bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Deformation Methods on the Accuracy of Deformable Image Registration From Kilovoltage CT to Tomotherapy Megavoltage CT
Authors: Nobnop Wannapha , Chitapanarux Imjai , Wanwilairat Somsak , Tharavichitkul Ekkasit , Lorvidhaya Vicharn , Sripan Patumrat
Published: January 2019

Introduction:

The registration accuracy of megavoltage computed tomography images is limited by low image contrast when compared to that of kilovoltage computed tomography images. Such issues may degrade the deformable image registration accuracy. This study evaluates the deformable image registration from kilovoltage to megavoltage images when using different deformation methods and assessing nasopharyngeal carcinoma patient images.

Methods:

The kilovoltage and the megavoltage images from the first day and the 20th fractions of the treatment day of 12 patients with nasopharyngeal carcinoma were used to evaluate the deformable image registration application. The deformable image registration image procedures were classified into 3 groups, including kilovoltage to kilovoltage, megavoltage to megavoltage, and kilovoltage to megavoltage. Three deformable image registration methods were employed using the deformable image registration and adaptive radiotherapy software. The validation was compared by volume-based, intensity-based, and deformation field analyses.

Results:

The use of different deformation methods greatly affected the deformable image registration accuracy from kilovoltage to megavoltage. The asymmetric transformation with the demon method was significantly better than other methods and illustrated satisfactory value for adaptive applications. The deformable image registration accuracy from kilovoltage to megavoltage showed no significant difference from the kilovoltage to kilovoltage images when using the appropriate method of registration.

Conclusions:

The choice of deformation method should be considered when applying the deformable image registration from kilovoltage to megavoltage images. The deformable image registration accuracy from kilovoltage to megavoltage revealed a good agreement in terms of intensity-based, volume-based, and deformation field analyses and showed clinically useful methods for nasopharyngeal carcinoma adaptive radiotherapy in tomotherapy applications.
Is a Picture Worth 1,000 Words? Investigating Fraction Magnitude Knowledge Through Analysis of Student Representations
Authors: Morano Stephanie , Riccomini Paul J.
Published: January 2019

The present study examines the features and quality of visual representations (VRs) created by middle school students with learning disabilities and difficulties in mathematics in response to a released fraction item from the National Assessment of Educational Progress (NAEP). Relations between VR quality and scores on other measures of fraction knowledge are also investigated. Results show that students used circular area models most frequently to represent the NAEP item, but used bar models most accurately. Based on results, bar models may be the most efficient and effective area model VRs for use in fractions instruction. Representation quality was associated with problem-solving accuracy, as well as with performance on fraction number line estimation and fraction magnitude comparison. Implications for practice are discussed.
Fournier’s Gangrene With Septic Shock and Multiple Organ Dysfunction Syndrome
Authors: Zhou Zengding , Guo Feng , Huan Jingning
Published: January 2019

Fournier’s gangrene is a rare, rapidly progressing, and life-threatening infection associated with necrotizing fasciitis in the perineal, genital, and/or lower abdominal regions. Septic shock and multiple organ dysfunction syndrome due to the condition are even rarer events. We describe the case of a 58-year-old man who visited the emergency department with severely painful swelling in the scrotal, perianal, and lower abdominal regions. Physical examination combined with computed tomography and clinical findings led to the diagnosis of Fournier’s gangrene with septic shock and multiple organ dysfunction syndrome. Broad-spectrum antibiotics, fluid resuscitation, sedative administration, and several surgeries that included perineum reconstruction were performed successfully, and the patient fully recovered. Comprehensive, timely treatments are critical for treating Fournier’s gangrene.
The Usage of Curcumin as Chemopreventive Agent for Oral Squamous Cell Carcinoma: An Experimental Study on Sprague-Dawley Rat
Authors: Maulina Tantry , Widayanti Retno , Hardianto Andri , Sjamsudin Endang , Pontjo Bambang , Yusuf Harmas Yazid
Published: January 2019

Background: Curcumin, a natural herb that can be isolated from turmeric has been known for its therapeutic potential, including its chemopreventive potential, while heme oxygenase-1 (HO-1) is an antioxidant enzyme that can act as the biomarker for the progression of oral squamous cell carcinoma (OSCC). The current study investigated the efficacy of curcumin as a chemopreventive agent for OSCC by evaluating the immunoexpression of HO-1 at epithelial dysplasia stage. Methods: The current experimental study was conducted at the Veterinary Medicine Faculty, Bogor Agricultural Institute, Indonesia, using 40 Sprague-Dawley rats. All rats were randomly divided into 1 of 2 groups: the experimental group that was fed with standard rat food and curcumin and the control group that was fed with standard rat food without curcumin. At the beginning of the fifth week, every animal was wounded on the right buccal mucosa and was exposed to 0.5% 7,12-dymethylbenz(a)anthracene 3 times a week for 4 weeks in order to induce epithelial dysplasia of OSCC. On the ninth week, the right buccal mucosa was biopsied and the immunoexpression of HO-1 in both groups was compared and analyzed. Results: Sample examination revealed that all rats showed moderate to severe dysplastic epithelial dysplasia stage of OSCC, while a Mann-Whitney test showed that there was no significant ( P = .09) difference found between the 2 groups for the immunoexpression of HO-1. Conclusion: With regard to its chemopreventive potential, the curcumin dose used in the study was not proven to be effective. Further study is of importance.
Incidence of Flexor Pollicis Longus Complications Following Volar Locking Plate Fixation of Distal Radius Fractures
Authors: Cook Alyssa , Baldwin Paul , Fowler John R.
Published: January 2019

