bluuebunny/crossref_metadata_2025 huggingface dataset:
Dose-rate effect of ultrashort electron beam radiation on DNA damage and repair in vitro
Authors: Babayan Nelly , Hovhannisyan Galina , Grigoryan Bagrat , Grigoryan Ruzanna , Sarkisyan Natalia , Tsakanova Gohar , Haroutiunian Samvel , Aroutiounian Rouben
Published: June 2017

Laser-generated electron beams are distinguished from conventional accelerated particles by ultrashort beam pulses in the femtoseconds to picoseconds duration range, and their application may elucidate primary radiobiological effects. The aim of the present study was to determine the dose-rate effect of laser-generated ultrashort pulses of 4 MeV electron beam radiation on DNA damage and repair in human cells. The dose rate was increased via changing the pulse repetition frequency, without increasing the electron energy. The human chronic myeloid leukemia K-562 cell line was used to estimate the DNA damage and repair after irradiation, via the comet assay. A distribution analysis of the DNA damage was performed. The same mean level of initial DNA damages was observed at low (3.6 Gy/min) and high (36 Gy/min) dose-rate irradiation. In the case of low-dose-rate irradiation, the detected DNA damages were completely repairable, whereas the high-dose-rate irradiation demonstrated a lower level of reparability. The distribution analysis of initial DNA damages after high-dose-rate irradiation revealed a shift towards higher amounts of damage and a broadening in distribution. Thus, increasing the dose rate via changing the pulse frequency of ultrafast electrons leads to an increase in the complexity of DNA damages, with a consequent decrease in their reparability. Since the application of an ultrashort pulsed electron beam permits us to describe the primary radiobiological effects, it can be assumed that the observed dose-rate effect on DNA damage/repair is mainly caused by primary lesions appearing at the moment of irradiation.
Mathematics Based on Fuzzy Logic
Authors: Bělohlávek Radim , Dauben Joseph W. , Klir George J.
Published: June 2017

Mathematical reasoning is governed by the laws of classical logic, based on the principle of bivalence. With the acceptance of intermediate truth degrees, the situation changed substantially. This chapter begins with a characterization of mathematics based on fuzzy logic, an identification of principal issues of its development, and an outline of this development. It then examines the role of fuzzy logic in the narrow sense for developing mathematics based on fuzzy logic and the main approaches developed toward its foundations. Next, some selected areas of mathematics based on fuzzy logic are presented, such as the theory of sets and relations, algebra, topology, quantities and mathematical analysis, probability, and geometry. The chapter concludes by examining various semantic questions regarding fuzzy logic and mathematics based on it.
“It’s Ethics, Jim, but Not as We Know It”
Authors: Keown Damien
Published: June 2017

This essay explores the paradox of how a religion as ethical as Buddhism appears to have no ethics, or at least to lack the philosophical discipline that normally goes by that name. Buddhism is rightly admired for its moral teachings, but the tradition itself has shown a curious lack of interest in critical reflection on those teachings. Ethical dilemmas are rarely explored, and discussion of meta-ethical issues is almost entirely lacking. Instead Buddhist intellectual energy appears to have been channeled predominantly into metaphysics and certain related fields like logic and epistemology. Not until modern times has a discipline of Buddhist ethics emerged. The background to this situation is explored in section 1.2, and in section 1.3 a number of possible explanations for the contrast between the Buddhist and Western philosophical traditions are suggested.
Buddhist Moral Thought and Western Moral Philosophy
Authors: Gowans Christopher W.
Published: June 2017

This essay discusses interpretations of Indian Buddhist moral thought in terms of common categories of Western moral philosophy. Problems are raised for interpretations of Buddhism as being committed to a theory of what makes an action morally right (specifically deontology, consequentialism, and virtue ethics). Following the lead of the poison arrow simile, a nontheoretical understanding of Buddhist moral thought is proposed: it was implicitly supposed that we do not need to act on the basis of universal moral principles but simply need to overcome the roots of unwholesome actions (greed, hatred, and delusion) and act skillfully. This interpretation is compared with other nontheoretical interpretations of Buddhist moral thought by reference to moral particularism, moral phenomenology, moral pluralism, and a nontheoretical conception of virtue ethics. It is also suggested that we should not be perplexed by the absence of explicit moral theory in Buddhism. Featured figures include Aristotle and Śāntideva.
Ethical Reading and the Ethics of Forgetting and Remembering
Authors: McClintock Sara
Published: June 2017

This essay is an experiment in ethical reading that engages three stories from the collection of Indian Buddhist narratives, the Divyāvadāna, with special attention to the ethics of forgetting and remembering. Ethical reading signifies an approach to reading in which the reader takes an active interest in the effects the reading may have on his or her own ethical self-fashioning or autopoiesis. Buddhist narratives are fertile soil for ethical reading both because they showcase instances of Buddhist ethical autopoiesis and because they often provoke ethical autopoiesis in their readers. Focusing on the shock (saṃvega) that may occur when one is reminded of things one has forgotten, the paper argues for the ethical significance not so much of remembering the past as of remembering that one has forgotten it. The colorful tales from the Divyāvadāna serve as brilliant and humorous reminders of the enormity of all we have forgotten.
Getting to Mexico City
Authors: Olcott Jocelyn
Published: June 2017

