bluuebunny/crossref_metadata_2025 huggingface dataset:
The Cambridge Guide to African American History
Authors: Gavins Raymond
Published: March 2016

This book emphasizes blacks' agency and achievements in the nineteenth and twentieth centuries, notably outcomes of the Civil Rights Movement. To consider the means or strategies that African Americans utilized in pursuing their aspirations and struggles for freedom and equality, readers can consult subjects delineating ideological, institutional, and organizational aspects of black priorities, with tactics of resistance or dissent, over time and place. The entries include but are not limited to Afro-American Culture; Anti-Apartheid Movement; Anti-lynching Campaign; Antislavery Movement; Black Power Movement; Constitution, US (1789); Conventions, National Negro; Desegregation; Durham Manifesto (1942); Feminism; Four Freedoms; Haitian Revolution; Jobs Campaigns; the March on Washington (1963); March on Washington Movement (MOWM); New Negro Movement; Niagara Movement; Pan-African Movement; Religion; Slavery; Violence, Racial; and the Voter Education Project. While providing an important reference and learning tool, this volume offers a critical perspective on the actions and legacies of ordinary and elite blacks and their non-black allies.
Targeted Killing
Authors: Gunneflo Markus
Published: March 2016

Looking beyond the events of the second intifada and 9/11, this book reveals how targeted killing is intimately embedded in both Israeli and US statecraft, and in the problematic relationship between sovereign authority and lawful violence underpinning the modern state system. It details the legal and political issues raised in targeted killing as it has emerged in practice, including questions of domestic constitutional authority, the use of force in international law, the law of belligerent occupation, the law of targeting and human rights law. The distinctive nature of Israeli and US targeted killing is analysed in terms of the compulsion of legality characteristic of the liberal constitutional state, a compulsion that demands the ability to distinguish between legal 'targeted killing' and extra-legal 'political assassination'. The effect is a highly legalized framework for the extraterritorial killing of designated terrorists that may significantly affect the international law of force.
Ming China and Vietnam
Authors: Baldanza Kathlene
Published: March 2016

Studies of Sino-Viet relations have traditionally focused on Chinese aggression and Vietnamese resistance, or have assumed out-of-date ideas about Sinicization and the tributary system. They have limited themselves to national historical traditions, doing little to reach beyond the border. Ming China and Vietnam, by contrast, relies on sources and viewpoints from both sides of the border, for a truly transnational history of Sino-Viet relations. Kathlene Baldanza offers a detailed examination of geopolitical and cultural relations between Ming China (1368–1644) and Dai Viet, the state that would go on to become Vietnam. She highlights the internal debates and external alliances that characterized their diplomatic and military relations in the pre-modern period, showing especially that Vietnamese patronage of East Asian classical culture posed an ideological threat to Chinese states. Baldanza presents an analysis of seven linked biographies of Chinese and Vietnamese border-crossers whose lives illustrate the entangled histories of those countries.
Unspoken Politics
Authors: Pérez Efrén O.
Published: March 2016

This book explains why people acquire implicit attitudes, how they affect political thinking, and where in the mass public they have their strongest - and weakest - influences. A theoretically ambitious book, Unspoken Politics establishes that implicit attitudes exist outside the tightly controlled confines of the laboratory, showing that they emerge in a public opinion survey setting, which underlines their real-world impact. It also lays bare, in painstaking detail, the mechanics of a leading measure of implicit attitudes, the implicit association test (IAT). Accordingly, it outlines the strengths and limitations of this measure, while providing an illustration of how to develop an IAT for one's own purposes. By explaining how to analyze and interpret the data produced by the IAT, this book leads to a better understanding of people's unspoken cognitions and the impacts these have on the politics that individuals openly profess.
Harmony in Beethoven
Authors: Damschroder David
Published: March 2016

David Damschroder's ongoing reformulation of harmonic theory continues with a dynamic exploration of how Beethoven molded and arranged chords to convey bold conceptions. This book's introductory chapters are organized in the manner of a nineteenth-century Harmonielehre, with individual considerations of the tonal system's key features illustrated by easy-to-comprehend block-chord examples derived from Beethoven's piano sonatas. In the masterworks section that follows, Damschroder presents detailed analyses of movements from the symphonies, piano and violin sonatas, and string quartets, and compares his outcomes with those of other analysts, including William E. Caplin, Robert Gauldin, Nicholas Marston, William J. Mitchell, Frank Samarotto, and Janet Schmalfeldt. Expanding upon analytical practices from the eighteenth and nineteenth centuries and strongly influenced by Schenkerian principles, this fresh perspective offers a stark contrast to conventional harmonic analysis – both in terms of how Roman numerals are deployed and how musical processes are described in words.
The Political Logic of Poverty Relief
Authors: Diaz-Cayeros Alberto , Estévez Federico , Magaloni Beatriz
Published: March 2016

Poverty relief programs are shaped by politics. The particular design which social programs take is to a large extent determined by the existing institutional constrains and politicians' imperative to win elections. The Political Logic of Poverty Relief places elections and institutional design at the core of poverty alleviation. The authors develop a theory with applications to Mexico about how elections shape social programs aimed at aiding the poor. Would political parties possess incentives to target the poor with transfers aimed at poverty alleviation or would they instead give these to their supporters? Would politicians rely on the distribution of particularistic benefits rather than public goods? The authors assess the welfare effects of social programs in Mexico and whether voters reward politicians for targeted poverty alleviation programs. The book provides a new interpretation of the role of cash transfers and poverty relief assistance in the development of welfare state institutions.
Contracts in the Real World
Authors: Cunningham Lawrence A.
Published: March 2016

