bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of Chronic Cough: Single‐Institution Experience Utilizing Behavioral Therapy
Authors: Soni Resha S. , Ebersole Barbara , Jamal Nausheen
Published: October 2016

Objective

Chronic cough remains a challenging condition, especially in cases where it persists despite comprehensive medical management. For these particular patients, there appears to be an emerging role for behavior modification therapy. We report a series of patients with refractory chronic cough to assess if there is any benefit of adding behavioral therapy to their treatment regimen.

Study Design

A case series with planned chart review of patients treated for chronic cough.

Setting

The review was performed with an outpatient electronic health record system at a tertiary care center.

Subjects and Methods

The charts of all patients treated for chronic cough by a single laryngologist over a 30‐month period were analyzed. Patients’ response to treatment and rate of cough improvement were assessed for those with refractory chronic cough who underwent behavior modification therapy.

Results

Thirty‐eight patients with chronic cough were initially treated empirically for the most common causes of cough, of which 32% experienced improvement. Nineteen patients who did not significantly improve with medical management underwent behavior modification therapy with a speech‐language pathologist. Of these patients, 84% experienced resolution or marked improvement of their symptoms.

Conclusion

Behavioral therapy may be underutilized in practice and could lead to improvement of otherwise recalcitrant cough.
Statistics for Sleep and Biological Rhythms Research
Authors: Bianchi Matt T. , Phillips Andrew J. K. , Wang Wei , Klerman Elizabeth B.
Published: October 2016

The Journal of Biological Rhythms will be publishing articles exploring analysis and statistical topics relevant to researchers in biological rhythms and sleep research. The goal is to provide an overview of the most common issues that arise in the analysis and interpretation of data in these fields. By using case examples and highlighting the pearls and pitfalls of statistical inference, the authors will identify and explain ways in which experimental scientists can avoid common analytical and statistical mistakes and use appropriate analytical and statistical methods in their research. In this first article, we address the first steps in analysis of data: understanding the underlying statistical distribution of the data and establishing associative versus causal relationships. These ideas are then applied to sample size, power calculations, correlation testing, differences between description and prediction, and the narrative fallacy.
Cerebral Blood Flow Autoregulation in Sepsis for the Intensivist: Why Its Monitoring May Be the Future of Individualized Care
Authors: Goodson Carrie M. , Rosenblatt Kathryn , Rivera-Lara Lucia , Nyquist Paul , Hogue Charles W.
Published: October 2016

Cerebral blood flow (CBF) autoregulation maintains consistent blood flow across a range of blood pressures (BPs). Sepsis is a common cause of systemic hypotension and cerebral dysfunction. Guidelines for BP management in sepsis are based on historical concepts of CBF autoregulation that have now evolved with the availability of more precise technology for its measurement. In this article, we provide a narrative review of methods of monitoring CBF autoregulation, the cerebral effects of sepsis, and the current knowledge of CBF autoregulation in sepsis. Current guidelines for BP management in sepsis are based on a goal of maintaining mean arterial pressure (MAP) above the lower limit of CBF autoregulation. Bedside tools are now available to monitor CBF autoregulation continuously. These data reveal that individual BP goals determined from CBF autoregulation monitoring are more variable than previously expected. In patients undergoing cardiac surgery with cardiopulmonary bypass, for example, the lower limit of autoregulation varied between a MAP of 40 to 90 mm Hg. Studies of CBF autoregulation in sepsis suggest patients frequently manifest impaired CBF autoregulation, possibly a result of BP below the lower limit of autoregulation, particularly in early sepsis or with sepsis-associated encephalopathy. This suggests that the present consensus guidelines for BP management in sepsis may expose some patients to both cerebral hypoperfusion and cerebral hyperperfusion, potentially resulting in damage to brain parenchyma. The future use of novel techniques to study and clinically monitor CBF autoregulation could provide insight into the cerebral pathophysiology of sepsis and offer more precise treatments that may improve functional and cognitive outcomes for survivors of sepsis.
Sources of Help for Dating Violence Victims: A Qualitative Inquiry Into the Perceptions of African American Teens
Authors: Madkour Aubrey Spriggs , Swiatlo Alison , Talan Allison , LeSar Kendra , Broussard Marsha , Kendall Carl , Seal David
Published: October 2016

Although teen dating violence victims’ reticence in seeking help from adults is well documented, little is known about youths’ comparative perceptions of the types of help offered by and effectiveness of various sources. This qualitative study solicited teens’ perceptions of sources of help for victims using in-depth interviews with African American youth (ages 13-18) in two public high schools in New Orleans ( N = 38). Participants were recruited purposively by researchers during lunchtime and via referral by school personnel. Interviews were transcribed verbatim and coded independently by two study team members. Thematic content analyses were conducted. Teens reported that victims were most likely to seek help from friends, who were largely expected to provide advice and comfort. Nearly half reported that teens would be likely to seek help from family, who would provide more active responses to dating violence (i.e., reporting to authorities, confronting the abuser). Fewer respondents believed teens would seek help from other adults, such as school personnel, who were also perceived as likely to enlist outside authorities. Fears about lack of confidentiality and over-reaction were the main perceived barriers to accessing help from adults. Furthermore, although respondents believed teens would be less likely to seek help from adults, adults were perceived as more effective at stopping abuse compared with peers. Interventions that train peer helpers, explain confidentiality to teens, increase school personnel’s ability to provide confidential counseling, and promote use of health services may improve access to help for teen dating violence victims.
An analysis of the tooth stress distribution of forged bi-metallic gears
Authors: Politis Denis J , Politis Nicholas J , Lin Jianguo , Dean Trevor A , Balint Daniel S
Published: October 2016

