bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation of Sustainable Development Goals in construction industry - a systemic consideration of synergies and trade-offs
Authors: Wieser A A , Scherz M , Maier S , Passer A , Kreiner H
Published: September 2019

According to sustainability research the world has exceeded four out of seven planetary boundaries. The areas of climate change, biodiversity loss, nitrogen cycle and land use have left the so called safe operating space for humanity. The built environment is one of the major contributors to environmental impacts. Especially the embodied energy during the construction phase of the built environment and the energy demands during the use of buildings contribute to a high energy and resource consumption. In the year 2015 the United Nations adopted the Sustainable Development Goals (SDGs), a universal development agenda, which goals need to be fulfilled by the year 2030 and by all UN countries worldwide. Amongst other countries Austria has adopted the 2030 agenda and has committed itself to the SDGs. Research objective was to explore the application of systemic approaches in the field of SDGs. The work presents a systematic literature review (SLR) and discusses an application of a qualitative system analysis (carried out with the tool iMODELER) on the SDGs. Results show how interdependencies among SDGs and among chosen concrete actions, e.g. for the built environment, can be visualized for a better systemic understanding. By visualizing synergies and trade-offs, effects of decisions taken can be estimated from a holistic perspective.
Quantitative biogeography of Orthoptera does not support classical qualitative regionalization of the Carpathian Mountains
Authors: Jarčuška Benjamín , Kaňuch Peter , Naďo Ladislav , Krištín Anton
Published: September 2019

The first biogeographical division of the Carpathians, the second largest mountain range in Europe, was based on qualitative observational floristic data > 100 years ago and has also been applied for the regional zoogeography. In this study, the recent availability of detailed quantitative data allowed us to perform a more powerful evaluation of the classical biogeographical regions of the area. Thus, we analysed updated distribution patterns of 137 Orthoptera species native to the Carpathian Mountains and, by using published species range maps, we compiled data on species presence or absence within 2576 cells of a 10 km × 10 km universal transverse mercator grid in the area. Pattern analysis of the data was based on non-metric multidimensional scaling and clustering using six different algorithms applied to a β sim dissimilarity matrix. The unweighted pair-group method using arithmetic averages, which gave the best performance in the analysis of species turnover, delineated four regions. Environmental variables and species richness were used in logistic regression as predictors of delineated clusters, and indicator species were identified for each of the inferred regions. The pattern can be explained, in part, by environmental variables and species richness (34.2%) and was also influenced by connections with the orthopterofauna from adjacent areas. The observed discrepancy between regionalization based on expert knowledge and the pattern revealed using quantitative data provides a warning that the biogeography of the Carpathians might also have been revised in other taxa, where only classical qualitative regionalization exists.
Chronic subthreshold cortical stimulation and stimulation-related EEG biomarkers for focal epilepsy
Authors: Lundstrom Brian Nils , Gompel Jamie Van , Khadjevand Fatemeh , Worrell Greg , Stead Matt
Published: September 2019

Brain stimulation offers an alternative to focal resection for the treatment of focal drug-resistant epilepsy. Chronic subthreshold cortical stimulation is an individualized biomarker-informed open-loop continuous electrical stimulation approach targeting the seizure onset zone and surrounding areas. Before permanent implantation, trial stimulation is performed during invasive monitoring to assess stimulation efficacy as well as to optimize stimulation location and parameters by modifying interictal EEG biomarkers. We present clinical and neurophysiological results from a retrospective analysis of 21 patients, showing a median percent reduction in seizure frequency of 100% and responder rate of 89% with a median follow-up of 27 months. About 40% of patients were free of disabling seizures for a 12-month period or longer. We find that stimulation-induced decreases in delta (1–4 Hz) power and increases in alpha and beta (8–20 Hz) power during trial stimulation correlate with improved long-term clinical outcomes. These results suggest chronic subthreshold cortical stimulation may be an effective alternative approach to treating focal drug-resistant epilepsy and that short-term stimulation-related changes in spectral power may be a useful interictal biomarker and relate to long-term clinical outcome.
Cardiac resynchronization therapy reduces expression of inflammation-promoting genes related to interleukin-1β in heart failure
Authors: Bilchick Kenneth , Kothari Hema , Narayan Aditya , Garmey James , Omar Abdullah , Capaldo Brian , McNamara Coleen
Published: September 2019

Aims

In light of recent data regarding inflammatory signalling pathways in cardiovascular disease and the recently demonstrated impact of pharmacologic inhibition of interleukin-1β (IL-1β) in heart failure, the primary aim was to assess the physiologic effects of cardiac resynchronization therapy (CRT) on the expression of systemic inflammatory, immune-modulatory, metabolic, and apoptotic genes in peripheral blood mononuclear cells (PBMCs) of patients with heart failure.

