bluuebunny/crossref_metadata_2025 huggingface dataset:
On the possibility of critiquing Israel: The Times’ engagement with Israel’s deployment of white phosphorous during the first Gaza war
Authors: Kaposi Dávid
Published: June 2016

This article comprises a discourse analysis of The Times’ (the British daily newspaper) coverage of Israeli deployment of white phosphorous during the first Gaza war. It argues that this issue is of special theoretical importance as it demonstrates a rare instance of a medium that is considered supportive of an agent (i.e. the state of Israel) offering apparently substantial criticism of that particular agent. The article progresses by uncovering layers of the newspaper’s coverage. It starts by introducing some quantitative characteristics, then moves on to analysis proper – explicit arguments and implicit meaning in editorials. In doing this, the author argues that an understanding of the discourse around criticism and the Israeli–Palestinian conflict needs to account not just for overt arguments but implicit meanings which, consciously or not, are sustaining those arguments.
Defining Taiwanese children’s health literacy abilities from a health promotion perspective
Authors: Liao Li-Ling , Liu Chieh-Hsing , Cheng Chi-Chia , Chang Tzu-Chau
Published: June 2016

Background:

Health literacy is related to health inequality, health behaviors, and health status. Globally, health literacy has primarily focused on adults and has been based on the medical model. It is necessary to understand children’s life experiences as they relate to health; thus, this study attempted to evaluate and describe the health literacy abilities of sixth-graders in Taiwan.

Methods:

Interviews were conducted with 10 teachers and 11 caregivers, and focus groups were conducted with 32 children. Health literacy abilities corresponding to real-life situations were identified from life skills and the Taiwanese Curriculum Guidelines for health education. Three expert meetings were held to redefine children’s health literacy using a health promotion perspective and confirmed indicators.

Results:

An operational definition of three aspects of children’s health literacy and 25 abilities was proposed: 11 functional health literacy abilities (e.g. understands the connection between personal health care behaviors and health); seven interactive health literacy abilities (e.g. obtains and understands information from various channels); and seven critical health literacy abilities (e.g. analyzes the relationship between personal needs and diet choices for a balanced diet). These indicators cover 10 health education categories.

Conclusions:

These findings highlight the importance of understanding Taiwanese children’s health literacy, and the urgency of developing an appropriate measurement tool. The definition and indicators in this study were identified using a child-centered approach focusing on children’s real-life experiences. The result serves as a solid basis for the development of the Taiwan Children’s Health Literacy Scale, and provides information for the decision-making sector on health education.
The relationship between insufficient milk perception and breastfeeding self-efficacy among Turkish mothers
Authors: Gökçeoğlu Emine , Küçükoğlu Sibel
Published: June 2016

Objective:

This study was conducted to investigate the relationship between perceived insufficient milk and breastfeeding self-efficacy levels among Turkish mothers.

Methods:

The study was conducted on 200 mothers whose infants were hospitalized and under treatment and who could breastfeed their infants in the newborn clinic of a university hospital in eastern Turkey between June 2013 and February 2014. A sampling method was not applied in the study, so the sample consisted of the population of the study. The ‘Personal Information Form’, ‘Breastfeeding Self-Efficacy Scale’ and ‘Perception of Insufficient Milk Questionnaire’ were used to collect the data. Data were analysed by using percentage distribution and arithmetic average; independent sample t test, Mann–Whitney U test, Kruskal–Wallis variance analysis, Pearson correlation analysis and Cronbach alpha reliability coefficiency in the SPSS 18.0 package program.

Results:

The study determined that advanced age, higher education level and higher income status, male gender of the child, planning of the pregnancy, many births, receiving breastfeeding education and the length of time that mothers planned to exclusively breastfeed affected breastfeeding self-efficacy and perception of milk sufficiency positively ( p<0.05). The study showed that, as breastfeeding self-efficacy levels of mothers increased, their perception of milk sufficiency also increased ( p<0.05).

Conclusion:

The study concluded that some factors related to the mother, infant, pregnancy and breastfeeding affected breastfeeding self-efficacy and the perception of milk insufficiency. As the breastfeeding self-efficacy level increased, the milk was perceived to be more sufficient.
Diagnoses Treated in Ambulatory Care Among Homeless-Experienced Veterans
Authors: Gabrielian Sonya , Yuan Anita H. , Andersen Ronald M. , Gelberg Lillian
Published: June 2016

