bluuebunny/crossref_metadata_2025 huggingface dataset:
Weather from incest: The politics of indigenous climate change knowledge on Palawan Island, the Philippines
Authors: Smith Will
Published: March 2018

Indigenous peoples' understandings of climate change are often interpreted through an instrumental prism that privileges the ecologically adaptive nature of belief and practice. This paper explores the limits of this perspective by considering the environmental narratives of self‐blame among households in the uplands of Palawan Island, the Philippines. In the south of the island, indigenous Pala'wan widely suggest that cyclical El Niño Southern Oscillation driven variation in rainfall and related food insecurity is the product of a linear change in climatic patterns occurring over the past several decades. This perceived climate change is explained in reference to the popularity of incestuous relationships and a decline in ritualised executions. Through an ethnographic focus on the politics of climate knowledge, I argue that Pala'wan narratives of self‐blame speak as much to ongoing struggles between indigenous people and the Philippine state over control of the forested uplands as it does to the grounded and empirical qualities of indigenous environmental knowledge.
A Relational Perspective on Everyday Mobility in the Barcelona Metropolitan Region: Individual and Household‐Related Differences in Daily Travel Time
Authors: Delclòs‐Alió Xavier , Miralles‐Guasch Carme
Published: March 2018

The collective dimension of everyday life plays a key role on how daily mobility patterns are drawn, especially considering relationships at the household level. However, previous literature regarding spatiotemporal behaviour has, above all, focused on individual characteristics detached from their immediate social contexts. By adopting a relational perspective this paper aims to explore how the combination of individual and household‐related variables can exert different mobilities in a Mediterranean metropolis such as Barcelona. Based on travel times and trip purposes reported in a traditional travel survey, both gender and social status are first confirmed as significant factors shaping daily mobility. Second, the relationships in the household emerge as relevant as individual characteristics when understanding one's everyday mobility patterns. In particular, the presence of children is regarded as a clear spatiotemporal constrictor, which is especially acute for women.
Inference and analysis across spatial supports in the big data era: Uncertain point observations and geographic contexts
Authors: Robertson Colin , Feick Rob
Published: March 2018

The ways in which geographic information are produced have expanded rapidly over recent decades. These advances have provided new opportunities for geographical information science and spatial analysis—allowing the tools and theories to be expanded to new domain areas and providing the impetus for theory and methodological development. In this light, old problems of inference and analysis are rediscovered and need to be reinterpreted, and new ones are made apparent. This article describes a new typology of geographical analysis problems that relates to uncertainties in the relationship between individual‐level data, represented as point features, and the geographic context(s) that they are associated with. We describe how uncertainty in context linkage (uncertain geographic context problem) is also related to, but distinct from, uncertainty in point‐event locations (uncertain point observation problem) and how these issues can impact spatial analysis. A case study analysis of a geosocial dataset demonstrates how alternative conclusions can result from failure to account for these sources of uncertainty. Sources of point observation uncertainties common in many forms of user‐generated and big spatial data are outlined and methods for dealing with them are reviewed and discussed.
A multicenter investigation of respiratory syncytial viral infection in children with hematopoietic cell transplantation
Authors: Rowan Courtney M. , Gertz Shira J. , Zinter Matt S. , Moffet Jerelyn , Bajwa Rajinder P. S. , Barnum Jessie L. , Kong Michele ,   the Hematopoietic Cell Transplant group of the Pediatric Acute Lung Injury and Sepsis Investigator (PALISI) network
Published: March 2018

Background

Hematopoietic cell transplant (HCT) may be a risk factor for morbidity and mortality from respiratory syncytial virus (RSV). Previous studies have been limited by small sample size. We took a multicenter approach with the goal of better understanding the epidemiology, risk factors, treatment, morbidity, and mortality associated with RSV infections among children with HCT in the United States.

Methods

A retrospective, multicenter, cohort study of pediatric HCT recipients were diagnosed with RSV infection between January 2010 and December 2014.

Results

Of the 1522 HCT, 47 (3%) patients were diagnosed with RSV. Of those with RSV, 9 (19.1%) were admitted to the pediatric intensive care unit (PICU), 6 (12.8%) received invasive mechanical ventilation, and 1 died. Prophylactic palivizumab was uncommon. All who required critical care received ribavirin vs 7.3% of those who did not (P = .004). Cobacterial infections were found in 16 patients and were not associated with the need for critical care. We examined potential risk factors for severity of RSV disease. In those who received invasive ventilation, 100% had one of the preidentified risk factors. Half of those requiring mechanical ventilation were diagnosed with RSV during their conditioning for transplant as opposed to only 2.4% of those that did not require invasive mechanical ventilation (P = .005).

