bluuebunny/crossref_metadata_2025 huggingface dataset:
Symptoms and Mucosal Changes Stable During Rapid Increase of Pediatric Celiac Disease in Norway
Authors: Beitnes Ann‐Christin R. , Vikskjold Florin B. , Jóhannesdóttir Gróa B. , Perminow Gøri , Olbjørn Christine , Andersen Solveig N. , Bentsen Beint S. , Rugtveit Jarle , Størdal Ketil
Published: June 2016

Objectives:

We aimed to study whether the incidence of pediatric celiac disease (CD) in South‐Eastern Norway changed from 2000 to 2010. We also examined whether there was a change in symptoms and histopathological morphology in the duodenal biopsies during the same period.

Methods:

In 3 hospitals in South‐Eastern Norway, records from pediatric patients (0–14.9 years) diagnosed with CD during two 3‐year periods (2000–2002 and 2008–2010) were reviewed. Only cases with a duodenal biopsy diagnosis of CD classified as Marsh grade 2 and 3a−c were included. Frequencies of symptoms, anthropometric data, and laboratory results were compared, in addition to re‐examinations of histological sections from one of the hospitals.

Results:

A total of 400 cases were diagnosed with a female to male ratio of 1.5:1. The incidence rate for 2000 to 2002 was 15.9 cases per 100,000 person‐years (95% confidence interval 12.8–19.4), compared with 45.5 cases per 100,000 person‐years during 2008 to 2010 (95% confidence interval 40.5–50.9), P < 0.001. The relative frequencies of symptoms and the distribution of histopathological changes were similar in the 2 periods, whereas weight z scores and hemoglobin levels were significantly lower in the first period.

Conclusions:

We found a 3‐fold increase in the incidence rate for CD in the Norwegian pediatric population during the decade 2000 to 2010. Slightly higher weight and hemoglobin levels at diagnosis in the latter period may be due to improved CD awareness. Unaltered relative frequencies of symptoms and histopathological changes in the gut, however, suggest a true increase of CD in Norwegian children.
Oral Pyogenic Granuloma After Bone Marrow Transplant in the Pediatric/Adolescent Population: Report of 5 Cases
Authors: Cheney-Peters Dianna , Lund Troy C.
Published: June 2016

Pyogenic granuloma (PG) is a benign, neoplastic, soft tissue growth of granulation and fibrous tissue that may rarely occur in the mouth of patients after hematopoietic cell transplant (HCT). This case series describes 5 pediatric/adolescent patients who developed oral PG after HCT for acute lymphoblastic leukemia, Fanconi anemia, nodular sclerosis Hodgkin’s lymphoma, or junctional epidermolysis bullosa. The underlying mechanism for the appearance of oral PG after HCT is unknown, but it is suggested that calcineurin inhibitors used for graft versus host disease (GVHD) may play a role, as all patients were on cyclosporine A or tacrolimus at the time of development of oral PG. Three of the patients were being treated for chronic GVHD, and 1 other treated for acute GVHD. Overall, this report illustrates that PG should be considered in the differential diagnoses when encountering oral lesions in pediatric/adolescent patients after undergoing HCT, especially in the context of chronic GVHD and calcineurin inhibitors use.
Subcortical DNET in a Patient With an Enzymatic Deficiency: A Rare Case and Review of the Literature
Authors: Infinger Libby K. , Karia Samir R. , Kinsman Stephen L. , Kosnik Edward J. , Welsh Cynthia T. , Roberts Donna R. , Bredlau Amy-Lee
Published: June 2016

Purpose:

This case report describes a toddler with a medical history of biotinidase deficiency who presented with atypical seizures due to a brain tumor.

Methods:

This is a case report.

Results:

Electroencephalogram revealed a frontal lobe mass, with magnetic resonance imaging confirmation of a mass extending from the frontal lobe into the genu and anterior corpus callosum. She underwent a near-total resection, and pathology identified a dysembryoplastic neuroepithelial tumor. The patient is now seizure free and clinically doing well.

Conclusions:

Children with biotinidase deficiency and atypical seizures should receive a full electroencephalogram evaluation, as brain tumors continue to be on the differential for seizures in this patient population.
Clinicoepidemiological Profile and Outcome of Children With Wilms Tumor in a Developing Country
Authors: Verma Nishant , Kumar Archana
Published: June 2016

Background:

Outcome of children with Wilms tumor (WT) has improved remarkably because of the advancements in Pediatric Oncology. However, in most developing countries survival rates are still poor. There is a paucity of data regarding the clinical profile and outcome of children with WT in India.

Methods:

Children with WT who were treated at our center between 2005 and 2014 were retrospectively analyzed.

Results:

Over the 10-year study period, 108 children with WT were treated in our unit. The median age at presentation was 30 months (male:female ratio of 4:1). Abdominal mass was the most common presenting feature (91%). The majority of children had stage 2 (30%) or stage 3 (35%) disease. Fifty-nine children had large or bilateral tumors requiring preoperative chemotherapy. Of the total 108 children, 11 died during primary treatment and 14 relapsed after completion of treatment. The projected 5-year overall survival is 74%, whereas the event-free survival is 73%.