Purpose: Little is known about how permanent supported housing influences ambulatory care received by homeless persons. To fill this gap, we compared diagnoses treated in VA Greater Los Angeles (VAGLA) ambulatory care between Veterans who are formerly homeless—now housed/case managed through VA Supported Housing (“VASH Veterans”)—and currently homeless. Methods: We performed secondary database analyses of homeless-experienced Veterans (n = 3631) with VAGLA ambulatory care use from October 1, 2010 to September 30, 2011. We compared diagnoses treated—adjusting for demographics and need characteristics in regression analyses—between VASH Veterans (n = 1904) and currently homeless Veterans (n = 1727). Results: On average, considering 26 studied diagnoses, VASH (vs currently homeless) Veterans received care for more ( P < .05) diagnoses (mean = 2.9/1.7). Adjusting for demographics and need characteristics, VASH Veterans were more likely ( P < .05) than currently homeless Veterans to receive treatment for diagnoses across categories: chronic physical illness, acute physical illness, mental illness, and substance use disorders. Specifically, VASH Veterans had 2.5, 1.7, 2.1, and 1.8 times greater odds of receiving treatment for at least 2 condition in these categories, respectively. Among participants treated for chronic illnesses, adjusting for predisposing and need characteristics, VASH (vs currently homeless) Veterans were 9%, 8%, and 11% more likely to have 2 or more visits for chronic physical illnesses, mental illnesses, and substance use disorder, respectively. Conclusion: Among homeless-experienced Veterans, permanent supported housing may reduce disparities in the treatment of diagnoses commonly seen in ambulatory care.
Acute Kidney Injury Following Cardiac Surgery in Neonates and Young Infants
Authors: Kumar T. K. Susheel , Allen, CCP Jerry , Spentzas, MD Thomas , Berrios, CCP Lindsay , Shah, MD Samir , Joshi, MD Vijaya M. , Ballweg, MD Jean A. , Knott-Craig, MD Christopher J.
Published: June 2016

Objective:

Acute kidney injury (AKI) following cardiac surgery is a serious complication with a reported incidence of 30% to 50%. This study sought to determine the prevalence and risk factors for AKI among neonates and young infants undergoing repair of cardiac defects at an institution using novel perioperative strategies.

Methods:

A retrospective analysis of 102 consecutive infants (<2 months) undergoing repair of cardiac defects on cardiopulmonary bypass formed the study group. Cardiac diagnoses were stratified according to the Society of Thoracic Surgeons Congenital Heart Surgery (STAT) mortality categories. The prevalence of AKI within 72 hours was defined according to the three-stage Acute Kidney Injury Network criteria. Novel bypass strategies to preserve renal function included maintenance of higher hematocrit and high flow rates on cardiopulmonary bypass despite systemic hypothermia, and avoidance of albumin and milrinone in the perioperative period.

Results:

Mean age was 24 ± 19 days. Eighteen patients were less than 7 days of age at the time of surgery. Patient distribution according to STAT categories was as follows: 1 (n = 21), 2 (n = 12), 3 (n = 22), 4 (n = 28), and 5 (n = 19). The incidence of stages 1, 2, and 3 AKI in the population was 8% (n = 9), 2% (n = 2), and 0% (n = 0), respectively. On multivariate analysis higher STAT category was the only significant risk factor for AKI.

Conclusion:

Current incidence of AKI following cardiac surgery in young infants at our institution is low. Novel perioperative strategies may have contributed to the low observed incidence of AKI in our patient population. Increased complexity of heart disease was a risk factor for AKI.
The Niger Delta Amnesty Program
Authors: Okonofua Benjamin A.
Published: June 2016

The armed conflict between militias and government forces in Nigeria’s Niger Delta region has spanned for more than two decades, defying all solutions. A disarmament, demobilization, and reintegration (DDR) program was established in August 2015 in effort to end the violence and has remained in place. It is a radically different approach from past approaches that displayed zero tolerance to all political challenges to oil production or the allocation of oil profits. The approach appeared to be immediately successful in that it forced a ceasefire, engaged militants in planned programs to rehabilitate and reintegrate them into civilian society, and opened up the oil wells (many of which had been shut due to the crisis) with the effect of increasing government revenue, which depends 85% on oil exports. Yet, few studies have attempted to understand the dynamics within the country that are responsible for the design and implementation of this broad policy shift or to understand whether and how the current initiative is able to end the conflict and institute peace beyond the short term. This study, therefore, is important because it provides a critical perspective that anticipates and explains emerging issues with the Niger Delta Amnesty Program, which have implications for DDR adaptation and implementation all over the world. Ultimately, the research demonstrates how the DDR program both transforms the Niger Delta conflict and becomes embroiled in intense contestations not only about the mechanism for transforming the targeted population but also whether and how the program incorporates women who are being deprioritized by the program.
Return to Sport After Operative Management of Osteochondritis Dissecans of the Capitellum
Authors: Westermann Robert W. , Hancock Kyle J. , Buckwalter Joseph A. , Kopp Benjamin , Glass Natalie , Wolf Brian R.
Published: June 2016

Background:

Capitellar osteochondritis dissecans (OCD) is commonly managed surgically in symptomatic adolesent throwers and gymnasts. Little is known about the impact that surgical technique has on return to sport.

Purpose:

To evaluate the clinical outcomes and return-to-sport rates after operative management of OCD lesions in adolescent athletes.

Study Design:

Systematic review; Level of evidence, 4.

Methods:

The PubMed, CINAHL, EMBASE, SPORTDiscus (EBSCO), and Cochrane Central Register of Controlled Trials databases were queried for studies evaluating outcomes and return to sport after surgical management of OCD of the capitellum. Two independent reviewers conducted a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies reporting patient outcomes with return-to-sport data and minimum 6-month follow-up were included in the review.

Results:

After review, 24 studies reporting outcomes in 492 patients (mean age ± SD, 14.3 ± 0.9 years) were analyzed. The overall return-to-sport rate was 86% at a mean 5.6 months. Return to the highest preoperative level of sport was most common after osteochondral autograft procedures (94%) compared with debridement and marrow stimulation procedures (71%) or OCD fixation surgery (64%). Elbow range of motion improved by 15.9° after surgery. The Timmerman-Andrews subjective and objective scores significantly improved after surgery. Complications were low (<5%), with 2 cases of donor site morbidity after osteoarticular autograft transfer (OAT) autograft harvest. The most common indications for reoperation were repeat debridement/loose body removal.