Conclusions

In this multicenter cohort, RSV was not common in children following HCT. Few children infected with RSV required critical care and mortality was low. Those diagnosed with RSV during conditioning for transplant were at higher risk for invasive mechanical ventilation.
De novo CMV‐associated collapsing focal segmental glomerulosclerosis in a kidney transplant recipient
Authors: Patel Anup M. , Zenenberg Robert D. , Goldberg Ryan J.
Published: March 2018

Collapsing focal segmental glomerulosclerosis (FSGS) is a variant of FSGS and is associated with severe nephrotic syndrome and acute kidney injury and can occur after kidney transplantation. The exact mechanism of collapsing FSGS after kidney transplantation is unknown, but potential causes include autoimmune diseases, certain malignancies, bisphosphonates, m‐TOR inhibitors, interferon‐alpha, HIV infection, and other viruses. We describe a case of de novo Cytomegalovirus (CMV)‐associated collapsing FSGS in a kidney transplant recipient with a UL97 phosphotransferase mutation that was successfully treated with intravenous ganciclovir, intravenous immunoglobulin, and steroids.
Molecular diversity and landscape genomics of the crop wild relative Triticum urartu across the Fertile Crescent
Authors: Brunazzi Alice , Scaglione Davide , Talini Rebecca Fiorella , Miculan Mara , Magni Federica , Poland Jesse , Enrico Pè Mario , Brandolini Andrea , Dell'Acqua Matteo
Published: March 2018

Modern plant breeding can benefit from the allelic variation that exists in natural populations of crop wild relatives that evolved under natural selection in varying pedoclimatic conditions. In this study, next‐generation sequencing was used to generate 1.3 million genome‐wide single nucleotide polymorphisms (SNPs) on ex situ collections of Triticum urartu L., the wild donor of the Au subgenome of modern wheat. A set of 75 511 high‐quality SNPs were retained to describe 298 T. urartu accessions collected throughout the Fertile Crescent. Triticum urartu showed a complex pattern of genetic diversity, with two main genetic groups distributed sequentially from west to east. The incorporation of geographical information on sampling points showed that genetic diversity was correlated to the geographical distance (R2 = 0.19) separating samples from Jordan and Lebanon, from Syria and southern Turkey, and from eastern Turkey, Iran and Iraq. The wild emmer genome was used to derive the physical positions of SNPs on the seven chromosomes of the Au subgenome, allowing us to describe a relatively slow decay of linkage disequilibrium in the collection. Outlier loci were described on the basis of the geographic distribution of the T. urartu accessions, identifying a hotspot of directional selection on chromosome 4A. Bioclimatic variation was derived from grid data and related to allelic variation using a genome‐wide association approach, identifying several marker–environment associations (MEAs). Fifty‐seven MEAs were associated with altitude and temperature measures while 358 were associated with rainfall measures. The most significant MEAs and outlier loci were used to identify genomic loci with adaptive potential (some already reported in wheat), including dormancy and frost resistance loci. We advocate the application of genomics and landscape genomics on ex situ collections of crop wild relatives to efficiently identify promising alleles and genetic materials for incorporation into modern crop breeding.
Towards a geography of informal transport: Mobility, infrastructure and urban sustainability from the back of a motorbike
Authors: Evans James , O'Brien Jennifer , Ch Ng Beatrice
Published: March 2018

Informal transport is vital to billions of people living in rapidly growing cities in the Global South, yet is increasingly marginalised as governments legislate against modes of transport that do not conform to ideals of the “modern city.” Using an innovative combination of GPS and qualitative methods, this paper investigates how the estimated 145,000 boda‐boda motorcycle taxis in Kampala, the rapidly growing capital of Uganda, provide mobility and income for its inhabitants. While careful not to over‐romanticise the informality of African cities, we argue that there is a pressing need to understand the contribution that uniquely adapted local transport solutions like motorcycle taxis make to the sustainability of the planet's most rapidly growing cities. The paper shows how mobile methods reveal the ways in which informal transport weaves the city and the lives of its residents together, and proposes a research agenda to make informal urban transport and the kinds of mobility it enables more visible within debates concerning the future of cities.
Detection, characterization, and enrollment of donors of Ebola convalescent plasma in Sierra Leone
Authors: Tedder Richard S. , Samuel Dhan , Dicks Steve , Scott Janet T. , Ijaz Samreen , Smith Catherine C. , Adaken Charlene , Cole Christine , Baker Samuel , Edwards Tansy , Kamara Philip , Kargbo Osman , Niazi Saidia , Nwakanma Davis , d'Alessandro Umberto , Burch Graham , Doughty Heidi , Brown Colin S. , Andrews Nick , Glynn Judith R. , van Griensven Johan ,   Ebola_CP Consortium Investigators, Pollakis Georgios , Paxton William A. , Semple Malcolm G.
Published: March 2018

BACKGROUND

Passive therapy with convalescent plasma provides an early opportunity to intervene in Ebola virus disease (EVD). Methods for field screening and selection of potential donors and quantifying plasma antibody are needed.