Background: Distal radius fractures are among the most common orthopedic injuries presenting to emergency departments. The complications of distal radius open reduction and internal fixation (ORIF) range from paresthesia to tendon ruptures. The Soong grading system was designed to evaluate volar plate position to predict postoperative flexor pollicis longus (FPL) ruptures. This study evaluates post-distal radius volar fixation FPL ruptures and other postoperative complication rates relative to Soong grade, surgical training, and plate design. Methods: A retrospective chart review was conducted to assess recorded complications after distal radius ORIF. Soong grade was determined on postoperative radiographs. Other demographic features, along with the surgeon fellowship training and plate design, were noted. Analysis was performed via t test, χ2 test, rank sum test, and Fisher exact test. Results: A total of 522 patients met inclusion criteria. Flexor tenosynovitis was the most commonly recorded complication (21% of total complications). No FPL ruptures were recorded. Soong grades between patients with and without complications were not significantly different. Soong grades between patients with flexor tenosynovitis and other complications were not significantly different. Flexor tenosynovitis had higher odds of occurring compared with other complications when the surgeon was hand-trained or when the plate type was designed by Acumed. These higher odds were not maintained under multivariate regression analysis. Conclusion: Lack of FPL ruptures in this large series may reflect improved plate technology and increased awareness. The association between flexor tenosynovitis and hand fellowship–trained surgeons may be associated with more complex cases being referred to specialists.
Valuing e-inclusion: Social media and the social networks of adolescents with intellectual disability
Authors: White Pippa , Forrester-Jones Rachel
Published: January 2019

Background:

Social media is a growing phenomenon, yet people with intellectual disability (ID) may not experience comparable access to this communication technology. Adolescents with ID may benefit from e-inclusion, especially as individuals with ID are at risk of having smaller social networks.

Materials and Methods:

The Social Network Guide was adapted to measure social media usage and used to examine the interpersonal relationships of adolescents with and without ID.

Results:

Adolescents with ID held smaller social networks with less developed informal relationships. However, friendship quality was comparable or superior to typically developing peers. Adolescents with ID interacted with a smaller percentage of contacts using social media. Social media use was predictive of the number of reported friendships and did not significantly predict critical comments.

Conclusions:

Findings suggest that adolescents with ID have comparable access to social media but use these sites to interact with a smaller number of social contacts.
Use of hemoadsorption in sepsis-associated ECMO-dependent severe ARDS: A case series
Authors: Kogelmann Klaus , Scheller Morten , Drüner Matthias , Jarczak Dominik
Published: January 2019

Introduction

Acute respiratory distress syndrome in the context of severe sepsis and septic shock represents a serious clinical disorder. A recent case series in patients with septic shock and renal failure receiving hemoadsorption treatment showed rapid hemodynamic stabilization and increased survival, particularly in pneumonia patients and in those where therapy was started early. We hypothesized that patients suffering from pneumonia and refractory acute respiratory distress syndrome to the extent that they required extracorporeal membrane oxygenation support could possibly demonstrate the most pronounced benefit from the treatment.

Methods

We assessed the association of hemoadsorption treatment with hemodynamics, ventilation, and outcome variables in a set of patients with septic shock, acute respiratory distress syndrome, need for veno-venous extracorporeal membrane oxygenation, and continuous renal replacement therapy.

Results

Key observations include a significant stabilization in hemodynamics as evidenced by a marked decrease in catecholamine need, which was paralleled by a clear reduction in hyperlactatemia. Respiratory variables improved significantly. In addition, severity of illness and overall organ dysfunction showed a considerable decrease during the course of treatment. Observed mortality was approximately half as predicted by APACHE II. Treatment with CytoSorb was safe and well tolerated with no device-related adverse events.

Discussion

This is the first case series reporting on outcome variables associated to CytoSorb therapy in critically ill patients with septic shock, acute respiratory distress syndrome, veno-venous extracorporeal membrane oxygenation, and continuous renal replacement therapy. Based on our observations in this small case series, CytoSorb might represent a potentially promising therapy option for patients with refractory extracorporeal membrane oxygenation-dependent acute respiratory distress syndrome in the context of septic shock.
Artificial intelligence for the real‐time classification of intrapapillary capillary loop patterns in the endoscopic diagnosis of early oesophageal squamous cell carcinoma: A proof‐of‐concept study
Authors: Everson M , Herrera LCGP , Li W , Luengo I Muntion , Ahmad O , Banks M , Magee C , Alzoubaidi D , Hsu HM , Graham D , Vercauteren T , Lovat L , Ourselin S , Kashin S , Wang Hsiu-Po , Wang Wen-Lun , Haidry RJ
Published: January 2019

Background

Intrapapillary capillary loops (IPCLs) represent an endoscopically visible feature of early squamous cell neoplasia (ESCN) which correlate with invasion depth – an important factor in the success of curative endoscopic therapy. IPCLs visualised on magnification endoscopy with Narrow Band Imaging (ME‐NBI) can be used to train convolutional neural networks (CNNs) to detect the presence and classify staging of ESCN lesions.