Contracts, the foundation of economic activity, are both vital and misunderstood. Contracts in the Real World, 2nd edition corrects common misunderstandings through a series of engaging stories involving such notable individuals as Martin Luther King, Maya Angelou, Lady Gaga, and Donald Trump. Capturing the essentials of this subject, the book explores recurring issues in contracting and shows how age-old precedents and wisdom still apply today and how contract law's inherent dynamism cautions against exuberant reforms. The accessible yet rigorous approach will appeal to the general reader and specialists alike, and to both teachers and students of contracts.
A Theory of Mediators' Ethics
Authors: Shapira Omer
Published: March 2016

Many aspects relating to the conduct of mediation are left to mediator choice, but mediators often lack adequate guidance on how their discretion ought to be exercised. In this book, Omer Shapira identifies the ethical norms that govern mediators' conduct. Adopting a professional ethics perspective on the basis of role-morality and applying it to a core definition of mediators' role, Shapira argues that all mediators are placed in ethical relationships with mediation parties, the mediation profession, the public and their employers. or principals that produce ethical obligations. The book goes on to explore the legitimate expectations of these groups and analyzes existing codes of conduct for mediators. Shapira constructs a theory of mediators' ethics that produces a proposed model code of conduct for mediators - a detailed set of norms of mediators' ethics that can be rationally justified and defended with regard to mediators at large.
General He Yingqin
Authors: Worthing Peter
Published: March 2016

A revisionist study of the career of General He Yingqin, one of the most prominent military officers in China's Nationalist period (1928–1949) and one of the most misunderstood figures in twentieth-century China. Western scholars have dismissed He Yingqin as corrupt and incompetent, yet the Chinese archives reveal that he demonstrated considerable success as a combat commander and military administrator during civil conflicts and the Sino-Japanese War. His work in the Chinese Nationalist military served as the foundation of a close personal and professional relationship with Chiang Kai-shek, with whom he worked closely for more than two decades. Against the backdrop of the Nationalist revolution of the 1920s through the 1940s, Peter Worthing analyzes He Yingqin's rise to power alongside Chiang Kai-shek, his work in building the Nationalist military, and his fundamental role in carrying out policies designed to overcome the regime's greatest obstacles during this turbulent period of Chinese history.
Science, Fiction, and the Fin-de-Siècle Periodical Press
Authors: Tattersdill Will
Published: March 2016

In this revisionary study, Will Tattersdill argues against the reductive 'two cultures' model of intellectual discourse by exploring the cultural interactions between literature and science embodied in late nineteenth-century periodical literature, tracing the emergence of the new genre that would become known as 'science fiction'. He examines a range of fictional and non-fictional fin-de-siècle writing around distinct scientific themes: Martian communication, future prediction, X-rays, and polar exploration. Every chapter explores a major work of H. G. Wells, but also presents a wealth of exciting new material drawn from a variety of late Victorian periodicals. Arguing that the publications in which they appeared, as well as the stories themselves, played a crucial part in the development of science fiction, Tattersdill uses the form of the general interest magazine as a way of understanding the relationship between the arts and the sciences, and the creation of a new literary genre.
Controlling Administrative Power
Authors: Cane Peter
Published: March 2016

This wide-ranging comparative account of the legal regimes for controlling administrative power in England, the USA and Australia argues that differences and similarities between control regimes may be partly explained by the constitutional structures of the systems of government in which they are embedded. It applies social-scientific and historical methods to the comparative study of law and legal systems in a novel and innovative way, and combines accounts of long-term and large-scale patterns of power distribution with detailed analysis of features of administrative law and the administrative justice systems of three jurisdictions. It also proposes a new method of analysing systems of government based on two different models of the distribution of public power (diffusion and concentration), a model which proves more illuminating than traditional separation-of-powers analysis.
What Causes the Strange Pulses in Saturn's Magnetosphere?
Authors: Stanley Sarah
Published: March 2016

A new model shows that a spiral wave may explain why many phenomena in the gas giant's magnetosphere undergo periodic cycles.
Satellite retrieval of cloud condensation nuclei concentrations by using clouds as CCN chambers
Authors: Rosenfeld Daniel , Zheng Youtong , Hashimshoni Eyal , Pöhlker Mira L. , Jefferson Anne , Pöhlker Christopher , Yu Xing , Zhu Yannian , Liu Guihua , Yue Zhiguo , Fischman Baruch , Li Zhanqing , Giguzin David , Goren Tom , Artaxo Paulo , Barbosa Henrique M. J. , Pöschl Ulrich , Andreae Meinrat O.
Published: March 2016

