bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and Safety of Nivolumab Alone or in Combination With Ipilimumab in Patients With Mucosal Melanoma: A Pooled Analysis
Authors: D’Angelo Sandra P. , Larkin James , Sosman Jeffrey A. , Lebbé Celeste , Brady Benjamin , Neyns Bart , Schmidt Henrik , Hassel Jessica C. , Hodi F. Stephen , Lorigan Paul , Savage Kerry J. , Miller Wilson H. , Mohr Peter , Marquez-Rodas Ivan , Charles Julie , Kaatz Martin , Sznol Mario , Weber Jeffrey S. , Shoushtari Alexander N. , Ruisi Mary , Jiang Joel , Wolchok Jedd D.
Published: February 2017

Purpose

Mucosal melanoma is an aggressive malignancy with a poor response to conventional therapies. The efficacy and safety of nivolumab (a programmed death-1 checkpoint inhibitor), alone or combined with ipilimumab (a cytotoxic T-lymphocyte antigen-4 checkpoint inhibitor), have not been reported in this rare melanoma subtype.

Patients and Methods

Data were pooled from 889 patients who received nivolumab monotherapy in clinical studies, including phase III trials; 86 (10%) had mucosal melanoma and 665 (75%) had cutaneous melanoma. Data were also pooled for patients who received nivolumab combined with ipilimumab (n = 35, mucosal melanoma; n = 326, cutaneous melanoma).

Results

Among patients who received nivolumab monotherapy, median progression-free survival was 3.0 months (95% CI, 2.2 to 5.4 months) and 6.2 months (95% CI, 5.1 to 7.5 months) for mucosal and cutaneous melanoma, with objective response rates of 23.3% (95% CI, 14.8% to 33.6%) and 40.9% (95% CI, 37.1% to 44.7%), respectively. Median progression-free survival in patients treated with nivolumab combined with ipilimumab was 5.9 months (95% CI, 2.8 months to not reached) and 11.7 months (95% CI, 8.9 to 16.7 months) for mucosal and cutaneous melanoma, with objective response rates of 37.1% (95% CI, 21.5% to 55.1%) and 60.4% (95% CI, 54.9% to 65.8%), respectively. For mucosal and cutaneous melanoma, respectively, the incidence of grade 3 or 4 treatment-related adverse events was 8.1% and 12.5% for nivolumab monotherapy and 40.0% and 54.9% for combination therapy.

Conclusion

To our knowledge, this is the largest analysis of data for anti–programmed death-1 therapy in mucosal melanoma to date. Nivolumab combined with ipilimumab seemed to have greater efficacy than either agent alone, and although the activity was lower in mucosal melanoma, the safety profile was similar between subtypes.
Predictors of and Trends in High-Intensity End-of-Life Care Among Children With Cancer: A Population-Based Study Using Health Services Data
Authors: Kassam Alisha , Sutradhar Rinku , Widger Kimberley , Rapoport Adam , Pole Jason D. , Nelson Katherine , Wolfe Joanne , Earle Craig C. , Gupta Sumit
Published: February 2017

Purpose

Children with cancer often receive high-intensity (HI) medical care at the end-of-life (EOL). Previous studies have been limited to single centers or lacked detailed clinical data. We determined predictors of and trends in HI-EOL care by linking population-based clinical and health-services databases.

Methods

A retrospective decedent cohort of patients with childhood cancer who died between 2000 and 2012 in Ontario, Canada, was assembled using a provincial cancer registry and linked to population-based health-care data. Based on previous studies, the primary composite measure of HI-EOL care comprised any of the following: intravenous chemotherapy < 14 days from death; more than one emergency department visit; and more than one hospitalization or intensive care unit admission < 30 days from death. Secondary measures included those same individual measures and measures of the most invasive (MI) EOL care (eg, mechanical ventilation < 14 days from death). We determined predictors of outcomes with appropriate regression models. Sensitivity analysis was restricted to cases of cancer-related mortality, excluding treatment-related mortality (TRM) cases.

Results

The study included 815 patients; of these, 331 (40.6%) experienced HI-EOL care. Those with hematologic malignancies were at highest risk (odds ratio, 2.5; 95% CI, 1.8 to 3.6; P < .001). Patients with hematologic cancers and those who died after 2004 were more likely to experience the MI-EOL care (eg, intensive care unit, mechanical ventilation, odds ratios from 2.0 to 5.1). Excluding cases of TRM did not substantively change the results.

Conclusion

Ontario children with cancer continue to experience HI-EOL care. Patients with hematologic malignancies are at highest risk even when excluding TRM. Of concern, rates of the MI-EOL care have increased over time despite increased palliative care access. Linking health services and clinical data allows monitoring of population trends in EOL care and identifies high-risk populations for future interventions.
Tumor Deposits in Colorectal Cancer: Improving the Value of Modern Staging—A Systematic Review and Meta-Analysis
Authors: Nagtegaal Iris D. , Knijn Nikki , Hugen Niek , Marshall Helen C. , Sugihara Kenichi , Tot Tibor , Ueno Hideki , Quirke Philip
Published: February 2017

Purpose

Colorectal cancer (CRC) treatment is largely determined by tumor stage. Despite improvements made in the treatment of various types of metastatic disease, staging has not been refined. The role of tumor deposits (TDs) in staging remains debated. We have assessed the relation of TDs with metastatic pattern to evaluate whether TDs might add significant new information to staging.

