bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Chemotherapy and Targeted Therapy in Early-Stage Non–Small Cell Lung Cancer
Authors: Gadgeel Shirish M.
Published: October 2018

On the basis of several randomized trials and meta-analyses, adjuvant chemotherapy is the accepted standard of care for certain patients with early-stage non–small cell lung cancer (NSCLC). Patients with stage II, IIIA, or large (≥ 4 cm) IB tumors are candidates for adjuvant chemotherapy. The survival improvement with adjuvant chemotherapy is approximately 5% at 5 years, though certain trials have suggested that it can be 8% to 10%. Neoadjuvant chemotherapy also has shown a survival advantage, though the volume of data with this approach is far less than that of adjuvant chemotherapy. The combination of cisplatin and vinorelbine is the most well-studied regimen, but current consensus is to use four cycles of any of the platinum-based chemotherapy regimens commonly used as front-line therapy for patients with advanced-stage NSCLC. Trials to define biomarkers that can predict benefit from adjuvant chemotherapy have not been successful, but results of other such trials are still awaited. On the basis of the benefit observed with targeted agents in patients with advanced-stage disease and driver genetic alterations in their tumors, ongoing trials are evaluating the utility of these targeted agents as adjuvant therapy. Similarly, clinical benefit observed with checkpoint inhibitors has prompted assessment of these drugs in patients with early-stage NSCLC. It is very likely, in the future, that factors other than the anatomy of the tumor will be used to select patients with early-stage NSCLC for systemic therapy and that the choice of systemic therapy will extend beyond platinum-based chemotherapy.
Gastric Cancer in Asia: Unique Features and Management
Authors: Irino Tomoyuki , Takeuchi Hiroya , Terashima Masanori , Wakai Toshifumi , Kitagawa Yuko
Published: October 2018

Gastric cancer (GC) poses a burden to patients across the globe as the third leading cause of cancer deaths worldwide. Incidence of GC is particularly high in Asian countries, which is attributed to the prevalence of Helicobacter pylori (H. pylori) infection and has prompted the establishment of unique treatment strategies. D2 gastrectomy, which was established in the 1950s in Japan, has served as a gold standard for locally advanced GC for over half a century. Since the beginning of the 21st century, endoscopic resection (ER) techniques and minimally invasive laparoscopic surgery have greatly changed the treatment of patients with early GC. S-1, which showed a striking survival benefit in a large randomized trial in Japan, has been used as adjuvant therapy for the last decade. Likewise, S-1–based chemotherapy regimens are currently the standard of care for the treatment of unresectable/metastatic GC in Asia. Along with the development of standardized therapy, novel techniques and new drugs have been rapidly brought into clinical practice. State-of-the-art sentinel node (SN) navigation surgery enables clinicians to perform truly minimally invasive surgery for early GC, and appropriate chemotherapy regimens are now determined by a tumor’s molecular expression. New classifications based on gene signatures are proposed and may replace conventional clinical classifications. Such highly individualized treatment has the potential to alter our clinical practice in GC in the near future. The best practice in each geographic region should be shared and integrated, resulting in the best practice without borders.
Biomarker Testing for Personalized Therapy in Lung Cancer in Low- and Middle-Income Countries
Authors: Hirsch Fred R. , Zaric Bojan , Rabea Ahmed , Thongprasert Sumitra , Lertprasertsuke Nirush , Dalurzo Mercedes Liliana , Varella-Garcia Marileila
Published: October 2018

There have been many important advances in personalized therapy for patients with lung cancer, particularly for those with advanced disease. Molecular testing is crucial for implementation of personalized therapy. Although the United States and many Western countries have come far in the implementation of personalized therapy for lung cancer, there are substantial challenges for low- and middle-income countries (LMICs). Globally, the LMICs display great heterogeneity in the pattern of implementation of molecular testing and targeted therapy. The current review presents an attempt to identify the challenges and obstacles for the implementation of molecular testing and the use of targeted therapies in these areas. Lack of infrastructure, lack of technical expertise, economic factors, and lack of access to new drugs are among the substantial barriers.
Breast Cancer in the Central Nervous System: Multidisciplinary Considerations and Management
Authors: Lin Nancy U. , Gaspar Laurie E. , Soffietti Riccardo
Published: October 2018

Breast cancer is the second most common primary tumor associated with central nervous system (CNS) metastases. Patients with metastatic HER2-positive or triple-negative (estrogen receptor (ER)–negative, progesterone receptor (PR)–negative, HER2-negative) breast cancer are at the highest risk of developing parenchymal brain metastases. Leptomeningeal disease is less frequent but is distributed across breast cancer subtypes, including lobular breast cancer. Initial treatment strategies can include surgery, radiation, intravenous or intrathecal chemotherapy, and/or targeted approaches. In this article, we review the epidemiology of breast cancer brain metastases, differences in clinical behavior and natural history by tumor subtype, and important considerations in the multidisciplinary treatment of these patients. We will highlight new findings that impact current standards of care, clinical controversies, and notable investigational approaches in clinical testing.
Optimizing Breast Cancer Adjuvant Radiation and Integration of Breast and Reconstructive Surgery
Authors: Kuerer Henry M. , Cordeiro Peter G. , Mutter Robert W.
Published: October 2018

