bluuebunny/crossref_metadata_2025 huggingface dataset:
The rate of and risk factors for frequent hospitalization in systemic lupus erythematosus: results from the Korean lupus network registry
Authors: Lee J W , Park D J , Kang J H , Choi S E , Yim Y R , Kim J E , Lee K E , Wen L , Kim T J , Park Y W , Sung Y K , Lee S S
Published: March 2016

Objectives

The survival rate of patients with systemic lupus erythematosus has improved in the last few decades, but the rate of hospitalization and health care costs for these patients remain higher than in the general population. Thus, we evaluated the rate of hospitalization and associated risk factors in an inception cohort of Korean patients with lupus.

Methods

Of the 507 patients with systemic lupus erythematosus enrolled in the KORean lupus NETwork, we investigated an inception cohort consisting of 196 patients with systemic lupus erythematosus presenting within 6 months of diagnosis based on the American College of Rheumatology classification criteria. We evaluated the causes of hospitalization, demographic characteristics, and laboratory and clinical data at the time of systemic lupus erythematosus diagnosis of hospitalized patients and during a follow-up period. We calculated the hospitalization rate as the number of total hospitalizations divided by the disease duration, and defined “frequent hospitalization” as hospitalization more than once per year.

Results

Of the 196 patients, 117 (59.6%) were admitted to hospital a total of 257 times during the 8-year follow-up period. Moreover, 22 (11.2%) patients were hospitalized frequently. The most common reasons for hospitalization included disease flares, infection, and pregnancy-related morbidity. In the univariate regression analysis, malar rash, arthritis, pericarditis, renal involvement, fever, systemic lupus erythematosus disease activity index > 12, hemoglobin level < 10 mg/dl, albumin level < 3.5 mg/dl, and anti-Sjögren’s syndrome A positivity were associated with frequent hospitalization. Finally, multivariate analysis showed that arthritis, pericarditis, and anti-Sjögren’s syndrome A antibody positivity at the time of diagnosis were risk factors for frequent hospitalization.

Conclusions

Our results showed that frequent hospitalization occurred in 11.2% of hospitalized patients and arthritis, pericarditis, and anti-Sjögren’s syndrome A antibody positivity at the time of diagnosis were risk factors for frequent hospitalization.
Reasons behind providing futile medical treatments in Iran
Authors: Aghabarary Maryam , Nayeri Nahid Dehghan
Published: March 2016

Background:

Despite their negative consequences, evidence shows that futile medical treatments are still being provided, particularly to terminally ill patients. Uncovering the reasons behind providing such treatments in different religious and sociocultural contexts can create a better understanding of medical futility and help manage it effectively.

Research objectives:

This study was undertaken to explore Iranian nurses’ and physicians’ perceptions of the reasons behind providing futile medical treatments.

Research design:

This was a qualitative exploratory study. Study data were gathered through conducting in-depth semi-structured personal interviews and analyzed using the conventional content analysis method.

Participants and research context:

Twenty-one nurses and nine medical specialists were recruited purposively from four teaching hospitals affiliated to Tehran University of Medical Sciences.

Ethical considerations:

This study was approved by the Nursing and Midwifery Research Center and the Research Ethics Committee of Tehran University of Medical Sciences. All participants gave informed consent for the research and that their anonymity was preserved.

Findings:

The main theme of the study was “having an obligation to provide medical treatments despite knowing their futility.” This theme consisted of three main categories including patients’ and family members’ request for continuing life-sustaining treatments, healthcare professionals’ personal motives, and organizational atmosphere and structure.

Discussion and conclusion:

Different personal and organizational factors contribute to providing futile medical treatments. Promoting the structure and the function of hospital ethics committees, establishing and developing home care facilities, increasing the number of palliative care centers and hospices, and educating healthcare professionals, patients, and family members about the services and the benefits of such centers can facilitate making wise decisions about continuing or discontinuing treatments which have been labeled as futile.
Discourses of the North Atlantic
Authors: Pascale Celine-Marie
Published: March 2016

In the 21st century, historic relations of power continue to shape the epistemic status of nations. Epistemologies of the North Atlantic consistently constitute the bases of institutionally valued scholarship. Indeed, control over the narrative of science has been constitutive of the discourse of modernity and North Atlantic intellectual hegemony. The premise of this article rests on the assertion that to effectively study life in the 21st century, we must abandon all notions of epistemic innocence. This analysis begins with the broad considerations of coloniality, modernity, and epistemology and takes up the specific mandates of formalization and interpretation that define North Atlantic epistemologies. It then considers the importance of critical rationalities, social epistemologies, and the need to robustly de-center research paradigms originating in the North Atlantic.
“Passing as Normal”
Authors: O’Connell Noel Patrick
Published: March 2016