This chapter examines how the IWY conference, originally planned to take place in Bogota, Colombia, came to be held in Mexico City. It considers both Mexican president Luis Echeverría’s personal ambitions as a global leader as well as the burgeoning feminist movement within Mexico. The Mexican government agreed to host not only the intergovernmental conference but also a parallel NGO tribune, creating the conditions for a transformative aspect of the International Women’s Year. The last-minute relocation to Mexico City also resulted in the New York–based NGO leaders taking charge of the tribune, drawing heavily on their involvement with the 1974 UN Population Conference and the World YWCA.
Follow the Money
Authors: Olcott Jocelyn
Published: June 2017

This chapter considers the ways that the paltry funding available for IWY resulted in considerable influence by states and organizations that contributed to the UN voluntary fund for IWY activities. Due to time constraints, IWY planners established a consultative committee to plan the intergovernmental conference; Princess Ashraf Pahlavi, who had pledged $2 million to the voluntary fund, was named chair. While drafting the World Plan of Action, the consultative committee deliberated about how to prioritize issues related to women’s status, particularly between those who wanted to emphasize equality between men and women and those who sought economic development to improve standards of living across societies. Australian delegate Elizabeth Reid established a reputation for her facility in adjudicating these debates.
Inauguration Day
Authors: Olcott Jocelyn
Published: June 2017

This chapter describes the ceremony and demonstrations that accompanied the inaugurations of the intergovernmental conference and the NGO tribune. It describes some of the protocols and procedures of a UN conference and the more informal atmosphere of the tribune. The conference would hold plenary sessions but also would convene two committees, the first charged with developing the World Plan of Action and the second charged with considering the integration of women into development and the impediments to women’s equality. The elaborate rituals and carefully crafted addresses fueled participants’ expectations that serious work might be accomplished at these gatherings that would effect a substantial improvement in women’s status around the world.
Unceremonious Closing
Authors: Olcott Jocelyn
Published: June 2017

This chapter describes the final day of the IWY intergovernmental conference and NGO tribune. Ironically, the more contentious tribune concluded amicably, while the consensus-seeking conference ended in division. The conference approved two final documents rather than one. The more technocratic World Plan of Action, which had been drafted before the conference, focused on programs with measurable outcomes, such as literacy rates. The more polemical Declaration of Mexico, which drew on earlier documents but was drafted during the conference, stressed social justice issues such as colonialism and apartheid and, most controversially, became the first of several UN documents that would equate Zionism with racism.
Introduction
Authors: Mills M.G.L. , Mills M.E.J.
Published: June 2017

Most cheetah studies have been confined to mesic savannahs, yet much of its distribution range covers arid systems. The prime objective in this study was to examine the species’ adaptations to an arid region, to compare the results with those from other cheetah studies, especially from the Serengeti, and to analyse the data within the framework of carnivore population and behavioural ecology. The study was conducted in the Kgalagadi Transfrontier Park South Africa/Botswana, an area receiving 180–250 mm rainfall per year. Tracking spoor with the help of Bushmen trackers and continuous follows of 21 VHF radio-collared cheetahs were the main study methods used. These were supported by photographic records for individual identification, DNA studies for genetic aspects including paternity, and the use of doubly labelled water and the fitting of miniature data loggers for energetic studies. The statistical tests used to analyse the data are described.
The Rise
Authors: David Deirdre
Published: June 2017

Deeply troubled by social injustice, Pamela became an active member of the Labour Party, writing newsletters and marching in protests against the Spanish Civil War and Franco. In 1935 she met an Australian journalist, Gordon Neil Stewart, whom she married in 1936; her mother, Amy, lived with them after the wedding. Neil and Pamela travelled together in France just before the war (where Neil had lived for a few years after leaving Australia) and she continued to write short stories and novels. Her most memorable fiction in these years is The Monument (1938), a political novel sympathetic to the working class and passionately critical of prejudice, particularly that directed against Jews, and the first novel in her ‘Helena’ trilogy, Too Dear for My Possessing (named for one of the central characters). It is set in Bruges, a city she dearly loved.
Cities-Before-Cities
Authors: Berman Daniel W.
Published: June 2017

Foundation myths are a crucial component of many Greek cities’ identities. But the mythic tradition also represents many cities and their spaces before they were cities at all. This study examines three of these ‘prefoundational’ narratives: stories of cities-before-cities that prepare, configure, or reconfigure, in a conceptual sense, the mythic ground for foundation. ‘Prefoundational’ myths vary in both form and function. Thebes, before it was Thebes, is represented as a trackless and unfortified backwater. Croton, like many Greek cities in south Italy, credited Heracles with a kind of ‘prefounding’, accomplished on his journey from the West back to central Greece. And the Athenian acropolis was the object of a quarrel between Athena and Poseidon, the results of which gave the city its name and permanently marked its topography. In each case, ‘prefoundational’ myth plays a crucial role in representing ideology, identity, and civic topography.
Fountains as Reservoirs of Myth and Memory
Authors: Robinson Betsey A.
Published: June 2017