Postmastectomy radiotherapy (PMRT) reduces the risk of locoregional and distant recurrence and improves overall survival in women with lymph node–positive breast cancer. Because of stage migration and improvements in systemic therapy and other aspects of breast cancer care, the absolute benefit of PMRT and regional nodal irradiation may be small in some favorable subsets of patients with very low nodal burden, and newer consensus guidelines do not mandate PMRT in all node-positive cases. The use and need for PMRT may considerably complicate breast reconstruction after mastectomy and therefore mandates multidisciplinary input that takes into account patient choice given potential risk of acute and long-term toxicities, benefits, life expectancy, the biology of the tumor, plans for systemic therapy, and actual tumor burden. Management of axillary lymph node metastases is changing with selective use of axillary lymph node dissection for advanced disease, sentinel lymph node biopsy alone for clinically and pathologic node-negative cases receiving mastectomy, and targeted axillary dissection alone among patients with eradication of initial biopsy-proven nodal metastases with neoadjuvant systemic therapy use. In general, when the need for PMRT is anticipated, autologous reconstruction should be delayed. This comprehensive article reviews the current indications and implications regarding integration of breast cancer surgery and timing of reconstruction with optimum radiation delivery to achieve the best possible patient outcomes.
New Insight Into the Biology, Risk Stratification, and Targeted Treatment of Myelodysplastic Syndromes
Authors: Haider Mintallah , Duncavage Eric J. , Afaneh Khalid F. , Bejar Rafael , List Alan F.
Published: October 2018

In myelodysplastic syndromes (MDS), somatic mutations occur in five major categories: RNA splicing, DNA methylation, activated cell signaling, myeloid transcription factors, and chromatin modifiers. Although many MDS cases harbor more than one somatic mutation, in general, there is mutual exclusivity of mutated genes within a class. In addition to the prognostic significance of individual somatic mutations, more somatic mutations in MDS have been associated with poor prognosis. Prognostic assessment remains a critical component of the personalization of care for patient with MDS because treatment is highly risk adapted. Multiple methods for risk stratification are available with the revised International Prognostic Scoring System (IPSS-R), currently considered the gold standard. Increasing access to myeloid gene panels and greater evidence for the diagnostic and predictive value of somatic mutations will soon make sequencing part of the standard evaluation of patients with MDS. In the absence of formal guidelines for their prognostic use, well-validated mutations can still refine estimates of risk made with the IPSS-R. Not only are somatic gene mutations advantageous in understanding the biology of MDS and prognosis, they also offer potential as biomarkers and targets for the treatment of patients with MDS. Examples include deletion 5q, spliceosome complex gene mutations, and TP53 mutations.
Improving Cancer Care Through the Patient Experience: How to Use Patient-Reported Outcomes in Clinical Practice
Authors: Mooney Kathi , Berry Donna L. , Whisenant Meagan , Sjoberg Daniel
Published: October 2018

Poorly controlled symptoms are common and debilitating during cancer treatment and can affect functional status and quality of life, health care resource utilization, treatment adherence, and cancer survivorship. Historically, the patient experience, including symptoms during treatment, has not been tracked or documented in the patient health record. Measurement of patient-reported outcomes (PROs), including symptoms, is an essential component to cancer care focused on the illness impact to the patient and family. PROs can be useful at the individual level for monitoring and promoting symptom care both in the clinic and remotely and at the population level for aggregating population data for use in research and quality improvement initiatives. Implementation of PROs in cancer clinical care requires a carefully thought out process to overcome challenges related to integrating PROs into existing electronic health records and clinical work flow. Issues with implementing PRO collection may include making decisions about measurement tools, modes of delivery, frequency of measurement, and interpretation that are guided by a clarification of the purpose for collecting PROs. We focus on three aspects of PRO use: (1) improving care for individual patients, (2) analyzing aggregated data to improve care and outcomes overall, and (3) considerations in implementing PRO collection.
Age and Sex in Non-Hodgkin Lymphoma Therapy: It’s Not All Created Equal, or Is It?
Authors: Pfreundschuh Michael
Published: October 2018

Age is the most prominent factor for survival in all patients diagnosed with lymphoma, and male sex implies an increased and independent risk for a worse progression-free survival (PFS) and overall survival (OS) in most lymphomas, possibly with the exception of mantle cell lymphoma (MCL). The worse outcome for elderly patients is only partially explained by decreased tolerance to treatment regimens associated with the increasing number and severity of comorbidities. Little is known about specific differences in lymphoma biology with respect to age and sex, and this is changing only slowly despite the recent rise in interest about these issues. To better understand the differences and their underlying mechanisms, questions of age- and sex-specific outcomes, their correlation with pharmacokinetic data, and planned and received doses, must be addressed and reported in prospective clinical trials. Such studies must be accompanied by translational research that investigates biologic differences of lymphomas between old and young and male and female patients by addressing the microenvironment, cytogenetics including next-generation sequencing and systems biology of lymphomas, and correlation of these findings with treatment results. This knowledge will enable us to adjust lymphoma treatment to the necessities of more personalized medicine.
Biomarkers for Checkpoint Inhibition
Authors: Weber Jeffrey S.
Published: October 2018