STUDY DESIGN AND METHODS

Recombinant Ebola virus glycoprotein (EBOV GP) was formatted into immunoglobulin G‐capture, competitive, and double‐antigen bridging enzyme immunoassays (EIAs). EVD survivors in Freetown, Sierra Leone, were recruited as potential plasma donors and assessed locally using sera alone and/or paired sera and oral fluids (ORFs). Uninfected controls comprised unexposed Gambians and communities in Western Area, Sierra Leone. Antibody neutralization in selected sera was measured retrospectively in a pseudotype virus assay.

RESULTS

A total of 115 potential donors were considered for enrollment: 110 plasma samples were concordantly reactive in the three EIAs; three were concordantly unreactive and two were reactive in two of three EIAs (98.2% agreement; 95% confidence interval [CI], 93.9%‐99.8%). In 88 donors with paired ORF and plasma, G‐capture EIA reactivity correlated well in the two analytes (R2 = 0.795). Plasma and ORF from 44 Gambians were unreactive. ORF samples from 338 of 339 unexposed Western Area community controls were unreactive (specificity, 99.7%; 95% CI, 98.4%‐99.7%); ORF samples from 113 of 116 Kerry Town EVD survivors were reactive (sensitivity, 97.4%; 95% CI, 92.5%‐99.5%). Strong reactivity in G‐capture and/or competitive EIAs identified donors with high plasma EBOV GP antibody levels in the double‐antigen bridging assay, correlating with high levels of neutralizing antibody.

CONCLUSIONS

In‐field testing can qualify convalescent donors for providing high‐titer antibody.
Red blood cell transfusion in perioperative pediatric anesthesia: a survey of current practice in Germany
Authors: Wittenmeier Eva , Troeber Claudius , Zier Ulrike , Schmidtmann Irene , Pirlich Nina , Becke Karin , Piepho Tim
Published: March 2018

BACKGROUND

Little is known about the current practice of the perioperative transfusion of red blood cells (RBCs) in pediatric patients. This study was performed to evaluate the practice of RBC transfusion in German pediatric anesthesia.

STUDY DESIGN AND METHODS

An online survey was conducted among members of the German Society of Anesthesiology and Intensive Care. Participants were asked to indicate the hemoglobin (Hb) thresholds for starting RBC transfusion in six cases of different bleeding situations in pediatric anesthesia. Demographics of participants, general knowledge, and application of transfusion rules and guidelines were assessed.

RESULTS

We included 1207 of 1396 returned questionnaires. Of the respondents, 89% were qualified specialists and 68% had experience in anesthesia in children aged less than 6 months. The lowest median Hb transfusion threshold was 6 g/dL in a 16‐year‐old and the highest was 10 g/dL in a premature neonate. Intraoperative Hb thresholds increased for clinically unstable (median difference to clinically stable children, +1 g/dL; p < 0.001) or neonate and premature children (median difference to older children, +1 and +2 g/dL; p < 0.001). The stated Hb threshold ranges were broad, especially in neonates or premature children (interquartile range, neonates 3, premature children 4 g/dL). Of the participants, only 16% had knowledge of a guideline that includes blood transfusion in children.

CONCLUSION

Striking variability exists in practice of perioperative pediatric RBC transfusion. A specialized guideline for perioperative blood transfusion in children could be helpful to define and promote optimal pediatric RBC transfusion strategies.
Seed biology of Mikania micrantha in Viti Levu, Fiji
Authors: Macanawai A R , Day M D , Adkins S W
Published: March 2018

Mikania micrantha (mile‐a‐minute) reproduces both by seed and vegetatively. A study to determine the possible pollinators, seed production rates, temperature and salinity limitations to germination and its seedbank size and persistence was conducted in Viti Levu, Fiji. Representatives of the Diptera had the greatest percentage of all floral visits (38%), followed by Hymenoptera (34%) and Lepidoptera (27%), while the honeybee was the most recurring visitor (18% of all visits). Flower heads (capitula) within the inflorescence commonly formed four viable seeds, resulting in 60 820 filled seed being produced per m2. However, the seedbanks formed were not massive (600 seed m−2) and they were moderately persistent (T50: 1–3 years). Seed germination from both high and moderate rainfall regions occurred rapidly, under a wide range of temperature regimes, with no primary dormancy being observed. This study indicates that the seed reproductive success of M. micrantha in the two rainfall regions of Fiji is due to a number of factors, including the production of large numbers of flowers, successful pollination by local insects and the subsequent production of a large number of viable seeds. These seeds have high viability, no dormancy and are capable of forming small‐to‐medium seedbanks that are moderately long‐lived. In addition, seeds can germinate under a wide range of temperature and salinity conditions. This knowledge on seed production, biology, longevity and salt tolerance is vital in the development of management plans of M. micrantha in Fiji.
Quantification of regulating ecosystem services provided by weeds in annual cropping systems using a systematic map approach
Authors: Blaix C , Moonen A C , Dostatny D F , Izquierdo J , Le Corff J , Morrison J , Von Redwitz C , Schumacher M , Westerman P R
Published: March 2018

