bluuebunny/crossref_metadata_2025 huggingface dataset:
The Current Status of the Pathology of Prostate Cancer
Authors: Murphy William M.
Published: August 2017

Background

The pathology of prostate cancer in modern day medicine cannot be understood simply in terms of tissue patterns or genetic abnormalities. Efforts to accommodate changes in patient care delivery and reimbursement, combined with an explosion in information, have wrought major changes in pathology.

Methods

The author summarizes the current status of the pathology of prostate cancer in light of these influences. The detection of prostate cancer in needle biopsies, the diagnostic interpretations that tend to confuse clinicians, the prognostic factors in prostate cancer, and the effects of radiotherapy and hormone therapy on prostatic tissue are discussed.

Results

Collegial associations are difficult to maintain when consultants are spatially separated and patients are shuttled between primary care and specialty centers. Economic forces cannot be ignored, regardless of the level of altruism of individual practitioners. A medical environment governed by judgment and wisdom is difficult to maintain when external forces and even patients themselves demand application of the latest information to each case.

Conclusions

Current trends in medicine offer almost as many pitfalls as promises. Information gathering and transfer tend to marginalize anatomic pathologists from patient care. Current pathology is affected by the influences of medicolegal and economic forces.
Trends in Cancer Pain Management
Authors: Lesage Pauline , Portenoy Russell K.
Published: August 2017

Background:

Pain is a prevalent symptom in cancer patients, affecting up to 50% of patients undergoing active cancer treatment and up to 90% of those with advanced disease. Although adequate relief can be achieved in the majority of cancer patients, pain is often treated inadequately in traditional settings.

Methods:

The authors use their experience and that of others to review the evaluation and diagnosis of pain syndromes and the principles of management.

Results:

The World Health Organization and other governmental agencies have recognized the importance of pain management as part of routine cancer care. Conducting a comprehensive assessment, competently providing analgesic drugs, and communicating with the patient and family allow effective management of pain in the cancer patient.

Conclusions:

Several approaches can promote adequate management of cancer pain, such as enhancing clinician knowledge of pain syndromes, improving pain assessment, and updating medical information related to pain and symptom control.
Ethical Issues in End-of-Life Care
Authors: Walker Robert M.
Published: August 2017

Background:

Physicians who treat patients approaching the end of life often face moral, ethical, and legal issues involving shared decision making, futility, the right to refuse medical treatment, euthanasia, and physician-assisted suicide.

Methods:

The author examines cases that involve these issues and also reviews the ethical principles that guide current medical practice. Issues such as end-of-life ethical questions, the right to life-sustaining therapy, medical futility, the distinction between killing and allowing to die, and physician-assisted suicide are discussed.

Results:

The principal problem involves the appropriate use of technology at the end of life. While developments in technology have enhanced our ability to prolong life, issues have also arisen regarding the resulting quality of life, the sometimes marginal benefits to our patients, and the burdens that this technology imposes on patients, families, and society.

Conclusions:

Legal and ethical issues continue to confront patients, courts, and physicians. A better understanding of these issues and an awareness of the availability of effective palliative care will help physicians, patients, and families adequately address the end-of-life issues that are an intrinsic part of medical care.
Nutrients in the Chemoprevention of Prostate Cancer: Current and Future Prospects
Authors: Kumar Nagi B. , Besterman-Dahan Karen
Published: August 2017

Background

External factors such as diet and lifestyle may be important in the etiology of invasive prostate cancer. Specific features of prostate cancer, including high prevalence, long latency, and significant mortality and morbidity, provide the opportunities for chemoprevention.

Methods

The authors examine the experimental and epidemiological data demonstrating the chemopreventive activity, safety, and toxicity of chronic administration of these specific nutrients as chemopreventive agents in prostate cancer.

Results

Several nutrients have been identified as agents that inhibit mutagenesis and hyperproliferation or induce apoptosis or differentiation, which are critical characteristics for chemoprevention. Successful chemopreventive strategies require well-characterized agents, suitable cohorts, and reliable intermediate biomarkers of cancer for evaluating efficacy. Phytoestrogens/isoflavones, vitamins D and E, selenium, and lycopene have been identified as promising nutrients in the role of chemoprevention of prostate cancer.

Conclusions

Clinical studies to evaluate the safety and effectiveness of these agents as future prospects in cancer chemoprevention, both individually and in combination, are warranted.
The Feasibility, Effectiveness, and Process of Change of Mindfulness-Based Cognitive Therapy for Adults With ADHD: A Mixed-Method Pilot Study
Authors: Janssen Lotte , de Vries Alicia M. , Hepark Sevket , Speckens Anne E. M.
Published: August 2017

