bluuebunny/crossref_metadata_2025 huggingface dataset:
MCAM abnormal expression and clinical outcome associations are highly cancer dependent as revealed through pan-cancer analysis
Authors: An Yunxia , Wei Nan , Cheng Xiangsong , Li Ying , Liu Haiyang , Wang Jia , Xu Zhiwei , Sun Zhifu , Zhang Xiaoju
Published: February 2019

MCAM (CD146) is a cell surface adhesion molecule that has been reported to promote cancer development, progression and metastasis and is considered as a potential tumor biomarker and therapeutic target. However, inconsistent reports exist, and its clinical value is yet to be confirmed. Here we took advantage of several large genomic data collections (Genotype-Tissue Expression, The Cancer Genome Atlas and Cancer Cell Line Encyclopedia) and comprehensively analyzed MCAM expression in thousands of normal and cancer samples and cell lines along with their clinical phenotypes and drug response information. Our results show that MCAM is very highly expressed in large vessel tissues while majority of tissues have low or minimal expression. Its expression is dramatically increased in a few tumors but significantly decreased in most other tumors relative to their pairing normal tissues. Increased MCAM expression is associated with a higher tumor stage and worse patient survival for some less common tumors but not for major ones. Higher MCAM expression in primary tumors may be complicated by tumor-associated or normal stromal blood vessels yet its significance may differ from the one from cancer cells. MCAM expression is weakly associated with the response to a few small molecular drugs and the association with targeted anti-BRAF agents suggests its involvement in that pathway which warrants further investigation.
Identifiability and estimation of structural vector autoregressive models for subsampled and mixed-frequency time series
Authors: Tank A , Fox E B , Shojaie A
Published: February 2019

Causal inference in multivariate time series is challenging because the sampling rate may not be as fast as the time scale of the causal interactions, so the observed series is a subsampled version of the desired series. Furthermore, series may be observed at different sampling rates, yielding mixed-frequency series. To determine instantaneous and lagged effects between series at the causal scale, we take a model-based approach that relies on structural vector autoregressive models. We present a unifying framework for parameter identifiability and estimation under subsampling and mixed frequencies when the noise, or shocks, is non-Gaussian. By studying the structural case, we develop identifiability and estimation methods for the causal structure of lagged and instantaneous effects at the desired time scale. We further derive an exact expectation-maximization algorithm for inference in both subsampled and mixed-frequency settings. We validate our approach in simulated scenarios and on a climate and an econometric dataset.
Initial Development of the Social Work Core Competency Inventory
Authors: Duan Wenjie , Guan Qiujie , Sheng Junrong , Qi Bo
Published: February 2019

The competency of social workers and social work students is pivotal. Using 931 social work undergraduates and social workers in China, the present study developed the Social Work Core Competency Inventory (SW-Core) to assess social work core competencies, and further examined its psychometric properties. This study comprised three phases. In the first phase, the ‘hierarchy competency model of social work’ was adopted as a framework to review the related literature. The six categories of competency and the corresponding item pool (fifty-five items) were constructed. In the second phase, six social work undergraduates, four Master of Social Work (MSW) students and ten social workers attended the semi-structural cognitive interviews. On the basis of their cognitive feedback and professional experience, eight core competencies were identified, and forty-seven items were retained. Finally, through exploratory factor analysis, a twenty-four-item eight-factor inventory was formulated among the first undergraduate sample (n = 315) that explained 75.87 per cent variances. The factor structure was further validated by a confirmatory factor analysis using the second undergraduate sample (n = 311). Results corroborated that the internal consistency of the eight subscales of the three samples ranged from 0.64 to 0.88. Furthermore, the multigroup confirmatory factor analysis indicated that the number of factors and factor loadings was invariant between genders, junior and senior students, and social work undergraduates and social workers. In sum, the twenty-four-item self-evaluative SW-Core was a valid measurement to assess the core competencies of social work. This also can be used as a tool to evaluate social work education in the future.
Radicalising Community Development within Social Work through Popular Education—A Participatory Action Research Project
Authors: Westoby Peter , Lathouras Athena , Shevellar Lynda
Published: February 2019

This article reports upon the efforts of three social work/social science academics in partnership with social and community practitioners, at radicalising community development (CD) within social work. The project was motivated by painful political events and processes unfolding around the world in 2017 and led to the design of a participatory action research approach with thirty-three practitioners. Engaging in several cycles of research (pre- and post questionnaires, observation, focus groups and interviews) and action learning (a popular education knowledge exchange day, a community of practice day and prototyping new projects) several new initiatives were implemented, including the formation of a new Popular Education Network. Reflections and discussion consider the implications of radicalising CD within social worker practice through combining education, organising and linking to progressive social movements. The article overall makes the case that popular education could be a crucial element in enabling the radicalisation of CD within social work.
Prognostic and predictive value of an autophagy-related signature for early relapse in stages I–III colon cancer
Authors: Mo Shaobo , Dai Weixing , Xiang Wenqiang , Li Yaqi , Feng Yang , Zhang Long , Li Qingguo , Cai Guoxiang
Published: February 2019

