bluuebunny/crossref_metadata_2025 huggingface dataset:
Risks of phase I research with healthy participants: A systematic review
Authors: Johnson Rebecca A , Rid Annette , Emanuel Ezekiel , Wendler David
Published: September 2015

Background/aims:

Tragedies suggest that phase I trials in healthy participants may be highly risky. This possibility raises concern that phase I trials may exploit healthy participants to develop new therapies, making the translation of scientific discoveries ethically worrisome. Yet, few systematic data evaluate this concern. This article systematically reviews the risks of published phase I trials in healthy participants and evaluates trial features associated with increased risks.

Methods:

Data on adverse events and trial characteristics were extracted from all phase I trials published in PubMed, Embase, Cochrane, Scopus, and PsycINFO (1 January 2008–1 October 2012). Inclusion criteria were phase I studies that enrolled healthy participants of any age, provided quantitative adverse event data, and documented the number of participants enrolled. Exclusion criteria included (1) adverse event data not in English, (2) a “challenge” study in which participants were administered a pathogen, and (3) no quantitative information about serious adverse events. Data on the incidence of adverse events, duration of adverse event monitoring, trial agent tested, participant demographics, and trial location were extracted.

Results:

In 475 trials enrolling 27,185 participants, there was a median of zero serious adverse events (interquartile range = 0–0) and a median of zero severe adverse events (interquartile range = 0–0) per 1000 treatment group participants/day of monitoring. The rate of mild and moderate adverse events was a median of 1147.19 per 1000 participants (interquartile range = 651.52–1730.9) and 46.07 per 1000 participants/adverse event monitoring day (interquartile range = 17.80–77.19).

Conclusion:

We conclude that phase I trials do cause mild and moderate harms but pose low risks of severe harm. To ensure that this conclusion also applies to unpublished trials, it is important to increase trial transparency.
Meeting the needs of women in secure mental health: a conceptual framework for nurses
Authors: Parkes Jacqueline , Freshwater Dawn
Published: September 2015

Within the wards of Britain’s high and medium secure mental health services, the needs of the female population differ significantly from those of their male counterparts. Although much smaller in number, the vast majority of female patients formally detained in secure services are young, Caucasian women, who are less likely to be prone to criminality and have a propensity to suffer from psychological distress. Many have experienced extensive trauma and exhibit both internally and externally driven violence. Drawn from the women’s own narratives and analysed using a descriptive phenomenological approach, the findings provide the basic structure for a new ‘humanistic conceptual framework for care’ which could be used by mental health practitioners to both inform and structure the daily provision of care and to better understand the physical and mental health needs of this unique patient group within secure mental health services.
The effects of contemporary behavioural weight loss maintenance interventions for long term weight loss: a systematic review
Authors: Gilmartin Jo , Murphy Monica
Published: September 2015

Background

A major challenge in the treatment of obesity is the long term maintenance of weight loss and prevention of weight regain. The Department of Health in England has recommended that health professionals should consider behavioural weight loss interventions.

Objective

To evaluate the effectiveness of behavioural weight loss interventions in maintaining long term weight loss.

Methods

Using the PRISMA statement we performed a systematic review of randomised controlled trials. Data sources involved in the study are the Cochrane Library, MEDLINE, EMBASE, psycINFO, CINAHL and the Web of Science. Studies were assessed independently by two authors to provide inter-rater reliability.

Results

This review presents the findings from 13 randomised controlled trials of weight loss maintenance utilising interventions that include diet strategies, behavioural strategies, lifestyle counselling and drug therapy, group therapy and the Internet. The sample population included adult participants of 18 years+ with a BMI > 30 kg/m2. The results revealed that lifestyle interventions targeting diet and physical activity are effective in sustaining weight loss up to two years with extended care. Moreover, pharmacology combined with lifestyle interventions was effective.

Conclusion

There is important evidence that the use of behavioural weight loss interventions are effective in sustaining long term weight loss, albeit limited. There was high heterogeneity among the studies; hence caution is required when interpreting the findings. Also, intentions to treat principles and methods to handle missing data are not clearly reported across some studies. Blinding of participants and outcome assessors is very limited.
The 6–8 week check
Authors: Subramanian Geeta , Shanmugananda Kala , Pitts James
Published: September 2015

Universal screening is offered to all children in the UK, as specified in the Department of Health’s core document National Service Framework for Children, Young People and Maternity. Screening programmes help early detection of health problems, maximising opportunities for timely intervention and best outcomes for children. Newborns are inspected immediately after birth. A full physical examination is conducted within 72 hours. Babies are screened for six inherited metabolic diseases in addition to hypothyroidism, cystic fibrosis and haemoglobinopathies. Newborn hearing screen is universal. The 6–8 week check is an integral part of the screening schedule for children in the UK.
Biosimilar Insulin and Costs
Authors: Heinemann Lutz
Published: September 2015