The work described in this paper is an evaluation of the contact characteristics of bi-metallic gears forged through a novel bi-metallic gear forging process. Finite element analysis of the contact characteristics of single material gears was first performed to validate the tooth contact and tooth root stresses with empirical American Gear Manufacturers Association and British Standard standards. Having verified the validity of the model, simulations were performed for gears comprising lightweight cores with teeth bounded by steel bands of uniform thicknesses, 1 mm, 2 mm, 4 mm, and 6 mm to evaluate the differences in stress distribution and compare to single material gear teeth. The forged profiles obtained experimentally by utilising 2 mm, 4 mm, and 6 mm thickness bands via the bi-metallic gear forging process are also discussed. The uniform thickness model is subsequently adapted to incorporate the experimental forged profiles in order to estimate the contact stress, root stress, and stress distribution within the teeth to identify performance differences between bi-metallic forged gears and traditional single material gears.
Experimental analysis of shock stand-off distance over spherical bodies in high-enthalpy flows
Authors: Thakur Ruchi , Jagadeesh G
Published: October 2016

The shock stand-off distance for basic spherical models was investigated in the flow regime of 1–2 km/s, a range for which data are unavailable in the open literature. Experiments were conducted on two hypersonic shock tunnels, at five different enthalpy conditions and two types of test gas, and the bow shock was captured using schlieren flow visualization technique. These results were compared with existing empirical relations and a good match was observed. To further corroborate the results, a computational analysis of the same problem was carried out using an in-house computational fluid dynamics code, HiFUN (High Resolution Flow Solver on UNstructured meshes), and the results were again seen to match well with the experiments. The shock stand-off distance is an important parameter for the design of high-speed airplanes, and therefore a solid quantitative understanding of this parameter is vital for all flow regimes. This paper aims to fill in the gap by investigating one of those regimes where available data are currently missing.
The Effects of Stress and Human Capital Perspective on Compulsive Buying: A Life Course Study in India
Authors: Singh Rashmi , Nayak J.K.
Published: October 2016

Compulsivity is a topic of interest among researchers, academicians and policy makers, particularly because previous studies reveal that it can influence consumer behaviour and well-being. However, researchers have not got clear-cut picture of this phenomenon. Here, authors have used an individuals’ life course paradigm as an integrative framework and derives hypothesis from two theoretical perspective (stress and human capital perspective), and uses a survey of adolescents (15–18) years in India to test the hypotheses. This article endeavours to contribute to the knowledge by suggesting that these two theoretical perspectives can provide an integrative, multi-theoretical structure by which these important phenomena might be better explained and predicted. The results indicate that one’s experience and events in earlier adolescence period are related to their compulsive buying behaviour in late adolescence period. Here, authors have developed a framework to elucidate them, and have discussed implications and future research.
Underweight and Pregnant: Designing Universal Maternity Entitlements to Improve Health
Authors: Coffey Diane , Hathi Payal
Published: October 2016

Poor maternal nutrition in India is a major cause for concern. The depth of India’s maternal nutrition problems is evident in its high neonatal mortality, widespread underweight pre-pregnancy, low weight gain during pregnancy and high rates of maternal anaemia. Poor maternal nutrition has negative consequences for the health and economic productivity for the next generation. Existing government programmes are insufficient to address widespread maternal malnutrition. With the passage of the National Food Security Act, which legislates a universal maternity entitlement, the government has a new opportunity to address poor maternal nutrition. This article posits that maternity entitlements should be used to encourage weight gain during pregnancy, and discusses the promise of such a programme as well as its potential limitations. It also recommends ways of designing and administering a maternity entitlements programme that would improve its chances for success.
Funding Australian economics research: Local benefits?
Authors: Doraisami Anita , Millmow Alex
Published: October 2016

In Australia there is a systematic ranking of academic research performance, with a major impact metric being based on publications in prestigious journals. Other countries like Britain with its Research Excellence Framework also have similar metrics. While much analysis and publicity is devoted to the rankings of the quality of research, there has been very little focus on how this ranked research has then gone on to make a public policy impact. In the case of the economics discipline, there has been little exploration of the relationship between publication in a high-ranked journal and contribution to an analysis of Australia’s most pressing economic issues. This article investigates the extent to which articles in the Diamond list of journals from 2001 to 2010 addressed Australian economic issues. Our results indicate that articles on current policy issues accounted for a very modest fraction of total Diamond list journal articles. One possible explanation for this finding, which is investigated further, is the correlation between an economics department’s Excellence in Research Australia ranking and the number of staff who obtained their doctorates from an overseas university. Such a correlation has implications for the status afforded to economics research with a specific national focus.
Sleeping Around, With, and Through Time
Authors: Ellis Carolyn
Published: October 2016