We postulated that expression differences of autophagy-related genes are instrumental in stratifying the risk of early relapse after surgery and evaluating the prognosis of patients with stages I–III colon cancer. Therefore, propensity score matching analysis was performed between patients in early relapse group and long-term survival group from GSE39582 test series and internal validation series. Using Cox regression model, a nine-autophagy-related signature (CAPN2, ATG16L2, TP63, SIRT1, RPS6KB1, PEX3, ATG5, UVRAG, NAF1) was established to classify patients into those at high risk of early relapse (high-risk group), and those at low risk of early relapse (low-risk group). Relapse-free survival (RFS) was significantly different between the two groups in test [hazard ratio (HR): 2.019, 95% confidence interval (CI): 1.362–2.992, P < 0.001], internal validation (HR: 2.464, 95% CI: 1.196–5.079, P < 0.001) and another two external validation series (GSE14333—HR: 2.250, 95% CI: 1.227–4.126, P = 0.007; GSE33113—HR: 5.552, 95% CI: 2.098–14.693, P < 0.001). Then, based on RFS, we developed a nomogram, integrating the nine-autophagy-related classifier and four clinicopathological risk factors to evaluate prognosis of stages I–III colon cancer patients. Time-dependent receiver operating curve at 2 years showed that the integrated signature (area under curve = 0.758) had better prognostic accuracy than American Joint Committee on Cancer TNM stage (area under curve = 0.620). In conclusion, we identified and built a nine-autophagy-related signature, a credible approach to early relapse prediction in stages I–III colon cancer patients, which can assist physicians in devising more efficient therapeutic strategies.
Risk of lung adenocarcinoma from smoking and radiation arises in distinct molecular pathways
Authors: Castelletti Noemi , Kaiser Jan Christian , Simonetto Cristoforo , Furukawa Kyoji , Küchenhoff Helmut , Stathopoulos Georgios T
Published: February 2019

KRAS mutations of lung adenocarcinoma (LADC) are associated with smoking but little is known on other exposure-oncogene associations. Hypothesizing that different inciting agents may cause different driver mutations, we aimed to identify distinct molecular pathways to LADC, applying two entirely different approaches. First, we examined clinicopathologic features and genomic signatures of environmental exposures in the large LADC Campbell data set. Second, we designed a molecular mechanistic risk model of LADC (M3LADC) that links environmental exposure to incidence risk by mathematically emulating the disease process. This model was applied to incidence data of Japanese atom-bomb survivors which contains information on radiation and smoking exposure. Grouping the clinical data by driver mutations revealed two main distinct molecular pathways to LADC: one unique to transmembrane receptor-mutant patients that displayed robust signatures of radiation exposure and one shared between submembrane transducer-mutant patients and patients with no evident driver mutation that carried the signature of smoking. Consistently, best fit of the incidence data was achieved with a M3LADC with two pathways: in one LADC risk increased with radiation exposure and in the other with cigarette consumption. We conclude there are two main molecular pathways to LADC associated with different environmental exposures. Future molecular measurements in lung cancer tissue of atom-bomb survivors may allow to further test quantitatively the M3LADC-predicted link of radiation to transmembrane receptor mutations. Moreover, the developed molecular mechanistic model showed that for low doses, as relevant e.g. for medical imaging, smokers have the same radiation risk compared with never smokers.
Friend or Foe: Cultural Fusion Theory and Media Coverage of Syrian Refugees in Turkey
Authors: Bilge Nurhayat
Published: February 2019

Using principles of Cultural Fusion Theory (Croucher & Kramer, 2017), this study focuses on representations of Syrian refugees in mainstream Turkish newspapers to determine: (a) how the host culture media portrays newcomers; and (b) what the implications of these portrayals are in terms of an effective cultural fusion between the two communities. The study entailed content analysis of five Turkish newspapers. A keyword search of the words Syrian (Suriyeli) and refugee (mülteci) were entered into the archives of these newspapers. The search yielded a total of 2,887 news articles and 373 commentary items. The results display the significance of Cultural Fusion Theory principles and challenges that exist to achieve effective cultural fusion.
“This is Not Who We Are:” Progressive Media and Post-Race in the New Era of Overt Racism
Authors: Bell Katherine M
Published: February 2019

This analysis explores how a liberal mainstream news outlet—MSNBC—grapples with the overt racism of the current right-wing populist presidential administration in the United States. With a plethora of “good” conservatives and its stable of liberal pundits, the cable network has painted the president as mentally ill or declining, an incompetent purveyor of chaos. In perpetuating a mantra of “this is not who we are” in coverage of overt racism, MSNBC pivots to a more comfortable mainstream space of post-race, an ideological stance that places racism as a fringe anomaly. The post-race pivot belies the country’s ongoing racist legacy, and potentially lulls viewers toward acceptance of official antiracisms that serve hegemonic interests. Thus, the news coverage of the current presidency plays a role in forestalling a meaningful reckoning with the country’s ongoing history of institutional and everyday racism.
Spatial Patterns of Brain Activity Preferentially Reflecting Transient Pain and Stimulus Intensity
Authors: Liang M , Su Q , Mouraux A , Iannetti G D
Published: February 2019

How pain emerges in the human brain remains an unresolved question. Neuroimaging studies have suggested that several brain areas subserve pain perception because their activation correlates with perceived pain intensity. However, painful stimuli are often intense and highly salient; therefore, using both intensity- and saliency-matched control stimuli is crucial to isolate pain-selective brain responses. Here, we used these intensity/saliency-matched painful and non-painful stimuli to test whether pain-selective information can be isolated in the functional magnetic resonance imaging responses elicited by painful stimuli. Using two independent datasets, multivariate pattern analysis was able to isolate features distinguishing the responses triggered by (1) intensity/saliency-matched painful versus non-painful stimuli, and (2) high versus low-intensity/saliency stimuli regardless of whether they elicit pain. This indicates that neural activity in the so-called “pain matrix” is functionally heterogeneous, and part of it carries information related to both painfulness and intensity/saliency. The response features distinguishing these aspects are spatially distributed and cannot be ascribed to specific brain structures.
Foxg1 Antagonizes Neocortical Stem Cell Progression to Astrogenesis
Authors: Falcone Carmen , Santo Manuela , Liuzzi Gabriele , Cannizzaro Noemi , Grudina Clara , Valencic Erica , Peruzzotti-Jametti Luca , Pluchino Stefano , Mallamaci Antonello
Published: February 2019

