bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated Cerebrospinal Fluid Tau Protein Concentrations on Admission Are Associated With Long-term Neurologic and Cognitive Impairment in Ugandan Children With Cerebral Malaria
Authors: Datta Dibyadyuti , Conroy Andrea L , Castelluccio Peter F , Ssenkusu John M , Park Gregory S , Opoka Robert O , Bangirana Paul , Idro Richard , Saykin Andrew J , John Chandy C
Published: April 2019

Background

Elevated concentrations of cerebrospinal fluid (CSF) tau, a marker of axonal injury, have been associated with coma in severe malaria (cerebral malaria [CM]). However, it is unknown whether axonal injury is related to long-term neurologic deficits and cognitive impairment in children with CM.

Methods

Admission CSF tau concentrations were measured in 145 Ugandan children with CM and compared to clinical and laboratory factors and acute and chronic neurologic and cognitive outcomes.

Results

Elevated CSF tau concentrations were associated with younger age, increased disease severity (lower glucose and hemoglobin concentrations, malaria retinopathy, acute kidney injury, and prolonged coma duration, all P < .05), and an increased CSF:plasma albumin ratio, a marker of blood–brain barrier breakdown (P < .001). Admission CSF tau concentrations were associated with the presence of neurologic deficits at hospital discharge, and at 6, 12, and 24 months postdischarge (all P ≤ .02). After adjustment for potential confounding factors, elevated log10-transformed CSF tau concentrations correlated with worse cognitive outcome z scores over 2-year follow-up for associative memory (β coefficient, –0.31 [95% confidence interval [CI], –.53 to –.10]) in children <5 years of age, and for overall cognition (–0.69 [95% CI, –1.19 to –.21]), attention (–0.78 [95% CI, –1.34 to –.23]), and working memory (–1.0 [95% CI, –1.68 to –.31]) in children ≥5 years of age (all P < .006).

Conclusions

Acute axonal injury in children with CM is associated with long-term neurologic deficits and cognitive impairment. CSF tau concentrations at the time of the CM episode may identify children at high risk of long-term neurocognitive impairment.
A Review of the Ecology and Management of Black Turpentine Beetle (Coleoptera: Curculionidae)
Authors: Munro Holly L , Sullivan Brian T , Villari Caterina , Gandhi Kamal J K
Published: April 2019

The black turpentine beetle, Dendroctonus terebrans Olivier is the largest pine-infesting bark beetle native to the southern and eastern United States. It generally reproduces in fresh stumps and bases of trees weakened or killed by other biotic or abiotic agents, although it can also infest and sometimes kills apparently healthy trees. Its numbers can build when large amounts of host material become available (typically through a disturbance), and black turpentine beetle-caused mortality at a local scale can become considerable. Here, we provide a complete review of the literature on this species, including its taxonomy, host, life history, chemical ecology, arthropod and microbial associates, and management options. We also provide original data on numbers of instars, acoustic signals, and pheromone chirality in this species. Our survey of the existing literature revealed that key biological characteristics of black turpentine beetles are known, but interactions with closely associated organisms, economic and ecological impacts, and improvements to monitoring and management practices have been only partially investigated.
Sex-Related Differences in Brain Volumes and Cerebral Blood Flow Among Overweight and Obese Adults With Type 2 Diabetes: Exploratory Analyses From the Action for Health in Diabetes Brain Magnetic Resonance Imaging Study
Authors: Espeland Mark A , Hayden Kathleen M , Lockhart Samuel N , Yassine Hussein N , Hoscheidt Siobhan , Yasar Sevil , Luchsinger Jose A , Neiberg Rebecca H , Diaz Brinton Roberta , Carmichael Owen
Published: April 2019

Background

Sex may be an important modifier of brain health in response to risk factors. We compared brain structure and function of older overweight and obese women and men with type 2 diabetes mellitus.

Methods

Cross-sectional cognitive assessments and magnetic resonance images were obtained in 224 women and 95 men (mean age 69 years) with histories of type 2 diabetes mellitus and overweight or obesity. Prior to magnetic resonance images, participants had completed an average of 10 years of random assignment to either multidomain intervention targeting weight loss or a control condition of diabetes support and education. Total (summed gray and white) matter volumes, white matter hyperintensity volumes, and cerebral blood flow across five brain regions of interest were analyzed using mixed-effects models.

Results

After covariate adjustment, women, compared with men, averaged 10.9 [95% confidence interval 3.3, 18.5; ≈1%] cc greater summed region of interest volumes and 1.39 [0.00002, 2.78; ≈54%] cc greater summed white matter hyperintensity volumes. Sex differences could not be attributed to risk factor profiles or intervention response. Their magnitude did not vary significantly with respect to age, body mass index, intervention assignment, or APOE-ε4 genotype. Sex differences in brain magnetic resonance images outcomes did not account for the better levels of cognitive functioning in women than men.

Conclusions

In a large cohort of older overweight or obese adults with type 2 diabetes mellitus, differences in brain volumes and white matter disease were apparent between women and men, but these did not account for a lower prevalence of cognitive impairment in women compared with men in this cohort.