This article includes autoethnographic vignettes that explore the emotional, embodied, relational, communal, and ritualized aspects of sleeping. As a Western, White, upper-middle-class professional woman in a long-term relationship with a partner who has similar characteristics, I describe sleeping in the familiar environment of our primary and vacation homes, where we both define ourselves as sleeping well together. To tease out important aspects of what counts as a good night’s sleep, I contrast sleeping at home to sleeping in other places, such as in an airplane, hotel in a foreign country, and a hospital, and then compare my experience of sleeping in a modern Western environment with sleeping practices in preindustrial society. I examine my definition of “a good night’s sleep” and how it is affected by historical and cultural narratives of normative sleep. Questioning my original conceptions of good sleeping and sleeping ritual, I explore and put into practice alternative storylines regarding how to accomplish a good night’s slumber.
Missing the Savoir for the Connaissance
Authors: Dunkerly-Bean Judith , Bean Thomas William
Published: October 2016

This conceptual review addresses the bifurcation of content area and disciplinary literacy by examining each as regimes of truth. We look specifically at the ways in which both approaches comprise, in Foucault’s terms, “regimes of truth” within their respective epistemological domains. Following a brief history of adolescent literacy, extant research is considered. By employing a theoretical framework based on Foucault’s notions of “ connaissance” referring to a particular corpus of knowledge, and “ savoir” or knowledge in general, research and discourse surrounding the current debate over content area literacy and disciplinary literacy are taken up to deconstruct stances within these domains with the aim of a reconstruction that captures the affordances of both. Suggestions for moving the field out of this binary through a collaborative focus on interdisciplinary approaches are discussed.
Compositional Models and Organizational Research
Authors: Campbell Joanna Tochman , Weese Maria L.
Published: October 2016

An emergent stream of research in management employs configurational and holistic approaches to understanding macro and micro phenomena. In this study, we introduce mixture models—a related class of models—to organizational research and show how they can be applied to nonexperimental data. Specifically, we reexamine the long-standing research question concerning the CEO pay–firm performance relationship using a novel empirical approach, treating individual pay elements as components of a mixture, and demonstrate its utility for other research questions involving mixtures or proportions. Through this, we provide a step-by-step guide for other researchers interested in compositional modeling. Our results highlight that a more nuanced approach to understanding the influence of executive compensation on firm performance brings new insights to this research stream, showcasing the potential of compositional models for other literatures.
Improved treatment satisfaction after switching therapy to rituximab in relapsing–remitting MS
Authors: de Flon Pierre , Laurell Katarina , Söderström Lars , Gunnarsson Martin , Svenningsson Anders
Published: October 2016

Objective:

New disease-modifying treatment strategies in multiple sclerosis offer possibilities for individualised treatment. In this study, we evaluated patient-reported outcome measures before and after a switch in therapy from first-line injectable treatments to rituximab.

Method:

A total of 75 patients with clinically stable relapsing–remitting multiple sclerosis (RRMS) receiving ongoing first-line injectable treatment at three Swedish centres had their treatment switched to rituximab in this open-label phase II multicentre study. Assessment of treatment satisfaction, patient-perceived impact of the disease on daily life, fatigue, cognitive symptoms and disease progression was performed 3 months before and at the time of the treatment shift and then for a subsequent 2-year period.

Results:

The overall treatment satisfaction rating improved significantly from a mean of 4.8 (scale range: 1–7), while on injectable therapies, to a mean of 6.3 after 1 year of rituximab treatment ( p < 0.001). This improvement was sustained after 2 years. There was no significant change in scores for patient-perceived impact of disease, fatigue or disease progression.

Conclusion:

A shift in therapy from first-line injectables to rituximab in a cohort of clinically stable RRMS patients was followed by improved treatment satisfaction. This is clinically relevant as it may influence long-term adherence to immunomodulating therapy.
The ogbanje who wanted to stay: The occult, belonging, family and therapy in Sierra Leone
Authors: Schneider Luisa T
Published: October 2016

Although prominent in literature on West Africa and especially Nigeria, the phenomenon of ogbanjes in Sierra Leone is little discussed. By following the story of one ogbanje, this paper unravels their significance for social life, for local epistemologies and cosmologies in Freetown. The paper discusses personhood and morality, conceptions of femininity and motherhood as well as the search for culprits. It argues that ogbanjes have to be understood as avengers who, in the name of society, penalize those deeds of women which meet with the disapproval of the community. Ogbanjes embody a breakdown of accepted social concepts as they are able to openly articulate criticism towards their parents and elders and thus serve as a way to negotiate the coming of age. The negotiations over appropriate treatment of ogbanjes highlight the interplay between different forms of belief. In addition, ogbanjes provide coping mechanisms and explanatory tools for untimely deaths.
Individuals with Alzheimer’s learn to play a tile placement game: Results of a pilot study: Innovative practice
Authors: Miltiades Helen B , Thatcher W Gregory
Published: October 2016