Neocortical astrogenesis follows neuronogenesis and precedes oligogenesis. Among key factors dictating its temporal articulation, there are progression rates of pallial stem cells (SCs) towards astroglial lineages as well as activation rates of astrocyte differentiation programs in response to extrinsic gliogenic cues. In this study, we showed that high Foxg1 SC expression antagonizes astrocyte generation, while stimulating SC self-renewal and committing SCs to neuronogenesis. We found that mechanisms underlying this activity are mainly cell autonomous and highly pleiotropic. They include a concerted downregulation of 4 key effectors channeling neural SCs to astroglial fates, as well as defective activation of core molecular machineries implementing astroglial differentiation programs. Next, we found that SC Foxg1 levels specifically decline during the neuronogenic-to-gliogenic transition, pointing to a pivotal Foxg1 role in temporal modulation of astrogenesis. Finally, we showed that Foxg1 inhibits astrogenesis from human neocortical precursors, suggesting that this is an evolutionarily ancient trait.
Foxg1 Directly Represses Dbx1 to Confine the POA and Subsequently Regulate Ventral Telencephalic Patterning
Authors: Du Ailing , Wu Xiaojing , Chen Hanhan , Bai Qing-Ran , Han Xiao , Liu Bin , Zhang Xiaohu , Ding Zhaoying , Shen Qin , Zhao Chunjie
Published: February 2019

During early development, signaling centers, such as the cortical hem and the preoptic area (POA), are critical for telencephalic patterning. However, the mechanisms underlying the maintenance of signal centers are poorly understood. Here, we report that the transcription factor Foxg1 is required to confine the POA, a resource of Sonic Hedgehog (Shh) that is pivotal for ventral telencephalic development. Cell-specific deletion of Foxg1 achieved by crossing Foxg1fl/fl with Dbx1-cre or Nestin-CreER combined with tamoxifen induction results in a dramatic expansion of the POA accompanied by the significantly increased activity of the Shh signaling pathway. Ventral pattern formation was severely impaired. Moreover, we demonstrated that Foxg1 directly represses Dbx1 to restrict the POA. Furthermore, we found that the ventral pallium was expanded, which might also contribute to the observed patterning defects. These findings will improve our understanding of the maintenance of signal centers and help to elucidate the mechanisms underlying ventral telencephalic patterning.
Premotor Cortex Provides a Substrate for the Temporal Transformation of Information During the Planning of Gait Modifications
Authors: Nakajima Toshi , Fortier-Lebel Nicolas , Drew Trevor
Published: February 2019

We tested the hypothesis that the premotor cortex (PMC) in the cat contributes to the planning and execution of visually guided gait modifications. We analyzed single unit activity from 136 cells localized within layer V of cytoarchitectonic areas 6iffu and that part of 4δ within the ventral bank of the cruciate sulcus while cats walked on a treadmill and stepped over an obstacle that advanced toward them. We found a rich variety of discharge patterns, ranging from limb-independent cells that discharged several steps in front of the obstacle to step-related cells that discharged either during steps over the obstacle or in the steps leading up to that step. We propose that this population of task-related cells within this region of the PMC contributes to the temporal evolution of a planning process that transforms global information of the presence of an obstacle into the precise spatio-temporal limb adjustment required to negotiate that obstacle.
The Western Sahara Cases before the Court of Justice of the European Union and International Law
Authors: Kahombo Balingene
Published: February 2019

This paper reviews the relevance of the Western Sahara cases brought before the Court of Justice of the European Union to international law. These cases relate to the contestations of the consistency of a number of economic agreements concluded between the European Union (EU) and the Kingdom of Morocco, as well as the EU acts that approved them, with the Treaty on the European Union (TEU) and the Treaty on the Functioning of the European Union (TFEU). The issues arising from these disputes include the legality of the Court’s jurisdiction to review the validity of a treaty which is already in force between parties and the rules of international law that the contested legal instruments have violated, perhaps entailing their invalidity under EU law. While the Court has rightly found that none of the aforementioned agreements is applicable to Western Sahara—since their territorial scope does not extend to a territory which is not subject to Moroccan sovereignty——this paper tries to answer a different question as to whether the Court’s decisions are in line with international law. It is demonstrated that though the Court’s competence to rule on the validity of EU unilateral acts is obvious, the establishment of its power to review the validity of a treaty which is in force, such as the fisheries agreement of 2006, is dubious because of the inconsistency of such power with the Vienna Convention on the Law of Treaties. In any event, the question which remains to be solved—and which was not submitted to the Court—pertains to the determination of the effects of the illegal application of the EU-Morocco agreements to Western Sahara on the rights of its people. It is concluded that such an application has violated the law of occupation and eventually international human rights law. These violations do not touch upon the validity of the contested legal instruments but relate to the question of responsibility for a wrongful act stemming from the illegal application of those agreements to occupied Western Sahara in a manner which is harmful to the interest of its people.
Implementation of the Core Elements of Antibiotic Stewardship in Nursing Homes Enrolled in the National Healthcare Safety Network
Authors: Palms Danielle L , Kabbani Sarah , Bell Jeneita M , Anttila Angela , Hicks Lauri A , Stone Nimalie D
Published: February 2019