Trial registration

NCT00017953.
Co-production of a pictorial recovery tool for people with psycho-social disability informed by a participatory action research approach—a qualitative study set in India
Authors: Mathias Kaaren , Pillai Pooja , Gaitonde Rakhal , Shelly Kakul , Jain Sumeet
Published: April 2019

Mental health problems are recognized as a leading cause of disability and have seen increased allocations of resources and services globally. There is a growing call for solutions supporting global mental health and recovery to be locally relevant and built on the knowledge and skills of people with mental health problems, particularly in low-income countries. Set in Dehradun district, North India, this study aimed to describe first, the process of co-production of a visual tool to support recovery for people affected by psycho-social disability; second, the key outputs developed and third, critical reflection on the process and outputs. The developmental process consisted of participatory action research and qualitative methods conducted by a team of action researchers and an experts by experience (EBE) group of community members. The team generated eight domains for recovery under three meta-domains of normalcy, belonging and contributing and the ensuing recovery tool developed pictures of activities for each domain. Challenges to using a participatory and emancipatory process were addressed by working with a mentor experienced in participatory methods, and by allocating time to concurrent critical reflection on power relationships. Findings underline the important contribution of an EBE group demonstrating their sophisticated and locally valid constructions of recovery and the need for an honest and critically reflective process in all co-productive initiatives. This study generated local conversations around recovery that helped knowledge flow from bottom-to-top and proposes that the grass-root experiences of participants in a disadvantaged environment are needed for meaningful social and health policy responses.
Real-time video kinematic evaluation of the in situ beating right ventricle after pulmonary valve replacement in patients with tetralogy of Fallot: a pilot study
Authors: Rozzi Giacomo , Lo Muzio Francesco P , Sandrini Camilla , Rossi Stefano , Fassina Lorenzo , Faggian Giuseppe , Miragoli Michele , Luciani Giovanni Battista
Published: April 2019

OBJECTIVES

The timing for pulmonary valve replacement (PVR) after tetralogy of Fallot repair is controversial, due to limitations in estimating right ventricular dysfunction and recovery. Intraoperative imaging could add prognostic information, but transoesophageal echocardiography is unsuitable for exploring right heart function. Right ventricular function after PVR was investigated in real time using a novel video-based contactless kinematic evaluation technology (Vi.Ki.E.), which calculates cardiac fatigue and energy consumption.

METHODS

Six consecutive patients undergoing PVR at 13.8 ± 2.6 years (range 6.9–19.8) after the repair of tetralogy of Fallot were enrolled. Mean right ventricular end-diastolic and end-systolic volume at magnetic resonance imaging were 115.6 ± 16.2 ml/m2 and 61.5 ± 14.6 ml/m2, respectively. Vi.Ki.E. uses a fast-resolution camera placed 45 cm above the open chest, recording cardiac kinematics before and after PVR. An algorithm defines cardiac parameters, such as energy, fatigue, maximum contraction velocity and tissue displacement.

RESULTS

There were no perioperative complications, with patients discharged in satisfactory clinical conditions after 7 ± 2 days (range 5–9). Vi.Ki.E. parameters describing right ventricular dysfunction decreased significantly after surgery: energy consumption by 45% [271 125 ± 9422 (mm/s)2 vs 149 202 ± 11 980 (mm/s)2, P = 0.0001], cardiac fatigue by 12% (292 671 ± 29 369 mm/s2 vs 258 755 ± 42 750 mm/s2, P = 0.01), contraction velocity by 54% (3412 ± 749 mm/s vs 1579 ± 400 mm/s, P = 0.0007) and displacement by 23% (27 ± 4 mm vs 21 ± 4 mm, P = 0.01). Patients undergoing PVR at lower end-diastolic volumes, had greater functional recovery of Vi.Ki.E. parameters.

CONCLUSIONS

Intraoperative Vi.Ki.E shows immediate recovery of right ventricular mechanics after PVR with less cardiac fatigue and energy consumption, providing novel insights that may have a prognostic relevance for functional recovery.
Establishing a heart transplant programme using donation after circulatory-determined death donors: a United Kingdom based single-centre experience
Authors: Mehta Vipin , Taylor Marcus , Hasan Joanne , Dimarakis Ioannis , Barnard Jim , Callan Paul , Shaw Steven , Venkateswaran Rajamiyer V
Published: April 2019

OBJECTIVES

Demand for heart transplant donors worldwide continues to outstrip supply. Transplanting hearts following donation after circulatory-determined death (DCD) is increasingly recognized as a safe and effective alternative. As the fourth centre worldwide to have established such a programme, our goal was to present our initial experience.

METHODS

This was a single-centre retrospective observational study. All DCD hearts were retrieved using direct procurement and perfusion. Continuous normothermic perfusion of the procured heart was then established on the TransMedics® Organ Care System. The primary outcome of this study was the 30-day survival rate.

RESULTS

Between May 2017 and December 2018, 8 DCD hearts were procured and 7 were subsequently implanted, including in 2 patients who had left ventricular assist devices explanted. During the same time period, 30 patients received donation after brainstem death heart transplants. Therefore, the DCD heart transplant programme led to a 23% increase in transplant activity. The median donation warm ischaemic time was 34 min [interquartile range (IQR) 31–39 min]. The median functional warm ischaemic time was 28 min (IQR 25–30 min). The median time spent by the organ on the Organ Care System was 263 min (IQR 242–296 min). The overall 30-day survival rate was 100% and the 90-day survival rate was 86%. Postoperative extracorporeal membrane oxygenation was required in 3/7 (43%).