Ecosystem services have received increasing attention in life sciences, but only a limited amount of quantitative data are available concerning the ability of weeds to provide these services. Following an expert focus group on this topic, a systematic search for articles displaying evidence of weeds providing regulating ecosystem services was performed, resulting in 129 articles. The most common service found was pest control and the prevailing mechanism was that weeds provide a suitable habitat for natural enemies. Other articles showed that weeds improved soil nutrient content, soil physical properties and crop pollinator abundance. Weeds were found to provide some important ecosystem services for agriculture, but only a small number of studies presented data on crop yield. Experimental approaches are proposed that can: (i) disentangle the benefits obtained from ecosystem services provisioning from the costs due to weed competition and (ii) quantify the contribution of diverse weed communities in reducing crop competition and in providing ecosystem services. Existing vegetation databases can be used to select weed species with functional traits facilitating ecosystem service provisioning while having a lower competitive capacity. However, for services such as pest control, there are hardly any specific plant traits that have been identified and more fundamental research is needed.
Building Capacity for Evidence‐Based Practice: Understanding How Licensed Practical Nurses (LPNs) Source Knowledge
Authors: Phillips Leah , Neumeier Melanie
Published: March 2018

Background

In Canada, all nurses are required to engage in evidence‐based practice (EBP) as an entry‐to‐practice competency; however, there is little research that examines Licensed Practical Nurses’ (LPNs’) information seeking behaviors or preferred sources of knowledge to conduct EBP.

Aims

Due to the differences in education and roles of LPNs and Registered Nurses (RNs), it is both necessary and important to gain an understanding of how LPNs utilize evidence in their unique nursing practice. The purpose of this study was to investigate how LPNs source knowledge for their nursing practice.

Methods

A descriptive, cross‐sectional survey of LPNs from Alberta, Canada asked participants to rank sources of knowledge that inform their practice. Responses were correlated with age and years of practice. Analysis of variance was used to determine if there were significant mean differences between average scores and place of employment.

Results

LPN participants used similar sources of knowledge as RNs. The top source of knowledge for both RNs and LPNs was the information they learn about each individual client and the least utilized sources of knowledge were articles published in nursing, medical, and research journals, tradition, and popular media. This finding is consistent with previous studies on RNs that found nurses do not often access current research evidence to inform their practice.

Linking Evidence to Action

Since relatively few LPNs access nursing and research journals, it is important to tailor EBP education information to the workplace context. Future avenues of research might explore the potential of using in‐services and webinars to disseminate information and skills training on EBP to the LPNs, as this was a popular source of practice knowledge.
Investigation of Entrepreneurship Trends and General Competency Levels of University Students Studying at Faculty of Sports Sciences
Authors: Karabulut Ebru Olcay , Doğan Pinar Karacan
Published: March 2018

The aim of this study is to determine the general competency beliefs and entrepreneurial levels of undergraduate students studying at faculty of sports sciences by different demographic variables.The sample group consists of total 1230 students, 541 women and 689 men, who have been educated in the sport sciences of five different universities and have been chosen by chance.In this study, the entrepreneurship scale, composed of 36 items, developed by Yılmaz and Sümbül (2009) and the entrepreneurship scale, developed by Jerusalem and Schwarzer (1992) and General Self-Efficacy Scale (GSES), composed of 10 items, developed and adapted to Turkish by Çelikkaleli and Çapri (2008) were used as data collection tool.For statistical analysis of the data obtained from the study, the mean and frequency distributions were obtained. In order to determine the relationship between gender variables and the scores of the participants, t-test was performed and ANOVA test was performed to determine the relationship between the grades (points/marks) of the participants. Kruskal Wallis test was used for non-parametric tests because the variables studied did not meet the normal distribution and homogeneity conditions. In order to determine the relationship between the two scales, Pearson correlation test was performed and presented as results and tables. For statistical significance .05 significance level was selected.The results of the study show that the group has a high level of competency and entrepreneurship, that there is no meaningful relationship between gender variables and general competency and entrepreneurship levels, but that there is a meaningful relationship with the university variables they are studying. It has been determined that there is a positive correlation between the general level of competence of the students and the levels of entrepreneurship.
Feedforward neural control of toe walking in humans
Authors: Lorentzen Jakob , Willerslev‐Olsen Maria , Hüche Larsen Helle , Svane Christian , Forman Christian , Frisk Rasmus , Farmer Simon Francis , Kersting Uwe , Nielsen Jens Bo
Published: March 2018

Key points

Activation of ankle muscles at ground contact during toe walking is unaltered when sensory feedback is blocked or the ground is suddenly dropped.

Responses in the soleus muscle to transcranial magnetic stimulation, but not peripheral nerve stimulation, are facilitated at ground contact during toe walking.

We argue that toe walking is supported by feedforward control at ground contact.

