bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pooled Analysis Safety Profile of Nivolumab and Ipilimumab Combination Therapy in Patients With Advanced Melanoma
Authors: Sznol Mario , Ferrucci Pier Francesco , Hogg David , Atkins Michael B. , Wolter Pascal , Guidoboni Massimo , Lebbé Celeste , Kirkwood John M. , Schachter Jacob , Daniels Gregory A. , Hassel Jessica , Cebon Jonathan , Gerritsen Winald , Atkinson Victoria , Thomas Luc , McCaffrey John , Power Derek , Walker Dana , Bhore Rafia , Jiang Joel , Hodi F. Stephen , Wolchok Jedd D. 
Published: September 2017

Purpose The addition of nivolumab (anti–programmed death-1 antibody) to ipilimumab (anti–cytotoxic T-cell lymphocyte–associated 4 antibody) in patients with advanced melanoma improves antitumor response and progression-free survival but with a higher frequency of adverse events (AEs). This cross-melanoma study describes the safety profile of the approved nivolumab plus ipilimumab regimen. Methods This retrospective safety review on data from three trials (phase I, II, and III) included patients with advanced melanoma who received at least one dose of nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks × 4 and then nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity while following established guidelines for AE management. Analyses were of all treatment-related AEs, select (immune-related) AEs, time to onset and resolution, and use of immune-modulating agents and their effects on outcome. Results Among 448 patients, median duration of follow-up was 13.2 months. Treatment-related grade 3/4 AEs occurred in 55.5% of patients; 35.7% had treatment-related AEs that led to discontinuation. The most frequent treatment-related select AEs of any grade were skin (64.3%) and GI (46.7%) and of grade 3/4, hepatic (17.0%) and GI (16.3%); 30.1% developed a grade 2 to 4 select AE in more than one organ category. Median time to onset of grade 3/4 treatment-related select AEs ranged from 3.1 (skin) to 16.3 (renal) weeks, and with the exclusion of endocrine AEs, median time to resolution from onset ranged from 1.9 (renal) to 4.5 (pulmonary) weeks, with resolution rates between 79% and 100% while using immune-modulating agents. Four (< 1%) on-study deaths were attributed to therapy. Conclusion Frequency of grade 3/4 treatment-related AEs was higher with nivolumab plus ipilimumab and occurred earlier than historical experience with either agent alone, but resolution rates were similar.
The expression ofLdh-cin the skeletal muscle of plateau pika (Ochotona curzoniae) enhances adaptation to a hypoxic environment
Authors: An Zhi F. , Wei Deng B. , Wei Lian , Wang Yang , Wei Lin N. 
Published: September 2017

ABSTRACTThe plateau pika (Ochotona curzoniae) is a species of sprint-running alpine animals in the Qinghai-Tibet Plateau, which is a harsh highland hypoxic environment. Ldh-c is expressed in the testis, sperm and somatic tissues of plateau pika. To reveal the role and physiological mechanisms of sperm-specific lactate dehydrogenase (LDH-C4), in plateau pika to adapt to hypoxic environment, an adenoviral line of pMultiRNAi-Ldhc was constructed and injected into the bilateral biceps femoris of the hind legs. The swimming times of the pikas, and the Ldh-c expression levels, total LDH activities and ATP levels in skeletal muscle, were measured after the pikas were raised in the trapped site for 5 days. Our results showed that after Ldh-c was silenced, the sprint-running ability (swimming time) of the plateau pikas was significant decreased, and the total LDH activities and ATP levels were reduced by 28.21% and 27.88%, respectively. Our results indicated that expression of Ldh-c in the skeletal muscle of plateau pika increased anaerobic glycolysis and enhanced adaptation to highland hypoxic environments.
POTENTIAL OFF-GRID MARKETS FOR SMRS IN CANADA
Authors: Wojtaszek Daniel Tadeusz 
Published: September 2017

