bluuebunny/crossref_metadata_2025 huggingface dataset:
Nāzik al-Malāʾikah and Edgar Allan Poe: Their Poetry and Related Poetics
Authors: Khaldi Boutheina
Published: April 2020

This study argues that Nāzik al-Malāʾikah’s poetics—as indicated in her “Introduction” to her collection Shaẓāyā wa-ramād and her book Qaḍāyā al-shiʿr al-muʿāṣir—is in conversation with the famous American poet, critic, and short story writer Edgar Allan Poe’s poetics. This affinity has not been properly noted by critics, as their discussions have been limited to issues of form, content, or borrowings from Poe’s poems. This article argues that al-Malāʾikah’s elaborations on Poe are more profound than hitherto assumed since they articulate a different kind of formal poetics altogether. The chief characteristics of this poetics can be identified as sound/rhythm, concision, refrain (or repetition, with variation). While these innovative instances are foundational in her literary criticism, her poetry also conveys other venues of indebtedness and conversation.
“Zahra’s Uncle, or Where Are Men in Women’s War Stories?”
Authors: Hartman Michelle
Published: April 2020

Scholarship in modern Arabic literary studies has treated the literature of the Lebanese Civil War, particularly novels written by women, in some depth. One of the most important texts used in both scholarship and teaching about this war is Ḥanān al-Shaykh’s Ḥikāyat Zahrah, translated as The Story of Zahra. This article focuses specifically on the one chapter in the novel narrated from the point of view of the protagonist’s uncle in order to explore how the English translation dramatically changes a number of elements in the original text. It uses insights from translation studies to show how significant changes to the novel in translation produce a text that serves particular ideological functions in English, consistent with a horizon of expectations that constructs Arab women as oppressed and passive victims of war. The article analyzes specific translation choices—most notably the extensive editing out of words, sentences, and passages—to demonstrate how the character of Zahrah’s uncle is changed in English and depicted as an unsavory and abusive man with little background, context, or history that would help the reader to better understand the character’s actions and motivations. It also shows how cutting out elements of the uncle’s story serves to depoliticize the text in English, divesting it of its local political context and changing its meaning and function as a novel about the Lebanese Civil War. The article is grounded in postcolonial, feminist translation studies, especially those dealing with Arabic fiction, to argue that the English-language novel The Story of Zahra functions within an ideological field that recycles stereotypes and tropes about Arab women. It will propose that the translation changes here depict Arab men against Arab women, rather than in relation to them, and subordinate the analysis of politics and communal relations to a more individual and individualized story of one exceptional woman.
The Rekom Shrine in North Ossetia-Alania and its Annual Ceremony
Authors: Foltz Richard
Published: April 2020

The Rekom Shrine located in the Tsey Valley of North Ossetia-Alania is one of the most important sites in the Ossetian popular religion, which in modern times is often referred to as the Uatsdin. The shrine is dedicated to Uastyrdzhi, an Ossetian cultic figure associated with the Christian St. George. Rekom is the site of a major festival held in mid-June, called Rekomy Bærægbon (Рекомы бæрæгбон), where certain aspects of the ritual may date back to Scythian times. These and similar ceremonies throughout North and South Ossetia are best understood as expressions of national identity and community solidarity.
Executions of Jewish Partisans in the Lithuanian Forests: The Case of Natan Ring
Authors: Ozacky-Stern Daniela
Published: April 2020

Jews joined the Soviet partisan movement spontaneously, after escaping from various ghettos in Lithuania and Belarus. Most of them had no military background, but they were eager to take part in fighting and revenge. They had to adjust to harsh living conditions in the forests and suffered hostility and antisemitism on the part of locals and non-Jewish fellow partisans. Internal relations amongst different political and ideological groups were often problematic as well. This article focuses on specific violent events which occurred in the Rudniki forests near Vilnius, Lithuania, and specifically on one controversial case study: the execution of the partisan commander Natan Ring in early November 1943, by his brothers in arms. Ring was suspected of collaboration with the Germans while he served as a Jewish policeman in the Vilnius ghetto. Based on the testimonies and memories of former partisans, recorded at different times between the end of the war until the present, the article rethinks morals and behaviour in that unique space and time and how the event has been perceived over the years which followed.
Adaptive fuzzy practical tracking control for flexible-joint robots via command filter design
Authors: Diao Shuzhen , Sun Wei , Yuan Wenxing
Published: April 2020

This paper investigates the issue of finite-time tracking control for flexible-joint robots. In the design scheme, the unknown continuous function is identified by a fuzzy system. By introducing the command filter technique, “explosion of complexity” problem which arises from repeated differentiation of virtual controllers is avoided. Meanwhile, errors resulting from the first-order filters can be reduced with the introduced compensation signal. Besides, the proposed method ensures that the tracking performance could be achieved within a limited time. Eventually, the simulation is given to demonstrate the effectiveness of the proposed scheme.
Training methodology in energy efficiency evaluation of induction motor drives and systems for enhancing educational programs
Authors: Dinolov Ognyan
Published: April 2020

