bluuebunny/crossref_metadata_2025 huggingface dataset:
Retino‐Dural Hemorrhage of Infancy
Authors: Squier Waney
Published: March 2013

The termshaken baby syndrome(SBS), defined by the triad of retinal hemorrhage (RH), encephalopathy, and subdural hemorrhage (SDH), despite being widely accepted for 40 years, can no longer be regarded as a valid diagnosis. Multiple lines of evidence, from biomechanics to advances in understanding the anatomy and pathophysiology of the developing infant brain and its coverings, have undermined the diagnosis, and the nomenclature has been revised to reflect this.

It is important to shift the focus to the objective pathological findings in babies with these closely interrelated phenomena rather than speculating on mechanisms; the term retino‐dural haemorrhage of infancy more accurately characterizes this syndrome.

RHs have many causes and are more common after natural disease and accidents than after inflicted injury. Encephalopathy results from hypoxic‐ischemic injury rather than from traumatic axonal injury. Trauma is a cause of infant SDH, but there are many natural causes; almost half of normal newborns have SDH identified on brain scan. Infant SDH is usually a thin bilateral film, its source traditionally ascribed to torn bridging veins, but this remains unproved and is rarely documented. The dura is an alternative source; the infant dura is richly vascularized and innervated and bleeding into it is common. SDH evolves into a reactive membrane containing thin‐walled capillaries. Recurrent bleeding into these membranes is seen on microscopy. In some cases, SDH evolves into a chronic fluid collection; the causes for this are unknown.

Biomechanical studies have shown that the forces generated by shaking are far less than those resulting from impact, but it remains correct to advise parents that babies should never be shaken.

This article examines the pathology of each of these signs and their pathophysiology.

The importance of considering the birth, early clinical history, and predisposing vulnerabilities when examining a case of suspected abuse is emphasized.
Friction Ridge Skin: Comparison and Identification
Authors: Langenburg Glenn , Hall Carey
Published: March 2013

Friction ridge skin covers the epidermal surface of the fingers, palms, toes, and soles of the feet. This specially adapted skin has long attracted the attention of many cultures and has a variety of forensic applications in modern contexts. Friction ridge examination has played an important part in modern criminal investigations, biometrics, and legal proceedings. Research continues to expand the boundaries of forensic uses of friction ridge skin and their impressions. A growing body of research has begun to provide a better understanding of the strengths and limitations present in friction ridge examinations.
Metallocenter Biosynthesis & AssemblyUpdate based on the original article by Scott B. Mulrooney and Robert P. Hausinger,Encyclopedia of Inorganic Chemistry© 2005, John Wiley & Sons, Ltd
Authors: Mulrooney Scott B. , Hausinger Robert P.
Published: March 2013

Cells synthesize biological metallocenters by use of several recurring themes, often with multiple themes combined into a single pathway. In the simplest situation, binding of a metal ion to a biological ligand occurs by reversible thermodynamic control; however, the prevalence of metallocenters deeply buried within macromolecules, the exceedingly low concentrations of free metal ions within cells, and the sophisticated structures of many metal‐containing active sites and cofactors provide evidence that alternative and more complex approaches must also exist. In some cases, metal binding is accompanied by posttranslational modification of the target protein, either before or after the metal binds. Many metallocenters contain additional components that are added along with the metal ion. In other cases, metallochaperones are used to deliver the metal of interest to an apoprotein. Another alternative is to incorporate the metal into a protein subunit that subsequently swaps for an apoprotein subunit in the native protein. In addition, electron‐transfer reactions may be coupled with metal assembly. Other proteins require a preassembled metal‐containing cofactor rather than just the free metal ions. The cofactor may bind reversibly or be delivered by a chaperone, and scaffolding proteins may be used to provide a framework for construction of such a cofactor. Covalent attachment of the cofactor occurs in some cases. Finally, molecular chaperones that directly or indirectly alter the conformation of the target apoprotein may be utilized. In many cases, the function of the molecular chaperone is coupled to nucleotide triphosphate hydrolysis. Examples are provided for each of these metallocenter biosynthetic mechanisms.
Learning Transfer and Its Intentionality in Adult and Continuing Education
Authors: Foley Jeffrey M. , Kaiser Leann M. R.
Published: March 2013

This chapter offers an introduction to learning transfer and the major concepts related to this topic. Encouraging the intentional use of learning transfer in adult and continuing education settings is emphasized.
3‐Chlorooxindoles: Versatile Starting Materials for Asymmetric Organocatalytic Synthesis of Spirooxindoles
Authors: Noole Artur , Ošeka Maksim , Pehk Tõnis , Öeren Mario , Järving Ivar , Elsegood Mark R. J. , Malkov Andrei V. , Lopp Margus , Kanger Tõnis
Published: March 2013

3‐Chlorooxoindoles have emerged as versatile precursors in the synthesis of spirocyclopropyl oxindoles. High enantio‐ and diastereoselectivity was attained under conditions of both iminium/enamine and H‐bonding catalysis.
Domain Purity, Miscibility, and Molecular Orientation at Donor/Acceptor Interfaces in High Performance Organic Solar Cells: Paths to Further Improvement
Authors: Ma Wei , Tumbleston John R. , Wang Ming , Gann Eliot , Huang Fei , Ade Harald
Published: March 2013