The identification of predictive biomarkers for the benefit of cancer immunotherapy is the holy grail of the burgeoning immunotherapy field. Recent work has shown that there are a core of concepts that establish the presence of an immune cell–infiltrate, an inflammatory signature of the tumor microenvironment, and the availability of target antigens defined by mutated neoantigens, as critical for the success of the checkpoint blockade. Genetic analyses have shown that resistance to PD-1 blockade, either innate or adaptive, may be due to existing or de novo mutations in signaling pathways critical for T-cell function in a modest proportion of cases. Major hurdles in the field that remain to be overcome are the difficulty of obtaining tumor biopsies for biomarker assessment, the heterogeneity of biomarker expression within tumors and within different tumors from the same patient, and the inducibility of some biomarkers by disease-related processes. Although assessment of peripheral blood or serum biomarkers would be ideal, few data suggest that they would reliably predict outcome with checkpoint blockade. Ultimately, some amalgamated biomarker that includes tumor and host factors will be required to predict which patients are likely to benefit from, or be resistant to, the effects of checkpoint inhibition.
Using the New ASCO Clinical Practice Guideline for Palliative Care Concurrent With Oncology Care Using the TEAM Approach
Authors: Smith Cardinale B. , Phillips Tanyanika , Smith Thomas J.
Published: October 2018

Palliative care alongside usual oncology care is now recommended by ASCO as the standard of care for any patient with advanced cancer on the basis of multiple randomized trials that show better results with concurrent care than with usual oncology care. Some benefits include better quality of life, better symptom management, reduced anxiety and depression, less caregiver distress, more accordance of care with the wishes of the patient, and less aggressive end-of-life care. Several studies show a survival advantage of several months, and many show considerable cost savings: better care at an affordable cost. However, there are not enough palliative care specialists available, so oncologists must practice exemplary primary palliative care. Protocols used in the clinical trials, similar to those designed for new chemotherapy agents, help oncologists use the TEAM approach of extra time, typically an hour a month spent with the palliative care team; education, especially about prognostic awareness and realistic options, which include formal setting of goals of care and discussion of advance directives; formal assessments for symptoms and for spiritual and psychosocial health; and management by an interdisciplinary team. These are all potentially accomplished by an oncology practice to replicate the services provided by concurrent palliative care.
Value-Based Medicine and Integration of Tumor Biology
Authors: Brooks Gabriel A. , Bosserman Linda D. , Mambetsariev Isa , Salgia Ravi
Published: October 2018

Clinical oncology is in the midst of a genomic revolution, as molecular insights redefine our understanding of cancer biology. Greater awareness of the distinct aberrations that drive carcinogenesis is also contributing to a growing armamentarium of genomically targeted therapies. Although much work remains to better understand how to combine and sequence these therapies, improved outcomes for patients are becoming manifest. As we welcome this genomic revolution in cancer care, oncologists also must grapple with a number of practical problems. Costs of cancer care continue to grow, with targeted therapies responsible for an increasing proportion of spending. Rising costs are bringing the concept of value into sharper focus and challenging the oncology community with implementation of value-based cancer care. This article explores the ways that the genomic revolution is transforming cancer care, describes various frameworks for considering the value of genomically targeted therapies, and outlines key challenges for delivering on the promise of personalized cancer care. It highlights practical solutions for the implementation of value-based care, including investment in biomarker development and clinical trials to improve the efficacy of targeted therapy, the use of evidence-based clinical pathways, team-based care, computerized clinical decision support, and value-based payment approaches.
Hematologic Malignancies: Plasma Cell Disorders
Authors: Dhodapkar Madhav V. , Borrello Ivan , Cohen Adam D. , Stadtmauer Edward A.
Published: October 2018