The costs for insulin treatment are high, and the steady increase in the number of patients with diabetes on insulin presents a true challenge to health care systems. Therefore, all measures to lower these costs are welcomed by patients, physicians, and health care providers. The market introduction of biosimilar insulins presents an option to lower treatment costs as biosimilars are usually offered at a lower price than the originator product. However, the assumption that a drastic reduction in insulin prices will take place, as was observed with many generic drugs, is most probably not realistic. As the first biosimilar insulin has now been approved in the EU, this commentary discusses a number of aspects that are relevant when it comes to the potential cost reduction we will see with the use of biosimilar insulins.
Psychological reactions of adolescent schoolgirls to human papillomavirus vaccination in western Uganda: A comparative cross-sectional study
Authors: Turiho Andrew Kampikaho , Okello Elialilia S , Muhwezi Wilson W , Nakasujja Noeline , Katahoire Anne R
Published: September 2015

Schoolgirls in two Ugandan districts were recently vaccinated against human papillomavirus that causes most cervical cancer. This cross-sectional comparative study used mixed research methods to assess influence of human papillomavirus vaccination on adolescents’ worrisome thoughts about being vaccinated and psychological distress. Vaccination predicted worrisome thoughts among the recently vaccinated (adjusted odds ratio: 1.65, confidence interval: 1.13–2.41; p = 0.01). Vaccination predicted distress (1.75, confidence interval: 1.09–2.82; p = 0.02), particularly among those recently vaccinated (1.92, confidence interval: 1.27–2.89; p = 0.001) and those who experienced worrisome thoughts (1.80, confidence interval: 1.06–3.07; p = 0.02). Parental communication mitigated distress (0.50, confidence interval: 0.35–0.72; p = 0.000).
Racial Disparities in Use of Chiropractic Services by Medicare Beneficiaries Aged 65 to 99 in Los Angeles County, California
Authors: Whedon James M. , Kimura Melissa N. , Phillips Reed B.
Published: September 2015

Racial and ethnic disparities in utilization of chiropractic services have been described at the state level, but little is known about such local disparities. We analyzed Medicare data for the year 2008 to evaluate by ZIP code for utilization of chiropractic services among older adults in Los Angeles County, California. We evaluated for availability and use of chiropractic services by racial/ethnic category, quantified geographic variations by coefficient of variation, and mapped utilization by selected racial/ethnic categories. Among 7502 beneficiaries who used chiropractic services, 72% were white, 12% Asian, 1% black, 1% Hispanic, and 14% other/unknown. Variation in the number of beneficiaries per ZIP code who used chiropractic services was highest among Hispanics, blacks, and Asians. We found evidence of racial disparities in use of chiropractic services at the local level in Los Angeles County. Older blacks and Hispanics in Los Angeles County may be underserved with regard to chiropractic care.
When Too Much Integration and Regulation Hurts
Authors: Abrutyn Seth , Mueller Anna S.
Published: September 2015

Durkheim’s model of suicide famously includes four types: anomic, egoistic, altruistic, and fatalistic suicides; however, sociology has primarily focused on anomic and egoistic suicides and neglected suicides predicated on too much integration or regulation. This article addresses this gap. We begin by elaborating Durkheim’s concepts of integration and regulation using insights from contemporary social psychology, the sociology of emotions, and cultural sociology. We then posit a more coherent theory of suicides resulting from too much integration and too much regulation. Importantly, we shift attention away from motives (altruism = self-sacrifice). We also reject the idea that high levels of integration and regulation are in and of themselves harmful. Instead, we propose three sociocultural explanations—(1) disruptions, (2) the spread of negative emotions and ideas, and (3) the pervasiveness of negative, suicide scripts—that elucidate how and why too much integration and regulation can become harmful and facilitate suicide.
Controlled Laboratory Comparison Study of Motion With Football Equipment in a Destabilized Cervical Spine
Authors: Prasarn Mark L. , Horodyski MaryBeth , DiPaola Matthew J. , DiPaola Christian P. , Del Rossi Gianluca , Conrad Bryan P. , Rechtine Glenn R.
Published: September 2015

Background

Numerous studies have shown that there are better alternatives to log rolling patients with unstable spinal injuries, although this method is still commonly used for placing patients onto a spine board. No previous studies have examined transfer maneuvers involving an injured football player with equipment in place onto a spine board.

Purpose

To test 3 different transfer maneuvers of an injured football player onto a spine board to determine which method most effectively minimizes spinal motion in an injured cervical spine model.

Study Design

Controlled laboratory study.

Methods

Five whole, lightly embalmed cadavers were fitted with shoulder pads and helmets and tested both before and after global instability was surgically created at C5-C6. An electromagnetic motion analysis device was used to assess the amount of angular and linear motion with sensors placed above and below the injured segment during transfer. Spine-boarding techniques evaluated were the log roll, the lift and slide, and the 8-person lift.

Results

The 8-person lift technique resulted in the least amount of angular and linear motion for all planes tested as compared with the lift-and-slide and log-roll techniques. This reached statistical significance for lateral bending ( P = .031) and medial-lateral translation ( P = .030) when compared with the log-roll maneuver. The lift-and-slide technique was significantly more effective at reducing motion than the log roll for axial rotation ( P = .029) and lateral bending ( P = .006).