Domain purity and interface structure are known to be critical for fullerene‐based bulk heterojunction (BHJ) solar cells, yet have been very difficult to study. Using novel soft X‐ray tools, we delineate the importance of these parameters by comparing high performance cells based on a novel naphtha[1,2‐c:5,6‐c]bis[1,2,5]thiadiazole (NT) material to cells based on a 2,1,3‐benzothiadiazole (BT) analogue. BT‐based devices exhibit ∼15 nm, mixed domains that differ in composition by at most 22%, causing substantial bimolecular recombination. In contrast, NT‐based devices have more pure domains that are >80 nm in size, yet the polymer‐rich phase still contains at least 22% fullerene. Power conversion efficiency >6% is achieved for NT devices despite a domain size much larger than the nominal exciton diffusion length due to a favourable trade‐off in the mixed domain between exciton harvesting, charge transport, and bimolecular recombination. The miscibility of the fullerene with the NT and BT polymer is measured and correlated to the purity in devices. Importantly, polarized x‐ray scattering reveals preferential face‐on orientation of the NT polymer relative to the PCBM‐rich domains. Such ordering has previously not been observed in fullerene‐based solar cells and is shown here to be possibly a controlling or contributing factor to high performance.
Reactive coupling between immiscible polymer chains: Acceleration by compressive flow
Authors: Song Jie , Baker Adam M. , Macosko Christopher W. , Ewoldt Randy H.
Published: March 2013

It is demonstrated that processing flow affects the kinetics of the interfacial coupling reaction between functional groups that are grafted to polymer chains. At melt temperatures the amine group on the end of nylon 6 chains reacts with maleic anhydride grafted polyethylene (PE‐MA) and forms graft copolymers. Bilayers were made by lamination and coextrusion and adhesion was measured using asymmetric dual cantilever beam (ADCB). The amount of graft copolymer in the interface was quantified by X‐ray photon spectroscopy (XPS). With quiescent lamination, adhesion increased with temperature and the concentration of PE‐MA. The adhesion metric, Gc (critical energy release rate), plotted as a function of Σ (interfacial copolymer density) fell on the same master curve, unifying reaction process, temperature and time. Gc was a linear function of Σ for low‐copolymer coverage and weak adhesion. For relatively high coverage and strong adhesion, Gc scaled with Σ. Coextrusion with compressive flow resulted in a reaction rate strikingly two‐orders of magnitude faster than that without compressive flow. The rate in the noncompressive die was close to quiescent lamination. Even for lamination, when compressive flow was applied normal to the interface, the coupling reaction rate was also greatly accelerated. Several mechanisms are speculated for this remarkable acceleration in polymer chain coupling. © 2013 American Institute of Chemical Engineers AIChE J, 59: 3391–3402, 2013
Three‐dimensional pore structure and ion conductivity of porous ceramic diaphragms
Authors: Wiedenmann Daniel , Keller Lukas , Holzer Lorenz , Stojadinović Jelena , Münch Beat , Suarez Laura , Fumey Benjamin , Hagendorfer Harald , Brönnimann Rolf , Modregger Peter , Gorbar Michal , Vogt Ulrich F. , Züttel Andreas , Mantia Fabio La , Wepf Roger , Grobéty Bernard
Published: March 2013

The ion conductivity of two series of porous ceramic diaphragms impregnated with caustic potash was investigated by electrochemical impedance spectroscopy. To understand the impact of the pore structure on ion conductivity, the three‐dimensional (3‐D) pore geometry of the diaphragms was characterized with synchrotron x‐ray absorption tomography. Ion migration was calculated based on an extended pore structure model, which includes the electrolyte conductivity and geometric pore parameters, for example, tortuosity (τ) and constriction factor (β), but no fitting parameters. The calculated ion conductivities are in agreement with the data obtained from electrochemical measurements on the diaphragms. The geometric tortuosity was found to be nearly independent of porosity. Pore path constrictions diminish with increasing porosity. The lower constrictivity provides more pore space that can effectively be used for mass transport. Direct measurements from tomographs of tortuosity and constrictivity opens new possibilities to study pore structures and transport properties of porous materials.
Modeling and simulation of conditionally volume averaged viscoelastic two‐phase flows
Authors: Habla Florian , Dietsche Laura , Hinrichsen Kai‐Olaf
Published: March 2013

Conditional volume averaging is used to develop a model capable of simulating two‐phase flows of viscoelastic fluids with surface tension effects. The study is started with the single‐phase mass and momentum balances, which are subsequently conditionally volume averaged. In doing so, we arrive at a set of equations having unclosed interfacial terms, for which closure relations for viscoelastic fluids are presented. The resulting equations possess a structure similar to the single‐phase equations; however, separate conservation equations are solved for each phase. As a result, each phase has its own pressure and velocity over the entire domain. Next, our numerical implementation is briefly outlined. We find that a Poiseuille single‐phase flow is predicted correctly. The closure terms are examined by considering a two‐phase shearing flow and a quiescient cylinder with surface tension. A convergence analysis is performed for a steady stratified two‐phase flow with both phases being viscoelastic. © 2013 American Institute of Chemical Engineers AIChE J, 59: 3914–3927, 2013
Bony pelvic canal size and shape in relation to body proportionality in humans
Authors: Kurki Helen K.
Published: March 2013

