bluuebunny/crossref_metadata_2025 huggingface dataset:
The sliding context of health: the challenges faced by patients with heart failure from the perspective of patients, healthcare providers and family members
Authors: Mangolian Shahrbabaki Parvin , Nouhi Esmat , Kazemi Majid , Ahmadi Fazlollah
Published: January 2017

Aims and objectives

To understand the challenges faced by patients with heart failure.

Background

Heart failure is a clinical syndrome that is increasing across the globe. People affected with it encounter various problems that reduce their quality of life and well‐being. Therefore, identifying the challenges faced by patients with heart failure is necessary for health care and treatment plans.

Design

This study was performed using the qualitative research approach and content analysis method.

Methods

Data were collected using semistructured interviews and notes in the field of 21 Iranian participants, namely 12 patients with heart failure, three cardiologists, three nurses and three members of patient family. The data were analysed using Lundman and Graneheim qualitative content analysis.

Results

The results of this study were revealed in the form of a theme: ‘sliding context of health’ in which the following three categories ‘perceived threat of health and life’, ‘the struggle between doubt and certainty’ and ‘in the downward slope of quality of life’ reflect the experiences of patients faced with heart failure.

Conclusions

The findings of this study showed that it is necessary to identify the challenges of facing heart failure, in order to support and educate patients with heart failure. Patients do not take care of themselves based on the fact that these challenges affect them psychologically and physically, and as such, the new situations are often misunderstood, thereby resulting in frequent recurrence of symptoms, mandatory hospitalisations and reduced quality of life.

Relevance to clinical practice

Nurses, as the first line of health care, play an important role in identifying problems and supporting patients with heart failure. By acquiring knowledge and listening to the complaints of patients, interventions can be developed to improve their situation.
Validation of an MRI Rating Scale for Amyloid‐Related Imaging Abnormalities
Authors: Bechten Arianne , Wattjes Mike P. , Purcell Derk D. , Aliaga Esther Sanchez , Daams Marita , Brashear H. Robert , Arrighi H. Michael , Barkhof Frederik
Published: January 2017

INTRODUCTION

Immunotherapeutic agents against amyloid beta (Aβ) are associated with adverse events, including amyloid‐related imaging abnormalities with edema and effusion (ARIA‐E). Recently, a magnetic resonance imaging (MRI) rating scale was developed for ARIA‐E detection and classification. The aim of this study was to validate the use of this rating scale in a larger patient group with multiple raters.

METHODS

MRI scans of 75 patients (29 with known ARIA‐E and 46 control subjects) were analyzed by five neuroradiologists with different degrees of expertise, according to the ARIA‐E rating scale. For each patient, we included a baseline and a follow‐up fluid‐attenuated inversion recovery image. Interrater agreement was calculated using intraclass correlation coefficient (ICC).

RESULTS

On average, 4.1% of the ARIA‐E cases were missed. We observed a high interrater agreement for scores of sulcal hyperintensity (SH; ICC = .915; 95% CI 85–95) and for the combined scores of the 2 ARIA‐E findings, parenchymal hyperintensity (PH) and SH (ICC = .878; 95% CI 79–93). A slightly lower agreement for PH (ICC = .678; 95% CI 51–81) was noted.

CONCLUSION

The ARIA‐E rating scale is a simple tool to evaluate the extent of ARIA‐E in patients recruited into Aβ‐lowering therapeutic trials. It shows high interrater agreement among raters with different degrees of expertise.
Eye Movements Converge on Vanishing Points during Visual Search
Authors: Ueda Yoshiyuki , Kamakura Yusuke , Saiki Jun
Published: January 2017

The vanishing point seems to be a useful cue for understanding scenes at a glance. The closer the objects are, the smaller their sizes become. Because the resolution of central vision is higher than that of peripheral vision, seeing a vanishing point enables individuals to perceive the whole scene. Here, we examined whether vanishing points attract eye movements during visual search. In Experiment 1, we conducted a free‐viewing task to examine whether vanishing points play a significant role. In Experiment 2, the participants searched for a Gabor patch that was embedded in manmade or natural scenes. In Experiment 3, to investigate the robustness of the vanishing point effect, visual search was conducted using simpler geometric backgrounds. We observed that eye movements converged around vanishing points, and that the first fixations are also located around them. These results suggest that vanishing points as well as salient locations can capture eye movements, and eye movements are guided by such environmental structures.
What is the true in vitro potency of oxytetracycline for the pig pneumonia pathogens Actinobacillus pleuropneumoniae and Pasteurella multocida?
Authors: Dorey L. , Hobson S. , Lees P.
Published: January 2017

The pharmacodynamics of oxytetracycline was determined for pig respiratory tract pathogens, Actinobacillus pleuropneumoniae and Pasteurella multocida. Indices of potency were determined for the following: (i) two matrices, broth and pig serum; (ii) five overlapping sets of twofold dilutions; and (iii) a high strength starting culture. For A. pleuropneumoniae, minimum inhibitory concentration (MIC) was similar for the two matrices, but for P. multocida, differences were marked and significantly different. MIC and minimum bactericidal concentration (MBC) serum: broth ratios for A. pleuropneumoniae were 0.83:1 and 1.22:1, respectively, and corresponding values for P. multocida were 22.0:1 and 7.34:1. For mutant prevention concentration (MPC) serum: broth ratios were 0.79:1 (A. pleuropneumoniae) and 20.9:1 (P. multocida). These ratios were corrected for serum protein binding to yield fraction unbound (fu) serum: broth MIC ratios of 0.24:1 (A. pleuropneumoniae) and 6.30:1 (P. multocida). Corresponding fu serum: broth ratios for MPC were almost identical, 0.23:1 and 6.08:1. These corrections for protein binding did not account for potency differences between serum and broth for either species; based on fu serum MICs, potency in serum was approximately fourfold greater than predicted for A. pleuropneumoniae and sixfold smaller than predicted for P. multocida. For both broth and serum and both bacterial species, MICs were also dependent on initial inoculum strength. The killing action of oxytetracycline had the characteristics of codependency for both A. pleuropneumoniae and P. multocida in both growth media. The in vitro potency of oxytetracycline in pig serum is likely to be closer to the in vivo plasma/serum concentration required for efficacy than potency estimated in broths.
Plant dispersal traits determine hydrochorous species tolerance to connectivity loss at the landscape scale
Authors: Favre‐Bac Lisa , Lamberti‐Raverot Barbara , Puijalon Sara , Ernoult Aude , Burel Françoise , Guillard Ludovic , Mony Cendrine
Published: January 2017

