bluuebunny/crossref_metadata_2025 huggingface dataset:
Diversity of RH and transfusion support in Brazilian sickle cell disease patients with unexplained Rh antibodies
Authors: Dinardo Carla L. , Kelly Shannon , Dezan Marcia R. , Ribeiro Ingrid H. , Castilho Shirley L. , Schimidt Luciana C. , Valgueiro Maria do C. , Preiss Liliana R. , Custer Brian , Sabino Ester C. , Westhoff Connie M. ,   for the NHLBI Recipient Epidemiology and Donor Evaluation Study (REDS)‐III
Published: August 2019

BACKGROUND

Genetic diversity in the RH genes among sickle cell disease (SCD) patients is well described but not yet extensively explored in populations of racially diverse origin. Transfusion support is complicated in patients who develop unexpected Rh antibodies. Our goal was to describe RH variation in a large cohort of Brazilian SCD patients exhibiting unexpected Rh antibodies (antibodies against RH antigens to which the patient is phenotypically positive) and to evaluate the impact of using the patient's RH genotype to guide transfusion support.

STUDY DESIGN AND METHODS

Patients within the Recipient Epidemiology and Evaluation Donor Study (REDS)‐III Brazil SCD cohort with unexpected Rh antibodies were selected for study. RHD and RHCE exons and flanking introns were sequenced by targeted next‐generation sequencing.

RESULTS

Fifty‐four patients with 64 unexplained Rh antibodies were studied. The majority could not be definitively classified as auto‐ or alloantibodies using serologic methods. The most common altered RH were RHD*DIIIa and RHD*DAR (RHD locus) and RHCE*ce48C, RHCE*ce733G, and RHCE*ceS (RHCE locus). In 53.1% of the cases (34/64), patients demonstrated only conventional alleles encoding the target antigen: five of 12 anti‐D (41.7%), 10 of 12 anti‐C (83.3%), 18 of 38 anti‐e (47.4%), and one of one anti‐E (100%).

CONCLUSION

RHD variation in this SCD cohort differs from that reported for African Americans, with increased prevalence of RHD*DAR and underrepresentation of the DAU cluster. Many unexplained Rh antibodies were found in patients with conventional RH allele(s) only. RH genotyping was useful to guide transfusion to determine which patients could potentially benefit from receiving RH genotyped donor units.
Can the Regional Comprehensive Economic Partnership minimise the harm from the United States–China trade war?
Authors: Mahadevan Renuka , Nugroho Anda
Published: August 2019

Using ex post tariff schedules for the first time, it was found that the global gains provided by the Regional Comprehensive Economic Partnership (RCEP) are not enough to overcome the negative impacts of the United States–China trade dispute. While trade tensions cause China's welfare loss to be more than twice as large as the United States, they provide some trade diversion to RCEP members. But of concern is if India successfully delays the conclusion of the RCEP even by a year, there will be a global loss of US$17.7 billion. The RCEP is also beneficial for the emerging economy of Vietnam and the high‐tariff‐imposing Korean economy. The results obtained here are, however, conservative as reduction in non‐tariff barriers and other positive spillover effects of trade liberalisation related to investment and productivity improvements due to competition or increased intra‐industry trade could not be accounted for.
Environmental risk factors for canine atopic dermatitis: a retrospective large‐scale study in Labrador and golden retrievers
Authors: Harvey Naomi D. , Shaw Stephen C. , Craigon Peter J. , Blott Sarah C. , England Gary C.W.
Published: August 2019

Background

Canine atopic dermatitis (cAD) is one the most common and distressing skin disorders seen in dogs. It is characterized by dysfunction in the skin barrier, with a complex pathogenesis combining both genetic and environmental factors.

Objectives

To evaluate associations between environmental factors and case‐control status in two closely related, at‐risk breeds, the Labrador retriever and golden retriever.

Animals

Two thousand four hundred and forty‐five pet dogs, of which 793 were classed as cases (575 Labrador and 218 golden retrievers) and 1,652 as controls (1,120 Labrador and 532 golden retrievers).

Methods and materials

Case‐control status was assigned based upon owner response to a standardized validated questionnaire. Retrospective data on rearing environment were collected via additional questions. Univariate and multivariate logistic regressions were utilized to evaluate associations between environmental factors and case‐control status.

Results

Risk factors included being reared in an urban environment (not living currently in an urban environment), being male, being neutered, receiving flea control and being allowed on upholstered furniture. Protective factors included living with other dogs (not cats) and walking in woodlands, fields or beaches. Additionally, amongst Labrador retrievers, chocolate‐coloured dogs were at greater risk of having cAD than black‐ or yellow‐coated dogs.

Conclusions and clinical importance

This study is the largest of its kind to date to investigate the role of the environment in cAD. Although precise triggers are unclear, this study complements earlier studies in highlighting the protective role of a rural environment and some novel associations with disease development.
Risk of infection after double locking plate and screw fixation of tibial plateau leveling osteotomies in dogs weighing greater than 50 kilograms
Authors: Tuan Jayson , Solano Miguel A. , Danielski Alan
Published: August 2019

Objective

To compare surgical site infection (SSI) rates after double locking plate and screw fixation (DLP), standard locking plate and screw fixation (LP), and conventional nonlocking plate and screw fixation (NLP) in dogs weighing >50 kg undergoing tibial plateau leveling osteotomy (TPLO).

