bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Mechanisms of Neurogenic Aging in the Adult Mouse Subventricular Zone
Authors: Lupo Giuseppe , Gioia Roberta , Nisi Paola Serena , Biagioni Stefano , Cacci Emanuele
Published: February 2019

In the adult rodent brain, the continuous production of new neurons by neural stem/progenitor cells (NSPCs) residing in specialized neurogenic niches and their subsequent integration into pre-existing cerebral circuitries supports odour discrimination, spatial learning, and contextual memory capabilities. Aging is recognized as the most potent negative regulator of adult neurogenesis. The neurogenic process markedly declines in the aged brain, due to the reduction of the NSPC pool and the functional impairment of the remaining NSPCs. This decline has been linked to the progressive cognitive deficits of elderly individuals and it may also be involved in the onset/progression of neurological disorders. Since the human lifespan has been dramatically extended, the incidence of age-associated neuropsychiatric conditions in the human population has increased. This has prompted efforts to shed light on the mechanisms underpinning the age-related decline of adult neurogenesis, whose knowledge may foster therapeutic approaches to prevent or delay cognitive alterations in elderly patients. In this review, we summarize recent progress in elucidating the molecular causes of neurogenic aging in the most abundant NSPC niche of the adult mouse brain: the subventricular zone (SVZ). We discuss the age-associated changes occurring both in the intrinsic NSPC molecular networks and in the extrinsic signalling pathways acting in the complex environment of the SVZ niche, and how all these changes may steer young NSPCs towards an aged phenotype.
Foreign policy anarchy in multiparty coalitions: When junior parties take rogue decisions
Authors: Greene Toby
Published: February 2019

How do disagreements within multiparty coalitions affect foreign policy, and how can junior parties exert their influence? These questions are of growing importance as new media increases domestic pressure on politicians to interject in international events, and as foreign affairs become more salient in domestic political contestation. Whereas prior research on foreign policy in multiparty coalitions focuses on the influence of junior parties over cabinet decisions, this article proposes a new theoretical concept of ‘rogue decisions’ to describe a distinct outcome of partisan disagreements. Rogue decisions are autonomous decisions by junior parties impacting foreign affairs, taken without cabinet coordination, that undermine their senior partners’ foreign policies. This resembles the ‘anarchy model’ of foreign policy previously attributed to less institutionalized systems. Having identified the necessary conditions that make rogue decisions possible, and the factors that increase their likelihood, the analysis is applied to cases in Britain and Israel. These represent polar opposite parliamentary systems, with Israel among the most proportional, where rogue decisions may be most expected, and Britain the most majoritarian, where they would be least expected. The identification of rogue decisions in contrasting parliamentary democracies challenges the assumption that cabinet is where foreign policy disagreements are managed, according to established decision-making rules. The article therefore prompts new thinking about the potential for junior parties to disrupt the foreign policy agendas of their senior partners, and challenges in new ways the assumption that states act as coherent units.
Understanding the effectiveness and desirability of de-radicalisation: How de-radicalisation is framed in The Daily Mail
Authors: Clubb Gordon , O’Connor Ryan
Published: February 2019

Research on de-radicalisation has been primarily concerned with the efficacy of de-radicalisation programmes and their negative consequences. However, there has been little research on how the public perceives de-radicalisation programmes and whether they are viewed as effective or desirable. It is important to understand public attitudes to de-radicalisation programmes because public opinion can affect the capacity to deliver the programmes. The following article takes a first step towards understanding these issues by examining how The Daily Mail has framed de-radicalisation in terms of whether or not the programmes are effective or desirable. We argue that an assumption of potential efficacy exists throughout the newspaper’s framing of de-radicalisation which presents the policy as desirable, despite also framing de-radicalisation as ineffective. While practitioners are reluctant to promote de-radicalisation programmes, The Daily Mail’s framing of de-radicalisation as natural, logical and desirable reflects the concept’s ideological flexibility as both a rehabilitative and normative endeavour.
Subsistence protection and mitigation ambition: Necessities, economic and climatic
Authors: Shue Henry
Published: February 2019

The distinction between subsistence emissions and luxury emissions was originally devised in 1992 to guard people so poor as to be able to afford only fossil fuels from being priced out of energy by market mechanisms like cap-and-trade that were proposed to assist with limiting climate change. Non-carbon energy can now be made as affordable and accessible as fossil fuel, but tensions remain between measures to support sustainable development and measures to control climate change. Consequently, the distinction between subsistence energy and luxury energy continues to be surprisingly relevant to current international political struggles. The most fully justified method for normative assessment of Nationally Determined Contributions under the Paris Agreement, the Climate Equity Reference Framework, presupposes the distinction. Normative evaluation of the choice between maximally ambitious ratcheting-up of Nationally Determined Contributions in the immediate future and lazy reliance upon hoped-for carbon dioxide removal in future decades depends on it.
A generalist approach to forensic social work: A qualitative analysis
Authors: Naessens Liesbeth , Raeymaeckers Peter
Published: February 2019

Forensic social work is often portrayed as a specialized area within the field of social work. Nevertheless, the target group of forensic social work is confronted with a variety of problems in different life domains. The literature reveals the importance of generalist social work to address the complex needs of vulnerable target groups. However, little has been written or studied about what generalist social work should entail in the field of forensic social work. This article addresses the value of generalist social work for the practice of forensic social work. We conduct 14 interviews with social workers affiliated with forensic social work organizations in Brussels, the capital of Belgium.