Aims

Landscape fragmentation has strong negative consequences on biodiversity. In networks of linear elements, connectivity loss results in a decreased length of connected elements and increased potential barriers, directly impacting the ability of plants to disperse. However, species vary in their tolerance to connectivity loss, likely due to differences in dispersal strategies. We investigated whether species tolerance to decreased ditch network connectivity is determined by seed traits. We selected, as a case study, water‐dispersed plant species in a ditch network.

Location

Ditch network in an intensive agricultural area in northern France.

Methods

We selected 27 sites of 500 m × 500 m, where we calculated connectivity indices based on the length of connected ditches, intersections and culvert number. For each parameter, we calculated plant tolerance levels by analysing species changes in occurrence in response to change in connectivity values. Concurrently, we measured in laboratory conditions five seed traits involved in plant movement and establishment in standing aquatic systems and analysed their explanatory power in plant tolerance to fragmentation.

Results

All traits were significantly related to at least one component of ditch network connectivity. We interpreted the following two strategies in plant tolerance to connectivity loss from the results: (1) in networks where the connected network length was short, plants displayed short‐distance dispersal with less efficient sexual reproduction, probably in favour of local vegetative multiplication; and (2) in networks with a high density of culverts or intersections, plants displayed seeds with reduced local retention, where seeds had the capacity to overcome long and frequent trapping events. In highly branched networks, plants also exhibited higher germination rates, promoting seed establishment when trapped along the banks. Seed capacity to be dispersed by wind at the water surface was only a marginal factor in plant tolerance to fragmentation.

Conclusions

Connectivity loss acted as a filter on species seed traits. The results of our study offer an enhanced understanding of plant dispersal in fragmented standing aquatic networks and emphasize the importance of developing functional approaches in landscape studies.
Adaptation of genetically monomorphic bacteria: evolution of copper resistance through multiple horizontal gene transfers of complex and versatile mobile genetic elements
Authors: Richard D. , Ravigné V. , Rieux A. , Facon B. , Boyer C. , Boyer K. , Grygiel P. , Javegny S. , Terville M. , Canteros B. I. , Robène I. , Vernière C. , Chabirand A. , Pruvost O. , Lefeuvre P.
Published: January 2017

Copper‐based antimicrobial compounds are widely used to control plant bacterial pathogens. Pathogens have adapted in response to this selective pressure. Xanthomonas citri pv. citri, a major citrus pathogen causing Asiatic citrus canker, was first reported to carry plasmid‐encoded copper resistance in Argentina. This phenotype was conferred by the copLAB gene system. The emergence of resistant strains has since been reported in Réunion and Martinique. Using microsatellite‐based genotyping and copLAB PCR, we demonstrated that the genetic structure of the copper‐resistant strains from these three regions was made up of two distant clusters and varied for the detection of copLAB amplicons. In order to investigate this pattern more closely, we sequenced six copper‐resistant X. citri pv. citri strains from Argentina, Martinique and Réunion, together with reference copper‐resistant Xanthomonas and Stenotrophomonas strains using long‐read sequencing technology. Genes involved in copper resistance were found to be strain dependent with the novel identification in X. citri pv. citri of copABCD and a cus heavy metal efflux resistance–nodulation–division system. The genes providing the adaptive trait were part of a mobile genetic element similar to Tn3‐like transposons and included in a conjugative plasmid. This indicates the system's great versatility. The mining of all available bacterial genomes suggested that, within the bacterial community, the spread of copper resistance associated with mobile elements and their plasmid environments was primarily restricted to the Xanthomonadaceae family.
Local myogenic pulp‐derived cell injection enhances craniofacial muscle regeneration in vivo
Authors: Jung J. E. , Song M. J. , Shin S. , Choi Y. J. , Kim K. H. , Chung C. J.
Published: January 2017

Structured Abstract

Objectives

To enhance myogenic differentiation in pulp cells isolated from extracted premolars by epigenetic modification using a DNA demethylation agent, 5‐aza‐2′‐deoxycytidine (5‐Aza), and to evaluate the potent stimulatory effect of 5‐Aza‐treated pulp cell injection for craniofacial muscle regeneration in vivo.

Setting and Sample Population

Pulp cells were isolated from premolars extracted for orthodontic purposes from four adults (age range, 18‐22.1 years).

Material and Methods

Levels of myogenic differentiation and functional contraction response in vitro were compared between pulp cells with or without pre‐treatment of 5‐Aza. Changes in muscle regeneration in response to green fluorescent protein (GFP)‐labelled myogenic pulp cell injection in vivo were evaluated using a cardiotoxin (CTX)‐induced muscle injury model of the gastrocnemius as well as the masseter muscle in mice.