In 2016, 42% of nursing homes enrolled in the National Healthcare Safety Network reported meeting all 7 of the Centers for Disease Control and Prevention’s Core Elements of Antibiotic Stewardship. Bivariate analyses suggested that implementation of all core elements differed by ownership type and amount of infection prevention staff hours.
Risk of Ectopic Pregnancy and Tubal Infertility Following Gonorrhea and Chlamydia Infections
Authors: Reekie Joanne , Donovan Basil , Guy Rebecca , Hocking Jane S , Kaldor John M , Mak Donna , Preen David , Ward James , Liu Bette ,   Chlamydia and Reproductive Health Outcome Investigators, Liu B , Preen D , Hocking J , Donovan B , Roberts C , Ward J , Mak D , Guy R , Kaldor J , Pearson S , Stewart L , Wand H , Reekie J
Published: February 2019

Gonorrhea and chlamydia are important causes of pelvic inflammatory disease. Chlamydia also causes long-term sequelae, but the role of gonorrhea is unclear. We followed 300 000 reproductive-aged women for 10 years for ectopic pregnancy and tubal infertility; our findings suggest both infections confer similar increases in risk of these outcomes.
Explaining the fame of Friedman’s Presidential Address
Authors: Forder James , Sømme Kardin
Published: February 2019

It is noted that although in fact it lacks the revolutionary content commonly ascribed to it, Friedman’s Presidential Address to the American Economic Association is very highly regarded as an original and formative contribution. It is argued that close attention to the literature shows that it was not initially seen as original, and only after an interval of five years did the idea of its revolutionary status retrospectively, but suddenly become widely accepted. The explanation of this change of view is considered. Four explanations are suggested: one involving terminological confusion, one involving a change in theoretical priorities, and two involving debates of the 1970s, which, although they did not in fact do so, appeared to build on Friedman’s presentation, and by this appearance gave it an undeserved stature.
Efficacy, Tolerability, and Safety of Low-Volume Bowel Preparations for Patients with Inflammatory Bowel Diseases: The French Multicentre CLEAN Study
Authors: Briot C , Faure P , Parmentier A L , Nachury M , Trang C , Viennot S , Altwegg R , Bulois P , Thomassin L , Serrero M , Ah-Soune P , Gilletta C , Plastaras L , Simon M , Dray X , Caillo L , Del Tedesco E , Abitbol V , Zallot C , Degand T , Rossi V , Bonnaud G , Colin D , Morel B , Winkfield B , Danset J B , Filippi J , Amiot A , Attar A , Levy J , Peyrin-Biroulet L , Vuitton L ,   The CLEAN Study Group, Boureille Arnaud , Blain Antoine , Gay Claire , Koch Stéphane , Ambregna Sylvain , Vaurie Fanny , François Stéphanie , Martin Bérenger , Agouzal Khadija , Boivineau Lucile , Branche Julien , Gerard Romain , Benezech Alban , Aider Belinda , Rouillon Clea , Perrod Guillaume , De Montigny Stéphanie , Aygalenq Philippe
Published: February 2019

Background

Standard high-volume polyethylene glycol [PEG] bowel preparations [PEG-4L] are recommended for patients with inflammatory bowel disease [IBD] undergoing colonoscopy. However, low-volume preparations [≤2 L of active volume] are often used in clinical practice. The aim of this study was to evaluate the efficacy, tolerability, and safety of the various bowel preparations for patients with IBD, including low-volume preparations.

Methods

We conducted a French prospective multicentre observational study over a period of 1 month. Patients aged 18–75 years with IBD with an indication of colonoscopy independent of the study were enrolled. The choice of the preparation was left to the investigators, as per their usual protocol. The patients’ characteristics, disease, and colonoscopy characteristics were recorded, and they were given self-reported questionnaires.

Results

Twenty-five public and private hospitals enrolled 278 patients. Among them, 46 had a disease flare and 41 had bowel stenoses. Bowel preparations for colonoscopy were as follows: 42% received PEG-2L, 29% received sodium picosulfate [Pico], 15% received PEG-4L, and 14% had other preparations. The preparation did not reach the Boston’s score efficacy outcome in the PEG-4L group in 51.2% of the patients [p = 0.0011]. The preparation intake was complete for 59.5% in the PEG-4L group, compared with 82.9% in the PEG-2L group and 93.8% in the Pico group [p < 0.0001]. Tolerability, as assessed by the patients’ VAS, was significantly better for both Pico and PEG-2L compared with PEG-4L, and better for Pico compared with PEG-2L [p = 0.008; p = 0.0003]. In multivariate analyses, low-volume preparations were independent factors of efficacy and tolerability. Adverse events occurred in 4.3% of the patients.