Conclusion:

A high rate of return to sport was observed after operative management of capitellar OCD. Patients were more likely to return to their highest level of preoperative sport after OAT autograft compared with debridement or fixation. Significant improvements in elbow range of motion and patient outcomes are seen with low complication rates after OCD surgery.
Biomechanical Comparison of Single- and Double-Leg Jump Landings in the Sagittal and Frontal Plane
Authors: Taylor Jeffrey B. , Ford Kevin R. , Nguyen Anh-Dung , Shultz Sandra J.
Published: June 2016

Background:

Double-leg forward or drop-jump landing activities are typically used to screen for high-risk movement strategies and to determine the success of neuromuscular injury prevention programs. However, research suggests that these tasks that occur primarily in the sagittal plane may not adequately represent the lower extremity biomechanics that occur during unilateral foot contact or non–sagittal plane movements that are characteristic of many multidirectional sports.

Purpose:

To examine the extent to which lower extremity biomechanics measured during a jump landing on a double leg (DL) after a sagittal plane (SAG) movement is representative of biomechanics measured during single-leg (SL) or frontal plane (FRONT) jump landing tasks.

Study Design:

Controlled laboratory study.

Methods:

Lower extremity biomechanics were measured in 15 recreationally active females (mean age [±SD], 19.4 ± 2.1 years; mean height, 163.3 ± 5.9 cm; mean weight, 61.1 ± 7.1 kg) while performing SAGDL, SAGSL, FRONTDL, and FRONTSL jump landing tasks. Repeated-measures analyses of variance examined differences in lower extremity biomechanics between the 4 tasks, and linear regressions examined the extent to which an individual’s biomechanics during SAGDL were representative of their biomechanics during SAGSL, FRONTDL, and FRONTSL.

Results:

Lower extremity kinematics and kinetics differed by condition, with the SAGDL task generally eliciting greater hip and knee flexion angles and lower hip and knee forces than the other tasks ( P < .05). Although biomechanics during the SAGDL task were strongly associated with those during the FRONTDL task ( R2, 0.41-0.82), weaker associations were observed between SAGDL and single-leg tasks for hip kinematics ( R2, 0.03-0.25) and kinetics ( R2, 0.05-0.20) and knee abduction moments ( R2, 0.06-0.18) ( P < .05).

Conclusion:

Standard double-leg sagittal plane jump landing tasks used to screen for ACL injury risk and the effectiveness of ACL injury prevention programs may not adequately represent the lower extremity biomechanics that occur during single-leg activities.

Clinical Relevance:

These results support further investigation of single-leg multidirectional landings to identify high-risk movement strategies in female athletes playing multidirectional sports.
The Association Between Student Reports of Classmates’ Disruptive Behavior and Student Achievement
Authors: Blank Carmel , Shavit Yossi
Published: June 2016

Classroom disciplinary climate and its correlation to students’ performance is a widely debated issue. Policy reports tend to assume that classroom disruptions interfere with the learning experience. Empirical evidence for this assumption, however, which carefully distinguishes classroom climate from the school climate in general, is still wanting. This study examines the relation between student reports regarding disciplinary infractions to student achievement, with a special focus on classroom disruptions. Multilevel regressions were used to estimate the contribution of classroom and school disciplinary infractions on eighth-grade students’ test scores. Reports of disruptive behavior proved to correlate negatively with test scores, whereas the effect of other school and classroom characteristics, including teachers’ attitudes and school disciplinary policy, were insignificant (controlling for students’ prior achievements). We conclude that a disruptive classroom climate can hinder the learning process and lower the achievement of the entire class, regardless of the conduct of any particular student. Therefore, a special focus on disruptions in the classroom, in contradistinction with school disciplinary climate in general—which is lacking in most studies—emerges as instrumental to the understanding of how school climate relates to student achievement.
In Which Neighborhoods Are Older Adult Populations Expanding? Sociodemographic and Built Environment Characteristics Across Neighborhood Trajectory Classes of Older Adult Populations in Four U.S. Cities Over 30 Years
Authors: Rummo Pasquale E. , Hirsch Jana A. , Howard Annie Green , Gordon-Larsen Penny
Published: June 2016

Objective: We sought to examine characteristics of neighborhoods with changing older adult populations. Method: We used 30 years (1980-2011) of data from four U.S. cities ( n = 392 neighborhoods; Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota; Oakland, California) and finite mixture modeling to identify trajectory classes: neighborhoods with “stable,” declining, or increasing older adult populations (≥65 years). We then compared mean baseline and change in their characteristics. Results: Neighborhoods with an increasing (vs. “stable”) percentage of older adult populations had lower initial poverty and greater increases in education and income, with lower increases in road connectivity, population density, and housing prices/debt over time. The same was true for neighborhoods with declining older adult populations, with the exception of having higher increases in housing prices/debt. We observed few significant differences in neighborhood amenities or parks across classes. Conclusion: Our results emphasize the need to consider built and social environments when planning communities for older adults.
New Phase of Internationalization of Higher Education and Institutional Change
Authors: Wadhwa Rashim
Published: June 2016