Obstetric selection acts on the female pelvic canal to accommodate the human neonate and contributes to pelvic sexual dimorphism. There is a complex relationship between selection for obstetric sufficiency and for overall body size in humans. The relationship between selective pressures may differ among populations of different body sizes and proportions, as pelvic canal dimensions vary among populations. Size and shape of the pelvic canal in relation to body size and shape were examined using nine skeletal samples (total female n = 57; male n = 84) from diverse geographical regions. Pelvic, vertebral, and lower limb bone measurements were collected. Principal component analyses demonstrate pelvic canal size and shape differences among the samples. Male multivariate variance in pelvic shape is greater than female variance for North and South Africans. High‐latitude samples have larger and broader bodies, and pelvic canals of larger size and, among females, relatively broader medio‐lateral dimensions relative to low‐latitude samples, which tend to display relatively expanded inlet antero‐posterior (A‐P) and posterior canal dimensions. Differences in canal shape exist among samples that are not associated with latitude or body size, suggesting independence of some canal shape characteristics from body size and shape. The South Africans are distinctive with very narrow bodies and small pelvic inlets relative to an elongated lower canal in A‐P and posterior lengths. Variation in pelvic canal geometry among populations is consistent with a high degree of evolvability in the human pelvis. Am J Phys Anthropol 151:88–101, 2013. © 2013 Wiley Periodicals, Inc.
Sinonasal anatomic variants and asthma are associated with faster development of chronic rhinosinusitis in patients with allergic rhinitis
Authors: Sedaghat Ahmad R. , Gray Stacey T. , Chambers Kyle J. , Wilke Claus O. , Caradonna David S.
Published: March 2013

Background

Allergic rhinitis (AR) and chronic rhinosinusitis (CRS) are a major burden to the healthcare system. Although no causal relationship has been established, previous work has demonstrated a strong association of AR with CRS. In this study, we sought to identify risk factors that may influence speed of development of CRS in patients with AR.

Methods

Retrospective review of all patients diagnosed with AR without CRS presenting to an otolaryngology clinic at a tertiary medical center as part of a multidisciplinary allergy evaluation between March 2004 and November 2011. Medical records were evaluated for clinicodemographic factors including age, gender, smoking history, medical comorbidities, categories of AR based on formal allergy testing, the presence of sinonasal anatomic variants on computed tomography as well as subsequent development of CRS.

Results

Faster progression to CRS in patients with AR was associated with comorbid asthma (hazard ratio [HR] = 3.97) as well as sinonasal anatomic variants, such as infraorbital cells (HR = 7.39), and frontal intersinus cells (HR = 68.03), on multivariate survival analysis. A statistically significant but negative interaction between infraorbital cells and frontal intersinus cells suggests that concomitant presence of both leads to a less than additive increase in the rate of CRS progression.

Conclusion

Sinonasal anatomical variants, infraorbital cells, and frontal intersinus cells, as well as comorbid asthma are associated with faster development of CRS in patients with AR. The presence of these clinical risk factors identifies patients who should be counseled on compliance with medical therapy for AR.
Are e‐books replacing print books? tradition, serendipity, and opportunity in the adoption and use of e‐books for historical research and teaching
Authors: Martin Kim , Quan‐Haase Anabel
Published: March 2013

This article aims to understand the adoption of e‐books by academic historians for the purpose of teaching and research. This includes an investigation into their knowledge about and perceived characteristics of this evolving research tool. The study relied on Rogers's model of the innovation‐decision process to guide the development of an interview guide. Ten semistructured interviews were conducted with history faculty between October 2010 and December 2011. A grounded theory approach was employed to code and analyze the data. Findings about tradition, cost, teaching innovations, and the historical research process provide the background for designing learning opportunities for the professional development of historians and the academic librarians who work with them. While historians are open to experimenting with e‐books, they are also concerned about the loss of serendipity in digital environments, the lack of availability of key resources, and the need for technological transparency. The findings show that Rogers's knowledge and persuasion stages are cyclical in nature, with scholars moving back and forth between these two stages. Participants interviewed were already weighing the five characteristics of the persuasion stage without having much knowledge about e‐books. The study findings have implications for our understanding of the diffusion of innovations in academia: both print and digital collections are being used in parallel without one replacing the other.
Finding subject terms for classificatory metadata from user‐generated social tags
Authors: Syn Sue Yeon , Spring Michael B.
Published: March 2013

With the increasing popularity of social tagging systems, the potential for using social tags as a source of metadata is being explored. Social tagging systems can simplify the involvement of a large number of users and improve the metadata‐generation process. Current research is exploring social tagging systems as a mechanism to allow nonprofessional catalogers to participate in metadata generation. Because social tags are not from controlled vocabularies, there are issues that have to be addressed in finding quality terms to represent the content of a resource. This research explores ways to obtain a set of tags representing the resource from the tags provided by users. Two metrics are introduced.Annotation Dominance(AD) is a measure of the extent to which a tag term is agreed to by users.Cross Resources Annotation Discrimination(CRAD) is a measure of a tag's potential to classify a collection. It is designed to remove tags that are used too broadly or narrowly. Using the proposed measurements, the research selects important tags (meta‐terms) and removes meaningless ones (tag noise) from the tags provided by users. To evaluate the proposed approach to find classificatory metadata candidates, we rely on expert users' relevance judgments comparing suggested tag terms and expert metadata terms. The results suggest that processing of user tags using the two measurements successfully identifies the terms that represent the topic categories of web resource content. The suggested tag terms can be further examined in various usages as semantic metadata for the resources.
Fear‐Potentiated Startle Response Is Unrelated to Social or Emotional Functioning in Adolescents With Autism Spectrum Disorders
Authors: Sterling Lindsey , Munson Jeffrey , Estes Annette , Murias Michael , Webb Sara Jane , King Bryan , Dawson Geraldine
Published: March 2013