Toe walking requires careful control of the ankle muscles in order to absorb the impact of ground contact and maintain a stable position of the joint. The present study aimed to clarify the peripheral and central neural mechanisms involved. Fifteen healthy adults walked on a treadmill (3.0 km h−1). Tibialis anterior (TA) and soleus (Sol) EMG, knee and ankle joint angles, and gastrocnemius–soleus muscle fascicle lengths were recorded. Peripheral and central contributions to the EMG activity were assessed by afferent blockade, H‐reflex testing, transcranial magnetic brain stimulation (TMS) and sudden unloading of the planter flexor muscle–tendon complex. Sol EMG activity started prior to ground contact and remained high throughout stance. TA EMG activity, which is normally seen around ground contact during heel strike walking, was absent. Although stretch of the Achilles tendon–muscle complex was observed after ground contact, this was not associated with lengthening of the ankle plantar flexor muscle fascicles. Sol EMG around ground contact was not affected by ischaemic blockade of large‐diameter sensory afferents, or the sudden removal of ground support shortly after toe contact. Soleus motor‐evoked potentials elicited by TMS were facilitated immediately after ground contact, whereas Sol H‐reflexes were not. These findings indicate that at the crucial time of ankle stabilization following ground contact, toe walking is governed by centrally mediated motor drive rather than sensory driven reflex mechanisms. These findings have implications for our understanding of the control of human gait during voluntary toe walking.
These Pipes Have Passed
Authors: O’Brien Colleen , Lobo Noel , Ramcharran Carlton
Published: March 2018

This article discusses need for introducing new standards for developing efficient piping systems. A barrier to wider adoption of the material has been the absence of non-metallic piping standards that could serve as a common language for manufacturers, fabricators, designers, and other stakeholders. The development of the new standards also reflects the growing international role of ASME standards. The intent of ASME NM-1 is to set engineering requirements for safe design and construction of thermoplastic piping installations. The ASMI NM-2 is expected to address pipe and piping components which are produced as standard products, as well as custom products designed for specific applications. The ASME NM-3 Standard intends to provide greater uniformity, consistency, and transparency for the identification and establishment of physical properties and allowable stress values for materials in non-metallic piping systems. The standards for thermoplastic and fiberglass reinforced plastic piping systems are being developed to fill the unmet need for comprehensive documents in these areas.
A Step Up
Authors: Fischer Bryan R.
Published: March 2018

This article presents work done by International Organization for Standardization in providing useful information. The International Organization for Standardization has released a new standard for the exchange of product-model data, ISO 10303-242, which is a new application protocol standard in the STEP family of standards. The standard significantly improves STEP’s capabilities, especially in providing useful information for an enterprise. STEP is commonly used in industry to share 3-D CAD model geometry with organizations using different CAD software with different proprietary data formats. The semantic information of the new standard is computer-interpretable; it can be used in semi-automated and automated systems and is intended to be used by software designed for tolerance analysis, inspection, and manufacturing. The CAx Implementor Forum is an essential part of STEP development. The CAx-IF works in parallel with the AP242 team to develop recommended practices for the implementation of AP242 in CAD and data translation software, to test the data models and best practices, and to provide critical feedback to the AP242 team.
Enabling Closed-Loop Surgery in MRI
Authors: Fischer Gregory S.
Published: March 2018

This article demonstrates on the use of closed-loop surgery methods in magnetic resonance imaging (MRI). MRI is a highly effective soft tissue imaging system, and the ability to utilize this procedure in-vivo coupled with precision computer controlled motion will prove to be an invaluable asset in the future development of minimally invasive surgery. Robotic assistance has been investigated for guiding instrument placement in MRI, beginning with neurosurgery and later percutaneous interventions with some examples shown in the paper. In order for a system to compatible with the MRI environment, it should: be safe in the MRI environment, preserve the image quality, and be able to operate unaffected by the scanner’s electric and magnetic fields. Closed loop control requires multiple levels of feedback. Optical encoders have proven to be successful for position sensing inside the scanner bore during imaging when coupled with differential line drivers, filtering appropriate electrical lines, and thoroughly shielding cables to minimize electromagnetic interference (EMI).
Autonomous Operation in Surgical Robotics
Authors: Rosen Jacob , Ma Ji
Published: March 2018

The article focuses on developing an algorithm for automation based on stereo computer vision and dynamic registration in a surgical robotic context. The performance of the algorithm was further tested experimentally utilizing the block transfer task which corresponds to tissue manipulation as designed by Fundamentals of Laparoscopic Surgery (FLS). The surgical robotics field as a whole progresses towards the reduction of invasiveness limiting the trauma at the periphery of the surgical site and increase of semi-autonomous operation while positioning the surgeon as a decision maker rather than as an operator. The autonomous FLS task is implemented successfully and tested experimentally with the Raven II surgical robot system. The data indicate that the autonomous operational mode has better overall performance and limited tool-environment interaction compared with the human teleoperation mode. Surgeon’s intention may also be extracted from a database that may lead to seamless switching between the human operator and the autonomous system and in that sense, it may allow the autonomous algorithm to cope with more complex surgical environments.
Neat Little Packages
Authors: Brown Alan S.
Published: March 2018