Study design

Retrospective study (January 2003‐October 2017).

Animals

Two hundred seventy‐five dogs weighing >50 kg with cranial cruciate ligament disease treated with TPLO.

Methods

Medical records of dogs weighing >50 kg that underwent TPLO by DLP, LP, and NLP with a minimum follow‐up period of 12 months were included. Data collected included signalment, details of any concurrent surgical procedure, type of implant used, use of postoperative antibiotic therapy, occurrence of perioperative complications, and presence of postoperative infection. The probability, risk difference, and relative risk of SSI were estimated for each fixation with a marginal model.

Results

Nonlocking plate and screw fixation was used in 114 (41.5%) dogs, LP was used in 128 (46.5%) dogs, and DLP was used in 33 (12%) dogs. Surgical site infection was diagnosed in 48 of 275 (17.5%) dogs. Postoperative antibiotic therapy was used in 74 (64.9%) dogs, 62 (48.4%) dogs, and 32 (97.0%) dogs in the NLP, LP, and DLP groups, respectively. Dogs with NLP, LP, and DLP had postoperative infection rates of 24.5%, 13.3%, and 9.1%, respectively. There were no risk differences for the three groups (Holm‐adjustedP > .05).

Conclusion

No difference in infection rates was detected between DLP, LP, or NLP for TPLO in these dogs weighing >50 kg.

Clinical significance

Fixation of TPLO with DLP in dogs weighing >50 kg does not seem to increase the risk of SSI compared with LP and NLP.
A Tri-state Investigation of Firearms Confiscation on Three Regional University Campuses
Authors: F. Anderson James , Reinsmith-Jones Kellie , Lee Tazinski , H. Langsam Adam
Published: August 2019

While the use of firearms is pronounced throughout the US, there are few studies that address the availability of firearms on university campuses in states that are adjacent to each other. This study uses a five-year longitudinal design to investigate three universities that were randomly selected in the neighboring states of North Carolina, Virginia, and South Carolina to examine the extent of firearm confiscation by public safety officers. In the final analysis, we conclude that unless viable strategies that target preventing firearms used in domestic violence, alleviating access to guns, and addressing mental health illnesses among college students are created to effectively confiscate firearms on university campuses, deadly violence could become an inevitable occurrence.
Improving Police Social Media Use Practices
Authors: L. Beshears Michael , L. Beshears Michelle , Bond Mark
Published: August 2019

Phenomenological study findings identified police social media site use practices that law enforcement leadership may wish to consider incorporating. Findings showed that members of the public in their lived experiences desired two-way asynchronous and synchronous interpersonal communication capabilities when accessing social media platforms maintained by law enforcement agencies. Improved police social media use practices in these areas may be a gateway to building stronger community relations and using social media as an instrument to aid in crime solving. The themes identified included crime solving, building community-relations, asynchronous versus synchronous engagement, humanistic branding, and public image.
Linguistic Distances Based on Counting of Equal Sounds in Numerals from 1 to 10 in Different Language Groups
Authors: Perdih Anton
Published: August 2019

The relative frequency of equal sounds in pairs of adjacent numerals from 1 to 10 in languages of eleven language groups is a basis for calculation of linguistic distances. By this criterion, the Slavic languages form a cluster separated from all other tested languages. Of other languages, Avestan and Sanskrit are the closest to them. The Germanic languages form another cluster but this cluster is within the space of other tested languages, which are widely dispersed. This is an additional indication that the aboriginal Proto-Indo-European was Proto-Slavic and their speakers were the aboriginal Europeans: mainly the Y Chromosome haplogroup I, mtDNA haplogroup U people. In contact with newcomers of other language groups either the newcomers turned to Proto-Slavic, or the previously Proto-Slavic speakers lost their Proto-Slavic at all, or they turned the non-Indo-European newcomers into Indo-European. A novel time line for Nostratic studies is proposed.
Retracted: Rubral modulation of breathing
Authors: Ghali Michael George Zaki
Published: August 2019

New Findings

What is the topic of this review?

Rubral modulation of pontomedullary respiratory rhythm and pattern generating circuitry powerfully contributes to regulation of breathing.

What advances does it highlight?

Studies have demonstrated extensive rubromedullary and rubrospinal projections to zones generating and organizing the respiratory rhythm and pattern. Rubral modulation of respiratory output effects inspiratory expiratory phase transitions with stimulation generating inhibitory or excitatory responses of medullary inspiratory and expiratory units. The red nucleus mediates hypoxic ventilatory depression, integrates respiratory output with oromotor and locomotor activity, and modulates respiratory output during noxious stimulation.

Although normal triphasic eupnoea can be produced by the pontomedullary respiratory network after pontomesencephalic transection, the midbrain provides important modulation of respiration. Specifically, stimulation of the red nucleus elicits inspiratory inhibition, as manifest in the phrenic neurogram, in addition to excitation and inhibition of individual medullary respiratory‐related units, with the majority of premotor units that receive rubral modulation being inhibited. Stimulation of the red nucleus also induces respiratory phase transitions, which appear to be pontine independent. These effects might be mediated by rubrobulbar and/or rubrospinal tracts. Although lesioning of the red nucleus does not alter respiration in normoxic conditions, it eliminates hypoxic ventilatory depression, which is the second phase of the biphasic ventilatory response to low oxygen tension. The finding that the red nucleus also plays a role in anti‐nociception suggests that it might coordinate respiratory responses during noxious stimulation and, given that the red nucleus regulates upper limb flexors, it might represent one region in a distributed bulbar network contributing to respiratory–locomotor integration. Modulation of jaw opening by the red nucleus would support a model whereby it coordinates oromotor activity with breathing. Thus, the multiplicity of roles played by the red nucleus aptly position it to coordinate respiration in a variety of behavioural states. In this review, we seek to highlight the different features and regional specializations of the rubral contribution to respiratory control and underscore its vital importance to breathing in the freely behaving mammal.
Modelling the effects of age and sex on the resistive and viscoelastic components of the work of breathing during exercise
Authors: Molgat‐Seon Yannick , Dominelli Paolo B. , Guenette Jordan A. , Sheel A. William
Published: August 2019

New Findings

What is the central question of this study?