It has been suggested that atypical amygdala function contributes to the social impairments characteristic of autism spectrum disorders (ASDs). Previous research has demonstrated that adolescents and adults with ASD generate normal response during a fear‐potentiated startle paradigm, suggesting this aspect of amygdala function is intact and may not account for the social dysfunction associated with the condition. The amygdala also plays a crucial role in the expression of anxiety and may contribute to high rates of reported anxiety in individuals with ASD. The present study partially replicates prior work by examining the fear‐potentiated startle response in adolescents with ASD, and extends this to investigate the relationship between startle response and anxiety. Eyeblink magnitude and latency (electromyographic activity; EMG) were collected from 20 adolescents with ASD and 19 typically developing (TD) age‐matched adolescents during a fear‐potentiated startle paradigm. Parent‐report and self‐report of anxiety and additional psychiatric symptoms were collected. Parental reports indicated higher rates of associated psychopathology in adolescents with ASD compared with TD adolescents. Consistent with previous results, both groups showed normal potentiated startle response, and no group differences in EMG were found. Symptoms of anxiety and level of social impairment were unrelated to startle response. These findings held for all levels of anxiety, suggesting that within the context of the fear‐potentiated startle paradigm, amygdala response is not associated with degree of atypical social or emotional functioning in ASD. Autism Res 2013, ●●: ●●–●●. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
Enantiomeric separation of tolperisone and eperisone by reversed‐phase HPLC with cellulose tris(3‐chloro‐4‐methylphenylcarbamate)‐coated chiral column
Authors: Owada Yuri , Takahashi Mizuho , Iwasa Sumiko , Ichiba Hideaki , Sadamoto Kiyomi , Fukushima Takeshi
Published: March 2013

Enantiomeric separations of centrally acting muscle relaxants, that is, tolperisone (TOL) and eperisone (EP), that are marketed as racemates were investigated by reversed‐phase high‐performance liquid chromatography (HPLC) on a polysaccharide‐based chiral column. Both TOL and EP are basic drugs because they contain a tertiary amino group and have similar chemical structures with the exception of the p‐methylphenyl and p‐ethylphenyl groups in TOL and EP, respectively. A reversed‐phase chiral column, that is, a Chiralcel OZ‐RH column, which bears cellulose tris(3‐chloro‐4‐methylphenylcarbamate) as the chiral moiety, was effective for the enantiomeric separation of TOL and EP enantiomers. The separation factor and resolution values obtained for TOL were 1.22 and 1.66, respectively, and those for EP were 1.21 and 2.24, respectively, using a 20 mm ammonium acetate in H2O (pH 8.0 and 7.0, respectively)–CH3CN (70:30) mobile phase. Using the proposed HPLC conditions, it was found that (R)‐TOL eluted faster than (S)‐TOL, as revealed by the optical rotation and circular dichroism spectroscopy. In contrast, EP was easily racemized under the experimental conditions, and hence, the elution order was not determined. Copyright © 2013 John Wiley & Sons, Ltd.
A liquid chromatography–mass spectrometric method for the quantification of azithromycin in human plasma
Authors: Ben‐Eltriki Mohamed , Somayaji Vishwa , Padwal Raj S. , Brocks Dion R.
Published: March 2013

A liquid chromatographic mass spectrometric assay for the quantification of azithromycin in human plasma was developed. Azithromycin and imipramine (as internal standard, IS) were extracted from 0.5 mL human plasma using extraction with diethyl ether under alkaline conditions. Chromatographic separation of drug and IS was performed using a C18 column at room temperature. A mobile phase consisting of methanol, water, ammonium hydroxide and ammonium acetate was pumped at 0.2 mL/min. The mass spectrometer was operated in positive ion mode and selected ion recording acquisition mode. The ions utilized for quantification of azithromycin and IS were m/z 749.6 (M + H) + and m/z 591.4 (fragment) for azithromycin, and 281.1 m/z for internal standard; retention times were 6.9 and 3.4 min, respectively. The calibration curves were linear (r2 > 0.999) in the concentration ranges of 10–1000 ng/mL. The mean absolute recoveries for 50 and 500 ng/mL azithromycin and 1 µg/ mL IS were >75%. The percentage coefficient of variation and mean error were <11%. Based on validation data, the lower limit of quantification was 10 ng/mL. The present method was successfully applied to determine azithromycin pharmacokinetic parameters in two obese volunteers. The assay had applicability for use in pharmacokinetic studies. Copyright © 2013 John Wiley & Sons, Ltd.
Self‐Sorting of Four Organic Molecules into a Heterowheel Polypseudorotaxane
Authors: Li Liang , Zhang Heng‐Yi , Zhao Jin , Li Nan , Liu Yu
Published: March 2013

The social self‐sorting supramolecular assembly is described by non‐covalent interactions among four organic components. Toward this goal, a series of self‐sorting systems have been investigated by mixing two or three different compounds; naphthyl‐bridged bis(α‐cyclodextrin), N,N′‐dioctyl‐4,4′‐bipyridinium, 2,6‐dihydroxynaphthalene, and cucurbit[8]uril. The influence of alkyl chains of viologen derivatives and the binding abilities of these systems have also been studied. Their integrative self‐sorting led to the exclusive formation of the purple supramolecular heterowheel polypseudorotaxane. The heterowheel polypseudorotaxane is a thermodynamically stable self‐sorted product, and consists of two different macrocycles with three sorts of different non‐covalent interactions. Its structure was established by NMR spectroscopy and UV/Vis absorption spectroscopy, transmission electron microscopy (TEM), atomic force microscopy (AFM), dynamic light‐scattering (DLS), diffusion‐ordered spectroscopy (DOSY), and viscosity measurements.
A predictive model to identify hospitalized cancer patients at risk for 30‐day mortality based on admission criteria via the electronic medical record
Authors: Ramchandran Kavitha J. , Shega Joseph W. , Von Roenn Jamie , Schumacher Mark , Szmuilowicz Eytan , Rademaker Alfred , Weitner Bing Bing , Loftus Pooja D. , Chu Isabella M. , Weitzman Sigmund
Published: March 2013