With the ongoing need to determine effective memory interventions for persons with dementia and other memory impairments, the purpose of this study was to create a unique learning opportunity, where persons with early to moderate Alzheimer’s engaged in game play activity. Six female participants, diagnosed with early to moderate dementia, were recruited from an adult day care center and participated in a 10-week study. The participants were placed in groups of three and were taught a tile placement game. Results indicate playing the game yielded inconsistent, but some significant, increases and eventual plateauing of knowing when it was their turn. The results also indicate the participant’s maintained improvement in tile placement over the study period. Tile placement accuracy increased over rounds, which points to the importance of practice to maintain learned behavior. The game provided a platform for learning, social engagement, and occupied their time meaningfully.
A field study of fluorescent and LED classroom lighting
Authors: Gentile N , Goven T , Laike T , Sjoberg K
Published: October 2016

Indoor lighting is facing a massive retrofit to LED lighting. Research is needed to assess whether LED-based lighting can promote energy efficiency, boost visual comfort and support biological functions. This field study considered the lighting of four identical classrooms in an upper secondary school in Helsingborg, Sweden. Two classrooms were fitted with state-of-the-art ceiling pendants containing T5 fluorescent tubes and that had a direct/indirect light distribution (the control rooms). The other two classrooms were fitted with an experimental LED indirect lighting system (the experimental rooms). In the classrooms, 72 students aged 17–18 years performed their usual educational activities over a whole academic year. The light environment, electricity consumption, and students’ mood, light perception and saliva cortisol concentration were monitored. The two lighting systems produced only marginal differences. Overall, the experimental rooms were slightly preferred but achieved only small energy savings due to high parasitic losses.
Flow characteristics of external gear pumps considering trapped volume
Authors: Hao Xiaoru , Zhou Xiaojun , Liu Xiaoguang , Sang Xiaohu
Published: October 2016

This article investigates the volume change law of trapped fluid in the meshing process and the flow characteristics of external gear pumps under the following two cases: the pump design with and without relief groove. In this study, a mathematical modeling of gear pairs is deduced based on the meshing theory and a complete set of mathematical equations of tooth profile, and the flow rate equation is derived based on law of conservation of mass across the changing boundaries of a control volume. During the process, the function of the pump displacement is established, which is formed by two parts: tooth space volume and trapped volume. In addition, using a control volume approach, the trapped volume and flow rate characteristics of the pump under different design parameters of gears are discussed. The results show that the curve of trapped volume is similar to a parabola and the pump designed with a large number of teeth, module, and pressure angle easily obtained good flow rate characteristics under the same condition, which have a great benefit for designing the relief grooves and external gear pumps.
Processing control of the forging integration based on force compliance
Authors: Li Geqiang , Zhang Jingwei , Wang Shuai , Guo Bingjing
Published: October 2016

The method of force compliance was proposed during process of the manipulator cooperating with the movement of the forging press, which could avoid the destructive effect generated by the deformation resistance of the workpiece for the key parts. Taking the 20T forging manipulator as the target, the inverse kinematics model and the dynamic model of the major-motion mechanism were established. Through taking the pressure as the controlled variable, the dynamic model of the hydraulic lifting system was built. Based on the buffering principle, the mathematics model of the horizontal buffering system was deduced. Taking the deformation model of workpiece as the input, the variations of the displacements and forces for hydraulic cylinders were obtained by the simulation. Finally, the effectiveness of active pressure compliance method of the lifting control system using the classical proportional–integral–derivative control strategy and that of the passive compliance method for the buffering system were verified.
Chrome nitride coating reduces wear of small, spherical CrCoMo metal-on-metal articulations in a joint simulator
Authors: Thorkildsen R. , Reigstad O. , Røkkum M.
Published: October 2016

Metal-on-metal articulations have fallen out of favour in larger joint replacements, but are still used in smaller joints. Coating the articulation has been suggested as one way of reducing wear. We compared a standard 6 mm CrCoMo articulation designed for the carpometacarpal joint of the thumb with a chromium nitride-coated version after 512,000 cycles in a joint simulator. A total of 6 articulations in each group were tested with a unidirectional load of 5 kg in Ringer’s solution. We found a statistically significant reduction in weight loss, amount of metallic wear produced and volumetric wear for the chromium nitride-coated articulation. Our findings support the use of chromium nitride coating in order to minimize the amount of metallic wear produced.
Targeting histone methylation for colorectal cancer
Authors: Huang Tao , Lin Chengyuan , Zhong Linda L. D. , Zhao Ling , Zhang Ge , Lu Aiping , Wu Jiang , Bian Zhaoxiang
Published: October 2016