Methods and results

We used RNA sequencing (RNA-Seq) and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) to identify gene expression changes in PBMCs in response to CRT. In total, 27 patients were analysed: 12 with heart failure undergoing CRT, 6 with heart failure undergoing standard implanted cardioverter defibrillators, and 9 with coronary artery disease but not heart failure. In CRT patients (median age 65.5 years, interquartile range 63.0–66.8 years, 33% female), RNA-Seq analysis identified 40 genes, including multiple genes associated with the IL-1β pathway, with significant correlations (false discovery rate < 0.05) with four key CRT response measures. CRT was associated with suppression of PBMC expression of IL-1β (1.80-fold decrease, P = 0.047), FOS proto-oncogene (FOS) (3.25-fold decrease, P = 0.01), dual specificity phosphatase 1 (DUSP1) (2.05-fold decrease, P = 0.001), and early growth response 1 (EGR1) (7.38-fold decrease, P = 0.03), and suppression was greater in responders vs. non-responders (P = 0.03 for IL-1β, P = 0.02 for FOS, P = 0.02 for DUSP1, and P = 0.11 for EGR1). Baseline FOS and DUSP-1 levels were greater in responders vs. non-responders (6.15-fold higher, FOS, P = 0.002; 2.60-fold higher, DUSP1, P = 0.0001). CRT responders but not non-responders showed higher baseline gene expression of FOS (P = 0.04) and DUSP1 (P = 0.06) compared with control patients without heart failure. Baseline serum high-sensitivity C-reactive protein levels were 3.47-fold higher in CRT responders vs. non-responders (P = 0.008).

Conclusion

Treatment of heart failure with CRT resulted in decreased PBMC expression of genes linked to inflammation. Moreover, CRT responders had higher expression of these inflammatory genes prior to CRT and greater suppression of these genes after CRT compared with non-responders.
Relationships Among Deaf/Hard-of-Hearing Siblings: Developing a Sense of Self
Authors: Eichengreen Adva , Zaidman-Zait Anat
Published: September 2019

While sibling relationships are known to be important for children’s social and emotional well-being, little is known about sibling relationships when both siblings are deaf or hard-of-hearing (DHH). In-depth interviews were conducted with 10 young DHH adults (20–30 years old) who had studied in mainstream schools to explore their retrospective experiences of growing up with a DHH sibling. Interviews were analyzed using interpretive phenomenological analysis. Findings revealed two superordinate themes: (1) sibling relationship and sense of self and (2) family coping and relationships, with each superordinate theme containing several subthemes. Findings highlighted the various ways sibling relationships contribute to siblings’ psychological development, identity formation, and coping with deafness. Potential challenges were identifed, as well as the role of parents’ attitudes and coping with hearing loss in promoting supportive sibling relationships. Parents and professionals should be aware of the valuable and unique aspects of DHH siblingship and attend to imporatnt relationship asepcts such as sibling communication, sibling comparisons, and parental differential treatment.
Regional myocardial work by cardiac magnetic resonance and non-invasive left ventricular pressure: a feasibility study in left bundle branch block
Authors: Larsen Camilla Kjellstad , Aalen John M , Stokke Caroline , Fjeld Jan Gunnar , Kongsgaard Erik , Duchenne Jürgen , Degtiarova Ganna , Gheysens Olivier , Voigt Jens-Uwe , Smiseth Otto A , Hopp Einar
Published: September 2019

Aims

Regional myocardial work may be assessed by pressure–strain analysis using a non-invasive estimate of left ventricular pressure (LVP). Strain by speckle tracking echocardiography (STE) is not always accessible due to poor image quality. This study investigated the estimation of regional myocardial work from strain by feature tracking (FT) cardiac magnetic resonance (CMR) and non-invasive LVP.

Methods and results

Thirty-seven heart failure patients with reduced ejection fraction, left bundle branch block (LBBB), and no myocardial scar were compared to nine controls without LBBB. Circumferential strain was measured by FT-CMR in a mid-ventricular short-axis cine view, and longitudinal strain by STE. Segmental work was calculated by pressure–strain analysis. Twenty-five patients underwent 18F-fluorodeoxyglucose (FDG) positron emission tomography. Segmental values were reported as percentages of the segment with maximum myocardial FDG uptake. In LBBB patients, net CMR-derived work was 51 ± 537 (mean ± standard deviation) in septum vs. 1978 ± 1084 mmHg·% in the left ventricular (LV) lateral wall (P < 0.001). In controls, however, there was homogeneous work distribution with similar values in septum and the LV lateral wall (non-significant). Reproducibility was good. Segmental CMR-derived work correlated with segmental STE-derived work and with segmental FDG uptake (average r = 0.71 and 0.80, respectively).

Conclusion

FT-CMR in combination with non-invasive LVP demonstrated markedly reduced work in septum compared to the LV lateral wall in patients with LBBB. Work distribution correlated with STE-derived work and energy demand as reflected in FDG uptake. These results suggest that FT-CMR in combination with non-invasive LVP is a relevant clinical tool to measure regional myocardial work.
Low quality of some generic cardiovascular medicinal products represents a matter for growing concern
Authors: Tamargo Juan , Rosano Giuseppe
Published: September 2019

Aims 

Generic medicinal products (GMPs) are low-priced copies of off-patent medicines that reduce healthcare costs and broaden access to healthcare. Thus, healthcare authorities, professionals, and providers recommend their use. In recent years, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved hundreds of GMPs based on specific bioequivalent trials. The question is whether the brand name drugs and GMPs or the different GMPs similar in purity, efficacy, and safety.