Small modular reactors (SMRs), with <300 MWe power capacity (∼1000 MWth), are being developed to improve the safety and economics of nuclear power and to expand the application of nuclear power beyond large-scale electricity grids. A key factor to improving the economics of SMRs is the ability to capitalize on the economies associated with replication. But to capitalize on these economies, there must be a market with demands for a sufficient number of the produced SMRs. The purpose of this analysis is to estimate the market for SMRs for off-grid applications in Canada. The potential market for SMRs in off-grid applications in Canada includes remote communities, remote mining projects, oil sands extraction and upgrading, cogeneration in a wide range of industries, and district energy systems. This study found that the potential market for off-grid SMRs in Canada consists of over 600 power plants, with a total power demand of 35 GWe. Another important finding was that most of these power plants require an installed capacity of <5 MWe.
Current predictive models do not accurately differentiate between single and multi gland disease in primary hyperparathyroidism: a retrospective cohort study of two endocrine surgery units
Authors: Edafe O , Collins EE , Ubhi CS , Balasubramanian SP 
Published: September 2017

Background Minimally invasive parathyroidectomy (MIP) for primary hyperparathyroidism is dependent upon accurate prediction of single-gland disease on the basis of preoperative imaging and biochemistry. The aims of this study were to validate currently available predictive models of single-gland disease in two UK cohorts and to determine if these models can facilitate MIP. Methods This is a retrospectively cohort study of 624 patients who underwent parathyroidectomy for primary hyperparathyroidism in two centres between July 2008 and December 2013. Two recognised models: CaPTHUS (preoperative calcium, parathyroid hormone, ultrasound, sestamibi, concordance imaging) and Wisconsin Index (preoperative calcium, parathyroid hormone) were validated for their ability to predict single-gland disease. Results The rates of single- and multi-gland disease were 491 (79.6%) and 126 (20.2%), respectively. Cure rates in centres 1 and 2 were 93.2% and 93.8%, respectively (P = 0.789). The positive predictive value (PPV) of CaPTHUS score . 3 in predicting single-gland disease was 84.6%, compared with 100% in the original report. CaPTHUS . 4 and 5 had a PPV of 85.1 and 87.1, respectively. There were no differences in Wisconsin Index (WIN) between patients with single- and multi-gland (P = 0.573). A WIN greater than 1600 and weight of excised gland greater than 1 g had a positive predictive value of 86.7% for single-gland disease. Conclusions The use of CaPTHUS and WIN indices without intraoperative adjuncts (such as IOPTH) had the potential to result in failure to cure in up to 15% (CaPTHUS) and 13% (WIN) of patients treated by MIP targeting a single enlarged gland.
Does a missed obstetric anal sphincter injury at time of delivery affect short-term functional outcome?
Authors: Ramage L , Yen C , Qiu S , Simillis C , Kontovounisios C , Tan E , Tekkis P 
Published: September 2017

Introduction This study aimed to ascertain whether missed obstetric anal sphincter injury at delivery had worse functional and quality of life outcomes than primary repair immediately following delivery. Materials and methods Two to one propensity matching was undertaken of patients presenting to a tertiary pelvic floor unit with ultrasound evidence of missed obstetric anal sphincter injury within 24 months of delivery with patients who underwent primary repair at the time of delivery by parity, grade of injury and time to assessment. Outcomes compared included Birmingham Bowel, Bladder and Urinary Symptom Questionnaire (BBUSQ), Wexner Incontinence Score, Short Form-36, Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire and anorectal physiology results. Results Thirty-two missed anal sphincter injuries were matched two to one with sixty-two patients who underwent primary repair of an anal sphincter defect. Mean time to follow-up was 9.31 ± 6.79 months. Patients with a missed anal sphincter injury had suffered more incontinence, as seen in higher the Birmingham Bowel, Bladder and Urinary Symptom Questionnaire (BBUSQ; 30.56% ± 14.41% vs. 19.75% ± 15.65%, P = 0.002) and Wexner scores (6.00 ± 3.76 vs. 3.67 ± 4.06, P = 0.009). They also had a worse BBUSQ urinary domain score (28.25% ± 14.9% vs. 17.01 ± 13.87%, P = 0.001) and worse physical functioning as measured by the Short Form-36 questionnaire (P = 0.045). There were no differences in other outcomes compared, including anorectal physiology and sexual function. Discussion In the short-term, patients with a missed obstetric anal sphincter injury had significantly worse faecal incontinence and urinary function scores, however quality of life and sexual function were largely comparable between groups. Conclusions Longer-term follow-up is needed to assess the effects of missed obstetric anal sphincter injury over time.
An assessment of pelvic binder placement at a UK major trauma centre
Authors: Naseem H , Nesbitt PD , Sprott DC , Clayson A 
Published: September 2017