This autoethnography presents a narrative account of the author’s experience of living and coping with the stigma of deafness. First, the autoethnographic stories explore the author’s experience of face-to-face encounters with hearing people in which he attempts to pass himself off as normal. The stories illustrate how stigma played a central role in the framing of social interactions inside and outside of school. Second, the article draws on Erving Goffman’s theories on stigma and identity management in an attempt to illuminate an understanding of what the author was coming to terms with. Finally, the author offers his own reflections on the stories including details of some life-changing moments that provided the impetus to transform the stigma of deafness into a positive attribute.
Mixed outpatient–inpatient autologous stem cell transplant for multiple myeloma: A cost-saving initiative in a resource constrained environment
Authors: Clemmons Amber B , Anderegg Samm
Published: March 2016

Background

Although administration of chemotherapy prior to autologous stem cell transplantation in the outpatient setting has been reported as safe and cost-effective, many limitations exist with previously reported methods of transitioning out of the hospital ward. Specifically, lack of a caregiver and distance from treatment facility are key factors particularly in rural settings. Given these limitations, not all institutions have transitioned the transplant process, or even portions of it, to the outpatient setting despite the known benefits.

Methods

To achieve financial benefit without compromising safety, a novel mixed outpatient–inpatient model was adopted at our institution. Eligible patients receive melphalan in the clinic the day prior to being admitted for peripheral blood stem cell re-infusion where they remain until recovery of myelosuppression.

Results

In the year since implementation, nineteen total patients received high-dose melphalan prior to autologous stem cell transplantation. Eighteen of these patients successfully received melphalan in the outpatient clinic with admission to the hospital on day zero for infusion of stem cells. No patient experienced any adverse event on the day or evening of chemotherapy or required early admission. The average estimated total reduction in cost per patient to the institution was over US$2,000. When comparing the cost of the chemotherapy drug, melphalan, from the year before and the year after implementation of the mixed model the total annual cost saving was approximately US$90,00 or 53% of the previous year’s expenditure.

Conclusions

The implementation of this mixed outpatient–inpatient model was safe, feasible, and cost-effective.
The Role of Psychopathic Traits in the Development of the Therapeutic Alliance Among Sexual Offenders
Authors: Walton Ashleigh , Jeglic Elizabeth L. , Blasko Brandy L.
Published: March 2016

There is a growing body of research demonstrating that the therapeutic alliance (TA) affects outcomes among specialized forensic populations, including sexual offenders. Despite this consensus, researchers continue to question whether higher levels of psychopathic traits are conducive to the formation of a therapeutic relationship for high-risk sexual offenders. Thus, the current study adds to the literature by examining the relationship between the TA and levels of psychopathy among a sample of incarcerated sexual offenders participating in sexual offender treatment. Overall, we found no significant relationships between Psychopathy Checklist–Revised (PCL-R) scores and the Working Alliance Inventory (WAI) for either client or therapist ratings. However, when we excluded those offenders who were participating in aftercare, a significant negative relationship was found between client ratings of the Bonds subscale and PCL-R total scores. Next, after controlling for risk and group status (aftercare/non-aftercare), we found no significant differences between either client or therapist total WAI scores when compared by level of psychopathy as measured by the PCL-R (low, >20; moderate, 20-30; and high, >30). Furthermore, when Factor 1 and Factor 2 scores of the PCL-R were examined individually, neither factor significantly predicted either client or therapist total WAI score after controlling for risk and group status. Findings are discussed as they pertain to the treatment of sexual offenders with elevated levels of psychopathic traits.
On the free vibration of angle-ply laminated composite and soft core sandwich plates
Authors: Sayyad Atteshamuddin S , Ghugal Yuwaraj M
Published: March 2016

In the present study, a simple four-variable trigonometric shear deformation theory considering the effects of transverse shear deformation and rotary inertia is evaluated for the free vibration analysis of antisymmetric laminated composite and soft core sandwich plates. The theory is displacement-based equivalent single-layer theory in which the in-plane displacements use trigonometric function in terms of thickness coordinate, for calculating out-of-plane shearing strains. The number of unknown variables involved in the present theory is only four as against five or more than five in case of other higher order theories. The equations of motion are obtained using the principle of virtual work. A closed-form solution for equations of motion is obtained using the Navier’s solution technique. The effects of side-to-thickness ratio, modular ratio and fibre angle are critically assessed for several problems of laminated composite and sandwich plates. The natural frequencies obtained by using present theory are verified by comparing the results with those of other theories and exact elasticity solution wherever applicable.
Cerebrospinal fluid biomarkers of inflammation and degeneration as measures of fingolimod efficacy in multiple sclerosis
Authors: Novakova Lenka , Axelsson Markus , Khademi Mohsen , Zetterberg Henrik , Blennow Kaj , Malmeström Clas , Piehl Fredrik , Olsson Tomas , Lycke Jan
Published: March 2016

Background:

The disease-modifying therapies (DMTs) in relapsing-remitting multiple sclerosis (RRMS) vary in their mode of action and when therapies are changed, the consequences on inflammatory and degenerative processes are largely unknown.

Objective:

We investigated the effect of switching from other DMTs to fingolimod on cerebrospinal fluid (CSF) biomarkers.