Methods and results 

We have reviewed the progressive increasing recalls and warning letters of cardiovascular GMPs issued recently by the FDA/EMA. Both Agencies found numerous irregularities in the purity, safety, effectiveness, and current good manufacturing practices in some GMPs widely used in cardiovascular therapy. This evidence and the recent identification of nitrosamine impurities classified as probable human carcinogens in several angiotensin receptor blockers confirm that the presence of low-quality/substandard GMPs represents a serious public health problem with significant impact on national clinical and economic burden.

Conclusion 

A global strategy that unifies the efforts of all the stakeholders, including drug manufacturers, healthcare providers, governments, health professionals, patients, and judicial systems are needed to protect the drug chain supply and ensure that only high-quality GMPs are available for use.
Description of Polaribacter aestuariivivens sp. nov., isolated from a tidal flat
Authors: Park Sooyeon , Park Ji-Min , Lee Jung-Sook , Yoon Jung-Hoon
Published: September 2019

A bacterial strain, DBTF-3T, was isolated from a tidal flat of Republic of Korea. Phylogenetic trees of 16S rRNA gene sequences showed that strain DBTF-3T belonged to the genus Polaribacter. Strain DBTF-3T exhibited 16S rRNA gene sequence similarities of 97.1–98.1% to type strains of P. dokdonensis, P. haliotis, P. marinaquae, P. insulae, P. vadi, P. glomeratus, P. irgensii and P. reichenbachii, and 94.0–96.9% to those of the other Polaribacter species. DNA–DNA relatedness values of strain DBTF-3T with type strains of P. marinaquae and P. insulae were 14–19%. Average nucleotide identity and digital DNA–DNA hybridization values between strain DBTF-3T and type strains of six other Polaribacter species were 76.5–83.5% and 20.9–27.1%, respectively. Strain DBTF-3T contained MK-6 as the predominant menaquinone, and iso-C15:0, summed feature 3, iso-C15:1 G and iso-C15:0 3-OH as the major fatty acids. The major polar lipids were phosphatidylethanolamine and one unidentified lipid. Differential phenotypic properties, together with its phylogenetic and genetic distinctiveness, revealed that strain DBTF-3T is separated from Polaribacter species. On the basis of the data presented, strain DBTF-3T (= KACC 19612T = NBRC 113191T) represents a novel species of the genus Polaribacter, for which the name Polaribacter aestuariivivens sp. nov. is proposed.
Is ‘Health for All’ synonymous with ‘antibiotics for all’: changes in antibiotic prescribing in a performance-based financing pilot in Zanzibar
Authors: Hadley Mary B , Beard James
Published: September 2019

Universal Health Coverage, to meet the Sustainable Development Goal of ‘Health for All’, aims to increase the access of preventative and curative care services, particularly to the poor and vulnerable. However, the very provision of curative services by health providers in the primary care setting in low-income countries is considered one of the major drivers of antimicrobial resistance. The Zanzibar Ministry of Health introduced performance-based financing (PBF) in 2 of 10 Health Districts in July 2013. Payments to health facilities and staff were on a fee-for-service basis using ‘direct quality indicators’. Results of an evaluation of secondary data of two indicators, ‘treatment according to guidelines’ and ‘antibiotics prescribed according to guidelines’ from 31 Primary Health Care Units in the two PBF pilot districts are compared with 28 in non-PBF districts. The proportion of patients treated with an antibiotic not in accordance with treatment guidelines after the introduction of PBF fell to 2%, 6% and 5% in 2014, 2015 and 2016, respectively, compared with an increase from 25% (2013) to 31% (2014) and 22% (2015, 2016) in non-PBF facilities. The key take-home messages from this evaluation are firstly that ‘direct quality indicators’ to improve the use of treatment guidelines, introduced into a national PBF reform that includes financial incentives and rigorous verification of register entries, have the potential to significantly reduce inappropriate use of antibiotics in high population density settings in Africa. Secondly, for a sustained reduction in the overall proportion of unnecessary antibiotic prescriptions rigorous monitoring of health worker behaviour is required to address changes in prescribing practice. A well-designed and monitored PBF with ‘direct quality indicators’ has the potential to ensure that ‘Health for All’, in terms of increased access to primary health services is not synonymous with ‘antibiotics for all’.
Going operational with health systems governance: supervision and incentives to health workers for increased quality of care in Tanzania
Authors: Francetic Igor , Tediosi Fabrizio , Salari Paola , de Savigny Don
Published: September 2019