BACKGROUND

This study sought to develop a predictive model for 30‐day mortality in hospitalized cancer patients, by using admission information available through the electronic medical record.

METHODS

Observational cohort study of 3062 patients admitted to the oncology service from August 1, 2008, to July 31, 2009. Matched numbers of patients were in the derivation and validation cohorts (1531 patients). Data were obtained on day 1 of admission and included demographic information, vital signs, and laboratory data. Survival data were obtained from the Social Security Death Index.

RESULTS

The 30‐day mortality rate of the derivation and validation samples were 9.5% and 9.7% respectively. Significant predictive variables in the multivariate analysis included age (P < .0001), assistance with activities of daily living (ADLs; P = .022), admission type (elective/emergency) (P = .059), oxygen use (P < .0001), and vital signs abnormalities including pulse oximetry (P = .0004), temperature (P = .017), and heart rate (P = .0002). A logistic regression model was developed to predict death within 30 days: Score = 18.2897 + 0.6013*(admit type) + 0.4518*(ADL) + 0.0325*(admit age) − 0.1458*(temperature) + 0.019*(heart rate) − 0.0983*(pulse oximetry) − 0.0123 (systolic blood pressure) + 0.8615*(O2 use). The largest sum of sensitivity (63%) and specificity (78%) was at −2.09 (area under the curve = −0.789). A total of 25.32% (100 of 395) of patients with a score above −2.09 died, whereas 4.31% (49 of 1136) of patients below −2.09 died. Sensitivity and positive predictive value in the derivation and validation samples compared favorably.

CONCLUSIONS

Clinical factors available via the electronic medical record within 24 hours of hospital admission can be used to identify cancer patients at risk for 30‐day mortality. These patients would benefit from discussion of preferences for care at the end of life. Cancer 2013;119:2074–2080. © 2013 American Cancer Society.
Decreasing incidence of late‐stage breast cancer after the introduction of organized mammography screening in Italy
Authors: Foca Flavia , Mancini Silvia , Bucchi Lauro , Puliti Donella , Zappa Marco , Naldoni Carlo , Falcini Fabio , Gambino Maria L. , Piffer Silvano , Sanoja Gonzalez Maria E. , Stracci Fabrizio , Zorzi Manuel , Paci Eugenio ,   the IMPACT Working Group
Published: March 2013

BACKGROUND

After the introduction of a mammography screening program, the incidence of late‐stage breast cancer is expected to decrease. The objective of the current study was to evaluate variations in the total incidence of breast cancer and in the incidence of breast cancers with a pathologic tumor (pT) classification of pT2 through pT4 after the introduction of mammography screening in 6 Italian administrative regions.

METHODS

The study area included 700 municipalities, with a total population of 692,824 women ages 55 to 74 years, that were targeted by organized mammography screening between 1991 and 2005. The year screening started at the municipal level (year 1) was identified. The years of screening were numbered from 1 to 8. The ratio of the observed 2‐year, age‐standardized (Europe) incidence rate to the expected rate (the incidence rate ratio [IRR]) was calculated. Expected rates were estimated assuming that the incidence of breast cancer was stable and was equivalent to that in the last 3 years before year 1.

RESULTS

The study was based on a total of 14,447 incident breast cancers, including 4036 pT2 through pT4 breast cancers. The total IRR was 1.35 (95% confidence interval, 1.03‐1.41) in years 1 and 2, 1.16 (95% confidence interval, 1.10‐1.21) in years 3 and 4, 1.14 (95% confidence interval, 1.08‐1.20) in years 5 and 6, and 1.14 (95% confidence interval, 1.08‐1.21) in years 7 and 8. The IRR for pT2 through pT4 breast cancers was 0.97 (95% confidence interval, 0.90‐1.04) in years 1 and 2, 0.81 (95% confidence interval, 0.75‐0.88) in years 3 and 4, 0.79 (95% confidence interval, 0.73‐0.87) in years 5 and 6, and 0.71 (95% confidence interval, 0.64‐0.79) in years 7 and 8.