Objective: Mindfulness-Based Cognitive Therapy (MBCT) is a promising psychosocial intervention for adult ADHD. The feasibility and effectiveness of an adapted MBCT program is explored, together with the possible process of change. Method: Mixed-method study with 31 ADHD patients participating in an adapted MBCT program. Self-report questionnaires on ADHD symptoms, executive functioning, mindfulness skills, self-compassion, patient functioning, and health status were administered before and after MBCT. Semi-structured interviews were conducted with 24 patients. Results: A modest drop-out of n = 5 (16%) was found. MBCT resulted in a significant reduction of ADHD symptoms and improvements of executive functioning, self-compassion, and mental health. Qualitative analysis provided insight in facilitators and barriers participants experienced, and their process of change. Conclusion: The adapted MBCT program seemed to be feasible for adults with ADHD and preliminary evidence for the effectiveness is shown. An adequately powered Randomized Controlled Trial (RCT) is needed to further examine the effectiveness of MBCT for ADHD.
African American Women and Obesity Through the Prism of Race
Authors: Knox-Kazimierczuk Francoise , Geller Karly , Sellers Sherrill , Taliaferro Baszile Denise , Smith-Shockley Meredith
Published: August 2017

Background. There are minimal studies focusing on African American women and obesity, and there are even fewer studies examining obesity through a critical race theoretical framework. African American obesity research has largely focused on individual and community interventions, which have not been sufficient to reverse the obesity epidemic. Purpose. The purpose of this study was to examine the relationship between race and body mass index (BMI) for African American women. Method. Previously collected data from the National Survey of American Life Self-Administered Questionnaire, 2001-2003 (NSAL-SAQ) was analyzed for this study. The NSAL-SAQ dedicated a section to the exploration of group and personal identity, along with having anthropometric data and health habit questions to be able to conduct analyses for associations between the racial identity dimensions and obesity. Results. Multiple linear regression was used to examine the constructs of racial identity on BMI comparing standardized coefficients (β) and R2adj values. Results indicated participants ascribing more to the stereotype of “Blacks giving up easily” (β = 0.527, p = .000) showed an increased BMI. Additionally, the negative stereotype of “Blacks being violent” (β = 0.663, p = .000) and “Blacks being lazy” (β = 0.506, p = .001) was associated with an increased BMI. Conclusions. Based on these finds high negative racial regard is associated with increased weight. This study contributes uniquely to the scientific literature, focusing on the construct of racial identity and obesity in African American women.
Loeffler Endocarditis: A Unique Presentation of Right-Sided Heart Failure Due to Eosinophil-Induced Endomyocardial Fibrosis
Authors: Alam Amit , Thampi Shankar , Saba Shahryar G , Jermyn Rita
Published: August 2017

Loeffler endocarditis is a rare restrictive cardiomyopathy caused by abnormal endomyocardial infiltration of eosinophils, with subsequent tissue damage from degranulation, eventually leading to fibrosis. Although an uncommon entity, it is still a disease with significant morbidity and mortality. Often identified only at late stages, treatment options are limited once fibrosis occurs, usually requiring heart failure medications or surgical intervention. We present a unique case of a woman with remote history of hypereosinophilic syndrome, attributed to treatment of rheumatoid arthritis with infliximab, who presented with symptoms of heart failure refractory to medical management and was found to have Loeffler endocarditis. The severe progression of the disease required surgical intervention with endocardial stripping to treat the right-sided diastolic heart failure.
Thermal comfort in semi-outdoor spaces within an office building in Shenzhen: A case study in a hot climate region of China
Authors: Cao Bin , Luo Maohui , Li Min , Zhu Yingxin
Published: August 2017

In regions with hot climate, most office buildings tend to use mechanical cooling for indoor thermal comfort, which results in high energy consumption throughout the year. In this article, we highlight a case study in an office building in Shenzhen, which is located in the Hot Summer and Warm Winter Zone of China. The building's most distinctive feature is that it makes sufficient use of semi-outdoor spaces, which plays an important role to achieve occupants' comfort, meanwhile contribute to saving energy. Field studies were conducted on an open terrace and in an auditorium with openable walls. Air temperature on the open terrace varied between 28.8℃ and 30.6℃ during working hours on a summer day. Most occupants felt comfortable, although their averaged thermal sensation vote tended to be higher than neutral condition. In the auditorium when it was occupied on an autumn day, air temperature ranged from 26.1℃ to 27.4℃. The averaged thermal sensation vote values in the three sitting areas were −0.5, 0.3, −0.2 respectively, while no less than 70% of people felt thermally comfortable. In both spaces, the sensible airflow had positively impacted on occupants' comfort. The case study has proven the effectiveness of the strategy of using semi-outdoor spaces and could be a grounded example for new building designs in hot regions in China.
Influences of spray angle and bowl center depth on power and exhaust emissions in a dual fuel direct injection engine
Authors: Shojae Kianoosh , Mahdavian Majid
Published: August 2017