Improving the quality of care is increasingly recognized as a priority of health systems in low- and middle-income countries. Given the labour-intensive nature of healthcare interventions, quality of care largely depends upon the number, training and management of health workers involved in service delivery. Policies available to boost the performance of health workers—and thus the quality of healthcare—include regulation, incentives and supervision—all of which are typically included in quality improvement frameworks and policies. This was the case in Tanzania, where we assessed the role of selected quality improvement policies. To do so, we analysed data from a representative sample of Tanzanian government-managed health facilities, part of the 2014/15 Service Provision Assessment component of the Demographic and Health Survey. We constructed two healthcare quality indicators from data on patient visits: (1) compliance with Integrated Management of Childhood Illness (IMCI) guidelines and (2) patient satisfaction. Using multilevel ordered logistic regression models, we estimated the associations between the outcomes and selected indicators of incentives and supervisory activity at health worker and health facility level. We did not identify any association for the different indicators of top-down supervision at facility and individual level, neither with IMCI compliance nor with patients’ satisfaction. Bottom-up supervision, defined as meetings between community and health facility staff, was significantly associated with higher patient satisfaction. Financial incentives in the form of salary top-ups were positively associated with both IMCI compliance and patient satisfaction. Both housing allowances and government-subsidized housing were positively associated with our proxies of quality of care. Good healthcare quality is crucial for promoting health in Tanzania not only through direct outcomes of the process of care but also through increased care-seeking behaviour in the communities. The results of this study highlight the role of community involvement, better salary conditions and housing arrangements for health workers.
Use of evidence and negotiation in the review of national standard treatment guidelines and essential medicines list: experience from Ghana
Authors: Koduah Augustina , Asare Brian A , Gavor Edith , Gyansa-Lutterodt Martha , Andrews Annan Edith , Ofei Francis W
Published: September 2019

Understanding how countries review their national standard treatment guidelines (STGs) and essential medicines list (EML) is important in the light of ever-changing trends in public health and evidence supporting the selection and use of medicines in disease management. This study examines the 2017 STGs and EML review process, the actors involved and how the list of medicines and disease conditions evolved between the last two editions. We examined expert committee reports, stakeholder engagement reports and the last two editions (2010, 2017) STGs and EML. The review process occurred in both bureaucratic and public arenas where various actors with varied power and interest engaged in ways to consolidate their influence with the use of evidence from research and practice. In the bureaucratic arena, a national medicines selection committee inaugurated by the Minister of Health assessed the 2010 edition through technical sessions considering the country’s disease burden, hierarchical healthcare structure and evidence on safety and efficacy and expert opinion. To build consensus and ensure credibility service providers, professional bodies and healthcare managers scrutinized the assessed guidelines and medicines list in public arenas. In such public arenas, technical discussions moved towards negotiations with emphasis on practicability of the policies. Updates in the 2017 guidelines involved the addition of 64 new disease conditions in the STG, with the EML including 153 additional medicines and excluding 56 medicines previously found in the 2010 EML. Furthermore, the level of care categorization for Level ‘A’ [i.e. community-based health planning and services (CHPS)] and Level ‘M’ (i.e. midwifery and CHPS with a midwife) evolved to reflect the current primary healthcare and community mobilization activities for healthcare delivery in Ghana. Ghana’s experience in using evidence from research and practice and engaging wide stakeholders can serve as lessons for other low and middle-income countries.
Systemic AAV8-mediated delivery of a functional copy of muscle glycogen phosphorylase (Pygm) ameliorates disease in a murine model of McArdle disease
Authors: McNamara Elyshia L , Taylor Rhonda L , Clayton Joshua S , Goullee Hayley , Dilworth Kimberley L , Pinós Tomàs , Brull Astrid , Alexander Ian E , Lisowski Leszek , Ravenscroft Gianina , Laing Nigel G , Nowak Kristen J
Published: September 2019

McArdle disease is a disorder of carbohydrate metabolism that causes painful skeletal muscle cramps and skeletal muscle damage leading to transient myoglobinuria and increased risk of kidney failure. McArdle disease is caused by recessive mutations in the muscle glycogen phosphorylase (PYGM) gene leading to absence of PYGM enzyme in skeletal muscle and preventing access to energy from muscle glycogen stores. There is currently no cure for McArdle disease. Using a preclinical animal model, we aimed to identify a clinically translatable and relevant therapy for McArdle disease. We evaluated the safety and efficacy of recombinant adeno-associated virus serotype 8 (rAAV8) to treat a murine model of McArdle disease via delivery of a functional copy of the disease-causing gene, Pygm. Intraperitoneal injection of rAAV8-Pygm at post-natal day 1–3 resulted in Pygm expression at 8 weeks of age, accompanied by improved skeletal muscle architecture, reduced accumulation of glycogen and restoration of voluntary running wheel activity to wild-type levels. We did not observe any adverse reaction to the treatment at 8 weeks post-injection. Thus, we have investigated a highly promising gene therapy for McArdle disease with a clear path to the ovine large animal model endemic to Western Australia and subsequently to patients.
Superior mesenteric flow pattern during counterpulsation: is simply a shorter balloon the solution for visceral hypoperfusion?
Authors: de Jong Monique M J , Parise Orlando , Matteucci Francesco , Tetta Cecilia , Maessen Jos G , Gelsomino Sandro
Published: September 2019

OBJECTIVES

We studied the flow pattern in the superior mesenteric artery (SMA) during intra-aortic balloon pump support, comparing 2 intra-aortic balloons of 2 different lengths.

METHODS

Sixteen Landrace pigs (mean weight 84.0 kg ± 6.0) were used in this study. The animals were randomly assigned to 2 groups: group 1 received an 8-Fr, 40-ml standard balloon; group 2 received an 8-Fr, 40-ml short balloon. SMA flow was measured during early, mid- and telediastole.