Methods

We performed a systematic literature search that was focused on the role of TDs in CRC. Studies with neoadjuvant-treated patients were excluded. Data on stage, histologic factors, and outcome were extracted. Data from four large cohorts were analyzed for the relevance of the presence of TDs, lymph node metastases (LNMs), and extramural vascular invasion (EMVI) on the pattern of metastases and outcomes.

Results

Of 10,106 included patients with CRC, 22% presented with TDs. TDs are invariably associated with poor outcome. Presence of TDs was associated with presence of LNMs and EMVI. In a pairwise comparison, effects of TD were stronger than those of both LNMs and EMVI. In the logistic regression model, TDs in combination with LNMs is the strongest predictor for liver (odds ratio [OR], 5.5), lung (OR, 4.3) and peritoneal metastases (OR, 7.0). Presence of EMVI adds information for liver and lung metastases, but not for peritoneal metastases.

Conclusion

We have shown that TDs are not equal to LNMs or EMVI with respect to biology and outcome. We lose valuable prognostic information by allocating TDs into nodal category N1c and only considering TDs in the absence of LNMs. Therefore, we propose that the number of TDs should be added to the number of LNMs to derive a final N stage.
Lung Cancer Risk Prediction Model Incorporating Lung Function: Development and Validation in the UK Biobank Prospective Cohort Study
Authors: Muller David C. , Johansson Mattias , Brennan Paul
Published: February 2017

Purpose

Several lung cancer risk prediction models have been developed, but none to date have assessed the predictive ability of lung function in a population-based cohort. We sought to develop and internally validate a model incorporating lung function using data from the UK Biobank prospective cohort study.

Methods

This analysis included 502,321 participants without a previous diagnosis of lung cancer, predominantly between 40 and 70 years of age. We used flexible parametric survival models to estimate the 2-year probability of lung cancer, accounting for the competing risk of death. Models included predictors previously shown to be associated with lung cancer risk, including sex, variables related to smoking history and nicotine addiction, medical history, family history of lung cancer, and lung function (forced expiratory volume in 1 second [FEV1]).

Results

During accumulated follow-up of 1,469,518 person-years, there were 738 lung cancer diagnoses. A model incorporating all predictors had excellent discrimination (concordance (c)-statistic [95% CI] = 0.85 [0.82 to 0.87]). Internal validation suggested that the model will discriminate well when applied to new data (optimism-corrected c-statistic = 0.84). The full model, including FEV1, also had modestly superior discriminatory power than one that was designed solely on the basis of questionnaire variables (c-statistic = 0.84 [0.82 to 0.86]; optimism-corrected c-statistic = 0.83; pFEV1 = 3.4 × 10−13). The full model had better discrimination than standard lung cancer screening eligibility criteria (c-statistic = 0.66 [0.64 to 0.69]).

Conclusion

A risk prediction model that includes lung function has strong predictive ability, which could improve eligibility criteria for lung cancer screening programs.
Phase I First-in-Human Study of Venetoclax in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma
Authors: Davids Matthew S. , Roberts Andrew W. , Seymour John F. , Pagel John M. , Kahl Brad S. , Wierda William G. , Puvvada Soham , Kipps Thomas J. , Anderson Mary Ann , Salem Ahmed Hamed , Dunbar Martin , Zhu Ming , Peale Franklin , Ross Jeremy A. , Gressick Lori , Desai Monali , Kim Su Young , Verdugo Maria , Humerickhouse Rod A. , Gordon Gary B. , Gerecitano John F.
Published: February 2017

Purpose

B-cell leukemia/lymphoma-2 (BCL-2) overexpression is common in many non-Hodgkin lymphoma (NHL) subtypes. A phase I trial in patients with NHL was conducted to determine safety, pharmacokinetics, and efficacy of venetoclax, a selective, potent, orally bioavailable BCL-2 inhibitor.

Patients and Methods

A total of 106 patients with relapsed or refractory NHL received venetoclax once daily until progressive disease or unacceptable toxicity at target doses from 200 to 1,200 mg in dose-escalation and safety expansion cohorts. Treatment commenced with a 3-week dose ramp-up period for most patients in dose-escalation cohorts and for all patients in safety expansion.

Results

NHL subtypes included mantle cell lymphoma (MCL; n = 28), follicular lymphoma (FL; n = 29), diffuse large B-cell lymphoma (DLBCL; n = 34), DLBCL arising from chronic lymphocytic leukemia (Richter transformation; n = 7), Waldenström macroglobulinemia (n = 4), and marginal zone lymphoma (n = 3). Venetoclax was generally well tolerated. Clinical tumor lysis syndrome was not observed, whereas laboratory tumor lysis syndrome was documented in three patients. Treatment-emergent adverse events were reported in 103 patients (97%), a majority of which were grade 1 to 2 in severity. Grade 3 to 4 events were reported in 59 patients (56%), and the most common were hematologic, including anemia (15%), neutropenia (11%), and thrombocytopenia (9%). Overall response rate was 44% (MCL, 75%; FL, 38%; DLBCL, 18%). Estimated median progression-free survival was 6 months (MCL, 14 months; FL, 11 months; DLBCL, 1 month).