Multiple myeloma (MM) is a plasma cell malignancy characterized by the growth of tumor cells in the bone marrow. Properties of the tumor microenvironment provide both potential tumor-promoting and tumor-restricting properties. Targeting underlying immune triggers for evolution of tumors as well as direct attack of malignant plasma cells is an emerging focus of therapy for MM. The monoclonal antibodies daratumumab and elotuzumab, which target the plasma cell surface proteins CD38 and SLAMF7/CS1, respectively, particularly when used in combination with immunomodulatory agents and proteasome inhibitors, have resulted in high response rates and improved survival for patients with relapsed and refractory MM. A number of other monoclonal antibodies are in various stages of clinical development, including those targeting MM cell surface antigens, the bone marrow microenvironment, and immune effector T cells such as antiprogrammed cell death protein 1 antibodies. Bispecific preparations seek to simultaneously target MM cells and activate endogenous T cells to enhance efficacy. Cellular immunotherapy seeks to overcome the limitations of the endogenous antimyeloma immune response through adoptive transfer of immune effector cells with MM specificity. Allogeneic donor lymphocyte infusion can be effective but can cause graft-versus-host disease. The most promising approach appears to be genetically modified cellular therapy, in which T cells are given novel antigen specificity through expression of transgenic T-cell receptors (TCRs) or chimeric antigen receptors (CARs). CAR T cells against several different targets are under investigation in MM. Infusion of CD19-targeted CAR T cells following salvage autologous stem cell transplantation (SCT) was safe and extended remission duration in a subset of patients with relapsed/refractory MM. CAR T cells targeting B-cell maturation antigen (BCMA) appear most promising, with dramatic remissions seen in patients with highly refractory disease in three ongoing trials. Responses are associated with degree of CAR T-cell expansion/persistence and often toxicity, including cytokine release syndrome (CRS) and neurotoxicity. Ongoing and future studies are exploring correlates of response, ways to mitigate toxicity, and “universal” CAR T cells.
New Developments and Challenges in Rare Genitourinary Tumors: Non-Urothelial Bladder Cancers and Squamous Cell Cancers of the Penis
Authors: Aragon-Ching Jeanny B. , Pagliaro Lance C.
Published: October 2018

The diagnosis and treatment of rare genitourinary tumors is inherently challenging. The Rare Diseases Act of 2002 initially defined a rare disorder as one that affects fewer than 200,000 Americans. The lack of widely available clinical guidelines, limited research funding, and inaccessible clinical trials often lead to difficulty with treatment decisions to guide practitioners in rendering effective care for patients with rare genitourinary cancers. This article will discuss basic tenets of diagnosis and treatment as well as recent developments and clinical trials in rare non-urothelial bladder cancers and penile squamous cell cancers.
American Society for Radiation Oncology 2016 Annual Meeting: Central Nervous System Abstracts
Authors: Chao Samuel
Published: October 2018

The American Society for Radiation Oncology's (ASTRO) 2016 scientific program presented a number of excellent abstracts focusing on brain and spine tumors. Selected abstracts will be reviewed in this article.
Personalizing Adjuvant Therapy for Stage II/III Colorectal Cancer
Authors: McCleary Nadine Jackson , Benson Al B. , Dienstmann Rodrigo
Published: October 2018

This review focuses on three areas of interest with respect to the treatment of stage II and III colon and rectal cancer, including (1) tailoring adjuvant therapy for the geriatric population, (2) the controversy as to the optimal adjuvant therapy strategy for patients with locoregional rectal cancer and for patients with colorectal resectable metastatic disease, and (3) discussion of the microenvironment, molecular profiling, and the future of adjuvant therapy. It has become evident that age is the strongest predictive factor for receipt of adjuvant chemotherapy, duration of treatment, and risk of treatment-related toxicity. Although incorporating adjuvant chemotherapy for patients who have received neoadjuvant chemoradiation and surgery would appear to be a reasonable strategy to improve survivorship as an extrapolation from stage III colon cancer adjuvant trials, attempts at defining the optimal rectal cancer population that would benefit from adjuvant therapy remain elusive. Similarly, the role of adjuvant chemotherapy for patients after resection of metastatic colorectal cancer has not been clearly defined because of very limited data to provide guidance. An understanding of the biologic hallmarks and drivers of metastatic spread as well as the micrometastatic environment is expected to translate into therapeutic strategies tailored to select patients. The identification of actionable targets in mesenchymal tumors is of major interest.
Breast Cancer After Childhood, Adolescent, and Young Adult Cancer: It’s Not Just About Chest Radiation
Authors: Hodgson David , van Leeuwen Flora , Ng Andrea , Morton Lindsay , Henderson Tara O.
Published: October 2018

Women who have been treated for a childhood, adolescent, or young adult cancer are at an increased risk for developing breast cancer at a young age, and breast cancer accounts for the most common subsequent malignant neoplasm among female childhood and adolescent cancer survivors. Risk of breast cancer in these survivors appears to be a multifaceted relationship between constitutional factors, exposures to radiation therapy (RT) and chemotherapy, and genetic predisposition. Given the significant morbidities and mortality associated with a breast cancer diagnosis, it is imperative that health care providers understand the risks, biology and genetics, recommended surveillance guidelines for early detection, and potential prevention strategies for women who have survived pediatric and young adult cancer.
Chronic Myeloid Leukemia: What Every Practitioner Needs to Know in 2017
Authors: Khoury Hanna Jean , Williams Loretta A. , Atallah Ehab , Hehlmann Rüdiger
Published: October 2018

The prognosis of chronic phase chronic myeloid leukemia (CML) has improved so that life expectancy for patients responding to tyrosine kinase inhibitors (TKIs) is now equivalent to age-matched controls. Attention should be paid to comorbidities that impact survival. The success of TKI therapy can be easily and reliably assessed at well-accepted time points using quantitative polymerase chain reaction (PCR) standardized to the international scale. Patient-reported outcome (PRO) tools are readily available for use in the clinic and provide complementary information on the tolerance of TKIs. Effectively managing adverse events of TKIs can improve compliance and quality of life. Discontinuation of TKIs is the next frontier in CML. In select patients with sustained deep molecular remission, a discontinuation of TKI is associated with a durable treatment-free remission in approximately 50%. Patient engagement in their discontinuation can be achieved through a provider multi-team coaching, is complementary to the available guidelines, and may provide an additional safety net so that these discontinuations remain safe when applied in general practices.
Managing Resistance to EFGR- and ALK-Targeted Therapies
Authors: Lovly Christine M. , Iyengar Puneeth , Gainor Justin F.
Published: October 2018