What is the effect of age and sex on the resistive and viscoelastic components of work of breathing (Wb) during exercise?

What is the main finding and its importance?

The resistive and viscoelastic components of Wb were higher in older adults, regardless of sex. The resistive, but not viscoelastic, component of Wb was higher in females than in males, regardless of age. These findings contribute to improving our understanding of the effects of ageing and sex on the mechanical ventilatory response to exercise.

Healthy ageing and biological sex each affect the work of breathing (Wb) for a given minute ventilation (). Age‐related structural changes to the respiratory system lead to an increase in both the resistive and viscoelastic components of Wb; however, it is unclear whether healthy ageing differentially alters the mechanics of breathing in males and females. We analysed data from 22 older (60–80 years, n = 12 females) and 22 younger (20–30 years, n = 11 females) males and females that underwent an incremental cycle exercise test to exhaustion. and Wb were assessed at rest and throughout exercise. Wb– data for each participant were fitted to a non‐linear equation (i.e. Wb = a3 + b2) that partitions Wb into resistive (i.e. a3) and viscoelastic (i.e. b2) components. We then modelled the effects of healthy ageing and biological sex on each component of Wb. Overall, the model fit was excellent (r2: 0.99 ± 0.01). There was a significant main effect of age and sex on the resistive component of Wb (both P < 0.05), and a significant main effect of age (P < 0.001), but not sex (P = 0.309), on the viscoelastic component of Wb. No significant interactions between age and sex on a3 or b2 were noted (both P > 0.05). Our findings indicate that during exercise: (i) the higher total Wb in females relative to males is due to a higher resistive, but not viscoelastic, component of Wb, and (ii) regardless of sex, the higher Wb in older adults relative to younger adults is due to higher resistive and viscoelastic components of Wb.
Growth of pulsed laser deposited few-layer WS2 films
Authors: Rathod Urmilaben P. , Cai Bimin , Iheomamere Chukwudi , Nyandoto Gilbert , Voevodin Andrey A. , Shepherd Nigel D.
Published: August 2019

X-ray photoelectron, Raman, and diffraction studies of few-layered pulsed laser deposited WS2 films were performed as a function of laser fluence and frequency to understand the impact on structure and properties. Supersaturation of the growth surface created by high fluence was conducive to nucleation and growth, but the obtained films were sulfur deficient. Sulfur desorption at high fluence is due to large kinetic energy transfer and energetic peening of the growing film from the impinging flux. Loss of sulfur was also observed at low frequency where the off period of the supply flux was relatively large. With improvement of the S/W ratio from 1.1 to 1.8, the mobility increased from 0.1 to 6.5 cm2 V−1 s−1, while the associated change in the electron sheet concentration followed the opposite trend. Annealing at high temperature under conditions that conserved stoichiometry dramatically improved the crystallinity and further improved the mobility from 6.5 to 19.5 cm2 V−1 s−1. The correlations between structure, Hall mobility, and Fermi level positions indicate that reducing chalcogen vacancies is critical for optimal mobility in all pulsed laser deposited transition metal dichalcogenide films.
Hybrid Cramér-Rao bound of direction finding, using a triad of cardioid sensors that are perpendicularly oriented and spatially collocated
Authors: Kitavi Dominic Makaa , Wong Kainam Thomas , Lin Tsair-Chuan , Wu Yue Ivan
Published: August 2019

Cardioid microphones/hydrophones are highly directional acoustical sensors, which enjoy easy availability via numerous commercial vendors for professional use. Collocating three such cardioids in orthogonal orientation to each other, the resulting triad would be sharply directional yet physically compact, while decoupling the incident signal's time-frequency dimensions from its azimuth-elevation directional dimensions, thereby simplifying signal-processing computations. This paper studies such a cardioid triad's azimuth-elevation direction-of-arrival estimation accuracy, which is characterized here by the hybrid Cramér-Rao bound. This analysis allows the cardioidicity index (α) to be stochastically uncertain, applies to any cardioidic order (k), and is valid for any real-valued incident signal regardless of the signal's time-frequency structure.
Utility of Targeted, Amplicon-Based Deep Sequencing To Detect Resistance to First-Line Tuberculosis Drugs in Botswana
Authors: Wang Qiao , Modongo Chawangwa , Allender Christopher , Engelthaler David M. , Warren Robin M. , Zetola Nicola M. , Shin Sanghyuk S.
Published: August 2019