CONCLUSIONS

A significant and stable decrease in the incidence of late‐stage breast cancer was observed from the third year of screening onward, when the IRR varied between 0.81 and 0.71. Cancer 2013;119:2022–2028. © 2013 American Cancer Society.
Don't take cancer sitting down
Authors: Lynch Brigid M. , Dunstan David W. , Vallance Jeff K. , Owen Neville
Published: March 2013

Cancer survival is associated with considerable physical and psychosocial burden. Broadly accessible, nonpharmacologic measures that may extend disease‐free survival, limit comorbid disease, and enhance quality of life are required. Sedentary behavior (too much sitting) is now understood to be a health risk that is additional to, and distinct from, the hazards of too little exercise. Of particular note, it is associated with adiposity, insulin resistance, and markers of inflammation. Therefore, it is plausible that sedentary behavior may contribute to adverse cancer outcomes (disease progression, recurrence, or death) and to the development of comorbid chronic disease. Initial studies indicate that cancer survivors spend two‐thirds of their waking hours sitting. Among colorectal cancer survivors, sedentary behavior may contribute to all‐cause and disease‐specific mortality, weight gain, comorbid cardiovascular disease, and diminished quality of life. There is a need for dose‐response evidence, and for a broader understanding of the underlying mechanisms by which prolonged sitting time may affect cancer survivors' health. Cancer 2013;119:1928–1935. © 2013 American Cancer Society.
Heart rate decrease during crizotinib treatment and potential correlation to clinical response
Authors: Ou Sai‐Hong Ignatius , Tong Wilson P. , Azada Michele , Siwak‐Tapp Christina , Dy Joni , Stiber Jonathan A.
Published: March 2013

BACKGROUND

Crizotinib is used for the treatment of advanced anaplastic lymphoma kinase (ALK)‐rearranged nonsmall cell lung cancer (NSCLC). Sinus bradycardia (SB) is a side effect listed in its package insert. We investigated the frequency and timing of SB, patient characteristics associated with SB during crizotinib treatment, and potential correlation between heart rate (HR) changes and clinical response to crizotinib.

METHODS

A retrospective chart review was conducted of the timing and frequency of SB, patient characteristics, and clinical response of patients to crizotinib treatment.

RESULTS

Forty‐twp patients who had ALK‐rearranged or mesenchymal epithelial transition (MET)‐amplified NSCLC and received treatment with oral crizotinib 250 mg twice daily who were enrolled in 2 crizotinib trials (PROFILE 1001 and PROFILE 1005) were analyzed. There was an average decrease of 26.1 beats per minute (bpm) from the pretreatment HR among all patients during crizotinib treatment. Twenty‐nine patients (69%) experienced at least 1 episode of SB (HR, <60 bpm). The average time to the lowest HR recorded was 18.6 weeks (range, 5‐72 weeks). Patients who experienced SB were significantly older (aged 55.8 years vs 47.8 years; P = .0336), had a lower pretreatment HR (mean, 77.9 bpm vs 100.6 bpm; P = .002), and were on crizotinib longer (52.9 weeks vs 24.6 weeks; P = .0050) than patients who did not experience SB. The overall response rate (P = .0195) and the maximum tumor shrinkage (P = .0205) were significantly greater in patients who experienced SB.

CONCLUSIONS

HR decrease is common during crizotinib treatment. It remains to be determined whether the correlation between HR decrease and clinical response to crizotinib reflects a biomarker of drug efficacy or a time/cumulative dose‐dependent phenomenon. Cancer 2013;119:1969–1975. © 2013 American Cancer Society.
Segregation of parallel inputs to the anteromedial and anteroventral thalamic nuclei of the rat
Authors: Wright Nicholas F. , Vann Seralynne D. , Erichsen Jonathan T. , O'Mara Shane M. , Aggleton John P.
Published: March 2013

Many brain structures project to both the anteroventral thalamic nucleus and the anteromedial thalamic nucleus. In the present study, pairs of different tracers were placed into these two thalamic sites in the same rats to determine the extent to which these nuclei receive segregated inputs. Only inputs from the laterodorsal tegmental nucleus, the principal extrinsic cholinergic source for these thalamic nuclei, showed a marked degree of collateralization, with approximately 13% of all cells labeled in this tegmental area projecting to both nuclei. Elsewhere, double‐labeled cells were very scarce, making up ∼1% of all labeled cells. Three general patterns of anterior thalamic innervation were detected in these other areas. In some sites, e.g., prelimbic cortex, anterior cingulate cortex, and secondary motor area, cells projecting to the anteromedial and anteroventral thalamic nuclei were closely intermingled, with often only subtle distribution differences. These same projections were also often intermingled with inputs to the mediodorsal thalamic nucleus, but again there was little or no collateralization. In other sites, e.g., the subiculum and retrosplenial cortex, there was often less overlap of cells projecting to the two anterior thalamic nuclei. A third pattern related to the dense inputs from the medial mammillary nucleus, where well‐defined topographies ensured little intermingling of the neurons that innervate the two thalamic nuclei. The finding that a very small minority of cortical and limbic inputs bifurcates to innervate both anterior thalamic nuclei highlights the potential for parallel information streams to control their functions, despite arising from common regions. J. Comp. Neurol. 521: 2966–2986, 2013. © 2013 Wiley Periodicals, Inc.
Influenza, but not HIV‐specific CTL epitopes, elicits delayed‐type hypersensitivity (DTH) reactions in HIV‐infected patients
Authors: Ruiz‐Riol Marta , Mothe Beatriz , Gandhi Rajesh T. , Bhardwaj Nina , Scadden David T. , Sanchez‐Merino Victor , Brander Christian
Published: March 2013