Conclusions

Preparations with PEG-2L and Pico were equally safe, with better efficacy and tolerability outcomes compared with PEG-4L preparations. The best efficacy/tolerance/safety profile was achieved with the Pico preparation.
Thermal Tolerance and Prediction of Northern Distribution of the Crapemyrtle Bark Scale (Hemiptera: Eriococcidae)
Authors: Wang Zinan , Chen Yan , Diaz Rodrigo
Published: February 2019

Physiological limits of non-native species to environmental factors are critical for their establishment and spread in the adventive range. The crapemyrtle bark scale, Acanthococcus lagerstroemiae (Kuwana), is a major pest of crapemyrtles. Despite concerns on its rapid spread, there is a lack of information on potential distribution range of this scale in the United States. To understand this scale’s distribution potential, its thermal tolerance was evaluated using higher and lower thermal limits. Exposure time leading to 50 and 90% mortality (Lt50 and Lt90) at extreme low or high temperatures were measured under controlled conditions. A model was then built to fit temperature data of cold fronts from 2001 to 2016 and to calculate potential mortalities along latitudes. Isothermal lines delineated at 90% mortality were defined as the northern limits. Modeling results suggested that A. lagerstroemiae nymphs collected in summer could tolerate heat; however, they were more susceptible to cold temperatures. Laboratory assays suggested that cold tolerance of A. lagerstroemiae nymphs varied from summer to winter. For example, SCP of nymphs collected in summer was higher than those collected in fall (−21 vs. −27°C), and the exposure time leading to Lt90 at 0°C was also different, which were 8 versus 50 h comparing nymphs collected in summer versus fall. Our prediction suggested that A. lagerstroemiae is likely to be limited by cold temperatures along the 43° N latitude. Based on these results, integrated management strategies can be developed for A. lagerstroemiae within the predicted range.
Severe right ventricular dilatation after repair of Tetralogy of Fallot is associated with increased left ventricular preload and stroke volume
Authors: Gnanappa Ganesh Kumar , Celermajer David S , Zhu Danyi , Puranik Rajesh , Ayer Julian
Published: February 2019

Aims

Pulmonary regurgitation (PR) and right ventricular (RV) dilatation are common in repaired tetralogy of Fallot (rTOF). Left ventricular (LV) dysfunction is an important risk factor in rTOF. The effect of PR/RV dilatation on LV performance and RV-LV interactions in rTOF are incompletely understood. We examined LV responses and exercise capacity in rTOF, both before and after pulmonary valve replacement (PVR).

Methods and results

Cardiac magnetic resonance imaging scans in 126 rTOF patients (age 17.3 ± 7.6 years) were analysed, comparing subjects with indexed RV end-diastolic volume (RVEDVi) <170 mL/m2 (mild/moderate dilatation, n = 95) and RVEDVi ≥170 mL/m2 (severe dilatation, n = 31). Indexed PR volume (PRVi), RV end-systolic (RVESVi), RV end-diastolic (RVEDVi), RV stroke volume (RVSVi), net pulmonary forward flow (NPFFi), LV end-diastolic (LVEDVi), LV end-systolic (LVESVi), LV stroke volume (LVSVi), RV and LV ejection fraction (EF), and diastolic septal curvature were obtained. Peak aerobic capacity (VO2 max) was measured. In a subset (n = 30), measures were obtained pre-and-post surgical PVR. Compared to those with mild/moderate RV dilatation, patients with severe RV dilation had greater PRVi (38 ± 12 vs. 24 ± 9 mL/m2, P < 0.0001), NPFFi (53 ± 9 vs. 44 ± 11 mL/m2, P < 0.0001), LVEDVi (87 ± 14 vs. 73 ± 13 mL/m2, P < 0.0001), LVESVi (39 ± 12 vs. 30 ± 8 mL/m2, P < 0.0001), and LVSVi (48 ± 7 vs. 43  ±  8 mL/m2, P = 0.002) but lower RV ejection fraction (46 ± 8 vs. 53 ± 7%, P < 0.0001). Septal curvature and VO2 max were similar in both groups. After PVR, there was no change in LVEDVi, LVSVi, septal curvature, or VO2 max.

Conclusions

Chronic PR with severe RV dilatation is associated with increased NPFFi, LVEDVi, and LVSVi. This may potentially explain preserved exercise capacity in rTOF with severe PR and RV dilatation.
Multidisciplinary approach utilizing early, intensive physical rehabilitation to accelerate recovery from veno-venous extracorporeal membrane oxygenation
Authors: Zhu Yuanjia , Bankar Deepali , Shudo Yasuhiro , Woo Y Joseph
Published: February 2019

This case demonstrates the benefits of our early, intensive physical rehabilitation intervention to prevent the natural sequelae occurring from prolonged bed rest. This minimizes neuromuscular weakness and optimizes strength, endurance and cardiorespiratory function, thus accelerating recovery from a long duration of femorally cannulated veno-venous extracorporeal membrane oxygenation.
Routine intraoperative jejunostomy placement and minimally invasive oesophagectomy: an unnecessary step?†
Authors: Kroese Tiuri E , Tapias Leonidas , Olive Jacqueline K , Trager Lena E , Morse Christopher R
Published: February 2019

OBJECTIVES:

Adequate nutrition is challenging after oesophagectomy. A jejunostomy is commonly placed during oesophagectomy for nutritional support. However, some patients develop jejunostomy-related complications and the benefit over oral nutrition alone is unclear. This study aims to assess jejunostomy-related complications and the impact of intraoperative jejunostomy placement on weight loss and perioperative outcomes in patients with oesophageal cancer treated with minimally invasive Ivor Lewis oesophagectomy (MIE).