Multidrug-resistant tuberculosis (TB) is an alarming threat, and targeted deep sequencing (DS) may be an effective method for rapid identification of drug-resistant profiles, including detection of heteroresistance. We evaluated the sensitivity and specificity of targeted DS versus phenotypic drug susceptibility testing (pDST) among patients starting first-line anti-TB therapy in Botswana. Overall, we found high concordance between DS and pDST.
Luminescent Nanosensors for Ratiometric Monitoring of Three-Dimensional Oxygen Gradients in Laboratory and Clinical Pseudomonas aeruginosa Biofilms
Authors: Jewell Megan P. , Galyean Anne A. , Kirk Harris J. , Zemanick Edith T. , Cash Kevin J.
Published: August 2019

Biofilm infections are more difficult to treat than planktonic infections for a variety of reasons, such as decreased antibiotic penetration. Their complex structure makes biofilms challenging to study without disruption. To address this limitation, we developed and demonstrated oxygen-sensitive luminescent nanosensors that can be incorporated into biofilms for studying oxygen penetration, distribution, and antibiotic efficacy—demonstrated here with our sensors monitoring antibiotic impacts on metabolism in biofilms formed from clinical isolates. The significance of our research is in demonstrating not only a nondisruptive method for imaging and measuring oxygen in biofilms but also that this nanoparticle-based sensing platform can be modified to measure many different ions and small molecule analytes.
Adaptation of Syntenic Xyloglucan Utilization Loci of Human Gut
Bacteroidetes
to Polysaccharide Side Chain Diversity
Authors: Déjean Guillaume , Tauzin Alexandra S. , Bennett Stuart W. , Creagh A. Louise , Brumer Harry
Published: August 2019

The catabolism of complex carbohydrates that otherwise escape the endogenous digestive enzymes of humans and other animals drives the composition and function of the gut microbiota. Thus, detailed molecular characterization of dietary glycan utilization systems is essential both to understand the ecology of these complex communities and to manipulate their compositions, e.g., to benefit human health. Our research reveals new insight into how ubiquitous members of the human gut microbiota have evolved a set of microheterogeneous gene clusters to efficiently respond to the structural variations of plant xyloglucans. The data here will enable refined functional prediction of xyloglucan utilization among diverse environmental taxa in animal guts and beyond.
Structural and Functional Characterization of an Electron Transfer Flavoprotein Involved in Toluene Degradation in Strictly Anaerobic Bacteria
Authors: Vogt Marian Samuel , Schühle Karola , Kölzer Sebastian , Peschke Patrick , Chowdhury Nilanjan Pal , Kleinsorge Daniel , Buckel Wolfgang , Essen Lars-Oliver , Heider Johann
Published: August 2019

This study documents the involvement of ETF in anaerobic toluene metabolism as the physiological electron acceptor for benzylsuccinyl-CoA dehydrogenase. While toluene-degrading denitrifying proteobacteria use a common ETF species, which is also used for other β-oxidation pathways, obligately anaerobic sulfate- or ferric-iron-reducing bacteria use specialized ETF paralogues for toluene degradation. Based on the structure and sequence conservation of these ETFs, they form a new clade that is only remotely related to the previously characterized members of the ETF family. An exhaustive analysis of the available sequences indicated that the protein family consists of several closely related clades of proven or potential electron-bifurcating ETF species and many deeply branching nonbifurcating clades, which either follow the host phylogeny or are affiliated according to functional criteria.
Dengue Virus M Protein Promotes NLRP3 Inflammasome Activation To Induce Vascular Leakage in Mice
Authors: Pan Pan , Zhang Qi , Liu Weiyong , Wang Wenbiao , Lao Zizhao , Zhang Wei , Shen Miaomiao , Wan Pin , Xiao Feng , Liu Fang , Zhang Wen , Tan Quiping , Liu Xiaohong , Wu Kailang , Liu Yingle , Li Geng , Wu Jianguo
Published: August 2019

Dengue virus (DENV) is a mosquito-borne pathogen, and infections by this virus are prevalent in over 100 tropical and subtropical countries or regions, with approximately 2.5 billion people at risk. DENV infection induces a spectrum of clinical symptoms, ranging from classical dengue fever (DF) to severe dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Therefore, it is important to understand the mechanisms underlying DENV pathogenesis. In this study, we reveal that the DENV membrane protein (M) interacts with the host NLRP3 protein to promote NLRP3 inflammasome activation, which leads to the activation and release of a proinflammatory cytokine, interleukin-1 beta (IL-1β). More importantly, we demonstrate that M protein can induce vascular permeability and vascular leakage and that NLRP3 is required for M-induced vascular leakage in mouse tissues. Collectively, this study reveals a distinct mechanism underlying DENV pathogeneses and provides new insights into the development of therapeutic agents for DENV-associated diseases.
Field Test and Validation of the Multiplier Measles, Mumps, Rubella, and Varicella-Zoster Multiplexed Assay System in the Democratic Republic of the Congo by Using Dried Blood Spots
Authors: Higgins Stephen G. , Hoff Nicole A. , Gadoth Adva , Fusellier Andrew , Mukadi Patrick , Alfonso Vivian , Randall Christina , Ashbaugh Hayley , Poncheri Melanie , Doshi Reena H. , Gerber Sue , Budd Roger , Wolfert Robert , Williams Russell , Okitolonda-Wemakoy Emile , Muyembe-Tamfum Jean-Jacque , Rimoin Anne W.
Published: August 2019