Quantifying the aerosol/cloud-mediated radiative effect at a global scale requires simultaneous satellite retrievals of cloud condensation nuclei (CCN) concentrations and cloud base updraft velocities (
W

b

). Hitherto, the inability to do so has been a major cause of high uncertainty regarding anthropogenic aerosol/cloud-mediated radiative forcing. This can be addressed by the emerging capability of estimating CCN and
W

b

of boundary layer convective clouds from an operational polar orbiting weather satellite. Our methodology uses such clouds as an effective analog for CCN chambers. The cloud base supersaturation (
S
) is determined by
W

b

and the satellite-retrieved cloud base drop concentrations (
N

db

), which is the same as
CCN
(
S
). Validation against ground-based CCN instruments at Oklahoma, at Manaus, and onboard a ship in the northeast Pacific showed a retrieval accuracy of ±25% to ±30% for individual satellite overpasses. The methodology is presently limited to boundary layer not raining convective clouds of at least 1 km depth that are not obscured by upper layer clouds, including semitransparent cirrus. The limitation for small solar backscattering angles of <25° restricts the satellite coverage to ∼25% of the world area in a single day.
Articulating Work and Family: Lay Papal Relatives in the Papal States, 1420–1549
Authors: DeSilva Jennifer Mara
Published: March 2016

In the fifteenth and sixteenth centuries popes increasingly depended on clerical and lay kin to supervise the implementation of papal policy. This article argues that the charge of papal nepotism is a result of the continuing idealization of the pope as separate from the issues of work and family. By acknowledging that the preoccupations of the early modern pope extended beyond pastoral activities into a world of administration, legislation, militarism, and diplomacy, historians can better understand the pope’s use of and observers’ criticism of nepotism.
Extreme femoral valgus and patella dislocation following lateral plate fixation of a pediatric femur fracture
Authors: Ezzat Ahmed , Iobst Christopher
Published: March 2016

A 15-year-old boy presented with a 35° femoral valgus deformity, leg-length discrepancy, painful retained hardware, and a lateral dislocation of the patella 4 years after undergoing lateral plate fixation of a distal femur fracture. Femoral valgus is a possible complication of lateral plate fixation in up to 30% of pediatric distal femur fractures. With this patient’s unusual combination of deformities as an example, we suggest early hardware removal after fracture union to prevent the development of deformity. If plate removal is not chosen, then continued close monitoring of the patient is necessary until skeletal maturity.
Pediatric isthmic spondylolisthesis showing radiologic evidence of slippage after physis injury
Authors: Hama Shingo , Tonogai Ichiro , Sakai Toshinori , Goda Yuichiro , Tezuka Fumitake , Matsuura Tetsuya , Suzue Naoto , Takahashi Rui , Terai Tomoya , Higashino Kosaku , Fukuta Shoji , Nagamachi Akihiro , Sairyo Koichi
Published: March 2016

The pathogenesis of slippage in pediatric spondylolisthesis is still unclear, although epiphyseal injury may account for many cases based on preclinical studies. However, no reports have described a pediatric case of isthmic spondylolisthesis showing radiologic evidence of epiphyseal injury. We report such evidence in a 13-year-old boy with low-back pain. Radiography revealed rounding of the S1 surface, a fracture line below the S1 endplate surface, and a bone marrow lesion in addition to slippage. Slippage and the rounding deformity were partially reversed (from 20 to 14% and from 42 to 27%, respectively) with conservative treatment and natural bone remodeling.
Evaluation of the Effects of CHF6001, an Inhaled PDE4 Inhibitor, on Cardiac Repolarization and Cardiac Arrhythmias in Healthy Volunteers
Authors: Ferrari Antonio , Compagnoni Anna , Nandeuil Anne , Maison-Blanche Pierre
Published: March 2016

Chronic obstructive pulmonary disease (COPD) is a multicomponent condition characterized by airway inflammation and associated to comorbidities, including cardiovascular diseases. Among anti-inflammatory agents in development for COPD, the phosphodiesterase inhibitors administrated by inhalation have the potential for increased efficacy and reduced systemic side effects. CHF6001 is an inhaled PDE4 inhibitor with proven anti-inflammatory properties in animal models. This randomized, double-blind, placebo-controlled study was aimed to demonstrate its cardiovascular safety and tolerability in healthy male volunteers with normal electrocardiogram and cardiac parameters. Single and multiple ascending doses (7 days of administration) of CHF6001 were administered. Three electrocardiograms were recorded at several pharmacokinetic time points and at each time points, postdose heart rate, QRS and PR intervals, and presence of arrhythmia were evaluated. In single ascending dose, QTcF intervals did not increase more than 30 milliseconds from the baseline, all heart rate was between 45 and 100 bpm, and no statistically significant differences were observed in PR and QRS intervals. In multiple ascending dose, cardiac parameters did not differ significantly from baseline. In the pharmacokinetic/pharmacodynamic analysis, no medically or clinically significant changes were found. Further studies are ongoing to demonstrate that CHF6001 is safe and well tolerated in COPD patients as well.
Transconjunctival Revision With Mitomycin-C Following Failed Trabeculectomy
Authors: Panarelli Joseph F. , Vinod Kateki , Huang Gintien , Sidoti Paul A.
Published: March 2016

Purpose:

To evaluate the efficacy of transconjunctival revision (TCR) with mitomycin-C (MMC) following failed trabeculectomy.

Materials and Methods:

The medical records of 27 patients (27 eyes) who underwent TCR with subconjunctival injection of MMC by a single surgeon between September 2001 and August 2013 were retrospectively reviewed. The same surgical protocol was followed for all patients. Revision was performed using a microvitreoretinal blade through a small conjunctival incision. Main outcome measures included visual acuity, intraocular pressure (IOP), and number of glaucoma medications. Failure was defined as an IOP<5 or >14 mm Hg, loss of light perception, or need for additional glaucoma surgery.