As a leading cause of cancer deaths worldwide, colorectal cancer (CRC) results from accumulation of both genetic and epigenetic alterations. Disruption of epigenetic regulation in CRC, particularly aberrant histone methylation mediated by histone methyltransferases (HMTs) and demethylases (HDMs), have drawn increasing interest in recent years. In this paper, we aim to review the roles of histone methylation and associated enzymes in the pathogenesis of CRC, and the development of small-molecule modulators to regulate histone methylation for treating CRC. Multiple levels of evidence suggest that aberrant histone methylations play important roles in CRC. More than 20 histone-methylation enzymes are found to be clinically relevant to CRC, including 17 oncoproteins and 8 tumor suppressors. Inhibitors of EZH2 and DOT1L have demonstrated promising therapeutic effects in preclinical CRC treatment. Potent and selective chemical probes of histone-methylation enzymes are required for validation of their functional roles in carcinogenesis and clinical translations as CRC therapies. With EZH2 inhibitor EPZ-6438 entering into phase I/II trials for advanced solid tumors, histone methylation is emerging as a promising target for CRC.
Everolimus in the management of metastatic neuroendocrine tumours
Authors: Chan David L. , Segelov Eva , Singh Simron
Published: October 2016

Neuroendocrine tumours are increasing in incidence and cause a variety of symptoms. The mammalian target of rapamycin (mTOR) pathway plays a key role in neuroendocrine tumour (NET) pathogenesis, leading to increased lipid synthesis, protein synthesis and cellular growth. Upregulation of this pathway is noted in both hereditary and sporadic NETs. This understanding has led to investigations of mTOR inhibitors as therapy for metastatic NETs. After promising preclinical findings, everolimus, an mTOR inhibitor, was trialled in the RADIANT-1−4 studies on patients with advanced, well differentiated NETs. RADIANT-3 and RADIANT-4 established the efficacy of everolimus in improving progression-free survival (PFS) for metastatic NET of pancreatic, lung and gastrointestinal origin, leading to the US Food and Drug Administration (FDA) approval for its use in tumour control in those settings. Everolimus treatment is generally well tolerated; common adverse events include stomatitis, diarrhoea, rash and hyperglycaemia. Although discontinuation rates are low, many patients may require dose modification to successfully continue therapy. The combination of everolimus with somatostatin analogues (SSAs) (such as octreotide or pasireotide) or other targeted agents such as bevacizumab has not produced additional incremental benefit, and dual biologic therapy is not used widely. Ongoing trials are investigating everolimus compared with chemotherapy, optimal sequencing of therapy and combination of everolimus with radiotherapy. Future research should concentrate on identification of predictive biomarkers for benefit from mTOR therapy and include quality of life as a measure.
Poorly recognized age-related downward deviation of the inguinal ligament
Authors: Nawaz Yassir , Barvalia Mihir , Rana Gurinder , Khakwani M Zain , Azim Khizr , Patel Rahul , Idrees Sohira , Baker Gail , Cohen Marc , Wasty Najam
Published: October 2016

Objective:

To determine factors affecting actual inguinal ligament course in live human subjects.

Introduction and hypothesis:

Although the expected inguinal ligament course is supposedly a straight line extending from anterior superior iliac spine to pubic tubercle, the actual inguinal ligament course is frequently depicted a priori by a downward bowing dotted line. There are no studies in a live subject supporting this assumption. We hypothesized this assumption is indeed valid and is related to among other factors a lifelong effect of gravity and lax abdominal musculature on the inguinal ligament course.

Methods:

We retrospectively reviewed 54 consecutive computed tomography scans of the abdomen and pelvis randomly distributed across all age groups. Actual inguinal ligament course was visualized by reconstructing images using Terracon software. Vertical distance from the lowest point of actual inguinal ligament course to the expected inguinal ligament course was measured. We used multiple linear regression analysis to study the correlation between degree of inguinal ligament deviation and several variables.

Results:

Actual inguinal ligament course was below the expected inguinal ligament course in 52 of 54 patients. The mean deviation was 8.2 ± 5.9 mm. Advanced age was significantly associated with greater downward bowing of the inguinal ligament (p = 0.001).

Conclusion:

Actual inguinal ligament course is often well below the expected inguinal ligament course; this downward bowing of the inguinal ligament is especially pronounced with advancing age. Operators need to be mindful as this downward bowing can lead to supra-inguinal sticks causing vascular complications.
Meet the Flexperts! How to bring in expert contributions around the contract in support of commercial interests
Authors: Unsworth Rory
Published: October 2016

The purpose of this paper is to highlight difficulties currently facing cross-disciplinary experts attempting to collaborate around commercial contracts in large businesses, and to suggest a means of addressing this in order to ease the process and enhance the client experience. The paper tells the story of a deal in short chapters, intercut with background explanations and reflections on the challenges and the solutions. This unusual approach in an academic essay allows the author to share a vision within a little-known commercial sector – reinsurance – which serves as a paradigm for complex cross-border contracting. This vision intends to provoke thinking and does not have the ambition of proving one approach over another. The author’s recommendation is an investment in a backbone technology allowing knowledge sharing, and a change in mindset which the author refers to as ‘Flexpertise’ to align the views of individuals to the view of the company.
Resistance to anti-CD19/CD3 BiTE in acute lymphoblastic leukemia may be mediated by disrupted CD19 membrane trafficking
Authors: Braig Friederike , Brandt Anna , Goebeler Mariele , Tony Hans-Peter , Kurze Anna-Katharina , Nollau Peter , Bumm Thomas , Böttcher Sebastian , Bargou Ralf C. , Binder Mascha
Published: October 2016