Internationalization of higher education has undergone significant change in the current scenario. The approach to traditional internationalization which was based on international co-operation and rarely a profit making activity were at the center of traditional internationalization has changed significantly from the last two decades. Emergence of the new phase of internationalization of higher education is characterized by self-economic interest of maximizing profit and capturing student market by expanding institutional reach in other countries. The intention of students to go abroad and the functioning of universities has changed substantially in the current scenario. The governance by comparison and competition for international students has made radical change in the governance of institutions. The remaining work is done by the globalization of higher education, essentially motivated by profits rather than by either government policy or goodwill. The observed competition in recent decades in the international higher education market has led to the marginalization of teaching–learning, which is assumed to be the central role of educational institutions. The central focus of the present article is to trace the change in internationalization of higher education in general, with special reference to student mobility and how it is changing the role of educational institutions in the new phase. In connection with this, the present article aims to contribute to the body of knowledge under the broad head of internationalization of higher education.
Evaluating the Relationships Among Teacher Characteristics, Implementation Factors, and Student Outcomes of Children Participating in an Experiential School-Based Nutrition Program
Authors: Linnell Jessica D. , Smith Martin H. , Briggs Marilyn , Brian Kelley M. , Scherr Rachel E. , Dharmar Madan , Zidenberg-Cherr Sheri
Published: June 2016

The purpose of this study was to examine whether teacher characteristics and implementation factors influenced the effectiveness of a multicomponent nutrition education program to improve nutrition-related knowledge and behavior among fourth-grade children. Schools implemented the Shaping Healthy Choices Program (SHCP), a multicomponent nutrition intervention, during 2013-2014. Fourth-grade teachers ( n = 8) at two schools facilitated nutrition education using an experiential, garden-enhanced nutrition curriculum among students ( n = 173) in their classrooms. Teacher characteristics of teaching experience, self-efficacy in teaching nutrition, and knowledge about nutrition were collected at baseline. Implementation factors of fidelity and completion were measured using self-reports and qualitative observations. Student outcomes included body mass index percentile-for-age, nutrition knowledge, critical thinking skills, and identification of vegetables and were measured pre/post. Relationships were analyzed using multivariate mixed-model regression with classroom as a random effect. Pre/post changes were analyzed using t tests. Students improved body mass index percentile-for-age (−1.99 ± 7.95) and increased nutrition knowledge (2.28 ± 3.40), critical thinking skills (1.98 ± 3.28), and the ability to identify vegetables (0.87 ± 1.09). Teachers’ characteristics of teaching experience, experience teaching nutrition, attendance in a college nutrition course, self-efficacy, and nutrition knowledge were significantly related to fidelity and completeness of program implementation. This study demonstrated implementation of SHCP by teachers can positively influence student outcomes, though program implementation depends on teacher characteristics.
The epidemiology of stroke in the Middle East
Authors: El-Hajj Maya , Salameh Pascale , Rachidi Samar , Hosseini Hassan
Published: June 2016

Purpose

The purpose of this paper is to review and synthesize data from different countries in the Middle East on stroke and its potential risk factors.

Method

A systematic review of all published stroke articles in the Middle East between 1980 and May 2015 was conducted.

Findings

Sixty-four papers were included in the review. The incidence rate for all strokes ranged between 22.7 and 250 per 100,000 population per year. The prevalence rate for stroke ranged between 508 and 777 per 100,000 population. Among studies reporting gender differences, 75% reported a high male-to-female ratio among stroke patients. The mean age of stroke was within the sixth and the seventh decade. Ischemic stroke was the most reported type followed by intracerebral hemorrhage and subarachnoid hemorrhage. Hypertension was the most reported risk factor followed by diabetes. The overall case-fatality rate within one month was 12–32%.

Discussion

During the last decades, there was an increase in stroke incidence and mortality rates in the Middle East. The Middle East faces low rates of self-awareness and control of noncommunicable diseases and also lacks knowledge for stroke risk factors, awareness, causes, and symptoms.

Conclusion

There is an urgent need to develop more efficient and accurate methods to measure stroke in the Middle East. There is also a significant call to increase public awareness and implement interventions on stroke and its risk factors and symptoms to help people understand the negative impact of stroke on quality of life and potentially prevent this disease.
Socio-economic Well-being—Impact of Wider Highways on the Rural Poor Living in Proximity
Authors: Sengupta Ramprasad , Coondoo Dipankor , Rout Bhisma
Published: June 2016

This article investigates the effect that a highway and its widening would have on the socio-economic lives of the poorer people living in its proximity. Such impact is positive at the micro-level because closer a household is to the highway, greater would be its connectivity. Increased mobility provides access to various economic opportunities and amenities of life. One would expect these positive welfare effects to decline as the approach distance of the highway from the household increases and ultimately to disappear beyond a threshold distance. This premise has been empirically verified here using a household-level baseline survey data pertaining to the project of widening of a stretch of the National Highway 2 (NH2), one of India’s oldest national highways. The article further examines how the widening of the highway enhances the benefit of proximity to the highway by comparing the baseline survey data and the resurvey data, the latter pertaining to a period after the completion of the project. It estimates the partial effect of widening of the highway on the socio-economic well-being of the household of the economies through which it passes using the methodology of non-parametric regression analysis (NRA) and propensity score matching technique (PSMT) cum single/double differencing technique.
Disseminated intravascular coagulation at diagnosis is a strong predictor for thrombosis in acute myeloid leukemia
Authors: Libourel Eduard J. , Klerk Clara P. W. , van Norden Yvette , de Maat Moniek P. M. , Kruip Marieke J. , Sonneveld Pieter , Löwenberg Bob , Leebeek Frank W. G.
Published: June 2016