Results

Pre‐treatment of 5‐Aza in pulp cells stimulated myotube formation, myogenic differentiation in terms of desmin and myogenin expression, and the level of collagen gel contraction. The local injection of 5‐Aza pre‐treated myogenic pulp cells was engrafted into the host tissue and indicated signs of enhanced muscle regeneration in both the gastrocnemius and the masseter muscles.

Conclusion

The epigenetic modification of pulp cells from extracted premolars and the local injection of myogenic pulp cells may stimulate craniofacial muscles regeneration in vivo.
A Single Center Study of 1,179 Heart Transplant Patients—Factors Affecting Pacemaker Implantation
Authors: WELLMANN PETRA , HERRMANN FLORIAN ERNST MARTIN , HAGL CHRISTIAN , JUCHEM GERD
Published: January 2017

Background

After around 10% of heart transplant patients require pacemaker implantation. The bradyarrhythmias causing pacemaker requirement include sinus node dysfunction (SND) and atrioventricular block (AVB). This study sought to define clinical predictors for pacemaker requirement as well as identify differences in the patient groups developing SND and AVB.

Methods

Our operative database was used to collect retrospective recipient, donor, and operative data of all patients receiving orthotopic heart transplants between 1981 and 2016.

Results

In the 35‐year period 1,179 transplants were performed (mean recipient age 45.5 ± 0.5 years, 20.4% female, 90.6% biatrial technique) with bradyarrhythmias requiring pacemaker implantation developing in 135 patients (11.5%). Independent risk factors were prolonged operative time 340 minutes versus 313 minutes (P = 0.027) and a biatrial anastomosis (P = 0.036). Ischemia time, cardiopulmonary bypass time, aortic cross clamp time, and reperfusion time all had no significant effect on pacemaker implantation rates. Similarly, whether the transplant was a reoperation, a retransplant, or performed after primary assist implantation had no effects on pacemaker implantation rates. There was no survival difference between the paced and nonpaced groups. The donor age was higher in the patients who developed AVB as the indication for pacemaker implantation (43 vs 34 years, P = 0.031). Patients with AVB had longer aortic cross clamp times and developed the arrhythmia later than those who developed SND.

Conclusions

Use of the bicaval instead of the biatrial technique and shortened operative times should reduce pacemaker requirement after heart transplantation. Survival is not affected by this complication.
Working to define professionalism in pediatric anesthesiology: a qualitative study of domains of the expert pediatric anesthesiologist as valued by interdisciplinary stakeholders
Authors: Lockman Justin L. , Schwartz Alan Jay , Cronholm Peter F.
Published: January 2017

Background

Unprofessional behavior is a significant problem throughout graduate medical education programs and medical centers. Some authors have suggested that professionalism curricula should be focused toward faculty, not trainees, to interrupt the modeling of unprofessionalism. Developing such curricula requires a needs assessment and is challenging given data indicating that the definition of professionalism varies based on medical specialty. Thus, a specialty‐specific definition of professionalism is needed as a first step in any curriculum development.

Aim

The aim of this study was to define professionalism in pediatric anesthesiology.

Methods

This is a qualitative study using focus groups for data collection and a grounded theory approach for analysis. Four relevant stakeholder groups, pediatric surgeons and endoscopists, perioperative nurses, pediatric anesthesiologists, and parents of children who had undergone surgery at our facility, were recruited for participation. De‐identified transcripts were analyzed and coded to derive major domains and component themes relevant to the definition of professionalism for pediatric anesthesiology. Member checking with participants from our stakeholder groups was used to validate thematic development and increase the trustworthiness of our findings.

Results

Focus group participants included 20 individuals, 14 of whom were female. Analysis of transcripts identified 11 major domains across the four groups: Patient Ownership, Specialty Expertise, Continuous Team Improvement, Expressive Communication, Active Listening, Care Coordination, Medical Hierarchy, Leadership, Teamwork, Personality Traits, and Physical Image. The data uncovered several controversies for future study.

Conclusion

A composite of these 11 domains may give a more complete image of what surgical and nursing colleagues, patient families, and anesthesiologist partners expect of the pediatric anesthesiologist. Despite some overlap and interdependence between domains, this research may contribute to the creation of future educational curricula and provides domains for evaluation of professionalism in pediatric anesthesiology.
Different expression of leptin and IGF1 in the adult and prepubertal testis in dogs
Authors: Müller L , Kowalewski MP , Reichler IM , Kollár E , Balogh O
Published: January 2017

Contents

Leptin (Lep) and insulin‐like growth factor 1 (IGF1) are implicated in the regulation of testicular function, but in dogs, our knowledge is limited to the possible role of the IGF1 system in testicular tumours. In this study, we aimed to describe and compare gene expression and protein localization of Lep, IGF1 and their receptors (LepR and IGF1R, respectively) in the testis of healthy adult and prepubertal dogs. Testes were collected from sexually healthy mature (n = 7) and from 8‐week‐old dogs (n = 7). Relative gene expression of Lep, LepR, IGF1 and IGF1R was determined by semi‐quantitative real‐time (TaqMan) PCR and cellular distribution in the testis by immunohistochemistry. Statistical analysis was carried out with Student's t test. Lep and LepR mRNA concentration was similar between the two groups, but IGF1 and IGF1R gene expression was significantly higher in the 8‐week‐old pups. Protein localization and the intensity of signals differed by age. In adults, Lep and LepR immunoreactivity was detected in spermatocytes and spermatids. Leydig cells showed sporadic, weak Lep staining. In prepubertal animals, intense Lep signals were present in Leydig and Sertoli cells, and LepR was found in Leydig cells. IGF1 and IGF1R protein was expressed in spermatogonia of the mature testis; IGF1 signals in Leydig cells seemed stronger than IGF1R. In the pups, IGF1 and IGF1R staining was detected in Leydig cells and in gonocytes. Sertoli cells showed weak IGF1 and sporadic, weak IGF1R signals. In conclusion, Lep and IGF1 may support spermatogenesis in adult dogs and mediate Leydig cell function. In the immature testis, they may promote development of Sertoli and Leydig cells and gonocytes.
Ten novel MHC‐DPB1 alleles identified in Tibetan macaque (Macaca thibetana)
Authors: Zhou Y. Y. , Yao Y. F. , Ni Q. Y. , Zhang M. W. , Xu H. L.
Published: January 2017