For improving the energy efficiency level in industrial systems, the service specialists should take appropriate measures to improve the efficiency in a timely manner. A necessity arises to provide adequate training for current and future specialists and practitioners. This training can be based on the digital technologies taking into account the information revolution we are witnessing and the future trends in this field. In this paper, a unified training methodology and laboratory equipment on energy efficiency investigation in induction motor drives is developed based on a developed automated computer system. The methodology is provided with created software products based on developed complex algorithms. The methodology procedure and the corresponding learning processes are organized into six main stages. In order to implement the method in the training of specialists, a computer laboratory bench is designed and implemented. The training is provided with three elaborated textbooks. The education conducted using the methodology improves the competence of the trained persons and gives them the opportunity to make justified and correct decisions and take relevant actions. The proposed development is used for educating number of students in some master programs in the University of Ruse. A major part of them already works in the field.
For-Profit Nursing Homes in the Netherlands: What Factors Explain Their Rise?
Authors: Bos Aline , Kruse Florien Margareth , Jeurissen Patrick Paulus Theodoor
Published: April 2020

This exploratory, mixed-methods study analyzes characteristics of the emerging for-profit nursing home industry in the Netherlands and identifies the interrelated set of factors (context, trends, and sector conditions) that contribute to its growth. Until recently, the Dutch nursing home sector relied almost exclusively on nonprofit providers. Even though profit distribution in nursing home care is still banned, the for-profit nursing home sector is expanding. The study uses economic theory on nonprofit organizations and mixed-form markets to understand this expansion. We find that changes in the regulatory framework have unlocked the potential of the for-profit nursing home sector, enabling for-profit nursing homes to circumvent the for-profit ban. The expansion of the for-profit sector was mainly driven by the low responsiveness of the nonprofit sector to increased and changed demands. For-profit providers took advantage of this void. Moreover, they exploited “cream-skimming” potential in the market and used the wider care system to reduce their labor costs by relying on external specialist care. Another main driver was the access to financial capital from private investors (e.g., private equity firms).
Recurrent arthritis: an unusual diagnosis
Authors: Sesama Meenakshi , Bhaskar Vikram , Meena Monika , Narang Manish , Aggarwal Anju , Kotru Mrinalini
Published: April 2020

Musculoskeletal complaints may be the initial manifestation of childhood leukaemias. When these symptoms predominate at the onset, a diagnosis of one of several rheumatic diseases may be entertained. Where blood tests are normal, no bone marrow examination would normally be indicated. The use of immune-suppressing medication, such as steroids, may lead to diagnostic delay or misdiagnosis.
Mediating Effect of Attributional Biases in the Impulsivity–Aggression Relationship Among Adolescents: Therapeutic Implications
Authors: Singh Parwinder
Published: April 2020

Aggression is a multidimensional phenomenon, and for its better understanding, specificity involved in its dynamics must be explored. This article explores the role of attributional bias as a mediator between impulsivity and aggressive tendencies among adolescents. The mediating effect of hostile attributional bias (HAB) on the impulsivity–aggression relationship has not been studied extensively so far, especially in the Indian context. For testing the hypotheses, 320 participants within the age range 12 to 15 years ( M age = 13.57 years) were selected and administered relevant standardized questionnaires. Baron and Kenny’s criterion was used for mediation analysis, demonstrating that HAB partially mediates the association between impulsivity and aggression. Findings imply that reducing HAB through some reattribution intervention may be an effective strategy to reduce impulsivity-induced aggression. Specific guidelines to implement such interventions are suggested in the discussion.
Use of 1D mechanical and thermal models to predetermine the heat transferable by a thermal interface material layer in space applications
Authors: Vandevelde Simon , Daidié Alain , Sartor Marc
Published: April 2020

This paper proposes the use of 1D basic models to build a design assistance tool capable of evaluating the heat transfer between a third-level electronic packaging and its support, considering a conventional configuration where a thermal interface material is placed between these two parts. Using this kind of tool early in the design process may facilitate choices concerning geometry and material. The packaging is modelled by a stepped beam (the equipment) and the interface layer by a nonlinear elastic foundation (the thermal interface material). Considering that the electronic equipment bends under the effect of the forces exerted by the fasteners, the tool makes it possible to determine the contact zone remaining operative after deformation, and the pressure distribution at the interface. Mechanical results are then used to calculate the steady-state heat transfer between the equipment and its support, taking into account the diffusion within the equipment and the thermal interface material, and also the thermal contact resistances, the latter being dependent on the contact pressure. A detailed case study is used to illustrate the utility of the approach. The 1D models are exploited to illustrate the interest of the design assistance tool. The influence of different parameters on the thermal performance is studied and a new innovative proposal is analyzed, which could lead to a significant increase in thermal performance.
Sociodemographic Profile, Reproductive Health and Nutritional Status Among the Juangs—A Particularly Vulnerable Tribal Group of Odisha, India
Authors: Kanrar Priyanka , Goswami Monali
Published: April 2020