CONCLUSIONS

DCD heart transplants can lead to a 23% increase in heart transplant activity and should be adopted by more institutions across the world. Already established transplant programmes with good early outcomes can start such a programme safely.
A Mobile Genetic Element Promotes the Association Between Serotype M28 Group A Streptococcus Isolates and Cases of Puerperal Sepsis
Authors: Jain Ira , Sarkar Poulomee , Danger Jessica L , Medicielo Josette , Roshika Roshika , Calfee Gregory , Ramalinga Anupama , Burgess Cameron , Sumby Paul
Published: April 2019

Background

Bacterial infections following childbirth—so-called puerperal infections—cause morbidity in 5%–10% of all new mothers. At low frequency, the infection can spread to the blood, resulting in life-threatening sepsis known as puerperal sepsis. Pathogens causing puerperal sepsis include group A Streptococcus (GAS), and epidemiological analyses have identified isolates of a single serotype, M28, as being nonrandomly associated with cases of puerperal sepsis. The genomes of serotype M28 GAS isolates harbor a 36.3-kb mobile genetic element of apparent group B Streptococcus origin, termed region of difference 2 (RD2).

Methods

The phenotypic (determined via tissue culture and a vaginal colonization model) and regulatory (determined via RNA sequencing analysis) contributions of RD2 were assessed by comparing parental, RD2 deletion mutant, and complemented mutant serotype M28 GAS strains.

Results

RD2 affords serotype M28 isolates an enhanced ability to adhere to human vaginal epithelial cells and to colonize the female reproductive tract in a mouse model of infection. In addition, RD2 influences the abundance of messenger RNAs from >100 core chromosomal GAS genes.

Conclusions

The data are consistent with RD2 directly, via encoded virulence factors, and indirectly, via encoded regulatory proteins, modifying the virulence potential of GAS and contributing to the decades-old association of serotype M28 isolates with cases of puerperal sepsis.
Maize-Produced Ag2 as a Subunit Vaccine for Valley Fever
Authors: Hayden Celine A , Hung Chiung-Yu , Zhang Hao , Negron Austin , Esquerra Raymond , Ostroff Gary , Abraham Ambily , Lopez Alejandro Gabriel , Gonzales Juliet Elizabeth , Howard John A
Published: April 2019

Coccidioides is the causative agent of San Joaquin Valley fever, a fungal disease prevalent in the semiarid regions of the Americas. Efforts to develop a fungal vaccine over the last 2 decades were unsuccessful. A candidate antigen, Antigen 2 (Ag2), is notoriously difficult to express in Escherichia coli, and this study sought to accumulate the antigen at high levels in maize. Transformed maize lines accumulated recombinant Ag2 at levels >1 g/kg. Mice immunized with this antigen and challenged with live Coccidioides arthroconidia showed a reduction in the fungal load when Ag2 derived from either E. coli or maize was loaded into glucan chitin particles. A fusion of Ag2 to dendritic cell carrier peptide (DCpep) induced a T-helper type 17 response in the spleen when orally delivered, indicative of a protective immune response. The maize production platform and the glucan chitin particle adjuvant system show promise for development of a Coccidioides vaccine, but further testing is needed to fully assess the optimal method of administration.
The Arabidopsis receptor kinase STRUBBELIG undergoes clathrin-dependent endocytosis
Authors: Gao Jin , Chaudhary Ajeet , Vaddepalli Prasad , Nagel Marie-Kristin , Isono Erika , Schneitz Kay
Published: April 2019

Signaling mediated by cell surface receptor kinases is central to the coordination of growth patterns during organogenesis. Receptor kinase signaling is in part controlled through endocytosis and subcellular distribution of the respective receptor kinase. For the majority of plant cell surface receptors, the underlying trafficking mechanisms are not characterized. In Arabidopsis, tissue morphogenesis requires the atypical receptor kinase STRUBBELIG (SUB). Here, we studied the endocytic mechanism of SUB. Our data revealed that a functional SUB–enhanced green fluorescent protein (EGFP) fusion is ubiquitinated in vivo. We further showed that plasma membrane-bound SUB:EGFP becomes internalized in a clathrin-dependent fashion. We also found that SUB:EGFP associates with the trans-Golgi network and accumulates in multivesicular bodies and the vacuole. Co-immunoprecipitation experiments revealed that SUB:EGFP and clathrin are present within the same protein complex. Our genetic analysis showed that SUB and CLATHRIN HEAVY CHAIN (CHC) 2 regulate root hair patterning. By contrast, genetic reduction of CHC activity ameliorates the floral defects of sub mutants. Taken together, the data indicate that SUB undergoes clathrin-mediated endocytosis, that this process does not rely on stimulation of SUB signaling by an exogenous agent, and that SUB genetically interacts with clathrin-dependent pathways in a tissue-specific manner.
Maize pentatricopeptide repeat protein DEK41 affects cis-splicing of mitochondrial nad4 intron 3 and is required for normal seed development
Authors: Zhu Chenguang , Jin Guangpu , Fang Peng , Zhang Yan , Feng Xuzhen , Tang Yuanping , Qi Weiwei , Song Rentao
Published: April 2019