Key Points

CD19− relapses are a major challenge in about 10% to 20% of patients treated with blinatumomab. Molecular workup of 1 case revealed a disrupted CD19 membrane export as the basis for blinatumomab resistance.
How I use anticoagulation in atrial fibrillation
Authors: Steinberg Benjamin A.
Published: October 2016

Atrial fibrillation is the most common cardiac arrhythmia and conveys a significant risk of morbidity and mortality due to related stroke and systemic embolism. Oral anticoagulation (OAC) is the mainstay of thromboembolism prevention, and management of anticoagulation can be challenging. For patients without significant valvular disease, decisions around anticoagulation therapy are first based on the presence of additional stroke risk factors, as measured by the CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75, diabetes, prior stroke or transient ischemic attack, vascular disease, age 65–74, and sex category [female]) score. Patients with increased CHA2DS2-VASc scores (by regional guidelines) should next be evaluated to determine if they are candidates for non–vitamin K antagonist oral anticoagulant (NOAC) therapy. This should focus on assessment of concomitant valve disease and/or impaired renal function. In eligible patients, the cumulative data support a preference for NOACs over warfarin, as NOACs appear safer and more effective as a group. However, there are no direct, randomized comparisons between NOACs, and therefore, selecting among them can be difficult. In addition, important patient groups remain underrepresented in major clinical trials, and their management is often left to clinician judgment. Data from emerging clinical trials will help guide physicians; however, patient engagement in decisions regarding OAC management will remain vital to ensuring appropriate balance of risks and optimizing health outcomes.
Identification of genes differentially expressed in a resistant reaction to Mycosphaerella pinodes in pea using microarray technology
Authors: Fondevilla Sara , Küster Helge , Krajinski Franziska , Cubero José I , Rubiales Diego
Published: October 2016

Background

Ascochyta blight, caused by Mycosphaerella pinodes is one of the most important pea pathogens. However, little is known about the genes and mechanisms of resistance acting against M. pinodes in pea. Resistance identified so far to this pathogen is incomplete, polygenic and scarce in pea, being most common in Pisum relatives. The identification of the genes underlying resistance would increase our knowledge about M. pinodes- pea interaction and would facilitate the introgression of resistance into pea varieties. In the present study differentially expressed genes in the resistant P. sativum ssp. syriacum accession P665 comparing to the susceptible pea cv. Messire after inoculation with M. pinodes have been identified using a M. truncatula microarray.

Results

Of the 16,470 sequences analysed, 346 were differentially regulated. Differentially regulated genes belonged to almost all functional categories and included genes involved in defense such as genes involved in cell wall reinforcement, phenylpropanoid and phytoalexins metabolism, pathogenesis- related (PR) proteins and detoxification processes. Genes associated with jasmonic acid (JA) and ethylene signal transduction pathways were induced suggesting that the response to M. pinodes in pea is regulated via JA and ET pathways. Expression levels of ten differentially regulated genes were validated in inoculated and control plants using qRT-PCR showing that the P665 accession shows constitutively an increased expression of the defense related genes as peroxidases, disease resistance response protein 39 (DRR230-b), glutathione S-transferase (GST) and 6a-hydroxymaackiain methyltransferase.

Conclusions

Through this study a global view of genes expressed during resistance to M. pinodes has been obtained, giving relevant information about the mechanisms and pathways conferring resistance to this important disease. In addition, the M. truncatula microarray represents an efficient tool to identify candidate genes controlling resistance to M. pinodes in pea.
Netrin1/DCC signaling promotes neuronal migration in the dorsal spinal cord
Authors: Junge Harald J. , Yung Andrea R. , Goodrich Lisa V. , Chen Zhe
Published: October 2016

Background

Newborn neurons often migrate before undergoing final differentiation, extending neurites, and forming synaptic connections. Therefore, neuronal migration is crucial for establishing neural circuitry during development. In the developing spinal cord, neuroprogenitors first undergo radial migration within the ventricular zone. Differentiated neurons continue to migrate tangentially before reaching the final positions. The molecular pathways that regulate these migration processes remain largely unknown. Our previous study suggests that the DCC receptor is important for the migration of the dorsal spinal cord progenitors and interneurons. In this study, we determined the involvement of the Netrin1 ligand and the ROBO3 coreceptor in the migration.

Results

By pulse labeling neuroprogenitors with electroporation, we examined their radial migration in Netrin1 (Ntn1), Dcc, and Robo3 knockout mice. We found that all three mutants exhibit delayed migration. Furthermore, using immunohistochemistry of the BARHL2 interneuron marker, we found that the mediolateral and dorsoventral migration of differentiated dorsal interneurons is also delayed. Together, our results suggest that Netrin1/DCC signaling induce neuronal migration in the dorsal spinal cord.