The present study is an endeavor to understand the sociodemographic profile, reproductive health, and nutritional status of the Juangs, a particularly vulnerable tribal population of Odisha, India. A total of 435 adult males and 515 adult females (≥18 years) were considered from 15 villages under two blocks of Keonjhar district of Odisha, India. A pre-structured schedule was used to collect data on the sociodemographic profile and reproductive health. Heights and weights were recorded using the standard protocol. Statistically significant ( p < 0.05) sex difference was found with respect to age, educational status, and occupational status between the males and the females. The present study reveals that the mean reproductive wastage was found to be 0.55. The maternal and child health care services unveil that only 29.9 percent of the women have taken iron and folic acid (IFA) tablets and 23.1 percent have taken at least one tetanus toxoid (TT) vaccine. Maximum percentage of women (75.9%) were assisted by elderly women during delivery, and only 35.1 percent adopted the sterilization method for fertility regulation. Among the mothers, 60.6 percent initiated breastfeeding on the third day, 55.9 percent breastfed their babies for a period of 2 years, and 66.2 percent mothers immunized their children with at least one vaccine. A significant sex difference of mean body mass index (BMI) ( t – 5.68; p < 0.001) was observed between the Juang males and females. The study reflects that the extents of undernutrition among the males (57.5%) and the females (62.9%) were very high, which indicates that the Juangs are under serious nutritional stress. Hence, immediate appropriate nutritional intervention programs are needed for implementation.
The role of Bruton’s tyrosine kinase inhibitors in the management of mantle cell lymphoma
Authors: Hanna Kirollos S , Campbell Maren , Husak Alex , Sturm Sabrina
Published: April 2020

Mantle cell lymphoma is a rare subtype of B-cell non-Hodgkin’s lymphomas that is generally classified as an aggressive lymphoma requiring front-line chemo-immunotherapy with stem cell rescue. Despite effective treatment, many patients relapse or are refractory to front-line therapy. In addition, these patients may also develop drug resistance requiring novel modalities for subsequent lines. Bruton’s tyrosine kinase inhibitors have demonstrated a well-tolerated safety and efficacy profile across several B-cell malignancies. Ibrutinib, acalabrutinib, and zanubrutinib are FDA-approved as treatment options for patients with Mantle cell lymphoma following one prior line of therapy. Various factors should be considered which include the adverse event profile of these agents and ability to adhere to therapy. In this article, we review the role of Bruton’s tyrosine kinase inhibitors for the management of Mantle cell lymphoma and review the clinical pharmacology, pharmacokinetics, safety and efficacy, and future directions.
Tamoxifen-induced acute mania: A case report
Authors: Duman Berker , Kuşman Adnan , Çolak Burçin , Şenler Filiz Çay , Kumbasar Hakan
Published: April 2020

Introduction

Tamoxifen is widely used for the treatment of hormone-responsive breast cancer, osteoporosis, and post-menopausal symptoms. Also, tamoxifen is currently under investigation for its anti-manic properties. In this article, we report a case who developed manic episode following the initiation of tamoxifen and remitted with discontinuation of the medication.

Case Report

A 58-year-old woman was diagnosed with breast cancer. Pathologic diagnosis was invasive ductal carcinoma. Following bilateral total mastectomy operation, trastuzumab was initiated with intervals of 21 days. Five days before the fourth application of trastuzumab, tamoxifen was added. On the sixth day following the initiation of tamoxifen, manic symptoms were developed and she was diagnosed as acute mania.

Management and Outcome

The oncology department suggested withdrawing tamoxifen due to a possible association between tamoxifen initiation and behavioral symptoms. Manic symptoms were rapidly (approximately 24 h) improved following cessation of tamoxifen. Psychiatric evaluation on the fifth day following cessation of tamoxifen revealed no manic symptoms. An aromatase inhibitor-exemestane was initiated and she showed no side effects with this medication since then.

Discussion

To our knowledge, this is the first case report of probable tamoxifen-induced mania. Our case report at least indicates that there were possibly some patients who were sensitive to the tamoxifen’s nervous system effects, mainly to manic effects. In conclusion, clinicians should be aware of these rare behavioral adverse effects of tamoxifen.
Fastidious chemical decontamination after cyclophosphamide vial breakage in a compounding unit
Authors: Petit Ophélie , Saint-Lorant Guillaume , Vasseur Michèle , Boucher Julie , Courtin Justin , Pinturaud Marine , Allorge Delphine , Decaudin Bertrand , Simon Nicolas , Odou Pascal
Published: April 2020

An important amount of cytotoxic drug may accumulate in the workplace following the breakage of a vial containing an anticancer drug. Thanks to the monthly monitoring of the surface contamination in our compounding unit, a strong increase of cyclophosphamide contamination was highlighted in the storage area following the breakage of the vial, despite application of the emergency procedure. This study presents an analysis of chemical decontamination in the context of massive contamination. Samples were taken on the floor and on the caster of a storage shelf where the vial broke. The residual contamination was measured with a liquid chromatography–mass spectrometry/mass spectrometry method. An admixture of 10−2 M sodium dodecyl sulfate and 70% isopropanol (SDS/IPA 8:2) was selected as the decontamination solution. High amounts of cyclophosphamide were retrieved. The initial contamination on the floor was over 20 ng/cm2. Three decontaminations with SDS/IPA were carried out at Day 61, Day 68, and Day 71. The amount of cyclophosphamide decreased to 0.45 ng/cm2 at D134. However, high values were still measured on the caster despite successive decontaminations, with a maximal value of 19.78 ng/cm2 observed at Day 106. Continuous monitoring in our unit led us to highlight the inefficiency of our emergency procedure to eliminate high cyclophosphamide contamination. The procedure involving the SDS/IPA admixture was more efficient on the floor compared to the caster, which is a different surface type and porosity. This work highlights the importance of improving the procedures of incident management using contamination monitoring and repeated decontamination procedures adapted to different contaminants and surfaces.
Pectin-based edible coating preserves antioxidative capacity of plum fruit during shelf life
Authors: Panahirad Sima , Naghshiband-Hassani Rahim , Mahna Nasser
Published: April 2020