Methods

A total of 7046 sequential high‐definition ME‐NBI images from 17 patients (10 ESCN, 7 normal) were used to train a CNN. IPCL patterns were classified by three expert endoscopists according to the Japanese Endoscopic Society classification. Normal IPCLs were defined as type A, abnormal as B1–3. Matched histology was obtained for all imaged areas.

Results

This CNN differentiates abnormal from normal IPCL patterns with 93.7% accuracy (86.2% to 98.3%) and sensitivity and specificity for classifying abnormal IPCL patterns of 89.3% (78.1% to 100%) and 98% (92% to 99.7%), respectively. Our CNN operates in real time with diagnostic prediction times between 26.17 ms and 37.48 ms.

Conclusion

Our novel and proof‐of‐concept application of computer‐aided endoscopic diagnosis shows that a CNN can accurately classify IPCL patterns as normal or abnormal. This system could be used as an in vivo, real‐time clinical decision support tool for endoscopists assessing and directing local therapy of ESCN.
Linking Identity Processes to Spending Self-Control Capacities in Emerging Adulthood: The Mediating Role of Self-Regulatory Identity Functions
Authors: Vosylis Rimantas , Žukauskienė Rita , Crocetti Elisabetta
Published: January 2019

Becoming financially independent requires financial capabilities, such as capacities to control spending, and prior research suggests that identity may play a role in developing such capacities. This cross-sectional study sought to investigate how identity formation is related to spending self-control through the mediating role of self-regulatory identity functions. Participants were 481 Lithuanian students (40% employed; 57.8% women; M age = 20.27, SD age = 1.39). Results revealed that general domain identity processes affected financial capabilities both directly and indirectly (through the mediation of identity functions). Specifically, the findings highlighted that (a) ruminative exploration may make individuals more vulnerable to impulsive buying, whereas exploration in depth can promote controlled spending (direct effects) and (b) exploration in breadth and identification with commitment may promote spending self-control by strengthening goal-setting capacities (indirect effects). In synthesis, this study contributes to the understanding of favorable and unfavorable implications of identity formation on financial capabilities in emerging adulthood.
Literature Review of Locomotive Assignment Problem from Service Operations Perspective: The Case of Indian Railways
Authors: Premkumar Prashant , Kumar P. N. Ram
Published: January 2019

Since the appearance of mechanized rail transport systems in England in the 1820s, the railway has evolved as an essential service and has become the primary mode of long-distance land transportation for people as well as for bulk material across the world. It is essential for every railway organization to maintain high quality of service to not only differentiate itself and create a competitive edge over other modes of transport but also to survive. Factors such as speed, reliability, passenger comfort, convenience, system safety, special services, innovations, efficiency, itinerary accuracy and so on are important to ensure satisfactory services. The locomotive assignment problem (LAP) is one problem which, if addressed properly, would go a long way to improve the quality of services provided by the railway organization. In this work, we thoroughly study the literature pertaining to LAP to identify the constraints that have been considered hitherto by various authors. We also try to single out constraints that are relevant but ignored by most of the studies. Finally, we review studies that are specific to the Indian context and highlight the scope for further work.
Enabling Confirmatory Secondary Data Analysis by Logging Data Checkout
Authors: Scott Kimberly M. , Kline Melissa
Published: January 2019

As more researchers make their data sets openly available, the potential of secondary data analysis to address new questions increases. However, the distinction between primary and secondary data analysis is unnecessarily confounded with the distinction between confirmatory and exploratory research. We propose a framework, akin to library-book checkout records, for logging access to data sets in order to support confirmatory analysis when appropriate. This system would support a standard form of preregistration for secondary data analysis, allowing authors to demonstrate that their plans were registered prior to data access. We discuss the critical elements of such a system, its strengths and limitations, and potential extensions.
A randomised controlled trial and cost‐consequence analysis of traditional and digital foot orthoses supply chains in a National Health Service setting: application to feet at risk of diabetic plantar ulceration
Authors: Parker D. J. , Nuttall G. H. , Bray N. , Hugill T. , Martinez‐Santos A. , Edwards R. T. , Nester C.
Published: January 2019

Background

Diabetic foot ulceration is a considerable cost to the NHS and foot orthotic provision is a core strategy for the management of the people with diabetes and a moderate to high risk of foot ulceration. The traditional process to produce a custom‐made foot orthotic device is to use manual casting of foot shape and physical moulding of orthoses materials. Parts of this process can be undertaken using digital tools rather than manual processes with potential advantages. The aim of this trial was to provide the first comparison of a traditional orthoses supply chain to a digital supply chain over a 6 month period. The trial used plantar pressure, health status, and health service time and cost data to compare the two supply chains.

Methods

Fifty‐seven participants with diabetes were randomly allocated to each supply chain. Plantar pressure data and health status (EQ5D, ICECAP) was assessed at point of supply and at six‐months. The costs for orthoses and clinical services accessed by participants were assessed over the 6 months of the trial. Primary outcomes were: reduction in peak plantar pressure at the site of highest pressure, assessed for non‐inferiority to current care. Secondary outcomes were: reduction in plantar pressure at foot regions identified as at risk (> 200 kPa), cost‐consequence analysis (supply chain, clinician time, service use) and health status.