Injection strategy and piston bowl geometry play a very effective role in engine design. Hydrogen fuel in liquid or gaseous form is high in energy, and engine that burns pure hydrogen produces almost no exhaust emissions. In this article, influences of spray angle and bowl center depth on engine performance (indicated power and efficiency), fuel economy, and exhaust emissions (CO, CO2, NO, soot, and hydrocarbon) are investigated for a hydrogen (6%) + diesel dual fuel engine under 1500, 2000, and 3000 r/min speeds. Numerical simulation was performed using computational fluid dynamics code. To ensure validity of simulation, calculated in-cylinder mean pressure and rate of heat release were compared to experimental data, and the results specified a good accordance (for 1200 r/min and 70% load). The results of studies show that 160° spray angle is the best to achieve balanced emissions and more power and efficiency in comparison to other spray angles (120°, 130°, 140°, and 180° spray angles). It is found that taking into account the 160° spray angle in comparison to 120° spray angle, indicated power and efficiency increase by 25%, and the amount of exhaust CO, soot, and hydrocarbon reduces approximately by 76%, 71%, and 95%, respectively. It is determined that a deep bowl center depth leads to higher temperature (further NO emissions) and lower brake-specific fuel consumption. Three bowl center depths (5, 10, and 20 mm) were chosen for further investigation, and the 10-mm depth showed a suitable balance between exhaust emissions and power generated.
Self-organizing moral systems
Authors: Gaus Gerald
Published: August 2017

This essay examines two different modes of reasoning about justice: an individual mode in which each individual judges what we all ought to do and a social mode in which we seek to reconcile our judgments of justice so that we can share common rules of justice. Social contract theory has traditionally emphasized the second, reconciliation mode, devising a central plan (the contract) to do so. However, I argue that because we disagree not only in our judgments of justice but also about the degree of reconciliation justice calls for, the social contract presupposes a single, controversial, answer to the proper degree of reconciliation. In place of the social contract’s ‘top-down’ approach, this article explores the idea of self-organizing moral systems, in which each individual, acting on her own views of justice (including the importance of reconciliation), responds to the decisions of others, forming systems of shared justice. Several basic agent-based models are explored to begin to understand the dynamics under which individuals with diverse views of justice may come to share common rules. It is found that, surprisingly, by increasing the diversity in a system, we can sometimes increase the possibility of agreement.
Complex Thinking as a Result of Incongruent Information Exposure
Authors: Erisen Cengiz , Redlawsk David P. , Erisen Elif
Published: August 2017

In this article, we explore whether incongruent information influences what people recall to mind about a presidential candidate’s policy statements. We investigate whether the volume of people’s political thoughts, their ability to produce arguments, the affective valence of these thoughts, and their integrative complexity are influenced by the congruency between new political information and prior political convictions. We conducted an experiment via MTurk manipulating the congruency of information with respect to ideology. Our results show that incongruency significantly alters how people think about politics. Incongruent information increases integrative complexity of the opposing thoughts, becomes more voluminous, and includes more rationales. Moreover, these defensive thoughts are significantly more negative and less positive about the incongruent information. Parallel to what studies on motivated reasoning demonstrated, we also find that politically knowledgeable people in particular seem to strengthen their thoughts’ cognitive structure while defending their priors against information counter to their political views. We further discuss the general effects of these results and the importance of challenges to existing beliefs in generating complex thought systems.
Arthroscopic debridement for primary elbow osteoarthritis with and without capsulectomy: a comparative cohort study
Authors: Isa Ahaoiza D , Athwal George S , King Graham J W , MacDermid Joy C , Faber Kenneth J
Published: August 2017

Background

Arthroscopic elbow debridement for primary osteoarthritis may be performed with or without a joint capsulectomy. The purpose of this comparative cohort study was to compare range of motion (ROM) and early complications between patients with and without anterior capsulectomy.

Methods

In total, 110 patients with primary osteoarthritis of the elbow who underwent an arthroscopic debridement for primary osteoarthritis were reviewed with a minimum of 3 months postoperative follow-up. The first group consisted of 51 patients who had a concomitant capsulectomy and the second group consisted of 59 patients who either had a capsulotomy or did not have the capsule addressed.

Results

There was significantly greater pre-operative stiffness in the group who had an anterior capsulectomy versus those who did not. A greater improvement in arc of ROM occurred in patients who had a concomitant capsulectomy compared to patients without (24° versus 12°) (p < 0.003); however, there were no significant differences in final ROM between groups. There were no statistically significant differences in the incidence of complications between the groups (16% capsulectomy versus 18% no capsulectomy).

Conclusions

Elbow arthroscopy and debridement for primary elbow osteoarthritis yields satisfactory motion at short-term follow-up with or without a capsulectomy. The incidence of early complications was low at this tertiary referral centre, with no significant differences between groups.
The Food–Energy–Water Nexus: A Framework to Address Sustainable Development in the Tropics
Authors: Wallington Kevin , Cai Ximing
Published: August 2017

Interactions between agriculture, energy, and tropical environments occur within a larger, interconnected food–energy–water (FEW) system context. These interactions both affect and are shaped by the FEW nexus (connected FEW natural processes, engineering and infrastructure, and institutions and governance), motivating the collective inclusion of many processes and institutions in the discussion of any individual member. Moreover, the important role of the tropics in the global environment and global food security raises the stakes of management, providing further impetus for a thorough, FEW nexus approach. We herein discuss FEW issues which are key to proper FEW nexus management in the tropics, including fundamental earth system processes, agricultural expansion and deforestation, the potential benefits and drawbacks of hydropower development, and technology and policy advancements.
Targeting Sustainable Intensification of Maize-Based Agriculture in East Africa
Authors: Palm Cheryl , Neill Christopher , Lefebvre Paul , Tully Katherine
Published: August 2017