The splicing of organelle-encoded mRNA in plants requires proteins encoded in the nucleus. The mechanism of splicing and the factors involved are not well understood. Pentatricopeptide repeat (PPR) proteins are known to participate in such RNA–protein interactions. Maize defective kernel 41 (dek41) is a seedling-lethal mutant that causes developmental defects. In this study, the Dek41 gene was cloned by Mutator tag isolation and allelic confirmation, and was found to encode a P-type PPR protein that targets mitochondria. Analysis of the mitochondrial RNA transcript profile revealed that dek41 mutations cause reduced splicing efficiency of mitochondrial nad4 intron 3. Immature dek41 kernels exhibited severe reductions in complex I assembly and NADH dehydrogenase activity. Up-regulated expression of alternative oxidase genes and deformed inner cristae of mitochondria in dek41, as revealed by TEM, indicated that proper splicing of nad4 is essential for correct mitochondrial functioning and morphology. Consistent with this finding, differentially expressed genes in the dek41 endosperm included those related to mitochondrial function and activity. Our results indicate that DEK41 is a PPR protein that affects cis-splicing of mitochondrial nad4 intron 3 and is required for correct mitochondrial functioning and maize kernel development.
Communicating the risks of genetically modified organisms: lessons learnt from an Irish field of cisgenic potatoes
Authors: Mullins Ewen
Published: April 2019

Providing relatable context is key to communicating to the public the justification and outputs of GM crop research in a non-scientific manner so as to maximize societal comprehension.
The function of S-nitrosothiols during abiotic stress in plants
Authors: Begara-Morales Juan C , Chaki Mounira , Valderrama Raquel , Mata-Pérez Capilla , Padilla Maria N , Barroso Juan B
Published: April 2019

Nitric oxide (NO) is an active redox molecule involved in the control of a wide range of functions integral to plant biology. For instance, NO is implicated in seed germination, floral development, senescence, stomatal closure, and plant responses to stress. NO usually mediates signaling events via interactions with different biomolecules, for example the modulation of protein functioning through post-translational modifications (NO-PTMs). S-nitrosation is a reversible redox NO-PTM that consists of the addition of NO to a specific thiol group of a cysteine residue, leading to formation of S-nitrosothiols (SNOs). SNOs are more stable than NO and therefore they can extend and spread the in vivo NO signaling. The development of robust and reliable detection methods has allowed the identification of hundreds of S-nitrosated proteins involved in a wide range of physiological and stress-related processes in plants. For example, SNOs have a physiological function in plant development, hormone metabolism, nutrient uptake, and photosynthesis, among many other processes. The role of S-nitrosation as a regulator of plant responses to salinity and drought stress through the modulation of specific protein targets has also been well established. However, there are many S-nitrosated proteins that have been identified under different abiotic stresses for which the specific roles have not yet been identified. In this review, we examine current knowledge of the specific role of SNOs in the signaling events that lead to plant responses to abiotic stress, with a particular focus on examples where their functions have been well characterized at the molecular level.
Accurately computing weak lensing convergence
Authors: Koksbang Sofie Marie , Clarkson Chris
Published: April 2019

Weak lensing will play an important role in future cosmological surveys, including e.g. Euclid and SKA. Sufficiently accurate theoretical predictions are important for correctly interpreting these surveys and hence for extracting correct cosmological parameter estimations. We quantify for the first time in a relativistic setting how many post-Born and lens–lens coupling corrections are required for sub-per cent accuracy of the theoretical weak lensing convergence for $z$ ≤ 2 (the primary weak lensing range for Euclid and SKA). We do this by ray tracing through a fully relativistic exact solution of the Einstein field equations, which consists of randomly packed mass-compensated underdensities of realistic amplitudes. We find that including lens–lens coupling terms and post-Born corrections up to second and third order respectively is sufficient for sub-per cent accuracy of the convergence along $94{{\ \rm per\ cent}}$ of the studied light rays. We also find that a significant percentage of the studied rays have post-Born corrections of size over $10{{\ \rm per\ cent}}$ of the usual gravitational convergence, κ(1), and several rays even have post-Born corrections several times the size of κ(1) at $z$ = 2.
Aquatic Adaptation and Depleted Diversity: A Deep Dive into the Genomes of the Sea Otter and Giant Otter
Authors: Beichman Annabel C , Koepfli Klaus-Peter , Li Gang , Murphy William , Dobrynin Pasha , Kliver Sergei , Tinker Martin T , Murray Michael J , Johnson Jeremy , Lindblad-Toh Kerstin , Karlsson Elinor K , Lohmueller Kirk E , Wayne Robert K
Published: April 2019