Case studies from Hellenistic and imperial Corinth and Ephesus demonstrate the ways in which springs and fountains were used to honour forces of nature, commemorate mythological figures and events, and strengthen, or even invent, local traditions. Famous for its natural water supply, Corinth capitalized on storied springs, both before and after its destruction and refoundation as a Roman colony. The fountains of Peirene and Glauce demonstrate different strategies for connecting past and present and establishing authority by the manipulation of architectural form and the selective retelling of stories. At Ephesus, Hellenistic and Roman fountains celebrated local nature and myth with increasingly extravagant architecture, statuary, and water displays. This chapter focuses on a series of fountains that featured the founding hero Androclus, from a monument erected in his honour to great facade fountains in which he was one of many figures communicating Ephesian identity and pride.
Institutional Investors in Global Markets
Authors: Clark Gordon L , Monk Ashby H B
Published: June 2017

This book is about what institutional investors do, how they do it, and when and where they do it: it is about the production of investment returns in the global economy. It also tackles some of the key issues found in the academic literature on the theory of the firm. It looks at ways other treatments of the modern corporation share an abiding interest in the management and organization of the production process. In this case, the focus is on the global financial services industry, where the building blocks underpinning the study of industrial corporations are less relevant. One of the publication’s goals is to explain how and why the production of investment returns differs from that of manufactured goods. Another is to provide an analytical framework that situates financial institutions within the complex web of the intermediaries that dominate developed financial markets. As such, the book is more than an analysis of the organization and management of institutional investors; it is also an analysis of the global financial services industry.
Transitive Nouns and Adjectives
Authors: Lowe John J.
Published: June 2017

This book explores the wealth of evidence from early Indo-Aryan for the existence of transitive nouns and adjectives, a rare linguistic phenomenon which, according to some categorizations of word classes, should not occur. The author shows that most transitive nouns and adjectives attested in early Indo-Aryan cannot be analysed as belonging to a type of non-finite verb category, but must be acknowledged as a distinct constructional type. The volume provides a detailed introduction to transitivity (verbal and adpositional), the categories of agent and action noun, and early Indo-Aryan. Four periods of early Indo-Aryan are selected for study: Rigvedic Sanskrit, the earliest Indo-Aryan; Vedic Prose, a slightly later form of Sanskrit; Epic Sanskrit, a form of Sanskrit close to the standardized ‘Classical’ Sanskrit; and Pali, the early Middle Indo-Aryan language of the Buddhist scriptures. The author shows that while each linguistic stage is different, there are shared features of transitive nouns and adjectives which apply throughout the history of early Indo-Aryan. The data is set in the wider historical context, from Proto-Indo-European to Modern Indo-Aryan, and a formal linguistic analysis of transitive nouns and adjectives is provided in the framework of Lexical-Functional Grammar.
Growth, Employment, and Poverty in Latin America
Authors: Cruces Guillermo , Fields Gary S. , Jaume David , Viollaz Mariana
Published: June 2017

This book examines the links between economic growth, changing employment conditions, and the reduction of poverty in Latin America in the 2000s. Its analysis answers the following broad questions: Has economic growth resulted in gains in standards of living and reductions in poverty via improved labour market conditions in Latin America in the 2000s, and have these improvements halted or been reversed since the international crisis of 2008? How do the rate and character of economic growth, changes in the various employment and earnings indicators, and changes in poverty and inequality indicators relate to each other? Our contribution is an in-depth study of the multi-pronged growth–employment–poverty nexus based on a large number of labour market indicators (twelve employment and earnings indicators and four poverty and inequality indicators) for a large number of Latin American countries (sixteen of them). The book presents a positive and hopeful set of findings for the period 2000 to 2012–13. Economic growth took place and brought about improvements in almost all labour market indicators and consequent reductions in poverty rates. But not all improvements were equal in size or caused by the same things. Some macroeconomic factors were associated with changes in labour market conditions, some of them always in the welfare-improving direction and others always in the welfare-reducing direction. Most countries in the region suffered a deterioration in at least some labour market indicators as a consequence of the international crisis of 2008, but the negative effects were reversed very quickly in most countries.
Introduction and Motivation for the Project
Authors: Cruces Guillermo , Fields Gary S. , Jaume David , Viollaz Mariana
Published: June 2017

This book examines the links between economic growth, changing employment conditions, and the reduction of poverty in Latin America in the 2000s. Its contribution is an in-depth study of the multi-pronged growth–employment–poverty nexus based on a large number of labour market indicators (twelve employment and earnings indicators and four poverty and inequality indicators) for a large number of Latin American countries (sixteen of them). It presents an exhaustive analysis of the growth–employment–poverty nexus which directly relates changes in all labour market indicators to economic growth, and changes in all employment and earnings indicators to changes in poverty. It also bases its analysis on a broader set of labour market indicators than those used in other studies.
Bolivia
Authors: Cruces Guillermo , Fields Gary S. , Jaume David , Viollaz Mariana
Published: June 2017