Conclusions:

Children with WT in our setting present late with advanced disease and large tumors, which are technically difficult to deliver at surgery. With a multidisciplinary approach, reasonably good survival rates were achieved even in the resource-limited Indian scenario.
Hematologic Findings in Children With Brucellosis: Experiences of 622 Patients in Eastern Turkey
Authors: Karaman Kamuran , Akbayram Sinan , Bayhan Gülsüm İ. , Dogan Murat , Parlak Mehmet , Akbayram Hatice T. , Geylan Hadi , Garipardic Mesut , Oner Ahmet F.
Published: June 2016

The aim of the present study was to present the hematologic findings of 622 cases diagnosed with acute brucellosis. Medical records of children with brucellosis, admitted to Yuzuncu Yil University Hospital over a 6-year period, were analyzed retrospectively. Three hundred ninety-seven (63.8%) patients were male and 225 (36.2%) were female. The mean age was 11 years (range, 1 to 16 y). The mean hematologic values were as follows: hemoglobin 9.4 (3.4 to 17) g/dL, hematocrite 28% (12% to 50%), leukopenia 2.8 (1.1 to 33)×109/L, leukocytosis 13.7 (1.1 to 33)×109/L, and platelets 79 (3 to 972)×109/L. An overall 28.6% of patients were found to have anemia, alone or in combination with leukopenia or thrombocytopenia. Sixteen percent of patients had thrombocytopenia, 13.9% had leukopenia, 7.7% had pancytopenia, and 4% had both leukopenia and thrombocytopenia. Hematologic complications such as anemia, thrombocytopenia, and leukopenia are more frequently seen in acute brucellosis cases. However, acute brucellosis should also be considered in the differential diagnosis in the presence of other hematologic abnormalities such as severe thrombocytopenia, bicytopenia, and pancytopenia.
A New Formulation of an Old Drug: A Potential New Therapy in the Management of Oral cGvHD
Authors: Bertelli Luca , Di Nardo Giovanni , Zama Daniele , Bardasi Giulia , Morello William , Masetti Riccardo , Belotti Tamara , Forchielli Maria Luisa , Prete Arcangelo , Pession Andrea
Published: June 2016

Oral chronic graft versus host disease (cGVHD) is often refractory to systemic therapies. Additional topical treatment is commonly required. The potency of the agent, the vehicle and formulation in which it is delivered are all critical factors in determining the effectiveness of topical therapies. High potency of budesonide, combined with its very low bioavailability when absorbed through mucosal surfaces, increased the potential role in topical application for oral cGVHD. Viscous formulation increases mucosal contact time resulting in a greater decrease in mucosal inflammation. This short communication suggests that oral viscous budesonide should be considered as a potential new therapy in the management of oral cGVHD.
Care Coordination Challenges Among High-Needs, High-Costs Older Adults in a Medigap Plan
Authors: Wells Timothy S. , Bhattarai Gandhi R. , Hawkins Kevin , Cheng Yan , Ruiz Joann , Barnowski Cynthia A. , Spivack Barney , Yeh Charlotte S.
Published: June 2016

Purpose of the Study:

Many adults 65 years or older have high health care needs and costs. Here, we describe their care coordination challenges.

Primary Practice Setting:

Individuals with an AARP Medicare Supplement Insurance plan insured by UnitedHealthcare Insurance Company (for New York residents, UnitedHealthcare Insurance Company of New York).

Methodology and Sample:

The three groups included the highest needs, highest costs (the “highest group”), the high needs, high costs (the “high group”), and the “all other group.” Eligibility was determined by applying an internally developed algorithm based upon a number of criteria, including hierarchical condition category score, the Optum ImpactPro prospective risk score, as well as diagnoses of coronary artery disease, congestive heart failure, or diabetes.

Results:

The highest group comprised 2%, although consumed 12% of health care expenditures. The high group comprised 20% and consumed 46% of expenditures, whereas the all other group comprised 78% and consumed 42% of expenditures. On average, the highest group had $102,798 in yearly health care expenditures, compared with $34,610 and $7,634 for the high and all other groups, respectively. Fifty-seven percent of the highest group saw 16 or more different providers annually, compared with 21% and 2% of the high and all other groups, respectively. Finally, 28% of the highest group had prescriptions from at least seven different providers, compared with 20% and 5% of the high and all other groups, respectively.

Implications for Case Management Practice:

Individuals with high health care needs and costs have visits to numerous health care providers and receive multiple prescriptions for pharmacotherapy. As a result, these individuals can become overwhelmed trying to manage and coordinate their health care needs. Care coordination programs may help these individuals coordinate their care.
A Rare Case of Epstein-Barr Virus Negative Inflammatory Pseudotumor-like Follicular Dendritic Cell Sarcoma Presenting as a Solitary Colonic Mass in a 53-Year-Old Woman; Case Report and Review of Literature
Authors: Kazemimood Rossana , Saei Hamedani Farid , Sharif Asma , Gaitonde Sujata , Wiley Elizabeth , Giulianotti Pier Cristoforo , Groth John Vincent
Published: June 2016