Introduction Pelvic binders are used to reduce the haemorrhage associated with pelvic ring injuries. Application at the level of the greater trochanters is required. We assessed the frequency of their use in patients with pelvic ring injuries and their positioning in patients presenting to a single major trauma centre. Methods A retrospective review of our trauma database was performed to randomly select 1000 patients for study from April 2012 to December 2016. Patients with a pelvic binder or a pelvic ring injury defined by the Young and Burgess classification were included. Computed tomography was used to identify and measure pelvic binder placement. Results 140 patients were identified: 110/140 had a binder placed. Of the total, 54 (49.1%) patients had satisfactory placement and 56 (50.9%) had unsatisfactory placement; 30/67 (44.8%) patients with a pelvic ring injury had no binder applied, of whom 6 (20%) had an unstable injury; 9/67 patients died. Discussion This is the first study assessing pelvic binder placement in patients at a UK major trauma centre. Unsatisfactory positioning of the pelvic binder is a common problem and it was not used in a large proportion of patients with pelvic ring injuries. This demonstrates that there is a need for continuing education for teams dealing with major trauma.
Aural exostoses (surfer’s ear) provide vital fossil evidence of an aquatic phase in Man’s early evolution
Authors: Rhys Evans PH , Cameron M 
Published: September 2017

For over a century, otolaryngologists have recognised the condition of aural exostoses, but their significance and aetiology remains obscure, although they tend to be associated with frequent swimming and cold water immersion of the auditory canal. The fact that this condition is usually bilateral is predictable since both ears are immersed in water. However, why do exostoses only grow in swimmers and why do they grow in the deep bony meatus at two or three constant sites? Furthermore, from an evolutionary point of view, what is or was the purpose and function of these rather incongruous protrusions? In recent decades, paleoanthropological evidence has challenged ideas about early hominid evolution. In 1992 the senior author suggested that aural exostoses were evolved in early hominid Man for protection of the delicate tympanic membrane during swimming and diving by narrowing the ear canal in a similar fashion to other semiaquatic species. We now provide evidence for this theory and propose an aetiological explanation for the formation of exostoses.
Besov regularity for solutions of p-harmonic equations
Authors: Clop Albert , Giova Raffaella , Passarelli di Napoli Antonia 
Published: September 2017

Abstract
We establish the higher fractional differentiability of the solutions to nonlinear elliptic equations in divergence form, i.e.,

{\operatorname{div}\mathcal{A}(x,Du)=\operatorname{div}F,}

when

{\mathcal{A}}

is a p-harmonic type operator, and under the assumption that

{x\mapsto\mathcal{A}(x,\xi\/)}

belongs to the critical Besov–Lipschitz space

{B^{\alpha}_{{n/\alpha},q}}

.
We prove that some fractional differentiability assumptions on F transfer to Du with no losses in the natural exponent of integrability.
When

{\operatorname{div}F=0}

, we show that an analogous extra differentiability property for Du holds true under a Triebel–Lizorkin assumption on the partial map

{x\mapsto\mathcal{A}(x,\xi\/)}

.
Biological and topochemical studies on the resistance of excavated oak piles (Quercus sp.) from a historical bridge in Bavaria
Authors: Koch Gerald , Melcher Eckhard , Lenz Marie-Therese , Bauch Josef 
Published: September 2017

Abstract
Archaeological wood of 13 excavated oak piles from five historical bridge generations in Bavaria, dated from 1447 to 1787, was investigated by means of light microscopy (LM) and cellular UV-microspectrophotometry (UMSP) to study the ageing and natural resistance of the excavated wood. Furthermore, the mineral content of the ancient wood was determined to evaluate the impact of mineral inclusions on microbial resistance, tested using a mini block fungal test. The LM and UMSP analyses revealed well preserved cell wall structures and no significant modification of the lignin composition and distribution in predominant parts of the piles. Slight microbial decay caused by soft rot and erosion bacteria was only detectable at the outermost millimetres of individual piles. The fungal mini block tests yielded mass losses of ancient oak samples between 15% and 30%, independent of their analysed mineral content. The results provided evidence that the fungal resistance of the investigated ancient wood is mainly determined from the special soil with its high mineral content.
Experimental Synchronization of Two Van der Pol Oscillators with Nonlinear and Delayed Unidirectional Coupling
Authors: Siewe Raoul Thepi , Talla Alain Francis , Woafo Paul 
Published: September 2017