The induction of cytotoxic T lymphocytes (CTLs) is believed to be an important defense mechanism against viral infections. The availability of simple, sensitive, specific and physiologically informative in vivo tests, applicable to humans, would greatly elucidate the nature of protective immune responses and facilitate immune monitoring in large vaccine trials. Here we studied the possibility of using defined HLA‐A*02:01‐restricted CTL epitopes from influenza matrix protein (GL9, GILGFVFTL) and HIV Gag p17 (SL9, SLYNTVATL) to elicit a cutaneous delayed‐type hypersensitivity (DTH) reaction. Our results show that the GL9 but not the SL9 epitope was able to induce a DTH reaction. HIV infection status, HIV RNA level and CD4+ T‐cell counts were not predictive of the extent of DTH reactions. However, a markedly reduced expression of skin homing markers CD103 and cutaneous lymphocyte associated Ag (CLA) on epitope‐specific CTL populations was associated with a lack of SL9 DTH reactivity. These data demonstrate that DTH reactions can be elicited by optimally defined CTL epitopes per se and point towards specific homing markers that are required for such reactions. These data may offer new insights into the immune pathogenesis of HIV infection and provide the basis of novel immune monitoring approaches for large‐scale HIV vaccine trials.
AMPK: A metabolic switch for CD8+T‐cell memory
Authors: Araki Koichi , Ahmed Rafi
Published: March 2013

Adenosine monophosphate‐activated protein kinase (AMPK) is a serine/threonine kinase and is crucial for cellular energy homeostasis. The exact role of AMPK during memory CD8+ T‐cell differentiation, a process that changes from the metabolically active state of effector T cells to one of quiescence in memory cells is not well understood; however, a report by Cantrell and colleagues [Eur. J. Immunol. 2013. 43: 889‐896] in this issue of the European Journal of Immunology shows that AMPK, by sensing glucose stress, is an important upstream molecule of mammalian target of rapamycin (mTOR) complex 1 for memory CD8+ T‐cell differentiation. This study provides new insights into how AMPK monitors energy stress to control effector and memory CD8+ T‐cell formation as discussed in this Commentary.
Highly Regioselective Assembly of Di‐ or Trisubstituted Pyridines from Arynes, Isocyanides, and 3‐Bromo‐ or 3‐Acetoxypropynes
Authors: Sha Feng , Shen Hui , Wu Xin‐Yan
Published: March 2013

A facile synthetic method for the preparation of di‐ and trisubstituted pyridines with high regioselectivity through an intramolecular pericyclization strategy is disclosed. The multicomponent reaction of isocyanides, arynes, and 3‐bromopropyne affords disubstituted pyridines in good yields. In contrast, the use of 3‐acetoxypropyne results in the formation of trisubstituted pyridines through intramolecular pericyclization of an in situ formed azatriene. In this way, desirable pyridines can be constructed in a one‐pot manner.
Assessment of status of white sucker (Catostomus commersoni) populations exposed to bleached kraft pulp mill effluent
Authors: Miller David H. , Tietge Joseph E. , McMaster Mark E. , Munkittrick Kelly R. , Xia Xiangsheng , Ankley Gerald T.
Published: March 2013

Credible ecological risk assessments often need to include analysis of population-level impacts. In the present study, a predictive model was developed to investigate population dynamics for white sucker (Catostomus commersoni) exposed to pulp mill effluent at a well-studied site in Jackfish Bay, Lake Superior, Canada. The model uniquely combines a Leslie population projection matrix and the logistic equation to translate changes in the fecundity and the age structure of a breeding population of white sucker exposed to pulp mill effluent to alterations in population growth rate. Application of this density-dependent population projection model requires construction of a life table for the organism of interest, a measure of carrying capacity, and an estimation of the effect of stressors on vital rates. A white sucker population existing at carrying capacity and subsequently exposed to pulp mill effluent equivalent to a documented exposure experienced during the period 1988 to 1994 in Jackfish Bay would be expected to exhibit a 34% to 51% annual decrease in recruitment during the first 5 yr of exposure and approach a population size of 71% of carrying capacity. The Jackfish Bay study site contains monitoring data for biochemical endpoints in white sucker, including circulating sex steroid concentrations, that could be combined with population modeling to utilize the model demonstrated at the Jackfish Bay study site for investigation of other white sucker populations at sites that are less data-rich. Environ Toxicol Chem 2013;32:1592–1603. © 2013 SETAC
Multi‐scale anomaly detection for high‐speed network traffic
Authors: Jiang Dingde , Yao Cheng , Xu Zhengzheng , Qin Wenda
Published: March 2013

Abnormal network traffic has an important impact on network activities and leads to the severe damage to our networks because they are usually related with network faults and network attacks. How to detect effectively network traffic anomalies is an open issue for network researchers. This paper proposes a novel method for detecting traffic anomalies in high‐speed backbone networks, based on multi‐scale analysis. Firstly, the continuous wavelet transforms are performed for network traffic in multiple continuous scales. We then use the principal component analysis for the continuous wavelet transforms in the different scales and extract the nature of the anomalous network traffic. And the new mapping function is constructed to detect the abnormal traffic. Finally, we use the traffic data from the real network to validate our method. Simulation results show that our approach is more promising than the previous method.Copyright © 2013 John Wiley & Sons, Ltd.
Reframing Retention Strategy: A Focus on Process
Authors: Schroeder Charles C.
Published: March 2013

The third “P” within a 4 Ps framework of student retention—process—gives priority attention to institutional processes and policies that either help or hinder the continuous enrollment of all students, not just students defined as “at risk.”
Process and Progress in Action: Examples of What Works
Authors: Schroeder Charles C.
Published: March 2013