Conclusion

The log roll resulted in the most motion at an unstable cervical injury as compared with the other 2 spine-boarding techniques examined. The 8-person lift and lift-and-slide techniques may both be more effective than the log roll at reducing unwanted cervical spine motion when spine boarding an injured football player. Reduction of such motion is critical in the prevention of iatrogenic injury.
Outcome of patients with distinct molecular genotypes and cytogenetically normal AML after allogeneic transplantation
Authors: Schmid Christoph , Labopin Myriam , Socié Gerard , Daguindau Etienne , Volin Liisa , Huynh Anne , Bourhis Jean Henri , Milpied Noel , Cornelissen Jan , Chevallier Patrice , Maertens Johan , Jindra Pavel , Blaise Didier , Lenhoff Stig , Ifrah Norbert , Baron Frédéric , Ciceri Fabio , Gorin Claude , Savani Bipin , Giebel Sebastian , Polge Emmanuelle , Esteve Jordi , Nagler Arnon , Mohty Mohamad
Published: September 2015

Key Points

In AML with normal cytogenetics, age, response to induction, and FLT3-ITD allow for an estimate of outcome after allogeneic HSCT in CR1. Neither variation of classical transplant techniques nor development of chronic GVHD outweighs the negative impact of FLT3-ITD.
Intra‐rater reliability of hallux flexor strength measures using the Nintendo Wii Balance Board
Authors: Quek June , Treleaven Julia , Brauer Sandra G. , O'Leary Shaun , Clark Ross A.
Published: September 2015

Background

The purpose of this study was to investigate the intra‐rater reliability of a new method in combination with the Nintendo Wii Balance Board (NWBB) to measure the strength of hallux flexor muscle.

Methods

Thirty healthy individuals (age: 34.9 ± 12.9 years, height: 170.4 ± 10.5 cm, weight: 69.3 ± 15.3 kg, female = 15) participated. Repeated testing was completed within 7 days. Participants performed strength testing in sitting using a wooden platform in combination with the NWBB. This new method was set up to selectively recruit an intrinsic muscle of the foot, specifically the flexor hallucis brevis muscle. Statistical analysis was performed using intra‐class coefficients and ordinary least product analysis. To estimate measurement error, standard error of measurement (SEM), minimal detectable change (MDC) and percentage error were calculated.

Results

Results indicate excellent intra‐rater reliability (ICC = 0.982, CI = 0.96‐0.99) with an absence of systematic bias. SEM, MDC and percentage error value were 0.5, 1.4 and 12 % respectively.

Conclusions

This study demonstrates that a new method in combination with the NWBB application is reliable to measure hallux flexor strength and has potential to be used for future research and clinical application.
Subsequent shock deliveries are associated with increased favorable neurological outcomes in cardiac arrest patients who had initially non-shockable rhythms
Authors: Kitamura Nobuya , Nakada Taka-aki , Shinozaki Koichiro , Tahara Yoshio , Sakurai Atsushi , Yonemoto Naohiro , Nagao Ken , Yaguchi Arino , Morimura Naoto ,   on behalf of the SOS-KANTO 2012 Study Group
Published: September 2015

Introduction

Previous studies evaluating whether subsequent conversion to shockable rhythms in patients who had initially non-shockable rhythms was associated with altered clinical outcome reported inconsistent results. Therefore, we hypothesized that subsequent shock delivery by emergency medical service (EMS) providers altered clinical outcomes in patients with initially non-shockable rhythms.

Methods

We tested for an association between subsequent shock delivery in EMS resuscitation and clinical outcomes in patients with initially non-shockable rhythms (n = 11,481) through a survey of patients after out-of-hospital cardiac arrest in the Kanto region (SOS-KANTO) 2012 study cohort, Japan. The primary investigated outcome was 1-month survival with favorable neurological functions. The secondary outcome variable was the presence of subsequent shock delivery. We further evaluated the association of interval from initiation of cardiopulmonary resuscitation to shock with clinical outcomes.

Results

In the univariate analysis of initially non-shockable rhythms, patients who received subsequent shock delivery had significantly increased frequency of return of spontaneous circulation, 24-hour survival, 1-month survival, and favorable neurological outcomes compared to the subsequent not shocked group (P <0.0001). In the multivariate logistic regression analysis, subsequent shock was significantly associated with favorable neurological outcomes (vs. not shocked; adjusted P = 0.0020, odds ratio, 2.78; 95 % confidence interval, 1.45–5.30). Younger age, witnessed arrest, initial pulseless electrical activity rhythms, and cardiac etiology were significantly associated with the presence of subsequent shock in patients with initially non-shockable rhythms.

Conclusions

In this study of cardiac arrest patients with initially non-shockable rhythms, patients who received early defibrillation by EMS providers had increased 1-month favorable neurological outcomes.
The accuracy of presepsin (sCD14-ST) for the diagnosis of sepsis in adults: a meta-analysis
Authors: Zhang Xin , Liu Dan , Liu You-Ning , Wang Rui , Xie Li-Xin
Published: September 2015

Introduction

The early diagnosis of sepsis remains a challenge. Recently, soluble cluster of differentiation 14 subtype (sCD14-ST), also known as presepsin, has been identified as a potential biomarker of sepsis. We performed a meta-analysis to assess the diagnostic accuracy of presepsin for sepsis in patients with systemic inflammation.

