+/CD13−/CD33− phenotype, T‐cell receptor and immunoglobulin genes in germline configuration, and no evidence of EBV, suggesting a true immature NK cell derivation. For this article, the authors reviewed the recent concepts and progress in clinicopathologic features, pathogenesis, genetic characteristics, diagnosis, differential diagnosis, treatment approaches, and outcomes of all subtypes of NK cell neoplasms. Cancer 2008. © 2008 American Cancer Society.
Outcome of patients who develop acute leukemia or myelodysplasia as a second malignancy after solid tumors treated surgically or with strategies that include chemotherapy and/or radiation
Authors: Abdelhameed Arwa , Pond Gregory R. , Mitsakakis Nicholas , Brandwein Joseph , Chun Kathy , Gupta Vikas , Kamel‐Reid Suzanne , Lipton Jeffrey H. , Minden Mark D. , Schimmer Aaron , Schuh Andre , Yee Karen , Messner Hans A.
Published: February 2008

BACKGROUND

Evaluation of therapeutic outcomes and risk factors was undertaken for patients with primary solid tumors (PST) developing acute leukemia or myelodysplasia (MDS) as a second malignancy.

METHODS

In all, 131 consecutive patients presenting to a single institution with leukemia or MDS after treatment for PST with surgery or chemotherapy/radiotherapy were examined. Management of the secondary acute leukemia and MDS consisted either of intensive therapy including allogeneic blood and marrow transplants or supportive measures.

RESULTS

The time from diagnosis of PST to development of acute leukemia or MDS, the cytogenetic profile of patients, and their survival were similar irrespective of PST therapy with surgery alone or strategies involving chemotherapy and/or radiation. The median survival of all 131 patients was 10.5 months with a 5‐year survival of 15.6%. Induction therapy and/or transplantation resulted in a median survival of 13.6 months and a 5‐year survival of 26.6% compared with 6.5 months and 2% with supportive measures. Subset analysis of transplant recipients revealed a median survival of 17.6 months and a 37.9% 5‐year survival. Despite a significantly lower recurrence rate the survival of transplant recipients was not improved secondary to a higher treatment‐related mortality (TRM) rate.

CONCLUSIONS

Patients developing acute leukemia or MDS after PST demonstrated similar cytogenetic profiles and clinical outcomes independent of the type of treatment. Survival was significantly better for patients able to undergo intensive therapy compared with supportive measures. The low recurrence rate for allograft recipients was consistent with a potent antileukemic effect that may translate into a survival benefit if TRM could be reduced. Cancer 2008. © 2008 American Cancer Society.
Matched case‐control phase 2 study to evaluate the use of a frozen sock to prevent docetaxel‐induced onycholysis and cutaneous toxicity of the foot
Authors: Scotté Florian , Banu Eugeniu , Medioni Jacques , Levy Eric , Ebenezer Christelle , Marsan Sandrine , Banu Adela , Tourani Jean Marc , Andrieu Jean‐Marie , Oudard Stéphane
Published: February 2008

BACKGROUND

Onycholysis occurs in approximately 30% of patients treated with docetaxel. The efficacy and safety of an Elasto‐Gel frozen sock (FS) was investigated for the prevention of docetaxel‐induced nail and skin toxicity of the feet.

METHODS

Patients receiving docetaxel at a dose of 70 to 100 mg/m2 every 3 weeks were eligible for this matched case‐control study. Each patient wore an FS for 90 minutes on the right foot. The unprotected left foot acted as control. Nail and skin toxicities were assessed using National Cancer Institute Common Toxicity Criteria (version 3) and compared using a 2‐sample Wilcoxon matched‐pairs rank test adjusted for tied values.

RESULTS

Fifty consecutive patients were included between April 2005 and January 2007. Nail toxicity was significantly lower in the FS‐protected foot compared with the control foot (grade 0: 100% versus 79%; and grade 1 and 2: 0% versus 21%, respectively) (P = .002). Skin toxicity was grade 0: 98% versus 94%; and grade 1 and 2: 2% versus 6% in the FS‐protected and the control feet, respectively. The median times until toxicity occurrence were not found to differ significantly between the groups. One patient experienced discomfort because of cold intolerance.