Follicular dendritic cell (FDC) sarcoma is a rare neoplasm that occurs predominantly in lymph nodes. One third of FDC sarcomas happens in extranodal sites. There are 2 morphologic variants of this tumor: conventional and inflammatory pseudotumor (IPT)-like. IPT-like FDC sarcomas are reported mostly in females and usually involve the spleen and liver. In all cases of IPT-like FDC sarcoma the Epstein-Barr virus (EBV) was positive by in situ hybridization except one instance. We report a case of 53-year-old woman who presented with abdominal discomfort. Colonoscopy identified a sessile polypoid mass. Microscopically, there was a prominent lymphoplasmacytic infiltrate. Interspersed among the reactive lymphoid cells were large, pleomorphic stromal cells with marked atypia, irregular and multilobed nuclei, and hyperchromatic smudged chromatin. Immunohistochemical studies demonstrated the atypical stromal cells to be strongly positive for CD10 and D2-40, but negative for CD21, CD23, Clusterin, and epidermal growth factor receptor. EBV-encoded mRNA was negative. A diagnosis of IPT-like FDC sarcoma was rendered. To our knowledge, this is the second case of EBV-negative IPT-like FDC sarcoma reported so far in the literature.
Benign and Malignant Brenner Tumors Show an Absence of TERT Promoter Mutations That Are Commonly Present in Urothelial Carcinoma
Authors: Khani Francesca , Diolombi Mairo L. , Khattar Pallavi , Huang Weihua , Fallon John T. , Epstein Jonathan I. , Zhong Minghao
Published: June 2016

Brenner tumors are uncommon ovarian neoplasms, which have morphologic and immunophenotypical features of transitional cell (urothelial) differentiation. The origin of Brenner tumors is perplexing, but they are believed to arise from transitional cell metaplasia occurring within the ovary and/or fallopian tube, although it is controversial whether this metaplasia is truly along transitional cell lines. Recently, TERT promoter mutations have been identified in urothelial carcinoma (UC) with high frequency (approximately 70%), and the current literature suggests a potential diagnostic and/or prognostic role of these mutations in UC. Molecular evidence supporting that Brenner tumors represent neoplasms exhibiting transitional cell differentiation is scant. To explore this further, we investigated a series of 19 Brenner tumors of the ovary (15 benign and 4 malignant) for the presence of TERT promoter mutations after genomic DNA extraction from formalin-fixed paraffin-embedded tissue blocks and standard polymerase chain reaction sequencing. TERT promoter mutations were not identified in any of the cases (0/19). The absence of TERT promoter mutations in Brenner tumors suggests that despite the morphologic and some immunophenotypical resemblance to non-neoplastic and neoplastic transitional epithelium, Brenner tumors may exhibit a molecularly distinct pathogenesis. The findings also may portend diagnostic utility in rare cases wherein it is difficult to distinguish a primary malignant Brenner tumor of the ovary from metastatic UC.
Mechanically Isolated Stromal Vascular Fraction Provides a Valid and Useful Collagenase-Free Alternative Technique: A Comparative Study
Authors: Chaput Benoit , Bertheuil Nicolas , Escubes Marina , Grolleau Jean-Louis , Garrido Ignacio , Laloze Jérôme , Espagnolle Nicolas , Casteilla Louis , Sensebé Luc , Varin Audrey
Published: June 2016

Background:

The use of stromal vascular fraction and adipose-derived stromal cells in tissue regeneration is now being increasingly investigated, and studies have demonstrated that adipose-derived stromal cells present differentiation and immunomodulatory capacities. The development of a rapid, inexpensive, and enzyme-free technique to isolate adipose-derived stromal cell–enriched stromal vascular fraction is a major goal for stem cell therapy. Therefore, the authors compared innovative mechanical procedures to the gold standard technique, collagenase digestion.

Methods:

Stromal vascular fraction was prepared from 21 liposuctions using either enzymatic digestion or two different mechanical methods: high vortexing/centrifugation and dissociation by intersyringe processing. The effects of tissue processing on cell count, viability, proliferation, clonogenic enrichment, and the phenotypes of the different native cell were determined. Adipose-derived stromal cell phenotypes from the different protocols, and their differentiation and immunosuppressive potential, were compared.

Results:

Enzymatic digestion isolated more viable cells than dissociation by intersyringe processing and vortexing/centrifugation. The expansion rate and clonogenic enrichment were higher for stromal vascular fraction isolated with collagenase. The proportion of adipose-derived stromal cells was higher in stromal vascular fraction extracted with dissociation than with enzymatic digestion and vortexing/centrifugation (p < 0.01). Interestingly, all cultured adipose-derived stromal cells displayed similar differentiation and immunosuppressive capacities.

Conclusions:

Enzymatic digestion extracts more adipose-derived stromal cells, but intersyringe dissociation enables the rapid extraction of adipose-derived stromal cell–enriched stromal vascular fraction. Moreover, mechanical methods enable adipose-derived stromal cell isolation with stemness and immunosuppressive properties, similar to enzymatic digestion. Such mechanical procedures could allow easier and more rapid isolation of adipose-derived stromal cell–enriched stromal vascular fraction for practitioners.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.
Long-Term Results of a One-Stage Secondary Debulking Procedure after Flap Reconstruction of the Foot
Authors: Lin Tsan-Shiun , Quing Richard
Published: June 2016

Background:

Free or local flaps that are used to reconstruct the foot are often associated with a multitude of problems, most with regard to poor aesthetic and functional outcomes. This is because of the bulkiness of the flap and its difference from the native glabrous skin of the weight-bearing region of the foot. Although these can be improved using various debulking procedures, the results are not satisfactory.