Conclusion

Selective targeting of BCL-2 with venetoclax was well tolerated, and single-agent activity varied among NHL subtypes. We determined 1,200 mg to be the recommended single-agent dose for future studies in FL and DLBCL, with 800 mg being sufficient to consistently achieve durable response in MCL. Additional investigations including combination therapy to augment response rates and durability are ongoing.
Genetic Basis of Acute Lymphoblastic Leukemia
Authors: Iacobucci Ilaria , Mullighan Charles G.
Published: February 2017

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, and despite cure rates exceeding 90% in children, it remains an important cause of morbidity and mortality in children and adults. The past decade has been marked by extraordinary advances into the genetic basis of leukemogenesis and treatment responsiveness in ALL. Both B-cell and T-cell ALL comprise multiple subtypes harboring distinct constellations of somatic structural DNA rearrangements and sequence mutations that commonly perturb lymphoid development, cytokine receptors, kinase and Ras signaling, tumor suppression, and chromatin modification. Recent studies have helped to understand the genetic basis of clonal evolution and relapse and the role of inherited genetic variants in leukemogenesis. Many of these findings are of clinical importance, and ongoing studies implementing clinical sequencing in the management of leukemia are expected to improve diagnosis, monitoring of residual disease, and early detection of relapse and to guide precise therapies. Here, we provide a concise review of genomic studies in ALL and discuss the role of genomic testing in clinical management.
Clinical Applications of the Genomic Landscape of Aggressive Non-Hodgkin Lymphoma
Authors: Moffitt Andrea B. , Dave Sandeep S.
Published: February 2017

In this review, we examine the genomic landscapes of lymphomas that arise from B, T, and natural killer cells. Lymphomas represent a striking spectrum of clinical behaviors. Although some lymphomas are curable with standard therapy, the majority of the affected patients succumb to their disease. Here, the genetic underpinnings of these heterogeneous entities are reviewed. We consider B-cell lymphomas, including Burkitt lymphoma, diffuse large B-cell lymphoma, Hodgkin lymphoma, and primary mediastinal B-cell lymphoma. We also examine T-cell lymphomas, including anaplastic large-cell lymphoma, angioimmunoblastic T-cell lymphoma, cutaneous T-cell lymphoma, adult T-cell leukemia/lymphoma, and other peripheral T-cell lymphomas. Together, these malignancies make up most lymphomas diagnosed around the world. Genomic technologies, including microarrays and next-generation sequencing, have enabled a better understanding of the molecular underpinnings of these cancers. We describe the broad genomics findings that characterize these lymphoma types and discuss new therapeutic opportunities that arise from these findings.
Pilot Survey of Breast Cancer Management in Sub-Saharan Africa
Authors: Vanderpuye Verna D.N.K. , Olopade Olufunmilayo I. , Huo Dezheng
Published: February 2017

Purpose

To understand the current state of breast cancer management in sub-Saharan Africa.

Methods

We conducted an anonymous online survey of breast cancer management among African Organization for Research and Treatment in Cancer (AORTIC) members by using a 42-question structured questionnaire in both English and French in 2013.

Results

Twenty members from 19 facilities in 14 countries responded to the survey. Twelve members (60%) belonged to a multidisciplinary breast cancer team. Radiotherapy equipment was available in seven facilities (36%), but equipment had down time at least once a week in four facilities. Available chemotherapy drugs included methotrexate, cyclophosphamide, fluorouracil, anthracyclines, and vincristine, whereas trastuzumab, taxanes, vinorelbine, and gemcitabine were available in few facilities. Core-needle biopsy was available in 16 facilities (84%); mammogram, in 17 facilities (89%); computed tomography scan, in 15 facilities (79%); magnetic resonance imaging, in 11 facilities (58%); and bone scans, in nine facilities (47%). It took an average of 1 to 3 weeks to report histopathology. Immunohistochemistry was available locally in eight facilities (42%), outside hospitals but within the country in seven facilities (37%), and outside the country in four facilities (21%). Thirteen facilities (68%) performed axillary node dissections as part of a breast protocol. Neoadjuvant chemotherapy was the most common therapy for locally advanced breast cancer in 13 facilities (68%). In three facilities (16%), receptor status did not influence the prescription of hormone treatment.

Conclusion

This pilot survey suggests that AORTIC members in sub-Saharan Africa continue to make gains in the provision of access to multidisciplinary breast cancer care, but the lack of adequate pathology and radiotherapy services is a barrier. Focused attention on in-country and regional training needs and improvement of health systems deliverables is urgently needed.
Model for Estimating Power and Downtime Effects on Teletherapy Units in Low-Resource Settings
Authors: McCarroll Rachel , Youssef Bassem , Beadle Beth , Bojador Maureen , Cardan Rex , Famiglietti Robin , Followill David , Ibbott Geoffrey , Jhingran Anuja , Trauernicht Christoph , Balter Peter , Court Laurence
Published: February 2017

Purpose

More than 6,500 megavoltage teletherapy units are needed worldwide, many in low-resource settings. Cobalt-60 units or linear accelerators (linacs) can fill this need. We have evaluated machine performance on the basis of patient throughput to provide insight into machine viability under various conditions in such a way that conclusions can be generalized to a vast array of clinical scenarios.

Materials and Methods

Data from patient treatment plans, peer-reviewed studies, and international organizations were combined to assess the relative patient throughput of linacs and cobalt-60 units that deliver radiotherapy with standard techniques under various power and maintenance support conditions. Data concerning the frequency and duration of power outages and downtime characteristics of the machines were used to model teletherapy operation in low-resource settings.