Results

At point of supply pressure reduction for the digital supply chain was non‐inferior to a predefined margin and superior (p < 0.1) to the traditional supply chain, but both supply chains were inferior to the margin after 6 months. Custom‐made orthoses significantly reduced pressure for at risk regions compared to a flat control (traditional − 13.85%, digital − 20.52%). The digital supply chain was more expensive (+£13.17) and required more clinician time (+ 35 min). There were no significant differences in health status or service use between supply chains.

Conclusions

Custom made foot orthoses reduce pressure as expected. Given some assumptions about the cost models we used, the supply chain process adopted to produce the orthoses seems to have marginal impact on overall costs and health status.

Trial registration

Retrospectively registered on ISRCTN registry (ISRCTN10978940, 04/11/2015).
Columnar cell lesions of the breast: a practical review for the pathologist
Authors: Logullo Angela Flavia , Nimir Cristiane
Published: January 2019

Background

Columnar cell lesions (CCLs) of the breast are characterized by the substitution of regular layer of cuboid epithelial by columnar cells covering the terminal duct lobular units (TDLUs). It also comprises a spectrum of lesions characterized by enlarged TDLUs with variably dilated acini lined by columnar epithelial cells, ranging from one or two layers of benign epithelium to stratified epithelium with atypia. With the increasing use of mammography screening scans in the last 30 years, columnar cell lesions (CCLs) have been diagnosed more frequently, often associated with microcalcifications and abnormal calcifications, requiring breast biopsies. This literature review presents the historical development of this entity description, with many terminologies, the CCLs categories, differential diagnoses, immunohistochemical profile and genetic alterations, reproducibility and clinical implications. In addition it discusses the significance of flat epithelial atypia (FEA), a CCL with low-grade cytological atypia.

Practical considerations

FEA are a frequent finding in breast biopsies and should be a warning sign for other possible entities within the lesion area. Since CCLs are an increasingly recognized entity in the diagnostic spectrum of breast proliferative lesions, proper training or tutorials are advisable for general pathologists in order to teach them how to identify CCLs with confidence. Intraductal proliferations with architectural complexities such as cribriform patterns, rigid cellular bridges, and true micropapillary pattern should not fall into the FEA category and are best classified as atypical ductal hyperplasia (ADH) or ductal carcinoma in situ (DCIS).

Conclusions

Among CCLs, FEA actually receives more attention due to atypia involved. FEA has been considered a non-obligate pre-neoplastic lesion and progression of these lesions to invasive cancer has been reported as increasingly low (2–7%). Therefore, controversy to the management of those lesions still remains and further intervention is restricted to cases with other premalignant lesions (ADH, DCIS) or in radiologic-pathologic disagreement.
Nivolumab for Relapsed/Refractory Diffuse Large B-Cell Lymphoma in Patients Ineligible for or Having Failed Autologous Transplantation: A Single-Arm, Phase II Study
Authors: Ansell Stephen M. , Minnema Monique C. , Johnson Peter , Timmerman John M. , Armand Philippe , Shipp Margaret A. , Rodig Scott J. , Ligon Azra H. , Roemer Margaretha G.M. , Reddy Nishitha , Cohen Jonathon B. , Assouline Sarit , Poon Michelle , Sharma Manish , Kato Kazunobu , Samakoglu Selda , Sumbul Anne , Grigg Andrew
Published: January 2019

Purpose

Treatment options are limited for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Tumor cells can exploit the programmed death-1 checkpoint pathway to evade immune surveillance. In the current study, we evaluated the efficacy and safety of programmed death-1 blockade by nivolumab in patients with relapsed/refractory DLBCL.

Methods

In this phase II, open-label study, patients with relapsed/refractory DLBCL who were ineligible for autologous hematopoietic cell transplantation (auto-HCT) or who had experienced failure with auto-HCT received nivolumab 3 mg/kg every 2 weeks. We assessed the efficacy and safety of nivolumab as well as genetic alterations of 9p24.1.

Results

Among 121 treated patients, patients in the auto-HCT–failed cohort (n = 87) received a median of four nivolumab doses and a median of three doses were administered to those in the auto-HCT–ineligible cohort (n = 34). At a median follow-up of 9 months in the auto-HCT–failed cohort and 6 months in the auto-HCT–ineligible cohort, independently assessed objective response rates were 10% and 3%, and median durations of response were 11 and 8 months, respectively. Median progression-free survival and overall survival were 1.9 and 12.2 months in the auto-HCT–failed cohort and 1.4 and 5.8 months in the auto-HCT–ineligible cohort respectively. All three patients with complete remission—3% of the auto-HCT–failed cohort—had durable response (11 or more, 14 or more, and 17 months). Treatment-related grade 3 and 4 adverse events were reported in 24% of patients. The most common were neutropenia (4%), thrombocytopenia (3%), and increased lipase (3%). Of all evaluable samples for 9p24.1 analysis, 16% exhibited low-level copy gain and 3% had amplification.