Key Points

A high D-dimer level strongly predicts symptomatic venous and arterial thrombosis in newly diagnosed AML. Thrombosis occurs in up to 10% of patients with newly diagnosed AML.
Human–animal chimeras: ethical issues about farming chimeric animals bearing human organs
Authors: Bourret Rodolphe , Martinez Eric , Vialla François , Giquel Chloé , Thonnat-Marin Aurélie , De Vos John
Published: June 2016

Recent advances in stem cells and gene engineering have paved the way for the generation of interspecies chimeras, such as animals bearing an organ from another species. The production of a rat pancreas by a mouse has demonstrated the feasibility of this approach. The next step will be the generation of larger chimeric animals, such as pigs bearing human organs. Because of the dramatic organ shortage for transplantation, the medical needs for such a transgressive practice are indisputable. However, there are serious technical barriers and complex ethical issues that must be discussed and solved before producing human organs in animals. The main ethical issues are the risks of consciousness and of human features in the chimeric animal due to a too high contribution of human cells to the brain, in the first case, or for instance to limbs, in the second. Another critical point concerns the production of human gametes by such chimeric animals. These worst-case scenarios are obviously unacceptable and must be strictly monitored by careful risk assessment, and, if necessary, technically prevented. The public must be associated with this ethical debate. Scientists and physicians have a critical role in explaining the medical needs, the advantages and limits of this potential medical procedure, and the ethical boundaries that must not be trespassed. If these prerequisites are met, acceptance of such a new, borderline medical procedure may prevail, as happened before for in-vitro fertilization or preimplantation genetic diagnosis.
Fixed point theorems and iterative approximations for monotone nonexpansive mappings in ordered Banach spaces
Authors: Song Yisheng , Kumam Poom , Cho Yeol Je
Published: June 2016

In this paper, we prove some existence theorems of fixed points of a monotone nonexpansive mappingTin a Banach spaceEwith the partial order ‘≤’, where a such mapping may be discontinuous. In particular, in finite dimensional spaces, such a mappingThas a fixed point inEif and only if the sequence$\{T^{n}0\}${Tn0}is bounded inE. In order to find a fixed point of such a mappingT, we prove the weak convergence of the Mann iteration scheme under the condition$\sum_{n=1}^{\infty}\beta_{n}(1-\beta_{n})=\infty$∑n=1∞βn(1−βn)=∞, which entails$\beta _{n}=\frac{1}{n+1}$βn=1n+1as a special case.
Protection of CD4+ T cells from hepatitis C virus infection-associated senescence via ΔNp63–miR-181a–Sirt1 pathway
Authors: Zhou Yun , Li Guang Y , Ren Jun P , Wang Ling , Zhao Juan , Ning Shun B , Zhang Ying , Lian Jian Q , Huang Chang X , Jia Zhan S , Moorman Jonathan P , Yao Zhi Q
Published: June 2016

T cell dysfunction has a crucial role in establishing and maintaining viral persistence. We have previously shown a decline in miR-181a, which regulates CD4+ T cell responses via DUSP6 overexpression, in individuals with hepatitis C virus (HCV) infection. Here, we describe accelerated T cell senescence in HCV-infected individuals compared with age- and sex-matched healthy subjects. Mechanistic studies revealed that up-regulation of transcription factor ΔNp63 led to the decline of miR-181a expression, resulting in an overexpression of the antiaging protein Sirt1, in CD4+ T cells from HCV-infected individuals. Either reconstituting miR-181a or silencing ΔNp63 or Sirt1 expression in CD4+ T cells led to accelerated T cell senescence, as evidenced by an increased senescence-associated β-galactosidase (SA-β-gal) expression, shortened telomere length, and decreased EdU incorporation; this suggests that HCV-induced T cell senescence is counterregulated by the ΔNp63–miR-181a–Sirt1 pathway. An increase of IL-2 production was observed in these senescent CD4+ T cells and was driven by a markedly reduced frequency of Foxp3+ regulatory T (Treg) cells and increased number of Foxp3− effector T (Teff) cells upon manipulating the ΔNp63–miR-181a–Sirt1 pathway. In conclusion, these findings provide novel mechanistic insights into how HCV uses cellular senescent pathways to regulate T cell functions, revealing new targets for rejuvenating impaired T cell responses during chronic viral infection.
At The Bedside: Clinical review of chimeric antigen receptor (CAR) T cell therapy for B cell malignancies
Authors: Oluwole Olalekan O , Davila Marco L
Published: June 2016