Findings

The results show that generalist social work plays a pivotal role in forensic social work. A generalist approach is indispensable to meeting the complex problems of the vulnerable target group of offenders. Our study makes a distinction between five different roles adopted by generalist social workers affiliated with forensic social work organizations when providing services and support to the target group of offenders. In addressing the needs of this target group, they act as a broker, a mediator, a key figure, a safety net and as an advocate.

Applications

Despite some specific needs and skills required in the field of forensic social work, a generalist approach is critical to a more responsive social work approach towards the target group of offenders.
Rheological response and quasi-static stab resistance of STF/MWCNTs-impregnated aramid fabrics with different textures
Authors: Li Ting-Ting , Cen Xixi , Peng Haokai , Ren Haitao , Han Lianhe , Lou Ching-Wen , Lin Jia-Horng
Published: February 2019

Terrorist attacks occur constantly, which subsequently arouses awareness of self-protection. In order to alleviate the harm caused by sharp objects of knives and daggers, a design of flexible stab-resistant materials that are impregnated with the shear thickening fluid (STF)/multi-walled carbon nanotubes (MWCNTs) system and different texture of fabrics is presented. STF/MWCNTs are composed of polyethylene glycol (PEG 200) as the dispersion medium and silica (SiO2) of 12 nm and 75 nm as disperse phase as well as MWCNTs as supplementary reinforcement, in expectation to provide the aramid fabrics with high strengths, low critical shear rate, and a short thickening response time. The textures of aramid fabrics—plain (P), twill (T), satin (S), or basket (B) weave—are saturated in the STF/MWCNTs system. The synergetic influences of silica size and texture on tensile strength, quasi-static knife, and spike stab resistances of the STF/MWCNTs-impregnated aramid fabrics are examined. Results show that the plain aramid fabric immersed in the STF/MWCNTs system containing 12 nm SiO2(SM12) exhibit the maximum tensile strength and quasi-static knife stab resistance, 14.7 MPa and 8.9 MPa, respectively, which is 1.15 and 1.43 times higher than pure aramid fabrics. Moreover, the basket-weave aramid fabric immersed in the STF/MWCNTs system containing 12 nm SiO2have the maximum quasi-static spike stab resistance of 17.12 MPa compared to other textures of fabrics, which is 1.05 times higher than those immersed in the 75 nm SiO2STF/MWCNTs (SM75) system and 1.33 times higher than that of pure basket aramid fabrics.
Surface hydrophilizing modification of polytetrafluoroethylene/glass fiber fabric through oxidant-induced polydopamine deposition
Authors: Zhou Yanfen , Jiang Liang , Jiang Zhiqing , Chen Shaojuan , Ma Jianwei
Published: February 2019

This paper reports surface hydrophilizing modification of polytetrafluoroethylene/glass fiber fabric by employing bio-inspired polydopamine functionalization. The modification process was accelerated by introducing sodium periodate (NaIO4) as oxidant. Surface morphology and chemical composition of the modified polytetrafluoroethylene/glass fiber fabric were characterized by using scanning electron microscopy, atomic force microscopy (AFM), and Fourier transform infrared spectroscopy, respectively. Hydrophilicity of the polytetrafluoroethylene/glass fiber fabric was investigated through water contact angle measurement. It was found that polydopamine successfully deposited on the surface of polytetrafluoroethylene/glass fiber fabric and the uniformity of the polydopamine coating increased with increasing modification time. Water contact angle of polytetrafluoroethylene/glass fiber fabric decreased after polydopamine modification and reached 29° when the sample was treated for 120 min, indicating an improved hydrophilic performance. The formed polydopamine coating was also demonstrated to have reliable chemical and mechanical stability.
Choline transport for phospholipid synthesis: An emerging role of choline transporter-like protein 1
Authors: Hedtke Vera , Bakovic Marica
Published: February 2019

This review provides a summary of recent discoveries in choline transport and the proteins mediating it with a specific focus on the choline transporter-like proteins (CTL)/solute carriers 44 A (SLC44A) and their role in phospholipid metabolism. Since its initial cloning, particularly, the CTL1/SLC44A1 transporter has been investigated further and its ubiquitous expression characterized in various cells and tissues of mouse, rat, and human origin. We describe the role of this choline transporter both in the plasma membrane and in the mitochondria and summarize novel aspects of choline transport regulation in the muscle, nervous system, and cancer.