Methods:

43 RRMS patients were followed up after 4–12 months of fingolimod treatment. Concentrations of C-X-C motif chemokine 13 (CXCL13), chemokine (C-C motif) ligand 2 (CCL2), chitinase-3-like protein 1 (CHI3L1), glial fibrillary acidic protein (GFAP), neurofilament light protein (NFL), and neurogranin (NGRN) were analyzed by enzyme-linked immunosorbent assay (ELISA), while chitotriosidase (CHIT1) was analyzed by spectrofluorometry.

Results:

The levels of NFL, CXCL13, and CHI3L1 decreased ( p < 0.05) after fingolimod treatment. Subgroup analysis revealed a reduction in NFL ( p < 0.001), CXCL13 ( p = 0.001), CHI3L1 ( p < 0.001), and CHIT1 ( p = 0.002) in patients previously treated with first-line therapies. In contrast, the levels of all analyzed biomarkers were essentially unchanged in patients switching from natalizumab.

Conclusion:

We found reduced inflammatory activity (CXCL13, CHI3L1, and CHIT1) and reduced axonal damage (NFL) in patients switching from first-line DMTs to fingolimod. Biomarker levels in patients switching from natalizumab indicate similar effects on inflammatory and degenerative processes. The CSF biomarkers provide an additional measure of treatment efficacy.
Th17 cells: A prognostic marker for MS rebound after natalizumab cessation?
Authors: Haas Jürgen , Schneider Katharina , Schwarz Alexander , Korporal-Kuhnke Mirjam , Faller Simon , von Glehn Felipe , Jarius Sven , Wildemann Brigitte
Published: March 2016

Background:

Multiple sclerosis (MS) patients are at risk of renewed disease activity after discontinuing natalizumab (NAT) treatment.

Objective:

Assessing the implication of T helper 17 (Th17) cells in MS reactivation after NAT cessation.

Methods:

We monitored frequencies of Th17 cells and interleukin (IL)-17 cytokine levels in blood samples of 57 MS patients, without, during, and after NAT exposure.

Results:

Frequencies of both Th17 cells and, in part, also IL-17 levels, in peripheral blood increased under prolonged NAT therapy, returned to baseline after NAT withdrawal and became almost undetectable in blood samples of individuals who experienced relapses during the wash-out phase.

Conclusion:

Assessing the Th17-cell/IL-17 axis might help to predict rebound MS activity after NAT withdrawal.
Prospective study on cost-effectiveness of home-based motor assessment in Parkinson’s disease
Authors: Cubo E , Mariscal N , Solano B , Becerra V , Armesto D , Calvo S , Arribas J , Seco J , Martinez A , Zorrilla L , Heldman D
Published: March 2016

Introduction

Treatment adjustments in Parkinson’s disease (PD) are in part dependent on motor assessments. The aim of this study was to evaluate the cost-effectiveness of home-based motor monitoring plus standard in-office visits versus in-office visits alone in patients with advanced PD.

Methods

The procedures consisted of a prospective, one-year follow-up, randomized, case-control study. A total of 40 patients with advanced PD were randomized into two groups: 20 patients underwent home-based motor monitoring by using wireless motion sensor technology, while the other 20 patients had in-office visits. Motor and non-motor symptom severities, quality of life, neuropsychiatric symptoms, and comorbidities were assessed every four months. Direct costs were assessed using a standardized questionnaire. Cost-effectiveness was assessed using the incremental cost-effectiveness ratio (ICER).

Results

Both groups of PD patients were largely comparable in their clinical and demographic variables at baseline; however, there were more participants using levodopa-carbidopa intestinal gel in the home-based motor monitoring group. There was a trend for lower Unified Parkinson’s Disease Rating Scale functional status (UPDRS II) scores in the patients monitored at home compared to the standard clinical follow-up ( p = 0.06). However, UPDRS parts I, III, IV and quality-adjusted life-years scores were similar between both groups. Home-based motor monitoring was cost-effective in terms of improvement of functional status, motor severity, and motor complications (UPDRS II, III; IV subscales), with an ICER/UPDRS ranging from €126.72 to €701.31, respectively.

Discussion

Home-based motor monitoring is a tool which collects cost-effective clinical information and helps augment health care for patients with advanced PD.
Healthism in Denmark: State, market, and the search for a “Moral Compass”
Authors: Kristensen Dorthe Brogård , Lim Ming , Askegaard Søren
Published: March 2016

This article focuses on contemporary responses to public health messages in Denmark, a country whose system of social welfare is, like that of the United Kingdom and the rest of Europe, undergoing increasing levels of marketization and privatization. Drawing primarily upon Robert Crawford’s analysis of healthism as a neoliberal project, the aim of this article is to develop critical understandings of how individuals respond both bodily and emotionally to ideologies of health and the body in the context of a changing marketplace for the consumption of health and its messages. This article will analyze perceptions and practices of health in Denmark. The findings will then be discussed in relation to dimensions inspired by the work of Crawford, who regards “health” as a “super-value,” an outcome of individual security strategies, and mode of citizenship in the marketplace. The article argues that Crawford’s discussion does not fully capture the ways in which people use their bodies to valorize themselves. First, the perception of the state is perceived as being aligned with commercial interests. As a consequence, neither state- nor market-based (i.e. commercial health product and service providers) health advice is fully trusted. Instead, the opinions of non-market actors such as peers and friends as well as of alternative practitioners that are considered outside the market since they do not represent corporate interests become more attractive among citizen-consumers who are concerned about their health. The article concludes with a discussion of the implications of our findings for theorization of public health and health policy.
The PF Disjunction Theorem to Southern Min/Mandarin code-switching
Authors: Wang Sung-Lan
Published: March 2016