Results

Modeled average daily throughput was decreased for linacs because of lack of power infrastructure and for cobalt-60 units because of limited and decaying source strength. For conformal radiotherapy delivered with multileaf collimators, average daily patient throughput over 8 years of operation was equal for cobalt-60 units and linacs when an average of 1.83 hours of power outage occurred per 10-hour working day. Relative to conformal treatments delivered with multileaf collimators on the respective machines, the use of advanced techniques on linacs decreased throughput between 20% and 32% and, for cobalt machines, the need to manually place blocks reduced throughput up to 37%.

Conclusion

Our patient throughput data indicate that cobalt-60 units are generally best suited for implementation when machine operation might be 70% or less of total operable time because of power outages or mechanical repair. However, each implementation scenario is unique and requires consideration of all variables affecting implementation.
Presentation, Treatment, and Outcomes of Haitian Women With Breast Cancer in Miami and Haiti: Disparities in Breast Cancer—A Retrospective Cohort Study
Authors: Gomez Alexandra , DeGennaro Vincent , George Sophia H.L. , Reis Isildinha M. , Santamaria Estefania , Westin Gustavo Figueiredo , Gabriel Dieudina , Hurley Judith
Published: February 2017

Purpose

We compared a cohort of Haitian immigrants with residents in Haiti with breast cancer (BC) to evaluate the effects of location on presentation, treatment, and outcomes.

Patients and Methods

Participants were Haitian women with BC living in Miami who presented to the University of Miami/Jackson Memorial Hospital and women with BC living in Haiti who presented to the Innovating Health International Women’s Cancer Center. The primary outcome was the relationship between location, cancer characteristics, and survival. The secondary objective was to compare our results with data extracted from the SEER database. Cox regression was used to compare survival.

Results

One hundred two patients from University of Miami/Jackson Memorial Hospital and 94 patients from Innovating Health International were included. The patients in Haiti, compared with the patients in Miami, were younger (mean age, 50.2 v 53.7 years, respectively; P = .042), presented after a longer duration of symptoms (median, 20 v 3 months, respectively; P < .001), had more advanced stage (44.7% v 25.5% with stage III and 27.6% v 18.6% with stage IV BC, respectively), and had more estrogen receptor (ER) –negative tumors (44.9% v 26.5%, respectively; P = .024). The percentage of women who died was 31.9% in Haiti died compared with 17.6% in Miami. Median survival time was 53.7 months for women in Haiti and was not reached in Miami. The risk of death was higher for women in Haiti versus women in Miami (adjusted hazard ratio, 3.09; P = .0024).

Conclusion

Women with BC in Haiti experience a significantly worse outcome than immigrants in Miami, which seems to be related to a more advanced stage and younger age at diagnosis, more ER-negative tumors, and lack of timely effective treatments. The differences in age and ER status are not a result of access to care and are unexplained.
Awareness and Perception About Cancer Among the Public in Chennai, India
Authors: Elangovan Vidhubala , Rajaraman Swaminathan , Basumalik Barsha , Pandian Dhivya
Published: February 2017

Purpose

Cancer-related stigma influences the way people perceive cancer, which renders cancer control—beginning with prevention and proceeding to palliation—a challenging task. This study aimed to assess the current levels of awareness and perceptions about cancer among people with various socioeconomic status and diverse backgrounds in the city of Chennai, India.

Patients and Methods

The sample population (N = 2,981; 18 to 88 years of age) was stratified into four groups: patients (n = 510), caregivers (n = 494) consulting at the Cancer Institute (Women Indian Association), college students (n = 978), and general public (n = 999). Fourteen statements related to cancer stigma or myths were identified and categorized by awareness (10 items) or perception (4 items). Responses to those statements were recorded by using a Likert scale (yes, no, and don’t know). The data were described by frequency analysis and χ2 test using SPSS Version 13 (SPSS, Chicago, IL).

Results

More than 70% of the study participants were aware that cancer is curable, that cancer is not contagious, and that cancer is not a curse or a death sentence. However, only approximately half believed that surgery or biopsy do not cause cancer to spread to other organs or that radiation therapy does not consist of receiving an electric shock. Higher education, younger age, male sex, personal experience with cancer (either as a patient or caregiver), and high socioeconomic status were the categories of people with increased awareness about cancer.

Conclusion

These factors need to be taken into consideration in tailoring information, education, and communication campaigns. Resource allocation for these campaigns is an investment in cancer control.
Ipilimumab in Pretreated Patients With Advanced Malignant Melanoma: Results of the South African Expanded-Access Program
Authors: Rapoport Bernardo L. , Vorobiof Daniel A. , Dreosti Lydia M. , Nosworthy Adam , McAdam Georgina , Jordaan Johan P. , Miller-Jansön Helen , de Necker Margreet , de Beer Janetta C. , Duvenhage Hennie
Published: February 2017

Purpose

The primary objective of this study was to evaluate 1- and 2-year survival rates and durable remissions in pretreated patients with advanced (unresectable or metastatic) malignant melanoma treated with ipilimumab in a South African expanded-access program (SA-EAP).

Patients and Methods

This multicenter, retrospective study obtained data from pretreated patients with advanced malignant melanoma who were eligible for the ipilimumab SA-EAP. Ipilimumab was administered at a dose of 3 mg/kg intravenously every 3 weeks for four cycles to adults with advanced melanoma for whom at least one line of treatment for metastatic disease had failed. Data from the medical records of 108 patients treated within the SA-EAP were collected and statistically analyzed to determine overall (OS) and progression-free survival (PFS) at 1 and 2 years.