Impact statement

This review will provide a summary of recent advances in choline transport research and highlight important novel areas of focus in the field.
Re(de)fining College Access and Its Association With Divergent Forms of Financial Aid: A Proposed Conceptual and Analytic Framework
Authors: González Canché Manuel S.
Published: February 2019

This manuscript proposes a conceptual framework to reconceptualize college access at the state level, while accounting for the heterogeneous impact different forms of financial aid have on access across sectors and levels. The use of this framework may strengthen our understanding of the relationship between aid and access by accounting for more than one form of financial aid, considering recent and nonrecent high school graduates (NRHGs) and modeling the potential impact of aid on access across sectors.
Strength distribution superiority of compact-Siro spun yarn
Authors: Lu Yuzheng , Wang Yang , Gao Weidong
Published: February 2019

This study examined the superiority of the strength of compact-Siro spun yarn. First, the strength properties of four types of yarn—ring, compact, Siro, and compact-Siro spun yarn—were compared based on an experiment with 9.7 tex and 14.6 tex polyester yarns. Yarn unevenness and compactness were analyzed in terms of their influence on yarn strength. It was determined that compact spinning enhanced the strength distribution by improving the overall yarn compactness. Siro spinning significantly increased the minimum yarn strength by reducing unevenness. Furthermore, compact-Siro spun yarn, which incorporates the advantages of both compact and Siro, remarkably improved the yarn strength distribution. These results were verified in the first part of the experiment. Finally, the four types of yarn were applied in the same weaving process. The results indicated that the efficiency of weaving with compact-Siro pure polyester yarn was higher than that of other methods by 3%–6%, thereby confirming the superior productivity of the method.
Abrasion resistance of textiles: Gaining insight into the damaging mechanisms of different test procedures
Authors: Textor Torsten , Derksen Leonie , Bahners Thomas , Gutmann Jochen S , Mayer-Gall Thomas
Published: February 2019

Three established test methods employed for evaluating the abrasion or wear resistance of textile materials were compared to gain deeper insight into the specific damaging mechanisms to better understand a possible comparability of the results of the different tests. The knowledge of these mechanisms is necessary for a systematic development of finishing agents improving the wear resistance of textiles. Martindale, Schopper, and Einlehner tests were used to analyze two different fabrics made of natural (cotton) or synthetic (polyethylene terephthalate) fibers, respectively. Samples were investigated by digital microscopy and scanning electron microscopy to visualize the damage. Damage symptoms are compared and discussed with respect to differences in the damaging mechanisms.
Experience of nail bed injuries at a tertiary hand trauma unit: a 12-month review and cost analysis
Authors: Yildirimer Lara , Brewster Colin T , Aziz Hina , Unluer Zeynep , Jemec Barbara , De Leo Anna
Published: February 2019

The aim of this study was to analyse the management of nail bed injuries from a clinical and economic perspective. We carried out a retrospective analysis of nail bed injuries treated operatively at a tertiary Plastic Surgery Hand Trauma Unit during 2016. The National Schedule of Reference Costs (2015–2016) was used to estimate the costs of treating 630 patients. The most common mechanism was a crush injury in a door (33%). Fifty-five per cent of patients had an associated tuft fracture. The minimum cost per annum for patients treated for nail bed injuries in our unit was calculated to be £511,560 (€573,362; US$666,664). Many nail bed injuries are preventable and because they present a very high financial burden on the National Health Service, targeted prevention strategies should be considered.

Level of evidence: IV
Mozobil® (Plerixafor, AMD3100), 10 years after its approval by the US Food and Drug Administration
Authors: De Clercq Erik
Published: February 2019

AMD3100 (plerixafor, Mozobil®) was first identified as an anti-HIV agent specifically active against the T4-lymphotropic HIV strains, as it selectively blocked the CXCR4 receptor. Through interference with the interaction of CXCR4 with its natural ligand, SDF-1 (also named CXCL12), it also mobilized the CD34+stem cells from the bone marrow into the peripheral blood stream. In December 2008, AMD3100 was formally approved by the US FDA for autologous transplantation in patients with Non-Hodgkin’s Lymphoma or multiple myeloma. It may be beneficially used in various other malignant diseases as well as hereditary immunological disorders such as WHIM syndrome, and physiopathological processes such as hepatopulmonary syndrome.
Economics of gastroenteropancreatic neuroendocrine tumors: a systematic review
Authors: Grande Enrique , Díaz Ángel , López Carlos , Munarriz Javier , Reina Juan-José , Vera Ruth , Bernárdez Beatriz , Aller Javier , Capdevila Jaume , Garcia-Carbonero Rocio , Jimenez Fonseca Paula , Trapero-Bertran Marta
Published: February 2019

Background:

Despite current interest, enthusiasm and progress in the development of therapies for gastroenteropancreatic (GEP) neuroendocrine tumors (NETs), there are substantial gaps in the published literature regarding cost-of-illness analyses, economic evaluation and budget impact analyses. Compounding the issue is that data on resource utilization and cost-effectiveness of different diagnostic and therapeutic modalities for GEP-NETs are scarce.

Methods:

A systematic review on the economic impact of GEP-NETs was carried out using four databases: EMBASE, PubMed, the National Health Service Economic Evaluation Database and Cochrane review. Fully published articles from January 2000 to May 2017, in English and Spanish, were included. All articles that satisfied the inclusion criteria were included in the systematic review; summary descriptive statistics were used to describe the methodological characteristics.

Results:

The 14 studies selected included cost-of-illness analyses ( n = 4), economic evaluations ( n = 7) and budget impact analyses ( n = 3). Almost all studies were performed in the United States. Healthcare costs for patients with NETs included medication, outpatient visits, hospitalizations, and check-ups/tests. Reducing adverse events is an area where cost savings could be achieved; however, there was not enough evidence on the cost impact of adverse events.