Methods:

From January of 2002 to July of 2014, one-stage debulking procedures were performed for 42 feet after flap reconstructions. Twelve patients (28.6 percent) had bulky flaps over the weight-bearing area of the foot compared with 30 (71.4 percent) on the non–weight-bearing area. The functional and cosmetic outcomes were reviewed after 12-month follow-up.

Results:

The overall mean follow-up time was 20 months. All the grafted skin took well, except for partial superficial skin necrosis, which healed by secondary intention, and one skin loss that needed further skin grafting. The patients were able to dress in their preinjury shoes without any difficulty and with ease of ambulation because of improvement in skin stability. The skin sensation and texture of the reconstructed feet matched the normal sides well. No long-term ulceration was noted. All of the patients were satisfied with the results.

Conclusion:

A one-stage debulking procedure can provide long-term constant, reliable, thin skin coverage for the feet after free flap or local flap reconstruction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
The Cancer Care Index: A Novel Metric to Assess Overall Performance of a Pediatric Oncology Program
Authors: Olshefski Randal , Vaughan Michele , YoungSaleme Tammi , Barr Daniel , Frost Randall , Nuss Kathryn E. , Wheeler T. Arthur , Brady Michael , Davis John Terrance , Bibart Mindy , Cripe Timothy , Brilli Richard J.
Published: June 2016

Objective

Childhood cancer metrics are currently primarily focused on survival rates and late effects of therapy. Our objectives were to design and test a metric that reflected overall quality and safety performance, across all cancer types, of an oncology–bone marrow transplant service line and to use the metric to drive improvement.

Method

The Cancer Care Index (CCI) aggregates adverse safety events and missed opportunities for best practices into a composite score that reflects overall program performance without regard to cancer type or patient outcome. Fifteen domains were selected in 3 areas as follows: (1) treatment-related quality and safety, (2) provision of a harm-free environment, and (3) psychosocial support. The CCI is the aggregate number of adverse events or missed opportunities to provide quality care in a given time frame. A lower CCI reflects better care and improved overall system performance. Multidisciplinary microsystem-based teams addressed specific aims for each domain. The CCI was widely followed by all team members, particularly frontline providers.

Results

The CCI was easy to calculate and deploy and well accepted by the staff. The annual CCI progressively decreased from 278 in 2012 to 160 in 2014, a 42% reduction. Improvements in care were realized across most index domains. Multiple new initiatives were successfully implemented.

Conclusions

The CCI is a useful metric to document performance improvement across a broad range of domains, regardless of cancer type. By the use of quality improvement science, progressive reduction in CCI has occurred over a 3-year period.
Antiviral resistance in herpes simplex virus and varicella-zoster virus infections: diagnosis and management
Authors: Piret Jocelyne , Boivin Guy
Published: June 2016

Purpose of review

Aciclovir (ACV) is the first-line drug for the management of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. Long-term administration of ACV for the treatment of severe infections in immunocompromised patients can lead to the development of drug resistance. Furthermore, the emergence of isolates resistant to ACV is increasingly recognized in immunocompetent individuals with herpetic keratitis. This review describes the mechanisms involved in drug resistance for HSV and VZV, the laboratory diagnosis and management of patients with infections refractory to ACV therapy.

Recent findings

Genotypic testing is more frequently performed for the diagnosis of infections caused by drug-resistant HSV or VZV isolates. Molecular biology-based systems for the generation of recombinant viruses have been developed to link unknown mutations with their drug phenotypes. Fast and sensitive methods based on next-generation sequencing will improve the detection of heterogeneous viral populations of drug-resistant viruses and their temporal changes during antiviral therapy, which could allow better patient management. Novel promising compounds acting on targets that differ from the viral DNA polymerase are under clinical development.

Antiviral drug resistance monitoring for HSV and VZV is required for a rational use of antiviral therapy in high-risk populations.
Impact of Impaired Renal Function on Gadolinium Retention After Administration of Gadolinium-Based Contrast Agents in a Mouse Model
Authors: Kartamihardja A. Adhipatria P. , Nakajima Takahito , Kameo Satomi , Koyama Hiroshi , Tsushima Yoshito
Published: June 2016

Objectives

The aim of this study was to investigate the impact of impaired renal function on gadolinium (Gd) retention in various organs after Gd-based contrast agent injection.

Materials and Methods

After local animal care and review committee approval, 23 normal mice and 26 with renal failure were divided into 4 treatment groups (Gd-DTPA-BMA, 5 mmol/kg; Gd-DOTA, 5 mmol/kg; GdCl3, 0.02 mmol/kg; and saline, 250 μL). Each agent was intravenously administered on weekdays for 4 weeks. Samples were collected on days 3 (short-term) and 45 (long-term) after the last injection. Gadolinium concentrations were quantified by inductively coupled plasma-mass spectrometry.

Results

Three mice with renal failure and 2 normal mice in the GdCl3 group and 1 mouse with renal failure in the Gd-DTPA-BMA group died. In the Gd-DTPA-BMA group, impaired renal function increased short-term Gd retention in the liver, bone, spleen, skin, and kidney (P < 0.01) but did not affect long-term Gd retention. Gd-DTPA-BMA showed higher Gd retention than Gd-DOTA. Although Gd retention in the Gd-DOTA group was generally low, impaired renal function increased only long-term hepatic Gd retention. Hepatic and splenic Gd retentions were significantly higher than other organs' Gd retention in the GdCl3 group (P < 0.01). Renal function did not affect brain Gd retention, regardless of the Gd compound used.