Conclusion

Nivolumab monotherapy is associated with a favorable safety profile but a low overall response rate among patients with DLBCL who are ineligible for auto-HCT or who experienced failure with auto-HCT. Genetic alterations of 9p24.1 are infrequent in DLBCL.
Generating mouse models for biomedical research: technological advances
Authors: Gurumurthy Channabasavaiah B. , Lloyd Kevin C. Kent
Published: January 2019

Over the past decade, new methods and procedures have been developed to generate genetically engineered mouse models of human disease. This At a Glance article highlights several recent technical advances in mouse genome manipulation that have transformed our ability to manipulate and study gene expression in the mouse. We discuss how conventional gene targeting by homologous recombination in embryonic stem cells has given way to more refined methods that enable allele-specific manipulation in zygotes. We also highlight advances in the use of programmable endonucleases that have greatly increased the feasibility and ease of editing the mouse genome. Together, these and other technologies provide researchers with the molecular tools to functionally annotate the mouse genome with greater fidelity and specificity, as well as to generate new mouse models using faster, simpler and less costly techniques.
Epistemologies of Biomedical Ethics: A Tribute to Dr. Engelhardt
Authors: Cutter Mary Ann G.
Published: January 2019

In this essay, and in his honor, I focus on two of physician-philosopher H. Tristram Engelhardt, Jr.’s many contributions, namely, his view that biomedical ethics (1) cannot offer a singular content-driven theoretical approach and (2) requires an appreciation of epistemologies of knowing in medicine. While these two positions remain controversial, because we all want definitive answers to our questions concerning what we ought to do in medicine and elsewhere, Dr. Engelhardt’s view makes possible discussion and debate in medicine to include diverse, defensible ways of knowing. In the end, Dr. Engelhardt’s approach in biomedical ethics is one of shared decision making and negotiation. This is an important model if we take respect for patients seriously in the clinical setting.
Bioethics and Reason in a Secular Society: Reclaiming Christian Bioethics
Authors: Wildes Kevin Wm.
Published: January 2019

Bioethics evolved from traditional physician ethics and theological ethics. It has become important in contemporary discussions of Medicine and ethics. But in contemporary secular societies the foundations of bioethics are minimal in their content and often rely on procedural ethics. The bioethics of particular communities, particularly religious communities, are richer than the procedural ethics of a secular society. Religious bioethics, situated within religious communities, are richer in content in general and in the lived reality.
Expanding Engelhardt’s cogitation: Claim for Panorthodox Bioethics
Authors: Ladas Ioannis
Published: January 2019

In June 2018 the Texan philosopher and distinguished bioethicist Tristram Engelhardt, Jr. crossed the great divide to meet his maker, as he would probably put it. His work remains till now the most systematic effort to fully revise Bioethics based on the doctrines of the Orthodox Christian theology, while it is also apreciseaccount ofEthics and Bioethics in the “after God” era. Engelhardt was anexcellent master of ancient Greek, medieval, western and eastern philosophy, and after heconverted from the Roman Catholic to the Eastern Orthodox Church – officially the Orthodox Catholic Church – he indulged in the works of the Holy Fathers andbecame greatly influenced by them. This is clearlymanifest in his views and continuous reference to Fathers and Ecclesiastical Writers. His conversion crucially influenced not only his bioethical views, but also his entire philosophical system. This magnificent journey obviously turned the Texan philosopher into a true Theologist – not in the academic sense, but in the one the Orthodox Catholic Church accepts, according to which “a Theologist is a person of God, from God, before God and speaks to praise God”. Engelhardt was not the first to deal with bioethical issues under the spectrum of Orthodox Theology, but he was the first to unravel both secular and Western-Church Bioethics and suggest a totally different version of Bioethicsbased on the principles of Orthodox ethics, the ceremonial and esoteric life of the Orthodox Church, having previously made himself a true communicant of both the paternal tradition and dogmatic teaching.
Managing vesicoureteral reflux in children: making sense of all the data
Authors: Edwards Angelena , Peters Craig A.
Published: January 2019

Current management of vesicoureteral reflux (VUR) in children is the result of a steady albeit controversial evolution of data and thinking related to the clinical impact of VUR and urinary tract infection (UTI) in children, the value of clinical screening, and the relative impact of testing and interventions for VUR. While controversy continues, there is consensus on the importance of bladder dysfunction on VUR outcomes, the likelihood of VUR resolution, and the fact that not all children with VUR require active treatment. Early efforts to define risk stratification hold the most promise to provide more patient-specific treatment of UTI and VUR in children.
Are we aiming to miss in translational autoimmunity treatments?
Authors: Vaitaitis Gisela M. , Wagner David H.
Published: January 2019

Autoimmunity treatments, fruitfully pioneered in mouse models, can be disappointing or result in immunosuppression and opportunistic infections in translational trials. Many possible reasons exist, but one major, overlooked reason may be the treatment timing in relation to circadian oscillations of the immune system. Mice and humans both have immunological circadian clocks and experience the same circulatory oscillations of immune cells with regards to their sleep/wake phases, but have opposite sleep/wake phases with regard to the daylight cycle. Therefore, researchers mainly study mice and potential autoimmunity treatments during the murine sleep/rest phase, which is when pro-inflammatory mediators and more adaptive immune cells are prevalent in the circulation. In translational trials, however, treatment administration happens primarily during a patient’s wake/activity phase, during the daytime, which is when more local and acute immune responses are active in the circulation. Therefore, we believe that the most opportune window for autoimmunity treatment may be missed in translational trials. Shifting the timing, and adjusting dosing to target only immune cells that are active at that time, may result in higher success with minimized immunosuppression or toxicities.
A nested randomised trial of the effect of tranexamic acid on intracranial haemorrhage and infarction in traumatic brain injury (CRASH-3 trial intracranial bleeding mechanistic study): Statistical analysis plan
Authors: Mahmood Abda , Roberts Ian , Shakur-Still Haleema
Published: January 2019

Background: The CRASH-3 trial is a randomised trial on the effect of tranexamic acid (TXA) on death and disability in traumatic brain injury (TBI). The CRASH-3 intracranial bleeding mechanistic study (IBMS) is a randomised trial nested within the CRASH-3 trial to examine the effect of TXA on intracranial bleeding and infarction.