RESULTS

The standard balloon led to a reduction in SMA flow in early diastole (P < 0.001), a negative flow in mid-diastole (P < 0.001) and a reincrease in telediastole (P < 0.001). In contrast, in early diastole a significant reduction was observed with the short balloon (P < 0.001), followed by another drop in mid-diastole (P < 0.001), without reaching negative values and by a telediastolic increase (P < 0.001). SMA flows were comparable between balloons during early diastole (P = 0.66), whereas they were higher with the short balloon during mid (P < 0.001) and telediastole (P = 0.02). Overall, the diastolic area was significantly larger when the short balloon was used (P < 0.001). Finally, during counterpulsation, mesenteric resistances increased significantly (P < 0.001), although, with the short balloon, they were lower than with the standard balloon (P = 0.01).

CONCLUSIONS

Despite better overall mean mesenteric diastolic flow, the short balloon leads to early- and mid-diastolic flow reduction, although to a lesser extent than the standard intra-aortic balloon pump balloon. Our data are a call for improvement in the design of the short balloon.
Skin marking with computed tomography at functional residual capacity to predict lung nodule site
Authors: Miyoshi Ryo , Yamashina Akihiko , Nishikawa Shigeto , Tamari Shigeyuki , Noguchi Misa , Hijiya Kyoko , Chihara Koji
Published: September 2019

Various marking techniques for lung nodules may be complex and can cause serious complications. In this study, we aimed to describe and evaluate the feasibility of CTFRC marking, a novel preoperative skin marking technique guided by computed tomography (CT) at functional residual capacity (FRC). This simple and non-invasive marking technique only requires a preoperative CT scan without any anaesthesia. We retrospectively reviewed CTFRC markings performed for 109 lung nodules in 108 patients. The mean nodule size was 11.4 ± 5.0 mm. The mean distance from the nodule to the lung marking point was 3.8 ± 7.3 mm. We found no procedure-associated complications. CTFRC marking is a simple, safe and non-invasive method to predict the precise location of lung nodules during thoracoscopic surgery.
Dietary n-3 polyunsaturated fatty acids, fish intake and healthy ageing
Authors: García-Esquinas Esther , Ortolá Rosario , Banegas Jose Ramón , Lopez-García Esther , Rodríguez-Artalejo Fernando
Published: September 2019

Background

Seafood consumption and dietary intake of n-3 polyunsaturated fatty acids (PUFA) protect from cardiovascular disease, muscle wasting and mortality; however, their role in delaying unhealthy ageing is uncertain.

Methods

A prospective cohort study with 1592 community-dwelling individuals aged ≥60 years recruited in 2008–2010, and followed through 2015. Intake of seafood and n-3 PUFA [eicosapentanoic acid (EPA) and docosahexanoic acid (DHA)] was estimated using a validated diet history and food composition tables. Unhealthy ageing was assessed across the domains of physical and cognitive function, mental health, morbidity, self-rated health and vitality.

Results

Higher blue fish consumption was negatively associated with unhealthy ageing in 2015 [multivariate ß (95% confidence interval) per interquartile range (IQR) increase of fish: −0.49 (−0.90; −0.08)] and, specifically, was associated with lower accumulation of functional impairments [−1.00 (−1.71; −0.28)] and morbidities [−0.30 (−0.73; 0.13)]. Individuals with high intakes of EPA (≥0.47 g/day) and DHA (≥0.89 g/day) presented the highest reductions in age-related deficits accumulation: −1.61 (−3.01; −0.22) and −1.34 (−2.76; 0.08), respectively. Intake of EPA and DHA were negatively associated with the accumulation of functional deficits [results per IQR increase: −0.79 (−1.64; −0.06) and −0.84 (−1.67; −0.01), respectively] and morbidities [−0.60 (−1.10; −1.11) and −0.60 (−1.09; −0.11)]. No associations were observed between n-3 PUFA and self-rated or mental health, or between white fish and unhealthy ageing.

Conclusions

In this cohort of Spanish individuals with elevated intake of fish and a high adherence to the Mediterranean diet, consumption of blue fish and n-3 PUFA had a prospective protective association with deficits accumulation.
Cytokine Induction in Nipah Virus–Infected Primary Human and Porcine Bronchial Epithelial Cells
Authors: Elvert Mareike , Sauerhering Lucie , Maisner Andrea
Published: September 2019

During the Nipah virus (NiV) outbreak in Malaysia, pigs and humans were infected. While pigs generally developed severe respiratory disease due to effective virus replication and associated inflammation processes in porcine airways, respiratory symptoms in humans were rare and less severe. To elucidate the reasons for the species-specific differences in NiV airway infections, we compared the cytokine responses as a first reaction to NiV in primary porcine and human bronchial epithelial cells (PBEpC and HBEpC, respectively). In both cell types, NiV infection resulted in the expression of type III interferons (IFN-λ). Upon infection with similar virus doses, viral RNA load and IFN expression were substantially higher in HBEpC. Even if PBEpC expressed the same viral RNA amounts as NiV-infected HBEpC, the porcine cells showed reduced IFN- and IFN-dependent antiviral gene expression. Despite this inherently limited IFN response, the expression of proinflammatory cytokines (IL-6, IL-8) in NiV-infected PBEpC was not decreased. The downregulation of antiviral activity in the presence of a functional proinflammatory cytokine response might be one of the species-specific factors contributing to efficient virus replication and acute inflammation in the lungs of pigs infected with the Malaysian NiV strain.
Pneumococci Can Become Virulent by Acquiring a New Capsule From Oral Streptococci
Authors: Nahm Moon H , Brissac Terry , Kilian Mogens , Vlach Jiri , Orihuela Carlos J , Saad Jamil S , Ganaie Feroze
Published: September 2019