Conclusions

The tendency of Gd retention varied according to the agent, regardless of renal function. Although renal impairment increased short-term Gd retention after Gd-DTPA-BMA administration, long-term Gd retention for Gd-based contrast agents was almost unaffected by renal function, suggesting that the chemical structures of retained Gd may not be consistent and some Gd is slowly eliminated after initially being retained.
Lung Cancer Screening Update
Authors: Ruchalski Kathleen L. , Brown Kathleen
Published: June 2016

Since the release of the US Preventive Services Task Force and Centers for Medicare and Medicaid Services recommendations for lung cancer screening, low-dose chest computed tomography screening has moved from the research arena to clinical practice. Lung cancer screening programs must reach beyond image acquisition and interpretation and engage in a multidisciplinary effort of clinical shared decision-making, standardization of imaging and nodule management, smoking cessation, and patient follow-up. Standardization of radiologic reports and nodule management will systematize patient care, provide quality assurance, further reduce harm, and contain health care costs. Although the National Lung Screening Trial results and eligibility criteria of a heavy smoking history are the foundation for the standard guidelines for low-dose chest computed tomography screening in the United States, currently only 27% of patients diagnosed with lung cancer would meet US lung cancer screening recommendations. Current and future efforts must be directed to better delineate those patients who would most benefit from screening and to ensure that the benefits of screening reach all socioeconomic strata and racial and ethnic minorities. Further optimization of lung cancer screening program design and patient eligibility will assure that lung cancer screening benefits will outweigh the potential risks to our patients.
Determining drug release rates of hydrophobic compounds from nanocarriers
Authors: D’Addio Suzanne M. , Bukari Abdallah A. , Dawoud Mohammed , Bunjes Heike , Rinaldi Carlos , Prud’homme Robert K.
Published: June 2016

Obtaining meaningful drug release profiles for drug formulations is essential prior to
in vivo
testing and for ensuring consistent quality. The release kinetics of hydrophobic drugs from nanocarriers (NCs) are not well understood because the standard protocols for maintaining sink conditions and sampling are not valid owing to mass transfer and solubility limitations. In this work, a new
in vitro
assay protocol based on ‘lipid sinks’ and magnetic separation produces release conditions that mimic the concentrations of lipid membranes and lipoproteins
in vivo
, facilitates separation, and thus allows determination of intrinsic release rates of drugs from NCs. The assay protocol is validated by (i) determining the magnetic separation efficiency, (ii) demonstrating that sink condition requirements are met, and (iii) accounting for drug by completing a mass balance. NCs of itraconazole and cyclosporine A (CsA) were prepared and the drug release profiles were determined. This release protocol has been used to compare the drug release from a polymer stabilized NC of CsA to a solid drug NP of CsA alone. These data have led to the finding that stabilizing block copolymer layers have a retarding effect on drug release from NCs, reducing the rate of CsA release fourfold compared with the nanoparticle without a polymer coating.

This article is part of the themed issue ‘Soft interfacial materials: from fundamentals to formulation’.
Cationic liposome–nucleic acid nanoparticle assemblies with applications in gene delivery and gene silencing
Authors: Majzoub Ramsey N. , Ewert Kai K. , Safinya Cyrus R.
Published: June 2016

Cationic liposomes (CLs) are synthetic carriers of nucleic acids in gene delivery and gene silencing therapeutics. The introduction will describe the structures of distinct liquid crystalline phases of CL–nucleic acid complexes, which were revealed in earlier synchrotron small-angle X-ray scattering experiments. When mixed with plasmid DNA, CLs containing lipids with distinct shapes spontaneously undergo topological transitions into self-assembled lamellar, inverse hexagonal, and hexagonal CL–DNA phases. CLs containing cubic phase lipids are observed to readily mix with short interfering RNA (siRNA) molecules creating double gyroid CL–siRNA phases for gene silencing. Custom synthesis of multivalent lipids and a range of novel polyethylene glycol (PEG)-lipids with attached targeting ligands and hydrolysable moieties have led to functionalized equilibrium nanoparticles (NPs) optimized for cell targeting, uptake or endosomal escape. Very recent experiments are described with surface-functionalized PEGylated CL–DNA NPs, including fluorescence microscopy colocalization with members of the Rab family of GTPases, which directly reveal interactions with cell membranes and NP pathways.In vitrooptimization of CL–DNA and CL–siRNA NPs with relevant primary cancer cells is expected to impact nucleic acid therapeuticsin vivo.

This article is part of the themed issue ‘Soft interfacial materials: from fundamentals to formulation’.
Lipid self-assembled structures for reactivity control in food
Authors: Sagalowicz L. , Moccand C. , Davidek T. , Ghanbari R. , Martiel I. , Negrini R. , Mezzenga R. , Leser M. E. , Blank I. , Michel M.
Published: June 2016

Lipid self-assembled structures (SASs) have recently gained considerable interest for their potential applications, especially for sustained nutrient release and protein crystallization. An additional property, which is underexploited, is their ability to control chemical reactions in food products. Here, we concentrate on SASs formed by phospholipids (PLs) and monoglycerides (MGs), those compounds being the most natural surfactants and therefore, the best compatible with food products, in view of providing new functionalities through the formation of SASs. In this work, the phase behaviour of these amphiphiles when mixed with oil and water is described and compared. Subsequently, we address the influence of these structures to the oxidation and Maillard-type reactions. Finally, we show that SASs formed by MGs can strongly increase the yield of key aroma impact compounds generated by Maillard-type reactions when compared with the reaction performed in aqueous precursor solutions. Various SASs are compared. In particular, addition of oil to a reversed bicontinuous structure formed by MG leads to a reversed microemulsion, which, considering its low viscosity, is particularly suitable for food products and act as a very efficient reactor system. The influence of oil and precursors on phase behaviour is discussed and related to the efficiency of the Maillard reactions.