Methods: Patients eligible for the CRASH-3 trial, with a GCS of 12 or less or intracranial bleeding on a pre-randomisation CT scan are eligible for the IBMS. The occurrence of intracranial bleeding, infarction, haemorrhagic oedematous lesions, mass effect and haemorrhage evacuation is examined within 28 days of randomisation using routinely collected brain scans. The primary outcome is the volume of intra-parenchymal bleeding in patients randomised within three hours of injury (adjusted for prognostic covariates). Secondary outcomes include a composite “poor” outcome, progressive and new intracranial bleeding, intracranial bleeding after neurosurgery and cerebral infarcts seen up to 28 days post-randomisation. All outcomes will be compared between treatment groups.

Statistical analyses: The primary outcome will be analysed using a covariate adjusted linear mixed model. The same analysis will be done separately for patients who undergo haemorrhage evacuation post-randomisation. We will express the effect of TXA on the composite outcome, new and progressive bleeding using relative risks and 95% CIs, and on cerebral infarcts using hazard ratios and 95% CIs. We will conduct sensitivity analyses assuming missing data are MCAR or MNAR.

Conclusion: The IBMS will provide information on the mechanism of action of TXA in TBI. This pre-specified statistical analysis plan is a technical extension of the published protocol.

Trial registration: The CRASH-3 trial was prospectively registered at the International Standard Randomised Controlled Trials registry (19 July 2011) and ClinicalTrials.gov (25 July 2011). The registries were updated with details for the IBMS on 20 December 2016.
Reducing catheter-associated urinary tract infections through best practice: Sherwood Forest Hospitals' experience
Authors: Palmer Sally , Dixon Rosie
Published: January 2019

A programme to standardise catheterisation practice was introduced in Sherwood Forest Hospitals NHS Trust in 2016, with the aim of reducing the incidence of catheter-associated urinary tract infections (CAUTIs). The initiative involved the use of a catheterisation pack (Bard®Tray). Within the first year following its introduction, the CAUTI rate had been reduced from 13.3% to 2.1% (between July 2016 and June 2017), which is a reduction of more than 80%. Standardisation has also brought cost savings for the Trust of about £33 000 a year. The Trust has maintained its standardisation approach and CAUTI rates remain at around 2%.
Promoting breast cancer awareness in older women during the seasonal flu vaccination campaign
Authors: Kaushal Aradhna , McCormick Katrina , Warburton Fiona , Burton Cathy , Ramirez Amanda J , Forbes Lindsay J
Published: January 2019

Background:

older women are at high risk of presenting with breast cancer when it has reached a late stage, which may be partly because of poor breast cancer awareness.

Aim:

the aim of this project was to implement and evaluate a new way of delivering the Promoting Early Presentation (PEP) Intervention during flu vaccination appointments in primary care. The PEP Intervention is a 1–minute intervention, accompanied by a booklet and delivered by primary care health professionals to provide older women with the knowledge, confidence and skills to present promptly on discovering symptoms of breast cancer.

Method:

health professionals delivered the PEP Intervention to older women at six general practices in south London. The authors measured changes in breast cancer awareness after the intervention and interviewed practice staff about their experiences of using it.

Findings:

knowledge of breast symptoms and breast checking was greater in women aged 70 years and above after the implementation than before. Health professionals' found it acceptable and feasible to implement.

Conclusion:

this intervention is a novel way of increasing breast cancer awareness in older women, which could contribute to earlier presentation and diagnosis of breast cancer in the UK.
Using community treatment orders: key provisions
Authors: Griffith Richard
Published: January 2019

Richard Griffith, Senior Lecturer in Health Law at Swansea University, continues his series on community mental health law with a review of community treatment orders under the Mental Health Act 1983
Gastric Schwannoma–Surgery or Endoscopic Treatment?
Authors: Luczak Martyna , Wojewodzic Nina , Paziewska Anna , Lykowska-Szuber Liliana , Eder Piotr , Szymczak Aleksandra , Linke Krzysztof , Malinger Stanislaw , Krela-Kaźmierczak Iwona
Published: January 2019

Schwannoma is a tumor formed of spindle cells that arise from the nerve plexus Schwann sheath cells of the gastrointestinal tract wall. It appears to be rare among the tumors of the gastrointestinal tract (GIT) and occurs mainly in the stomach, representing only 0.2% of all cancers of the stomach. It is usually a benign and slow growing tumor, and malignant transformation is very rare. For a long time it may remain clinically silent. Endoscopy of the upper gastrointestinal tract is considered to be the basic diagnostic tool. At this stage, the differential diagnosis is very difficult, based mainly on the exclusion of the presence of GIST (gastrointestinal stromal tumors), which appear more commonly in this location.
This study presents the case of a 44-year-old man with non-specific epigastric pain whose gastroscopy revealed a sub mucosal polyp of the body of stomach which was subsequently removed by endoscopic polypectomy. Based on histopathological and immunohistochemical findings, an Schwannoma Antoni type A was diagnosed.
Functional PEG Macromers for Biomedical Applications
Authors: Ayhan Fatma , Ayhan Hakan
Published: January 2019