Results

In the population of 108 patients, a median OS of 8.98 months (95% CI, 7.47 to 10.79 months) was observed. One-year OS was 36% (95% CI, 26% to 45%), and 2-year survival was observed as 20% (95% CI, 12% to 27%). The median survival without progression (ie, PFS) was 3.44 months (95% CI, 2.98 to 4.16 months), and 1- and 2-year PFS were 22% (95% CI, 14% to 29%) and 14% (95% CI, 8% to 21%), respectively. The longest recorded survival was 3.4 years. No independent prognostic variables were identified to predict for OS by multivariate Cox proportional hazards model.

Conclusion

In this multicenter South African setting, ipilimumab at a dose of 3 mg/kg was an effective treatment with long-term OS in a subset of patients with pretreated advanced malignant melanoma.
Neoadjuvant Chemotherapy With Capecitabine Plus Cisplatin in Patients With Locally Advanced Nasopharyngeal Cancer: Case Series Study
Authors: Dada Reyad , El Sayed Mohamed , Zekri Jamal
Published: February 2017

Purpose

Capecitabine, an oral fluorouracil (5-FU) derivative, has replaced 5-FU in many chemotherapy regimens used in various GI tract cancers. The experience with capecitabine in nasopharyngeal carcinoma (NPC) is limited.

Patients and Methods

We report on eight patients with locally advanced NPC treated with neoadjuvant chemotherapy with capecitabine and cisplatin.

Results

All eight patients responded well to the chemotherapy combination and achieved complete remission after definitive chemoradiotherapy. No grade 3/4 toxicities were observed. Five patients experienced a relapse after 6, 8, 9, 12, and 17 months.

Conclusion

In the patients studied, capecitabine (in combination with cisplatin) was a safe and effective substitution for 5-FU for the neoadjuvant treatment of locally advanced NPC. Larger prospective clinical studies are required to confirm these results.
Medical Oncologists’ Experiences in Using Genomic Testing for Lung and Colorectal Cancer Care
Authors: Gray Stacy W. , Kim Benjamin , Sholl Lynette , Cronin Angel , Parikh Aparna R. , Klabunde Carrie N. , Kahn Katherine L. , Haggstrom David A. , Keating Nancy L.
Published: February 2017

Purpose:

Genomic testing improves outcomes for many at-risk individuals and patients with cancer; however, little is known about how genomic testing for non–small-cell lung cancer (NSCLC) and colorectal cancer (CRC) is used in clinical practice.

Patients and Methods:

In 2012 to 2013, we surveyed medical oncologists who care for patients in diverse practice and health care settings across the United States about their use of guideline- and non–guideline-endorsed genetic tests. Multivariable regression models identified factors that are associated with greater test use.

Results:

Of oncologists, 337 completed the survey (participation rate, 53%). Oncologists reported higher use of guideline-endorsed tests (eg, KRAS for CRC; EGFR for NSCLC) than non–guideline-endorsed tests (eg, Onco typeDX Colon; ERCC1 for NSCLC). Many oncologists reported having no patients with CRC who had mismatch repair and/or microsatellite instability (24%) or germline Lynch syndrome (32%) testing, and no patients with NSCLC who had ALK testing (11%). Of oncologists, 32% reported that five or fewer patients had KRAS and EGFR testing for CRC and NSCLC, respectively. Oncologists, rather than pathologists or surgeons, ordered the vast majority of tests. In multivariable analyses, fewer patients in nonprofit integrated health care delivery systems underwent testing than did patients in hospital or office-based single-specialty group settings (all P < .05). High patient volume and patient requests (CRC only) were also associated with higher test use (all P < .05).

Conclusion:

Genomic test use for CRC and NSCLC varies by test and practice characteristics. Research in specific clinical contexts is needed to determine whether the observed variation reflects appropriate or inappropriate care. One potential way to reduce unwanted variation would be to offer widespread reflexive testing by pathology for guideline-endorsed predictive somatic tests.
Treatment Strategies for Low-Grade Glioma in Adults
Authors: Oberheim Bush Nancy Ann , Chang Susan
Published: February 2017

Diffuse low-grade gliomas include oligodendrogliomas and astrocytomas. The recent 2016 WHO classification has now updated the definition of these tumors to include molecular characterization, including the presence of isocitrate dehydrogenase mutation and 1p/19q codeletion. In this new classification, the histologic subtype of grade II mixed oligoastrocytoma has been eliminated. Treatment recommendations are currently evolving, mainly because of a change in the prognostic factors that are based on molecular and cytogenetic features. Standard of care includes maximal safe surgical resection. Prior randomized clinical trials stratified treatment arms on the basis of extent of resection and age, with patients stratified into low risk (age younger than 40 years and gross total resection) and high risk (age older than 40 years or subtotal resection). Patients who are low risk may undergo routine magnetic resonance imaging surveillance after resection. On the basis of recently published data, it is now recommended that high-risk patients undergo a combination of both radiation and chemotherapy after surgery. These studies, however, do not address the management of patients with low-grade gliomas in the era of genomic medicine. These treatments can also have great impact on quality of life, and therefore treatment recommendations should be done on an individual basis taking into account the current pathology classification, age, extent of resection, quality of life, and patient preference.
Clear Preferences Under Partial Distribution Information
Authors: Tan Chin Hon , Luo Chunling
Published: February 2017