Conclusions

Netrin1, DCC, and ROBO3 have been extensively studied for their functions in regulating axon guidance in the spinal commissural interneurons. We reveal that during earlier development of dorsal interneurons including commissural neurons, these molecules play an important role in promoting cell migration.
Flow characteristics and a permeability model in nanoporous media with solid-liquid interfacial effects
Authors: Wang Jiulong , Song Hongqing , Zhu Weiyao , Wang Yuhe , Killough John
Published: October 2016

Molecular dynamics simulations of water flow through nanotubes have demonstrated higher flow rates than the flow rates predicted using classical models and a significant change in flow patterns due to the thin film that forms on the solid wall of the tubes. We have developed a two-region analytical model that described the flow characteristics and permeability of fluid flow through nanoporous media and considered the solid-liquid interfacial effects. Our model considers the influence of various interfacial effects, including long-range van der Waals forces, double-layer repulsive forces, and short-range structure repulsive forces, and it establishes relationships between the permeability and the average pore diameter, porosity, surface diffusion, and contact angle by numerical calculations. Our results indicate that the permeability calculated using the present model (with interfacial effects) is more than 30 times the results that were calculated using the Kozeny-Carman equation (without interfacial effects). The thickness of the thin film significantly affects the flow characteristics. We have gained new insight and guidance regarding the development of nanoscale pore reservoirs, such as shale gas and shale oil.
Time-variant wavelet extraction with a local-attribute-based time-frequency decomposition for seismic inversion
Authors: Zhang Rui , Fomel Sergey
Published: October 2016

Seismic impedance inversion has been widely used to estimate subsurface properties. Conventional inversion assumes that seismic data are the convolution result of seismic wavelet and reflectivity, implying that seismic data are stationary when a constant wavelet is considered. However, seismic data are nonstationary because of noise contamination and attenuation during wave propagation, which means that the frequency spectrum of the seismic signal changes from shallow to deep formations. We have developed a time-variant wavelet extraction method by using a local-attribute-based spectral decomposition technique. Time-variant wavelets are generated according to the local frequency spectrum, which can be used to construct a time-variant wavelet kernel matrix. By using this time-variant kernel matrix, we can obtain a better correlation between synthetic and extracted seismograms than by using constant wavelet on a field data example. Using this example, we have also compared the time-variant and constant wavelets for inverting the field data to estimate subsurface acoustic impedance. Our results showed improved resolution and a better fit to well-log-measured impedance by using the time-variant wavelets.
Prostatic Acid Phosphatase Alters the RANKL/OPG System and Induces Osteoblastic Prostate Cancer Bone Metastases
Authors: Kirschenbaum Alexander , Izadmehr Sudeh , Yao Shen , O’Connor-Chapman Kieley L. , Huang Alan , Gregoriades Elias M. , Yakar Shoshana , Levine Alice C.
Published: October 2016

Prostate cancer (PCa) is unique in its tendency to produce osteoblastic (OB) bone metastases. There are no existing therapies that specifically target the OB phase that affects 90% of men with bone metastatic disease. Prostatic acid phosphatase (PAP) is secreted by PCa cells in OB metastases and increases OB growth, differentiation, and bone mineralization. The purpose of this study was to investigate whether PAP effects on OB bone metastases are mediated by autocrine and/or paracrine alterations in the receptor activator of nuclear factor κ-B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system. To investigate whether PAP modulated these factors and altered the bone reaction, we knocked down PAP expression in VCaP cells and stably overexpressed PAP in PC3M cells, both derived from human PCa bone metastases. We show that knockdown of PAP in VCaP cells decreased OPG while increasing RANK/RANKL expression. Forced overexpression of PAP in PC3M cells had the inverse effect, increasing OPG while decreasing RANK/RANKL expression. Coculture of PCa cells with MC3T3 preosteoblasts also revealed a role for secretory PAP in OB-PCa cross talk. Reduced PAP expression in VCaP cells decreased MC3T3 proliferation and differentiation and reduced their OPG expression. PAP overexpression in PC3M cells altered the bone phenotype creating OB rather than osteolytic lesions in vivo using an intratibial model. These findings demonstrate that PAP secreted by PCa cells in OB bone metastases increases OPG and plays a critical role in the vicious cross talk between cancer and bone cells. These data suggest that inhibition of secretory PAP may be an effective strategy for PCa OB bone lesions.
Preoperative Three-Dimensional Strain Imaging Identifies Reduction in Left Ventricular Function and Predicts Outcomes After Cardiac Surgery
Authors: Howard-Quijano Kimberly , Salem Ali , Barkulis Charles , Mazor Einat , Scovotti Jennifer C. , Ho Jonathan K. , Shemin Richard J. , Grogan Tristan , Elashoff David , Mahajan Aman
Published: October 2016

BACKGROUND:

Echocardiography-based speckle-tracking strain imaging is an emerging modality to assess left ventricular function. The aim of this study was to investigate the change in left ventricular systolic function after cardiac surgery with 3-dimensional (3D) speckle-tracking strain imaging and to determine whether preoperative 3D strain is an independent predictor of acute and long-term clinical outcomes after aortic valve, mitral valve, and coronary artery bypass grafting operations.