Aim and research question:

The aim of this study is to test Macswan’s ((1999). A minimalist approach to intrasentential code switching. New York, NY: Garland; (2000). The architecture of the bilingual language faculty: Evidence from intrasentential code-switching. Bilingualism: Language and Cognition, 3, 37–54; (2005). Codeswitching and generative grammar: A critique of the MLF model and some remarks on “modified minimalism”. Bilingualism: Language and Cognition, 8, 1–22.) PF Disjunction Theorem (PFDT), which was proposed based on Chomsky’s ((1995). The minimalist program. Cambridge, MA: MIT Press.) minimalist programme, to answer the following question: Is code-switching (CS) behaviour governed by CS-specific grammar or an innate mechanism that produces monolingual and bilingual utterances in our language faculty?

Methodology:

A quantitative approach was adopted to test the PFDT with the Southern Min/Mandarin CS data.

Data and analysis:

811 lexical items extracted from 343 bilingual clauses in my Southern Min/Mandarin CS corpus, and almost no violation against this model (i.e., a word-internal switch) was found, except one example that was regarded as the informant’s slip of tongue.

Findings/conclusions:

The results of this study confirm the prediction of the PFDT that phonological systems cannot be mixed within a word.

Originality:

Although the morphosyntactic structures and in some cases the pronunciations of morphemes are identical, tonal differences of these two languages still prohibit word-internal switches.

Significance/implications:

This study thus supports the PFDT and argues that CS behaviour is governed by a single innate mechanism that governs both monolingual and bilingual language production and that the so-called CS-specific grammar/mechanism is not necessary.
New Empiricisms and New Materialisms
Authors: St. Pierre Elizabeth A. , Jackson Alecia Y. , Mazzei Lisa A.
Published: March 2016

This article, which introduces this special issue on new empiricisms and new materialisms, focuses on two of the many conditions that enable this new work: first, an ethical imperative to rethink the nature of being to refuse the devastating dividing practices of the dogmatic Cartesian image of thought and, second, a heightened curiosity and accompanying experimentation in the becoming of existence. The article includes a brief description of how matter matters differently in this new work, of Deleuze and Guattari’s description of philosophy as the laying out of a plane that enables new concepts, a discussion of the “new,” and how/if methodology can be thought in the “new.”
A nurse’s phenomenological enquiry into doctors’ end-of-life decision making
Authors: Charman Lesley Ann , Esterhuizen Philip
Published: March 2016

This paper is based on an exploratory study conducted in a UK NHS oncology unit, informed by the interpretation of hermeneutic phenomenology by Van Manen and Dahlberg et al. Four senior oncology doctors (trainees) were recruited using homogenous purposive sampling. In-depth interviews were conducted to understand participants’ lived experience of decision making for oncology patients near the end of life. Analysis followed a line-by-line approach, with consideration of the lifeworld existentials identified by ( Van Manen, 1990 ). Common themes were uncovered of empathy, the unacknowledged influence; dichotomy and conflict; and subverted emotion (uncovered through reflection). Findings are discussed in relation to current clinical decision-making theory, particularly cognitive continuum theory, current UK end of life care policy and practice, role socialisation and inter-professional team working.
Clinical experience with infliximab biosimilar Remsima (CT-P13) in inflammatory bowel disease patients
Authors: Jahnsen Jørgen
Published: March 2016

Many reference biological therapies have now reached or are near to patent expiry, and therefore a number of biosimilars have been or will be developed. The term biosimilar can be defined as a biotherapeutic product that is similar in efficacy, safety and quality to the licensed reference product. Biosimilars may lead to a reduced price and significant cost savings for the health community and hopefully more patients globally will have easier access to biological therapy when indicated. CT-P13, which is a TNF-alfa inhibitor, is the first monoclonal antibody biosimilar being used in clinical practice. The drug is approved for all indications as an innovator product although clinical efficacy has only been demonstrated in rheumatic diseases. Until now the number of patients with inflammatory bowel disease (IBD) treated with CT-P13 is confined, but experience is continuously growing. Based on current data, CT-P13 seems to be efficacious and generally well tolerated in IBD especially in patients who are naïve to biological therapy. Knowledge with regard to interchangeability between CT-P13 and the originator infliximab is however, still rather sparse and more data are desired. Immunogenicity and long-term safety related to CT-P13 are other areas of great importance and good and reliable postmarketing pharmacovigilance is therefore required in the coming years.
Elbow hemiarthroplasty for the management of distal humeral fractures: current technique, indications and results
Authors: Phadnis Joideep , Watts Adam C , Bain Gregory I
Published: March 2016