During the 2000s, Bolivia experienced moderate economic growth and improved all labour market indicators. The economy suffered a slowdown as a consequence of the international crisis of 2008, but Bolivia sustained positive growth rates during that episode. The unemployment rate fell between 2000 and 2012. The composition of employment by occupational groups, occupational positions, economic sectors, and educational levels improved, and the share of registered workers increased. The chapter shows that all poverty and inequality indicators decreased substantially between 2000 and 2012. The only negative impact of the international crisis of 2008 was an interruption in the declining trend of unemployment.
Brazil
Authors: Cruces Guillermo , Fields Gary S. , Jaume David , Viollaz Mariana
Published: June 2017

During the 2000s, Brazil experienced slow economic growth and a substantial improvement in labour market indicators. From 2001 to 2012, Brazil grew less than the Latin American average. However, the unemployment rate decreased, the employment composition by occupational group, economic sector, and employment position improved, the educational level of workers rose, the share of registered workers increased, and average labour earnings went up. At the same time, poverty and inequality largely diminished. The international economic crisis had a mild effect on the Brazilian economy and some labour market indicators such as the unemployment rate, but the negative effects had been reversed by 2011.
The General in Winter
Authors: Harris Frances
Published: June 2017

The book tells the story of the ‘glories of the age of Anne’: the union of England and Scotland to form Great Britain and its establishment, through the victories of the War of the Spanish Succession, as a European and a global power. This was the achievement of two men above all: Queen Anne’s Captain-General, John Churchill, 1st Duke of Marlborough, and her Lord Treasurer, Sidney, 1st Earl of Godolphin, of whom it was said that each ‘was the greatest of his kind that hardly any age has afforded’. Their partnership not only embodied the emerging military-fiscal state; it was also a close and lifelong friendship which fully encompassed Marlborough’s beautiful and tempestuous wife Sarah. Tracing the partnership as it proved itself in a succession of victorious summer campaigns in the field and bitterly contested ‘winter campaigns’ at home connects aspects of a complex period which are often studied in isolation. But was the partnership in the end too successful, too self-contained, too mutually supportive; a dangerous concentration of power in fact and a threat to the queen and the constitution? ‘Rebellion and blood’ were always undercurrents of the last Stuart reign. A troubled dynasty would end with Queen Anne’s death and a contested succession depended on the outcome of the European war that occupied almost the whole of her reign. This is a story of sovereignty and ambition, glory and defeat, but above all of love and friendship, which helped to shape the modern world.
Grip Strength in Women Being Treated for Breast Cancer and Receiving Adjuvant Endocrine Therapy: Systematic Review
Authors: Van der Weijden-Van Doornik E. M. , Slot Dagmar E. , Burtin Chris , van der Weijden G. A.
Published: June 2017

Background

Adjuvant endocrine therapy in breast cancer has increased survival rates; however, it is not without musculoskeletal side effects.

Purpose

The purpose of this review was to systematically and critically appraise the available scientific evidence concerning the effect of adjuvant endocrine treatment on grip strength in women being treated for breast cancer.

Data sources and study selection

The National Library of Medicine (MEDLINE-PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), Excerpta Medical Database by Elsevier (EMBASE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Physiotherapy Evidence Database (PEDro) were searched from inception to February 2017 for appropriate papers that could answer the focused question. The searches were independently screened by 2 reviewers. The data from 7 papers that met the eligibility criteria were processed for further analysis.

Data extraction and synthesis

The collective data and the statistical analysis of all included studies were summarized and presented in a descriptive manner. If not provided, based on data from the individual included studies, a mean percent change in grip strength was calculated. The included studies evaluating aromatase inhibitors had inconclusive outcomes, and studies with a follow-up of 6 or 12 months showed a percent reduction in grip strength varying from 0.1% to 9.7%. None of the included studies showed a significant decrease in grip strength in tamoxifen users, with a percent reduction in grip strength varying from 1.4% to 2.2%.

Limitations

The 7 studies included cohort studies lacking a control group.

Conclusions

There is inconclusive evidence for a small decrease in grip strength in women treated for breast cancer who are also receiving aromatase inhibitors. In those that use tamoxifen, grip strength did not change significantly.
Safety and efficacy of neublastin in painful lumbosacral radiculopathy: a randomized, double-blinded, placebo-controlled phase 2 trial using Bayesian adaptive design (the SPRINT trial)
Authors: Backonja Miroslav , Williams Leslie , Miao Xiaopeng , Katz Nathaniel , Chen Crystal
Published: June 2017