Conclusion:

There is a lack of data related to resource utilization in the field of GEP-NETs. Therefore, cost-effectiveness and budget impact studies of existing and emerging treatments are urgently needed to help the decision-making process for patients with NETs.
London calling Gaza: The role of international collaborations in the globalisation of postgraduate burn care education
Authors: Theodorakopoulou Evgenia , Goutos Ioannis , Mason Katrina , Ghanem Ali M , Myers Simon
Published: February 2019

Burn injuries represent a significant epidemiological problem, with the vast majority occurring in low- to middle-income countries. These regions also represent areas where lack of socioeconomic growth and geopolitical instability pose additional barriers not only to healthcare provision but also to the acquisition of continuing professional development. Long-distance, web-based learning programmes (‘tele-education’) have been identified as a successful and powerful means of propagating up-to-date medical education and training in poor-resource, isolated or conflict-ridden regions.

This report evaluates the role of tele-education in delivering a distance-learning Master’s degree in Burn Care to a group of 11 healthcare professionals working in the occupied Palestinian territories (OPT), which was funded as part of a collaboration between Queen Mary University of London and IMET-Pal (International Medical Education Trust – Palestine).

We present our experience in delivering the programme in a conflict-ridden part of the world, which includes the specific adaptations to tailor the programme to regional needs as well the unique challenges faced by students and faculty in enhancing the educational value of this unique initiative.

The academic achievements of this group of healthcare professionals were found to be comparable to historical student cohorts from privileged socioeconomic backgrounds and the majority of students felt that participation in the programme contributed to a direct improvement to their daily burn care practices.

The successful outcomes achieved by our students support the constantly emerging evidence that targeted, well-delivered, long-distance learning programmes can become powerful tools in combating inequalities in global healthcare and health education.
A bizarre parosteal osteochondromatous proliferation at the sesamoid bone of the hallux: A case report
Authors: Takeda Shinsuke , Nishimura Akinobu , Nakazora Shigeto , Sudo Akihiro , Hirata Hitoshi , Kato Ko
Published: February 2019

A bizarre parosteal osteochondromatous proliferation (BPOP) is a rare, benign, osseous tumor that presents as an exophytic cortical growth consisting of bone, cartilage, and fibrous tissue. However, the identification of BPOP by preoperative imaging along with appropriate diagnosis and treatment without recurrence is challenging, particularly for BPOPs that rarely develop in certain parts of the body. Herein, we report a rare case involving a BPOP at the sesamoid bone of the hallux that was first suspected on preoperative computed tomography imaging. There has been no recurrence 3 years after surgical resection.
Biomechanical Differences Between Japanese and American Professional Baseball Pitchers
Authors: Oi Takanori , Yoshiya Shinichi , Slowik Jon , Diffendaffer Alek , Takagi Yohei , Tanaka Hiroshi , Nobuhara Katsuya , Fleisig Glenn S.
Published: February 2019

Background:

Although baseball injuries are common in both Japan and the United States, the majority of pitching injuries in Japanese players occur at the shoulder, whereas most pitching injuries in American players occur at the elbow. A biomechanical comparison between Japanese and American pitchers may help to identify the different injury mechanisms.

Hypothesis:

Japanese pitchers produce greater shoulder kinetics whereas American pitchers generate greater elbow kinetics. Also, kinematic differences will be found between the 2 groups, including longer stride and greater lead knee flexion for Japanese pitchers.

Study Design:

Descriptive laboratory study.

Methods:

Biomechanical data for 19 Japanese professional baseball pitchers and an age-matched group of 19 American professional baseball pitchers were collected by use of a 3-dimensional, automated, high-speed optical motion capture system. Anthropometric, kinetic, and kinematic data for both groups were compared by use of t tests ( P < .05).

Results:

American pitchers were taller and heavier and generated greater ball velocity (38.1 ± 1.6 vs 34.7 ± 1.1 m/s; P < .001) than their Japanese counterparts. Most elbow and shoulder kinetic parameters, including elbow varus torque (99 ± 17 vs 86 ± 17 N·m; P = .018), were greater for American pitchers. However, when normalized by bodyweight and height, shoulder horizontal adduction torque was greater for Japanese pitchers (6.8% ± 1.0% vs 5.8% ± 1.1%; P = .005). Japanese pitchers had longer stride (86% ± 5% vs 82% ± 6% of height; P = .023), greater shoulder abduction at ball release (101° ± 8° vs 94° ± 9°; P = .014), and greater knee flexion after ball release (39° ± 18° vs 28° ± 14°; P = .039). Japanese pitchers also demonstrated greater shoulder internal rotation velocity, elbow flexion, and elbow extension velocity.

Conclusion:

Greater elbow varus torque may predispose American pitchers to greater risk of elbow injury. Japanese pitchers may have increased risk of shoulder injury due to greater normalized horizontal adduction torque and greater abduction angle. Japanese pitchers may be able to reduce their shoulder torque and risk of injury by shortening their stride, reducing their lead knee flexion, and decreasing their throwing arm abduction.