There has been a growing recent interest in the use of elbow hemiarthroplasty for the treatment of distal humeral trauma in select patients. However, the current available evidence regarding outcome after elbow hemiarthroplasty is limited to case series and biomechanical data. Consequently, the procedure remains unfamiliar to many surgeons. The aim of the present review is to outline the evidence regarding elbow hemiarthroplasty and to use this, along with the author’s experience, to better describe the indications, surgical technique and outcomes after this procedure.
Treatment of Chronic Achilles Tendon Ruptures With Large Defects
Authors: Ahmad Jamal , Jones Kennis , Raikin Steven M.
Published: March 2016

Background. When Achilles tendon ruptures become chronic, a defect often forms at the rupture site. There is scant literature regarding the treatment of chronic Achilles ruptures with defects of 6 cm or larger. We examined outcomes from combining a turndown of the proximal, central Achilles with a flexor hallucis longus (FHL) tendon transfer to treat this condition. Materials. Between September 2002 and December 2013, 32 patients presented with a chronic Achilles rupture and a defect of 6 cm or more. Twenty patients were male and 12 were female. Patient age was between 20 and 74 years, with a mean of 53.3 years. Eighteen and 14 patients had their right and left Achilles tendon affected, respectively. The number of days between injury and surgery ranged from 30 to 315 days, with a mean of 102 days. Reconstruction of the Achilles involved a turndown of the proximal, central tendon and FHL augmentation. Final patient follow-up ranged from 18 to 150 months, with a mean of 62.3 months. Results: At surgery, the gap between the ruptured ends of the Achilles ranged from 6 to 12 cm, with a mean gap of 7.5 cm. Full healing was achieved in all 32 patients (100%) by 5 months postoperatively. Mean Foot and Ankle Ability Measures scores increased from 36.3% to 90.2% between initial and latest follow-up (P < .05). Mean visual analogue scales of pain decreased from 6.6 to 1.8 of 10 between first and last encounter (P < .05). Postoperative complications occurred in 5 patients (15.6%), including 3 (9.4%) superficial wound problems, 1 (3.1%) deep wound infection, and 1 (3.1%) deep vein thrombosis. Discussion. Outcomes from treating chronic Achilles ruptures with large defects are scant within the orthopaedic literature. Our method of Achilles reconstruction results in a high rate of improved function and pain relief.

Levels of Evidence: Therapeutic, Level IV: Case series
The “inflammatory penumbra” in ischemic stroke: From clinical data to experimental evidence
Authors: Gauberti Maxime , De Lizarrondo Sara Martinez , Vivien Denis
Published: March 2016

Purpose

The objective of the present review is to provide an overview of the available clinical and preclinical data supporting the existence of an “inflammatory penumbra” in ischemic stroke.

Findings

Recent data from clinical trials suggest the existence of an inflammatory area at risk, surrounding the initial ischemic lesion and secondarily infiltrated by lymphocytes, that is ultimately recruited by the ischemic core: called the “inflammatory penumbra.” Experimental results support this concept. Lymphocytes, especially T-cells, enter the brain in the perilesional area in a vascular-cell adhesion molecule-1 dependent manner and participate in delayed neuronal cell death.

Methods

For writing this review, we used the more recent publications in the field, including the preclinical and clinical studies. We have also used our own experise in the field of in vivo imaging of inflammatory processes.

Discussion

Consequently, the intensity of the inflammatory reaction and the size of the inflammatory penumbra may vary considerably in patients, as it is the case in experimental stroke models in mice. By analogy with the ischemic penumbra of the acute phase of stroke, this secondary inflammatory penumbra represents a therapeutic opportunity during the subacute phase of stroke. Large clinical trials that target lymphocyte trafficking are currently taking place. However, to improve the benefit of such therapeutic strategies, adequate patient selection may be mandatory.

Conclusion

In this context, innovative imaging methods including magnetic resonance imaging of adhesion molecules may contribute to noninvasively detect this inflammatory penumbra and thus to select patients eligible for such therapy.
IL-4 enhances expression and function of surface IgM in CLL cells
Authors: Aguilar-Hernandez Maria M. , Blunt Matthew D. , Dobson Rachel , Yeomans Alison , Thirdborough Stephen , Larrayoz Marta , Smith Lindsay D. , Linley Adam , Strefford Jonathan C. , Davies Andrew , Johnson Peter M. W. , Savelyeva Natalia , Cragg Mark S. , Forconi Francesco , Packham Graham , Stevenson Freda K. , Steele Andrew J.
Published: March 2016

Key Points

IL-4 treatment augments sIgM expression and subsequent downstream signalling in a JAK3/STAT6 dependent manner within CLL samples. IL-4 exposure partially opposes the activity of Bruton tyrosine kinase or PI3K inhibitors on sIgM-mediated signalling.
Leveraging protein quaternary structure to identify oncogenic driver mutations
Authors: Ryslik Gregory A. , Cheng Yuwei , Modis Yorgo , Zhao Hongyu
Published: March 2016

Background

Identifying key “driver” mutations which are responsible for tumorigenesis is critical in the development of new oncology drugs. Due to multiple pharmacological successes in treating cancers that are caused by such driver mutations, a large body of methods have been developed to differentiate these mutations from the benign “passenger” mutations which occur in the tumor but do not further progress the disease. Under the hypothesis that driver mutations tend to cluster in key regions of the protein, the development of algorithms that identify these clusters has become a critical area of research.