METHODS:

From a prospectively maintained database, patients were identified who underwent MIE with gastric reconstruction. Between 2007 and 2016, a jejunostomy was routinely placed during MIE. After 2016, a jejunostomy was not utilized. Postoperative feeding was performed according to a standardized protocol and similar for both groups. The primary outcomes were jejunostomy-related complications, relative weight loss at 3 and 6 months postoperative and perioperative outcomes, including anastomotic leak, pneumonia and length of stay, respectively.

RESULTS:

A total of 188 patients were included, of whom 135 patients (72%) received a jejunostomy. Ten patients (7.4%) developed jejunostomy-related complications, of whom 30% developed more than 1 complication. There was no significant difference in weight loss between groups at 3 months (P = 0.73) and 6 months postoperatively (P = 0.68) and in perioperative outcomes (P-value >0.999, P = 0.591 and P = 0.513, respectively).

CONCLUSIONS:

The use of a routine intraoperative jejunostomy appears to be an unnecessary step in patients undergoing MIE. Intraoperative jejunostomy placement is associated with complications without improving weight loss or perioperative outcomes. Its use should be tailored to individual patient characteristics. Early oral nutrition allows patients to maintain an adequate nutritional status.
Reduced risk of gastrointestinal bleeding associated with proton pump inhibitor therapy in patients treated with dual antiplatelet therapy after myocardial infarction
Authors: Sehested Thomas S G , Carlson Nicholas , Hansen Peter W , Gerds Thomas A , Charlot Mette G , Torp-Pedersen Christian , Køber Lars , Gislason Gunnar H , Hlatky Mark A , Fosbøl Emil L
Published: February 2019

Aims

Guidelines differ in their recommendations on therapy to prevent gastrointestinal bleeding for patients treated with dual antiplatelet treatment (DAPT). We sought to investigate the effectiveness of proton pump inhibitors (PPIs) to prevent upper gastrointestinal (UGI) bleeding in patients using DAPT following myocardial infarction (MI) in relation to current European Society of Cardiology guidelines recommendations.

Methods and results

We linked Danish nationwide registries to identify patients taking DAPT 7 days following hospital discharge for an acute MI, and excluded individuals on anticoagulation therapy. We used multiple Cox regression modelling, to compute average risk of UGI bleeding in relation to PPI use. The associated treatment efficacy was compared based on guideline risk assessment. We studied 46 301 patients on DAPT after MI. Only 35% of patients at higher risk of UGI bleeding received recommended treatment with a PPI based on the guideline criteria. The 1--year risk of UGI bleeding was 1.0% [95% confidence interval (CI) 0.9–1.1%] and 1.7% (CI 1.5–2.0%) for high-risk patients. Overall PPI compared with no therapy, was associated with a risk ratio for UGI bleeding of 0.62 (CI 0.48–0.77) corresponding to an absolute risk difference of 0.44% (CI 0.39–0.48%). Proton pump inhibitor therapy was associated with a similar absolute risk difference [0.47% (CI 0.43–0.51%)] for high-risk patients.

Conclusion

Proton pump inhibitor therapy is used less than suggested by guidelines in patients treated with DAPT following MI and was generally associated with reduced risk of UGI bleeding. Considering the overall low risk of bleeding, more focus should be on identifying patients benefiting the most from PPI therapy.
Cardiac resynchronization therapy non-responder to responder conversion rate in the more response to cardiac resynchronization therapy with MultiPoint Pacing (MORE-CRT MPP) study: results from Phase I
Authors: Leclercq Christophe , Burri Haran , Curnis Antonio , Delnoy Peter Paul , Rinaldi Christopher A , Sperzel Johannes , Lee Kwangdeok , Calò Leonardo , Vicentini Alfredo , Concha Joaquin Fernandez , Thibault Bernard
Published: February 2019

Aims

To assess the impact of MultiPoint™ Pacing (MPP)—programmed according to the physician’s discretion—in non-responders to standard biventricular pacing after 6 months.

Methods and results

The study enrolled 1921 patients receiving a quadripolar cardiac resynchronization therapy (CRT) system capable of MPP™ therapy. A core laboratory assessed echocardiography at baseline and 6 months and defined volumetric non-response to biventricular pacing as <15% reduction in left ventricular end-systolic volume (LVESV). Clinical sites randomized patients classified as non-responders in a 1:1 ratio to receive MPP (236 patients) or continued biventricular pacing (231 patients) for an additional 6 months and evaluated rate of conversion to echocardiographic response. Baseline characteristics of both groups were comparable. No difference was observed in non-responder to responder conversion rate between MPP and biventricular pacing (31.8% and 33.8%, P = 0.72). In the MPP arm, 68 (29%) patients received MPP programmed with a wide LV electrode anatomical separation (≥30 mm) and shortest LV1–LV2 and LV2–RV timing delays (MPP-AS); 168 (71%) patients received MPP programmed with other settings (MPP-Other). MPP-AS elicited a significantly higher non-responder conversion rate compared to MPP-Other (45.6% vs. 26.2%, P = 0.006) and a trend in a higher conversion rate compared to biventricular pacing (45.6% vs. 33.8%, P = 0.10).