Exploiting safer methods for fruit preservation such as application of edible coatings can improve shelf life, valuable characteristics, and antioxidative capacity. The current study aimed to investigate the effect of a pectin-based edible coating on antioxidative capacity of plum fruit during shelf life (19 ± 2 ℃ and 65% relative humidity for eight days). To do this, three solutions (0.5, 1, and 1.5%) of pectin, plasticized by glycerol (0.3% w/v), were applied on plum fruit and compared to a control treated with only distilled water. Ascorbic acid, total phenolics, anthocyanin and flavonoid contents, total antioxidative capacity based on 1,1-diphenyl-2-picryl-hydrazyl hydrate method, peroxidase (as an antioxidant enzyme), and polyphenol oxidase (as an oxidant enzyme) activities were recorded during this period. The results demonstrated that pectin-based edible coating was significantly effective on maintaining ascorbic acid, anthocyanin and flavonoid contents, and antioxidative capacity in plum fruits (P ≤ 0.01). The activities of enzymes were significantly affected by the coatings; peroxidase activity increased and polyphenol oxidase activity decreased (P ≤ 0.01). All pectin concentrations significantly caused higher ascorbic acid and anthocyanin contents, antioxidative capacity, and peroxidase activity but a lower polyphenol oxidase activity than the control; however, just 1 and 1.5% concentrations were effective in terms of total phenolic compounds and flavonoid content, respectively, and the other concentrations acted the same as the control. In general, the coating constituted from 1.5% pectin showed the best results for most measured parameters. Considering the influences of pectin-based edible coating on antioxidative characteristics of plum fruits, its application can be potentially regarded as a favorable method to enhance nutritional value of fruits.
Selection On synonymous Mutations Revealed by 1135 Genomes of Arabidopsis thaliana
Authors: Wei Lai
Published: April 2020

Synonymous mutations do not change the amino acid but do change the synonymous codon usage. In genomes of different organisms, the gene conversion process is biased toward GC, which is irrespective of mutation bias. In the coding region, this trend is especially obvious and it is possibly caused by the preference on G/C-ending codons over the A/T-ending ones. If the G/C-ending codons are advantageous, then the synonymous mutations that change A/T to G/C would be “optimal” compared to the opposite ones. In theory, one should observe signals of positive selection on these optimal synonymous mutations. The recently released single-nucleotide polymorphism (SNP) data from the 1001 genome project of Arabidopsis thaliana provided researchers with an unprecedented opportunity to verify this assumption. I fully take advantage of the SNP data from 1,135 A thaliana lines and came to the conclusion that synonymous mutations in natural populations are not strictly neutral: the synonymous mutations that increase GC content (from A/T to G/C) tend to have higher derived allele frequencies (DAFs) and, therefore, are likely to be positively selected. My current study broadens our knowledge of the selection patterns of synonymous mutations and should be appealing to evolutionary biologists.

One sentence summary: In 1135 genomes of Arabidopsis thaliana, the synonymous mutations that increase the GC content tend to have higher derived allele frequencies (DAFs) and are likely to be positively selected.
Study on shear behavior of reinforced coral aggregate concrete beam
Authors: Da Bo , Yu Hongfa , Ma Haiyan , Yu Bo , Wu Zhangyu , Guo Jianbo
Published: April 2020

Reinforced coral aggregate concrete beam and reinforced ordinary aggregate concrete beam with different concrete type, concrete strength, and steel type were designed in this study to investigate their shear behavior. The shear behavior of reinforced coral aggregate concrete beam was tested, the failure mode and deflection behavior were studied, and the calculating model for the ultimate shear capacity ( Vcs) of reinforced coral aggregate concrete beam was proposed. Results showed that the failure mode of reinforced ordinary aggregate concrete beam and reinforced coral aggregate concrete beam were basically the same. As the concrete strength increases, the normal section cracking load ( Vcr), inclined section Vcr, and Vcs of reinforced coral aggregate concrete beam increased gradually. Furthermore, Vcr and Vcs of reinforced coral aggregate concrete beam were as follows: 316 stainless steel > common steel > zinc-chromium coated steel > new organic coated steel. For the coral aggregate concrete structure in ocean engineering, in order to prolong its service life, the use of new organic coated steel was suggested. At the same time, the influence of high-strength coral aggregate concrete and stirrup corrosion was comprehensively considered and the calculation model for the Vcs of reinforced coral aggregate concrete beam was presented and was then verified.
Investigation on adaptive method of torque characteristic in dual clutch transmission during launch phase
Authors: Hao Hongtao , Lu Tongli , Zhang Jianwu , Ding Wenjie
Published: April 2020