Abstract
This paper presents the experimental investigation on synchronization of two Van der Pol oscillators with polynomial and delay unidirectional couplings. The intervals of coupling coefficients and delay leading to synchronization are determined experimentally using analog electronic circuits. Three cases are considered: autonomous Van der Pol oscillators, sinusoidally exited Van der Pol oscillators in the chaotic state and Van der Pol oscillators with two slowly sinusoidal excitations delivering periodic patterns of periodic pulses. It is found that the degree of the polynomial coupling reduces the intervals of coupling coefficients leading to synchronization and the delay affects the coupling intervals in a periodic way. The experimental results agree well with the results of the theoretical (mathematical and numerical) investigation.
Anti-arthritic and gastroprotective activities of Ardisia crispa root partially mediated via its antioxidant effect
Authors: Hamid Roslida Abdul , Fong Lau Moi , Ting Yeong Looi 
Published: September 2017

Abstract

Background

Ardisia crispa Thunb A.DC (Myrsinaceae), commonly known as “hen’s eyes”, has been traditionally used in treating various inflammatory diseases. The present study evaluated anti-arthritic, gastroprotective and antioxidant activities of Ardisia crispa root hexane extract (ACRH) in various animal models.

Methods
Anti-arthritic activity was evaluated in complete Freund adjuvant (CFA)-induced adjuvant arthritis and gastroprotective effect was studied in the ethanol-induced ulcer model in rats. ACRH was further isolated to yield quinone-rich fraction (QRF) and both were analyzed for their total phenolic content, total flavonoid content and antioxidant activities in various antioxidant assays. Both ACRH and QRF were also analyzed for the quinone composition via gas chromatography analysis.

Results
ACRH exerted significant reduction of IL-1β and TNF-α at a lower dose range in CFA-induced arthritis, as well as exhibited its cytoprotective effect against ethanol-induced ulcer lesion via involvement of mucosal nonprotein sulfhydryl (NP-SH) groups. ACRH also showed higher phenolic and flavonoid contents, as well as better antioxidant activities than QRF.

Conclusions
These findings demonstrated the plant as a potential anti-inflammatory agent, with ACRH succeeded in inhibiting both arthritic and ulcerogenic effect, possibly mediated via its antioxidant effect.
Social class and the inequality of English speakers in a globalized world
Authors: Darvin Ron 
Published: September 2017

AbstractResponding to observations in ELF research that Anglophone-centric attitudes towards English are eroding among speakers of a younger generation, this paper demonstrates that attitudes towards English can in fact vary among youth of different social class backgrounds. Drawing on a case study of immigrant Filipino adolescents in Vancouver, this paper examines how class differences of these youth impinge on their lived experiences and the material conditions of their migration, shaping how they negotiate their linguistic capital, particularly their use of English. Data illustrate how such conditions shape their dispositions, their sense of agency, and feelings of linguistic confidence and insecurity. Using Darvin and Norton’s (2015. Identity and a model of investment in applied linguistics.Annual Review of Applied Linguistics35. 36–56) model of investment as a lens to investigate the interplay of identity, capital, and ideology in communicative contexts, this paper asserts how contrasting language attitudes are constructed by asymmetrical relations of power between speakers. In the spirit of accommodation and adaptation that characterizes ELF communication, this paper calls for a critical pedagogy that enables speakers to reflect on how they position themselves and others in these contexts, and assert their place as legitimate speakers of English.
“Co-certification”: a close encounter with ELF for an international examining board
Authors: Newbold David 
Published: September 2017

Abstract
Over the last decade ELF has become a reality in European universities, but this is not reflected in the major international language tests designed for access to higher education and for university students. In this paper I describe an experiment in “co-certification,” a test of English set at level C1 of the Common European Framework of Reference (CEFR), jointly developed by Trinity College London and the University of Ca’ Foscari Venice, in which an international version of the test was adapted locally to include locally relevant components and enhance validity and task authenticity. One feature of the co-certification was the introduction of an independent listening task which took the form of understanding an extract from a lecture given in English by a non-native speaker. Possible problems we had anticipated ranged from the kind of discourse features they should include, and whether or not there was a fairness issue related to accent recognition. In fact, the overall results showed no significant difference from the previous version of the exam, while the listening part had a higher pass rate than the overall oral test which involved interaction with a native speaker. As far as we know, the co-certification is the first example of an internationally recognized board engaging systematically with characteristic features of ELF communication, notably non-native phonology and intonation patterns, in a test of listening. The findings so far suggest that, for the test takers at least, this can be unproblematic and uncontroversial.
Delayed diagnosis of proopiomelanocortin (POMC) deficiency with type 1 diabetes in a 9-year-old girl and her infant sibling
Authors: Ozsu Elif , Bahm Allison 
Published: September 2017