Conclusions

After 6 months, investigator-discretionary MPP programming did not significantly increase echocardiographic response compared to biventricular pacing in CRT non-responders.
Short- and long-term outcomes of alcohol septal ablation for hypertrophic obstructive cardiomyopathy in patients with mild left ventricular hypertrophy: a propensity score matching analysis
Authors: Veselka Josef , Faber Lothar , Liebregts Max , Cooper Robert , Januska Jaroslav , Kashtanov Maksim , Dabrowski Maciej , Hansen Peter Riis , Seggewiss Hubert , Hansvenclova Eva , Bundgaard Henning , ten Berg Jurriën , Stables Rodney Hilton , Jensen Morten Kvistholm
Published: February 2019

Aims

Based on European guidelines, alcohol septal ablation (ASA) for hypertrophic obstructive cardiomyopathy (HOCM) is indicated only in patients with interventricular septum (IVS) thickness >16 mm. The aim of this study was to evaluate the short- and long-term outcomes in ASA patients with mild hypertrophy (IVS ≤ 16 mm).

Methods and results

We retrospectively evaluated 1505 consecutive ASA patients and used propensity score to match 172 pairs (344 patients) in groups IVS ≤ 16 mm or IVS > 16 mm. There was no occurrence of post-ASA ventriculoseptal defect in the whole cohort (n = 1505). Matched patients had 30-day mortality rate 0% in IVS ≤ 16 mm group and 0.6% in IVS > 16 mm group (P = 1). Patients in IVS ≤ 16 mm group had more ASA-attributable early complications (16% vs. 9%; P = 0.049), which was driven by higher need for pacemaker implantation (13% vs. 8%; P = 0.22). The mean follow-up was 5.4 ± 4.3 years and the annual all-cause mortality rate was 1.8 and 3.2 deaths per 100-patient-years in IVS ≤ 16 group and IVS > 16 group, respectively (log-rank test P = 0.04). There were no differences in symptom relief and left ventricular (LV) gradient reduction. Patients with IVS ≤ 16 mm had less repeated septal reduction procedures (log-rank test P = 0.03).

Conclusion

Selected patients with HOCM and mild hypertrophy (IVS ≤ 16 mm) had more early post-ASA complications driven by need for pacemaker implantation, but their long-term survival is better than in patients with IVS >16 mm. While relief of symptoms and LV obstruction reduction is similar in both groups, a need for repeat septal reduction is higher in patients with IVS > 16 mm.
Temporal variations in the triggering of myocardial infarction by air temperature in Augsburg, Germany, 1987–2014
Authors: Chen Kai , Breitner Susanne , Wolf Kathrin , Hampel Regina , Meisinger Christa , Heier Margit , von Scheidt Wolfgang , Kuch Bernhard , Peters Annette , Schneider Alexandra ,   for the KORA Study Group, Peters A , Schulz H , Schwettmann L , Leidl R , Heier M , Strauch K
Published: February 2019

Aims

The association between air temperature and mortality has been shown to vary over time, but evidence of temporal changes in the risk of myocardial infarction (MI) is lacking. We aimed to estimate the temporal variations in the association between short-term exposures to air temperature and MI in the area of Augsburg, Germany.

Methods and results

Over a 28-years period from 1987 to 2014, a total of 27 310 cases of MI and coronary deaths were recorded. Daily meteorological parameters were measured in the study area. A time-stratified case-crossover analysis with a distributed lag non-linear model was used to estimate the risk of MI associated with air temperature. Subgroup analyses were performed to identify subpopulations with changing susceptibility to air temperature. Results showed a non-significant decline in cold-related MI risks. Heat-related MI relative risk significantly increased from 0.93 [95% confidence interval (CI): 0.78–1.12] in 1987–2000 to 1.14 (95% CI: 1.00–1.29) in 2001–14. The same trend was also observed for recurrent and non-ST-segment elevation MI events. This increasing population susceptibility to heat was more evident in patients with diabetes mellitus and hyperlipidaemia. Future studies using multicentre MI registries at different climatic, demographic, and socioeconomic settings are warranted to confirm our findings.

Conclusion

We found evidence of rising population susceptibility to heat-related MI risk from 1987 to 2014, suggesting that exposure to heat should be considered as an environmental trigger of MI, especially under a warming climate.
Spotlight on S-ICD™ therapy: 10 years of clinical experience and innovation
Authors: Bögeholz Nils , Willy Kevin , Niehues Philipp , Rath Benjamin , Dechering Dirk G , Frommeyer Gerrit , Kochhäuser Simon , Löher Andreas , Köbe Julia , Reinke Florian , Eckardt Lars
Published: February 2019

Subcutaneous ICD (S-ICD™) therapy has been established in initial clinical trials and current international guideline recommendations for patients without demand for pacing, cardiac resynchronization, or antitachycardia pacing. The promising experience in ‘ideal’ S-ICD™ candidates increasingly encourages physicians to provide the benefits of S-ICD™ therapy to patients in clinical constellations beyond ‘classical’ indications of S-ICD™ therapy, which has led to a broadening of S-ICD™ indications in many centres. However, the decision for S-ICD™ implantation is still not covered by controlled randomized trials but rather relies on patient series or observational studies. Thus, this review intends to give a contemporary update on available empirical evidence data and technical advancements of S-ICD™ technology and sheds a spotlight on S-ICD™ therapy in recently discovered fields of indication beyond ideal preconditions. We discuss the eligibility for S-ICD™ therapy in Brugada syndrome as an example for an adverse and dynamic electrocardiographic pattern that challenges the S-ICD™ sensing and detection algorithms. Besides, the S-ICD™ performance and defibrillation efficacy in conditions of adverse structural remodelling as exemplified for hypertrophic cardiomyopathy is discussed. In addition, we review recent data on potential device interactions between S-ICD™ systems and other implantable cardio-active systems (e.g. pacemakers) including specific recommendations, how these could be prevented. Finally, we evaluate limitations of S-ICD™ therapy in adverse patient constitutions, like distinct obesity, and present contemporary strategies to assure proper S-ICD™ performance in these patients. Overall, the S-ICD™ performance is promising even for many patients, who may not be ‘classical’ candidates for this technology.
Recombinant multicopy plasmids in yeast – interactions with the endogenous 2 μm
Authors: Hohnholz Ruben , Achstetter Tilman
Published: February 2019