To reduce sliding friction work and clutch judder, an adaptive method of torque characteristic in dual clutch transmission during launch phase is presented in this paper. The proposed approach provides a tool to identify the change of torque characteristic and adapt it in real time. Firstly, to reduce the influence of the error between the nominal engine torque and the actual engine torque, the estimator based on the extended Kalman filter is designed to estimate the transmitted torque of the dual-clutch transmission during launch phase. Furthermore, the torque characteristic adaptive method is presented by a combination of the estimator with the improved Least Square Method. Then, based on the established driveline model of the dual-clutch transmission, the torque characteristic adaptive method during launch phase is validated by MATLAB/Simulink. Finally, in order to further evaluate the application potential of the adaptive method, the experiments are conducted on a production vehicle equipped with the wet dual-clutch transmission. The simulation and experiment results show that the proposed algorithms work well.
Improving Social Support for a Veteran With PTSD Using a Manualized Acceptance and Commitment Therapy Approach
Authors: Kelly Megan M. , Reilly Erin D. , Ahern Meghan , Fukuda Seiya
Published: April 2020

Posttraumatic stress disorder (PTSD) often negatively impacts social functioning, which can lead to increased risk of morbidity and mortality. Although current evidence-based and exposure-specific treatments can improve PTSD symptoms, they rarely target the interpersonal difficulties that impact quality of life. This case study describes the use of a manualized treatment for a veteran who continues to experience poor social functioning even after previous exposure-based treatment for PTSD. This treatment, ACT to Improve Social Support for Veterans with PTSD (ACT-SS), explicitly targeted the veteran’s maladaptive patterns of interpersonal difficulties, feelings of detachment from others, irritability, and avoidance of social situations. Following treatment, the veteran reported significant improvements in social relationships, quality of life, and depressive symptoms, even though he still met the clinical threshold for PTSD. This case study provides preliminary evidence for the efficacy of a psychosocial intervention that directly targets social functioning issues for veterans with PTSD, and the importance of incorporating social goals and exercises into treatment.
Public broadcasting service under austerity: Cross-comparison between Portugal and Spain
Authors: Costa e Silva Elsa , Díaz-González María-Jesús
Published: April 2020

Following the global financial crisis of 2007/2008, five European countries called for external financial assistance. Austerity policies were implemented, but the extent to which the bailout deal impacted the Portuguese and Spanish public service broadcasters has not been yet thoroughly investigated. Both born in dictatorial regimes, these public service broadcasters in democratic contexts followed different solutions for governance and funding. This article investigates the changes produced in the Portuguese and Spanish public media under the austerity era, analysing the policy measures implemented, as well as the economic and ratings performance of both public service broadcasters. The aim is to assess if external factors (such as external assistance) originated similar effects in both countries. Results show that, in spite of different funding and governance models adopted, both public services were heavily impacted in terms of revenues and ratings and that the austerity period provided the context to set up a neoliberal ideological point-of-view. Both public services lost legitimacy and their cultural and political role was undermined by a discussion that was grounded on economic factors alone.
Non-genetic risk factors for atrial fibrillation are equally important in both young and old age: A nationwide population-based study
Authors: Kim Yun Gi , Han Kyung-Do , Choi Jong-Il , Choi Yun Young , Choi Ha Young , Boo Ki Yung , Kim Do Young , Lee Kwang-No , Shim Jaemin , Kim Jin-Seok , Park Yong Gyu , Kim Young-Hoon
Published: April 2020

Aims

There are several non-genetic risk factors for new-onset atrial fibrillation, including age, sex, obesity, hypertension, diabetes, and alcohol consumption. However, whether these non-genetic risk factors have equal significance among different age groups is not known. We performed a nationwide population-based analysis to compare the clinical significance of non-genetic risk factors for new-onset atrial fibrillation in various age groups.

Methods and results

A total of 9,797,409 people without a prior diagnosis of atrial fibrillation who underwent a national health check-up in 2009 were included. During 80,130,090 person-years of follow-up, a total of 196,136 people were diagnosed with new-onset atrial fibrillation. The impact of non-genetic risk factors on new-onset atrial fibrillation was examined in different age groups. Obesity, male sex, heavy alcohol consumption, smoking, hypertension, diabetes and chronic kidney disease were associated with an increased risk of new-onset atrial fibrillation. With minor variations, these risk factors were consistently associated with the risk of new-onset atrial fibrillation among various age groups. Using these risk factors, we created a scoring system to predict future risk of new-onset atrial fibrillation in different age groups. In receiver operating characteristic curve analysis, the predictive value of these risk factors ranged between 0.556 and 0.603, and no significant trends were observed.