Ten novel MHC‐DPB1 alleles of Tibetan macaque, were identified by cloning and sequencing.
EDTA is superior to DTT treatment for overcoming the prozone effect in HLA antibody testing
Authors: Wang J. , Meade J. R. , Brown N. K. , Weidner J. G. , Marino S. R.
Published: January 2017

A limitation of solid‐phase human leukocyte antigen (HLA) antibody assays is the falsely low/negative result of samples with high‐titer antibodies, a phenomenon known as the prozone effect. Here we compared the efficacy of ethylenediaminetetraacetic acid (EDTA) and dithiothreitol (DTT) treatment of serum samples in overcoming the prozone effect. A total of 21 serum samples were treated with either EDTA or DTT before HLA single antigen bead assay. The efficacy of prozone effect reversal, compared with untreated samples, was examined on fourfold, serially diluted samples, from neat to 1:256, using PBS as diluent. EDTA reversed the prozone effect in all tested samples, with an efficiency of greater than 84%, estimated by the ratio of undiluted sample mean fluorescence intensity (MFI) to peak MFI, for any given dilution. In contrast, the efficiency of DTT treatment was as low as 47%. These results show superior prozone effect reversal with EDTA treatment, compared with DTT.
Common and well‐documented HLA alleles over all of Europe and within European sub‐regions: A catalogue from the European Federation for Immunogenetics
Authors: Sanchez‐Mazas A. , Nunes J. M. , Middleton D. , Sauter J. , Buhler S. , McCabe A. , Hofmann J. , Baier D. M. , Schmidt A. H. , Nicoloso G. , Andreani M. , Grubic Z. , Tiercy J.‐M. , Fleischhauer K.
Published: January 2017

Background

A catalogue of common and well‐documented (CWD) human leukocyte antigen (HLA), previously established by the American Society for Histocompatibility and Immunogenetics (ASHI), is widely used as indicator for typing ambiguities to be resolved in tissue transplantation or for checking the universality of any HLA allele in the world. However, European population samples, which are characterized by a substantial level of genetic variation, are underrepresented in the ASHI catalogue. Therefore, the Population Genetics Working Group of the European Federation for Immunogenetics (EFI) has facilitated data collection for an European CWD catalogue.

Materials and Methods

To this end, 2nd‐field HLA‐A, ‐B, ‐C,‐ DRB1,‐ DQA1,‐ DQB1 and ‐DPB1 data of 77 to 121 European population samples (21 571‐3 966 984 individuals) from 3 large databases, HLA‐net/Gene[VA], allelefrequencies.net and DKMS, were analysed.

Results

The total number of CWD alleles is similar in the EFI (N = 1048) and ASHI (N = 1031) catalogues, but the former counts less common (N = 236 vs 377) and more well‐documented (N = 812 vs 654) alleles than the latter, possibly reflecting differences in sample numbers and sizes. Interestingly, approximately half of the CWD alleles reported by EFI were not reported by ASHI and vice‐versa, underlining the distinct features of the two catalogues. Also, although 78 common alleles are widely distributed across Europe, some alleles are only common within specific sub‐regions, showing regional variability.

Conclusion

Although the definition of CWD alleles itself is affected by different parameters, calling for current updates of the list, the EFI CWD catalogue provides new insights into European population genetics and will be a very useful tool for tissue‐typing laboratories in and beyond Europe.
Identification of a novel HLA‐B*40 allele, HLA‐B*40:332, in a Korean individual
Authors: Han S.‐H. , Kwon O.‐J. , Lim H.‐S. , Hwang S.‐Y. , Lee K.‐R.
Published: January 2017

HLA‐B*40:332 differs from B*40:01:02 by 1 nucleotide difference at nucleotide position 439.
Identification of the novel HLA‐B*39:01:01:04 allele in a Chinese individual by sequence‐based typing
Authors: Kwok J. , Ho J. C. Y. , Chan Y. S. , Soormally A. , Marsh S. G. E.
Published: January 2017

The new HLA‐B*39:01:01:04 allele differs from HLA‐B*39:01:01 by a C → T substitution in intron 1.
A multi‐hit hypothesis of bullous pemphigoid and associated neurological disease: Is HLA‐DQB1*03:01, a potential link between immune privileged antigen exposure and epitope spreading?
Authors: Amber K. T. , Zikry J. , Hertl M.
Published: January 2017