Results:

Mean interval between trabeculectomy and TCR was 56.4±57.2 months. Mean preoperative IOP was 21.9±6.8 mm Hg using 4.0±1.2 glaucoma medications. Fifteen (55.6%) patients met success criteria. At most recent follow-up, mean IOP and number of glaucoma medications for successful patients were 9.7±3.8 mm Hg and 0.6±1.1, respectively. Kaplan-Meier analysis revealed 1-, 2-, and 3-year success rates of 62%, 58%, and 53%, respectively. Three additional patients achieved success after undergoing a second TCR, and 1 patient achieved success after a third TCR. Postoperative complications included transient choroidal effusion (n=8), shallow anterior chamber requiring reformation (n=5), 5-fluorouracil-related corneal epitheliopathy (n=10), and bleb leak (n=1).

Conclusions:

TCR with adjunctive MMC is a safe and effective procedure following failure of a trabeculectomy. More than 1 revision may be necessary to achieve long-term IOP reduction.
Modified Hotz Procedure Combined With Modified Z-Epicanthoplasty Versus Modified Hotz Procedure Alone for Epiblepharon Repair
Authors: Ni Jianxin , Shao Congqin , Wang Kaiyuan , Chen Xi , Zhou Shengjie , Lin Hemin
Published: March 2016

Purpose:

To compare the outcomes of the modified Hotz procedure alone and combined with modified Z-epicanthoplasty for correction of epiblepharon.

Methods:

Seventy-one Chinese patients who underwent epiblepharon repair were divided into 2 groups. In group 1, 33 patients (59 eyes) were operated on with the modified Hotz procedure. In group 2, 38 patients (71 eyes) were operated on with the modified Hotz procedure combined with modified Z-epicanthoplasty. Treatment outcomes were classified as “excellent” with no cilium-ocular surface touching, “fair” with 5 or fewer cilia-ocular surface touchings, and “poor” with more than 5 cilia-ocular surface touchings. Incision scars were evaluated by the Vancouver scar scale (VSS).

Results:

There were no significant differences in the age or sex distribution between the two groups. For group 1, the outcome was excellent for 46 eyes (78%) and fair or poor for 13 eyes (22%). For group 2, the outcome was excellent for 70 eyes (98.6%) and fair for only 1 eye (1.4%). Thus, group 2 had significantly more excellent outcomes compared with group 1 (p < 0.001). The Vancouver scar scale of the lower eyelids in group 1 was 1.10 ± 0.30 and 1.04 ± 0.20 in group 2 after correcting for the follow-up period (p = 0.292). The medial canthus Vancouver scar scale in group 2 was 1.13 ± 0.37, which was not different from the lower eyelid Vancouver scar scale (p = 0.471).

Conclusions:

The modified Hotz procedure combined with modified Z-epicanthoplasty is more effective in correcting lower eyelid epiblepharon than the modified Hotz procedure alone. The combined procedure does not produce obvious lower eyelid or medial canthus scars.
Intralesional Rituximab for the Treatment of Recurrent Ocular Adnexal Lymphoma
Authors: Demirci Hakan , Kauh Courtney Y. , Rajaii Fatemeh , Elner Victor M.
Published: March 2016

A 41-year-old female with Sjogren syndrome presented with a 5-month history of bilateral upper eyelid swelling. Incisional biopsy of the left lacrimal gland revealed mucosa-associated lymphoid tissue lymphoma. Due to bilateral severe dry eyes, the patient declined external beam radiotherapy and systemic rituximab was initiated. The patient responded well to intravenous rituximab and the follow-up CT revealed decrease in size of both lacrimal glands. Eleven months after systemic rituximab, the patient developed bilateral lacrimal gland recurrence. The patient declined external beam radiotherapy. Intralesional rituximab (50 mg/1 ml) was injected into the left lacrimal gland, followed by injection in the right lacrimal gland 7 months later. Twenty-three months follow-up after the injection into the right lacrimal gland, there was significant decrease in size of bilateral lacrimal glands and subjective improvement of dry eye symptoms. This case highlights the intralesional rituximab as an alternative therapy for recurrent orbital mucosa-associated lymphoid tissue lymphoma in selected cases.
A Simple New Technique for Treatment of Tarsal Kink Syndrome
Authors: Vahdani Kaveh , Konstantinidis Aristeidis , Thaller Vladimir Theodor
Published: March 2016

Congenital tarsal kink syndrome is a rare type of upper eyelid entropion associated with keratitis due to trichiasis. The authors describe a new technique for treatment of congenital horizontal tarsal kink syndrome by means of absorbable everting sutures via a posterior approach. A neonate was referred to eye clinic with right eye redness and corneal opacity since birth. Clinical examination revealed inversion of the eyelid margin with a horizontal kink in the tarsal plate and corneal ulcer. Surgical treatment resulted in successful correction of upper eyelid malpositioning, rapid resolution of the corneal ulcer with excellent anatomical outcome, visual development and cosmesis, with no evidence of recurrence after 6 years. Absorbable everting sutures via a posterior approach is a simple, minimally invasive, and effective surgical technique for treatment of congenital horizontal tarsal kink syndrome.
Evaluation of the concordance between the stage of the disease and Ki-67 proliferation index in gastroenteropancreatic neuroendocrine tumors
Authors: Özaslan Ersin , Demir Sinan , Karaca Halit , Güven Kadri
Published: March 2016

Aim

This study aimed to determine the degree of concordance between TNM staging used in the determination of the prognosis of gastroenteropancreatic neuroendocrine tumor (GEP-NET) patients and the Ki-67 proliferation index value used in the grading of these tumors and investigate the most reliable prognostic parameter among them.