Despite its recent invasion into the marine realm, the sea otter (Enhydra lutris) has evolved a suite of adaptations for life in cold coastal waters, including limb modifications and dense insulating fur. This uniquely dense coat led to the near-extinction of sea otters during the 18th–20th century fur trade and an extreme population bottleneck. We used the de novo genome of the southern sea otter (E. l. nereis) to reconstruct its evolutionary history, identify genes influencing aquatic adaptation, and detect signals of population bottlenecks. We compared the genome of the southern sea otter with the tropical freshwater-living giant otter (Pteronura brasiliensis) to assess common and divergent genomic trends between otter species, and with the closely related northern sea otter (E. l. kenyoni) to uncover population-level trends. We found signals of positive selection in genes related to aquatic adaptations, particularly limb development and polygenic selection on genes related to hair follicle development. We found extensive pseudogenization of olfactory receptor genes in both the sea otter and giant otter lineages, consistent with patterns of sensory gene loss in other aquatic mammals. At the population level, the southern sea otter and the northern sea otter showed extremely low genomic diversity, signals of recent inbreeding, and demographic histories marked by population declines. These declines may predate the fur trade and appear to have resulted in an increase in putatively deleterious variants that could impact the future recovery of the sea otter.
Safety and effectiveness of transjugular renal biopsy for systemic lupus erythematosus and antiphospholipid antibody syndrome patients taking antithrombotics
Authors: Nielly Hubert , Mathian Alexis , Cazenave Maud , Izzedine Hassan , Haroche Julien , Cohen-Aubart Fleur , Hie Miguel , Miyara Makoto , Pineton de Chambrun Marc , Benameur Neila , Hausfater Pierre , Pha Micheline , Boutin-Lê Thi Huong Du , Rouvier Philippe , Brocheriou Isabelle , Cluzel Philippe , Amoura Zahir
Published: April 2019

Background

Renal biopsy is the cornerstone of systemic lupus erythematosus (SLE) nephritis and antiphospholipid syndrome (APS) nephropathy management. However, transcutaneous renal biopsy (TCRB) is hampered by the antithrombotic treatment frequently prescribed for those diseases. Transjugular renal biopsy (TJRB) offers an attractive alternative for patients at increased risk of bleeding. The primary objective of the study was to describe the safety profile and diagnostic performance of TJRB in SLE and APS patients.

Methods

All SLE and/or APS patients who underwent a renal biopsy in our department (between January 2004 and October 2016) were retrospectively reviewed. Major complications were death, haemostasis nephrectomy, renal artery embolization, red blood cell transfusion, sepsis and vascular thrombosis; macroscopic haematuria, symptomatic perirenal/retroperitoneal bleeding and renal arteriovenous fistula without artery embolization were considered as minor complications.

Results

Two hundred and fifty-six TJRBs—119 without antithrombotics (untreated), 69 under aspirin and 68 on anticoagulants and 54 TCRBs without antithrombotics—were analysed. Their major and minor complication rates, respectively, did not differ significantly for the four groups: 0 and 8% for untreated TJRBs, 1 and 6% for aspirin-treated, 6 and 10% for anticoagulant-treated and 2 and 2% for TCRBs. The number of glomeruli sampled and the biopsy contribution to establishing a histological diagnosis was similar for the four groups.

Conclusions

TJRBs obtained from SLE and APS patients taking antithrombotics had diagnostic yields and safety profiles similar to those of untreated TCRBs. Thus, TJRB should be considered for SLE and APS patients at risk of bleeding.
Body mass index, weight-adjusted immunosuppression and the risk of acute rejection and infection after kidney transplantation: a cohort study
Authors: Flabouris Katerina , Chadban Steven , Ladhani Maleeka , Cervelli Matthew , Clayton Philip
Published: April 2019

Background

Body mass index (BMI) is associated with patient outcomes after kidney transplantation. We hypothesized that immunosuppression (IS) dosing is a contributing factor.

Methods

Using Australia and New Zealand Dialysis and Transplant registry data, we included all adult kidney-only transplant recipients over 2000–14 treated with prednisolone, mycophenolate and tacrolimus/cyclosporin (n = 7919). The exposure was BMI and the outcomes were time to: (i) acute rejection, (ii) fatal infection, (iii) cancer and (iv) graft; and (v) patient survival. We modelled BMI and IS dosing (in quartiles) as time-varying covariates in extended Cox models.

Results

Compared with a BMI of 25 kg/m2, a BMI of 35 was associated with acute rejection after adjusting for demographics and comorbidities [adjusted hazard ratio (aHR) = 1.29, 95% confidence interval (CI) 1.12–1.49]. This association virtually disappeared after correcting for IS (aHR = 1.09, 95% CI 0.93–1.29). A BMI of 35 was non-significantly associated with fewer fatal infections (aHR = 0.91, 95% CI 0.66–1.25), but this reversed after adjusting for IS (aHR = 1.54, 95% CI 1.03–2.28). Results for cancer were not significantly altered after adjusting for IS. Results for lower BMI were similarly not significantly altered though generally associated with worse outcomes.