CONCLUSIONS

Cold therapy using FS significantly reduced the incidence of docetaxel‐induced foot nail toxicity, as previously demonstrated using frozen gloves for the hands. Cancer 2008. © 2008 American Cancer Society.
Distinction between isolated tumor cells and micrometastases in breast cancer
Authors: de Mascarel Isabelle , MacGrogan Gaetan , Debled Marc , Brouste Veronique , Mauriac Louis
Published: February 2008

BACKGROUND

In routine practice, the distinction between isolated tumor cells (ITC) and micrometastases (MIC) in patients with breast cancer is sometimes difficult to discern. The authors assessed differences in classifying patients according to the American Joint Commission on Cancer (AJCC) and the International Union Against Cancer (UICC) definitions and method of sizing.

METHODS

We assessed the characteristics of metastatic deposits in only 1 involved lymph node in 337 patients with operable breast cancer (median follow‐up, 15.3 years). When sizing multiple clusters, either the diameter of the area with close clusters (Method 1) or the size of the largest cluster (Method 2) was taken into account. Patients were classified and their survival was assessed according to the 2 sizing methods and the criteria used for definitions (size in AJCC; size and topography in UICC).

RESULTS

With the AJCC definitions, 32 patients would be differently classified according to the method of sizing. With the UICC definitions, some patients with parenchymal ITC would be classified as pN1mi, 38 by Method 1 and 53 by Method 2. Some pathologists would classify the 66 patients who had isolated capsular vascular invasion as pN0. Classification was uncertain in 136 (40%) to 151 (45 %) patients. Survival was not significantly different between pN0(i+) and pN1(mi) patients.

CONCLUSIONS

The distinction between ITC and MIC was often difficult and without any prognostic significance. Precise guidelines are more useful for staging than for therapy. Thus, complete axillary dissection is usually performed in pN0(i+) and pN1(mi) patients, whereas chemotherapy is not indicated or debatable when MIC is the only 1 pejorative criterion. Cancer 2008. © 2008 American Cancer Society.
Metastable Dissociation of Anions Formed by Electron Attachment
Authors: Zappa Fabio , Beikircher Manuel , Mauracher Andreas , Denifl Stephan , Probst Michael , Injan Natcha , Limtrakul Jumras , Bacher Arntraud , Echt Olof , Märk Tilmann D. , Scheier Paul , Field Thomas A. , Graupner Karola
Published: February 2008

A comprehensive analysis of metastable dissociation of 2,4‐dinitrotoluene (DNT) parent anions formed by attachment of electrons of controlled energy is presented. We characterize the energy dependence and kinetic energy release of the reaction which competes with autodetachment. A surprising finding is a highly exothermic metastable reaction triggered by the attachment of thermal electrons which we relate to the well‐known electrostatic ignition hazards of DNT and other explosives. Quantum chemical calculations are performed for dinitrobenzene in order to elucidate the process of NO abstraction.
A computer touch screen system and training procedure for use with primate infants: Results from pigtail monkeys (Macaca nemestrina)
Authors: Mandell Dorothy J. , Sackett Gene P.
Published: February 2008

Computerized cognitive and perceptual testing has resulted in many advances towards understanding adult brain–behavior relations across a variety of abilities and species. However, there has been little migration of this technology to the assessment of very young primate subjects. We describe a training procedure and software that was developed to teach infant monkeys to interact with a touch screen computer. Eighteen infant pigtail macaques began training at 90‐postnatal days and five began at 180‐postnatal days. All animals were trained to reliably touch a stimulus presented on a computer screen and no significant differences were found between the two age groups. The results demonstrate the feasibility of using computers to assess cognitive and perceptual abilities early in development. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 160–170, 2008.
Temporal association between food distribution and human caregiver presence and the development of affinity to humans in lambs
Authors: Tallet Céline , Veissier Isabelle , Boivin Xavier
Published: February 2008