Clinical Relevance:

Understanding anthropometric, kinetic, and kinematic differences between pitchers from the 2 countries may be of value to clinicians and coaches working to maximize performance of the pitchers while minimizing the risk of injury.
The Link Between a Set of Tangram-Based Tasks and Chinese and English Reading and Related Skills Among Chinese Kindergarteners
Authors: Wong Simpson W. L. , Cheng Rebecca Wing-yi , Chow Bonnie Wing-Yin , Chung Sandrine Man-Chi
Published: February 2019

Learning to read two scripts at a young age is a demanding task. This study aims to develop games for building fundamental code-related emergent literacy skills among biscriptal preschoolers. We developed five games and tested them on a sample of 102 Chinese kindergarteners. The participants were aged 4 to 5 years and were learning English as a second language. The children’s reading skills were measured with a battery of literacy tests as well as estimated by their teachers using a literacy-related behavior checklist. Correlational analysis revealed that the performances of the children in the tangram games were significantly correlated with teachers’ ratings and children’s Raven’s IQ. Further regression analysis confirmed that the tangram hand-copying game predicted unique variances for visual-orthographic skills and word identification abilities in Chinese and English. This study provides valuable evidence regarding the application of tangram games for assessing code-related emergent literacy skills in the visual domain.
A Pilot Study on Histopathology of the Jejunoileal Atresia—Can it Be Used as a Guide to Determine the Length of Adequate Resection?
Authors: Pandey Anand , Singh Abhishek , Agarwal Preeti , Gupta Archika , Rawat Jiledar , Kureel Shiv Narain
Published: February 2019

Introduction:

Some studies reported that there is abnormality in the histopathology of atretic bowel in jejunoileal atresia (JIA). We have made an attempt to assess sequential histopathologic changes in the resected atretic segment.

Material and methods:

The histopathology of the resected segment was evaluated at 1, 3, 5, 7, 9, and 11 cm from atretic end (Sections A to F, respectively). The ratio of inner and outer muscle layer (measured by NIS-Element D software) was calculated at every section. Immunohistochemistry for α-smooth muscle actin (α-SMA) was also done. The findings were compared with control.

Results:

In control set (n = 5), the ratio of inner and outer muscle layer was 1.03. In patients with JIA, the ratio was 0.68 to 0.9 at section A. This ratio varied at various sections in all specimens. In section F, this ratio was 0.95 to 1.09, which is close to control ratio. There were no specific findings related to α-SMA staining.

Conclusions:

It appears that the bowel proximal to the atresia is abnormal for a varied length. It may be a possibility that this abnormality is present at least up to about 10 cm proximal to atresia. Adequate resection is important for optimal outcome.
Genetic drivers of oncogenic pathways in molecular subgroups of peripheral T-cell lymphoma
Authors: Heavican Tayla B. , Bouska Alyssa , Yu Jiayu , Lone Waseem , Amador Catalina , Gong Qiang , Zhang Weiwei , Li Yuping , Dave Bhavana J. , Nairismägi Maarja-Liisa , Greiner Timothy C. , Vose Julie , Weisenburger Dennis D. , Lachel Cynthia , Wang Chao , Fu Kai , Stevens Jadd M. , Lim Soon Thye , Ong Choon Kiat , Gascoyne Randy D. , Missiaglia Edoardo , Lemonnier Francois , Haioun Corinne , Hartmann Sylvia , Pedersen Martin Bjerregård , Laginestra Maria Antonella , Wilcox Ryan A. , Teh Bin Tean , Yoshida Noriaki , Ohshima Koichi , Seto Masao , Rosenwald Andreas , Ott German , Campo Elias , Rimsza Lisa M. , Jaffe Elaine S. , Braziel Rita M. , d’Amore Francesco , Inghirami Giorgio , Bertoni Francesco , de Leval Laurence , Gaulard Philippe , Staudt Louis M. , McKeithan Timothy W. , Pileri Stefano , Chan Wing C. , Iqbal Javeed
Published: February 2019

Peripheral T-cell lymphoma (PTCL) is a group of complex clinicopathological entities, often associated with an aggressive clinical course. Angioimmunoblastic T-cell lymphoma (AITL) and PTCL-not otherwise specified (PTCL-NOS) are the 2 most frequent categories, accounting for >50% of PTCLs. Gene expression profiling (GEP) defined molecular signatures for AITL and delineated biological and prognostic subgroups within PTCL-NOS (PTCL-GATA3 and PTCL-TBX21). Genomic copy number (CN) analysis and targeted sequencing of these molecular subgroups revealed unique CN abnormalities (CNAs) and oncogenic pathways, indicating distinct oncogenic evolution. PTCL-GATA3 exhibited greater genomic complexity that was characterized by frequent loss or mutation of tumor suppressor genes targeting the CDKN2A/B-TP53 axis and PTEN-PI3K pathways. Co-occurring gains/amplifications of STAT3 and MYC occurred in PTCL-GATA3. Several CNAs, in particular loss of CDKN2A, exhibited prognostic significance in PTCL-NOS as a single entity and in the PTCL-GATA3 subgroup. The PTCL-TBX21 subgroup had fewer CNAs, primarily targeting cytotoxic effector genes, and was enriched in mutations of genes regulating DNA methylation. CNAs affecting metabolic processes regulating RNA/protein degradation and T-cell receptor signaling were common in both subgroups. AITL showed lower genomic complexity compared with other PTCL entities, with frequent co-occurring gains of chromosome 5 (chr5) and chr21 that were significantly associated with IDH2R172 mutation. CN losses were enriched in genes regulating PI3K–AKT–mTOR signaling in cases without IDH2 mutation. Overall, we demonstrated that novel GEP-defined PTCL subgroups likely evolve by distinct genetic pathways and provided biological rationale for therapies that may be investigated in future clinical trials.
The response to lymphodepletion impacts PFS in patients with aggressive non-Hodgkin lymphoma treated with CD19 CAR T cells
Authors: Hirayama Alexandre V. , Gauthier Jordan , Hay Kevin A. , Voutsinas Jenna M. , Wu Qian , Gooley Ted , Li Daniel , Cherian Sindhu , Chen Xueyan , Pender Barbara S. , Hawkins Reed M. , Vakil Aesha , Steinmetz Rachel N. , Acharya Utkarsh H. , Cassaday Ryan D. , Chapuis Aude G. , Dhawale Tejaswini M. , Hendrie Paul C. , Kiem Hans-Peter , Lynch Ryan C. , Ramos Jorge , Shadman Mazyar , Till Brian G. , Riddell Stanley R. , Maloney David G. , Turtle Cameron J.
Published: February 2019