Bullous pemphigoid (BP) is the most common autoimmune blistering disease and is linked to IgG recognition of 2 hemidesmosomal antigens, that is, BP230 (BP antigen 1) and BP180 (BP antigen 2, collagen XVII). The association of BP with other systemic diseases, particularly neurocognitive diseases, provides a potential clue in the underlying pathogenesis of BP. The role of
HLA‐DQB1*03:01 binding to the immunogenic portion of BP180 provides a potential mechanism by which exposure to neuronal collagen BP180 may lead to cutaneous disease. In our proposed multi‐hit hypothesis, patients with underlying neuronal disease are exposed to previously sequestered self‐antigen, most importantly BP180. Patients with the
HLA‐DQB1*03:01 allele show an increased T‐cell avidity to several epitopes of BP180, particularly the BP180‐NC16a domain. Thus, they have a genetic susceptibility to developing BP upon exposure to the target antigen. In a patient with dysregulation of Th1/Th2 balance, anergy is lost and T‐cells are subsequently primed resulting in the development of functional autoimmunity against the BP180‐NC16a domain leading to clinically overt disease.
Outcomes of HIV‐positive patients lost to follow‐up in African treatment programmes
Authors: Zürcher Kathrin , Mooser Anne , Anderegg Nanina , Tymejczyk Olga , Couvillon Margaret J. , Nash Denis , Egger Matthias ,   the IeDEA and MESH consortia
Published: January 2017

Objective

The retention of patients on antiretroviral therapy (ART) is key to achieving global targets in response to the HIV epidemic. Loss to follow‐up (LTFU) can be substantial, with unknown outcomes for patients lost to ART programmes. We examined changes in outcomes of patients LTFU over calendar time, assessed associations with other study and programme characteristics and investigated the relative success of different tracing methods.

Methods

We performed a systematic review and logistic random‐effects meta‐regression analysis of studies that traced adults or children who started ART and were LTFU in sub‐Saharan African treatment programmes. The primary outcome was mortality, and secondary outcomes were undocumented transfer to another programme, treatment interruption and the success of tracing attempts.

Results

We included 32 eligible studies from 12 countries in sub‐Saharan Africa: 20 365 patients LTFU were traced, and 15 708 patients (77.1%) were found. Compared to telephone calls, tracing that included home visits increased the probability of success: the adjusted odds ratio (aOR) was 9.35 (95% confidence interval [CI] 1.85–47.31). The risk of death declined over calendar time (aOR per 1‐year increase 0.86, 95% CI 0.78–0.95), whereas undocumented transfers (aOR 1.13, 95% CI 0.96–1.34) and treatment interruptions (aOR 1.31, 95% CI 1.18–1.45) tended to increase. Mortality was lower in urban than in rural areas (aOR 0.59, 95% CI 0.36–0.98), but there was no difference in mortality between adults and children. The CD4 cell count at the start of ART increased over time.

Conclusions

Mortality among HIV‐positive patients who started ART in sub‐Saharan Africa, were lost to programmes and were successfully traced has declined substantially during the scale‐up of ART, probably driven by less severe immunodeficiency at the start of therapy.
TRATAMIENTO SUSTANTIVO DE LAS COSTAS EN LA JURISPRUDENCIA DE LA CORTE INTERAMERICANA DE DERECHOS HUMANOS
Authors: Leiva-Poveda Jorge
Published: January 2017

El presente trabajo es la primera parte de un minucioso y exhaustivo análisis de los diversos criterios en materia de costas desarrollados por la Corte Interamericana de Derechos Humanos, concretamente respecto de las consideraciones sustantivas sobre este tema, verbigracia: fundamento normativo, procedencia según tipos de representación, criterios para la cuantificación y exoneración de este extremo en las sentencias condenatorias de ese Tribunal.
El objetivo de este estudio es ofrecer a investigadores universitarios y a potenciales litigantes en el Sistema Interamericano, una sistematización de los criterios utilizados por el Tribunal Continental, que permita conocer el tratamiento práctico de este instituto, más allá de las consideraciones genéricas y puramente teóricas frecuentemente expuestas en distintos foros. Como se verá a continuación, este documento muestra que la falta de regulación normativa de las costas ha impactado negativamente la seguridad jurídica del sistema, dados los diversos abordajes que la Corte Interamericana ha establecido en sus resoluciones en lo que hace a este tema.
Advanced single precursor based pSiCOH k = 2.4 for ULSI interconnects
Authors: Priyadarshini Deepika , Nguyen Son V. , Shobha Hosadurga , Liniger Eric , Chen James H.-C. , Huang Huai , Cohen Stephan A. , Grill Alfred
Published: January 2017

A single precursor, octamethylcyclotetrasiloxane (OMCTS), was used to develop a pSiCOH interconnect dielectric with an ultralow dielectric constant k = 2.4. With no added porogen, the advanced pSiCOH dielectric has low pore size and low pore interconnectivity. The new OEx2.4 dielectric has a high carbon content with a significant fraction in the form of Si-CH2-Si bridging bond resulting in a film with relatively high modulus and increased resistance to process induced damage. The new OEx2.4 film shows significant improvement in device reliability (time dependent dielectric breakdown) over the reference k 2.55 and other k 2.4 dielectrics. This dielectric not only addresses the integration challenges but also provides capacitance benefit by retaining an overall lower integrated k value over the reference films. The results discussed in this paper indicate that the single-precursor OMCTS-based advanced pSiCOH, OEX2.4 dielectric is a strong candidate for sub-10 nm Cu/low k interconnects.
Combined effect of noise and room acoustics on vocal effort in simulated classrooms
Authors: Cipriano Marcella , Astolfi Arianna , Pelegrín-García David
Published: January 2017