The critical evaluation of immunization programs is key to identifying areas of suboptimal vaccination coverage, monitoring activities, and aiding development of public health policy. For evaluation of vaccine effectiveness, direct antibody binding assay methods, including enzyme immunoassay, enzyme-linked fluorescence assays, and indirect immunofluorescence assay, are most commonly used for detection of IgG antibodies. However, despite their well-demonstrated, reliable performance, they can be labor-intensive and time-consuming and require separate assays for each individual marker. This necessitates increased sample volumes, processing time, and personnel, which may limit assessment to a few key targets in resource-limited settings, that is, low- and middle-income locations where funding for public health or general infrastructure that directly impacts public health is restricted, limiting access to equipment, infrastructure, and trained personnel. One solution is a multiplexed immunoassay, which allows for the detection of multiple analytes in a single reaction for increased efficiency and rapid surveillance of infectious diseases in limited-resource settings. Thus, the scope of the project precluded a full validation, and here we present abbreviated validation studies demonstrating adequate sensitivity, specificity, and reproducibility.
Genetic Determinants of Virulence between Two Foot-and-Mouth Disease Virus Isolates Which Caused Outbreaks of Differing Severity
Authors: Nishi Tatsuya , Morioka Kazuki , Saito Nobuko , Yamakawa Makoto , Kanno Toru , Fukai Katsuhiko
Published: August 2019

Efforts to understand the universal mechanism of foot-and-mouth disease virus (FMDV) infection may be aided by knowledge of the molecular mechanisms which underlie differences in virulence beyond multiple topotypes and serotypes of FMDV. Here, we demonstrated independent genetic determinants of two FMDV isolates which have different transmissibility in cattle, namely, VP1 and 3D protein. Findings suggested that the selectivity of VP1 for host cell receptors and replication fidelity during replication were important individual factors in the induction of differences in virulence in the host as well as in the severity of outbreaks in the field. These findings will aid the development of safe live vaccines and antivirals which obstruct viral infection in natural hosts.
Atypical cutaneous targetoid lesions after bone marrow transplant
Authors: Zhong Connie S , Richardson Edward T , Laga Canales Alvaro C , Nambudiri Vinod E
Published: August 2019

A 69-year-old man with esophageal EBV-positive diffuse large B cell lymphoma status post allogeneic bone marrow transplant (BMT) five months prior presented to his oncologist with three days of maculopapular rash that was initially diagnosed as grade 1 graft-versus-host disease and started on oral prednisone. However, due to worsening of the rash, the patient presented to dermatology clinic, where skin biopsy revealed a diagnosis of erythema multiforme (EM). The patient improved with the use of topical steroids. This case highlights the atypical morphology of post-BMT EM and the potential causes for this atypical appearance.
Longitudinal changes in axial length in high myopia: a 4-year prospective study
Authors: Lee Min Woo , Lee Seong-Eun , Lim Hyung-Bin , Kim Jung-Yeul
Published: August 2019

Aim

To determine the longitudinal changes in the axial length (AL) in patients with high myopia without any other ophthalmic disease

Methods

Participants were divided into two groups: a high myopia group (60 eyes) without myopic degeneration, such as chorioretinal atrophy or posterior staphyloma, and a control group (60 eyes). Both groups were further divided into subgroups according to the AL: subgroup 1 (≥27.5 mm), subgroup 2 (26.0–27.5 mm), subgroup 3 (24.5–26.0 mm) and subgroup 4 (<24.5 mm). The ALs were measured five times at 1-year interval using an IOL master, and the AL was fitted with linear mixed models.

Results

In the high myopia group, the AL showed a relatively constant increase at each visit, and they were significantly different with previous measurements at most visits, whereas the control group showed no significant change of AL. Subgroups 1,2 and 3 showed significant changes in AL over time (0.064, 0.032 and 0.012 mm/y, respectively). In univariate analyses, age, best-corrected visual acuity, baseline AL and anterior chamber depth were significantly correlated with changes in the AL in the high myopia group. In multivariate analysis, only baseline AL remained significant (p<0.001).

Conclusions

Myopic eyes, including moderately myopic eyes, showed a consistent increase in AL over 4 years, and eyes with a longer baseline AL showed a greater increase in AL than eyes with a shorter AL.
Nomogram for visual acuity outcome after iodine-125 plaque radiotherapy and prophylactic intravitreal bevacizumab for uveal melanoma in 1131 patients
Authors: Dalvin Lauren A , Zhang Qiang , Hamershock Rose A , Chang Michael , Yu Michael D , Mashayekhi Arman , Shields Carol L
Published: August 2019

Aims

To develop a nomogram for prediction of visual acuity outcome following plaque radiotherapy for uveal melanoma.

Methods

Retrospective review of uveal melanoma treated with plaque radiotherapy and prophylactic intravitreal bevacizumab injections at 4-month intervals for 2 years duration. Two nomograms for poor visual acuity outcome (Snellen <20/200) were developed based on (1) Clinical risk factors. (2) Or clinical and treatment risk factors.

Results

There were 1131 included cases. The most important clinical risk factors (points for nomogram) for poor visual acuity outcome included subretinal fluid involving four quadrants (100), tumour thickness >4 mm (69), presenting visual acuity ≤20/30 (65), non-Caucasian race (58), tumour shape mushroom, bilobed, or multilobulated (57), and insulin-dependent diabetes (54). Risk of poor visual acuity at 2 years and 4 years increased from 11% and 24% with 40 points to 97% and >99% with 304 points. A second analysis was performed using both clinical and treatment risk factors. The most important factors included presenting visual acuity ≤20/30 (100), tumour largest basal diameter >11 mm (80), radiation dose rate to tumour base ≥164 cGy/hour (78), tumour thickness >4 mm (76), insulin-dependent diabetes (75) and abnormal foveolar status by optical coherence tomography at presentation (72). Risk of poor visual acuity at 2 years and 4 years increased from 6% and 14% with 56 points to 88% and 99% with 496 points.