This article is part of the themed issue ‘Soft interfacial materials: from fundamentals to formulation’.
Physical basis of some membrane shaping mechanisms
Authors: Simunovic Mijo , Prévost Coline , Callan-Jones Andrew , Bassereau Patricia
Published: June 2016

In vesicular transport pathways, membrane proteins and lipids are internalized, externalized or transported within cells, not by bulk diffusion of single molecules, but embedded in the membrane of small vesicles or thin tubules. The formation of these ‘transport carriers’ follows sequential events: membrane bending, fission from the donor compartment, transport and eventually fusion with the acceptor membrane. A similar sequence is involved during the internalization of drug or gene carriers inside cells. These membrane-shaping events are generally mediated by proteins binding to membranes. The mechanisms behind these biological processes are actively studied both in the context of cell biology and biophysics. Bin/amphiphysin/Rvs (BAR) domain proteins are ideally suited for illustrating how simple soft matter principles can account for membrane deformation by proteins. We review here some experimental methods and corresponding theoretical models to measure how these proteins affect the mechanics and the shape of membranes. In more detail, we show how an experimental method employing optical tweezers to pull a tube from a giant vesicle may give important quantitative insights into the mechanism by which proteins sense and generate membrane curvature and the mechanism of membrane scission.

This article is part of the themed issue ‘Soft interfacial materials: from fundamentals to formulation’.
An ecometric analysis of the fossil mammal record of the Turkana Basin
Authors: Fortelius Mikael , Žliobaitė Indrė , Kaya Ferhat , Bibi Faysal , Bobe René , Leakey Louise , Leakey Meave , Patterson David , Rannikko Janina , Werdelin Lars
Published: June 2016

Although ecometric methods have been used to analyse fossil mammal faunas and environments of Eurasia and North America, such methods have not yet been applied to the rich fossil mammal record of eastern Africa. Here we report results from analysis of a combined dataset spanning east and west Turkana from Kenya between 7 and 1 million years ago (Ma). We provide temporally and spatially resolved estimates of temperature and precipitation and discuss their relationship to patterns of faunal change, and propose a new hypothesis to explain the lack of a temperature trend. We suggest that the regionally arid Turkana Basin may between 4 and 2 Ma have acted as a ‘species factory’, generating ecological adaptations in advance of the global trend. We show a persistent difference between the eastern and western sides of the Turkana Basin and suggest that the wetlands of the shallow eastern side could have provided additional humidity to the terrestrial ecosystems. Pending further research, a transient episode of faunal change centred at the time of the KBS Member (1.87–1.53 Ma), may be equally plausibly attributed to climate change or to a top-down ecological cascade initiated by the entry of technologically sophisticated humans.

This article is part of the themed issue ‘Major transitions in human evolution’.
A Pleistocene palaeovegetation record from plant wax biomarkers from the Nachukui Formation, West Turkana, Kenya
Authors: Uno Kevin T. , Polissar Pratigya J. , Kahle Emma , Feibel Craig , Harmand Sonia , Roche Hélène , deMenocal Peter B.
Published: June 2016

Reconstructing vegetation at hominin fossil sites provides us critical information about hominin palaeoenvironments and the potential role of climate in their evolution. Here we reconstruct vegetation from carbon isotopes of plant wax biomarkers in sediments of the Nachukui Formation in the Turkana Basin. Plant wax biomarkers were extracted from samples from a wide range of lithologies that include fluvial–lacustrine sediments and palaeosols, and therefore provide a record of vegetation from diverse depositional environments. Carbon isotope ratios from biomarkers indicate a highly dynamic vegetation structure (ca5–100% C4vegetation) from 2.3 to 1.7 Ma, with an overall shift towards more C4vegetation on the landscape after about 2.1 Ma. The biomarker isotope data indicateca25–30% more C4vegetation on the landscape than carbon isotope data of pedogenic carbonates from the same sequence. Our data show that the environments of earlyParanthropusandHomoin this part of the Turkana Basin were primarily mixed C3–C4to C4-dominated ecosystems. The proportion of C4-based foods in the diet ofParanthropusincreases through time, broadly paralleling the increase in C4vegetation on the landscape, whereas the diet ofHomoremains unchanged. Biomarker isotope data associated with the Kokiselei archaeological site complex, which includes the site where the oldest Acheulean stone tools to date were recovered, indicate 61–97% C4vegetation on the landscape.