This work investigated the relationships between room acoustics, background noise level, and vocal effort of a speaker in simulated classrooms of various volumes. Under simulated acoustic environments, talkers adjusted their vocal effort linearly with the voice support, i.e., the degree of amplification offered by the room to the voice of a speaker, at his own ears. The slope of this relationship, called the room effect, of −0.24 dB/dB was significant only in the case of the highest noise levels of 62 dB. The vocal comfort for the speaker, however, was found to be more closely related to noise annoyance than to room reverberance.
Tambora and the mackerel year: Phenology and fisheries during an extreme climate event
Authors: Alexander Karen E. , Leavenworth William B. , Willis Theodore V. , Hall Carolyn , Mattocks Steven , Bittner Steven M. , Klein Emily , Staudinger Michelle , Bryan Alexander , Rosset Julianne , Carr Benjamin H. , Jordaan Adrian
Published: January 2017

Two hundred years ago, the volcano Tambora caused an extreme climate event that altered fisheries halfway around the world.
Pure iron grains are rare in the universe
Authors: Kimura Yuki , Tanaka Kyoko K. , Nozawa Takaya , Takeuchi Shinsuke , Inatomi Yuko
Published: January 2017

The extremely low sticking probability of iron inhibits the formation of metallic iron grains around evolved stars.
Human tissues in a dish: The research and ethical implications of organoid technology
Authors: Bredenoord Annelien L. , Clevers Hans , Knoblich Juergen A.
Published: January 2017

Ethics of organoid research

Growing functional human tissues and organs would provide much needed material for regeneration and repair. New technologies are taking us in that direction. In addition to their use in regenerative medicine, stem cells that grow and morph into organ-like structures known as organoids can be used in drug development and toxicology testing. The potential developments and possibilities are numerous and affect not only biomedicine but also areas of ongoing ethical debate, such as animal experimentation, research on human embryos and fetuses, ethics review, and patient consent. Bredenoord
et al.
review how organoids affect existing ethical debates and how they raise novel ethical dilemmas and professional responsibilities.

Science
, this issue p.
10.1126/science.aaf9414
The role of dimer asymmetry and protomer dynamics in enzyme catalysis
Authors: Kim Tae Hun , Mehrabi Pedram , Ren Zhong , Sljoka Adnan , Ing Christopher , Bezginov Alexandr , Ye Libin , Pomès Régis , Prosser R. Scott , Pai Emil F.
Published: January 2017

Working as a pair

Enzymes provide scaffolds that facilitate chemical reactions. Enzyme dynamics often enhance reactivity by allowing the enzyme to sample the transition state between reactants and products. Kim
et al.
explored the role of dynamics in the dimeric enzyme fluoroacetate dehalogenase (see the Perspective by Saleh and Kalodimos). They found that the two protomers are asymmetric, with only one being able to bind substrate at a time. The nonbinding protomer contributed to catalysis by becoming more dynamic to compensate for the entropy loss of its partner.

Science
, this issue p.
10.1126/science.aag2355
; see also p.
247
Big-data approaches to protein structure prediction
Authors: Söding Johannes
Published: January 2017

Metagenomics sequence data give protein structure prediction a boost
Assistance magnitude versus metabolic cost reductions for a tethered multiarticular soft exosuit
Authors: Quinlivan B. T. , Lee S. , Malcolm P. , Rossi D. M. , Grimmer M. , Siviy C. , Karavas N. , Wagner D. , Asbeck A. , Galiana I. , Walsh C. J.
Published: January 2017

Evaluation of a soft exosuit designed to reduce metabolic requirements during walking.
Bioinspired photocontrollable microstructured transport device
Authors: Kizilkan Emre , Strueben Jan , Staubitz Anne , Gorb Stanislav N.
Published: January 2017

A transportation device can be tunably controlled by the ultraviolet actuation of a liquid crystal elastomer.
Use of Selective Fungal Culture Media Increases Rates of Detection of Fungi in the Respiratory Tract of Cystic Fibrosis Patients
Authors: Hong Gina , Miller Heather B. , Allgood Sarah , Lee Richard , Lechtzin Noah , Zhang Sean X.
Published: January 2017

The prevalence of fungi in the respiratory tracts of cystic fibrosis (CF) patients has risen. However, fungal surveillance is not routinely performed in most clinical centers in the United States, which may lead to an underestimation of the true prevalence of the problem. We conducted a prospective study comparing the rates of detection for clinically important fungi (CIF), defined as
Aspergillus
,
Scedosporium
, and
Trichosporon
species and
Exophiala dermatitidis
, in CF sputa using standard bacterial and selective fungal culture media, including Sabouraud dextrose agar with gentamicin (SDA), inhibitory mold agar (IMA), and brain heart infusion (BHI) agar with chloramphenicol and gentamicin. We described the prevalence of these fungi in an adult CF population. A total of 487 CF respiratory samples were collected from 211 unique participants. CIF were detected in 184 (37.8%) samples. Only 26.1% of CIF-positive samples were detected in bacterial culture medium, whereas greater rates of detection for fungi were found in IMA (65.8%;
P
< 0.001), in SDA (at 30°C, 64.7%;
P
= 0.005), and in BHI agar (63.0%;
P
= 0.001). The prevalences of
Aspergillus
and
Scedosporium
species were 40.8% and 5.2%, respectively, which are greater than the nationally reported prevalence numbers of 20.4% and 1.9%. Selective fungal culture media and longer incubation periods yielded higher rates of detection for CIF in CF sputum samples compared with that detected in bacterial culture medium, resulting in an underdetection of fungi by bacterial culture alone. The prevalence of fungi in CF may be better estimated by using selective fungal culture media, and this may translate to important clinical decisions.
Investigation of a Candida guilliermondii Pseudo-outbreak Reveals a Novel Source of Laboratory Contamination
Authors: Kirby James E. , Branch-Elliman Westyn , LaSalvia Mary T. , Longhi Lorinda , MacKechnie Matthew , Urman Grigoriy , Baldini Linda M. , Muriel Fatima R. , Sullivan Bernadette , Yassa David S. , Gold Howard S. , Wagner Trevor K. , Diekema Daniel J. , Wright Sharon B.
Published: January 2017