Stochastic dominance is often used to study preference between different distributions of outcomes. In the stochastic dominance literature, distributions of outcomes are often assumed to be known. However, complete distribution information is rarely available in practice. In this paper, we study weighted almost first-degree stochastic dominance (WAFSD) under limited distribution information. In particular, we show that it is possible to determine WAFSD with linear canonical utility based on expected rewards when outcomes are bounded from below. Furthermore, we illustrate how WAFSD based on more general forms of canonical utility functions can be ensured when additional moment information is available. The key insight is that finite distribution moments can be sufficient for revealing clear preferences in practice, despite the fact that finite distribution moments are generally insufficient for ensuring preferences across all utility functions.
The Car Sharing Economy: Interaction of Business Model Choice and Product Line Design
Authors: Bellos Ioannis , Ferguson Mark , Toktay L. Beril
Published: February 2017

Several auto manufacturers have recently introduced car sharing programs. Although the structure of most programs is the same, there is no clear dominant strategy for the type of vehicles that should be provided through car sharing. In this paper, we consider an original equipment manufacturer (OEM) that contemplates car sharing and designs its product line by accounting for the trade-off between driving performance and fuel efficiency under CAFE standards. Customers have different valuations of driving performance and decide whether to buy, join car sharing or rely on their outside options. We find that the OEM increases the fuel efficiency of the vehicles it provides through car sharing. This higher efficiency enables the OEM to charge a higher selling price to the higher end of the market, thus increasing its profit. This is especially beneficial to higher-end OEMs that face greater cannibalization and can explain why Daimler and BMW have been particularly active in introducing car sharing. Offering car sharing is not always environmentally beneficial. Even when it is, we find that doing so may reduce the OEM’s Corporate Average Fuel Economy (CAFE) level. In such cases, incentive multipliers should be granted for each shared car. Finally, if anticipating aggressive CAFE standards, OEMs may introduce car sharing to better absorb the increase in the production cost.

The online appendix is available at https://doi.org/10.1287/msom.2016.0605 .
Ambulatory care for haematology and oncology patients
Authors: Ingram Bethan
Published: February 2017

Bethan Ingram, Advanced Nurse Practitioner, Teenage Cancer Trust Unit, University Hospital of Wales, Cardiff, discusses alternatives to inpatient-focused services
Core decompression and biotechnologies in the treatment of avascular necrosis of the femoral head
Authors: Calori Giorgio Maria , Mazza Emilio , Colombo Alessandra , Mazzola Simone , Colombo Massimiliano
Published: February 2017

Avascular necrosis (AVN) of the femoral head (FH) causes 5% to 12% of total hip arthroplasties (THA). It especially affects active male adults between the third and fifth decades of life. The exact worldwide incidence is unknown. There are only few data related to each country, but most of it relates to the United States. Non-surgical management has a very limited role in the treatment of AVN of the FH and only in its earliest stages. Core decompression (CD) of the hip is the most common procedure used to treat the early stages of AVN of the FH. Recently, surgeons have considered combining CD with autologous bone-marrow cells, demineralised bone matrix or bone morphogenetic proteins or methods of angiogenic potential to enhance bone repair in the FH. Manuscripts were deemed eligible for our review if they evaluated treatment of early stage AVN of the FH with biotechnology implanted via CD. After application of eligibility criteria, we selected 19 reports for final analysis. The principal results showed that only by correctly mastering the therapeutic principles and adopting proper methods specifically oriented to different stages can the best therapeutic effect be achieved. Combining CD with biotechnology could result in a novel long-lasting hip- preserving treatment option. Furthermore, more refined clinical studies are needed to establish the effectiveness of biotechnology treatments in AVN of the FH.

Cite this article: EFORT Open Rev 2017;2:41-50. DOI: 10.1302/2058-5241.2.150006
La teoría de los modelos de mundo a la luz de Heidegger, Lacan y McCarthy
Authors: Asensi Pérez Manuel
Published: February 2017

Con el fin de proseguir un análisis de la noción de «modelo de mundo» tal y como fue expuesta en el modelo teórica de la así llamada «Crítica como sabotaje» (2011), este texto lleva a cabo una lectura de la noción de mundo en Heidegger según la modalidad y los términos de la misma crítica como sabotaje. Más allá de lo que sean las «intenciones» de Heidegger en su reflexión sobre la relación entre ser y lenguaje, este ensayo subraya cómo el concepto de «precomprensión» está en la línea de lo que llamamos capacidad modalizadora de los discursos. Esa aproximación a Heidegger se ve acompañada por las referencias de Lacan y de Marx, y es ilustrada a partir de la novela de Cormac McCarthy No Country for Old Men.
Effect of Micronaire on Oil Sorption Capacity of Three Different Types of Greige Cotton-Based Nonwoven Substrates
Authors: Singh Vinitkumar , Sawhney Paul , Reynolds Michael , Condon Brian , Kendall Ronald , Kitten Luke , Jain Akshay , Parameswaran Siva , Kendall Ronald J. , Ramkumar Seshadri
Published: February 2017

Satisfactory oil sorption properties and biodegradability of natural fibers have generated renewed interest in the development of oil sorbents for potential use in the cleanup and recovery of offshore oil spills. The objective of this study was to compare the oil sorption capacity of three different types of nonwoven substrates made with two distinctly different grades of greige (raw) cotton of low and high micronaire. These substrates included a needlepunched fabric, a hydroentangled fabric, and a bundle of only loose cotton fibers. The study showed that substrates made with low micronaire cotton exhibited a greater oil sorption capacity compared to those made with high micronaire cotton. The loose-fiber substrate had a greater oil sorption capacity compared to the other two types of substrates.
Characterization and taste masking evaluation of microparticles with cetirizine dihydrochloride and methacrylate-based copolymer obtained by spray drying
Authors: Amelian Aleksandra , Szekalska Marta , Ciosek Patrycja , Basa Anna , Winnicka Katarzyna
Published: February 2017