Conclusions

Our findings show that the associations between high BMI, acute rejection and fatal infection after kidney transplantation were significantly altered after correcting for IS suggesting that relative under-dosing of obese patients may partially explain these associations.
When the Total is Less than the Sum of the Parts
Authors: Zahar Marie-Joëlle
Published: April 2019

This chapter examines the impact of territorial restructuring in Bosnia and Herzegovina (BiH) and the context in which it took place. It first considers the context that accompanied the breakup of the Socialist Federal Republic of Yugoslavia before discussing the period of constitutional engagement in the BiH. In particular, it highlights two major issues: the process (or lack thereof) of constitutional change and the centrality of territory. It then explores the role played by international engagement in the implementation of the Dayton Peace Agreement (which made the territorial reorganization of BiH possible), the activism of BiH’s Constitutional Court, and the influence of the European Court of Human Rights. Finally, it analyzes two important lessons from Bosnia with respect to how territorial cleavages ought to be handled in constitutional processes: state capture and citizen loyalties.
Inequality in a global perspective
Authors: Kanbur Ravi
Published: April 2019

The basic story of global inequality in the last three decades has been an overall decline, but one which is composed of quite intricate patterns. There has been a decline in between-country inequality as China and India have grown relative to the US and other rich countries. This has been accompanied by an increase in within-country inequality, but this is itself composed of rising inequality in some countries such as China, India, and the US, and declining inequality in other countries, including large economies in Latin America. Section II of the paper reviews these patterns, highlighting country diversity to make the central point that policy matters. Section III addresses a normative question—what relative weight should be given to within-country and between-country inequality in making an overall global assessment? This section brings on board recent philosophical discourse, including on inequality of opportunity in a global frame. Section IV returns to the ‘policy matters’ theme and takes up global constraints on national redistribution policy in a globalized world: for example, a race to the bottom on taxation to attract and keep capital and talent, and possible global institutional responses to alleviate these constraints.
Variation in the Role and Impact of Standing Committees: The Case of the French Senate
Authors: Morel Benjamin
Published: April 2019

The aim of this article is to question the variation in standing committees’ roles and impacts and to explore how the uniqueness of their constitutional role can obscure a variety of approaches and practices. The present study reflects on the diversity of these committees by examining the case of the French Senate. This article demonstrates that the heterogeneity of Senate committees may have consequences for the legislative process. Considering Parliament reform through a re-evaluation of the role of standing committees must therefore involve questioning committee differences. This article considers the different roles committees play in the Senate and examines their influence on the legislative process.
Predictors of low disease activity and clinical remission following belimumab treatment in systemic lupus erythematosus
Authors: Parodis Ioannis , Johansson Petter , Gomez Alvaro , Soukka Sofia , Emamikia Sharzad , Chatzidionysiou Katerina
Published: April 2019

Objectives

To identify predictors of low disease activity and clinical remission following belimumab treatment in SLE.

Methods

SLE patients who received belimumab 10 mg/kg (N = 563) in the BLISS-52 and BLISS-76 clinical trials were surveyed. The performance of baseline factors in predicting attainment of low disease activity (defined as Lupus Low Disease Activity State) or clinical remission [defined as clinical (c)SLEDAI-2K = 0] at week 52 from treatment initiation was evaluated using logistic regression. Organ damage was assessed using the SLICC/ACR Damage Index (SDI).

Results

We demonstrated a negative impact of established organ damage on attainment of Lupus Low Disease Activity State [SDI > 0; odds ratio (OR): 0.44; 95% CI 0.22, 0.90; P = 0.024] and the primary Lupus Low Disease Activity State condition, i.e. SLEDAI-2K ⩽ 4 with no renal activity, pleurisy, pericarditis or fever (SDI > 1; OR: 0.46; 95% CI 0.27, 0.77; P = 0.004); cognitive impairment/psychosis was found to mainly account for the latter association. Baseline SDI scores > 1 predicted failure to attain cSLEDAI-2K = 0 (OR: 0.53; 95% CI 0.30, 0.94; P = 0.030), with cutaneous damage mainly driving this association. Anti–dsDNA positivity increased (OR: 1.82; 95% CI 1.08, 3.06; P = 0.025) and cardiovascular damage reduced (OR: 0.13; 95% CI 0.02, 0.97; P = 0.047) the probability of attaining cSLEDAI-2K = 0 along with a daily prednisone equivalent intake restricted to ⩽7.5 mg.

Conclusion

Belimumab might be expected to be more efficacious in inducing low disease activity and clinical remission in SLE patients with limited or no organ damage accrued prior to treatment initiation. Patients with positive anti–dsDNA titres might be more likely to achieve clinical remission along with limited or no CS use.
Association of central adiposity with psoriasis, psoriatic arthritis and rheumatoid arthritis: a cross-sectional study of the UK Biobank
Authors: Ferguson Lyn D , Brown Rosemary , Celis-Morales Carlos , Welsh Paul , Lyall Donald M , Pell Jill P , McInnes Iain B , Siebert Stefan , Sattar Naveed
Published: April 2019

Objectives

To determine the independent association of central adiposity, assessed by waist circumference, with odds of psoriasis, PsA and RA prevalence after controlling for general adiposity (BMI).

Methods

A cross-sectional study of UK Biobank participants aged 40–70 years was performed. Logistic regression was used to calculate the odds of psoriasis, PsA and RA occurrence compared with controls without these conditions by waist circumference, adjusting for covariates: age, sex, smoking status, socioeconomic deprivation and self-reported physical activity (Model 1), followed additionally by BMI (Model 2).