Agricultural intensification in Sub-Saharan Africa has the chance to increase yields and food security while minimizing environmental contamination and protecting remaining native ecosystems. Targeting intensification to areas of high production potential including clayey, deep tropical soils on gently sloping lands will reduce leaching and runoff of nitrogen into water bodies. This holds particularly for rates of nitrogen fertilizer applications of less than 150 N ha−1 yr−1 rates at which nitrous oxide emissions also remain low. Overlays of maps of maize production potential, soil properties, and topography for East Africa indicate almost half of that area has high production potential and a third of that is on favorable soils. More than 70% of this area identified for targeting is already in cropland, thus reducing the need to clear additional native ecosystems. Targeting intensification must also include factors such as climate and seasonality. Incorporating results from field studies of agricultural impacts, assessing these impacts at larger scales, and developing planning maps with national partners and other stakeholders are key steps toward promoting increased crop production while minimizing environmental consequences.
Response assemblages and their socioecological fit
Authors: Briassoulis Helen
Published: August 2017

Safeguarding the integrity of critical ecological functions that secure the continuous provision of ecosystem services requires the assessment of the effectiveness of human responses to environmental degradation. Narrowly defined response options, for example, isolated actions targeting the resources impacted or the drivers and proximate causes of environmental degradation, together with attention to ‘best practices’ and ‘proper policies’, may not align with empirical evidence and scientific developments, demonstrating that human responses are contextual and contingent. Embracing a nonreductionist ontology, this article proposes that the ‘response assemblage’ is a suitable analytic to represent ‘responses-in-context’. It redefines the effectiveness of human responses to environmental degradation as the ‘socioecological fit of the response assemblage’. Response assemblages (RAs) are geographically and historically unique, provisional wholes emerging from processes of assembling heterogeneous biophysical and human components of a sociospatial hierarchy into purposeful, place- and time-specific associations that are shaped by and shape human responses. Their socioecological fit (SEFRA) concerns the degree to which the match among all components furthers the maintenance of socioecological resilience. After reviewing the pertinent literature, the RA and its SEFRA are detailed by synthesizing assemblage theory and the ‘problem of fit’ literature within a Complex Adaptive system and Resilience perspective. Their implications for theorizing human responses and their effectiveness, developing integrated methodologies, guiding decision and policy making, as well as for future research, are discussed in conclusion.
Law for ethnographers
Authors: Elliott Tracey , Fleetwood Jennifer
Published: August 2017

Despite a long history of ethnographic research on crime, ethnographers have shied away from examining the law as it relates to being present at, witnessing and recording illegal activity. However, knowledge of the law is an essential tool for researchers and the future of ethnographic research on crime. This article reviews the main relevant legal statutes in England and Wales and considers their relevance for contemporary ethnographic research. We report that researchers have no legal responsibility to report criminal activity (with some exceptions). The circumstances under which legal action could be taken to seize research data are specific and limited, and respondent’s privacy is subject to considerable legal protection. Our review gives considerable reason to be optimistic about the future of ethnographic research.
Challenges and Change: Integrating Grammar Teaching With Communicative Work in Senior High School EFL Classes
Authors: Underwood Paul R.
Published: August 2017

This article reports a multiple case study that explores the potential impact of Japan’s national curriculum for senior high school English as a foreign language (EFL), specifically in relation to the integration of grammar teaching with communicative work, a key component of the curriculum and an area globally underresearched in high schools. The beliefs and practices of four Japanese EFL teachers from different public and private high schools were investigated over a 16-month period. Quantitative data were collected from four classroom observations, while qualitative data were gathered through a preliminary beliefs questionnaire, 10 teacher journals, and postobservation and semistructured interviews. Extending the EFL literature to date, this article draws on the theory of planned behavior as an analytical framework to reveal a complex interrelationship between the various attitudinal, social, and contextual factors that would both obstruct and facilitate teachers’ integration of grammar teaching with communicative work. Importantly, the findings also bring to light a number of concrete ways in which some teachers manage severe social and other contextual pressures to successfully achieve integration, despite the influence of university entrance examinations that emphasize reading.
The Green Manufacturer’s Compliance With Green Criteria Throughout the Life Cycle of Building Material
Authors: Ishak Nuril Izzeaty , Mustafa Kamal Ernawati , Yusof Nor’Aini
Published: August 2017

The construction industry has significant impacts on the environment. Abound the efforts to induce a greater green implementation in the construction project, it has been argued that the usage of green building materials in construction projects can help to minimize the production of waste and greenhouse gas (GHG) emission. This article’s objective is to identify the degree of compliance with the green building materials criteria by wood and cement manufacturers. The green building materials criteria were conceptualized as part of the sustainability movement in which the term green is used to refer to a clean environment and unpolluted atmosphere. To verify the compliance of the manufacturers through the green building materials criteria, a questionnaire survey supported by an interview was conducted. The results show that most Malaysian green manufacturers complied with the green criteria, which converged all three principles including environmental impact, resource management, and recycling implementation. This article provides a basis upon which existing and new manufacturers can produce green building materials thoroughly in accordance with the listed criteria. Clearly, the manufacturers’ compliance with the green building materials criteria has several impacts on the development of the construction industry such that a green building material production process will stimulate a balanced ecosystem and prevent an environmental catastrophe.
The Historical Development of the “Sunnah” Reform Ideology in the State of Perlis, Malaysia
Authors: Malik Maszlee , Mat Hamidah
Published: August 2017