Neublastin (BG00010) is a first-in-class, glial cell–derived neurotrophic factor shown in preclinical studies and an early clinical trial to have potential for the treatment of neuropathic pain. SPRINT was a phase 2, multicenter, double-blinded, placebo-controlled study to evaluate efficacy/safety of 5 neublastin doses (50, 150, 400, 800, and 1200 μg/kg) administered as an intravenous injection 3 times/week for 1 week in patients with chronic painful lumbosacral radiculopathy, utilizing Bayesian response-adaptive study design. Primary endpoint was change from baseline in mean 24-hour average general pain intensity over a 5-day period (week 1) after the last dose, analyzed using a Bayesian normal dynamic linear model. One hundred seventy-six patients were randomized and received treatment (placebo n = 48, 50 μg/kg n = 38, 150 μg/kg n = 13, 400 μg/kg n = 16, 800 μg/kg n = 20, 1200 μg/kg n = 41). Among the tested neublastin doses, the lowest dose (50 μg/kg) showed the greatest difference from placebo for change from baseline in mean average general pain intensity at week 1 after last dose, followed by the highest dose (1200 μg/kg) (posterior mean difference −1.36 [95% credible interval −2.22 to −0.52] and −0.75 [−1.59 to 0.08], respectively). Similar trends were observed in secondary efficacy endpoints. The most common adverse event in all neublastin dose groups was pruritus (79% vs 10% with placebo). There was no dose–response relationship with respect to primary/secondary efficacy outcomes or incidence of pruritus, despite dose-proportional increases in serum neublastin concentrations. In conclusion, while this study showed some evidence of pain relief with neublastin, particularly at the lowest dose, there was no clear dose–response relationship for pain reduction or the most common adverse event of pruritus.
Disrupted offset analgesia distinguishes patients with chronic pain from healthy controls
Authors: Kobinata Hiroyuki , Ikeda Eri , Zhang Shuo , Li Tianjiao , Makita Koshi , Kurata Jiro
Published: June 2017

Offset analgesia (OA) represents a disproportionately large decrease of pain perception after a brief, temporary increment of thermal pain stimulus and was reported attenuated in patients with neuropathic pain. We examined whether OA depends on the increment duration before offset, and whether individual features of OA distinguish patients with chronic pain and healthy controls. We used a Peltier-type thermal stimulator and OA paradigms including 5-, 10-, or 15-s duration of 1°C-increment (T2) over 45°C. We first examined OA response, on the left volar forearm, at 3 different T2's in 40 healthy volunteers, and OA and constant stimulus responses in 12 patients with chronic pain and 12 matched healthy controls. We measured magnitude of OA (∆OA) and maximum visual analogue scale (VAS) latency (time to peak VAS) during constant stimulus for each individual. Pain perception kinetics were compared with analysis of variance and sought for correlations with psychophysical parameters with a significance threshold at P < 0.05. In healthy controls, longer T2 at 10 or 15 seconds resulted in larger ∆OA compared with T2 at 5 seconds (P = 0.04). In patients, ∆OA was significantly smaller than controls at T2 = 5 or 10 seconds (P < 0.05) but grew comparable at T2 = 15 seconds with controls. Maximum VAS latency was longer in patients than in controls and negatively correlated with ∆OA in patients. An OA index (∆OA/[maximum VAS latency]) proved diagnostic of chronic pain with an area under the receiver operating characteristic curve at 0.897. Patients with chronic pain showed impairment of OA and reduced temporal sharpening of pain perception, which might imply possible disturbance of the endogenous pain modulatory system.
Estrogens synthesized and acting within a spinal oligomer suppress spinal endomorphin 2 antinociception: ebb and flow over the rat reproductive cycle
Authors: Liu Nai-Jiang , Murugaiyan Vijaya , Storman Emiliya M. , Schnell Stephen A. , Wessendorf Martin W. , Gintzler Alan R.
Published: June 2017

The magnitude of antinociception elicited by intrathecal endomorphin 2 (EM2), an endogenous mu-opioid receptor (MOR) ligand, varies across the rat estrous cycle. We now report that phasic changes in analgesic responsiveness to spinal EM2 result from plastic interactions within a novel membrane-bound oligomer containing estrogen receptors (mERs), aromatase (aka estrogen synthase), metabotropic glutamate receptor 1 (mGluR1), and MOR. During diestrus, spinal mERs, activated by locally synthesized estrogens, act with mGluR1 to suppress spinal EM2/MOR antinociception. The emergence of robust spinal EM2 antinociception during proestrus results from the loss of mER-mGluR1 suppression, a consequence of altered interactions within the oligomer. The chemical pairing of aromatase with mERs within the oligomer containing MOR and mGluR1 allows estrogens to function as intracellular messengers whose synthesis and actions are confined to the same signaling oligomer. This form of estrogenic signaling, which we term “oligocrine,” enables discrete, highly compartmentalized estrogen/mER-mGluR1 signaling to regulate MOR-mediated antinociception induced by EM2. Finally, spinal neurons were observed not only to coexpress MOR, mERα, aromatase, and mGluR1 but also be apposed by EM2 varicosities. This suggests that modulation of spinal analgesic responsiveness to exogenous EM2 likely reflects changes in its endogenous analgesic activity. Analogous suppression of spinal EM2 antinociception in women (eg, around menses, comparable with diestrus in rats) as well as the (pathological) inability to transition out of that suppressed state at other menstrual cycle stages could underlie, at least in part, the much greater prevalence and severity of chronic pain in women than men.
The Use of a Stylet in Endoscopic Ultrasound With Fine-Needle Aspiration
Authors: Lai Andrew , Davis-Yadley Ashley , Lipka Seth , Lalama Miguel , Rabbanifard Roshanak , Bromberg David , Nehaul Roger , Kumar Ambuj , Kulkarni Prasad
Published: June 2017

Background:

Endoscopic ultrasound with fine-needle aspiration (EUS-FNA) is the most efficacious way to collect specimens from a solid lesion adjacent to the gastrointestinal tract and is performed with an internal stylet during puncture. However, its reinsertion into the needle is time-consuming. Controversy surrounds whether quality of cytology specimen improves with stylet use. We performed a meta-analysis comparing the use of stylet versus no stylet with EUS-FNA of gastrointestinal–related masses.