Biomedical technology combines medicine and technology to diagnose, replace damaged site or regenerate tissue, and delivery of bioactive agent in a temporally controlled manner. Modified and unmodified natural and synthetic polymeric biomaterialsare currently formed in various structural shapes and chemical ingredients to overcome challenges. The recent developments in engineered PEG based hydrogel materials shows a great attractive research area due to its relatively high biocompatibility. The synthetic acrylated PEG or PEG-diacrylate and –multiacrylate monomers are the main backbone of photoinitiated radical polymerization of acrylates and polyesters used in non-degradable and degradable biomaterials. The physicochemical properties also enable to reinforce natural polymers structural characteristics. Recently published different classes of materials comprised of acrylated PEG macromers are summarized in this review.
Effects of Different Ripening Stage and Varieties on Quality Characteristics and Antioxidant Activity of Aronia (Aronia Melaocarpa)
Authors: Park Ji Hyun , Kim Kyung Mi , Cho Yong Sik , Kim Ha Yun
Published: January 2019

Aronia has low preference because of astringent and bitter taste. Appropriate processing is essential for eating aronia. For the processing of aronia, the aim of this study is to provide basic information on the cultivar and ripening stages. Three varieties (Viking, Nero and McKenzie) were studied. We divided the stages of maturity into four levels based on color. The physicochemical properties were analyzed. In the case of hardness, the first stage of maturity was the highest, and there was no difference between varieties. As maturation progressed, brightness and yellowness gradually decreased, and redness was highest at the second stage. The sugar content was the lowest in the Viking and significantly increased with the maturity stage. The acidity was highest in the Viking. Nero showed the highest radical scavenging ability. Total polyphenols and flavonoids were the highest in Nero. The highest level was shown at the first stage by the ripening stage.
Optimization of Expression Condition, Two Dimensional And Melting Point-Based Characterization of Recombinant Human Interferon Alpha-2a Fusion and Non Fusion Forms
Authors: Ningrum Ratih Asmana , Wardhani Widdya Kusuma , Wahyuni Ike , Mustopa Apon Zaenal
Published: January 2019

Recombinant Human Interferon Alpha-2a (rhIFNα-2a) is a therapeutic protein that used in hepatitis and cancer treatments. In our previous research, we developed higher molecular weight of the protein through human serum albumin fusion. The fusion and non fusion form of rhIFNα-2a were produced in Pichia pastoriswith 86 kDa and 19 kDa in size respectively. In previous research, protein yield was not reproducible due to unoptimized expression conditions. This reseach was aimed to optimize expression condition process and to characterize the fusion and non fusion forms of rhIFNα-2a. The parameters to observe in overproduction include nutrient (media and methanol concentration) and non nutrient (temperature andincubation period). Affinity and size exclusion cromatographicwere compared in protein purification. BCA assay was used to determine quantity of protein. Protein characterization was conducted using two-dimensional SDS PAGE and denaturation analyses. The optimal condition of expression was achieved using complex media with 1% of methanol for 3 day incubation period at 25°C. The protein yield was reproducible and higher comparing to previous research. Affinity chromatography resulted in higher purity of the proteins comparing to size exclusions. Characterization using two dimensional gel analysis revealed that isoelectric point of rhIFNα-2a is 6.5 for fusion form and 6.0 for non fusion form. The melting points of fusion protein were 56°C and 62°C whilst that of non fusion was 56°C.
DNA Condensation Study of Fully Synthesized Lipopeptide-Based Transfection Agent for Gene Delivery Vehicle
Authors: Tarwadi Tarwadi , Rachmawati Heni , Kartasasmita Rahmana E. , Pambudi Sabar , Arbianto Alfan Danny , Restiani Dewi Esti , Asyarie Sukmadjaja
Published: January 2019

The main requirement of transfection agent has to condense DNA in nanoparticle size, protect the DNA from nucleases and other degrading enzymes during its transport in cell cytoplasm and nucleus and should not toxic to target cells. In this research, lipopeptide composed of palmitoyl (C-16) and short peptide sequence have been designed fully synthesized and tested to DNA condensation capability and toxicity. The DNA condensation study was performed using EtBr exclusion assay and cytotoxicity determination was carried out by colorimetric MTT assay. It was revealed that lipopeptide-based transfection agent of Pal-CKKHH and Pal-CKKHH-YGRKKRRQRRR-PKKKRKV condensed DNA molecules efficiently. The lipopeptide was less toxic compared to Lipofectamine and Poly-L-Lysine, that shown by 90% of CHO-K1 cells remained viable when they were treated with 4.36 µM Pal-CKKHHYGRKKRRQRRR-PKKKRKV. Meanwhile, there were only ~75% and 80% of CHO-K1 viable cells when it was treated with PLL and Lipofectamine®2000, respectively. Moreover, cell viability of HepG2 was ~ 75% after treated with 2.18 µM of Pal-CKKHH-YGRKKRRQRRR-PKKKRKV and decreased to ~65% when the lipopeptide concentration increased to 8.72 M. In summary, the synthesized lipopeptide condenses DNA molecules efficiently, less toxic than Lipofectamine®2000 and PLL and has possibility to be explored as a non-viral gene delivery vehicle.
PALEONTOLOGY OF ACROPORA CORALS AND STANDARD FACIES BELT FROM UJUNGGENTENG AREA, WEST JAVA
Authors: Santoso Wahyu Dwijo , Zaim Yahdi , Rizal Yan
Published: January 2019