Since the arrival of Islam in Tanah Melayu or Malaya, traditionalist scholars have dominated the Islamic discourse through their close relations with the rulers (Sultans). Their domination over the religious authorities and the Islamic educational institutions has shaped the state version of Islam in Malaysia. However, in Perlis, the northernmost state in Malaysia, Middle Eastern graduate reformists, also known as Kaum Muda, were already preaching the earliest version of Salafism in the early 20th century. They found political patronage from the rulers of the state, hence imposing their version of Islamic teachings as the prevailing Islamic discourse of the state, which is also known until today as the “ Sunnah Perlis” teachings. The widely presumptuous masses and researchers point that the dominating influence of the reform agenda or “ Sunnah” in the state of Perlis is due to the state authority’s patronage based on historical facts that the “ Sunnah” itself first emerged in Perlis in the early 20th century with the blessings of the ruler. This article attempts to look at the historical development of the “ Sunnah Perlis” and to scrutinize the state authority’s patronage and influence in the state of Perlis. To achieve this, it employs a historical method of study to look at important milestones in the historical account of the Sunnah reform agenda in Perlis and its development at different periods hitherto through literatures, reports, interviews, and focus group discussions.
Comparison Between S2-Alar-Iliac Screw Fixation and Iliac Screw Fixation in Adult Deformity Surgery: Reoperation Rates and Spinopelvic Parameters
Authors: Ishida Wataru , Elder Benjamin D. , Holmes Christina , Lo Sheng-Fu L. , Goodwin C. Rory , Kosztowski Thomas A. , Bydon Ali , Gokaslan Ziya L. , Wolinsky Jean-Paul , Sciubba Daniel M. , Witham Timothy F.
Published: August 2017

Study Design:

Retrospective cohort study.

Objective:

The S2-alar-iliac (S2AI) technique has been described as an alternative method for pelvic fixation in place of iliac screws (ISs) in spinal deformity surgery. The objective of this study was to analyze the impact of S2AI screws on radiographical outcomes, including spinopelvic parameters.

Methods:

A retrospective review of 17 patients receiving ISs and 46 patients receiving S2AI screws for correction of adult spinal deformity between 2010 and 2015 with minimum 1-year follow-up was conducted. Patient data on postoperative complications, including reoperation rates and proximal junctional kyphosis (PJK), and radiographical parameters was collected and statistically analyzed.

Results:

With mean follow-up of 21.1 months, the overall reoperation rate was significantly lower in the S2AI group than in the IS group (21.7% vs 58.8%, P = .01), but the incidence of PJK was similar (32.6% vs 35.3%, P > .99). Moreover, the time to reoperation in the IS group was significantly shorter than in the S2AI group ( P = .001), and the S2AI group trended toward a longer time to reoperation due to PJK ( P = .08). There was a significantly higher change in pelvic incidence (PI) in the S2AI group (−6.0°) compared with the IS group ( P = .001).

Conclusions:

Compared with the IS technique, the S2AI technique demonstrated a lower rate of overall reoperation, a similar rate of PJK, longer time to reoperation, and possible reduction in PI. Future studies may be warranted to clarify the mechanism of these results and how they can be translated into improved patient care.
Gap healing after medial open-wedge high tibial osteotomy using injectable beta-tricalcium phosphate
Authors: Choi Won Chul , Kim Banghyun , Kim Uk , Lee Yohan , Kim Jae-Hwa
Published: August 2017

Purpose:

The study aim was to evaluate gap healing after medial open-wedge high tibial osteotomy (MOWHTO) using novel injectable beta-tricalcium phosphate (β-TCP) as gap filler. We also aimed to evaluate radiographic and clinical outcome of MOWHTO using injectable β-TCP.

Methods:

Consecutive 28 patients underwent MOWHTO using anatomical locking plate fixation, and β-TCP was injected as gap filler. Serial radiographs and computed tomography were taken at postoperative 3 and 12 months, and gap healing was assessed. Lower extremity alignment was measured on radiographs, and clinical outcome was evaluated by determining International Knee Documentation Committee, Western Ontario and McMaster Universities Arthritis Index, and visual analogue scales for pain scores.

Results:

Progress of bone union was found on plain radiographs, and the mean ratio (β-TCP/host bone) of computed tomography attenuation values significantly changed from postoperative 3 months to 12 months, which indicates maturation of β-TCP. The average mechanical femoro-tibial angle changed from 4.1° varus (preoperative) to 4.8° valgus (3 months) and maintained until 12 months (4.3° valgus). All clinical outcome scores were significantly improved and no significant complication occurred.