Conclusions

Non-genetic risk factors for new-onset atrial fibrillation may have a similar impact on different age groups. Except for sex, these non-genetic risk factors can be modifiable. Therefore, efforts to control non-genetic risk factors might have relevance for both the young and old.
Discordant responses of plasma low-density lipoprotein cholesterol and lipoprotein(a) to alirocumab: A pooled analysis from 10 ODYSSEY Phase 3 studies
Authors: Mahmood Tahir , Minnier Jessica , Ito Matthew K , Li Qian H , Koren Andrew , Kam Ivy W , Fazio Sergio , Shapiro Michael D
Published: April 2020

Aims

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors consistently reduce low-density lipoprotein cholesterol (LDL-C) by 50–60% and lipoprotein(a) (Lp(a)) by 20–30%, but the mechanism of Lp(a) lowering remains unclear. If Lp(a) is cleared by the LDL receptor, similar to LDL-C, then one would expect PCSK9 inhibition to induce a concordant LDL-C/Lp(a) response in an approximately 2:1 ratio. We aim to determine the prevalence of discordant plasma LDL-C/Lp(a) response to the PCSK9 inhibitor alirocumab.

Methods

This is a post hoc, pooled analysis of 10 randomized controlled trials from the ODYSSEY Phase 3 clinical trial program for alirocumab. Patients enrolled in the trials were high cardiovascular risk and/or with heterozygous familial hypercholesterolemia. The primary end point was prevalence of discordant LDL-C/Lp(a) response to alirocumab at 24 weeks. Discordant response was defined as LDL-C reduction >35% and Lp(a) reduction ≤10%, or LDL-C reduction ≤35% and Lp(a) reduction >10%.

Results

Of the 1709 patients in the pooled study cohort, 62.4% were male, and the mean age was 59.2 (SD: 11.0) years. Baseline mean LDL-C was 126.5 (SD: 46.3) mg/dL and baseline median Lp(a) was 46.9 (interquartile range: 21.8-89.0) mg/dL. Total prevalence of discordant LDL-C/Lp(a) response was 21.5% (12.6% with LDL-C >35% reduction and Lp(a) ≤10% reduction; 8.9% with LDL-C ≤35% reduction and Lp(a) >10% reduction). Baseline Lp(a) and familial hypercholesterolemia status did not affect discordance.

Conclusion

A high prevalence of discordant LDL-C/Lp(a) response was observed with alirocumab, further suggesting that PCSK9 inhibitor therapy with alirocumab reduces plasma Lp(a) through alternative pathways to LDL receptor clearance.
Breathometer: Shut Down by the Federal Trade Commission
Authors: Miller Marc D. , Jackson Lonnie , Campbell Nathan
Published: April 2020

Breathometer was the first Shark Tank pitch where all five sharks invested in one deal. This case examines how Charles Yim created a product that tests blood alcohol levels that is connected to an iPhone or Android smartphone. The product was reported to be innovative in its design and functionality. In the early stages of the company, Yim was able to raise over 2 million dollars from Silicon Valley VC’s, Shark Tank, and Indiegogo. Ultimately, the product’s advertising claims were found to be dubious by the Federal Trade Commission, and they were ordered to provide refunds to all customers. The case examines the processes of value proposition development and investor due diligence. In addition, the case explores the issues related to board composition and the value that board members with extensive industry experience bring to the success of the company. Ultimately, the company underwent a major pivot, transforming its product into one that measures bad breath and oral health. The case and instructor materials provide the vehicle for class discussion and analysis of the early-stage venture success and failure and how industry experience is essential to long-term survivability.
Caco-2 Cells for Measuring Intestinal Cholesterol Transport - Possibilities and Limitations
Authors: Hiebl Verena , Schachner Daniel , Ladurner Angela , Heiss Elke H. , Stangl Herbert , Dirsch Verena M.
Published: April 2020

Background

The human Caco-2 cell line is a common in vitro model of the intestinal epithelial barrier. As the intestine is a major interface in cholesterol turnover and represents a non-biliary pathway for cholesterol excretion, Caco-2 cells are also a valuable model for studying cholesterol homeostasis, including cholesterol uptake and efflux. Currently available protocols are, however, either sketchy or not consistent among different laboratories. Our aim was therefore to generate a collection of optimized protocols, considering the different approaches of the different laboratories and to highlight possibilities and limitations of measuring cholesterol transport with this cell line.

Results

We developed comprehensive and quality-controlled protocols for the cultivation of Caco-2 cells on filter inserts in a single tight monolayer. A cholesterol uptake as well as a cholesterol efflux assay is described in detail, including suitable positive controls. We further show that Caco-2 cells can be efficiently transfected for luciferase reporter gene assays in order to determine nuclear receptor activation, main transcriptional regulators of cholesterol transporters (ABCA1, ABCB1, ABCG5/8, NPC1L1). Detection of protein and mRNA levels of cholesterol transporters in cells grown on filter inserts can pose challenges for which we highlight essential steps and alternative approaches for consideration. A protocol for viability assays with cells differentiated on filter inserts is provided for the first time.

Conclusions

The Caco-2 cell line is widely used in the scientific community as model for the intestinal epithelium, although with highly divergent protocols. The herein provided information and protocols can be a common basis for researchers intending to use Caco-2 cells in the context of cellular cholesterol homeostasis.
A prospective cohort study of MTHFR C677T gene polymorphism and its influence on the therapeutic effect of homocysteine in stroke patients with hyperhomocysteinemia
Authors: Du Xiaoxia , Xiao Lin , Sun Rong , Li Kunpeng , Liang Lin , Song Luping , Liu Zhizhong
Published: April 2020

Background

Hyperhomocysteinemia (HHCY) is a risk factor for cardiovascular and cerebrovascular diseases. The C677T 5, 10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism increases homocysteine (HCY) levels. This study analyzed the relationship between C677T MTHFR polymorphism and the therapeutic effect of lowering HCY in stroke patients with HHCY.