Targeted therapies have transformed the management of non–small cell lung cancer (NSCLC) and placed an increased emphasis on stratifying patients on the basis of genetic alterations in oncogenic drivers. To date, the best characterized molecular targets in NSCLC are the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK). Despite steady advances in targeted therapies within these molecular subsets, however, acquired resistance to therapy is near universal. Recent preclinical models and translational efforts have provided critical insights into the molecular mechanisms of resistance to EGFR and ALK inhibitors. In this review, we present a framework for understanding resistance to targeted therapies. We also provide overviews of the molecular mechanisms of resistance and strategies to overcome resistance among EGFR-mutant and ALK-rearranged lung cancers. To date, these strategies have centered on the development of novel next-generation inhibitors, rationale combinations, and use of local ablative therapies, such as radiotherapy.
Social Media for Networking, Professional Development, and Patient Engagement
Authors: Markham Merry Jennifer , Gentile Danielle , Graham David L.
Published: October 2018

Social media has become an established method of communication, and many physicians are finding these interactive tools and platforms to be useful for both personal and professional use. Risks of social media, or barriers to its use, include perceived lack of time, privacy concerns, and the risk of damage to one’s reputation by unprofessional behavior. Of the social media platforms, Twitter has become favored by physicians and other health care professionals. Although one of the most obvious uses of social media is for rapid dissemination and receipt of information, oncologists are finding that social media is important for networking through blogs, Facebook, and Twitter. These platforms also have potential for providing opportunities for professional development, such as finding collaborators through networking, participation in Twitter journal clubs, and participating in online case-based tumor boards. Social media can also be used for patient engagement, such as through participation in tweet chats. There is emerging data that patient engagement through these platforms may lead to improvement in some health-related outcomes; however, data are sparse for oncology-specific outcomes. Efforts are underway to determine how to assess how social media engagement impacts health outcomes in oncology patients.
Pharmacokinetic/Pharmacodynamic Modeling for Drug Development in Oncology
Authors: Garralda Elena , Dienstmann Rodrigo , Tabernero Josep
Published: October 2018

High drug attrition rates remain a critical issue in oncology drug development. A series of steps during drug development must be addressed to better understand the pharmacokinetic (PK) and pharmacodynamic (PD) properties of novel agents and, thus, increase their probability of success. As available data continues to expand in both volume and complexity, comprehensive integration of PK and PD information into a robust mathematical model represents a very useful tool throughout all stages of drug development. During the discovery phase, PK/PD models can be used to identify and select the best drug candidates, which helps characterize the mechanism of action and disease behavior of a given drug, to predict clinical response in humans, and to facilitate a better understanding about the potential clinical relevance of preclinical efficacy data. During early drug development, PK/PD modeling can optimize the design of clinical trials, guide the dose and regimen that should be tested further, help evaluate proof of mechanism in humans, anticipate the effect in certain subpopulations, and better predict drug-drug interactions; all of these effects could lead to a more efficient drug development process. Because of certain peculiarities of immunotherapies, such as PK and PD characteristics, PK/PD modeling could be particularly relevant and thus have an important impact on decision making during the development of these agents.
Prognostication in Kidney Cancer: Recent Advances and Future Directions
Authors: Graham Jeffrey , Dudani Shaan , Heng Daniel Y.C.
Published: October 2018

The most common type of cancer originating in the kidney is renal cell carcinoma (RCC). In both localized and advanced RCC, a number of clinical, pathologic, and molecular factors have been identified as having prognostic significance. In localized disease, risk stratification has traditionally involved the anatomic extent of disease, and several integrated scoring systems have been developed to help predict outcomes after definitive local therapy. In metastatic RCC, integrated prognostic models have also been established. These are used to stratify patients in contemporary clinical trials and to guide risk-directed treatment selection in clinical practice. Although many prognostic factors are common to both localized and advanced disease, there are some important distinctions. In both of these types of disease, the prognostic role of specific molecular and genomic alterations is an area of active investigation. In this review, we highlight the current staging systems and prognostic factors in localized and metastatic RCC. We also explore future directions in this area, including the expanding role of molecular biomarkers and their integration into the traditional prognostic models.
Kidney Cancer: Toxicity Management, Symptom Control, and Palliative Care
Authors: Sinibaldi Victoria J. , Pratz Caroline F. , Yankulina Olga
Published: October 2018