Pneumococcal conjugate vaccines have been successful, but their use has increased infections by nonvaccine serotypes. Oral streptococci often harbor capsular polysaccharide (PS) synthesis loci (cps). Although this has not been observed in nature, if pneumococcus can replace its cps with oral streptococcal cps, it may increase its serotype repertoire. In the current study, we showed that oral Streptococcus strain SK95 and pneumococcal strain D39 both produce structurally identical capsular PS, and their genetic backgrounds influence the amount of capsule production and shielding from nonspecific killing. SK95 is avirulent in a well-established in vivo mouse model. When acapsular pneumococcus was transformed with SK95 cps, the transformant became virulent and killed all mice. Thus, cps from oral Streptococcus strains can make acapsular pneumococcus virulent, and interspecies cps transfer should be considered a potential mechanism of serotype replacement. Our findings, along with publications from the US Centers for Disease Control and Prevention, highlight potential limitations of the 2013 World Health Organization criterion for studying pneumococcal serotypes carried without isolating bacteria.

We show that an oral streptococcal strain, SK95, and a pneumococcal strain, D39, both produce chemically identical capsular PS. We also show that transferring SK95 cps into noncapsulated, avirulent pneumococcus gave it the capacity for virulence in a mouse model.
The International Trade Regime and the Quest for Free Digital Trade
Authors: Azmeh Shamel , Foster Christopher , Echavarri Jaime
Published: September 2019

The global economy is experiencing the digitalization of production, exchange, and consumption of goods and services. The internet and cross-border data flows are becoming important channels of trade as more products are traded through the web or integrate features that rely on digital connectivity. Reflecting the autonomy states have to enact such policies, national variations in internet governance have expanded over the previous decade, with states increasingly looking to use internet and data policies for economic and trade objectives. These dynamics are having important implications on the international trade regime through challenging existing trade rules and creating demands for new rules. This has resulted in growing debates in the trade arena around “digital trade,” as a number of states, led by the United States, push for rules as a way to discipline national internet policies and support trade in digital goods and services. This paper examines the political economy of this campaign. We argue that the objectives of this campaign go beyond updating rules to better fit the “Internet age” into achieving further liberalization of trade in goods and services. We highlight the technological contingency of existing international rules and show how technological shifts have been a driver of competitive regime creation and forum shifting contributing to processes of fragmentation of the international trade regime.
Opportunities to reduce antibiotic prescribing for patients with COPD in primary care: a cohort study using electronic health records from the Clinical Practice Research Datalink (CPRD)
Authors: Rockenschaub Patrick , Jhass Arnoupe , Freemantle Nick , Aryee Anna , Rafiq Meena , Hayward Andrew , Shallcross Laura
Published: September 2019

Background

In primary care there is uncertainty about which patients with acute exacerbations of COPD (AECOPD) benefit from antibiotics.

Objectives

To identify which types of COPD patients get the most antibiotics in primary care to support targeted antibiotic stewardship.

Methods

Observational study of COPD patients using a large English primary care database with 12 month follow-up. We estimated the incidence of and risk factors for antibiotic prescribing relative to the number of AECOPD during follow-up, considering COPD severity, smoking, obesity and comorbidity.

Results

From 157 practices, 19594 patients were diagnosed with COPD, representing 2.6% of patients and 11.5% of all prescribed antibiotics. Eight hundred and thirty-three (4.5%) patients with severe COPD and frequent AECOPD were prescribed six to nine prescriptions per year and accounted for 13.0% of antibiotics. Individuals with mild to moderate COPD and zero or one AECOPD received one to three prescriptions per year but accounted for 42.5% of all prescriptions. In addition to COPD severity, asthma, chronic heart disease, diabetes, heart failure and influenza vaccination were independently associated with increased antibiotic use.

Conclusions

Patients with severe COPD have the highest rates of antibiotic prescribing but most antibiotics are prescribed for patients with mild to moderate COPD. Antibiotic stewardship should focus on the dual goals of safely reducing the volume of prescribing in patients with mild to moderate COPD, and optimizing prescribing in patients with severe disease who are at significant risk of drug resistance.
People Rely Less on Consumer Reviews for Experiential than Material Purchases
Authors: Dai Hengchen , Chan Cindy , Mogilner Cassie
Published: September 2019