Methods:

Multiple databases were searched from inception until April 28, 2016. Discordant findings from independent extractions were reviewed by at least 2 investigators. Methods were executed as per the standards of the Cochrane Collaboration. Primary outcomes assessed were diagnostic adequacy of individual specimen samples, accuracy, and yield. Secondary outcomes included overall diagnostic accuracy of per-malignant lesion, cellularity, contamination, and bloodiness of the sample, and adverse events.

Results:

Five randomized control trials were identified comparing stylet versus no stylet use, which enrolled 504 patients, evaluated 537 lesions, and 1914 distinct specimens. There was no difference in diagnostic adequacy [risk ratio (RR)=1.00; 95% confidence interval (CI), 0.95-1.07], accuracy (RR=0.98; 95% CI, 0.90-1.06), or yield (RR=0.96; 95% CI, 0.89-1.03). No stylet use was favored in per-lesion malignant diagnosis (RR=0.85; 95% CI, 0.76-0.96). There was no difference in representative cellularity, contamination, or bloodiness of specimens obtained with or without stylet use.

Conclusions:

Stylet use confers no significant advantage in diagnostic adequacy, accuracy, yield, contamination, bloodiness, or cellularity over no stylet. We reinforce that no stylet use may be used preferentially in EUS-FNA as a more convenient technique and is favored with a higher per-lesion malignant diagnosis.
Prone or Left for Colonoscopy? A Randomized Controlled Trial of Prone Versus Left-sided Starting Position for Colonoscopy
Authors: Vergis Nikhil , Scarborough Alexander J. , Morris James A. , Hoare Jonathan M.
Published: June 2017

Background and Aims:

Data have emerged supporting the right-lateral starting position in reducing time to cecum and improving patient comfort for minimally sedated colonoscopy. We aimed to test whether prone starting position results in similar advantages in procedure time and patient tolerability in comparison to traditional left-sided starting position.

Materials and Methods:

We conducted a randomized controlled trial in which patients were randomized to begin in either the prone or left-lateral (LL) position. A total of 181 adult patients undergoing scheduled colonoscopy were stratified by age, gender, body mass index, and experience of the endoscopist. Patients were then randomized 1:1 in permuted blocks. The primary outcome measure was time to cecal intubation and secondary outcome measures included patient comfort that was measured by visual analog scale.

Results:

There was no benefit from prone starting positioning over conventional left-sided starting positioning. Further, prone starting position led to an increase in time to reach cecum (701 vs. 511 s; P=0.01). This could be in part explained by an increased time to reach transverse colon in patients positioned prone (332 vs. 258 s; P=0.06). Comfort levels were similar between patients positioned prone and LL (4 vs. 4 visual analog scale; P=0.6) although endoscopists found colonoscopies in which patients started prone more technically challenging than if started LL (5 vs. 4; P=0.002).

Conclusions:

Prone starting position did not improve time to reach cecum or patient comfort for minimally sedated patients undergoing colonoscopy. The ClinicalTrials.gov identifier is NCT02305706.
The prevalence of irritable bowel syndrome-type symptoms in inflammatory bowel disease patients in remission
Authors: Hoekman Daniël R. , Zeevenhooven Judith , D’Haens Geert R. , Benninga Marc A.
Published: June 2017

Objective

Symptoms of irritable bowel syndrome (IBS) are common in inflammatory bowel disease (IBD) and are believed to reflect ongoing inflammation. Consequently, a low prevalence of IBS-type symptoms in IBD patients with normal inflammatory markers is expected. We aimed to investigate the prevalence of IBS-type symptoms in IBD patients in biochemical remission (evidenced by low fecal calprotectin levels) and the relationship of these symptoms with fecal calprotectin levels.

Patients and methods

In this observational, cross-sectional study, we included all adults with a history of IBD who had calprotectin levels less than 200 µg/g during routine follow-up between August 2014 and May 2015 at our hospital. Patients were excluded if calprotectin was measured because of gastrointestinal complaints. All patients were approached by telephone to evaluate the presence of IBS-type symptoms using Rome III questionnaires. Patients fulfilling IBS criteria were subclassified according to bowel habits.

Results

In total, 74 patients were included; 33 (45%, 95% confidence interval: 34–56%) fulfilled the IBS criteria. A larger proportion of Crohn’s disease patients with IBS-type symptoms had ileal disease compared with Crohn’s disease patients without IBS symptoms (55 vs. 24%; P=0.03). Other characteristics were similar between groups. No difference was found in calprotectin levels between patients with and without IBS-type symptoms (P=0.91). The majority of patients with IBS-type symptoms had diarrhea-predominant or mixed-type IBS (64 and 27% of patients with IBS-type symptoms, respectively).