Results

We have developed a novel methodology,QuartPAC(QuaternaryProteinAmino acidClustering), that identifies non-random mutational clustering while utilizing the protein quaternary structure in 3D space. By integrating the spatial information in the Protein Data Bank (PDB) and the mutational data in the Catalogue of Somatic Mutations in Cancer (COSMIC),QuartPACis able to identify clusters which are otherwise missed in a variety of proteins. The R package is available on Bioconductor at:http://bioconductor.jp/packages/3.1/bioc/html/QuartPAC.html.

Conclusion

QuartPACprovides a unique tool to identify mutational clustering while accounting for the complete folded protein quaternary structure.
pcaReduce: hierarchical clustering of single cell transcriptional profiles
Authors: žurauskienė Justina , Yau Christopher
Published: March 2016

Background

Advances in single cell genomics provide a way of routinely generating transcriptomics data at the single cell level. A frequent requirement of single cell expression analysis is the identification of novel patterns of heterogeneity across single cells that might explain complex cellular states or tissue composition. To date, classical statistical analysis tools have being routinely applied, but there is considerable scope for the development of novel statistical approaches that are better adapted to the challenges of inferring cellular hierarchies.

Results

We have developed a novel agglomerative clustering method that we call pcaReduce to generate a cell state hierarchy where each cluster branch is associated with a principal component of variation that can be used to differentiate two cell states. Using two real single cell datasets, we compared our approach to other commonly used statistical techniques, such as K-means and hierarchical clustering. We found that pcaReduce was able to give more consistent clustering structures when compared to broad and detailed cell type labels.

Conclusions

Our novel integration of principal components analysis and hierarchical clustering establishes a connection between the representation of the expression data and the number of cell types that can be discovered. In doing so we found that pcaReduce performs better than either technique in isolation in terms of characterising putative cell states. Our methodology is complimentary to other single cell clustering techniques and adds to a growing palette of single cell bioinformatics tools for profiling heterogeneous cell populations.
Incorporating Androgen Deprivation With Dose-Escalated External-Beam Radiotherapy for Prostate Cancer
Authors: Dosoretz Arie P. , Yu James B.
Published: March 2016

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.

A 71-year-old man was seen by his primary care physician for routine evaluation in early 2015. On digital rectal examination, his prostate was moderately enlarged, although he had no obvious areas of palpable disease. His prostate-specific antigen (PSA) level was 7.1 ng/mL. A standard ultrasound-guided biopsy of his prostate revealed a 60-mL prostate volume and a single core (out of 12) of Gleason 3 + 3 disease. He chose to undergo surveillance. Six months later, his PSA level had risen to 10.0 ng/mL; there was still no palpable disease on digital rectal examination. Multiparametric magnetic resonance imaging of his prostate and pelvis revealed two suspicious intraprostatic lesions with restricted diffusion, focal and earlier enhancement with contrast than adjacent normal prostate, and hypointense features on T2-weighted imaging; these findings were highly suspicious for high-grade prostate cancer ( Fig 1 ). Magnetic resonance imaging–ultrasound fusion targeted biopsy of each lesion yielded a total of four positive biopsy cores of Gleason 4 + 3 = 7, involving 50% to 80% of each core, with perineural invasion noted. The patient’s medical history is notable for overweight (but not morbidly obese), hypercholesterolemia, hypertension, cataract surgeries, and inguinal hernia repair, but the patient is otherwise healthy. He has decided against prostatectomy and brachytherapy because of strong personal preference. In particular, he wanted to avoid anesthesia, and was concerned about the potential for greater urinary incontinence and/or urinary irritation associated with these treatments compared with external-beam radiotherapy (RT). 1 , 2
Fibroblast Growth Factor-23 (FGF-23) Levels Differ Across Populations by Degree of Industrialization
Authors: Yuen Shennin N. , Kramer Holly , Luke Amy , Bovet Pascal , Plange-Rhule Jacob , Forrester Terrence , Lambert Vicki , Wolf Myles , Camacho Pauline , Harders Regina , Dugas Lara , Cooper Richard , Durazo-Arvizu Ramon
Published: March 2016

Context:

Compensatory increases in fibroblast growth factor 23 (FGF23) with increasing phosphate intake may adversely impact health. However, population and clinical studies examining the link between phosphate intake and FGF23 levels have focused mainly on populations living in highly industrialized societies in which phosphate exposure may be homogenous.

Objective:

The objective of the study was to contrast dietary phosphate intake, urinary measures of phosphate excretion, and FGF23 levels across populations that differ by the level of industrialization.

Design:

This was a cross-sectional analysis of three populations.