T cells kill microbial-infected and malignant cells by detection of nonself antigens with the TCR. Tumor reactivity can be encoded genetically by introducing a chimeric antigen receptor (CAR) into T cells. CARs are composed of an antigen-binding domain and an intracellular T cell activation domain. Early human trials evaluating CD19-targeted CAR T cells for chronic lymphocytic leukemia (CLL) showed limited responses until CARs included a costimulation domain, and conditioning chemotherapy was given before T cell infusion. Clinical trials evaluating CD19-targeted CAR T cells for B cell acute lymphoblastic leukemia (B-ALL) are demonstrating response rates up to 90%. However, these clinical outcomes are associated with a cytokine release syndrome (CRS), which is caused by T cell activation and manifests as high-grade fever, hypotension, and other cardiovascular complications. It is currently managed conservatively but can be treated with cytokine-directed therapy or with high-dose steroids. Current efforts are dedicated to confirming the clinical efficacy and managing toxicities in multicenter Phase II trials. We present a thorough overview of the preclinical and clinical development of CAR T cell therapy that will highlight important areas for the basic researcher to investigate in the laboratory and contribute to this exciting field.
DISCUSSION AND COMMUNICATIONS
Authors: SHARPE JOSEPH A.
Published: June 2016

In a letter dated May 9, Mr. B. G. Swan, geophysicist with the Continental Oil Company of Ponca City, Oklahoma, submitted for my inspection an index of wells shot for seismic velocity which he had assembled, and suggested that the Society of Exploration Geophysicists might sponsor the preparation of as complete as possible an index of well velocity surveys, and publish this in GEOPHYSICS for the convenience of the industry, and that furthermore this index might be brought up to date at convenient intervals by publication of the locations of the wells shot for velocity since the last publication.
Publication Received
Authors: Kintz G. M.
Published: June 2016

The Federal Explosives Act will remain in effect until the war is officially over or action is taken by Congress or the President.
FOREWORD
Authors: Van Melle F. A.
Published: June 2016

At the time that the December issue had to leave our office (mid-August), not enough papers were on hand to fill an issue with reports on field techniques and field-office interpretation. How-ever, a number of papers were awaiting publication that deal with subjects within the realm of interest of the practicing geophysicist.
To Bayes or not to Bayes?
Authors: Scales John A. , Snieder Roel
Published: June 2016

The goal of geophysical inversion is to make quantitative inferences about the Earth from noisy, finite data. The limitations of noise and the inadequacy of the data mean that geophysical inversion problems are fundamentally problems of statistical inference. We do not invert data to find “models.” as much as we might like to; we invert data to make inferences about models. There will usually be an infinity of models that fit the data. Thus we must look to probability theory for help.
The Inelastic Input Energy Spectra for Main Shock–Aftershock Sequences
Authors: Zhai Changhai , Ji Duofa , Wen Weiping , Lei Weidong , Xie Lili , Gong Maosheng
Published: June 2016

This study investigates the input energy spectra for inelastic single-degree-of-freedom (SDOF) systems under main shock–aftershock sequences. The input energy spectra quantitatively reveal the effects of aftershocks on input energy, which verifies the necessity of incorporating aftershocks in energy-based seismic design. The investigation selects the sequences including one aftershock or two aftershocks respectively, according to the proposed criteria for selecting earthquake records. Then, the input energy for sequences is normalized by mass, m, and expressed in terms of the equivalent velocity, V E, seq. Next, the variation of V E, seq is studied in consideration of the hysteretic models, ductility values, periods of vibration, site conditions, relative intensities of aftershocks and number of aftershocks. The results indicate that the effects of aftershocks on input energy are significant in almost the whole period region. Finally, a simplified expression of input energy is proposed for incorporating aftershocks in energy-based seismic design.
Association Between Plasma Genotyping and Outcomes of Treatment With Osimertinib (AZD9291) in Advanced Non–Small-Cell Lung Cancer
Authors: Oxnard Geoffrey R. , Thress Kenneth S. , Alden Ryan S. , Lawrance Rachael , Paweletz Cloud P. , Cantarini Mireille , Yang James Chih-Hsin , Barrett J. Carl , Jänne Pasi A.
Published: June 2016

Purpose

Third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated potent activity against TKI resistance mediated by EGFR T790M. We studied whether noninvasive genotyping of cell-free plasma DNA (cfDNA) is a useful biomarker for prediction of outcome from a third-generation EGFR-TKI, osimertinib.

Methods

Plasma was collected from all patients in the first-in-man study of osimertinib. Patients who were included had acquired EGFR-TKI resistance and evidence of a common EGFR-sensitizing mutation. Genotyping of cell-free plasma DNA was performed by using BEAMing. Plasma genotyping accuracy was assessed by using tumor genotyping from a central laboratory as reference. Objective response rate (ORR) and progression-free survival (PFS) were analyzed in all T790M-positive or T790M-negative patients.

Results

Sensitivity of plasma genotyping for detection of T790M was 70%. Of 58 patients with T790M-negative tumors, T790M was detected in plasma of 18 (31%). ORR and median PFS were similar in patients with T790M-positive plasma (ORR, 63%; PFS, 9.7 months) or T790M-positive tumor (ORR, 62%; PFS, 9.7 months) results. Although patients with T790M-negative plasma had overall favorable outcomes (ORR, 46%; median PFS, 8.2 months), tumor genotyping distinguished a subset of patients positive for T790M who had better outcomes (ORR, 69%; PFS, 16.5 months) as well as a subset of patients negative for T790M with poor outcomes (ORR, 25%; PFS, 2.8 months).