The presence of the caregiver around feeding favors the development of a human–animal relationship. To understand the underlying mechanism, we tested various temporal associations between food distribution and human presence: from an early age, a person was repeatedly present for 2 min just before milk distribution (“Forward”), during milk distribution (“Simultaneous”), and 20 min afterwards (“Delayed”). The “Control” group received no human contacts. During the treatments, “Forward” and “Delayed” lambs had more physical contacts with the person than “Simultaneous” lambs. When tested in unfamiliar environments, they stood longer near the person than did “Control” or “Simultaneous” lambs, which did not differ. Only “Forward” and “Delayed” lambs bleated when separated from the person. Fasting before testing had no effect. “Forward” and “Delayed” seemed to produce the same human–animal relationship, showing that this did not rely only on a conditioning process associating the caregiver with food. The caregiver may acquire properties for social support through other mechanisms (attachment and/or postingestive effects). © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 147–159, 2008.
Return to school accompanied by changing associations between family ecology and cortisol
Authors: DeCaro Jason A. , Worthman Carol M.
Published: February 2008

This study examines everyday family life as a social regulator of child adrenocortical activity during the normative challenge of return to school. If positive family function facilitates child adaptation, we expected that mother‐child relationships following school entry would predict individual differences in evening cortisol, a context‐sensitive marker for the response to concurrent demands. Among 28 children followed longitudinally, late in pre‐kindergarten those living with single and/or employed mothers had higher evening cortisol. Yet early during the following school year, children with poorer mother‐child relationships had higher evening cortisol. Cortisol awakening response, a comparatively stable marker of anticipated demands, was higher with maternal employment, single parents, and busier child schedules before school re‐entry, and with maternal employment afterwards. We argue for a layered ecological approach to social regulation, recognizing that family structure, family functioning, and proximal features of everyday life within the family moderate child adrenocortical activity differently across contexts. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 183–195, 2008.
Diurnal and nocturnal nursing behavior in the OLETF rat
Authors: Schroeder Mariana , Lavi‐Avnon Yael , Dagan Michal , Zagoory‐Sharon Orna , Moran Timothy H. , Weller Aron
Published: February 2008

The Otsuka Long Evans Tokushima Fatty (OLETF) rat model of obesity has been recently found to develop hyperphagia and obesity early in life. Our goal was to investigate the dams' nursing behavior during the day and the night in order to elucidate their contribution to the pre‐obesity of the pups. We examined nursing bout number, length, posture, initiative, nursing total time and frequency of other maternal behaviors over the three postpartum (PP) weeks. In the first week, OLETF dams nursed more during the day and presented more self‐directed activities during the night. In the third PP week, OLETF dams displayed increased nursing time, bout number, nursing frequency, and supine postures at the beginning of the nursing episodes and less active self‐directed behaviors, both day and night, while OLETF pups displayed more initiative in starting nursing bouts. The results suggest a circadian difference in nursing behavior and self‐directed activities between the strains on PP week 1 and a strong influence of the OLETF pups on the nursing behavior of the dam on PP week 3, which contributes to their obese features. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 203–203, 2008.
A role for ARF6 in dendritic cell podosome formation and migration
Authors: Svensson Henrik G. , West Michele A. , Mollahan Pamela , Prescott Alan R. , Zaru Rossana , Watts Colin
Published: February 2008

ADP‐ribosylation factor 6 (ARF6) is a widely expressed GTPase that influences both membrane traffic and actin cytoskeleton function. Its role in dendritic cells (DC) has not previously been investigated. We analysed the effect of retroviral expression of ARF6 GDP/GTP binding and other functional mutants in primary murine DC. Maturation in response to lipopolysaccharide (LPS) proceeded normally in DC expressing ARF6 mutants and production of inflammatory cytokines was similarly unaffected. Although LPS‐stimulated macropinocytosis was suppressed by expression of the GTP‐binding Q67L ARF6 mutant we detected no overall activation of ARF6 by LPS. The ability of immature DC to migrate towards CCL3 and to a lesser extent, of mature DC to migrate towards CCL19, was compromised by expression of either the Q67L or the GDP‐binding T44N mutant. Examination of the actin cytoskeleton in these cells revealed that both mutants strongly inhibited the formation of F‐actin‐rich podosomes, providing a possible explanation for the effects of ARF6 mutants on DC migration. Thus, these studies identify responses in DC that require normal ARF6 function, though not necessarily further ARF6 activation. They reveal for the first time a role for ARF6 in podosome formation and demonstrate functional effects of the T44N ARF6 mutant.
IRAK4 in TLR/IL‐1R signaling: Possible clinical applications
Authors: Li Xiaoxia
Published: February 2008