Conclusions

A nomogram using clinical or treatment risk factors can predict visual acuity outcome following plaque radiotherapy and prophylactic intravitreal bevacizumab for uveal melanoma and is available online at https://fighteyecancer.com/nomograms/.
Practice patterns to decrease myopia progression differ among paediatric ophthalmologists around the world
Authors: Leshno Ari , Farzavandi Sonal K , Gomez-de-Liaño Rosario , Sprunger Derek T , Wygnanski-Jaffe Tamara , Mezer Eedy
Published: August 2019

Introduction

Myopia is a worldwide epidemic. Plethora of treatments are offered to decrease myopia progression. In this study, we compared between different geographical areas worldwide the practice patterns used by paediatric ophthalmologists to decrease the progression of myopia.

Methods

Global responses to a questionnaire were analysed (n=794) for demographic variations. Pharmacological, optical and behavioural categories were defined as effective or ineffective based on the current scientific peer reviewed literature.

Results

Treatment rates varied significantly between geographical regions (mean 57%, range 39%–89%, p<0.001). Nearly all participants who treat myopia used at least one form of effective treatment, regardless of location (98%, p=0.16). Among those prescribing pharmacological treatments, European physicians offered the lowest rate of effective treatment compared with other regions (85% vs mean 97%). Rates of effective optical treatment varied significantly between locations (p<0.001), from 16% (Central-South America) to 56% (Far East). Most treating respondents advocated behavioural modifications (92%), between 87% (North America) and 100% (Central Asia). Nearly all respondents used combinations of treatment modalities (95%)—mostly pharmacological, optical and behavioural combination. However, combination rates varied significantly between regions (p<0.001).

Discussion

The utility of treatment to decrease myopia progression differs significantly across the world both in type, combination and efficacy.

Conclusion

Paediatric ophthalmologists involvement and proficiency in myopia progression treatment varies around the world. This may entail promoting continuous medical education and other incentives to increase the number and proficiency of paediatric ophthalmologist to have a more effective impact to control the myopia epidemic in children.
ENT Quality Improvement Program as a tool to improve the collection of morbidity and mortality data: a multisite audit carried out over 6 months
Authors: Edmiston Rachel , Anmolsingh Rajesh , Khwaja Sadie , Kumar B Nirmal
Published: August 2019

Objective

This project aims to assess the role of a standardised process of data collection to improve morbidity and mortality data across the region.

Design

Six hospitals within the North West (UK) were recruited and adopted the ENT Quality Improvement Program (QIP) into their daily practice. Monthly anonymous data were sent back to the reviewer for trend analysis.

Outcome measures

Four outcome measures were defined: (1) number of cases recorded within the region each month; (2) assessment of the severity of cases and trends; (3) assessment of action plans reviewing any changes in practice made as a result of using this tool; (4) long-term use of the tool and qualitative feedback from units.

Results

162 patients over the 6 months were included with 180 case discussions. 170 of these were morbidities and 10 were mortalities. Mortality was more frequent in patients with a diagnosis of head and neck cancer. Of the 162 patients, 133 encountered postoperative complications. Post-tonsillectomy (62/133 47%) and post-thyroid surgery (19/133 14%) complications were the most frequently encountered. 66% of the complications were low grade with 18% requiring management under general anaesthetic. Actions plans included four policy reviews with the introduction of three new policies. All sites found the tool user-friendly and are continuing to use it beyond the data collection period.

Conclusions

The ENT QIP has been found to be a simple, user-friendly tool which has improved the quality of data over the six sites and resulted in improvements in practice. Implementation of the tool allows clinicians to critically appraise their practice and to reflect as well as to demonstrate how complications have resulted in change.
Let the kids play: gamification as a CPR training methodology in secondary school students. A quasi-experimental manikin simulation study
Authors: Otero-Agra Martín , Barcala-Furelos Roberto , Besada-Saavedra Iker , Peixoto-Pino Lucía , Martínez-Isasi Santiago , Rodríguez-Núñez Antonio
Published: August 2019

Objective

Gamification is a non-evaluation and competition-based training methodology with high emotional involvement. The goal of this study was to evaluate gamification methodology as compared with other existing methodologies when teaching cardiopulmonary resuscitation (CPR) to secondary school students.

Methods

489 secondary school students from two high schools in Spain participated in this randomised-block quasi-experimental study in February 2018. The students were classified into different groups. Each group received CPR training with a different methodology: GAM (gamification-based training as a compulsory but non-tested academic activity to learn by playing in teams, with instructor and visual feedback); EVA (training based on subsequentevaluationas a motivational incentive, with instructor and visual feedback); VFC (visual feedback complementary, training based on a non-compulsory and non-tested academic activity, with instructor and visual feedback); TC (traditional complementary, training based on a non-compulsory and non-tested academic activity, with instructor feedback). After a week, each student performed a 2 min hands-only CPR test and quality of CPR was assessed. Visual feedback in training and CPR variables in test were provided by the QCPR Instructor App using a Little Anne manikin, both from Laerdal (Norway).