Factors associated with durable remission after CD19 chimeric antigen receptor (CAR)-modified T-cell immunotherapy for aggressive B-cell non-Hodgkin lymphoma (NHL) have not been identified. We report multivariable analyses of factors affecting response and progression-free survival (PFS) in patients with aggressive NHL treated with cyclophosphamide and fludarabine lymphodepletion followed by 2 × 106 CD19-directed CAR T cells/kg. The best overall response rate was 51%, with 40% of patients achieving complete remission. The median PFS of patients with aggressive NHL who achieved complete remission was 20.0 months (median follow-up, 26.9 months). Multivariable analysis of clinical and treatment characteristics, serum biomarkers, and CAR T-cell manufacturing and pharmacokinetic data showed that a lower pre-lymphodepletion serum lactate dehydrogenase (LDH) level and a favorable cytokine profile, defined as serum day 0 monocyte chemoattractant protein-1 (MCP-1) and peak interleukin-7 (IL-7) concentrations above the median, were associated with better PFS. MCP-1 and IL-7 concentrations increased after lymphodepletion, and higher intensity of cyclophosphamide and fludarabine lymphodepletion was associated with higher probability of a favorable cytokine profile. PFS was superior in patients who received high-intensity lymphodepletion and achieved a favorable cytokine profile compared with those who received the same intensity of lymphodepletion without achieving a favorable cytokine profile. Even in high-risk patients with pre-lymphodepletion serum LDH levels above normal, a favorable cytokine profile after lymphodepletion was associated with a low risk of a PFS event. Strategies to augment the cytokine response to lymphodepletion could be tested in future studies of CD19 CAR T-cell immunotherapy for aggressive B-cell NHL. This trial was registered at www.clinicaltrials.gov as #NCT01865617.
НЕКОТОРЫЕ ОСОБЕННОСТИ РЕГУЛИРОВАНИЯ СОЦИАЛЬНЫХ КОНФЛИКТОВ У КАБАРДИНЦЕВ И БАЛКАРЦЕВ В 1870–1917 гг.
Authors: Abazov Alexei Hasanovich
Published: February 2019

Цель. В статье на материалах Нальчикского горского словесного суда исследуются формы социальных конфликтов у кабардинцев и балкарцев в 1870–1917 гг. Социальные конфликты дифференцированы в зависимости от сферы общественной жизни, морально-этических и ценностных ориентиров, количества участников, уровня социальной иерархии и степени социальной напряженности. Автор ставит целью раскрыть особенности социальных конфликтов у кабардинцев и балкарцев в 1870–1917 гг. на примере споров, разбираемых горским словесным судом Нальчикского округа Терской области.Методы. Методологическая база статьи основана на принципах и методах исторических исследований. В ходе работы применялись принципы научности, объективности, историзма, системности. Кроме того, использовались структурно-функциональный, социально-правовой, социокультурный и аксиологический методы познания права. Статья подготовлена на основе материалов Центрального государственного архива Кабардино-Балкарской Республики (ф. И-22 «Нальчикский горский словесный суд»).Результаты. В ходе исследования рассмотрены конфликты, связанные с умешенными и неумышленными убийствами, причинением ран и телесных повреждений (в том числе и повлекших утрату трудоспособности потерпевшим), «умыканием» (кражей) невесты, кражей скота и т.п. Установлено, что в деятельности суда доминировали экономические конфликты (споры, связанные с наследством, имущественные вопросы, связанные с опекой и попечительством, пользованием земельными участками и т.п.). Отмечается, что значительное количество конфликтов были двусторонними (большинство из них – материальные компенсации за украденный скот). Главной причиной двусторонних конфликтов было нарушение имущественных прав сторон. Делается вывод, что деятельность Нальчикского горского словесного судов была направлена в основном на урегулирование двусторонних межличностных экономических конфликтов у кабардинцев и балкарцев.Область применения результатов. Результаты данного исследования могут быть использованы в образовательном процессе и научно-исследовательской деятельности, касающейся вопросов изучения истории суда и судебных учреждений северокавказского региона, и исторического опыта применения традиционных миротворческих практик в условиях интеграции в политико-правовое пространство Российской империи в последней трети XIX – начале ХХ в.
ЛИЧНОСТНЫЕ МОТИВЫ РЕАЛИЗАЦИИ СОЦИАЛЬНОГО ОБРАЗОВАНИЯ В МОЛОДЕЖНОЙ СРЕДЕ
Authors: Reshetnikova Ekaterina Vladimirovna
Published: February 2019