Taste of a pharmaceutical formulation is an important parameter for the effectiveness of pharmacotherapy. Cetirizine dihydrochloride (CET) is a second-generation antihistamine that is commonly administered in allergy treatment. CET is characterized by extremely bitter taste and it is a great challenge to successfully mask its taste; therefore the goal of this work was to formulate and characterize the microparticles obtained by the spray drying method with CET and poly(butyl methacrylate-co-(2-dimethylaminoethyl) methacrylate-co-methyl methacrylate 1:2:1 copolymer (Eudragit E PO) as a barrier coating. Assessment of taste masking by the electronic tongue has revealed that designed formulations created an effective taste masking barrier. Taste masking effect was also confirmed by the in vivo model and the in vitro release profile of CET. Obtained data have shown that microparticles with a drug/polymer ratio (0.5:1) are promising CET carriers with efficient taste masking potential and might be further used in designing orodispersible dosage forms with CET.
A superior preparation method for daidzein-hydroxypropyl-β-cyclodextrin complexes with improved solubility and dissolution: Supercritical fluid process
Authors: Pan Hao , Wang Han-Bing , Yu Yi-Bin , Cheng Bing-Chao , Wang Xiao-Yu , Li Ying
Published: February 2017

Advantages of the supercritical fluid (SCF) process compared to the conventional solution stirring method (CSSM) in the preparation of daidzein-hydroxypropyl-β-cyclodextrin (HPβCD) complexes were investigated. Formation of daidzein/ HPβCD inclusion complexes was confirmed by Fourier transformed-infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM). Particle size, inclusion yield, drug solubility and dissolution of daidzein/HPβCD complexes were evaluated. Compared to CSSM, the SCF process resulted in higher inclusion yield and higher solubility. Also, extended dissolution of daidzein from the SCF processed HPβCD inclusion complexes was observed, with only 22.94 % released in 45 min, compared to its rapid release from those prepared by CSSM, with 98.25 % drug release in 15 min. This extended release of daidzein from SCF prepared inclusion complexes was necessary to avoid drug precipitation and improve drug solubilisation in the gastrointestinal tract. The results showed that the SCF process is a superior preparation method for daidzein-hydroxypropyl-β-cyclodextrin complexes.
Public health care system, a quasi-experimental study: Acceptance and attitude to implicate clinical services
Authors: Gillani Syed Wasif , Abdul Mohi Iqbal Mohammad
Published: February 2017

A six-month longitudinal intervention arm study with a pre-post cross-sectional questionnaire-based survey was performed. A 3-phase objective structured clinical examination (OSCE) design was utilized for evaluation of acceptance and attitude of pharmacy students towards clinical pharmacy services. The pre-OSCE survey showed increased disagreement with the role of clinical pharmacists, compared to a significant positive shift in attitude towards their services in the healthcare team after 6 months of the trial. Responses improved for awareness (the current healthcare system could be improved by involving pharmacists, p < 0.02) and positive attitude categories (doctors and nurses would be happy to welcome the services of competent clinical pharmacists as part of their team, p < 0.01) in addition to competency (pharmacists have sufficient clinical training to advise doctors and nurses, p < 0.01). The predictive model suggested a strong positive effect on patient interaction, medical information tasks, clinical decisions on drug-related problems (DRPs), and communication with healthcare professionals (R2= 0.41, F = 1.51, p < 0.001).
Pulmonary prophylactic impact of melatonin and/or quercetin: A novel therapy for inflammatory hypoxic stress in rats
Authors: Al-Rasheed Nouf M. , Fadda Laila , Attia Hala A. , Sharaf Iman A. , Mohamed Azza M. , Al-Rasheed Nawal M.
Published: February 2017

The study aims to compare, through histological and biochemical studies, the effects of quercetin, melatonin and their combination in regulation of immuno-inflammatory mediators and heat shock protein expressions in sodium nitrite induced hypoxia in rat lungs. The results revealed that NaNO2 injection caused a significant decrease in Hb in rats, while serum levels of TNF-α, IL-6 and CRP, VEGF and HSP70 were elevated compared to the control group. Administration of melatonin, quercetin or their combination before NaNO2 injection markedly reduced these parameters. Histopathological examination of the lung tissue supported these biochemical findings. The study suggests that melatonin and/or quercetin are responsible for lung tissue protection in hypoxia by downregulation of immuno-inflammatory mediators and heat shock protein expressions. Pre-treatment of hypoxic animals with a combination of melatonin and quercetin was effective in modulating most of the studied parameters to near-normal levels.
The role of extracellular vesicle microRNAs in cancer biology
Authors: Takahashi Ryou-u , Prieto-Vila Marta , Hironaka Ai , Ochiya Takahiro
Published: February 2017

microRNAs (miRNAs) constitute a large family of small, approximately 20–22 nucleotide non-coding RNAs that regulate the expression of target genes, mainly at the post-transcriptional level. Multiple studies report that miRNAs are involved in homeostatic maintenance and that aberrant expression of miRNAs is often observed in various types of diseases, including cancer. In cancer biology, miRNAs exert functional roles in tumor initiation, drug resistance, and metastasis. miRNAs are also secreted through small vesicles called exosomes, which are endosome-derived vesicles derived from various cell types including immune and tumor cells. In addition to cellular miRNAs (ce-miRNAs), secreted miRNAs (se-miRNAs) play important roles in cancer development and metastasis. Therefore, se-miRNAs in body fluids have been investigated as a promising biomarkers and therapeutic targets for cancer treatment. In this review, we summarize the current knowledge of miRNA functions in cancer development and discuss the potential clinical applications of se-miRNAs, e.g. as diagnostic markers and therapeutic targets.
Malignant perivascular epitheloid cell tumour (PEComa) of the lung – a rare entity
Authors: Chakrabarti Amitabha , Bandyopadhyay Manujesh , Purkayastha Biswarup
Published: February 2017