Conclusion:

Using injectable β-TCP as gap filler for MOWHTO resulted in satisfactory gap healing without complication. Radiographic and clinical results were satisfactory. The injectable β-TCP can be a safe and effective option for gap filling after MOWHTO.
Comparative Effectiveness of Tumor Response Assessment Methods: Standard of Care Versus Computer-Assisted Response Evaluation
Authors: Allen Brian C. , Florez Edward , Sirous Reza , Lirette Seth T. , Griswold Michael , Remer Erick M. , Wang Zhen J. , Bieszczad Jacob E. , Cox Kelly L. , Goenka Ajit H. , Howard-Claudio Candace M. , Kang Hyunseon C. , Nandwana Sadhna B. , Sanyal Rupan , Shinagare Atul B. , Henegan J. Clark , Storrs Judd , Davenport Matthew S. , Ganeshan Balaji , Vasanji Amit , Rini Brian , Smith Andrew D.
Published: August 2017

Purpose

To compare the effectiveness of metastatic tumor response evaluation with computed tomography using computer-assisted versus manual methods.

Materials and Methods

In this institutional review board–approved, Health Insurance Portability and Accountability Act–compliant retrospective study, 11 readers from 10 different institutions independently categorized tumor response according to three different therapeutic response criteria by using paired baseline and initial post-therapy computed tomography studies from 20 randomly selected patients with metastatic renal cell carcinoma who were treated with sunitinib as part of a completed phase III multi-institutional study. Images were evaluated with a manual tumor response evaluation method (standard of care) and with computer-assisted response evaluation (CARE) that included stepwise guidance, interactive error identification and correction methods, automated tumor metric extraction, calculations, response categorization, and data and image archiving. A crossover design, patient randomization, and 2-week washout period were used to reduce recall bias. Comparative effectiveness metrics included error rate and mean patient evaluation time.

Results

The standard-of-care method, on average, was associated with one or more errors in 30.5% (6.1 of 20) of patients, whereas CARE had a 0.0% (0.0 of 20) error rate ( P < .001). The most common errors were related to data transfer and arithmetic calculation. In patients with errors, the median number of error types was 1 (range, 1 to 3). Mean patient evaluation time with CARE was twice as fast as the standard-of-care method (6.4 minutes v 13.1 minutes; P < .001).

Conclusion

CARE reduced errors and time of evaluation, which indicated better overall effectiveness than manual tumor response evaluation methods that are the current standard of care.
Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography After Concurrent Chemoradiotherapy in Locally Advanced Head-and-Neck Squamous Cell Cancer: The ECLYPS Study
Authors: Van den Wyngaert Tim , Helsen Nils , Carp Laurens , Hakim Sara , Martens Michel J. , Hutsebaut Isabel , Debruyne Philip R. , Maes Annelies L.M. , van Dinther Joost , Van Laer Carl G. , Hoekstra Otto S. , De Bree Remco , Meersschout Sabine A.E. , Lenssen Olivier , Vermorken Jan B. , Van den Weyngaert Danielle , Stroobants Sigrid ,   on behalf of the ECLYPS investigators
Published: August 2017

Purpose

To assess the standardized implementation and reporting of surveillance [18F]fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) scan of the neck in locoregionally advanced head-and-neck squamous cell carcinoma (LAHNSCC) after concurrent chemoradiotherapy (CCRT).

Patients and Methods

We performed a prospective multicenter study of FDG-PET/CT scanning 12 weeks after CCRT in newly diagnosed patients with LAHNSCC (stage IVa/b) that used standardized reconstruction and Hopkins reporting criteria. The reference standard was histology or > 12 months of clinical follow-up. The primary outcome measure was the negative predictive value (NPV) of FDG-PET/CT scans and other supporting diagnostic test characteristics, including time dependency with increasing follow-up time.

Results

Of 152 patients, 125 had adequate primary tumor control after CCRT and entered follow-up (median, 20.4 months). Twenty-three (18.4%) had residual neck disease. Overall, NPV was 92.1% (95% CI, 86.9% to 95.3%; null hypothesis: NPV = 85%; P = .012) with sensitivity of 65.2% (95% CI, 44.9% to 81.2%), specificity of 91.2% (95% CI, 84.1% to 95.3%), positive predictive value of 62.5% (95% CI, 45.5% to 76.9%), and accuracy of 86.4% (95% CI, 79.3% to 91.3%). Sensitivity was time dependent and high for residual disease manifesting up to 9 months after imaging but lower (59.7%) for disease detected up to 12 months after imaging. Standardized reporting criteria reduced the number of equivocal reports (95% CI for the difference, 2.6% to 15.0%; P = .003). Test characteristics were not improved with the addition of lymph node CT morphology criteria.