A member of the IL‐1 receptor (IL‐1R)‐associated kinase (IRAK) family, IRAK4, has been shown to play an essential role in Toll‐like receptor (TLR)‐mediated signaling. IRAK4 kinase‐inactive knockin mice have been shown to be completely resistant to LPS‐ and CpG‐induced shock, due to impaired TLR‐mediated induction of pro‐inflammatory cytokines and chemokines. A reduction of LPS‐, R848‐ and IL‐1‐mediated mRNA stability contributes to the reduced cytokine and chemokine production in bone marrow (BM)‐derived macrophages from IRAK4 kinase‐inactive knockin mice: however, not all of the TLR/IL‐1R signaling events are ablated in IRAK4 kinase‐inactive knockin mice. A paper in this issue of the European Journal of Immunology shows that, while JNK activation is significantly impaired, NF‐κB and IRF3 activation are retained in the absence of IRAK4 kinase activity. These residual TLR/IL‐1R‐induced signaling events allow the production of some cytokines and chemokines (including TNFα and CXCL1); at early times after the stimulation and induction of a group of TLR‐mediated MyD88/IRAK4‐independent genes in IRAK4 kinase‐inactive knockin cells. Therefore, pharmacological blocking of IRAK4 kinase activity will retain some levels of host defence, while reducing the levels and duration of inflammatory responses, which should provide beneficial therapies for sepsis and chronic inflammatory diseases.

See accompanying article: http://dx.doi.org/10.1002/eji200737886
Cover Picture: Accelerating the secondary immune response by inactivating CD4+CD25+ T regulatory cells prior to BCG vaccination does not enhance protection against tuberculosis – Eur. J. Immunol. 3/2008
Authors: Quinn Kylie M. , Rich Fenella J. , Goldsack Lisa M. , de Lisle Geoffrey W. , Buddle Bryce M. , Delahunt Brett , Kirman Joanna R.
Published: February 2008

The cover shows a lung section taken from mice treated i.p. with PC61 (a mAb to CD25), vaccinated with bacillus Calmette‐Guérin (BCG) 3 days later and then challenged with Mycobacterium bovis via aerosol a further 42 days later. The section is stained with hematoxylin and eosin, and shows that pulmonary inflammation, although present, is limited. The image is taken from Quinn et al. (pp. 695–705) in which the authors demonstrate that inactivation of CD4+CD25+ natural Treg does not influence the development of protective immunity following BCG vaccination, even though the immune response to mycobacterial antigens early after vaccination is increased.
Dimeric Complexes of a Tridentate Schiff Base Ligand – Crystal Structure of a CuII Complex with Uncommon μ2‐Nsulfonamido Bridges and Ferromagnetic Behaviour
Authors: Sanmartín Jesús , Novio Fernando , García‐Deibe Ana M. , Fondo Matilde , Ocampo Noelia , Bermejo Manuel R.
Published: February 2008