В статье рассматривается специфика развития личностных мотивов современной молодёжи в участии в различных проектах социального образования. Обозначается разрыв между идеальными ценностями и идеалами социального образования, декларируемыми в образовательных стандартах и официальных документах и реальными рационально-практическими стратегиями молодых людей, рассчитывающих получить определенные выгоды от участия в тех или иных социальных проектах, выстроить социальную карьеру в виде социального лифта или приобрести новые знакомства и связи для преумножения социального капитала. В работе используются материалы опроса, проведенного среди молодежи 18–23 лет в разных городах России, в количестве 2400 человек, а также приводятся данные контент-анализа СМИ (газеты «Аргументы и Факты», «Московский комсомолец») и социальных сетей (VK, Fasebook, Инстаграмм), показывающих динамику общественного звучания социального образования, изменение смыслов, целей и задачи, инструментов его получения, как на формальном уровне (официальные публикации в СМИ с 2000 по 2018 годы), так и на неофициальном уровне (информирование об участии в том или ином социальном проекте у себя на странице в различных социальных сетях). Это также выявило общие черты конструирования общественного дискурса – через официальные публикации, формирующие отношение к социальному образованию и личные страницы в социальных сетях; индивидуально показать личную вовлеченность и включенность в определенные сообщества, наличие значимых социальных контактов и связей, конструирующих социальный капитал молодого человека, его возможные дальнейшие жизненные траектории и стратегии построения социальных лифтов. На сегодняшний день, мы констатируем наличие несогласованности официального и неформального дискурса получения социального образования, но прагматизм и рациональное осмысление перспектив этого вида деятельности дает надежду на конструктивное соединение и воплощение на практике в прикладных и универсальных программах обучения механизмам социального образования молодых людей в вузах страны. Примером тому могут служить различные формы дополнительного образования, с получением удостоверений государственного образца о социальном образовании или приложение к диплому в виде свидетельства государственного образца, выдаваемого вузами для лиц прошедших подготовку в рамках социального образования.
Treatment of early onset spinal deformities with magnetically controlled growing rods: A single centre experience of 30 cases
Authors: Studer D. , Heidt C. , Büchler P. , Hasler C. C.
Published: February 2019

Purpose

The treatment of early onset scoliosis continues to be a major challenge, even when using motorized growth-sparing implants. We report on 30 cases operated on with magnetically controlled growing rods (MCGRs) at our institution, analyzing radiological parameters and complications, comparing our results with the literature and presenting a special implant fixation technique. A separate focus highlights the challenges of conversion from previous non-motorized implants.

Methods

Consecutive case series. The nature and effects of complications were recorded for all patients. Radiographic evaluations were performed for patients with a minimum follow-up of two years. Separate analyses were carried out for patients who were previously treated with non-motorized growth-sparing implants

Results

There were 12 documented complications in 11/30 (37%) patients leading to 13 unplanned returns to the operating room. In all, 18/30 patients had a minimum follow-up of two years. Major curve and main kyphosis, as well as T1 to T12 and T1 to S1 distances significantly improved with MCGR implantation, however, less in patients converted from previous growth-sparing surgical treatment. While the achieved correction of the major curve was maintained, there was a loss of kyphosis correction with subsequent implant lengthening. Gain in implant length decreased with increasing number of extensions.

Conclusion

Despite improved patient's comfort, MCGR show a considerable complication rate. Coronal plane deformities can be well controlled, but diminished implant lengthening is already apparent within two years after MCGR implantation. Central databases should help to clarify unresolved aspects and optimize the treatment of these young patients.

Level of Evidence

IV
A Comprehensive LC-QTOF-MS Metabolic Phenotyping Strategy: Application to Alkaptonuria
Authors: Norman Brendan P , Davison Andrew S , Ross Gordon A , Milan Anna M , Hughes Andrew T , Sutherland Hazel , Jarvis Jonathan C , Roberts Norman B , Gallagher James A , Ranganath Lakshminarayan R
Published: February 2019

BACKGROUND

Identification of unknown chemical entities is a major challenge in metabolomics. To address this challenge, we developed a comprehensive targeted profiling strategy, combining 3 complementary liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) techniques and in-house accurate mass retention time (AMRT) databases established from commercial standards. This strategy was used to evaluate the effect of nitisinone on the urinary metabolome of patients and mice with alkaptonuria (AKU). Because hypertyrosinemia is a known consequence of nitisinone therapy, we investigated the wider metabolic consequences beyond hypertyrosinemia.

METHODS

A total of 619 standards (molecular weight, 45–1354 Da) covering a range of primary metabolic pathways were analyzed using 3 liquid chromatography methods—2 reversed phase and 1 normal phase—coupled to QTOF-MS. Separate AMRT databases were generated for the 3 methods, comprising chemical name, formula, theoretical accurate mass, and measured retention time. Databases were used to identify chemical entities acquired from nontargeted analysis of AKU urine: match window theoretical accurate mass ±10 ppm and retention time ±0.3 min.

RESULTS

Application of the AMRT databases to data acquired from analysis of urine from 25 patients with AKU (pretreatment and after 3, 12, and 24 months on nitisinone) and 18 HGD−/− mice (pretreatment and after 1 week on nitisinone) revealed 31 previously unreported statistically significant changes in metabolite patterns and abundance, indicating alterations to tyrosine, tryptophan, and purine metabolism after nitisinone administration.