Conclusion

FDG-PET/CT surveillance using Hopkins criteria 12 weeks after CCRT is reliable in LAHNSCC except for late manifesting residual disease, which may require an additional surveillance scan at 1 year after CCRT to be detected.
Paravertebral Block Does Not Reduce Cancer Recurrence, but Is Related to Higher Overall Survival in Lung Cancer Surgery: A Retrospective Cohort Study
Authors: Lee Eun Kyung , Ahn Hyun Joo , Zo Jae Ill , Kim Kyunga , Jung Dae Myung , Park Joo Hyun
Published: August 2017

BACKGROUND:

Postoperative analgesic methods are suggested to have an impact on long-term prognosis after cancer surgery through opioid-induced immune suppression. We hypothesized that regional analgesia that reduces the systemic opioid requirement would be related to lower cancer recurrence and higher overall survival compared to intravenous patient-controlled analgesia (PCA) for lung cancer surgery.

METHODS:

Records for all patients who underwent open thoracotomy for curative resection of primary lung cancer between 2009 and 2013 in a tertiary care hospital were retrospectively analyzed. Patients were divided by postoperative analgesic methods: PCA (n = 574), thoracic epidural analgesia (TEA, n = 619), or paravertebral block (PVB, n = 536). Overall and recurrence-free survivals were compared among 3 analgesic methods via a multivariable Cox proportional hazard model and a log-rank test after adjusting confounding factors using propensity score matching (PSM).

RESULTS:

Analgesic method was associated with overall survival (P= .0015; hazard ratio against TEA [95% confidence intervals]: 0.58 [0.39–0.87] for PCA, 0.60 [0.45–0.79] for PVB). After confounder adjustment using PSM, PVB showed higher overall survival than PCA (log-rank P= .0229) and TEA (log-rank P= .0063) while PCA and TEA showed no difference (log-rank P= .6). Hazard ratio for PVB was 0.66 [0.46–0.94] against PCA and 0.65 [0.48–0.89] against TEA after PSM. However, there was no significant association between the analgesic methods and recurrence-free survival (P= .5; log-rank P with PSM = .5 between PCA and TEA, .5 between PCA and PVB, .1 between TEA and PVB).

CONCLUSIONS:

Pain-control methods are not related to cancer recurrence. However, PVB may have a beneficial effect on overall survival of patients with lung cancer.
A Comparison of Three Frailty Indices in Predicting Morbidity and Mortality After On-Pump Aortic Valve Replacement
Authors: Esses Gary , Andreopoulos Evie , Lin Hung-Mo , Arya Shipra , Deiner Stacie
Published: August 2017

BACKGROUND:

Aortic valve replacement is a high-risk surgery (3%–5%, 30-day mortality) performed on approximately 30,000 elderly patients a year in the United States. Currently, preoperative risk assessment is based on a composite of medical examination and a subjective evaluation for frailty (“eyeball test”). Objective frailty assessment using validated indices has the potential to improve risk stratification. The purpose of this study was to (1) establish whether frailty can predict 30-day mortality and composite morbidity in patients undergoing aortic valve replacement and (2) compare the predictive ability of 3 frailty indices in this population.

METHODS:

This study was a retrospective cohort study of 3088 patients 65 years old and older undergoing aortic valve replacement surgery (based on current procedure terminology codes) between the years 2006 and 2012 extracted from the American College of Surgeons National Surgical Quality Improvement Program database. Frailty was assessed using the modified frailty index, risk analysis index, and Ganapathi indices. Outcomes measured were 30-day mortality and composite morbidity (myocardial infarction, cardiac arrest, pulmonary embolism, pneumonia, reintubation, renal insufficiency, coma >24 hours, urinary tract infections, sepsis, deep vein thrombosis, deep wound surgical site infection, superficial site infection, and reoperation).

RESULTS:

Frailty was a better predictor of mortality than morbidity, and it was not markedly different among any of the 3 indices. Frailty was associated with an increased risk of 30-day mortality and longer lengths of stay.

CONCLUSIONS:

Frailty can predict mortality in patients undergoing aortic valve replacement. Choice of frailty index does not make a difference in this patient population.
Association of FK506 binding proteins with RyR channels – effect of CLIC2 binding on sub-conductance opening and FKBP binding
Authors: Richardson Spencer J. , Steele Gregory A. , Gallant Esther M. , Lam Alexander , Schwartz Charles E. , Board Philip G. , Casarotto Marco G. , Beard Nicole A. , Dulhunty Angela F.
Published: August 2017

Ryanodine receptor (RyR) Ca2+ channels are central to striated muscle function and influence signalling in neurons and other cell types. Beneficially low RyR activity and maximum conductance opening may be stabilised when RyRs bind to FK506 binding proteins (FKBPs) and destabilised by FKBP dissociation, with submaximal opening during RyR hyperactivity associated with myopathies and neurological disorders. However, the correlation with submaximal opening is debated and quantitative evidence is lacking. Here, we have measured altered FKBP binding to RyRs and submaximal activity with addition of wild-type (WT) CLIC2, an inhibitory RyR ligand, or its H101Q mutant that hyperactivates RyRs, which probably causes cardiac and intellectual abnormalities. The proportion of sub-conductance opening increases with WT and H101Q CLIC2 and is correlated with reduced FKBP–RyR association. The sub-conductance opening reduces RyR currents in the presence of WT CLIC2. In contrast, sub-conductance openings contribute to excess RyR ‘leak’ with H101Q CLIC2. There are significant FKBP and RyR isoform-specific actions of CLIC2, rapamycin and FK506 on FKBP–RyR association. The results show that FKBPs do influence RyR gating and would contribute to excess Ca2+ release in this CLIC2 RyR channelopathy.
Rib kinematics during lung ventilation in the American alligator (Alligator mississippiensis): an XROMM analysis
Authors: Brocklehurst Robert J. , Moritz Sabine , Codd Jonathan , Sellers William I. , Brainerd Elizabeth L.
Published: August 2017