Malignant Perivascular Epitheloid Cell Tumour (PEComa) of the lung is very rare, with only six cases reported in literature. This case presented with a large mass originating from right upper lobe of the lung with dilemma in its histopathological diagnosis and management. Postoperative histopathology after a right upper and middle lobectomy describes a tumour with an alveolar/nested pattern of growth and epitheloid morphology with expression of TFE-3 and diagnosed as PEComa. After 6 months the patient had a local recurrence inside the thorax & chest wall.This case qualifies it as a rare type of malignant PEComa with younger age of presentation, aggressive clinical behaviour & malignant histological features along with TFE3 positivity on immunohistochemistry. This case is probably the first of its kind with the largest reported size involving two lobes of the lung.
Idealization of The Real Stirling Cycle
Authors: Červenka Libor
Published: February 2017

The paper presents a potential idealization of the real Stirling cycle. This idealization is performed by modifying the piston movement corresponding to the ideal Stirling cycle. The focus is on the cycle thermodynamics with respect to the indicated efficiency and indicated power. A detailed 1-D simulation model of a Stirling engine is used as a tool for this assessment. The model includes real non-zero volumes of heater, regenerator, cooler and connecting pipe. The model is created in the GT Power commercial simulation software.
Valuing environmental health for informed policy-making
Authors: Máca Vojtěch , Melichar Jan , Ščasný Milan , Kohlová Markéta Braun
Published: February 2017

Background:

Monetized environmental health impact assessments help to better evaluate the environmental burden of a wide range of economic activities. Apart from the limitations and uncertainties in physical and biological science used in such assessments, assumptions taken from economic valuation may also substantially influence subsequent policy-making considerations.

Aim:

This study attempts to demonstrate the impact of normative policy assumptions on quantified external costs using a case study of recently discussed variants of future coal mining and use of extracted coal in electricity and heat generation in the Czech Republic.

Methods:

A bottom-up impact-pathway approach is used for quantification of external costs. Several policy perspectives are elaborated for aggregating impacts that differ in geographic coverage and in how valuation of quantified impacts is adjusted in a particular perspective.

Results:

We find that the fraction of monetized external impacts taken into policy-making considerations may vary according to choice of decision perspective up to a factor of 10.

Conclusion:

At present there are virtually no hard rules for defining geographical boundaries or adjusting values for a summation of monetized environmental impacts. We, however, stress that any rigorous external cost assessment should, for instance in a separate calculation, take account of impacts occurring beyond country borders.
Environmental life cycle assessment of railway bridge materials using UHPFRC
Authors: Bizjak Karmen Fifer , Šajna Aljoša , Slanc Katja , Knez Friderik
Published: February 2017

The railway infrastructure is a very important component of the world’s total transportation network. Investment in its construction and maintenance is significant on a global scale. Previously published life cycle assessment (LCA) studies performed on road and rail systems very seldom included infrastructures in detail, mainly choosing to focus on vehicle manufacturing and fuel consumption. This article presents results from an environmental study for railway steel bridge materials for the demonstration case of the Buna Bridge in Croatia. The goal of these analyses was to compare two different types of remediation works for railway bridges with different materials and construction types. In the first part, the environmental impact of the classical concrete bridge construction was calculated, whereas in the second one, an alternative new solution, namely, the strengthening of the old steel bridge with ultra-high-performance fibre-reinforced concrete (UHPFRC) deck, was studied. The results of the LCA show that the new solution with UHPFRC deck gives much better environmental performance. Up to now, results of LCA of railway open lines, railway bridges and tunnels have been published, but detailed analyses of the new solution with UHPFRC deck above the old bridge have not previously been performed.
Interpretation of aeromagnetic data over Abeokuta and its environs, Southwest Nigeria, using spectral analysis (Fourier transform technique)
Authors: Olurin Oluwaseun T. , Ganiyu Saheed A. , Hammed Olaide S. , Aluko Taiwo J.
Published: February 2017

This study presents the results of spectral analysis of magnetic data over Abeokuta area, Southwestern Nigeria, using fast Fourier transform (FFT) in Microsoft Excel. The study deals with the quantitative interpretation of airborne magnetic data (Sheet No. 260), which was conducted by the Nigerian Geological Survey Agency in 2009. In order to minimise aliasing error, the aeromagnetic data was gridded at spacing of 1 km. Spectral analysis technique was used to estimate the magnetic basement depth distributed at two levels. The result of the interpretation shows that the magnetic sources are mainly distributed at two levels. The shallow sources (minimum depth) range in depth from 0.103 to 0.278 km below ground level and are inferred to be due to intrusions within the region. The deeper sources (maximum depth) range in depth from 2.739 to 3.325 km below ground and are attributed to the underlying basement.