N‐[2‐(Tosylamino)benzylidene]‐2‐[(tosylamino)methyl]aniline(H2L) has afforded MII2(L)2·xMeCN·yH2O complexes (M = Ni, Pd, Cu, Zn and Cd; x = 0 or 2; y = 0, 4, 6 or 8). Physicochemical characterisation data are indicative of the dinuclear nature of the complexes obtained, where the potential N,N,N‐donor L behaves as a dianionic and tridentate ligand. The crystal structure of Cu2(L)2·2MeCN was solved, and it demonstrates that a double μ2‐Nsulfonamido bridge assembles the neutral Cu2(L)2 dimers. This uncommon connection gives rise to a totally planar and nearly square‐shaped Cu2N2 metallacycle. The planar geometries around the copper ions undergo a seesaw‐shaped distortion, which is probably related to secondary Cu···O interactions with neighbouring tosyl groups. This spatial arrangement seems related to the ferromagnetic behaviour shown by the complex.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Reactions of Thorium Atoms with Polyhalomethanes: Infrared Spectra of the CH2=ThX2, HC÷ThX3, and XC÷ThX3 Molecules (Eur. J. Inorg. Chem. 7/2008)
Authors: Lyon Jonathan T. , Andrews Lester
Published: February 2008

the cover picture shows the HC÷ThF3 complex product of the Th and CHF3 reaction. The two singly occupied SOMO orbitals on the right reveal a strong overlap with the thorium center. A portion of the DFT‐predicted infrared spectrum for this complex is illustrated over the background image of a typical laser‐ablation experiment in progress in our vacuum chamber. Details are discussed in the article by J. T. Lyon and L. Andrews on p. 1047 ff.
Numerical model for the prediction of dilute, three‐dimensional, turbulent fluid–particle flows, using a Lagrangian approach for particle tracking and a CVFEM for the carrier phase
Authors: Oliveira L. A. , Costa V. A. F. , Baliga B. R.
Published: February 2008

A numerical model for dilute, three‐dimensional, turbulent, incompressible fluid–solid particle flows and its application to a demonstration problem are presented. An Eulerian description is used to model the flow of the fluid (carrier) phase, and the governing equations are solved using a control‐volume finite element method (CVFEM). The motion of the solid (particulate) phase is simulated using a Lagrangian approach. An efficient algorithm is proposed for locating the particles in the finite element mesh. In the demonstration problem, which involves a particle‐laden axisymmetric jet, a modified k–ε turbulence model is used to characterize the velocity and length scales of the turbulent flow of the fluid phase. The effect of turbulence on the particle trajectories is accounted for through a stochastic model. The effect of the particles on the fluid time–mean velocity and turbulence (two‐way coupling) is also addressed. Comparisons between predictions and available experimental data for the demonstration problem are presented. Satisfactory agreement is obtained. Copyright © 2008 John Wiley & Sons, Ltd.
Somatosensory system in two types of motor reorganization in congenital hemiparesis: Topography and function
Authors: Wilke Marko , Staudt Martin , Juenger Hendrik , Grodd Wolfgang , Braun Christoph , Krägeloh‐Mann Ingeborg
Published: February 2008

This study investigates the (re‐)organization of somatosensory functions following early brain lesions. Using functional magnetic resonance imaging (fMRI), passive hand movement was studied. Transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG) were used as complementary methods. fMRI data was analyzed on the first level with regard to topographical variability; second‐level group effects as well as the overall integrity of the somatosensory circuitry were also assessed. Subjects with unilateral brain lesions occurring in the third trimester of pregnancy or perinatally with different types of motor reorganization were included: patients with regular, contralateral motor organization following middle cerebral artery strokes (CONTRAMCA, n = 6) and patients with reorganized, ipsilateral motor functions due to periventricular lesions (IPSIPL, n = 8). Motor impairment was similar, but sensory impairment was more pronounced in the CONTRAMCA group. Using fMRI and MEG, both groups showed a normal pattern with a contralateral somatosensory representation, despite the transhemispherically reorganized primary motor cortex in the IPSIPL group, as verified by TMS. Activation topography for the paretic hands was more variable than for the nonparetic hand in both groups. The cortico‐cerebellar circuitry was well‐preserved in almost all subjects. We conclude that in both models of motor reorganization, no interhemispheric reorganization of somatosensory functions occurred. Also, no relevant intrahemispheric reorganization was observed apart from a higher topographical variability of fMRI activations. This preserved pattern of somatosensory organization argues in favor of a differential lesion effect on motor and somatosensory functions and demonstrates a limited compensatory potential for the latter. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.
Catastrophic medical payment and financial protection in rural China: evidence from the New Cooperative Medical Scheme in Shandong Province
Authors: Sun Xiaoyun , Jackson Sukhan , Carmichael Gordon , Sleigh Adrian C.
Published: February 2008

Objective: To measure the impact of China's New Cooperative Medical Scheme (NCMS) on catastrophic medical payments of rural households in Linyi County, Shandong Province.