The detail taxonomy analysis was performed to classify Acropora corals in Ujunggenteng Area. The research area was selected because the continuously exposed Quaternary coralline limestones, indicated the high variation and wide distribution of coral fossils. Moreover, the facies changes and contacts with shoreface sediments were clearly observed in this area. Detail taxonomy based on morphological description can classify Acropora corals in Ujunggenteng area into four species: Acropora cervicornis, Acropora palifera, Acropora gemmifera, and Acropora humilis. The study of coral paleontology and the application of the presence of corals as a standard facies belt were still rarely performed in Indonesia. Previous studies classified the coralline limestone into one standard facies belt, which was the organic build- up standard facies belt. Another approach was required to capture many conditions of coral fossil occurrences; not only in build-up condition but also in transported condition. Therefore, another purpose of this study is to modify the standard facies belt with a different approach using coral taphonomy and sediment association.Analisis taksonomi secara detil dilakukan untuk mengklasifikasikan koral Acropora di daerah Ujunggenteng. Daerah penelitian dipilih karena tersingkapnya batugamping terumbu berumur Kuarter yang menerus, yang menunjukkan tingginya jumlah spesies dan distribusi fosil koral yang luas. Selain itu, perubahan fasies dan kontak dengan batupasir pantai dapat jelas diamati pada daerah ini. Taksonomi detil berdasarkan deskripsi morfologi dapat mengelompokkan koral Acropora di daerah Ujunggenteng menjadi empat spesies: Acropora cervicornis, Acropora palifera, Acropora gemmifera, dan Acropora humilis. Selain itu, studi mengenai paleontologi dan penggunaan kehadiran koral sebagai dasar pembagian sabuk standar fasies batugamping masih jarang dilakukan di Indonesia. Studi sebelumnya mengelompokkan batugamping terumbu menjadi satu sabuk standar fasies, yaitu organic build up. Pendekatan yang lain diperlukan untuk menjelaskan kondisi koral lainnya pada batugamping, tidak hanya dalam kondisi tumbuh, tetapi juga dalam kondisi tertransportasi. Oleh karena itu, penelitian ini bertujuan untuk memodifikasi sabuk standar fasies dengan pendekatan berbeda menggunakan tafonomi koral dan asosiasi sedimen.
A tantervi szabályozás dilemmái és lehetőségei az irodalomtanításban
Authors: Fenyő György D.
Published: January 2019

Nagy felelősség új Nemzeti Alaptantervet készíteni. Nem változik meg tőle egészen a magyar iskolaügy, de azért nagy a hatása, s az oktatás minden szereplőjének munkájára hatással van. Ezért nagy a felelőssége annak is, aki egy, a Nemzeti Alaptantervről szóló vitához hozzászól, aki véleményét, elképzeléseit érvényesíteni akarja. Nem is egyetlen szakma belügye az alaptanterv tartalma, hanem sok egymásra épülő vagy egymástól külön-külön fejlődő és vizsgáló diszciplína előmunkálatainak közös eredője lehet a majdani végeredmény. Tanulmányomban már csak ezért is nemcsak az irodalomtudomány tudására hivatkozom, de különböző szociológiai, pedagógiai, didaktikai, oktatáskutatási, olvasáskutatási eredményekre is. Mert miképp a vizsgált és befolyásolni kívánt jelenség – nevezetesen az iskolaügy – rendkívül összetett, úgy vizsgálata is szükségképpen ilyen kell legyen, s amikor egy hozzászólás az iskolarendszer egy szegmensének jogi eszközökkel történő módosítására, befolyásolására vagy megváltoztatására kíván érveket felhozni, akkor bizony mindezen aspektusok közül minél többre kell, hogy a figyelme kiterjedjen.
Az egyetemes társadalmi-kulturális jelenségek (humán univerzálék) tanításában rejlő lehetőségek az iskola bevezető és kezdő szakaszában
Authors: Kinyó László
Published: January 2019

A fogalom – amelyet más terminusokkal társadalmi, vagy humán univerzálénak, illetve egyetemes társadalmi-kulturális jelenségeknek is neveznek – a kulturális antropológiából szivárgott át a neveléstudomány területére, és az emberiség számára nélkülözhetetlen társadalmi jelenségek megnevezésére szolgál (Brown, 2013), amelyek kulturális különbségektől függetlenül szükségszerűen megjelentek és megjelennek minden jelenkori, múlt- és jövőbeni társadalomban, kultúrában, emberi közösségben. Az univerzálék számos formában és absztrakciós szinten megnyilvánulhatnak. Jelen lehetnek a mindennapi életben, az emberi viselkedésben, a gondolkodásban és az érzelmekben, az intézményi struktúrákban és a tárgyi kultúra bizonyos formáiban is (pl. étkezés, öltözködés, lakáskörülmények, családstruktúrák, kormányzat, kommunikáció, szállítás, pénz vagy a gazdasági csere egyéb formái, vallás, hivatás, kikapcsolódás stb.).