The current hypothesis regarding the mechanics of breathing in crocodylians is that the double-headed ribs, with both a capitulum and tuberculum, rotate about a constrained axis passing through the two articulations; moreover, this axis shifts in the caudal thoracic ribs, as the vertebral parapophysis moves from the centrum to the transverse process. Additionally, the ventral ribcage in crocodylians is thought to possess additional degrees of freedom through mobile intermediate ribs. In this study, X-ray reconstruction of moving morphology (XROMM) was used to quantify rib rotation during breathing in American alligators. Whilst costovertebral joint anatomy predicted overall patterns of motion across the ribcage (decreased bucket handle motion and increased calliper motion), there were significant deviations: anatomical axes overestimated pump handle motion and, generally, ribs in vivo rotate about all three body axes more equally than predicted. The intermediate ribs are mobile, with a high degree of rotation measured about the dorsal intracostal joints, especially in the more caudal ribs. Motion of the sternal ribs became increasingly complex caudally, owing to a combination of the movements of the vertebral and intermediate segments. As the crocodylian ribcage is sometimes used as a model for the ancestral archosaur, these results have important implications for how rib motion is reconstructed in fossil taxa, and illustrate the difficulties in reconstructing rib movement based on osteology alone.
Rapid expansion of pigmentation genes in penaeid shrimp with absolute preservation of function
Authors: Budd Alyssa M. , Hinton Tracey M. , Tonks Mark , Cheers Sue , Wade Nicholas M.
Published: August 2017

Crustaceans form their distinct patterns and colors through the interaction of the carotenoid astaxanthin with a protein called crustacyanin (CRCN). Presently, the expression of just two CRCN genes is thought to provide the protein subunits that combine to form the crustacyanin complex and associated carotenoid colour change from red to blue. This study aimed to explore the genetic complexity underlying the production of pigmentation and camouflage in penaeid shrimp. We isolated 35 new CRCN genes from 12 species, and their sequence analysis indicated that this gene family has undergone significant expansion and diversification in this lineage. Despite this duplication and sequence divergence, the structure of the CRCN proteins and their functional role in shrimp colour production has been strictly conserved. Using CRCN isoforms from Penaeus monodon (Fabricius, 1798) as an example, we showed that isoforms were differentially expressed, and that subtle phenotypes were produced by the specific down regulation of individual isoforms. These findings demonstrate that our knowledge of the molecular basis of pigmentation in shrimp was overly simplistic, and suggests that multiple copies of the CRCN genes within species may be advantageous for colour production. This result is of interest for the origin and evolution of pigmentation in crustaceans, and the mechanisms by which gene function is maintained, diversified or sub-functionalized.
Transcription elongation rate has a tissue-specific impact on alternative cleavage and polyadenylation in Drosophila melanogaster
Authors: Liu Xiaochuan , Freitas Jaime , Zheng Dinghai , Oliveira Marta S. , Hoque Mainul , Martins Torcato , Henriques Telmo , Tian Bin , Moreira Alexandra
Published: August 2017

Alternative polyadenylation (APA) is a mechanism that generates multiple mRNA isoforms with different 3′UTRs and/or coding sequences from a single gene. Here, using 3′ region extraction and deep sequencing (3′READS), we have systematically mapped cleavage and polyadenylation sites (PASs) in Drosophila melanogaster, expanding the total repertoire of PASs previously identified for the species, especially those located in A-rich genomic sequences. Cis-element analysis revealed distinct sequence motifs around fly PASs when compared to mammalian ones, including the greater enrichment of upstream UAUA elements and the less prominent presence of downstream UGUG elements. We found that over 75% of mRNA genes in Drosophila melanogaster undergo APA. The head tissue tends to use distal PASs when compared to the body, leading to preferential expression of APA isoforms with long 3′UTRs as well as with distal terminal exons. The distance between the APA sites and intron location of PAS are important parameters for APA difference between body and head, suggesting distinct PAS selection contexts. APA analysis of the RpII215C4 mutant strain, which harbors a mutant RNA polymerase II (RNAPII) with a slower elongation rate, revealed that a 50% decrease in transcriptional elongation rate leads to a mild trend of more usage of proximal, weaker PASs, both in 3′UTRs and in introns, consistent with the “first come, first served” model of APA regulation. However, this trend was not observed in the head, suggesting a different regulatory context in neuronal cells. Together, our data expand the PAS collection for Drosophila melanogaster and reveal a tissue-specific effect of APA regulation by RNAPII elongation rate.