Materials and methods

The medical files of the patients with GEP-NET who were diagnosed or followed up in Erciyes University Faculty of Medicine were retrospectively examined and demographic characteristics, survival times, grade of these tumors, histopathologically detected Ki-67 values, and histopathological characteristics were recorded and evaluated statistically.

Results

The mean age (53.09±14.6 years; range, 16–85 years) of all (n=141) the patients was estimated. The patient population included 72 (51.1%) female and 69 (48.9%) male patients, with a male/female ratio of 0.95. The most frequently encountered primary sites were the stomach (33.3%), and then in decreasing oder of frequency the pancreas (27%), colon-rectum (15.6%), the small intestine (12.8%), and the appendix (11.3%). The GEP-NET of the patients was in grade 1 (G1) (n: 103; 73%), grade 2 (G2) (n: 24; 17%), and grade 3 (G3) (n: 14; 10%). The GEP-NET of the patients was stage I (n: 66; 46.8%), stage II (n: 14; 9.9%), stage III (n: 12; 8.5%), and stage IV (n: 49; 34.8%). In the statistical analysis, Ki-67 increased in parallel with the stage of the disease (P<0.001). As Ki-67 increased at a rate of 1%, survival rates of the patients decreased 1.027 times (P=0.01). Five-year survival rates of the patients were 88% in G1, 44% in G2, and 24% in G3. Patients in G2 and G3 had a 6.67 and 12.38 times lower chance of survival compared with G1 patients, respectively. Survival rates of stage IV patients were 5.6 times lower relative to stages I and II patients, respectively (P<0.001). The median 5-year survival rates of the patients were 90% in stage I, 100% in stage II, 47% in stage III, and 46% in stage IV. In univariate analysis, age of the patients, grade, stage of the tumor, and lymph node metastases were found to be parameters that affected overall survival, whereas no significant correlation was found between the sex of the patient and the primary organ from which the tumor originated and survival rates. However, in the multivariate analysis, survival rates decreased inversely with age, whereas no significant correlation was found between grade and stage of the tumor and survival rates.

Conclusion

In conclusion, a decrease in the average survival rate in parallel with an increase in the grade of the tumor was more prominent compared with a decrease in survival rates in accordance with an increase in the stage of the tumor. This indicates that in the prediction of prognosis in patients with GEP-NET, the Ki-67 value can be a more important evaluation factor relative to staging.
Deregulation of the HOXA9/MEIS1 axis in acute leukemia
Authors: Collins Cailin T. , Hess Jay L.
Published: March 2016

Purpose of review

HOXA9 is a homeodomain transcription factor that plays an essential role in normal hematopoiesis and acute leukemia, in which its overexpression is strongly correlated with poor prognosis. The present review highlights recent advances in the understanding of genetic alterations leading to deregulation of HOXA9 and the downstream mechanisms of HOXA9-mediated transformation.

Recent findings

A variety of genetic alterations including MLL translocations, NUP98-fusions, NPM1 mutations, CDX deregulation, and MOZ-fusions lead to high-level HOXA9 expression in acute leukemias. The mechanisms resulting in HOXA9 overexpression are beginning to be defined and represent attractive therapeutic targets. Small molecules targeting MLL-fusion protein complex members, such as DOT1L and menin, have shown promising results in animal models, and a DOT1L inhibitor is currently being tested in clinical trials. Essential HOXA9 cofactors and collaborators are also being identified, including transcription factors PU.1 and C/EBPα, which are required for HOXA9-driven leukemia. HOXA9 targets including IGF1, CDX4, INK4A/INK4B/ARF, mir-21, and mir-196b and many others provide another avenue for potential drug development.

HOXA9 deregulation underlies a large subset of aggressive acute leukemias. Understanding the mechanisms regulating the expression and activity of HOXA9, along with its critical downstream targets, shows promise for the development of more selective and effective leukemia therapies.
Comparison of a Panel of Biomarkers Between Gastric Primary Cancer and the Paired Krukenberg Tumor
Authors: Wang Bo , Sun Ke , Zou Yinying
Published: March 2016

To compare a panel of selected biomarkers between gastric primary cancer and the paired Krukenberg tumor, a total of 21 cases of metastatic tumors originating from stomach and the paired gastric primary cancers were collected. The expressions of a panel of selected biomarkers were tested by IHC. FISH was used to determine the status of HER2/neu in cases scored IHC 2+. The differences of the expressions of the biomarkers were evaluated between metastatic tumors and the paired gastric primary cancers. Bcl-2 was negative in all the cases. The HER2/neu expression was consistent between the gastric primary cancers and the paired metastatic tumors in 17 patients. In the other 4 cases, the HER2/neu expression was negative in gastric primary cancers but positive in the matched metastatic tumors. The concordance rate of c-MET, p53, and Ki-67 expression was 71.4%, 81.0%, and 76.2%, respectively. In conclusion, the expression of Bcl-2 is negative in all gastric primary tumors and the paired metastatic cancers. There is major concordance of the expression of HER2/neu, c-MET, p53, and Ki-67 between gastric primary cancers and the paired metastatic tumors, which suggests that the status of these biomarkers remain stable during the metastatic process.
Neuroendocrine Carcinoma of the Endometrium
Authors: Pocrnich Cady E. , Ramalingam Preetha , Euscher Elizabeth D. , Malpica Anais
Published: March 2016