This study presents different researches on developing genetic medicines and efficient engineered delivery systems. Researchers have developed a range of approaches to deliver cancer drugs. Many of these techniques would adapt easily for genetic medicine. In fact, many researchers are already putting them to work. Arcturus Therapeutics in San Diego, a ribonucleic acid (RNA) medicines company, is working on development of an advancement over previous lipid-based delivery systems. Arcturus’s solution is a biodegradable lipid with a temporary charge, just enough to wrap medicines and RNA in a loose, yarn-like bundle. When the bundle reaches the targeted cell, the cell engulfs it, trapping it in a small sac that travels into the cell. As engineers test the design of delivery systems, they will find themselves working with scientists to understand how all the pieces fit together. Experts foresee that clinics in 30 years from the present will sequence patients’ genomes and biopsy their conditions, and prescribe treatments that target the precise cause of disease.
Comparative study on antibody immobilization strategies for efficient circulating tumor cell capture
Authors: Ates Hatice Ceren , Ozgur Ebru , Kulah Haluk
Published: March 2018

Methods for isolation and quantification of circulating tumor cells (CTCs) are attracting more attention every day, as the data for their unprecedented clinical utility continue to grow. However, the challenge is that CTCs are extremely rare (as low as 1 in a billion of blood cells) and a highly sensitive and specific technology is required to isolate CTCs from blood cells. Methods utilizing microfluidic systems for immunoaffinity-based CTC capture are preferred, especially when purity is the prime requirement. However, antibody immobilization strategy significantly affects the efficiency of such systems. In this study, two covalent and two bioaffinity antibody immobilization methods were assessed with respect to their CTC capture efficiency and selectivity, using an anti-epithelial cell adhesion molecule (EpCAM) as the capture antibody. Surface functionalization was realized on plain SiO2 surfaces, as well as in microfluidic channels. Surfaces functionalized with different antibody immobilization methods are physically and chemically characterized at each step of functionalization. MCF-7 breast cancer and CCRF-CEM acute lymphoblastic leukemia cell lines were used as EpCAM positive and negative cell models, respectively, to assess CTC capture efficiency and selectivity. Comparisons reveal that bioaffinity based antibody immobilization involving streptavidin attachment with glutaraldehyde linker gave the highest cell capture efficiency. On the other hand, a covalent antibody immobilization method involving direct antibody binding by N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC)-N-hydroxysuccinimide (NHS) reaction was found to be more time and cost efficient with a similar cell capture efficiency. All methods provided very high selectivity for CTCs with EpCAM expression. It was also demonstrated that antibody immobilization via EDC-NHS reaction in a microfluidic channel leads to high capture efficiency and selectivity.
Stem Cell Properties of Normal Human Keratinocytes Determine Transformation Responses to Human Papillomavirus 16 DNA
Authors: Woappi Yvon , Hosseinipour Maria , Creek Kim E. , Pirisi Lucia
Published: March 2018

Human papillomavirus (HPV) infection of the genital tract is common; however, only about 10 to 15% of infections persist, and approximately 10 to 15% of these persistent infections result in cancer. Basal epidermal stem cells are the presumed target cells for HPV infection, providing a reservoir of latently infected cells that persist over time and initiate lesions. However, it is not known whether stem cell density has any influence on transformation of human keratinocytes by HPV. We explored the relationship between stem cell properties of normal human keratinocytes and their susceptibility to transformation by HPV16 DNA. Normal human keratinocyte isolates (NHKc) derived from different donors were cultured in three-dimensional anchorage-free suspension to assess their spheroid-forming ability. NHKc spheroids were then plated back into plastic monolayer culture and transfected with full-length HPV16 DNA, which we have previously shown to integrate into the host cell genome upon transfection. Spheroid-derived NHKc (SD-NHKc) and fluorescence-activated cell sorting-purified populations of basal stem-like keratinocytes, expressing low levels of epidermal growth factor receptor and high levels of integrin alpha 6 (EGFR
lo
/ITGα6
hi
), responded to transfection with HPV16 DNA with more vigorous proliferation, greater immortalization efficiency, and faster progression to differentiation resistance than autologous mass-cultured cells. Conversely, cells committed to terminal differentiation (EGFR
hi
/ITGα6
lo
) grew slowly after transfection with HPV16 and failed to generate immortalized or DR clones. HPV16 DNA induced stem cell properties in mass-cultured NHKc. We conclude that HPV16 preferentially immortalizes basal keratinocytes with stem cell properties and that these cells readily achieve a differentiation-resistant phenotype upon immortalization by HPV16.