Candida guilliermondii
was isolated from sterile specimens with increasing frequency over a several-month period despite a paucity of clinical evidence suggesting true
Candida
infections. However, a health care-associated outbreak was strongly considered due to growth patterns in the microbiology laboratory that were more consistent with true infection than environmental contamination. Therefore, an extensive investigation was performed to identify its cause. With the exception of one case, patient clinical courses were not consistent with true invasive fungal infections. Furthermore, no epidemiologic link between patients was identified. Rather, extensive environmental sampling revealed
C. guilliermondii
in an anaerobic holding jar in the clinical microbiology laboratory, where anaerobic plates were prereduced and held before inoculating specimens.
C. guilliermondii
grows poorly under anaerobic conditions. Thus, we postulate that anaerobic plates became intermittently contaminated. Passaging from intermittently contaminated anaerobic plates to primary quadrants of aerobic media during specimen planting yielded a colonial growth pattern typical for true specimen infection, thus obscuring laboratory contamination. A molecular evaluation of the
C. guilliermondii
isolates confirmed a common source for pseudo-outbreak cases but not for the one true infection. In line with Reason's model of organizational accidents, active and latent errors coincided to contribute to the pseudo-outbreak. These included organism factors (lack of growth in anaerobic conditions obscuring plate contamination), human factors (lack of strict adherence to plating order, leading to only intermittent observation of aerobic plate positivity), and laboratory factors (novel equipment). All of these variables should be considered when evaluating possible laboratory-based pseudo-outbreaks.
Dynamic Modulation of Expression of Lentiviral Restriction Factors in Primary CD4+T Cells following Simian Immunodeficiency Virus Infection
Authors: Rahmberg Andrew R. , Rajakumar Premeela A. , Billingsley James M. , Johnson R. Paul
Published: January 2017

Although multiple restriction factors have been shown to inhibit HIV/SIV replication, little is known about their expressionin vivo. Expression of 45 confirmed and putative HIV/SIV restriction factors was analyzed in CD4+T cells from peripheral blood and the jejunum in rhesus macaques, revealing distinct expression patterns in naive and memory subsets. In both peripheral blood and the jejunum, memory CD4+T cells expressed higher levels of multiple restriction factors compared to naive cells. However, relative to their expression in peripheral blood CD4+T cells, jejunal CCR5+CD4+T cells exhibited significantly lower expression of multiple restriction factors, includingAPOBEC3G,MX2, andTRIM25, which may contribute to the exquisite susceptibility of these cells to SIV infection.In vitrostimulation with anti-CD3/CD28 antibodies or type I interferon resulted in upregulation of distinct subsets of multiple restriction factors. After infection of rhesus macaques with SIVmac239, the expression of most confirmed and putative restriction factors substantially increased in all CD4+T cell memory subsets at the peak of acute infection. Jejunal CCR5+CD4+T cells exhibited the highest levels of SIV RNA, corresponding to the lower restriction factor expression in this subset relative to peripheral blood prior to infection. These results illustrate the dynamic modulation of confirmed and putative restriction factor expression by memory differentiation, stimulation, tissue microenvironment and SIV infection and suggest that differential expression of restriction factors may play a key role in modulating the susceptibility of different populations of CD4+T cells to lentiviral infection.

IMPORTANCERestriction factors are genes that have evolved to provide intrinsic defense against viruses. HIV and simian immunodeficiency virus (SIV) target CD4+T cells. The baseline level of expressionin vivoand degree to which expression of restriction factors is modulated by conditions such as CD4+T cell differentiation, stimulation, tissue location, or SIV infection are currently poorly understood. We measured the expression of 45 confirmed and putative restriction factors in primary CD4+T cells from rhesus macaques under various conditions, finding dynamic changes in each state. Most dramatically, in acute SIV infection, the expression of almost all target genes analyzed increased. These are the first measurements of many of these confirmed and putative restriction factors in primary cells or during the early events after SIV infection and suggest that the level of expression of restriction factors may contribute to the differential susceptibility of CD4+T cells to SIV infection.
Azacytidine Treatment Inhibits the Progression of Herpes Stromal Keratitis by Enhancing Regulatory T Cell Function
Authors: Varanasi Siva Karthik , Reddy Pradeep B. J. , Bhela Siddheshvar , Jaggi Ujjaldeep , Gimenez Fernanda , Rouse Barry T.
Published: January 2017

Ocular infection with herpes simplex virus 1 (HSV-1) sets off an inflammatory reaction in the cornea which leads to both virus clearance and chronic lesions that are orchestrated by CD4 T cells. Approaches that enhance the function of regulatory T cells (Treg) and dampen effector T cells can be effective to limit stromal keratitis (SK) lesion severity. In this report, we explore the novel approach of inhibiting DNA methyltransferase activity using 5-azacytidine (Aza; a cytosine analog) to limit HSV-1-induced ocular lesions. We show that therapy begun after infection when virus was no longer actively replicating resulted in a pronounced reduction in lesion severity, with markedly diminished numbers of T cells and nonlymphoid inflammatory cells, along with reduced cytokine mediators. The remaining inflammatory reactions had a change in the ratio of CD4 Foxp3+Treg to effector Th1 CD4 T cells in ocular lesions and lymphoid tissues, with Treg becoming predominant over the effectors. In addition, compared to those from control mice, Treg from Aza-treated mice showed more suppressor activityin vitroand expressed higher levels of activation molecules. Additionally, cells inducedin vitroin the presence of Aza showed epigenetic differences in the Treg-specific demethylated region (TSDR) of Foxp3 and were more stable when exposed to inflammatory cytokines. Our results show that therapy with Aza is an effective means of controlling a virus-induced inflammatory reaction and may act mainly by the effects on Treg.