Methods

We systematically searched the PubMed, Embase, Web of Knowledge and Cochrane databases. Studies were included if they assessed the diagnostic accuracy of presepsin for sepsis in adult patients with systemic inflammatory response syndrome (SIRS). Furthermore, a 2 × 2 contingency table was constructed based on these results. Two authors independently judged the studies and extracted the data. The diagnostic accuracy of presepsin in sepsis was calculated using a bivariate meta-analysis model. The Q-test and I2 index were used to test the heterogeneity.

Results

Eight studies involving a total of 1,815 patients were included in the present study. The pooled sensitivity, specificity, diagnostic odds ratio, positive likelihood ratio and negative likelihood ratio were 0.86 (95 % CI: 0.79-0.91), 0.78 (95 % CI: 0.68-0.85), 22 (95 % CI: 10–48), 3.8 (95 % CI: 2.6-5.7), and 0.18 (95 % CI: 0.11-0.28), respectively. The area under the summary receiver operator characteristic curve was 0.89 (95 % CI: 0.86–0.92). Meta-regression analysis revealed that consecutive patient selection, sample size and setting significantly accounted for the heterogeneity of sensitivity.

Conclusions

Our findings suggest that presepsin exhibits very good diagnostic accuracy (AUC=0.89) for the diagnosis for sepsis. Nevertheless, an overall assessment of all the clinical indexes for sepsis diagnosis and continual re-evaluation of presepsin during the course of the disease are needed.
Nonmelanoma Cutaneous Head and Neck Cancer and Merkel Cell Carcinoma: Current Concepts, Advances, and Controversies
Authors: Porceddu Sandro V. , Veness Michael J. , Guminski Alexander
Published: September 2015

Nonmelanoma skin cancer (NMSC) is the most common cancer worldwide and the most frequently observed malignancy in whites. Approximately 75% to 80% are basal cell carcinomas and 20% to 25% are squamous cell carcinomas. Incidence is increasing, partly reflecting an ageing population, and NMSC is more commonly seen in men. The predominant causative agent is ultraviolet solar radiation exposure, with the majority of cases occurring on the head and neck. Surgical excision is typically the treatment of choice, providing histopathologic information, high cure rates, and acceptable cosmetic and functional outcomes. Radiation therapy is reserved for cases where surgery is not the preferred choice or for high-risk cases where adjuvant therapy is recommended. Although overall mortality rates are low, patients with complex cases such as those with immunosuppression should be considered for management within multidisciplinary tumor boards. In contrast, Merkel cell carcinoma is a rare and aggressive malignancy, frequently arising on the head and neck in older whites, with a poorer prognosis. This article focuses on the current evidence guiding practice, recent advances, and areas of controversy in NMSC and Merkel cell carcinoma of the head and neck.
Human Papillomavirus–Negative Pharyngeal Cancer
Authors: Dillon Magnus T. , Harrington Kevin J.
Published: September 2015

Human papillomavirus–negative head and neck squamous cell carcinoma (HNSCC) carries a poor prognosis, and despite optimal treatment with chemoradiotherapy to the limit of tolerance, many patients will relapse. A number of methods for intensifying treatment of HNSCC have been investigated, leading to the current standards of care. Novel agents targeting tumor cell and stromal signaling, DNA damage response, and immune system are now reaching clinical trials in combination with chemoradiotherapy. In this review, we discuss the evidence for the current treatment of locally advanced human papillomavirus–negative HNSCC, as well as investigational therapies, such as hypoxia modification, molecular targeting of epidermal growth factor receptor family, vascular endothelial growth factor receptor or DNA damage response proteins in combination with radiation therapy.
Management of Nasopharyngeal Carcinoma: Current Practice and Future Perspective
Authors: Lee Anne W.M. , Ma Brigette B.Y. , Ng Wai Tong , Chan Anthony T.C.
Published: September 2015

Nasopharyngeal carcinoma of the undifferentiated subtype is endemic to southern China, and patient prognosis has improved significantly over the past three decades because of advances in disease management, diagnostic imaging, radiotherapy technology, and broader application of systemic therapy. Despite the excellent local control with modern radiotherapy, distant failure remains a key challenge. Advances in molecular technology have helped to decipher the molecular pathogenesis of nasopharyngeal carcinoma as well as its etiologic association with the Epstein-Barr virus. This in turn has led to the discovery of novel biomarkers and drug targets, rendering this cancer site a current focus for new drug development. This article reviews and appraises the key literature on the current management of nasopharyngeal carcinoma and future directions in clinical research.
Management of Squamous Cancer Metastatic to Cervical Nodes With an Unknown Primary Site
Authors: Galloway Thomas J. , Ridge John A.
Published: September 2015