Conclusion

In this retrospective analysis, patients positive for T790M in plasma have outcomes with osimertinib that are equivalent to patients positive by a tissue-based assay. This study suggests that, upon availability of validated plasma T790M assays, some patients could avoid a tumor biopsy for T790M genotyping. As a result of the 30% false-negative rate of plasma genotyping, those with T790M-negative plasma results still need a tumor biopsy to determine presence or absence of T790M.
Nivolumab Monotherapy for First-Line Treatment of Advanced Non–Small-Cell Lung Cancer
Authors: Gettinger Scott , Rizvi Naiyer A. , Chow Laura Q. , Borghaei Hossein , Brahmer Julie , Ready Neal , Gerber David E. , Shepherd Frances A. , Antonia Scott , Goldman Jonathan W. , Juergens Rosalyn A. , Laurie Scott A. , Nathan Faith E. , Shen Yun , Harbison Christopher T. , Hellmann Matthew D.
Published: June 2016

Purpose

Nivolumab, a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, has demonstrated improved survival over docetaxel in previously treated advanced non–small-cell lung cancer (NSCLC). First-line monotherapy with nivolumab for advanced NSCLC was evaluated in the phase I, multicohort, Checkmate 012 trial.

Methods

Fifty-two patients received nivolumab 3 mg/kg intravenously every 2 weeks until progression or unacceptable toxicity; postprogression treatment was permitted per protocol. The primary objective was to assess safety; secondary objectives included objective response rate (ORR) and 24-week progression-free survival (PFS) rate; overall survival (OS) was an exploratory end point.

Results

Any-grade treatment-related adverse events (AEs) occurred in 71% of patients, most commonly: fatigue (29%), rash (19%), nausea (14%), diarrhea (12%), pruritus (12%), and arthralgia (10%). Ten patients (19%) reported grade 3 to 4 treatment-related AEs; grade 3 rash was the only grade 3 to 4 event occurring in more than one patient (n = 2; 4%). Six patients (12%) discontinued because of a treatment-related AE. The confirmed ORR was 23% (12 of 52), including four ongoing complete responses. Nine of 12 responses (75%) occurred by first tumor assessment (week 11); eight (67%) were ongoing (range, 5.3+ to 25.8+ months) at the time of data lock. ORR was 28% (nine of 32) in patients with any degree of tumor PD–ligand 1 expression and 14% (two of 14) in patients with no PD–ligand 1 expression. Median PFS was 3.6 months, and the 24-week PFS rate was 41% (95% CI, 27 to 54). Median OS was 19.4 months, and the 1-year and 18-month OS rates were 73% (95% CI, 59 to 83) and 57% (95% CI, 42 to 70), respectively.

Conclusion

First-line nivolumab monotherapy demonstrated a tolerable safety profile and durable responses in first-line advanced NSCLC.
The Thyroid Hormone Inactivating Enzyme Type 3 Deiodinase is Present in Bactericidal Granules and the Cytoplasm of Human Neutrophils
Authors: van der Spek Anne H. , Bloise Flavia F. , Tigchelaar Wikky , Dentice Monica , Salvatore Domenico , van der Wel Nicole N. , Fliers Eric , Boelen Anita
Published: June 2016

Neutrophils are important effector cells of the innate immune system. Thyroid hormone (TH) is thought to play an important role in their function. Intracellular TH levels are regulated by the deiodinating enzymes. The TH-inactivating type 3 deiodinase (D3) is expressed in infiltrating murine neutrophils, and D3 knockout mice show impaired bacterial killing upon infection. This suggests that D3 plays an important role in the bacterial killing capacity of neutrophils. The mechanism behind this effect is unknown. We aimed to assess the presence of D3 in human neutrophils, and determine its subcellular localization using confocal and electron microscopy, because this could give important clues about its function in these cells. D3 appeared to be present in the cytoplasm and in myeloperoxidase containing azurophilic granules and as well as lactoferrin containing specific granules within human neutrophils. This subcellular localization did not change upon activation of the cells. D3 is observed intracellularly during neutrophil extracellular trap formation, followed by a reduction of D3 staining after release of the neutrophil extracellular traps into the extracellular space. At the transcriptional level, human neutrophils expressed additional essential elements of TH metabolism, including TH transporters and TH receptors. Here, we demonstrate the presence and subcellular location of D3 in human neutrophils for the first time and propose a model, in which D3 plays a role in the bacterial killing capacity of neutrophils either through generation of iodide for the myeloperoxidase system or through modulation of intracellular TH bioavailability.
Seminal Plasma Induces Ovulation in Llamas in the Absence of a Copulatory Stimulus: Role of Nerve Growth Factor as an Ovulation-Inducing Factor
Authors: Berland Marco A. , Ulloa-Leal Cesar , Barría Miguel , Wright Hollis , Dissen Gregory A. , Silva Mauricio E. , Ojeda Sergio R. , Ratto Marcelo H.
Published: June 2016