Results

GAM (89.56%; 95% CI 86.71 to 92.42) methodology resulted in significantly higher scores for CPR quality than VFC and TC (81.96%; 95% CI 78.04% to 85.88% and 64.11%; 95% CI 58.23 to 69.99). GAM (61.77%; 95% CI 56.09 to 67.45) methodology also resulted in significantly higher scores for correct rate than VFC and TC (48.41%; 95% CI 41.15% to 55.67% and 17.28%; 95% CI 10.94 to 23.62). 93.4% of GAM methodology participants obtained >50 mm of compression mean depth which was a significantly higher proportion than among students in VFC and TC (78.0% and 71.9%). No differences between GAM and EVA were found. A confidence level of 95% has been assigned to all values.

Conclusions

GAM methodology resulted in higher CPR quality than non-tested methods of academic training with instructor feedback or visual feedback. Gamification should be considered as an alternative teaching method for Basic Life Support (BLS) in younger individuals.
Fragile X mental retardation protein protects against tumour necrosis factor-mediated cell death and liver injury
Authors: Zhuang Yuan , Xu Haifeng C , Shinde Prashant V , Warfsmann Jens , Vasilevska Jelena , Sundaram Balamurugan , Behnke Kristina , Huang Jun , Hoell Jessica I , Borkhardt Arndt , Pfeffer Klaus , Taha Mohamed S , Herebian Diran , Mayatepek Ertan , Brenner Dirk , Ahmadian Mohammad Reza , Keitel Verena , Wieczorek Dagmar , Häussinger Dieter , Pandyra Aleksandra A , Lang Karl S , Lang Philipp A
Published: August 2019

Objective

The Fragile X mental retardation (FMR) syndrome is a frequently inherited intellectual disability caused by decreased or absent expression of the FMR protein (FMRP). Lack of FMRP is associated with neuronal degradation and cognitive dysfunction but its role outside the central nervous system is insufficiently studied. Here, we identify a role of FMRP in liver disease.

Design

Mice lacking Fmr1 gene expression were used to study the role of FMRP during tumour necrosis factor (TNF)-induced liver damage in disease model systems. Liver damage and mechanistic studies were performed using real-time PCR, Western Blot, staining of tissue sections and clinical chemistry.

Results

Fmr1null mice exhibited increased liver damage during virus-mediated hepatitis following infection with the lymphocytic choriomeningitis virus. Exposure to TNF resulted in severe liver damage due to increased hepatocyte cell death. Consistently, we found increased caspase-8 and caspase-3 activation following TNF stimulation. Furthermore, we demonstrate FMRP to be critically important for regulating key molecules in TNF receptor 1 (TNFR1)-dependent apoptosis and necroptosis including CYLD, c-FLIPS and JNK, which contribute to prolonged RIPK1 expression. Accordingly, the RIPK1 inhibitor Necrostatin-1s could reduce liver cell death and alleviate liver damage in Fmr1null mice following TNF exposure. Consistently, FMRP-deficient mice developed increased pathology during acute cholestasis following bile duct ligation, which coincided with increased hepatic expression of RIPK1, RIPK3 and phosphorylation of MLKL.

Conclusions

We show that FMRP plays a central role in the inhibition of TNF-mediated cell death during infection and liver disease.
Imbalance of the renin–angiotensin system may contribute to inflammation and fibrosis in IBD: a novel therapeutic target?
Authors: Garg Mayur , Royce Simon G , Tikellis Chris , Shallue Claire , Batu Duygu , Velkoska Elena , Burrell Louise M , Patel Sheila K , Beswick Lauren , Jackson Anvesh , Britto Kaushali , Lukies Matthew , Sluka Pavel , Wardan Hady , Hirokawa Yumiko , Tan Chin Wee , Faux Maree , Burgess Antony W , Hosking Patrick , Monagle Shaun , Thomas Merlin , Gibson Peter R , Lubel John
Published: August 2019

Objective

We evaluated the influence of the renin–angiotensin system (RAS) on intestinal inflammation and fibrosis.

Design

Cultured human colonic myofibroblast proliferation and collagen secretion were assessed following treatment with angiotensin (Ang) II and Ang (1–7), their receptor antagonists candesartan and A779, and the ACE inhibitor captopril. Circulating and intestinal RAS components were evaluated in patients with and without IBD. Disease outcomes in patients with IBD treated with ACE inhibitors and angiotensin receptor blockers (ARBs) were assessed in retrospective studies.

Results

Human colonic myofibroblast proliferation was reduced by Ang (1–7) in a dose-dependent manner (p<0.05). Ang II marginally but not significantly increased proliferation, an effect reversed by candesartan (p<0.001). Colonic myofibroblast collagen secretion was reduced by Ang (1–7) (p<0.05) and captopril (p<0.001), and was increased by Ang II (p<0.001). Patients with IBD had higher circulating renin (mean 25.4 vs 18.6 mIU/L, p=0.026) and ACE2:ACE ratio (mean 0.92 vs 0.69, p=0.015) than controls without IBD. RAS gene transcripts and peptides were identified in healthy and diseased bowels. Colonic mucosal Masson’s trichrome staining correlated with Ang II (r=0.346, p=0.010) and inversely with ACE2 activity (r=−0.373, p=0.006). Patients with IBD who required surgery (1/37 vs 12/75, p=0.034) and hospitalisation (0/34 vs 8/68, p=0.049) over 2 years were less often treated with ACE inhibitors and ARBs than patients not requiring surgery or hospitalisation.