Squamous cell carcinoma of an unknown primary (SCCUP) of the head and neck is a rare disease. As a diagnosis of exclusion, the manner in which it is assigned merits consideration. Despite the development and refinement of several techniques designed to locate an occult tumor, including cross-sectional anatomic imaging, functional imaging, and transoral surgical techniques, delineating SCCUP remains an active clinical problem. Its relative rarity has prevented prospective study of the entity. Hence, investigators must rely on retrospective analyses to understand the disease and its appropriate treatment. The current understanding of SCCUP differs substantially from when it was initially described decades ago. The most common site of a small primary tumor initially thought to represent SCCUP is the tonsil or base of the tongue, and an increasing percentage are associated with human papilloma virus. Modern treatment of SCCUP by neck dissection alone, neck dissection followed by radiation with or without concurrent chemotherapy, or primary chemoradiation according to initial nodal disease burden produces extraordinarily low recurrence rates. Whether the potential mucosal primary site and/or the contralateral neck should be electively treated is controversial. Efficacy data seem to be similar; therefore, an evaluation of the toxicity of both treatment paradigms is warranted.
Immunology and Immunotherapy of Head and Neck Cancer
Authors: Ferris Robert L.
Published: September 2015

The immune system plays a key role in the development, establishment, and progression of head and neck squamous cell carcinoma (HNSCC). A greater understanding of the dysregulation and evasion of the immune system in the evolution and progression of HNSCC provides the basis for improved therapies and outcomes for patients. HNSCC cells evade the host immune system through manipulation of their own immunogenicity, production of immunosuppressive mediators, and promotion of immunomodulatory cell types. Through the tumor's influence on the microenvironment, the immune system can be exploited to promote metastasis, angiogenesis, and growth. This article provides a brief overview of key components of the immune infiltrating cells in the tumor microenvironment, reviewing immunological principles related to head and neck cancer, including the concept of cancer immunosurveillance and immune escape. Current immunotherapeutic strategies and emerging results from ongoing clinical trials are presented.
Organ Preservation for Advanced Larynx Cancer: Issues and Outcomes
Authors: Forastiere Arlene A. , Weber Randal S. , Trotti Andy
Published: September 2015

Purpose

To provide a review of the clinical data, controversies, and limitations that underpin current recommendations for approaches to larynx preservation for locally advanced larynx cancer requiring total laryngectomy.

Methods

The key findings from pivotal randomized controlled trials are discussed, including quality of life, late effects, and function assessments. Trials investigating taxane inclusion in induction chemotherapy and trials of epidermal growth factor receptor inhibition for radiosensitization are put into perspective for larynx cancer. Controversies in the management of T4 primaries and the opportunities for conservation laryngeal surgery are reviewed.

Results

There are data from clinical trials to support induction chemotherapy, followed by radiotherapy (preferred approach in Europe) and concomitant cisplatin plus radiotherapy (preferred in North America) for nonsurgical preservation of the larynx. Treatment intensification by a sequential approach of induction, followed by concomitant treatment, is investigational. Transoral laryngeal microsurgery and transoral robotic partial laryngectomy have application in selected patients.

Conclusion

The management of locally advanced larynx cancer is challenging and requires an experienced multidisciplinary team for initial evaluation, response assessment, and support during and after treatment to achieve optimal function, quality of life, and overall survival. Patient expectations, in addition to tumor extent, pretreatment laryngeal function, and coexisting chronic disease, are critical factors in selecting surgical or nonsurgical primary treatment.
Randomized, Double-Blind, Phase II Study of Ruxolitinib or Placebo in Combination With Capecitabine in Patients With Metastatic Pancreatic Cancer for Whom Therapy With Gemcitabine Has Failed
Authors: Hurwitz Herbert I. , Uppal Nikhil , Wagner Stephanie A. , Bendell Johanna C. , Beck J. Thaddeus , Wade Seaborn M. , Nemunaitis John J. , Stella Philip J. , Pipas J. Marc , Wainberg Zev A. , Manges Robert , Garrett William M. , Hunter Deborah S. , Clark Jason , Leopold Lance , Sandor Victor , Levy Richard S.
Published: September 2015

Purpose

Patients with advanced pancreatic adenocarcinoma have a poor prognosis and limited second-line treatment options. Evidence suggests a role for the Janus kinase (JAK)/signal transducer and activator of transcription pathway in the pathogenesis and clinical course of pancreatic cancer.

Patients and Methods

In this double-blind, phase II study, patients with metastatic pancreatic cancer who had experienced treatment failure with gemcitabine were randomly assigned 1:1 to the JAK1/JAK2 inhibitor ruxolitinib (15 mg twice daily) plus capecitabine (1,000 mg/m2 twice daily) or placebo plus capecitabine. The primary end point was overall survival (OS); secondary end points included progression-free survival, clinical benefit response, objective response rate, and safety. Prespecified subgroup analyses evaluated treatment heterogeneity and efficacy in patients with evidence of inflammation.

Results

In the intent-to-treat population (ruxolitinib, n = 64; placebo, n = 63), the hazard ratio was 0.79 (95% CI, 0.53 to 1.18; P = .25) for OS and was 0.75 (95% CI, 0.52 to 1.10; P = .14) for progression-free survival. In a prespecified subgroup analysis of patients with inflammation, defined by serum C-reactive protein levels greater than the study population median (ie, 13 mg/L), OS was significantly greater with ruxolitinib than with placebo (hazard ratio, 0.47; 95% CI, 0.26 to 0.85; P = .011). Prolonged survival in this subgroup was supported by post hoc analyses of OS that categorized patients by the modified Glasgow Prognostic Score, a systemic inflammation–based prognostic system. Grade 3 or greater adverse events were observed with similar frequency in the ruxolitinib (74.6%) and placebo (81.7%) groups. Grade 3 or greater anemia was more frequent with ruxolitinib (15.3%; placebo, 1.7%).