Flp-mediated site specific intramolecular recombination in Saccharomyces cerevisiae is considered responsible for amplification of the endogenous 2 μm plasmid. For YEp-type vectors, a similar mechanism can be imagined by which such plasmids achieve high copy numbers, a trait desired for many research applications and necessary for industrial production. We have cultivated yeast carrying one of six isomeric YEp-type model expression plasmids under two different conditions and back transformed the shuttle vectors into Escherichia coli. Our analysis of 586 ampR clones represents a high-resolution snapshot of plasmid forms present in the transformed yeast cells with a detection limit of structural changes of <2%. Altered forms summed up to about 11%, constituting likely a lower limit. We have observed two categories of recombination events. One is Flp based, with products of intermolecular recombination with the 2 μm, likely intermediates that are prerequisites for YEp-type plasmid amplification. The other type is based on Flp-independent homologous recombination leading to oligomerization of such plasmids also in a 2μm-free [cir°] strain, i.e. in the absence of Flp. Beyond the general maintenance and its functional sequences, only the gene of interest and its expression might have an impact on the physiology of the host.
A Case for Promoting Movement Medicine: Preventing Disability in the LIFE Randomized Controlled Trial
Authors: Fanning Jason , Rejeski W Jack , Chen Shyh-Huei , Nicklas Barbara J , Walkup Michael P , Axtell Robert S , Fielding Roger A , Glynn Nancy W , King Abby C , Manini Todd M , McDermott Mary M , Newman Anne B , Pahor Marco , Tudor-Locke Catrine , Miller Michael E ,   LIFE Study Investigators
Published: February 2019

Background

The movement profile of older adults with compromised function is unknown, as is the relationship between these profiles and the development of major mobility disability (MMD)—a critical clinical outcome. We first describe the dimensions of movement in older adults with compromised function and then examine whether these dimensions predict the onset of MMD.

Methods

Older adults at risk for MMD (N = 1,022, mean age = 78.7 years) were randomized to receive a structured physical activity intervention or health education control. We assessed MMD in 6-month intervals (average follow-up of 2.2 years until incident MMD), with activity assessed at baseline, 6-, 12- and 24-month follow-up via accelerometry.

Results

A principal components analysis of 11 accelerometer-derived metrics yielded three components representing lifestyle movement (LM), extended bouts of moderate-to-vigorous physical activity (MVPA), and stationary body posture. LM accounted for the greatest proportion of variance in movement (53%). Within health education, both baseline LM (HR = 0.74; 95% CI 0.62 to 0.88) and moderate-to-vigorous physical activity (HR = 0.69; 95% CI 0.54 to 0.87) were associated with MMD, whereas only LM was associated with MMD within physical activity (HR = 0.74; 95% CI 0.61 to 0.89). There were similar nonlinear relationships present for LM in both physical activity and health education (p < .04), whereby risk for MMD was lower among individuals with higher levels of LM.

Conclusions

Both LM and moderate-to-vigorous physical activity should be central in treatment regimens for older adults at risk for MMD.

Trial Registration

clinicaltrials.gov Identifier NCT01072500
Poor-quality antimalarials further health inequities in Uganda
Authors: Evans Daniel R , Higgins Colleen R , Laing Sarah K , Awor Phyllis , Ozawa Sachiko
Published: February 2019

Substandard and falsified medications are a major threat to public health, directly increasing the risk of treatment failure, antimicrobial resistance, morbidity, mortality and health expenditures. While antimalarial medicines are one of the most common to be of poor quality in low- and middle-income countries, their distributional impact has not been examined. This study assessed the health equity impact of substandard and falsified antimalarials among children under five in Uganda. Using a probabilistic agent-based model of paediatric malaria infection (Substandard and Falsified Antimalarial Research Impact, SAFARI model), we examine the present day distribution of the burden of poor-quality antimalarials by socio-economic status and urban/rural settings, and simulate supply chain, policy and patient education interventions. Patients incur US$26.1 million (7.8%) of the estimated total annual economic burden of substandard and falsified antimalarials, including $2.3 million (9.1%) in direct costs and $23.8 million (7.7%) in productivity losses due to early death. Poor-quality antimalarials annually cost $2.9 million to the government. The burden of the health and economic impact of malaria and poor-quality antimalarials predominantly rests on the poor (concentration index −0.28) and rural populations (98%). The number of deaths among the poorest wealth quintile due to substandard and falsified antimalarials was 12.7 times that of the wealthiest quintile, and the poor paid 12.1 times as much per person in out-of-pocket payments. Rural populations experienced 97.9% of the deaths due to poor-quality antimalarials, and paid 10.7 times as much annually in out-of-pocket expenses compared with urban populations. Our simulations demonstrated that interventions to improve medicine quality could have the greatest impact at reducing inequities, and improving adherence to antimalarials could have the largest economic impact. Substandard and falsified antimalarials have a significant health and economic impact, with greater burden of deaths, disability and costs on poor and rural populations, contributing to health inequities in Uganda.