CONCLUSIONS

The comprehensive targeted profiling strategy described here has the potential of enabling discovery of novel pathways associated with pathogenesis and management of AKU.
Populism, art and the city: An interdisciplinary pedagogy for our time
Authors: Marino Angela , Luger Jason
Published: February 2019

Populism on the far left and the far right is reshaping the contemporary city and the urban condition. In this special short-form section, we put forward populism, art and the city as a linked theoretical and methodological framework through the UC Berkeley Global Urban Humanities Initiative. Our conversations brought together new research in urban studies, art, architecture, public policy, and performance studies into what many people described as a decidedly populist age. Following a short introduction, we share a collection of four papers from such conversations that offer ‘focus sites’ from San Francisco to Palm Springs, Hong Kong to Mexico City, with a diverse set of theoretical proposals that branch from our discussions and shared readings in art, populism, and the city.
The Effect of Citicoline Injections on Children with Organic Brain Syndrome Caused by Infection
Authors: Warsiki Endang
Published: February 2019

Forty children with organic brain syndrome caused by injections were given Citicoline intramuscular injections. Twenty of these children were within 3 months postencephalitis, the other 20 children were over 3 months postencephalitis. There were statistically significant negative correlations between the length of time from recovery from encephalitis to the initiation of administration of CDP choline and the improvement of many of the symptoms of OJ'8anic brain syndrome. In other words, these patients who began receiving Citicoline (CDP choline) within 3 months showed greater improvement than those who began receiving CDP choline over 3 months after recoveries from encephalitis.
Risk factors of stunting in children aged 24-59 months
Authors: Manggala Arya Krisna , Kenwa Komang Wiswa Mitra , Kenwa Made Me Lina , Sakti Anak Agung Gede Dwinaldo Putra Jaya , Sawitri Anak Agung Sagung
Published: February 2019

Abstract

Background Childhood stunting (low height-for-age) still remains a global health problem because it increases the risk of disturbances in growth and development as well as mortality. The prevalence of stunting in Bali is 32.5%, with the highest in Gianyar District at 41%. However, little is known about the risk factors of stunting children in Gianyar.

Objective  To investigate the risk factors of stunting in children aged 24-59 months in Gianyar.

Methods  This cross-sectional study involved 166 children, collected consecutively, aged 24-59 months, who visited the integrated health posts in 13 community health centers in Gianyar District, Bali from September to November 2016. Stunting is defined as -2SD below the WHO height-for-age z-score (HAZ), according to sex. Statistical analyses were done with Chi-square and multivariate logistic regression tests.

Results Of 166 subjects, 37 (22.3%) children were stunted. Multivariate analysis revealed that low paternal education (AOR 2.88; 95%CI 1.10 to 7.55; P=0.031), maternal height less than 150 cm (AOR 7.64; 95%CI 2.03 to 28.74; P=0.003), high risk maternal age (AOR 4.24; 95%CI 1.56 to 11.49; P= 0.005), low birth weight (AOR 5.09; 95%CI 1.03 to 25.31; P=0.047), and low birth length (AOR 9.92; 95%CI 1.84 to 53.51; P=0.008) were strongly associated with stunting.

Conclusion  Risk factors for stunting in children are low paternal education, maternal height less than 150 cm, high risk maternal age, low birth weight, and low birth length.
Liver iron overload and hepatic function in children with thalassemia major
Authors: Wahidiyat Pustika Amalia , Iskandar Stephen Diah , Rahmartani Ludi Dhyani , Sekarsari Damayanti
Published: February 2019

Background Routine blood transfusions and increased intestinal iron absorption lead to iron accumulation in various organs, especially the liver. To date, T2-star magnetic resonance imaging (T2*MRI) is a valuable tool to evaluate iron level in organs.

Objective To assess the degree of liver iron overload among children with thalassemia major (TM) and its possible correlations with hepatic function laboratory values.

Methods This cross-sectional study was conducted in Cipto Mangunkusumo Hospital. The degree of liver iron overload was evaluated by T2*MRI. Assessments of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, and bilirubin levels were done to evaluate liver function.

Results A total of 291 TM children were included in this study. The mean age of subjects was 12 years. Most of the subjects were diagnosed as β-thalassemia homozygote (54.6%) and β-thalassemia/HbE (41.2%). Deferiprone (DFP) was the most commonly used iron chelator. Less than 10% of the subjects had normal liver iron deposition. The AST and ALT values increased proportionally with the severity of liver iron overload, with significant, moderately negative correlation coefficients (r=-0.388 and -0.434, respectively). However, albumin level decreased proportionally with the severity of liver iron overload, with a significant, moderately positive correlation coefficient (r=0.323). Liver T2* MRI had no significant correlations with direct, indirect, and ratio of direct/total bilirubin levels.

Conclusion Most of the children with TM have mild to severe liver iron overload. Liver T2* MRI had significant, moderate correlations with AST, ALT, and albumin values. Bilirubin level has no correlation with T2* MRI. Our findings suggest that monitoring of AST, ALT, and albumin levels is important because they may reflect the severity of liver iron overload. However, they should not be used as the only predictors of iron overload.