Conclusion

Ruxolitinib plus capecitabine was generally well tolerated and may improve survival in patients with metastatic pancreatic cancer and evidence of systemic inflammation.
Epidemiology of Human Papillomavirus–Positive Head and Neck Squamous Cell Carcinoma
Authors: Gillison Maura L. , Chaturvedi Anil K. , Anderson William F. , Fakhry Carole
Published: September 2015

Human papillomavirus (HPV) is now established as the principal cause of an increase in incidence of a subset of head and neck squamous cell cancers (HNCs) in numerous geographic regions around the world. Further study of the epidemiology of HPV-positive HNC will be critical to the development and implementation of public health interventions to reverse these global incidence trends. Here, recent data are reviewed to provide insight into several topics, including incidence trends and projections for HPV-positive HNC; the worldwide HPV-attributable fraction; sex disparities in cancer risk; the epidemiology of oral HPV infection; the latency period between infection and cancer; the potential impact of prophylactic HPV vaccination; and prospects for secondary prevention through screening for oral HPV infection or seroreactivity to viral antigens. The identification of a single necessary cause for any cancer provides a rare and perhaps extraordinary opportunity for cancer prevention.
Oncologic Surveillance After Surgical Resection for Renal Cell Carcinoma: A Novel Risk-Based Approach
Authors: Stewart-Merrill Suzanne B. , Thompson R. Houston , Boorjian Stephen A. , Psutka Sarah P. , Lohse Christine M. , Cheville John C. , Leibovich Bradley C. , Frank Igor
Published: September 2015

Purpose

The appropriate duration of surveillance for renal cell carcinoma (RCC) after radical or partial nephrectomy remains unknown, and evidence to support current guidelines are lacking. Herein, we provide an approach to surveillance that balances the risk of recurrence versus the risk of non-RCC death.

Patients and Methods

We identified 2,511 patients who underwent surgery for M0 RCC between 1990 and 2008. Patients were stratified for analysis by pathologic stage (pT1Nx-0, pT2Nx-0, pT3/4Nx-0, and pTanyN1), relapse location (abdomen, chest, bone, and other), age (< 50, 50 to 59, 60 to 69, 70-79 and ≥ 80 years), and Charlson comorbidity index (CCI; ≤ 1 and ≥ 2). Risks of disease recurrence and non-RCC death were estimated by using parametric models for time-to-failure with Weibull distributions. Surveillance duration was estimated at the point when the risk of non-RCC death exceeded the risk of recurrence.

Results

At a median follow-up of 9.0 years (interquartile range, 6.4 to 12.7 years), a total of 676 patients developed recurrence. By using a competing-risk model, vastly different surveillance durations were appreciated. Specifically, among patients with pT1Nx-0 disease and a CCI ≤ 1, risk of non-RCC death exceeded that of abdominal recurrence risk at 6 months in patients age 80 years and older but failed to do so for greater than 20 years in patients younger than age 50 years. For patients with pT1Nx-0 disease but a CCI ≥ 2, the risk of non-RCC death exceeded that of abdominal recurrence risk already at 30 days after surgery, regardless of patient age.

Conclusion

We present an individualized approach to RCC surveillance that bases the duration of follow-up on the interplay between competing risk factors of recurrence and non-RCC death. This strategy may improve the balance between the derived benefit from surveillance and medical resource allocation.
Genetic Landscape of Human Papillomavirus–Associated Head and Neck Cancer and Comparison to Tobacco-Related Tumors
Authors: Hayes D. Neil , Van Waes Carter , Seiwert Tanguy Y.
Published: September 2015

Head and neck cancer is the fifth most common cancer worldwide. It is often amenable to curative intent therapy when localized to the head and neck region, but it carries a poor prognosis when it is recurrent or metastatic. Therefore, initial treatment decisions are critical to improve patient survival. However, multimodality therapy used with curative intent is toxic. The balance between offering intensive versus tolerable and function-preserving therapy has been thrown into sharp relief with the recently described epidemic of human papillomavirus–associated head and neck squamous cell carcinomas characterized by improved clinical outcomes compared with smoking-associated head and neck tumors. Model systems and clinical trials have been slow to address the clinical questions that face the field to date. With this as a background, a host of translational studies have recently reported the somatic alterations in head and neck cancer and have highlighted the distinct genetic and biologic differences between viral and tobacco-associated tumors. This review seeks to summarize the main findings of studies, including The Cancer Genome Atlas, for the clinician scientist, with a goal of leveraging this new knowledge toward the betterment of patients with head and neck cancer.
Transoral Endoscopic Head and Neck Surgery and Its Role Within the Multidisciplinary Treatment Paradigm of Oropharynx Cancer: Robotics, Lasers, and Clinical Trials
Authors: Holsinger F. Christopher , Ferris Robert L.
Published: September 2015