IMPORTANCE
This paper explores the relationship between the stem cell properties of normal human epidermal cells in culture and these cells' susceptibility to transformation by HPV16 DNA, the HPV type present in about 50% of cervical cancers. We report variable susceptibilities to HPV16-mediated transformation among different keratinocyte isolates derived from neonatal foreskin. Our findings provide strong experimental evidence that HPV16 preferentially transforms basal keratinocytes with stem cell properties. Insights gained from these studies increase our understanding of the host cell-specific factors influencing individual susceptibility to HPV-driven transformation and the contributing factors leading to preneoplastic and neoplastic progression of HPV-positive lesions.
Delayed neurological deficits after endovascular placement of a pipeline embolisation device: clinical manifestation and treatment
Authors: Sablani Naveen , Hasan Maryam Mumtaz , Shrestha Ashik , Farkas Jeffrey
Published: March 2018

Endovascular treatment has been the mainstay of therapy for repair of both ruptured and unruptured cerebral aneurysms. Flow diverter devices offer a new option for the treatment of complex aneurysms that were previously not amenable to coiling. Procedural adverse effects include intracranial haemorrhage and ischaemic stroke, which usually occur on the same day. Delayed complications are rare. We report a case of a patient who underwent placement of a pipeline embolisation device and developed delayed neurological deficits, which were thought to be an inflammatory reaction to the hydrophilic coating used in guidewires and microcatheters. Our patient was treated with a course of steroids, with improvement of her neurological deficits and resolution of MRI findings. As the use of flow diverter devices has increased, variable and delayed complications of such therapy are increasingly being reported in the literature.
Patient demographic and surgical characteristics in anterior cruciate ligament reconstruction: a description of registries from six countries
Authors: Prentice Heather A , Lind Martin , Mouton Caroline , Persson Andreas , Magnusson Henrik , Gabr Ayman , Seil Romain , Engebretsen Lars , Samuelsson Kristian , Karlsson Jon , Forssblad Magnus , Haddad Fares S , Spalding Tim , Funahashi Tadashi T , Paxton Liz W , Maletis Gregory B
Published: March 2018

Objective

Findings from individual anterior cruciate ligament reconstruction (ACLR) registry studies are impactful, but how various registries from different countries compare with different patient populations and surgical techniques has not been described. We sought to describe six ACLR registry cohorts to understand variation across countries.

Methods

Five European registries and one US registry participated. For each registry, all primary ACLR registered between registry establishment through 31December 2014 were identified. Descriptive statistics included frequencies, proportions, medians and IQRs. Revision incidence rates following primary ACLR were computed.

Results

101 125 ACLR were included: 21 820 in Denmark, 300 in Luxembourg, 17 556 in Norway, 30 422 in Sweden, 2972 in the UK and 28 055 in the US. In all six cohorts, males (range: 56.8%–72.4%) and soccer injuries (range: 14.1%–42.3%) were most common. European countries mostly used autografts (range: 93.7%–99.7%); allograft was most common in the US (39.9%). Interference screw was the most frequent femoral fixation in Luxembourg and the US (84.8% and 42.9%), and suspensory fixation was more frequent in the other countries (range: 43.9%–75.5%). Interference was the most frequent tibial fixation type in all six cohorts (range: 64.8%–98.2%). Three-year cumulative revision probabilities ranged from 2.8% to 3.7%.

Conclusions

Similarities in patient demographics and injury activity were observed between all cohorts of ACLR. However, graft and fixation choices differed. Revision rates were low. This work, including >100 000 ACLR, is the most comprehensive international description of contemporary practice to date.
Randomised controlled trial of exercise to prevent shoulder problems in women undergoing breast cancer treatment: study protocol for the prevention of shoulder problems trial (UK PROSPER)
Authors: Bruce Julie , Williamson Esther , Lait Clare , Richmond Helen , Betteley Lauren , Lall Ranjit , Petrou Stavros , Rees Sophie , Withers Emma J , Lamb Sarah E , Thompson Alastair M
Published: March 2018

Musculoskeletal shoulder problems are common after breast cancer treatment. Early postoperative exercises targeting the upper limb may improve shoulder function. This protocol describes a National Institute for Health Research-funded randomised controlled trial (RCT) to evaluate the clinical and cost-effectiveness of an early supervised structured exercise programme compared with usual care, for women at high risk of developing shoulder problems after breast cancer surgery.

Methods

This pragmatic two-armed, multicentre RCT is underway within secondary care in the UK. PRevention Of Shoulder ProblEms tRial (PROSPER) aims to recruit 350 women from approximately 15 UK centres with follow-up at 6 weeks, 6 and 12 months after randomisation. Recruitment processes and intervention development were optimised through qualitative research during a 6-month internal pilot phase. Participants are randomised to the PROSPER intervention or best practice usual care only. The PROSPER intervention is delivered by physiotherapists and incorporates three main components: shoulder-specific exercises targeting range of movement and strength; general physical activity and behavioural strategies to encourage adherence and support exercise behaviour. The primary outcome is upper arm function assessed using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire at 12 months postrandomisation. Secondary outcomes include DASH subscales, acute and chronic pain, complications, health-related quality of life and healthcare resource use. We will interview a subsample of 20 participants to explore their experiences of the trial interventions.

Discussion

The PROSPER study is the first multicentre UK clinical trial to investigate the clinical and cost-effectiveness of supported exercise in the prevention of shoulder problems in high-risk women undergoing breast cancer surgery. The findings will inform future clinical practice and provide valuable insight into the role of physiotherapy-supported exercise in breast cancer rehabilitation.