Setting:

The study was conducted in Maywood, Illinois; Mahé Island, Seychelles; and Kumasi, Ghana.

Participants:

Adults with African ancestry aged 25–45 years participated in the study.

Main Outcome:

FGF23 levels were measured.

Results:

The mean age was 35.1 (6.3) years and 47.9% were male. Mean phosphate intake and fractional excretion of phosphate were significantly higher in the United States vs Ghana, whereas no significant difference in phosphate intake or fractional excretion of phosphate was noted between the United States and Seychelles for men or women. Overall, median FGF23 values were 57.41 RU/mL (interquartile range [IQR] 43.42, 75.09) in the United States, 42.49 RU/mL (IQR 33.06, 55.39) in Seychelles, and 33.32 RU/mL (IQR 24.83, 47.36) in Ghana. In the pooled sample, FGF23 levels were significantly and positively correlated with dietary phosphate intake (r = 0.11; P < .001) and the fractional excretion of phosphate (r = 0.13; P < .001) but not with plasma phosphate levels (r = −0.001; P = .8). Dietary phosphate intake was significantly and positively associated with the fractional excretion of phosphate (r = 0.23; P < .001).

Conclusion:

The distribution of FGF23 levels in a given population may be influenced by the level of industrialization, likely due to differences in access to foods preserved with phosphate additives.
Right Ventricular Longitudinal Strain Is Depressed in a Bovine Model of Pulmonary Hypertension
Authors: Bartels Karsten , Brown R. Dale , Fox Daniel L. , Bull Todd M. , Neary Joseph M. , Dorosz Jennifer L. , Fonseca Brian M. , Stenmark Kurt R.
Published: March 2016

BACKGROUND:

Pulmonary hypertension and resulting right ventricular (RV) dysfunction are associated with significant perioperative morbidity and mortality. Although echocardiography permits real-time, noninvasive assessment of RV function, objective and comparative measures are underdeveloped, and appropriate animal models to study their utility are lacking. Longitudinal strain analysis is a novel echocardiographic method to quantify RV performance. Herein, we hypothesized that peak RV longitudinal strain would worsen in a bovine model of pulmonary hypertension compared with control animals.

METHODS:

Newborn Holstein calves were randomly chosen for induction of pulmonary hypertension versus control conditions. Pulmonary hypertension was induced by exposing animals to 14 days of hypoxia (equivalent to 4570 m above sea level or 430 mm Hg barometric pressure). Control animals were kept at ambient pressure/normoxia. At the end of the intervention, transthoracic echocardiography was performed in awake calves. Longitudinal wall strain was analyzed from modified apical 4-chamber views focused on the RV. Comparisons between measurements in hypoxic versus nonhypoxic conditions were performed using Student t test for independent samples and unequal variances.

RESULTS:

After 14 days at normoxic versus hypoxic conditions, 15 calves were examined with echocardiography. Pulmonary hypertension was confirmed by right heart catheterization and associated with reduced RV systolic function. Mean systolic strain measurements were compared in normoxia-exposed animals (n = 8) and hypoxia-exposed animals (n = 7). Peak global systolic longitudinal RV strain after hypoxia worsened compared to normoxia (−10.5% vs −16.1%, P = 0.0031). Peak RV free wall strain also worsened after hypoxia compared to normoxia (−9.6% vs −17.3%, P = 0.0031). Findings from strain analysis were confirmed by measurement of tricuspid annular peak systolic excursion.

CONCLUSIONS:

Peak longitudinal RV strain detected worsened RV function in animals with hypoxia-induced pulmonary hypertension compared with control animals. This relationship was demonstrated in the transthoracic echocardiographic 4-chamber view independently for the RV free wall and for the combination of the free and septal walls. This innovative model of bovine pulmonary hypertension may prove useful to compare different monitoring technologies for the assessment of early events of RV dysfunction. Further studies linking novel RV imaging applications with mechanistic and therapeutic approaches are needed.
Evolution of bright colours in animals: worlds of prohibition and oblivion
Authors: Alonso Wladimir J.
Published: March 2016

Because the ability to hide in plain sight provides a major selective advantage to both prey and predator species, the emergence of the striking colouration of some animal species (such as many coral reef fish) represents an evolutionary conundrum that remains unsolved to date. Here I propose a framework by which conspicuous colours can emerge when the selective pressures for camouflage are relaxed (1) because camouflage is not essential under specific prey/predator conditions or (2) due to the impossibility of reducing the signal-to-background noise in the environment. The first case is found among non-predator-species that possess effective defences against predators (hence a “Carefree World”), such as the strong macaws’ beaks and the flight abilities of hummingbirds. The second case is found in diurnal mobile fish of coral reef communities, which swim in clear waters against highly contrasting and unpredictable background (hence an "Hyper-Visible World”). In those contexts the selective pressures that usually come secondary to camouflage (such as sexual, warning, species recognition or territorial display) are free to drive the evolution of brilliant and diverse colouration. This theoretical framework can also be useful for studying the conditions that allow for conspicuousness in other sensory contexts (acoustic, chemical, electrical, etc.).
Book Reviews
Authors: Shen Wenjing
Published: March 2016

In Book Reviews, we review an extensive and diverse range of books. They cover theory and applications in operations research, statistics, management science, econometrics, mathematics, computers, and information systems. In addition, we include books in other fields that emphasize technical applications. The editor will be pleased to receive an email from those willing to review a book, with an indication of specific areas of interest. If you are aware of a specific book that you would like to review, or that you think should be reviewed, please contact the editor.