Transoral endoscopic head and neck surgery is a new approach for the treatment of oropharyngeal tumors. Using either a robotic system and/or laser, surgeons gain access through the mouth via minimally invasive technique and thus have improved visualization of the tumors of the oropharynx, without disfiguring incisions. This transoral route of access minimizes long-term speech and swallowing dysfunction. Surgeons view this approach as a considerable technologic advance, analogous to the evolution in radiation therapy from conventional two- and three-dimensional conformal techniques to intensity-modulated techniques. Although the use of radiation with or without chemotherapy to treat oropharyngeal cancer (OPC) is supported by evidence from prospective clinical trials, there are no prospective data supporting the use of this new surgical approach for OPC. Here, we review the fundamentals of transoral endoscopic head and neck surgery, with robotics and laser technology, and discuss ongoing clinical trials for patients with OPC.
The Use of Handheld near Infrared Reflectance Spectroscopy for the Proximate Analysis of Poultry Feed and to Detect Melamine Adulteration of Soya Bean Meal
Authors: Haughey Simon A. , Galvin-King Pamela , Malechaux Astrid , Elliott Christopher T.
Published: September 2015

This paper describes a comparison between handheld near infrared (NIR) and benchtop instruments for determination of proximate analysis of poultry feed using off-the-shelf calibration models and including statistical analysis. In an additional application, melamine-adulterated soya bean products were used to develop qualitative and quantitative calibration models from the NIR spectral data collected. Excellent calibration models and prediction statistics were obtained.
Hierarchical Discrimination of Bamboo Species by near Infrared Spectroscopy
Authors: Gahkani Ali , Woodley Chris , Beer Andy
Published: September 2015

A hierarchical classification approach based on the K nearest neighbour algorithm is proposed for effective discrimination of bamboo species. The use of generalised least squares weighting pre-processing proved essential to achieve optimum discriminant accuracy and allowed near infrared spectra of both leaves and stem to be merged and used together. This work can have significant implications for the conservation of Giant Pandas.
A Framework for the Symmetric Generalisation of the Miura-ori
Authors: Sareh Pooya , Guest Simon D.
Published: September 2015

The Miura fold pattern, or the Miura-ori, is a flat-foldable origami tessellation which has been applied to the folding of deployable structures for various engineering and architectural applications. In recent years, researchers have proposed systematic (see, e.g., [1] or [2]), and also free-form [3], variations on the Miura pattern.

This paper develops a geometric framework for the symmetric generalisation of the Miura-ori while preserving the ‘stacking while folding’ behaviour of the pattern. We present a number of novel concepts and definitions which help us apply systematic variations on the original pattern. We study the Miura crease pattern as a pmg wallpaper pattern which is one of the seventeen distinct wallpaper groups. We reduce the symmetry of the Miura-ori to obtain new patterns while preserving the flat-foldability condition at each node. We conclude that we are able to use the Miura-ori, which is a globally planar pattern in its partially folded states, to systematically design either ‘globally planar’ or ‘globally curved’ patterns, through appropriate design variations on the original pattern.
From Folds to Structures, a Review
Authors: Lebée Arthur
Published: September 2015

Starting from simple notions of paper folding, a review of current challenges regarding folds and structures is presented. A special focus is dedicated to folded tessellations which are raising interest from the scientific community. Finally, the different mechanical modeling of folded structures are investigated. This reveals efficient applications of folding concepts in the design of structures.
Translational Method for Designing Folded Plate Structures
Authors: Beatini Valentina
Published: September 2015

This paper concerns non–developable folded plate structures. It presents the translational method; a design technique that creates three-dimensional non-developable systems that can approximate any surface made by translating a generic curve along another generic curve. The continuous folding process is guaranteed by keeping the value of dihedral angles throughout the structure constant at each phase. Once solved the kinematic constraints, the lengths of sides are opportunely varied to approximate any translational surface. The translational method allows for free setting of the target curvature, the approximation span, and the sharpness of the plates.
Computer‐Aided Diagnosis of Parkinson’s Disease Using Complex‐Valued Neural Networks and mRMR Feature Selection Algorithm
Authors: Peker Musa , Şen Baha , Delen Dursun
Published: September 2015

Parkinson’s disease (PD) is a neurological disorder which has a significant social and economic impact. PD is diagnosed by clinical observation and evaluations, coupled with a PD rating scale. However, these methods may be insufficient, especially in the initial phase of the disease. The processes are tedious and time‐consuming, and hence systems that can automatically offer a diagnosis are needed. In this study, a novel method for the diagnosis of PD is proposed. Biomedical sound measurements obtained from continuous phonation samples were used as attributes. First, a minimum redundancy maximum relevance (mRMR) attribute selection algorithm was applied for the identification of the effective attributes. After conversion to a complex number, the resulting attributes are presented as input data to the complex‐valued artificial neural network (CVANN). The proposed novel system might be a powerful tool for effective diagnosis of PD.
Integration of Value Stream Map and Healthcare Failure Mode and Effect Analysis into Six Sigma Methodology to Improve Process of Surgical Specimen Handling
Authors: Hung Sheng-Hui , Wang Pa-Chun , Lin Hung-Chun , Chen Hung-Ying , Su Chao-Ton
Published: September 2015