AbstractBackground:Proopiomelanocortin (POMC) protein, encoded by theCase presentation:A 9-year-old girl from a consanguineous family of Iraqi origin was diagnosed with type 1 diabetes. She also had a tall stature. Her laboratory assessment showed low cortisol and ACTH concentrations, normal renin and poor response to ACTH stimulation. Genetic testing revealed a novel biallelic mutation in theConclusions:POMC deficiency results in significant morbidity due to obesity, and it is also a potentially life threatening disease because of adrenal insufficiency. Therefore any suggestive symptom or sign of POMC deficiency warrants detailed investigations.
Ultrasound study of fetal movements in singleton and twin pregnancies at 12–19 weeks
Authors: AboEllail Mohamed Ahmed Mostafa , Kanenishi Kenji , Mori Nobuhiro , Noguchi Junko , Marumo Genzo , Hata Toshiyuki 
Published: September 2017

Abstract

Objective
To evaluate fetal behavioral differences between singleton and twin fetuses before 20 weeks of gestation using four-dimensional (4D) ultrasound.

Methods
4D ultrasound was used to examine fetal movements in 58 singleton and 48 twin normal fetuses at 12–19 weeks. The frequencies of eight fetal movements were assessed through 15-min recordings. The fetuses were divided into two gestational age groups (12–13 and 14–19 weeks) to evaluate the changes with advancing gestation in twin versus singleton fetuses.

Results
Arm and general movements were the most frequent movements in singleton fetuses, whereas only general movement was significantly more frequent than the other seven fetal movements in twin fetuses at 12–13 weeks. At 14–19 weeks, frequencies of arm and leg movements were significantly higher than those of the other six movements in singleton fetuses, while only arm movement was significantly more frequent than the other fetal movements in twin fetuses. Comparisons of fetal movements between singleton and twin fetuses revealed that only arm movement showed a significant difference at 12–13 weeks, while the frequencies of all movements in singleton fetuses were significantly higher than those in twin fetuses at 14–19 weeks.

Conclusion
Our results suggest that the limitation of available space and crowding of twin fetuses with advancing gestation may have a marked impact on twin fetal movements compared with singleton fetuses, even in the first half of pregnancy. Further studies are needed to assess whether decreased fetal movements in twin pregnancy can affect fetal and neonatal development and maturation before and after birth.
An observation of umbilical coiling index in a low risk population in Nigeria
Authors: Adesina Kikelomo T. , Ogunlaja Olumuyiwa A. , Olarinoye Adebunmi O. , Aboyeji Abiodun P. , Akande Halimat J. , Fawole Adegboyega A. , Adeniran Abiodun S. 
Published: September 2017

AbstractObjectives:The umbilical coiling index (UCI) is one of cord parameters for foetal assessment with limited studies in our environment. With recent advances in its evaluation, its significance, pattern, abnormalities and correlates need to be defined in our parturients.Methods:The umbilical cords of 436 neonates were examined. Gross examination was done within 5 min of delivery. The UCI was defined as the number of complete coils per centimetre of cord. Normal UCI was defined as values between the 10thand 90thpercentiles of the study population.Results:The mean umbilical cord length was 52.7±11.5 cm, mean number of coils was 10.8±5.1 and mean UCI was 0.21±0.099. The range was between 0.0 and 1.0. UCI values of 0.13 and 0.30 were 10thand 90thpercentiles, respectively. Normal UCI was observed in 351 (80.5%) neonates, 44 (10.4%) and 41 (9.1%) had hypo- and hypercoiled cords, respectively. Congenital abnormalities occurred in the normocoiled and hypercoiled groups but was not demonstrated in the hypocoiled group. The mean value of UCI in neonates with congenital abnormalities was 0.29±0.12 (P=0.011). There was no significant statistical relationship between foetal outcome and degree of UCI.Conclusion:The UCI was not associated with adverse perinatal outcome in this study.