Llamas are considered to be reflex ovulators. However, semen from these animals is reported to be rich in ovulation-inducing factor(s), one of which has been identified as nerve growth factor (NGF). These findings suggest that ovulation in llamas may be elicited by chemical signals contained in semen instead of being mediated by neural signals. The present study examines this notion. Llamas displaying a preovulatory follicle were assigned to four groups: group 1 received an intrauterine infusion (IUI) of PBS; group 2 received an IUI of seminal plasma; group 3 was mated to a male whose urethra had been surgically diverted (urethrostomized male); and group 4 was mated to an intact male. Ovulation (detected by ultrasonography) occurred only in llamas mated to an intact male or given an IUI of seminal plasma and was preceded by a surge in plasma LH levels initiated within an hour after coitus or IUI. In both ovulatory groups, circulating β-NGF levels increased within 15 minutes after treatment, reaching values that were greater and more sustained in llamas mated with an intact male. These results demonstrate that llamas can be induced to ovulate by seminal plasma in the absence of copulation and that copulation alone cannot elicit ovulation in the absence of seminal plasma. In addition, our results implicate β-NGF as an important mediator of seminal plasma-induced ovulation in llamas because ovulation does not occur if β-NGF levels do not increase in the bloodstream, a change that occurs promptly after copulation with an intact male or IUI of seminal plasma.
Glucocorticoids Have Opposing Effects on Liver Fibrosis in Hepatic Stellate and Immune Cells
Authors: Kim Kang Ho , Lee Jae Man , Zhou Ying , Harpavat Sanjiv , Moore David D.
Published: June 2016

Liver fibrosis is a reversible wound-healing process that is protective in the short term, but prolonged fibrotic responses lead to excessive accumulation of extracellular matrix components that suppresses hepatocyte regeneration, resulting in permanent liver damage. Upon liver damage, nonparenchymal cells including immune cells and hepatic stellate cells (HSCs) have crucial roles in the progression and regression of liver fibrosis. Here, we report differential roles of the glucocorticoid receptor (GR), acting in immune cells and HSCs, in liver fibrosis. In the carbon tetrachloride hepatotoxin-induced fibrosis model, both steroidal and nonsteroidal GR ligands suppressed expression of fibrotic genes and decreased extracellular matrix deposition but also inhibited immune cell infiltration and exacerbated liver injury. These counteracting effects of GR ligands were dissociated in mice with conditional GR knockout in immune cells (GRLysM) or HSC (GRhGFAP): the impacts of dexamethasone on immune cell infiltration and liver injury were totally blunted in GRLysM mice, whereas the suppression of fibrotic gene expression was diminished in GRhGFAP mice. The effect of GR activation in HSC was further confirmed in the LX-2 HSC cell line, in which antifibrotic effects were mediated by GR ligand inhibition of Sma and mad-related protein 3 (SMAD3) expression. We conclude that GR has differential roles in immune cells and HSCs to modulate liver injury and liver fibrosis. Specific activation of HSC-GR without alteration of GR activity in immune cells provides a potential therapeutic approach to treatment of hepatic fibrosis.
Targets and Systems of Health Care Cost Control
Authors: White Joseph
Published: June 2016

Discussion of health care cost control policy and politics tends to focus on terms such as “market,” “government,” and “managed care” that are either too general or too value laden to encourage sound analysis. This article proposes an alternative framework for classifying cost control policies. It first distinguishes targets from systems of control. Targets can then be divided into categories of service (e.g., hospital care, pharmaceutical treatment) and components of cost (e.g., price and volume). Systems can be classified in terms of the degree of pooling of finance, ranging from no insurance to a single pool of funds, and how payment of providers is organized, ranging from all payers paying all providers on the same terms to extensive selective contracting among payers and providers. The article analyzes examples of target policy and politics, system policy and politics, and how system choices can influence which targets are targeted how well, so as to show that both policy consequences and political alignments become clearer by using these terms. As one instance, discussions of “managed care” are often confused because the term has two meanings, one referring to target policy and one to system policy.
Effect of Fibrin Glue Injection Into the Cavernous Sinus for Hemostasis During Transcavernous Surgery on the Cerebral Venous Draining System
Authors: Toyooka Terushige , Otani Naoki , Wada Kojiro , Tomiyama Arata , Ueno Hideaki , Fujii Kazuya , Yamamoto Takuji , Nakao Yasuaki , Mori Kentaro
Published: June 2016

BACKGROUND: The extradural temporopolar transcavernous approach can be used to treat central skull base pathologies, but control of bleeding from the opened cavernous sinus is essential. Oxidized cellulose cotton packing and fibrin glue injection can be used, but the effect on the postoperative venous draining pattern remains unclear.

OBJECTIVE: To investigate changes in the venous drainage pattern immediately after transcavernous surgery with and without fibrin glue injection into the bleeding cavernous sinus.

METHODS: A total of 82 patients treated via the transcavernous approach were retrospectively divided into 2 groups based on the hemostasis methods. Both pre- and postoperative angiography and/or 3-dimensional computed tomography venography were available for 24 patients in the cotton packing group and 12 patients in the fibrin glue group.

RESULTS: Postoperative change in the venous draining pattern was observed in 5 of the 24 patients in the cotton packing group and in 3 of the 12 patients in the fibrin glue group. One of the 82 patients showed postoperative brain swelling due to obstruction of the sphenoparietal sinus. The volume of injected fibrin glue ranged from 0.5 to 2.5 mL (mean, 1.1 ± 0.5 mL), but none of the patients had brain swelling.

CONCLUSION: Direct fibrin glue injection into the opened cavernous sinus is relatively safe, but a change in the venous draining pattern occurs in 25% of patients. The study indicates the potential danger of the change in the venous draining pattern and recommends limiting the injection volume of fibrin glue in transcavernous surgery to avoid complications related to venous congestion.