Method: In 2005, from a stratified cluster sample of 3101 rural households, we identified 375 households that might be at risk of catastrophic payments by searching through NCMS claims and interviewing key informants. We interviewed these 375 households and confirmed that 231 had had catastrophic payments (≥ 40% of the households' capacity to pay; CTP) during 2004. A validity test of our screening method found another eight cases among immediate neighbours of these 375 households; by extrapolation, we obtained an adjusted total of 289 catastrophic households in the sample of 3101. We measured the impact of the NCMS on hardship alleviation by counterfactual analysis, comparing catastrophic payments before and after NCMS reimbursements.

Result: The effect was twofold. Before NCMS intervention 8.98% of Linyi population had had catastrophic out‐of‐pocket payments compared with 8.25% after reimbursements. Catastrophic severity for households remaining in catastrophe after reimbursement dropped by 18.7% to an average of 6.34 times the household's CTP.

Conclusion: Out‐of‐pocket medical payments remain a burden for rural households. Financial protection from the NCMS, with an average reimbursement of 17.8%, was modest and should be restructured to provide better benefits that are targeted to those in most need. Copyright © 2008 John Wiley & Sons, Ltd.
Composite hemangioendothelioma of the oral cavity: Case report and review of the literature
Authors: Fasolis Massimo , Iaquinta Caterina , Montesco Maria Cristina , Garzino‐Demo Paolo , Tosco Paolo , Tanteri Giulia , Bonandini Elena , Ninfo Vito , Berrone Sid
Published: February 2008

Background

Composite hemangioendothelioma is a rare histopathologic feature, which is part of the hemangioendothelioma family. This is a heterogeneous group of vascular neoplasiae with a high tendency to local relapse but a rare predisposition to metastatic spread. Composite hemangioendothelioma mainly affects adults and is usually localized in the distal extremity of the limbs. To date, only 1 case has been detected in the oral cavity.

Methods

A case of composite hemangioendothelioma in a 38‐year‐old man is reported. The lesion was localized in the left cheek vestibular mucosa. It was surgically excised with a 1‐cm safety margin. Reconstruction was performed with a platysma myocutaneous flap.

Results

At present, the patient is free from recurrence. The aesthetic and functional outcomes are satisfactory.

Conclusion

This case demonstrates how a composite hemangioendothelioma histological diagnosis can be difficult to achieve. Furthermore, therapy must be surgical and excision should be wide. © 2008 Wiley Periodicals, Inc. Head Neck, 2008
Right common carotid artery crossing the midline neck anterior to the trachea: A cadaver case report
Authors: Conoyer Ben M. , Varvares Mark A. , Cooper Margaret H.
Published: February 2008

Background

The course of the proximal common carotid artery is reasonably uniform. Its normal position is taken for granted when performing invasive procedures, but variations should be in back of the mind of the surgeon.

Methods

This is a case report from an anatomical dissection of the neck and mediastinum of a cadaver.

Results

The right common carotid artery was the first branch of the aorta and ascended on the left side, anterolateral to the trachea. It crossed the midline anterior to the trachea between the sternal notch and the isthmus of the thyroid gland. Once on the right side, the artery resumed a normal course. A retro‐esophageal right subclavian artery was also found.

Conclusion

Anomalous variations in anatomy do occur, the possibilities of which the surgeon needs to be aware. This case illustrates a previously unreported anatomical anomaly that would clearly have had catastrophic consequences had this not been noted during surgery on the anterior neck. © 2008 Wiley Periodicals, Inc. Head Neck, 2008