The challenges of managing the toxicities associated with the current armamentarium to combat kidney cancer continue to grow. It is therefore paramount for providers to not only have knowledge of the disease, but to also have an understanding of the potential adverse effects associated with the various treatments. In addition, it is important to incorporate palliative care strategies to help manage symptoms, improve quality of life, and support patients and their families throughout the continuum of the disease. This article will discuss the general toxicities and symptomatic issues encountered in patients with kidney cancer who are receiving targeted therapies and immunotherapies. It will also define the components of palliative care and its benefits. The recommendations in this article are from source documentation noted in various guidelines of the Oncology Nursing Society, ASCO, the National Comprehensive Cancer Network, and the Society for Immunotherapy of Cancer. We feel it is appropriate to modify and individualize management as deemed necessary to provide the best outcome for patients and their families.
Ablative Therapies for Cervical Intraepithelial Neoplasia in Low-Resource Settings: Findings and Key Questions
Authors: Cremer Miriam L. , Conzuelo-Rodriguez Gabriel , Cherniak William , Randall Thomas
Published: October 2018

Barriers to access for cervical precancer care in low-resource settings go beyond cost. Gas-based cryotherapy has emerged as the standard treatment in these areas, but there are barriers to this technology that have necessitated the development and implementation of affordable and portable alternatives. This review identifies knowledge gaps with regard to technologies primarily used in low-resource settings, including standard cryotherapy, nongas-based cryotherapy, and thermoablation. These gaps are addressed using evidence-based guidelines, patient and provider acceptability, long-term obstetric outcomes, and treatment of women with HIV infection. This review highlights the need for prospective studies that compare ablative methods, especially given the increasing use of thermoablation.
Portable and Precarious
Authors: Lam Tong
Published: October 2018

Migrant construction workers play a major role in China’s rapid urbanization. In order to increase efficiency, construction companies routinely house their workers in prefabricated metal shelters. These portable, temporary, and container-like dormitories resonate strikingly with the precarious and disposable conditions of Chinese migrant construction workers. Meanwhile, within these enclosed and highly regulated spaces, the management also periodically uses outdoor film screenings to increase the morale of the workers as well as to prevent them from discussing their working conditions and alienated existence. As such, these open-air film screenings inside China’s construction compounds are at once scenes of cinematic magic and disenchantment.
Effect of Ice Slurry Ingestion on Cardiovascular Drift and V˙O2max during Heat Stress
Authors: NG JASON , DOBBS WARD C. , WINGO JONATHAN E.
Published: October 2018

External body cooling by fan airflow mitigates the decrease in maximal oxygen uptake (V˙O2max) associated with cardiovascular (CV) drift during cycling in hot conditions. It remains unknown whether internal body cooling via ice slurry ingestion elicits a similar response.

Purpose

This study aimed to test the hypothesis that ice slurry ingestion attenuates the magnitude of CV drift and accompanying decrement in V˙O2max during heat stress.

Methods

Eight men completed a graded exercise test on a cycle ergometer in 22°C to measure V˙O2max. Then on three separate occasions (in randomly assigned counterbalanced treatment orders), they cycled at 60% V˙O2max in hot conditions (35°C, 40% RH) for 15 min, 45 min with tepid (23°C) fluid ingestion (45FL), or 45 min with ice (−1°C) slurry ingestion (45ICE), followed immediately by measurement of V˙O2max. The purpose of the separate 15- and 45-min trials was to measure CV drift and V˙O2max over the same time interval.

Results

The increase in heart rate between 15 and 45 min was twice as large in 45FL (8.6%) compared with 45ICE (4.6%; P = 0.02). Stroke volume declined by 6.2% in 45FL but was maintained with 45ICE (P = 0.02). V˙O2peak decreased from 15 to 45 min by 8.6% and 9.0% in 45FL and 45ICE, respectively, but was not different between conditions (P = 0.79).

Conclusion

Although ice slurry ingestion attenuated CV drift more than fluid ingestion, it did not mitigate the decline in V˙O2max. Contrary to previous findings, when ice slurry is ingested, changes in heart rate may not reflect changes in relative metabolic intensity during prolonged exercise in the heat.
Innovation, Reallocation, and Growth
Authors: Acemoglu Daron , Akcigit Ufuk , Alp Harun , Bloom Nicholas , Kerr William
Published: October 2018

We build a model of firm-level innovation, productivity growth, and reallocation featuring endogenous entry and exit. A new and central economic force is the selection between high- and low-type firms, which differ in terms of their innovative capacity. We estimate the parameters of the model using US Census microdata on firm-level output, R&D, and patenting. The model provides a good fit to the dynamics of firm entry and exit, output, and R&D. Taxing the continued operation of incumbents can lead to sizable gains (of the order of 1.4 percent improvement in welfare) by encouraging exit of less productive firms and freeing up skilled labor to be used for R&D by high-type incumbents. Subsidies to the R&D of incumbents do not achieve this objective because they encourage the survival and expansion of low-type firms. (JEL D21, D24, H25, L52, O31, O34)
Areca nut extract demonstrated apoptosis-inducing mechanism by increased caspase-3 activities on oral squamous cell carcinoma
Authors: Sari Liza Meutia , Subita Gus Permana , Auerkari Elza Ibrahim
Published: October 2018

Background: Oral squamous cell carcinoma is a neoplasm of keratinocyte cells of oral mucosa epithelium that can potentially spread through lymphatic tissue or blood vessel. Although areca nut is one of the plants with a risk of inducing that cancer, areca nut is believed to have high antioxidant properties. Due to the current interest in the apoptosis effects from areca nut for oral cancer treatment, we investigated its ability to induce apoptosis and caspase-3 activity in oral cancer cell lines: HSC-2 and HSC-3.