Specimen handling is a critical patient safety issue. Problematic handling process, such as misidentification (of patients, surgical site, and specimen counts), specimen loss, or improper specimen preparation can lead to serious patient harms and lawsuits. Value stream map (VSM) is a tool used to find out non‐value‐added works, enhance the quality, and reduce the cost of the studied process. On the other hand, healthcare failure mode and effect analysis (HFMEA) is now frequently employed to avoid possible medication errors in healthcare process. Both of them have a goal similar to Six Sigma methodology for process improvement. This study proposes a model that integrates VSM and HFMEA into the framework, which mainly consists of define, measure, analyze, improve, and control (DMAIC), of Six Sigma. A Six Sigma project for improving the process of surgical specimen handling in a hospital was conducted to demonstrate the effectiveness of the proposed model.
Examining the Factors Affecting PDA Acceptance among Physicians: An Extended Technology Acceptance Model
Authors: Basak Ecem , Gumussoy Cigdem Altin , Calisir Fethi
Published: September 2015

This study aims at identifying the factors affecting the intention to use personal digital assistant (PDA) technology among physicians in Turkey using an extended Technology Acceptance Model (TAM). A structural equation‐modeling approach was used to identify the variables that significantly affect the intention to use PDA technology. The data were collected from 339 physicians in Turkey. Results indicated that 71% of the physicians’ intention to use PDA technology is explained by perceived usefulness and perceived ease of use. On comparing both, the perceived ease of use has the strongest effect, whereas the effect of perceived enjoyment on behavioral intention to use is found to be insignificant. This study concludes with the recommendations for managers and possible future research.
Economic Development and Democratic Institutions
Authors: Щербаков  , Shcherbakov A.
Published: September 2015

The article attempts to analyze the relationship of democratic institutions and

economic growth. It emphasized the importance of developing this problem at

the theoretical level to improve the relations between society and the authorities

at various levels of the political, economic and social problems. The mechanisms

of influence of the most important institutions of a democratic society on the

pace and quality of economic growth. The first is the institution of private

property, free enterprise and trade, as well as the inviolability of the person. It is

also crucial to a certain form of government in which the supreme power

belongs to the people. This can be achieved when the society adopted and

approved in advance declared legal rules based on the priority of basic individual

rights and freedoms.
Problems of Russian Agrarian Sector Development within Import Substitution Policy
Authors: Дацко  , Datsko Tatyana , Гагиев  , Gagiyev Nikolay
Published: September 2015

The article is devoted to topical problems of Russian agricultural sector caused

by both internal and external factors.The degree of influence of foreign sanctions

and Russian food embargo on the volume and structure of external trade

turnover of our country has been analyzed. The main measures of state support

of agricultural producers in the implementation of import substitution policy

have been considered. Special attention is paid to ensuring the availability of

credit financial resources, modernization of enterprises’ production base and

improvement of agricultural market infrastructure. In conclusion the author

highlights priority directions of further development of Russian agricultural

complex. The main emphasis is placed on the necessary adaptation of the

agricultural policy to a rapidly changing economic environment in order to

preserve state sovereignty and develop national agroindustry.
Estimation of Beauty Contest Auctions
Authors: Yoganarasimhan Hema
Published: September 2015

Beauty contests are auction mechanisms used to buy or sell differentiated products where the auctioneer does not specify a decision rule to pick the winning bidder. Beauty contests are widely used in procuring welfare-to-work projects, freelance services, selling online ads, real estate transactions, and hiring, dating/marriage decisions. Unlike price-only auctions, beauty contests have no closed-form bidding strategies and suffer from nonmultiplicatively separable unobserved auction heterogeneity, which makes their estimation challenging. To address these challenges, we formulate beauty contests as incomplete information games and present a two-step estimator. A key contribution of our method is its ability to account for common-knowledge auction-specific unobservables using finite unobserved types. We show that unobserved auction types and distributions of bids are nonparametrically identified and recoverable in the first step using a nonparametric Expectation-Maximization (EM)-like algorithm, and that these can then be used in the second step to recover cost distributions. We present an application of our method in the online freelancing context. We find that seller margins in this marketplace are around 15% of the bid, and that not accounting for unobserved heterogeneity can significantly bias cost estimates in this setting. Based on our estimates, we run counterfactual simulations and provide guidelines to managers of freelance firms.

Data, as supplemental material, are available at http://dx.doi.org/10.1287/mksc.2015.0929 .
Online Shopping Intermediaries: The Strategic Design of Search Environments
Authors: Dukes Anthony , Liu Lin
Published: September 2015

An online shopping intermediary is an Internet platform on which consumers and third-party sellers transact. Shopping intermediaries provide a search environment (e.g., search aids) to lower the search costs incurred by consumers when finding and evaluating sellers’ products. We study strategic incentives of an intermediary in the design of its search environment as a means to ease search costs. An important aspect of our analysis is that consumers optimally decide how many sellers to evaluate and how deeply (e.g., number of attributes) to evaluate each of them. We find that the equilibrium search environment embeds sufficiently high search costs to prevent consumers from evaluating too many sellers, but not too high to cause them to evaluate sellers’ products at partial depth.

This paper was accepted by J. Miguel Villas-Boas, marketing.