The following books are reviewed in this issue of Interfaces, 46(2), March–April 2016: Causes of Supply Chain Disruptions: An Empirical Analysis in Cold Chains for Food and Pharmaceuticals, Verena Brenner; Multichannel Commerce: A Consumer Perspective on the Integration of Physical and Electronic Channels, Manuel Trenz.
Signaling Low Margin Through Assortment
Authors: Kuksov Dmitri , Lin Yuanfang
Published: March 2016

Oftentimes, close competitors carry partially overlapping assortments in seeming contradiction to the principle of maximum differentiation. One of the justifications of such practice is that an overlapping assortment with competitive prices on the common products may prevent further consumer search and therefore could be useful even when profits from the overlapping products do not justify the costs of carrying them. In this paper, we examine the validity of this intuition and show that such strategy may indeed be optimal when consumers are uncertain about prices they might find elsewhere and face shopping costs for discovery of all prices. Specifically, we show that the (larger) assortment with product overlap may signal a “competitive” price of the relatively unique product and prevent further consumer search for a lower price on it. An implication of this finding is that a consumer may rationally behave as if she likes a larger assortment even if the assortment is enlarged by adding products the consumer has no interest in. Furthermore, we show that the optimal pricing strategy may include pricing of common products or products with known costs at a loss, which provides a novel explanation of loss-leader pricing.

Data, as supplemental material, are available at http://dx.doi.org/10.1287/mnsc.2015.2384 .

This paper was accepted by Pradeep Chintagunta, marketing.
Using Future Information to Reduce Waiting Times in the Emergency Department via Diversion
Authors: Xu Kuang , Chan Carri W.
Published: March 2016

The development of predictive models in healthcare settings has been growing; one such area is the prediction of patient arrivals to the emergency department (ED). The general premise behind these works is that such models may be used to help manage an ED that consistently faces high congestion. In this work, we propose a class of proactive policies that utilize future information of potential patient arrivals to effectively manage admissions into an ED while reducing waiting times for patients who are eventually treated. Instead of the standard strategy of waiting for queues to build before diverting patients, the proposed policy utilizes the predictions to identify when congestion is going to increase and proactively diverts patients before things get “too bad.” We demonstrate that the proposed policy provides delay improvements over standard policies used in practice. We also consider the impact of errors in the information provided by the predictive models and find that even with noisy predictions, our proposed policies can still outperform (achieving shorter delays while serving the same number of patients) standard diversion policies. If the quality of the predictive model is insufficient, then it is better to ignore the future information and simply rely on real-time, current information for the basis of decision making. Using simulation, we find that our proposed policy can reduce delays by up to 15%.
Forming a balanced opinion
Authors: Docherty B.
Published: March 2016

Practitioners are often asked for their opinions by patients and colleagues, making it vital that they keep up to date, reflect on past experience and learn from each other, says Brendan Docherty
Is blood pressure a clinical predictor of pressure ulcer development?
Authors: Pedley G.
Published: March 2016

It is not clear from the literature whether blood pressure measurements can be used to predict pressure ulcer development. This review examines the evidence and identifies the type of research needed to clarify this issue
A comparison of hydrofibre and alginate dressings on open acute surgical wounds
Authors: Foster L. , Moore P. , Clark S.
Published: March 2016

This study aimed to compare the performance of a hydrofibre (Aquacel) and an alginate (Sorbsan) dressing on acute surgical wounds left to heal by secondary intention.

A total of 100 patients were prospectively randomised pre-operatively to receive either the hydrofibre or the alginate dressing. Dressing performance was measured at operation, at 24 hours and seven days.

Parameters measured included ease of: application and removal of the first dressing; re-application on the first postoperative day; and removal and re-application one week postoperatively. The hydrofibre dressing received higher scores for all of these categories. Patients in this group also experienced less pain (mild or none) on removal of the first dressing and at one week. However, these results did not achieve statistical significance, and should be seen as a trend. Nevertheless, the authors recommend the use of hydrofibre dressings on open acute surgical wounds.
A Singular Value Inequality Related to a Linear Map
Authors: Lin Minghua
Published: March 2016

If $\begin{bmatrix}A & X \\ X^* & B\end{bmatrix}$ is positive semidefinite with each block $n\times n$, we prove that $$2s_j\Big(\Phi(X)\Big)\le s_j\Big(\Phi(A+B)\Big), \qquad j=1, \ldots, n,$$ where $\Phi: X\mapsto X+(\tr X)I$ and $s_j(\cdot)$ means the $j$-th largest singular value. This confirms a conjecture of the author in [Linear Algebra Appl. 459 (2014) 404-410].