An increasingly prevalent form of social influence occurs online where consumers read reviews written by other consumers. Do people rely on consumer reviews differently when making experiential purchases (events to live through) versus when making material purchases (objects to keep)? Though people often use consumer reviews both when making experiential and material purchases, an analysis of more than six million reviews on Amazon.com and four laboratory experiments reveal that people are less likely to rely on consumer reviews for experiential purchases than for material purchases. This effect is driven by beliefs that reviews are less reflective of the purchase’s objective quality for experiences than for material goods. These findings not only indicate how different types of purchases are influenced by word of mouth, but also illuminate the psychological processes underlying shoppers’ reliance on consumer reviews. Furthermore, as one of the first investigations into how people choose among various experiential and material purchase options, these findings suggest that people are less receptive to being told what to do than what to have.
Effect of increased expression of both ras-related C3 botulinum toxin substrate 1 and p21-activated kinase 1 in patients with N0M0 upper urinary tract urothelial carcinoma and cancer-free surgical margins
Authors: Kuroda Kenji , Asano Takako , Horiguchi Akio , Ito Keiichi
Published: September 2019

Background

As a member of the Rho small guanosine triphosphatase family, ras-related C3 botulinum toxin substrate 1 (RAC1) interacts with various specific effectors, and p21-activated kinase 1 (PAK1), which has a role in both carcinogenesis and cellular invasion, binds to RAC1, after which activated PAK1 regulates cellular functions. There have been few reports about the simultaneous analysis of RAC1 and its downstream effector PAK1 in upper urinary tract urothelial carcinoma (UTUC). We assessed the expressions of both RAC1 and PAK1 and evaluated their association with clinicopathological parameters.

Methods

Immunohistochemical studies of RAC1 or PAK1 were performed with specimens from 104 patients with N0M0 UTUC and cancer-free surgical margins. Correlation of the positive expression of RAC1 or PAK1 or both with clinicopathological parameters was evaluated.

Results

A hazard model showed that the presence of mixed histologic features and moderate or strong positive expression of both RAC1 and PAK1 were independent factors for shortened disease-specific survival time (Ps = 0.041 and 0.016, respectively), and another hazard model revealed that only moderate or strong positive expression of both RAC1 and PAK1 was an independent factor for shortened recurrence-free survival time in the multivariate analysis (P = 0.036). Neither moderate or strong positive expression of RAC1 alone nor moderate or strong positive expression of PAK1 alone was an independent factor for a worse rate of disease-specific or recurrence-free survival in multivariate analysis.

Conclusions

Patients with N0M0 UTUC, cancer-free surgical margins and moderate or strong positive expression of both RAC1 and PAK1 should be carefully monitored after surgery.
An unusual case of phytobezoar-induced small bowel obstruction
Authors: Taha Yasser , Salman Khaled , Alrayyes Fahad , Alrayyes Saad
Published: September 2019

Bezoars, and to lesser extent phytobezoars, are among the rare causes of small bowel obstruction. A bezoar generally describes retained concretions of indigestible foreign material that accumulate and conglomerate in the gastrointestinal tract, most commonly in the stomach. We present an unusual case of phytobezoar-induced sub-acute small bowel obstruction originating from unfamiliar plant material in a 74-year-old woman. The past history was insignificant regarding comorbidities other than depression. Presenting complaints were history of abdominal pain and vomiting. Imaging studies and physical examination suggested small bowel obstruction. The patient underwent exploratory laparotomy after 1 day of conservative treatment. We found a 4.5 cm obstructing phytobezoar intraoperatively. The undigested plant material caused the obstruction. Postoperatively, the plant was identified as Scorzonera papposa. The patient was discharged uneventfully. The elderly patients should avoid semi-cooked vegetables, plants of unknown origin and high-fibre diet.
Expression of starch-binding factor CBM20 in barley plastids controls the number of starch granules and the level of CO2 fixation
Authors: Zhong Yingxin , Sagnelli Domenico , Topbjerg Henrik Bak , Hasler-Sheetal Harald , Andrzejczak Olga Agata , Hooshmand Kourosh , Gislum René , Jiang Dong , Møller Ian Max , Blennow Andreas , Hebelstrup Kim Henrik
Published: September 2019

Interference in protein–starch interactions in barley by the expression of an exogenous high-affinity starch-binding factor (Carbohydrate-Binding Motif 20, CBM20) reveals a link between starch granule biosynthesis and the level of photosynthesis.
QTLs for constitutive aerenchyma from Zea nicaraguensis improve tolerance of maize to root-zone oxygen deficiency
Authors: Gong Fangping , Takahashi Hirokazu , Omori Fumie , Wang Wei , Mano Yoshiro , Nakazono Mikio
Published: September 2019

A maize introgression line is developed harboring QTLs from Zea nicaraguensis for constitutive aerenchyma, which allows oxygen to diffuse along roots immediately after waterlogging and contributes to oxygen deficiency tolerance.
Arabidopsis cargo receptor NBR1 mediates selective autophagy of defective proteins
Authors: Jung Hyera , Lee Han Nim , Marshall Richard S , Lomax Aaron W , Yoon Min Ji , Kim Jimi , Kim Jeong Hun , Vierstra Richard D , Chung Taijoon
Published: September 2019

Arabidopsis cargo receptor NBR1 contributes to protein quality control by promoting the formation of protein aggregates and mediating their clearance via selective autophagy.
A carbohydrate-binding protein, B-GRANULE CONTENT 1, influences starch granule size distribution in a dose-dependent manner in polyploid wheat
Authors: Chia Tansy , Chirico Marcella , King Rob , Ramirez-Gonzalez Ricardo , Saccomanno Benedetta , Seung David , Simmonds James , Trick Martin , Uauy Cristobal , Verhoeven Tamara , Trafford Kay
Published: September 2019