Conclusion

The prevalence of IBS-type symptoms in IBD patients in biochemical remission is high. A significant proportion of IBS-type symptoms is unrelated to ongoing inflammation and probably reflects ‘true IBS’.
Hyperuricemia is associated with nonalcoholic fatty liver disease activity score in patients with nonalcoholic fatty liver disease: a systematic review and meta-analysis
Authors: Jaruvongvanich Veeravich , Ahuja Wasin , Wirunsawanya Kamonkiat , Wijarnpreecha Karn , Ungprasert Patompong
Published: June 2017

Background

Hyperuricemia is a significant risk factor for nonalcoholic fatty liver disease (NAFLD). It may also have an impact on the histologic severity of NAFLD. However, data on this association are limited. We conducted this meta-analysis to investigate the relationship of serum uric acid with liver histologic severity as determined by NAFLD activity score (NAS) in patients with NAFLD.

Patients and methods

MEDLINE and EMBASE databases were searched through August 2016 for studies that investigated the association between hyperuricemia and NAS among patients with biopsy-proven NAFLD. Pooled odds ratio and 95% confidence interval were calculated using a random-effects model (generic inverse variance method). The between-study heterogeneity of effect size was quantified using the Q statistic and I
2.

Results

Five observational studies with 777 NAFLD patients were identified. Patients with NAFLD who had hyperuricemia had a high NAS (defined as score of ≥5) significantly more often than did those without hyperuricemia with a pooled odds ratio of 2.17 (95% confidence interval: 1.51–3.12). The statistical heterogeneity was low, with I
2 of 16% (P
heterogeneity=0.31).

Conclusion

In patients with NAFLD, hyperuricemia is associated with a higher degree of histological liver damage. Further studies are required to establish the role of uric acid-lowering therapy among these patients.
The Associations of Height-for-Age, Weight-for-Age, and Weight-for-Height With Pediatric Acute Lymphoblastic Leukemia
Authors: Schraw Jeremy M. , Henson Ann T. , Scheurer Michael E. , Forman Michele R.
Published: June 2017

Height at diagnosis has been analyzed in connection with acute lymphoblastic leukemia (ALL). Most prior studies have compared cases to national reference data derived from previous birth cohorts. Our objective was to determine the association of height-for-ageZscore (HAZ) at time of diagnosis with the odds ratio (OR) of ALL in a case-control study (N=498) with a contemporaneous population of age-matched, sex-matched, and ethnicity-matched controls. We hypothesized that cases would have greater mean HAZ at time of diagnosis/interview, after adjustment for weight-for-age (WAZ) and weight-for-height (WHZ). HAZ was not associated with ALL. For each 1 SD increase in WAZ the OR of ALL was 0.83 (95% confidence interval [CI], 0.68-0.99). The OR of ALL was increased among children who had either a WAZ ≤−2 (OR, 5.10; 95% CI, 1.85-16.75) or WHZ of ≤−2 (OR, 5.27; 95% CI, 1.65-23.61). Previous findings of taller height among ALL cases may arise from the choice of control populations. Children with low WAZ or WHZ were at increased odds of ALL.
Risk Factors, Etiological Classification, Topographical Location, and Outcome in Medullary Infarctions
Authors: Gökçal Elif , Baran Gözde , Niftaliyev Elvin , Güzel Vildan , Asil Talip
Published: June 2017

An understanding of the etiological mechanisms is important for therapeutic decisions and prognostic evaluation of patients with ischemic stroke. The object of this study was to evaluate the risk factors, etiological subtypes, and topography of lesion in patients with medullary infarctions (MIs). Besides, we also investigated early neurological deterioration, new vascular events, and functional outcome of all patients at 3-month follow-up. We analyzed our database consisting of patients who were diagnosed with acute MI and who were admitted within 24 hours of onset. Etiological classification of stroke was made on the basis of the Trial of Org 1972 in Acute Stroke Treatment criteria. All of the infarctions were grouped into anteromedial, anterolateral, lateral, and posterior arterial territories and also categorized into those involving the upper, middle, or lower medulla oblongata. Early neurological deterioration, major vascular events within the first 3 months of follow-up and modified Rankin Score at 3 months were reviewed. A total of 65 patients with medullary infarctions were reviewed. Involved arterial territories differed according to the etiological classification. Large artery atherosclerosis was the most common etiological subtype; however, small vessel disease was the most common subtype in medial MIs. The lesions involving the anteromedial territory were common in the upper medullary region, whereas the lesions involving the posterior and lateral territories were common in the lower medulla oblangata. Recurrent stroke was seen in the posterior and lateral territories; however, early progression and poor functional outcome were mostly seen in lesions involving the anteromedial territories.
A conserved homo-dimerization interface in human IFIT1 provides insights into IFIT interactome assembly
Authors: Abbas Yazan M. , Martínez-Montero Saúl , Cencic Regina , Pelletier Jerry , Pawelek Peter D. , Damha Masad J. , Nagar Bhushan
Published: June 2017