IMPORTANCEHSV-1 infection has been shown to initiate an inflammatory reaction in the cornea that leads to tissue damage and loss of vision. The inflammatory reaction is orchestrated by gamma interferon (IFN-γ)-secreting Th1 cells, and regulatory T cells play a protective role. Hence, novel therapeutics that can rebalance the ratio of regulatory T cells to effectors are a relevant issue. This study opens up a new avenue in treating HSV-induced SK lesions by increasing the stability and function of regulatory T cells using the DNA methyltransferase inhibitor 5-azacytidine (Aza). Aza increased the function of regulatory T cells, leading to enhanced suppressive activity and diminished lesions. Hence, therapy with Aza, which acts mainly by its effects on Treg, can be an effective means to control virus-induced inflammatory lesions.
Advances in Myeloid-Like Cell Origins and Functions in the Model OrganismDrosophila melanogaster
Authors: El Chamy Laure , Matt Nicolas , Reichhart Jean-Marc
Published: January 2017

Drosophilahas long served as a valuable model for deciphering many biological processes, including immune responses. Indeed, the genetic tractability of this organism is particularly suited for large-scale analyses. Studies performed during the last 3 decades have proven that the signaling pathways that regulate the innate immune response are conserved betweenDrosophilaand mammals. This review summarizes the recent advances onDrosophilahematopoiesis and immune cellular responses, with a particular emphasis on phagocytosis.
Optimized CRISPR-Cas9 Genome Editing for
Leishmania
and Its Use To Target a Multigene Family, Induce Chromosomal Translocation, and Study DNA Break Repair Mechanisms
Authors: Zhang Wen-Wei , Lypaczewski Patrick , Matlashewski Greg
Published: January 2017

Leishmania
parasites cause human leishmaniasis. To accelerate characterization of
Leishmania
genes for new drug and vaccine development, we optimized and simplified the CRISPR-Cas9 genome-editing tool for
Leishmania
. We show that co-CRISPR targeting of the miltefosine transporter gene and serial transfections of an oligonucleotide donor significantly eased isolation of edited mutants. This cotargeting strategy was efficiently used to delete all 11 members of the A2 virulence gene family. This technical advancement is valuable, since there are many gene clusters and supernumerary chromosomes in the various
Leishmania
species and isolates. We simplified this CRISPR system by developing a gRNA and Cas9 coexpression vector which could be used to delete genes in various
Leishmania
species. This CRISPR system could also be used to generate specific chromosomal translocations, which will help in the study of
Leishmania
gene expression and transcription control. This study also provides new information about double-strand DNA break repair mechanisms in
Leishmania
.
Gastrointestinal stromal tumour (GIST) presenting as a strangulated inguinal hernia with small bowel obstruction
Authors: Massani Marco , Capovilla Giovanni , Ruffolo Cesare , Bassi Nicolò
Published: January 2017

Gastrointestinal stromal tumours (GISTs) can arise everywhere along the gastrointestinal (GI) tract. Their presentation in unusual locations should always be taken into account. A 74-year-old man referred to the emergency department for small bowel obstruction caused by an incarcerated inguinal hernia. A CT scan showed a mesenchymal tumour originating from the herniated bowel loop and a mass in the ascending colon. Laparoscopic resection of the mass and laparoscopic right hemicolectomy were performed. The histology showed a ruptured GIST arising from the herniated small bowel and a high-grade dysplasia villous adenoma of the right colon. GISTs can present with symptoms spanning from vague abdominal discomfort to surgical urgencies. Strangulated hernia is an extremely rare presentation, with only two cases described in the literature. A safe surgical approach was obtained with laparoscopy, maintaining surgical radicality. The ileal localisation and the pseudocapsule rupture were the main risk factors on prognostic stratification.
Incidence of delivery wire recapture failure with the Pipeline Flex device
Authors: Mooney Michael A , Moon Karam , Gross Bradley A , Ducruet Andrew F , Albuquerque Felipe C
Published: January 2017

Background

The Pipeline Flex embolization device has several advantages over the first-generation Pipeline embolization device (Covidien, Dublin, Republic of Ireland). Despite these advantages, we have observed frequent difficulty in recapturing the device's delivery wire.

Objective

To prospectively document the incidence of failure to recapture the delivery wire.

Methods

We tracked our experience in patients undergoing endovascular treatment with a flow-diverting stent for cerebral aneurysms between 1 May and 30 September 2016. Patient and lesion characteristics, device dimensions, and technical outcomes of delivery wire recapture were prospectively recorded for each device.

Results

Eighteen devices were deployed in 15 patients by the senior author (FCA) during this period. Failure to recapture the delivery wire occurred in 10 of 18 (56%) cases. No adverse outcomes of delivery wire recapture failure were encountered in this series.

Conclusions

The incidence of delivery wire recapture failure with the Pipeline Flex device is high. Failure to recapture the delivery wire carries a theoretical risk of stent displacement when re-navigating across the device, and endovascular surgeons should be aware of this limitation. Authors are encouraged to report delivery wire recapture failure rates in future clinical series in which the Pipeline Flex device is used.