In Triticeae endosperm (e.g. wheat and barley), starch granules have a bimodal size distribution (with A- and B-type granules) whereas in other grasses the endosperm contains starch granules with a unimodal size distribution. Here, we identify the gene, BGC1 (B-GRANULE CONTENT 1), responsible for B-type starch granule content in Aegilops and wheat. Orthologues of this gene are known to influence starch synthesis in diploids such as rice, Arabidopsis, and barley. However, using polyploid Triticeae species, we uncovered a more complex biological role for BGC1 in starch granule initiation: BGC1 represses the initiation of A-granules in early grain development but promotes the initiation of B-granules in mid grain development. We provide evidence that the influence of BGC1 on starch synthesis is dose dependent and show that three very different starch phenotypes are conditioned by the gene dose of BGC1 in polyploid wheat: normal bimodal starch granule morphology; A-granules with few or no B-granules; or polymorphous starch with few normal A- or B-granules. We conclude from this work that BGC1 participates in controlling B-type starch granule initiation in Triticeae endosperm and that its precise effect on granule size and number varies with gene dose and stage of development.
Coccidioides (spherulin) skin testing in patients with pulmonary coccidioidomycosis in an endemic region†
Authors: Mafi Neema , Murphy C Brian , Girardo Marlene E , Blair Janis E
Published: September 2019

Coccidioidomycosis is an endemic fungal infection of the desert southwestern United States. Intact cellular immunity is critical to the control of this infection. A recently released reformulated spherulin antigen (Spherusol; Nielsen BioSciences, Inc.) was approved to detect delayed-type hypersensitivity, which implies the presence of cellular immunity, to Coccidioides species. We aimed to summarize our experience with this test in patients with primary pulmonary coccidioidomycosis. We retrospectively reviewed clinical data for all patients with primary pulmonary coccidioidomycosis who had a Coccidioides (spherulin) skin test (CST) placed at our institution between January 1, 2015, and August 31, 2017. During the study period, 172 patients had a CST placed, and 122 met our inclusion criteria for proven or probable pulmonary coccidioidomycosis. Of these 122, 88 (72.1%) had a positive CST result and 34 (27.9%) had a negative result. In the positive CST group, 74 of the 79 treated patients (93.7%) had antifungal treatment stopped, 1 of whom (1.4%) had relapsed infection. In contrast, 27 of the 33 treated patients in the negative CST group (81.8%) had their antifungal treatment stopped, and none had a relapse. Seven patients overall (5.7%), all of whom had a positive CST, experienced mild local adverse reactions to the CST. Although previous controlled studies of CST showed sensitivity and specificity greater than 98%, our real-world experience with the CST showed lower rates of positivity. Negative CST results did not predict relapse with antifungal agent withdrawal.
PL1.1 CDKN2A homozygous deletion is a strong adverse prognosis factor in diffuse malignant IDHmutant gliomas
Authors: Appay R , Dehais C , Colin C , Alentorn A , Carpentier C , Ducray F , Ibdaih A , Kamoun A , Mokhtari K , Tabouret E , Uro-Coste E , Delattre J , Figarella-Branger D
Published: September 2019

The 2016 WHO classification of the central nervous system tumors stratifies diffuse adult gliomas into three major groups depending on the presence or absence of two main genetic alterations: IDH mutation and 1p/19q-codeletion. However, the grading system initially based on histological criteria remains unchanged and it is now controversial whether it can be still applied to this updated molecular classification. Therefore, in a large cohort of 911 high grade IDH-mutant gliomas from the French national POLA network, we investigated the prognostic value of pathological criteria (mitoses, microvascular proliferation and necrosis) as well as CDKN2A gene homozygous deletion, with the aim to highlight a new grading approach for these tumors. We analyzed 212 anaplastic astrocytoma (AA), IDH-mutant, 216 glioblastoma (GB), IDH-mutant and 483 anaplastic oligodendroglioma (AO), IDH-mutant and 1p/19q-codeleted. In this series, the 2016 WHO integrated diagnosis was of prognostic value for progression free survival (PFS) and overall survival (OS) (p<0.0001 for both). CDKN2A homozygous deletion was associated with worse outcome among gliomas lacking 1p/19q-codeletion (p<0.0001 for PFS and p=0.004 for OS) as well as among AO, IDH-mutant and 1p/19q-codeleted (p=0.002 for PFS and p<0.0001 for OS). In both groups, the presence of microvascular proliferation and/or necrosis remained of prognostic value only in cases lacking CDKN2A homozygous deletion, whereas its prognostic value was lost in the subgroup of gliomas presenting with CDKN2A homozygous deletion. Thereby, our study pointed out the utmost relevance of CDKN2A homozygous deletion as an adverse prognostic factor in the two broad categories of IDH-mutant gliomas stratified on 1p/19q-codeletion as well as the prognostic relevance of microvascular proliferation (associated or not to necrosis) among tumors lacking this alteration. We believe that these prognostic factors could be of great interest for a future grading approach of IDH-mutant gliomas.