This article is part of the themed issue ‘Major transitions in human evolution’.
Lazarus effects: the frequency and genetic causes ofEscherichia colipopulation recovery under lethal heat stress
Authors: Hug Shaun M. , Gaut Brandon S.
Published: June 2016

Sometimes populations crash and yet recover before being lost completely. Such recoveries have been observed incidentally in evolution experiments usingEscherichia coli, and this phenomenon has been termed the “Lazarus effect.” To investigate how often recovery occurs and the genetic changes that drive it, we evolved ~300 populations ofE. coliat lethally high temperatures (43.0°) for five days and sequenced the genomes of recovered populations. Our results revealed that the Lazarus effect is uncommon, but frequent enough, at ~9% of populations, to be a potent source of evolutionary innovation. Population sequencing uncovered a set of mutations adaptive to lethal 43.0°C that were mostly distinct from those that were beneficial at a high but nonlethal temperature (42.2°). Mutations within two operons—the heat shockhslUVoperon and the RNA polymeraserpoBCoperon—drove adaptation to lethal temperature. Mutations inhslUVexhibited little antagonistic pleiotropy at 37.0°C and may have arisen neutrally prior to subjection to lethal temperature. In contrast,rpoBCmutations provided greater fitness benefits thanhslUVmutants, but were less prevalent and caused stronger fitness tradeoffs at lower temperatures. Recovered populations fixed mutations in only one operon or the other, but not both, indicating that epistatic interactions between beneficial mutations were important even at the earliest stages of adaptation.
Modeling and Analysis of Hormone and Mitogenic Signal Integration in Prostate Cancer
Authors: Rogers Katharine V. , Wayman Joseph A. , Tasseff Ryan , Gee Caitlin , DeLisa Matthew P. , Varner Jeffrey D.
Published: June 2016

Prostate cancer is the most common cancer in men and the second leading cause of cancer related death in the United States. Androgens, such as testosterone, are required for androgen dependent prostate cancer (ADPC) growth. Androgen ablation in combination with radiation or chemotherapy remains the primary non-surgical treatment for ADPC. However, androgen ablation typically fails to permanently arrest cancer progression, often resulting in castration resistant prostate cancer (CRPC). In this study, we analyzed a population of mathematical models that described the integration of androgen and mitogenic signaling in androgen dependent and independent prostate cancer. An ensemble of model parameters was estimated from 43 studies of signaling in androgen dependent and resistant LNCaP cell lines. The model population was then validated by comparing simulations with an additional 33 data sets from LNCaP cell lines and clinical trials. Analysis of the model population suggested that simultaneously targeting the PI3K and MAPK pathways in addition to anti-androgen therapies could be an effective treatment for CRPC. We tested this hypothesis in both ADPC LNCaP cell lines and LNCaP derived CRPC C4-2 cells using three inhibitors: the androgen receptor inhibitor MDV3100 (enzalutamide), the Raf kinase inhibitor sorafenib, and the PI3K inhibitor LY294002. Consistent with model predictions, cell viability decreased at 72 hrs in the dual and triple inhibition cases in both the LNCaP and C4-2 cell lines, compared to treatment with any single inhibitor. Taken together, this study suggested that crosstalk between the androgen and mitogenic signaling axes led to robustness of CRPC to any single inhibitor. Model analysis predicted potentially efficacious target combinations which were confirmed by experimental studies in multiple cell lines, thereby illustrating the potentially important role that mathematical modeling can play in cancer.
AtypicalSalmonella entericaserovars in murine and human infection models: Is it time to reassess our approach to the study of salmonellosis?
Authors: Hurley Daniel , Hoffmann Maria , Muruvanda Tim , Allard Marc W. , Brown Eric W. , Martins Marta , Fanning Séamus
Published: June 2016

NontyphoidalSalmonellaspecies are globally disseminated pathogens and the predominant cause of gastroenteritis. The pathogenesis of salmonellosis has been extensively studied usingin vivomurine models and cell lines typically challenged withSalmonellaTyphimurium. Although serovars Enteritidis and Typhimurium are responsible for the most of human infections reported to the CDC, several other serovars also contribute to clinical cases of salmonellosis. Despite their epidemiological importance, little is known about their infection phenotypes. Here, we report the virulence characteristics and genomes of 10 atypicalS. entericaserovars linked to multistate foodborne outbreaks in the United States. We show that the murine RAW 264.7 macrophage model of infection is unsuitable for inferring human relevant differences in nontyphoidalSalmonellainfections whereas differentiated human THP-1 macrophages allowed these isolates to be further characterised in a more relevant, human context.
ICGenealogy: Mapping the Function of Neuronal Ion Channels in Model and Experiment
Authors: Podlaski William F , Seeholzer Alexander , Groschner Lukas N , Miesenböck Gero , Ranjan Rajnish , Vogels Tim P
Published: June 2016

Ion channel models are the building blocks of computational neuron models. Their biological fidelity is therefore crucial for the interpretability of simulations. However, the number of published models, and the lack of standardization, make the comparison of models with one another and with experimental data difficult. Here, we present a framework for the automated large-scale classification of ion channel models. Using annotated metadata and model responses to a set of voltage-clamp protocols, we assigned 2378 models of voltage- and calcium-gated ion channels coded inNEURONto 211 clusters. TheIonChannelGenealogyweb interface provides an interactive resource for the categorization of new and existing models and experimental recordings. It enables quantitative comparisons of simulated and/or measured ion channel kinetics, and facilitates field-wide standardization of experimentally-constrained modeling.
Operant Behavior in Model Systems
Authors: Brembs Bjöern
Published: June 2016