Neuroendocrine carcinoma (NECa) of the endometrium is an uncommon tumor. In this study, we present the clinicopathologic features of 25 such cases. The patients ranged in age from 37 to 87 years (median, 57 y) and most commonly presented with vaginal bleeding. The tumors were either pure NECa (10) or mixed with other histotypes (15), most commonly endometrioid carcinoma. The NECas were large cell type (15), small cell type (4), or a mixture of both (6). NECa was underrecognized in 89% of referral/consultation cases. All tumors were positive for ≥1 neuroendocrine marker (chromogranin, synaptophysin, CD56). Additional immunohistochemical (IHC) studies were obtained in 18 cases, with positive results as follows: keratin cocktail (17), diffuse p16 (6), PAX-8 (6), CD117 (6), and TTF-1 (1). Mismatch-repair protein expression by IHC was abnormal in 8 of 18 cases (6 MLH1/PMS2 loss; 1 MSH2/MSH6 loss; 1 MSH6 loss). According to FIGO staging, cases were distributed as follows: I (6), II (2), III (10), and IV (7). All patients underwent surgical treatment, and 20 patients received adjuvant therapy. Twelve patients died of disease (mean survival 12.3 mo). Eleven patients were alive 5 to 134 months after diagnosis, including 7 who achieved a 5-year survival (3 stage I; 4 stage III). In summary, most of our endometrial NECas were large cell type, mixed with other histotypes, and underrecognized. These tumors tend to be PAX-8 negative and may be associated with microsatellite instability. The recognition of NECa may have an impact on the treatment of the patients affected by this disease. Although NECa usually has an aggressive behavior, 28% of our patients survived at least 5 years.
Emergency Department Use and Postvisit Care for Anxiety and Stress Disorders Among Children
Authors: Newton Amanda S. , Rosychuk Rhonda J. , Niu Xiaoqing , Radomski Ashley D. , McGrath Patrick J.
Published: March 2016

Objective

We examined sociodemographic trends in emergency department ED visits and postvisit health care for anxiety and stress disorders.

Methods

Emergency department visits (N = 11,289) by children younger than 18 years were extracted from population-based administrative databases from Alberta, Canada (2002–2011). We examined health services use by demographics and socioeconomic proxy (First Nations status, family subsidy type: government, human services program, none). We calculated visit rates and described physician visits after discharge (n = 8075 children). Multivariable survival analyses (with 95% confidence intervals [CIs]) estimate time to first physician visit and ED return.

Results

During 2002–2011, visit rates increased by age, First Nations, and subsidy status. The largest increase was for children (all ages) from families receiving government subsidy (491.43/100,000, P < 0.001). Thirty days after an index visit, most physician follow-up visits were made by children aged 15 to 17 years (61.0%) and from families receiving no subsidy (66.5%). The median time to physician follow-up for First Nations children was 32 days (95% CI, 27–37) compared with 19 days for children from families receiving government subsidy whose median time was shortest (95% CI, 18–23). Children (all ages) in the government and human services program subsidy groups and those who had First Nations status returned earlier to the ED compared with children in the no subsidy group.

Conclusions

Adolescents had high ED use and physician follow-up, whereas First Nations children and those from families receiving subsidy (all ages) had high ED use and low physician follow-up. Efforts to improve disorder identification and treatment among high ED user groups and low physician follow-up user groups are needed.
A susceptible mouse model for Zika virus infection
Authors: Dowall S.D. , Graham V.A. , Rayner E. , Atkinson B , Hall G. , Watson R. , Bosworth A. , Bonney L. , Kitchen S , Hewson R.
Published: March 2016

Zika virus (ZIKV) is a mosquito-borne pathogen which has recently spread beyond Africa and into Pacific and South American regions. Despite first being detected in 1947, very little information is known about the virus and its spread has been associated with increases in Guillain-Barre syndrome and microcephaly. There are currently no known vaccines or antivirals against ZIKV infection. Progress in assessing interventions will require the development of animal models to test efficacies; however, there are only limited reports onin vivostudies. The only susceptible murine models have involved intracerebral inoculations or juvenile animals, which do not replicate natural infection. Our report has studied the effect of ZIKV infection in type-I interferon receptor deficient (A129) mice and the parent strain (129Sv/Ev) after subcutaneous challenge in the lower leg to mimic a mosquito bite. A129 mice developed severe symptoms with viral RNA being detected widespread in the blood, brain, spleen, liver and ovaries. Histological changes were also striking in these animals. 129Sv/Ev mice developed no clinical symptoms or histological changes, despite viral RNA being detectable in the blood, spleen and ovaries, albeit at lower levels to those seen in A129 mice. Our results identify A129 mice as being highly susceptible to ZIKV and thus a suitable small animal model for the testing of vaccines and antivirals which are urgently required.