The Interferon-Induced Proteins with Tetratricopeptide Repeats (IFITs) are a group of potently expressed Interferon Stimulated Genes that mediate antiviral innate immunity. Previous studies have revealed that most IFITs partake in higher order structures, potentially as part of an ‘IFIT interactome’ that results in viral inhibition. Recent crystal structures of a mutated, monomeric form of IFIT1 revealed the molecular basis of how it recognizes non-self, capped viral mRNAs to selectively inhibit their translation. However, wild-type IFIT1 forms dimers in solution and the role of dimerization was not examined in detail. Here we present a structural and biochemical analysis of wild-type IFIT1 in complex with capped and uncapped RNA. Wild-type IFIT1 forms an antiparallel, elongated dimer that is in stark contrast to the domain-swapped, parallel dimer found in IFIT2. Dimerization takes place through a small, C-terminal interface that is evolutionarily conserved in IFIT1 and IFIT1B proteins. The interface is modular and can be grafted onto IFIT5, which is natively monomeric, to induce dimerization. Mutational analysis of this interface showed that homo-dimerization is not required for full RNA binding or translational inhibition by IFIT1. Sedimentation velocity analytical ultracentrifugation measurements demonstrated a reversible monomer-dimer equilibrium, suggesting that dimerization is of low affinity and could play a role under physiological concentrations, possibly in regulating IFIT interactome assembly. Finally, conformational changes in IFIT1 that occur upon RNA binding provide insight into how RNA enters its binding site in solution.
Doubling healthy lifespan using drug synergy
Authors: Dessale Tesfahun , Batchu Krishna Chaithanya , Barardo Diogo , Fang Ng Li , Man Lam Vanessa Yuk , Xiao Linfan , Wenk Markus R. , Tolwinski Nicholas S. , Gruber Jan
Published: June 2017

Pharmacological interventions that target human ageing would extend individual healthspan and result in dramatic economic benefits to rapidly ageing societies worldwide. For such interventions to be contemplated they need to comprise drugs that are efficacious when given to adults and for which extensive human safety data are available. Here we show that dramatic lifespan extension can be achieved inC.elegansby targeting multiple, evolutionarily conserved ageing pathways using drugs that are already in human use. By targeting multiple synergistic ageing pathways, we are able to slow ageing rate, double lifespan and improves healthspan while minimize developmental and fitness trade-offs. Moreover, we established that there is no synergistic benefit in adaf-2ordaf-7background, implying the involvement of the TGFβ and IGF pathways in this synergy. Employing lipidomics and transcriptomics analysis we found lipid metabolism to be affected resulting in increased monounsaturated fatty acids (MUFA) and decrease membrane peroxidation index. Our best drug combination showed a conserved lifespan extension in fruit flies. To the best of our knowledge, this is the largest lifespan effect ever reported for any adult-onset drug treatment inC. elegans. This drug-repurposing approach, using drugs already approved for humans to target multiple conserved aging pathways simultaneously, could lead to interventions that prevent age-related diseases and overall frailty in a rapidly ageing population.
Low dimensional morphospace of topological motifs in human fMRI brain networks
Authors: Morgan Sarah E. , Achard Sophie , Termenon Maite , Vértes Petra E. , Bullmore Edward T.
Published: June 2017

We present a low-dimensional morphospace of fMRI brain networks, where axes are defined in a data-driven manner based on the network motifs. The morphospace allows us to identify the key variations in healthy fMRI networks in terms of their underlying motifs and we observe that two principal components (PCs) can account for 97% of the motif variability. The first PC corresponds to the small-world axis and correlates strongly with the networks’ global efficiency. There is also some evidence that PC1 correlates with the average length of the 5% of longest edges in the network. Hence this axis represents the trade-off between the cost of long distance edges and their topological benefits. The second PC correlates with the networks’ assortativity. Finally, we show that the economical clustering generative model proposed by Vértes et al. can approximately reproduce the motif PC space of the real fMRI brain networks, in contrast to other generative models. Overall, the motif morphospace provides a powerful way to visualise the relationships between network properties and to study the driving forces behind the topology of fMRI brain networks.
LPP3 mediates self-generation of chemotactic LPA gradients by melanoma cells
Authors: Susanto Olivia , Koh Yvette W.H. , Morrice Nick , Tumanov Sergey , Thomason Peter A. , Nielson Matthew , Tweedy Luke , Muinonen-Martin Andrew J. , Kamphorst Jurre J. , Mackay Gillian M. , Insall Robert H.
Published: June 2017

Melanoma cells steer out of tumours using self-generated lysophosphatidic acid (LPA) gradients. The cells break down LPA, which is present at high levels around the tumours, creating a dynamic gradient that is low in the tumour and high outside. They then also migrate up this gradient, creating a complex and evolving outward chemotactic stimulus. Here we introduce a new assay for self-generated chemotaxis, and show that raising LPA levels causes a delay in migration rather than loss of chemotactic efficiency. Knockdown of the lipid phosphatase LPP3 - but not its homologues LPP1 or LPP2 - diminishes the cell’s ability to break down LPA. This is specific for chemotactically active LPAs, such as the 18:1 and 20:4 species. Inhibition of autotaxin-mediated LPA production does not diminish outward chemotaxis, but loss of LPP3-mediated LPA breakdown blocks it. Similarly, in both 2D and 3D invasion assays, knockdown of LPP3 diminishes melanoma cells’ ability to invade. Our results demonstrate that LPP3 is the key enzyme in melanoma cells’ breakdown of LPA, and confirm the importance of attractant breakdown in LPAmediated cell steering.