In contrast to the long-held assumption that the organization of behavior is best characterized as the perception of a sensory stimulus followed by appropriate response (i.e., “sensorimotor hypothesis”), recent converging evidence from multiple systems and fields of study instead suggests that both ancestral and extant general brain function is best described in operant terms. Rather than specifyng precise behaviors, sensory information - if at all present - interacts with ongoing neural activity to instruct the organism which type of spontaneous, exploratory behavior to generate. Evaluating the ensuing reafferent feedback modifies the nervous system such that ongoing neural activity patterns become biased towards activity that has generated increased appetitive and decreased aversive feedback in the past. The neurobiological mechanisms underlying both the exploratory, spontaneous behaviors as well as those underlying the modifications caused by the feedback are becoming increasingly understood, even on a molecular level. It is straightforward to hypothesize that the constant interaction between ongoing neural activity and the incoming sensory stream allows the organism to balance behavioral flexibility with efficiency to accomplish adaptive behavioral choice in an often unpredictably changing environment.
Integration through cross-functional teams in a service company
Authors: Oliveira Eider Arantes de , Pimenta Márcio Lopes , Hilletofth Per , Eriksson David
Published: June 2016

Purpose

The purpose of this paper is to characterize the internal dynamics of cross-functional teams (CFTs) in different organizational processes in a service company.

Design/methodology/approach

A case study from a Brazilian service company was conducted. CFTs in five different organizational processes (strategy development, product development, portfolio management, sales channels management and business analysis) were analyzed through in-depth interviews, documents and non-participant observation.

Findings

A framework with four pillars was constructed: constitution of the CFT, task drivers, behavior and attitudes of the team and personal motivators. It was possible to analyze the process of how a group acts and reacts under changing circumstances based on the pillars included in the framework.

Research limitations/implications

The study is focused on creating analytical generalizability. Several insights in the 12 propositions presented in this study may be investigated in future research to validate the identified relationships among the pillars included in the framework. Moreover, the proposed framework allows the teams to be analyzed through a multidimensional view: structure, processes and impacts.

Practical implications

If the semantic boundaries of the communication are not well delineated, the differences in understanding can generate manifest conflicts. Moreover, the workload in a CFT seems to be larger and more complex than working in a functional activity; however, members perceive that it reduces the risk of unemployment and increases motivation.

Originality/value

The present study contributes to the extant literature with the proposal of a set of new exploratory propositions that can support future quantitative research about the use of CFTs in the service industry context.
Transforming SNCF’s business model through the evolution of participative innovation routine
Authors: Deslée Carine , Ammar Oussama
Published: June 2016

Purpose

Many barriers prevent firms from changing their business models. Inertia, as it accumulates over time, transforms into organizational routines that doom change; however, it can also be a source of organizational flexibility. How does a business model evolve in interaction with organizational routines? This paper aims to study the interactions between forms of participative innovation (PI) and existing business models.

Design/methodology/approach

The exploratory approach includes interviews, participant and non-participant observations and archive analysis. It adapts an existing framework, based on the notion of scripts, to the evolutionary dynamic of organizational routines at the French railway company SNCF. The analysis of a set of contextual elements clarifies events over time and interactions between PI and the company’s business model.

Findings

The empirical insights indicate how existing routines can help reinvent business models. Business model components evolve along the transformation phases of PI. The case reveals co-evolutionary dynamics: evolution of the organizational routine from bureaucratic suggestion, to structured innovation, to PI leads to the transformation of the business model from functionalist, to customer-centric, to open business model.

Practical implications

Firm managers can think more proactively about how to reinvent established business models by innovating their existing routines, according to the position and role of routines, shifting from sources of rigidity and inertia to levers for innovation and change.

Originality/value

The business model concept serves as a prism of analysis for organizational routines. Organizational routines are sources of flexibility, strategic renewal and business model reinvention.
Probing social media harassment
Authors: Beal Brian
Published: June 2016

Purpose

The purpose of this paper is to examine the process of investigation of employee harassment via social media to develop best practices to help organizations conduct such investigations more effectively.

Design/methodology/approach

It reviews the technical, managerial and legal literature to develop guidance for organizations conducting investigations of employee harassment via social media.

Findings

Organizations may not have effective procedures for the investigation of social media misuse, in general, and employee harassment via social media, in particular. This paper provides guidance for organizations to conduct investigation of employee harassment via social media more effectively.

Originality/value

The paper consolidates the fragmented discussion of investigation of social media misuse with regard to employee harassment via a literature review across technical, managerial and legal disciplines. The paper provides guidance to support organizations for conducting investigations of employee harassment via social media more effectively.
A search for new paths in Chinese industrial relations
Authors: Wheatcroft John
Published: June 2016

Purpose

Collective bargaining (CB) in China is perceived as inadequate, thanks to the lack of trade union independence and representation. However, there are interesting developments in some parts of the country, including Wenling, a massive manufacturing center examined here.

Design/methodology/approach

This qualitative case study covers all stakeholders, including the government, trade unions, sweater association, workers and employers.

Findings

This paper examines initially the way that trade unions are constrained by corporatism in China. Increased industrial conflicts could push employers to become the engine of change. It finds that employers endeavor to use CB as a tool to stabilize employment relations and neutralize workers resistance. A gradual transition in labor relations system is on the way. The “Wenling Way” described here could become more widely used and is seen in some quarters as a possible model.

Originality/value

This paper offers new insights into the under-reported area of Chinese industrial relations.