Methods

Baseline data were collected from stroke patients with HHCY for this prospective cohort study. The C677T MTHFR genotype was detected by polymerase chain reaction-restriction fragment length polymorphism and the therapeutic effect to reduce HCY was compared.

Results

Of 200 stroke patients 162 (81.0%) completed follow-up and were evaluated. Most of them responded well to treatment (103 cases, 63.5%), but 59 (36.4%) patients were in the poor efficacy group. There was a significant difference in terms of age (P < 0.001), hypertension (P = 0.041), hyperuricemia (P = 0.042), HCY after treatment (P < 0.001), and MTHFR genotype (P < 0.001) between the poor efficacy and effective groups, with increased frequency of the TT genotype in the poor efficacy group. Logistic regression showed that the T allele was associated with poor efficacy (OR = 0.733, 95%CI: 0.693, 0.862, P < 0.001). In the codominant model the TT genotype was associated with poor outcome (OR = 0.862, 95%CI: 0.767, 0.970, P = 0.017) and this was also the case in the recessive model (OR = 0.585, 95%CI: 0.462, 0.741, P < 0.001) but there was no association between CT and TT in the dominant model.

Conclusions

The T allele and TT genotype of the MTHFR C677T polymorphism was associated with poor HCY reduction treatment efficacy in stroke patients with HHCY.

Trial registration

The registration number of the clinical trial is ChiCTR1800020048. Registration date: December 12, 2018.
Cement augmentation of an angular stable plate osteosynthesis for supracondylar femoral fractures - biomechanical investigation of a new fixation device
Authors: Bäumlein Martin , Klasan Antonio , Klötzer Christine , Bockmann Benjamin , Eschbach Daphne , Knobe Matthias , Bücking Benjamin , Ruchholtz Steffen , Bliemel Christopher
Published: April 2020

Background

Implant anchorage in highly osteoporotic bone is challenging, since it often leads to osteosynthesis failure in geriatric patients with supracondylar femoral fractures. Cementation of screws is presumed to prevent such osteosynthesis failure. This study aimed to investigate the effect of a newly designed, cementable fenestrated condylar screw for plate fixation in a biomechanical setting.

Methods

Eight pairs of osteoporotic cadaver femora with an average age of 77 years, ranging between 62 and 88 years, were randomly assigned to either an augmented or a non-augmented group. In both groups an instable 33-A3 fracture according to the AO / OTA classification was fixed with an angular stable locking plate. All right samples received a cement augmentation of their fenestrated condylar screws with calcium phosphate bone cement (CPC). Mechanical testing was performed at a load to failure mode by cyclic axial loading, using a servohydraulic testing machine.

Results

With a mean of 2475 N (95% CI: 1727–3223 N), the pressure forces resulting in osteosynthesis failure were significantly higher in specimen with cemented condylar screws as compared to non-cemented samples (1875 N (95% CI: 1320–2430 N)) (p = 0.024). In both groups the deformation of the constructs, with the distal screws cutting through the condylar bone, were the most frequent cause for failure. Analysis of axial stiffness (p = 0.889) and irreversible deformity of the specimens revealed no differences between the both groups (p = 0.161). No cement leakage through the joint line or the medial cortex was observed.

Conclusion

Based on the present study results, the newly introduced, cementable condylar screw could be an encouraging feature for the fixation of supracondylar femoral fractures in patients with reduced bone quality in terms of load to failure accuracy of the cement application.
Protocol for a multicenter prospective cohort study evaluating sport activity and development of femoroacetabular impingement in the adolescent hip
Authors:   PREVIEW investigators, Öhlin Axel , Simunovic Nicole , Duong Andrew , Ayeni Olufemi R.
Published: April 2020

Background

Femoroacetabular impingement (FAI) is an important cause of hip pain in young and active individuals and occurs as a result of size and shape mismatch between the femoral head and acetabulum. Open physes in children can make hips more susceptible to injury, and high impact forces have been suggested to affect the developing femur. The diagnosis of FAI has recently risen, especially within adolescent populations, and there is an increasing trend towards year-round participation in sports with early specialization. The PREVIEW study is an international longitudinal study designed to determine the association between sport specialization in adolescence and the development of hip impingement.

Methods

This is a multicentre prospective cohort study evaluating 200 participants between the ages of 12–14 that include sport specialists at the moderate to vigorous physical activity (MVPA) level and non-sport specialists at any activity level. We will monitor physical activity levels of all participants using an activity log and a wrist-mounted activity tracker, with synced data collected every 3 months during the study period. In addition, participants will be evaluated clinically at 6, 12, and 18 months and radiographically at the time of enrolment and 24 months. The primary outcome is the incidence of FAI between groups at 2 years, determined via MRI. Secondary outcomes include hip function and health-related quality of life between subjects diagnosed with FAI versus no FAI at 2 years, as determined by the Hip Outcome Score (HOS) and Pediatric Quality of Life (PedsQL) questionnaires.