Results

A total of 502 417 participants were included; 5074 with psoriasis (1.02%), 905 with PsA (0.18%), 5532 with RA (1.11%) and 490 906 controls without these conditions. Adjusted odds ratios (ORs) (Model 1) for psoriasis, PsA and RA, per s.d. (13.5 cm) higher waist circumference were 1.20 (95% CI 1.16, 1.23), 1.30 (95% CI 1.21, 1.39) and 1.21 (95% CI 1.17, 1.24), respectively (all P < 0.001). These ORs remained significant after further adjustment for BMI (Model 2) in psoriasis [OR 1.19 (95% CI 1.12, 1.27), P < 0.001] and RA [OR 1.19 (95% CI 1.12, 1.26), P < 0.001], but not in PsA [OR 1.11 (95% CI 0.95, 1.29), P = 0.127].

Conclusion

Central adiposity as measured by waist circumference is associated with greater odds of psoriasis and RA prevalence after adjustment for confounders and for BMI. Our findings add support for central adiposity as a long-term clinically relevant component of these conditions.
ANNUAL EFFECTIVE DOSE ASSESSMENT DUE TO RADON AND THORON PROGENIES IN DWELLINGS OF KILIMAMBOGO, KENYA
Authors: Nyambura C , Tokonami S , Hashim N O , Chege M W , Suzuki T , Kudo H , Hosoda M
Published: April 2019

Human beings are continuously exposed to ionising radiation originating from natural or artificial sources. Uranium-238 and Thorium-232 found in building materials are important sources of radon and thoron in the indoor environment. The concentration levels of radon, thoron and thoron progeny were measured in mud-walled, metallic or iron sheet-walled and stone-walled modern houses in Kilimambogo region, Kenya for 3 months. Radon and thoron concentration levels were measured using passive radon–thoron discriminative monitors (RADUET), while thoron progeny concentrations as the equilibrium equivalent thoron concentration (EETC) were measured using thoron progeny monitors. The mean radon concentration levels in mud, metallic and stone-walled dwellings were 67 ± 11, 60 ± 10 and 75 ± 10 Bq m−3, respectively. The mean thoron concentration levels in the corresponding dwellings were 195 ± 36, 71 ± 24 and 161 ± 31 Bq m−3, respectively, while EETCs were 12 ± 2, 3 ± 1 and 7 ± 1 Bq m−3, respectively. The annual effective doses for radon were 1.3 ± 0.2, 1.1 ± 0.1 and 1.4 ± 0.2 mSv y−1 in mud, metallic and stone-walled houses while those from thoron estimated from EETC were 2.4 ± 0.4, 0.5 ± 0.1 and 1.5 ± 0.2 mSv y−1 in the corresponding houses, respectively.
A Feasibility Study to Attribute Patients to Primary Interns on Inpatient Ward Teams Using Electronic Health Record Data
Authors: Schumacher Daniel J. , Wu Danny T.Y. , Meganathan Karthikeyan , Li Lezhi , Kinnear Benjamin , Sall Dana R. , Holmboe Eric , Carraccio Carol , van der Vleuten Cees , Busari Jamiu , Kelleher Matthew , Schauer Daniel , Warm Eric
Published: April 2019

Purpose

To inform graduate medical education (GME) outcomes at the individual resident level, this study sought a method for attributing care for individual patients to individual interns based on “footprints” in the electronic health record (EHR).

Method

Primary interns caring for patients on an internal medicine inpatient service were recorded daily by five attending physicians of record at University of Cincinnati Medical Center in August 2017 and January 2018. These records were considered gold standard identification of primary interns. The following EHR variables were explored to determine representation of primary intern involvement in care: postgraduate year, progress note author, discharge summary author, physician order placement, and logging clicks in the patient record. These variables were turned into quantitative attributes (e.g., progress note author: yes/no), and informative attributes were selected and modeled using a decision tree algorithm.

Results

A total of 1,511 access records were generated; 116 were marked as having a primary intern assigned. All variables except discharge summary author displayed at least some level of importance in the models. The best model achieved 78.95% sensitivity, 97.61% specificity, and an area under the receiver-operator curve of approximately 91%.

Conclusions

This study successfully predicted primary interns caring for patients on inpatient teams using EHR data with excellent model performance. This provides a foundation for attributing patients to primary interns for the purposes of determining patient diagnoses and complexity the interns see as well as supporting continuous quality improvement efforts in GME.
SQUIRE-EDU (Standards for QUality Improvement Reporting Excellence in Education): Publication Guidelines for Educational Improvement
Authors: Ogrinc Greg , Armstrong Gail E. , Dolansky Mary A. , Singh Mamta K. , Davies Louise
Published: April 2019

The SQUIRE 2.0 (Standards for QUality Improvement Reporting Excellence) guidelines were published in 2015 to increase the completeness, precision, and transparency of published reports about efforts to improve the safety, value, and quality of health care. The principles and methods applied in work to improve health care are often applied in educational improvement as well. In 2016, a group was convened to develop an extension to SQUIRE that would meet the needs of the education community. This article describes the development of the SQUIRE-EDU extension over a three-year period and its key components. SQUIRE-EDU was developed using an international, interprofessional advisory group and face-to-face meeting to draft initial guidelines; pilot testing of a draft version with nine authors; and further revisions from the advisory panel with a public comment period. SQUIRE-EDU emphasizes three key components that define what is necessary in systematic efforts to improve the quality and value of health professions education. These are a description of the local educational gap; consideration of the impacts of educational improvement to patients, families, communities, and the health care system; and the fidelity of the iterations of the intervention. SQUIRE-EDU is intended for the many and complex range of methods used to improve education and education systems. These guidelines are projected to increase and standardize the sharing and spread of iterative innovations that have the potential to advance pedagogy and occur in specific contexts in health professions education.
Vestibular Function Modulates the Benefit of Hearing Aids in People With Hearing Loss During Static Postural Control
Authors: Maheu M. , Behtani L. , Nooristani M. , Houde M. S. , Delcenserie A. , Leroux T. , Champoux F.
Published: April 2019

Objectives:

To evaluate the influence of auditory cues on postural sway in normal-hearing (NH) individuals, hearing-impaired individuals with vestibular impairment (HIVL), or hearing-impaired (HI) individuals without vestibular impairment.