Author summary

Since first being recognised in 1947, Zika virus (ZIKV) has mainly been a mild illness with symptoms including a limited fever and rash. In 2007 the virus spread from Africa into French Polynesia and then onwards across Pacific regions and into South America. In these new regions, ZIKV has been associated with more severe clinical conditions including Gullain-Barre syndrome and microcephaly. There are no currently approved antivirals or vaccines available with proven activity against ZIKV, and the World Health Organisation declared the spread of ZIKV as a Public Health Emergency of International Concern. Here, we have used a mouse strain with a deficiency in the type-I interferon receptor (A129) and shown that they are susceptible to ZIKV infection after inoculation that closely resembles the natural route via mosquito bite. Although A129 mice are deficient in the innate interferon response, they retain their adaptive immunity and thus have successfully been used as suitable models for the testing of vaccinations and antivirals. Our study provides details on a suitable model for the testing of future interventions against ZIKV.
Resolving the conflict between associative overdominance and background selection
Authors: Zhao Lei , Charlesworth Brian
Published: March 2016

In small populations, genetic linkage between a polymorphic neutral locus and loci subject to selection, either against partially recessive mutations or in favor of heterozygotes, may result in an apparent selective advantage to heterozygotes at the neutral locus (associative overdominance), and a retardation of the rate of loss of variability by genetic drift at this locus. In large populations, selection against deleterious mutations has previously been shown to reduce variability at linked neutral loci (background selection). We describe analytical, numerical and simulation studies that shed light on the conditions under which retardation versus acceleration of loss of variability occurs at a neutral locus linked to a locus under selection. We consider a finite, randomly mating population initiated from an infinite population in equilibrium at a locus under selection, with no linkage disequilibrium. With mutation and selection, retardation only occurs whenS, the product of twice the effective population size and the selection coefficient, is of order one. WithS≫ 1, background selection always causes an acceleration of loss of variability. Apparent heterozygote advantage at the neutral locus is, however, always observed when mutations are partially recessive, even if there is an accelerated rate of loss of variability. With heterozygote advantage at the selected locus, there is nearly always a retardation of loss of variability. The results shed light on experiments on the loss of variability at marker loci in laboratory populations, and on the results of computer simulations of the effects of multiple selected loci on neutral variability.
Telemetry research on elusive wildlife: A synthesis of studies on giant pandas
Authors: CONNOR Thomas , HULL Vanessa , LIU Jianguo
Published: March 2016

Telemetry studies that track animals through space and time can lead to advances in scientific understanding that are vital in conservation efforts. For example, telemetry studies of the giant panda (Ailuropoda melanoleuca) have shed light on many aspects of panda biology, but small sample sizes in each separate study make it difficult to draw broad conclusions. To overcome this problem we conducted the first synthesis of all 5 panda telemetry studies conducted to date. Using these data we investigated patterns in 6 main topics: home range, space–use interactions, core areas, movement patterns, seasonal migration and natal dispersal. We found that panda home range sizes do not vary between 2 main mountain ranges (Qionglai and Qinling), as was previously believed. Our results also suggest that female pandas increase their movement in the mating season: a behavior typically attributed only to males. We found and summarized telemetry and genetic evidence for female natal dispersal in the giant panda. Our synthesis highlights the need for additional research relating panda behavior to human disturbance factors, and can aid future studies on giant pandas as well as other species.
Anaesthetists stress is induced by patient ASA grade and may impair non‐technical skills during intubation
Authors: Doleman B. , Blackwell J. , Karangizi A. , Butt W. , Bhalla A. , Lund J. N. , Williams J. P.
Published: March 2016

Background

The aims of this study were to determine if patient ASA grade was associated with increased stress in anaesthetists with a subsequent effect on non‐technical skills.

Methods

Stress was measured using a validated objective (heart rate variability or heart rate) and subjective tool. We studied eight consultant anaesthetists at baseline (rest) and during 16 episodes of intubation with an ASA 1 or 2 patient vs. an ASA 3 or 4 patient. The primary outcome for the study was objective and subjective stress between both patient groups. Secondary outcomes were non‐technical skill ratings and the association between stress measurements.

Results

ASA 3 or 4 patients were associated with increases in objective stress when compared to baseline (mean 4.6 vs. 6.7; P = 0.004). However, ASA 1 or 2 patients were not associated with increases in stress when compared to baseline (mean 4.6 vs. 4.7; P = 1). There was no significant difference in subjective stress between the groups (P = 0.18). Objective stress negatively affected situational awareness (P = 0.03) and decision‐making (P = 0.03); however, these did not decline to a clinically significant threshold. Heart rate variability (r = 0.60; P = 0.002) better correlated with subjective stress when compared to heart rate (r = 0.30; P = 0.15). Agreement between raters for Anaesthetic Non‐Technical Skills (ANTS) scores was acceptable (ICC = 0.51; P = 0.003).

Conclusion

This study suggests that higher patient ASA grade can increase stress in anaesthetists, which may impair non‐technical skills.
A Swiss‐Army Knife? A Critical Assessment of the Extractive Industries Transparency Initiative (EITI) in Ghana
Authors: Andrews Nathan
Published: March 2016

Within the current global atmosphere where a universally accepted police force is nonexistent, there are several voluntary norms and codes of conduct that exist to guide how corporations behave worldwide. These have come as a result of many years of poor performance in the areas of social, financial, and environmental responsibility. Such norms are expected to prescribe and proscribe certain types of corporate behavior but when one examines the reality on the ground, the story is not that straightforward. This article assesses the effectiveness of the Extractive Industries Transparency Initiative (EITI) in the Ghanaian context with a focus on the mining sector. Based on primary qualitative data the argument is that even though the EITI is performing some function, it has ways to go before it can become an across‐the‐board viable tool for transparency and proper accountability. Five prevailing weaknesses are discussed to underscore this case.
Will the Truth Set Us Free? An Exploration of CSR Motive and Commitment
Authors: Dare Julia
Published: March 2016