This chapter offers several principles and institutional examples of the ways that student‐centered process‐ and progress‐related improvements enhance students' experiences and outcomes.
Faldaprevir combined with peginterferon alfa-2a and ribavirin in chronic hepatitis C virus genotype-1 patients with prior nonresponse: SILEN-C2 trial
Authors: Sulkowski Mark S. , Bourlière Marc , Bronowicki Jean-Pierre , Asselah Tarik , Pawlotsky Jean-Michel , Shafran Stephen D. , Pol Stanislas , Mauss Stefan , Larrey Dominique , Datsenko Yakov , Stern Jerry O. , Kukolj George , Scherer Joseph , Nehmiz Gerhard , Steinmann Gerhard G. , Böcher Wulf O.
Published: March 2013

Faldaprevir (BI 201335) is a potent, hepatitis C virus (HCV) NS3/4A protease inhibitor. In all, 290 noncirrhotic HCV genotype (GT)-1 patients with prior null (<1 log10 viral load [VL] drop at any time on treatment) or partial response (≥1 log10 VL drop but never undetectable on treatment) were randomized 2:1:1 to receive 48 weeks of peginterferon alfa-2a and ribavirin (PegIFN/RBV) in combination with faldaprevir 240 mg once daily (QD) with 3 days PegIFN/RBV lead-in (LI), 240 mg QD without LI, or 240 mg twice daily (BID) with LI. Patients in the 240 mg QD/LI group achieving maintained rapid virologic response (mRVR; VL <25 IU/mL [Roche TaqMan] at week 4 and undetectable at weeks 8 to 20) were rerandomized to cease all treatment at week 24 or continue PegIFN/RBV up to week 48. Sustained virologic response (SVR) rates were 32%, 50%, and 42% in prior partial responders, and 21%, 35%, and 29% in prior null responders in the faldaprevir 240 mg QD/LI, 240 mg QD, and 240 mg BID/LI groups, respectively. In the 240 mg QD/LI group, a significantly higher proportion of mRVR patients rerandomized to 48 weeks' treatment achieved SVR compared with those assigned to 24 weeks treatment (72% versus 43%;

P

= 0.035). Rates of gastrointestinal disorders, jaundice, dry skin, and photosensitivity were increased at 240 mg BID compared with the 240 mg QD dose. Faldaprevir discontinuations owing to adverse events occurred in 6%, 4%, and 23% of patients in the 240 mg QD/LI, 240 mg QD, and 240 mg BID/LI groups, respectively.

Conclusion

: Faldaprevir 240 mg QD with PegIFN/RBV was safe and tolerable and produced substantial SVR rates in prior null and partial responders. The 240 mg QD dose is currently undergoing phase 3 evaluation.
Vitamin D And Nonalcoholic Fatty Liver Disease (Nafld): Is It More Than Just An Association?
Authors: Kwok Ryan M. , Torres Dawn M. , Harrison Stephen A.
Published: March 2013

Vitamin D is a secosteroid with known effects on calcium homeostasis that has recently been shown to have other significant functions regarding immune modulation, cell differentiation and proliferation, and the inflammatory response. As our understanding of the many functions of vitamin D has grown, the presence of vitamin D deficiency (VDD) has become more evident in Western populations. Concomitantly, nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease. NAFLD and VDD are often found together, and while this is not unexpected, given their similar associations with obesity and sedentary lifestyle, a growing body of evidence points to a closely linked and potentially causative relationship between VDD and NAFLD. The epidemiologic association between VDD and NAFLD as well as the role of VDD in the pathogenesis of NAFLD and the available evidence on the clinical utility of vitamin D replacement in NAFLD populations are discussed. (Hepatology 2013;53:1166–1174)
Signal Regulatory Protein α Is Associated With Tumor-Polarized Macrophages Phenotype Switch and Plays a Pivotal Role in Tumor Progression
Authors: Pan Yu-fei , Tan Ye-xiong , Wang Min , Zhang Jian , Zhang Bo , Yang Chun , Ding Zhi-wen , Dong Li-wei , Wang Hong-yang
Published: March 2013

Macrophages (Mψ) are the major component of infiltrating leukocytes in tumors and exhibit distinct phenotypes according to the microenvironment. We have recently found that signal regulatory protein α (SIRPα), the inhibitory molecule expressed on myeloid cells, plays a critical role in controlling innate immune activation. Here, we identify that SIRPα is down-regulated on monocytes/Mψ isolated from peritumoral areas of hepatocellular carcinoma (HCC) samples, while its level is moderately recovered in intratumor Mψ.

In vitro

assays demonstrate that SIRPα expression is significantly reduced on Mψ when cocultured with hepatoma cells. This reduction is partly due to the soluble factors in the tumor microenvironment. Knockdown (KD) of SIRPα prolongs activation of nuclear factor kappa B (NF-κB) and PI3K-Akt pathways as Mψ encounter tumor cells, leading to an increased capacity of Mψ for migration, survival, and proinflammatory cytokine production. Enhanced Stat3 and impaired Stat1 phosphorylation are also observed in tumor-exposed SIRPα-KD Mψ. Adoptive transfer with SIRPα-KD Mψ accelerates mouse hepatoma cells growth

in vivo

by remolding the inflammatory microenvironment and promoting angiogenesis. SIRPα accomplishes this partly through its sequestration of the signal transducer Src homology 2-containing phosphotyrosine phosphatase (SHP2) from IκB kinase β (IKKβ) and PI3K regulatory subunit p85 (PI3Kp85).

Conclusion

: These findings suggest that SIRPα functions as an important modulator of tumor-polarized Mψ in hepatoma, and the reduction of SIRPα is a novel strategy used by tumor cells to benefit their behavior. Therefore, SIRPα could be utilized as a potential target for HCC therapy. (Hepatology 2013;58:680–691)