Design:

Thirty-two participants received a hearing and a vestibular evaluation (vHIT, oVEMP, cVEMP) and then were separated in to three groups (NH, HI, HIVL). All participants had to stand on a force platform in four postural conditions (A: EO/firm, B: EC/firm, C: EO/Foam, D: EC/Foam) under two auditory conditions, with or without auditory cues.

Results:

Results revealed that first, there was a significant difference between HIVL and both HI and NH groups in conditions C and D without auditory cues. Second, greater improvement for HIVL compared to NH and HI groups in condition C and D was observed with auditory cues. Finally, somatosensory reliance significantly decreased for the HIVL participants using hearing aids compared to NH and HI.

Conclusions:

Our results suggest that hearing aids benefit for postural control may be modulated by vestibular function.
The Fear of Tinnitus Questionnaire: Toward a Reliable and Valid Means of Assessing Fear in Adults with Tinnitus
Authors: Fuller Thomas E. , Cima Rilana F. F. , Van den Bussche Eva , Vlaeyen Johan W. S.
Published: April 2019

Objectives:

The purpose of this study was to assess the factor structure, reliability, and validity of the Fear of Tinnitus Questionnaire (FTQ); a brief self-report measure of people’s fears about potential cognitive, emotional, behavioral, and social consequences of living with tinnitus.

Design:

Five hundred eighty-eight Dutch-speaking adults with tinnitus completed an online battery of questionnaires measuring tinnitus-related distress, fear, catastrophizing, and quality of life. The sample was randomly split into two to perform exploratory and Bayesian confirmatory factor analyses. A subsample of participants (n = 144) completed the battery of questionnaires a second time after a 2-week interval to calculate test-retest reliability and conduct a Bland-Altman analysis. Convergent and concurrent validity of the FTQ was assessed with the complete data set and measures of tinnitus-related distress as the outcome.

Results:

Exploratory factor analyses indicated that single- and three-factor FTQ models were both valid solutions. Posterior predictive p values for the Bayesian confirmatory factor analyses ranged between 0.51 and 0.53 indicating that the respective models were an excellent fit for the data. The FTQ showed excellent test-retest reliability (average value intraclass correlation coefficient (ICC) = 0.92; 95% confidence interval, 0.89–0.95) and in the Bland-Altman analysis, satisfactory agreement between participants’ scores after a 2-week interval. Furthermore, the FTQ demonstrated good internal reliability (α = 0.83, 95% confidence interval, 0.81–0.85) and added statistically significant amounts of variance to models predicting tinnitus-related distress and interference in daily life.

Conclusions:

The FTQ has good psychometric properties and can be used to assess people’s fear of tinnitus in research or clinical settings. Further work to establish the reliability and validity should be conducted and include an examination of a version of the FTQ that uses Likert-type response scales which might offer improved sensitivity.
The Use of Static and Dynamic Cues for Vowel Identification by Children Wearing Hearing Aids or Cochlear Implants
Authors: Hedrick Mark , Thornton Kristen E. T. , Yeager Kelly , Plyler Patrick , Johnstone Patti , Reilly Kevin , Springer Cary
Published: April 2019

Objective:

To examine vowel perception based on dynamic formant transition and/or static formant pattern cues in children with hearing loss while using their hearing aids or cochlear implants. We predicted that the sensorineural hearing loss would degrade formant transitions more than static formant patterns, and that shortening the duration of cues would cause more difficulty for vowel identification for these children than for their normal-hearing peers.

Design:

A repeated-measures, between-group design was used. Children 4 to 9 years of age from a university hearing services clinic who were fit for hearing aids (13 children) or who wore cochlear implants (10 children) participated. Chronologically age-matched children with normal hearing served as controls (23 children). Stimuli included three naturally produced syllables (/ba/, /bi/, and /bu/), which were presented either in their entirety or segmented to isolate the formant transition or the vowel static formant center. The stimuli were presented to listeners via loudspeaker in the sound field. Aided participants wore their own devices and listened with their everyday settings. Participants chose the vowel presented by selecting from corresponding pictures on a computer screen.

Results:

Children with hearing loss were less able to use shortened transition or shortened vowel centers to identify vowels as compared to their normal-hearing peers. Whole syllable and initial transition yielded better identification performance than the vowel center for /ɑ/, but not for /i/ or /u/.

Conclusions:

The children with hearing loss may require a longer time window than children with normal hearing to integrate vowel cues over time because of altered peripheral encoding in spectrotemporal domains. Clinical implications include cognizance of the importance of vowel perception when developing habilitative programs for children with hearing loss.