Discussion

It is important to mitigate the risk of developing hip deformities at a young age. Our proposed prospective evaluation of the impact of sport activity and hip development is relevant in this era of early sport specialization in youth. Improving the understanding between sport specialization and the development of pre-arthritic hip disease such as FAI can lead to the development of training protocols that protect the millions of adolescents involved in sports annually.

Trial registration

PREVIEW is registered with clinicaltrials.gov (NCT03891563).
Diagnosis of Klippel-Trenaunay syndrome and extensive heterotopic ossification in a patient with a femoral fracture: a case report and literature review
Authors: Zhu Wanbo , Xie Kai , Yang Jiazhao , Li Li , Wang Xujin , Xu Lei , Fang Shiyuan
Published: April 2020

Background

Klippel-Trenaunay syndrome (KTS) is a rare complex vessel malformation syndrome characterized by venous varicosities, capillary malformations, and limb hypertrophy. However, extensive heterotopic ossification (HO) secondary to this syndrome is extremely rare.

Case presentation

We report the case of a patient with previously undiagnosed KTS and extensive HO who presented with a femoral fracture secondary to a motor vehicle accident. Extensive ossification, which leads to compulsive contracture deformity and dysfunction of the leg, was distributed on the flexor muscle side, as revealed by the radiograph. The diagnosis was finally established by combining imaging and histological analysis with classical clinical symptoms. Amputation was performed at the fracture site proximal to the infected necrotic foci. Open management of the fracture was challenging owning to the pervasive ossification and tendency for excessive bleeding. Gene sequencing analysis showed homozygous mutation of FoxO1 gene.

Conclusions

Definitive diagnosis of a combination of KTS and extensive HO requires detailed imaging analysis and pathologic evidence. Mutation of the FoxO1 gene, which regulates bone formation by resistance to oxidative stress in osteoblasts, is a potential factor in the microenvironment of malformed vessels caused by KTS.
Are dietary intake and nutritional status influenced by gender? The pattern of dietary intake in Lao PDR: a developing country
Authors: Ratsavong Kethmany , van Elsacker Tessa , Doungvichit Daovieng , Siengsounthone Latsamy , Kounnavong Sengchanh , Essink Dirk
Published: April 2020

Background

Recognition of discrepancies between men and women in nutritional intake is important to tackle food and nutrition insecurity and the often-double burden of malnutrition. The purpose of this study was to assess nutritional status and dietary intake of the Lao population, with a focus on possible influences of gender.

Methods

Dietary intake was assessed in a national cross-sectional study of 1771 randomized participants aged from 1.01 to 89 years, using 24-h dietary recall. Dietary reference intakes were used to assess nutrient insufficiency. Chi-square test was used to evaluate gender differences and multiple univariate logistic regression to examine associations between gender, nutritional status, demographics and nutrient insufficiency.

Results

Nutrient insufficiencies were higher among pregnant and lactating women than other adult men and women, especially for protein and micronutrients such as vitamin B3, B1, C and other vitamins. Dietary intake and BMI were similar between men and women; all had insufficient intake of all types of nutrients, except sodium. However, women had lower intake than men for almost all nutrients and age groups. The prevalence of overnutrition was higher among those aged 18 years and over for both sexes. Among adult women (15–49.9 years old) and older adult women (50 years old or above), the proportions were: underweight 8.6% (both groups), overweight 18.4 and 20.5%, and obese 34.2 and 39.1%, respectively. Among pregnant and lactating women, the rates of underweight were 7.5 and 1.4%, of overweight were 17.8 and 27.1%, and obese, 21.9 and 40.0%. Among adult and older men, 3.2 and 8.3% were underweight; 21.0 and 18.6% were overweight and 28.2 and 27.6% were obese. Multiple univariate logistic regressions revealed that the factors rural area, dry season and Northern-Lowland region were associated with inadequate micronutrient intake among children, adolescents and adults of both genders.

Conclusions

Dietary intakes were alarmingly micronutrient-insufficient. Macronutrient imbalance and double burden of malnutrition were confirmed in both sexes. Gender differences were limited; men and women had similarly insufficient intakes, but pregnant and lactating women were disproportionately affected. Nutritional interventions should also take men and older people into account to solve nutrition problems.
Can an effective SARS-CoV-2 vaccine be developed for the older population?
Authors: Pawelec Graham , Weng Nan-ping
Published: April 2020

The emergence of SARS-CoV-2 and its inordinately rapid spread is posing severe challenges to the wellbeing of millions of people worldwide, health care systems and the global economy. While many younger people experience no or mild symptoms on infection, older adults are highly susceptible to life-threatening respiratory and systemic conditions which demand a full understanding and leveraging of knowledge of the differences between immunity in young and old people. Consequently, we welcome papers addressing any issues relevant to immunity and ageing in the context of SARS-CoV-2, and will endeavour to fast-track peer-review. We aim to provide a platform exclusively for discussions of individual and age differences in susceptibility and immune responses to COVID caused by SARS-CoV-2 infection and how to prevent or reduce severity of disease in older adults.