METHODS:

In total, 163 adult patients undergoing aortic valve, mitral valve, and coronary artery bypass surgeries were enrolled prospectively and had complete data sets. Demographic, operative, and outcome data were collected. 3D transthoracic echocardiograms were preformed preoperatively and on second to fourth postoperative day. Blinded off-line analysis was performed for left ventricular 2-dimensional (2D) ejection fraction (EF2D) and 3D ejection fraction (EF3D) and global peak systolic area, longitudinal, circumferential, and radial strain.

RESULTS:

3D global strain correlated well with EF3D. Ventricular function as measured by strain imaging decreased significantly after all types of cardiac surgery. When preoperative EF3D was used, receiver operating characteristic curves identified reference values for 3D global strain corresponding to normal, mildly reduced, and severely reduced ventricular function. Normal ventricular function (EF3D ≥ 50%) corresponded to 3D global area strain −25%, with area under curve = 0.86 (0.81–0.89). Patients with reduced preoperative 3D global area strain had worse postoperative outcomes, including length of intensive care unit stay (4 vs 3 days, P = .001), major adverse events (27% vs 11%, P = .03), and decreased 1-year event-free survival (69% vs 88%, P = .005). After we controlled for baseline preoperative risk models including European System for Cardiac Operative Risk Evaluation score and surgery type, preoperative strain was an independent predictor of both short- and long-term outcomes, including length of intensive care unit stay, postoperative inotrope score, and 1-year event-free survival.

CONCLUSIONS:

This study shows that cardiac surgery was associated with an acute reduction in postoperative left ventricular function, when evaluated with 3D strain imaging. In addition, preoperative 3D strain was demonstrated to be an independent predictor of acute and long-term clinical outcomes after cardiac surgery. The use of noninvasive 3D transthoracic echocardiogram strain imaging before cardiac surgery may provide added information to aid in perioperative risk stratification and management for these high-risk patients.
Remote Effects of Electromagnetic Millimeter Waves on Experimentally Induced Cold Pain: A Double-Blinded Crossover Investigation in Healthy Volunteers
Authors: Partyla Tomasz , Hacker Henriette , Edinger Hardy , Leutzow Bianca , Lange Joern , Usichenko Taras
Published: October 2016

BACKGROUND:

The hypoalgesic effect of electromagnetic millimeter waves (MW) is well studied in animal model; however, the results of human research are controversial. The aim of this study was to evaluate the effects of various frequency ranges of MW on hypoalgesia using the cold pressor test (CPT).

METHODS:

Experimental pain was induced using standardized CPT protocols in 20 healthy male volunteers. The skin of the lower part of sternum was exposed to MW with a frequency of 42.25 GHz (active generator); MW within 50–75 GHz frequency range (noise generator); or an inactive MW device (placebo generator) in a random crossover double-blinded manner. Pain threshold, measured using the CPT, was the primary outcome. Other CPT parameters, heart rate, blood pressure, incidence of subjective sensations (paresthesia) during exposure, as well as quality of volunteers’ blinding were also recorded. The end points of the condition with exposure to 42.25 GHz, were compared with baseline; exposure to noise 50-75 GHz; and placebo generators.

RESULTS:

Pain threshold increased during exposure to the 42.25 GHz generator when compared with baseline: median difference (MD), 1.97 seconds (95% confidence interval [CI], 0.35–3.73) and noise generator: MD, 1.27 seconds (95% CI, 0.05–2.33) but not compared with the placebo generator. Time to onset of cold and increasing pain sensations as well as diastolic blood pressure increased under the exposure to the 42.25 GHz generator when compared with baseline and noise generator. Other outcome measures were comparable among the study conditions.

CONCLUSIONS:

We were able to partially confirm the previously suggested hypoalgesic effects of low-intensity electromagnetic MW. However, the effect was indistinguishable from the placebo condition in our investigation.
Pax8 controls thyroid follicular polarity through Cadherin-16
Authors: Koumarianou Petrina , Goméz-López Gonzalo , Santisteban Pilar
Published: October 2016

Organization of epithelial cells during follicular lumen formation is crucial for thyroid morphogenesis and function of the thyroid gland; however, the molecular mechanisms underlying this are poorly understood. To investigate this process, we established three-dimensional (3D) epithelial culture model systems using Fischer rat thyroid (FRT) cells or murine primary thyrocytes that developed polarized spherical structures with a central lumen mimicking thyroid follicles. Using microarray-based differential expression analysis of FRT cells grown under 2D or 3D conditions followed by RNA-mediated interference (RNAi) and morphogenetic analysis, we identified a key role for the thyroid transcription factor Pax8 and its target Cadherin-16 (Cdh16) in the generation of polarized follicle-like structures. Silencing Pax8 expression inhibited the acquisition of apical-basal membrane polarity and impaired lumen formation. Both laminin and β1-integrin (Itgb1) expression was reduced, while cell cytoskeleton polarized distribution was altered. Silencing Cdh16 expression also led to the formation of defective structures characterized by very low laminin expression at the follicle-matrix interface, down-regulation of Itgb1, and unpolarized distribution of cell cytoskeleton. Our results demonstrate that Pax8 controls apical-basal follicular polarization and follicle formation through Cdh16.