This article examines why firms engage in Corporate Social Responsibility (CSR). Specifically, it investigates the relationship between a firm's motivation to engage in CSR and the depth of its commitment. I propose that the enduring debate over CSR and financial performance is misaligned, and that scholars should instead focus on the underlying components of CSR engagement. This research sheds light on the motivational antecedents of a firm's engagement in CSR and their effect on CSR commitment. Despite calls for scientific investigation of this linkage, it has received scant attention in the literature. Pursuing this area of research requires the construction of measures of CSR motivation and CSR commitment, as prior work generally lacks objective analysis. I present measures and a research methodology that test hypotheses about how CSR motivation relates to different levels of CSR commitment. The results of this research both validate and challenge current theory. This refined understanding of CSR engagement may enhance firm transparency and accountability to stakeholders. It may reduce the uncertainty in both internal and external assessments of firm CSR and the potential for social and financial impact.
Protein Partners of α‐Synuclein in Health and Disease
Authors: Lassen Louise Berkhoudt , Reimer Lasse , Ferreira Nelson , Betzer Cristine , Jensen Poul Henning
Published: March 2016

α‐synuclein is normally situated in the nerve terminal but it accumulates and aggregates in axons and cell bodies in synucleinopathies such as Parkinson's disease. The conformational changes occurring during α‐synucleins aggregation process affects its interactions with other proteins and its subcellular localization. This review focuses on interaction partners of α‐synuclein within different compartments of the cell with a focus on those preferentially binding aggregated α‐synuclein. The aggregation state of α‐synuclein also affects its catabolism and we hypothesize impaired macroautophagy is involved neuronal excretion of α‐synuclein species responsible for the prion‐like spreading of α‐synuclein pathology.
Latent cytomegalovirus infection enhances anti-tumour cytotoxicity through accumulation of NKG2C+ NK cells in healthy humans
Authors: Bigley A B , Rezvani K , Shah N , Sekine T , Balneger N , Pistillo M , Agha N , Kunz H , O'Connor D P , Bollard C M , Simpson R J
Published: March 2016

Cytomegalovirus (CMV) infection markedly expands NKG2C+/NKG2A− NK cells, which are potent killers of infected cells expressing human leucocyte antigen (HLA)-E. As HLA-E is also over-expressed in several haematological malignancies and CMV has been linked to a reduced risk of leukaemic relapse, we determined the impact of latent CMV infection on NK cell cytotoxicity against four tumour target cell lines with varying levels of HLA-E expression. NK cell cytotoxicity against K562 (leukaemia origin) and U266 (multiple myeloma origin) target cells was strikingly greater in healthy CMV-seropositive donors than seronegative donors and was associated strongly with target cell HLA-E and NK cell NKG2C expression. NK cell cytotoxicity against HLA-E transfected lymphoma target cells (221.AEH) was ∼threefold higher with CMV, while NK cell cytotoxicity against non-transfected 721.221 cells was identical between the CMV groups. NK cell degranulation (CD107a+) and interferon (IFN)-γ production to 221.AEH cells was localized almost exclusively to the NKG2C subset, and antibody blocking of NKG2C completely eliminated the effect of CMV on NK cell cytotoxicity against 221.AEH cells. Moreover, 221.AEH feeder cells and interleukin (IL)−15 were found to expand NKG2C+/NKG2A– NK cells preferentially from CMV-seronegative donors and increase NK cell cytotoxicity against HLA-E+ tumour cell lines. We conclude that latent CMV infection enhances NK cell cytotoxicity through accumulation of NKG2C+ NK cells, which may be beneficial in preventing the initiation and progression of haematological malignancies characterized by high HLA-E expression.
MICA*A4 protects against ulcerative colitis, whereas MICA*A5.1 is associated with abscess formation and age of onset
Authors: Martinez-Chamorro A , Moreno A , Gómez-García M , Cabello M J , Martin J , Lopez-Nevot M Á
Published: March 2016

Ulcerative colitis (UC) is one of the two major forms of inflammatory bowel disease, the aetiology of which remains unknown. Several studies have demonstrated the genetic basis of disease, identifying more than 130 susceptibility loci. The major histocompatibility complex class I chain-related gene A (MICA) is a useful candidate to be involved in UC pathogenesis, because it could be important in recognizing the integrity of the epithelial cell and its response to stress. The aim of this study was to analyse the relationship between polymorphisms in the transmembrane domain of MICA and susceptibility to develop UC. A total of 340 patients with UC and 636 healthy controls were genotyped for MICA transmembrane polymorphism using a polymerase chain reaction (PCR) combined with fluorescent technology. Different MICA alleles were determined depending on the PCR product size. The allele MICA*A4 was less frequent in patients than in controls (P = 0·003; OR = 0·643), and this protective role is higher when it forms haplotype with B*27 (P = 0·002; OR = 0·294). The haplotype HLA-B*52/MICA*A6 was also associated with UC [P = 0·001; odds ratio (OR) = 2·914]. No other alleles, genotypes or haplotypes were related with UC risk. Moreover, MICA*A5.1 is associated independently with abscesses (P = 0·002; OR = 3·096) and its frequency is lower in patients diagnosed between ages 17 and 40 years (P = 0·007; OR = 0·633), meaning an extreme age on onset. No association with location, extra-intestinal manifestations or need for surgery was found.