Methods: We examined the effect of areca nut on apoptosis and caspase-3 activity in HSC-2 and HSC-3 cells. Flow cytometry was conducted for the quantification of the cells that were apoptotic and expressing the caspase-3 enzyme for 24 and 48 hours.

Results: Areca nut induced a significant increase (p<0.01) in late apoptosis of HSC-2 cells and mostly occurred over 48 hours. The study also found that in HSC-3, there were significant increases (p<0.01) the percentage of cells in early apoptosis after 24 hours and late apoptosis at 48 hours. Caspase-3 activity increased after 24 and 48 hours of areca nut exposure in both cells.

Conclusions: The study showed that areca nut could be considered as a potential anticancer agent through its capability in inducing a caspase-dependent apoptosis.
Screening of protease, cellulase, amylase and xylanase from the salt-tolerant and thermostable marine Bacillus subtilis strain SR60
Authors: de Veras Bruno Oliveira , dos Santos Yago Queiroz , Diniz Katharina Marquez , Carelli Gabriela Silva Campos , dos Santos Elizeu Antunes
Published: October 2018

Background: The marine environment harbours different microorganisms that inhabit niches with adverse conditions, such as temperature variation, pressure and salinity. To survive these particular conditions, marine bacteria use unique metabolic and biochemical features, producing enzymes that may have industrial value.

Methods: The aim of this study was to observe the production of multiple thermoenzymes and haloenzymes, including protease, cellulase, amylase and xylanase, from bacterial strains isolated from coral reefs Cabo Branco, Paraiba State, Brazil. Strain SR60 was identified by the phylogenetic analysis to be Bacillus subtilis through a 16S ribosomal RNA assay. To screening of multiples enzymes B. subtilis SR60 was inoculated in differential media to elicit the production of extracellular enzymes with the addition of a range of salt concentrations (0, 0.25, 0.50, 1.0, 1.25 and 1.5 M NaCl).

Results: The screening showed a capacity of production of halotolerant protease, cellulase, amylase and xylanase and thermostable by the isolate (identified as B. subtilis SR60). Protease, cellulase, amylase and xylanase production were limited to 1.5, 1.5, 1.0 and 1.25 M NaCl, respectively.

Conclusions: Bacillus subtilis SR60 was shown in this study be capable of producing protease, cellulase, amylase and xylanase when submitted to a high salinity environment. These data demonstrate the halophytic nature of SR60 and its ability to produce multiples enzymes.
Ethical considerations in Controlled Human Malaria Infection studies in low resource settings: Experiences and perceptions of study participants in a malaria Challenge study in Kenya
Authors: Njue Maureen , Njuguna Patricia , Kapulu Melissa C. , Sanga Gladys , Bejon Philip , Marsh Vicki , Molyneux Sassy , Kamuya Dorcas
Published: October 2018

Background: The range and amount of volunteer infection studies, known as Controlled Human Infection Model (CHMI) studies, in Low-Middle Income Countries (LMICs) is increasing with rapid technological advancement, world-class laboratory facilities and increasing capacity development initiatives. However, the ethical issues these studies present in LMICs have not been empirically studied. We present findings of a descriptive social science study nested within a malaria volunteer infection study, on-going at the time of writing, at the KEMRI-Wellcome Trust Research Programme (KWTRP) on the Kenyan Coast.

Methods: The study included non-participant observations, five group discussions with more than half of the CHMI study participants, two in-depth interviews with study team members, and an exit questionnaire administered to the participants.

Results: Participants understood the key elements of the study, including that they would be deliberately infected with malaria parasites and may get malaria as a result, there would be regular blood draws, and they would spend up to 24 days in a residence facility away from their homes. The greatest motivation for participation was the monetary compensation of 20 USD per overnight stay given as a lump-sum at the end of their residency stay. Also appreciated were the health screening tests prior to enrolment and the positive relations with the study team. Concerns raised included the amount and regularity of blood draws experienced, and concerns that this type of research may feed into on-going rumours about research generally.

Conclusion: With the increasing range and number of CHMI studies being conducted in LMICs, current ethical guidance are inadequate. This study highlights some of the ethical issues that could emerge in these settings, emphasizing the heavy responsibility placed on research review and regulatory systems, researchers and funders, as well as the importance of carefully tailored community engagement and consent processes.
Health risk behavior among perinatally HIV exposed uninfected adolescents: A systematic review
Authors: Ssewanyana Derrick , Mwangala Patrick N , Kachama Nyongesa Moses , van Baar Anneloes , Newton Charles R , Abubakar Amina
Published: October 2018

Background: Perinatally HIV exposed uninfected (PHEU) adolescents are an increasing sub-population, especially in high HIV epidemic settings. HIV exposure may have some lasting implications for adolescents’ development, however, longer term health outcomes such as health risk behavior (HRB) are so far not well understood in this adolescent sub-population.