Conclusions

The RAS mediates fibrosis in human cell cultures, is expressed in the intestine and perturbed in intestinal inflammation, and agents targeting this system are associated with improved disease outcomes.
What’s in it for the animals? Symbiotically considering ‘therapeutic’ human-animal relations within spaces and practices of care farming
Authors: Gorman Richard
Published: August 2019

Human-animal relations are increasingly imbricated, encountered and experienced in the production of medicine and health. Drawing on an empirical study of care farms in the UK, this article uses the language of symbiosis to develop a framework for critically considering the relationships enrolled within interspecies therapeutic practices. Care farming is an emerging paradigm that aims to deploy farming practices as a form of therapeutic intervention, with human-animal relations framed as providing important opportunities for human health. This article moves to attend to multispecies therapeutic interventions and relationships from a more-than-human perspective, drawing attention to the often-troubling anthropocentrism in which such practices are framed and performed. Attempting to perform and realise human imaginations of ‘therapeutic’ affects, spaces and relationships can rely on processes that reduce animals’ own opportunities for flourishing. Yet, the therapeutic use of other species does not have to be forever anthropocentric or utilitarian. The article explores whether relations between humans and animals might result in a level of mutual proliferation of affective capacities, reciprocally beneficial. These human-animal entanglements highlight opportunities to think more critically about how to practice interspecies relationships and practices in ways that are less parasitic, and instead framed more by attempts at producing opportunities for mutualistic flourishing.
Parroting patriots: interspecies trauma and becoming-well-together
Authors: Bolman Brad
Published: August 2019

At a Veterans Affairs (VA) Medical Center in West Los Angeles, traumatised parrots and former soldiers participate in an experimental therapy programme aimed at overcoming the wounds of war and abandonment. Drawing on the work of Giorgio Agamben and Peter Sloterdijk, this article uses the VA parrot therapy programme to develop an interspecies account of trauma in and beyond language that emphasises the dangers of isolation and denaturalisation. Looking after parrots, veterans reacclimate themselves to an alternative mode of existence centred around care for the other. This article reflects on the possibilities for therapeutic encounter-value in processes such as this, where humans and non-humans are ‘becoming-well-together’. At stake in these multispecies encounters is a form of care critical for a world filled with too many traumatised beings.
Ferments and the AIDS virus: interspecies counter-conduct in the history of AIDS
Authors: Linds Justin Abraham
Published: August 2019

In the first three decades after AIDS started infecting people in the USA and Canada, before, during and after the emergence of anti-retroviral therapies, numerous “alternative and holistic treatments” for AIDS were debated, tested, circulated, written about and taught. This paper, taking a narrow focus, examines documents that reveal how some people with AIDS developed a logic of care predicated on intimate interactions with microscopic lifeforms—the AIDS virus and the bacteria involved in fermentation, in particular. Focusing on the writings of Jon Greenberg and Sandor Katz, two former members of ACT UP/NY, I show that the men did not just dissent from management by biomedical authority but found new authority about how to care for themselves as people with AIDS from their interactions with non-human microscopic life. The practices and writings of both men demonstrate that Foucault’s theory of counter-conduct exists in the history of AIDS as an interspecies process in which microscopic existents lead humans. From Katz and Greenberg, I argue there is an interspecies dimension to counter-conduct that exists as a frame for understanding people who find in non-human life a guide towards unconventional forms of care, revised forms of human behaviour and philosophies for persisting with illness.
Educational inequalities in the impact of chronic diseases on exit from paid employment among older workers: a 7-year prospective study in the Netherlands
Authors: Oude Hengel Karen , Robroek Suzan J W , Eekhout Iris , van der Beek Allard J , Burdorf Alex
Published: August 2019

Objectives

The study aimed to investigate the relative and absolute risks of early exit from paid employment among older workers with a chronic disease, and to assess whether these risks differ across educational groups.

Methods

Data on chronic diseases and demographics from 9160 Dutch workers aged 45–64 years were enriched with monthly information on employment status from Statistics Netherlands. Subdistribution hazard ratios (SHR) and 7-year probabilities among workers with a chronic disease of exit from paid employment through disability benefits, unemployment benefits, early retirement benefits or economic inactivity were estimated using competing risks regression analyses based on Fine and Gray’s models.

Results

Workers with one chronic disease had a higher risk to exit paid employment through disability benefits (SHR 4.48 (95%CI 3.22 to 6.25)) compared with workers without chronic disease, and this risk further increased for multiple chronic diseases (SHR 8.91 (95%CI 6.33 to 12.55)). As occurrence of chronic diseases was highest among low educated workers, the 7-year probabilities to exit paid employment through disability benefits were highest among this group. Cardiovascular, musculoskeletal, psychological and respiratory diseases were associated with disability benefits (SHRs ranging from 2.11 (95%CI 1.45 to 3.07) to 3.26 (95%CI 2.08 to 5.12)), whereas psychological diseases were also related to unemployment (SHR 1.78 (95%CI 1.33 to 2.38)).

Conclusions

Older workers with a chronic disease have a higher risk to exit paid employment through disability benefits. As multimorbidity has an additive effect, addressing multimorbidity as a risk factor for sustainable employment is needed.