Protocol version

Version 2.1; dated 11 January 2017

Trial registration number

ISRCTN35358984; Pre-results.
Lifestyle and vascular risk effects on MRI-based biomarkers of Alzheimer’s disease: a cross-sectional study of middle-aged adults from the broader New York City area
Authors: Mosconi Lisa , Walters Michelle , Sterling Joanna , Quinn Crystal , McHugh Pauline , Andrews Randolph E , Matthews Dawn C , Ganzer Christine , Osorio Ricardo S , Isaacson Richard S , De Leon Mony J , Convit Antonio
Published: March 2018

Objective

To investigate the effects of lifestyle and vascular-related risk factors for Alzheimer’s disease (AD) on in vivo MRI-based brain atrophy in asymptomatic young to middle-aged adults.

Design

Cross-sectional, observational.

Setting

Broader New York City area. Two research centres affiliated with the Alzheimer’s disease Core Center at New York University School of Medicine.

Participants

We studied 116 cognitively normal healthy research participants aged 30–60 years, who completed a three-dimensional T1-weighted volumetric MRI and had lifestyle (diet, physical activity and intellectual enrichment), vascular risk (overweight, hypertension, insulin resistance, elevated cholesterol and homocysteine) and cognition (memory, executive function, language) data. Estimates of cortical thickness for entorhinal (EC), posterior cingulate, orbitofrontal, inferior and middle temporal cortex were obtained by use of automated segmentation tools. We applied confirmatory factor analysis and structural equation modelling to evaluate the associations between lifestyle, vascular risk, brain and cognition.

Results

Adherence to a Mediterranean-style diet (MeDi) and insulin sensitivity were both positively associated with MRI-based cortical thickness (diet: βs≥0.26, insulin sensitivity βs≥0.58, P≤0.008). After accounting for vascular risk, EC in turn explained variance in memory (P≤0.001). None of the other lifestyle and vascular risk variables were associated with brain thickness. In addition, the path associations between intellectual enrichment and better cognition were significant (βs≥0.25 P≤0.001), as were those between overweight and lower cognition (βs≥-0.22, P≤0.01).

Conclusions

In cognitively normal middle-aged adults, MeDi and insulin sensitivity explained cortical thickness in key brain regions for AD, and EC thickness predicted memory performance in turn. Intellectual activity and overweight were associated with cognitive performance through different pathways. Our findings support further investigation of lifestyle and vascular risk factor modification against brain ageing and AD. More studies with larger samples are needed to replicate these research findings in more diverse, community-based settings.
Opioid use and harms associated with a sustained-release tapentadol formulation: a postmarketing study protocol
Authors: Peacock Amy , Larance Briony , Farrell Michael , Cairns Rose , Buckley Nicholas , Degenhardt Louisa
Published: March 2018

Introduction

It has been argued that tapentadol may pharmacologically have lower abuse potential than other pharmaceutical opioids currently available. However, there has been no comprehensive triangulation of data regarding use and harms associated with this formulation. A sustained-release formulation (SRF) of tapentadol (Palexia) was released in Australia in 2011 and listed for public subsidy in 2013. We summarise here the methods of a postmarketing study which will measure postintroduction: (1) population level availability, (2) extramedical use and diversion, (3) attractiveness for extramedical use and (4) associated harms, of tapentadol compared against other pharmaceutical opioids.

Methods and analysis

We evaluated key sources on pharmaceutical use and harms in Australia. This review indicateddata from four sources that disaggregate pharmaceutical opioid formulations and capture tapentadol SRF could be triangulated. These data sources comprised: (1) national pharmaceutical opioid community sales data from 2011 to 2017, (2) national pharmaceutical opioid poisonings reported to Poison Information Centres (PICs) from 2011 to 2017, (3) number of vendors on online marketplaces listing pharmaceutical opioids for sale and (4) data on pharmaceutical opioid extramedical use, attractiveness and harms from interviews with people who regularly inject drugs in Australia.

Ethics and dissemination

Ethics approval is not required for use of pharmaceutical sales data. Ethics approval has been obtained for use of national pharmaceutical opioid poisonings reported to PICs (LNR/16/SCHN/44) and for use of online marketplace data and interview data from people who inject drugs (HC12086). Key findings will be published mid-2018 in a peer-reviewed academic journal, and presented at various conferences and professional meetings.
Pregnancy-associated liver disease: a curriculum-based review
Authors: Kelly Claire , Pericleous Marinos
Published: March 2018

Pregnancy is associated with changes in normal physiology, including changes to the normal parameters for blood tests. Abnormal liver function tests are a common reason for referral to gastroenterology. However, in the pregnant patient, there are unique potential causes. It is of prime importance to be aware of pregnancy-specific liver diseases as they can be serious and progress rapidly affecting outcomes for both the mother and fetus. Here, we provide an overview of the manifestations of pregnancy-related liver diseases and discuss their potential consequences.