Methods: In this systematic review, we identify the prevalent forms, burden, and underlying risk factors for HRB of PHEU adolescents. We searched in PubMed, PsycINFO and Applied Social Sciences Index & Abstracts for peer reviewed empirical studies published between 1980 and August 2018 on HRB among PHEU adolescents aged 10 – 19 years.

Results: Eleven eligible studies, all conducted in North America were identified and they showed that sexual risk behavior such as lifetime unprotected sex increased drastically especially in mid-adolescence. PHEU adolescents’ substance use (especially alcohol and marijuana) was high and increased over time. In a significant minority (10-18%) substance use disorder was screened. Some intra and interpersonal risk factors such as caregiver and PHEU adolescents’ mental health problems, age and HIV status were shared across the two forms of HRB. However, other risk factors like race, gender and experience of traumatic life events were behavior specific.

Conclusion: Overall, there is need to conduct similar research in other settings especially those with high HIV burden where the PHEU adolescent sub-population is rising. Future research in this area could benefit from examining more forms of HRB and exploring the clustering of HRB among PHEU adolescents.
Business Game as a Tool of Recruitment in Retail Organizations
Authors: Казакова М. , Kazakova M. , Шурмина Т. , Shurmina T.
Published: October 2018

The article is devoted to the problems of attracting personnel to vacancies of mass positions in the companies of the retail sphere of activity. In particular, the results of the research of the practice of attracting sales and service office specialists in the largest retail of mobile communications, whose management faced problems of high staff turnover and insufficient staffing, are presented. The study showed that the reason for these negative phenomena lies in the sources used to attract staff, namely: traditional job-resources do not create a sufficient flow of candidates so that the financial costs of many of them are not appropriate. On the basis of the survey of sales staff the authors developed a number of recommendations of practical importance: a portrait of the real applicant of the company, identified alternative sources of attracting the target audience of candidates. As the main development, the scenario of business game for participation in career events in various educational institutions is proposed. It will allow to distinguish retail from similar companies-employers, presented at the job fair, as well as to assess the potential employees according to the required competencies in practice, which is impossible to do in the framework of interviews of the traditional format. The implementation of this development requires minimal financial costs and can be carried out in any telecommunication organizations in the retail sector.
Development of the Recruiting Process According to Talent Management Conception (a Telecommunication Company Experiense)
Authors: Коробкина М. , Korobkina M. , Ширяева Л. , Shiryaeva L.
Published: October 2018

Recruiting is one of the key elements of the work of the HR department of any organization, since the effectiveness of the company depends on the quality of the selected personnel. In the modern sense, recruiting and hiring should be implemented in close interaction with such areas as personnel planning, adaptation, training, evaluation of the results and potential of employees, as well as planning their further development and grows. The innovative technology that unites these areas is talent management. The introduction of talent management practices in Russian organizations demonstrates the understanding of the importance of this process. The article reveals the definition of talent management, gives examples of the application of this technology in Russian and foreign companies, and also examines the process of transforming the recruiting function into talent management in a telecommunication organization.
INFLUENCE OF CULTURAL EPOCH ON ECONOMIC IDEAS
Authors: Лузгина Юлия , Luzgina Yuliya , Филатов Дмитрий , Filatov Dmitry
Published: October 2018

Culture is a display of everything that man has ever created. It determines the course of the society on which the society will be built, and the economy is an indivisible part of this trend, which is guided by culture. Only a person directly influences the development and formation of a culture in which each sphere of society is interconnected and where each of them is an inseparable link. The article presents a brief overview of the mutual influence of two sciences - economics and culture
Estresse ocupacional em profissionais de enfermagem
Authors: Llapa-Rodriguez Eliana Ofélia , Oliveira Júlian Katrin Albuquerque de , Lopes Neto David Lopes , Gois Cristiane Franca Lisboa , Campos Maria Pontes de Aguiar , Mattos Maria Claúdia Tavares de
Published: October 2018

Objetivo: analisar os fatores de estresse em enfermeiros de um hospital universitário da cidade de Aracaju, Sergipe, Brasil. Método: pesquisa descritiva e correlacional. A amostra foi composta por 101 profissionais de enfermagem. Os dados foram coletados pela técnica de entrevista, com aplicação do Inventário para Estresse em Enfermeiros e posteriormente analisados utilizando o teste t de Student para amostras independentes. O projeto do estudo foi aprovado por Comitê de Ética em Pesquisa. Resultados: 43% dos itens analisados foram fontes de estresse ocupacional entre os profissionais de enfermagem, sendo o fator papéis estressores da carreira o responsável por maior influência ao estresse (54%). O local de trabalho foi a única variável que apresentou diferença significativa quando associada aos fatores analisados. Conclusão: a enfermagem se revelou como uma profissão de risco para o estresse ocupacional, sofrendo diversas influências dos fatores analisados, relacionados à organização e ao processo de trabalho.