bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating the epidemiology of emerging Xylella fastidiosa outbreaks in olives
Authors: White Steven M. , Navas‐Cortés Juan A. , Bullock James M. , Boscia Donato , Chapman Daniel S.
Published: June 2020

Xylella fastidiosa is an important insect‐vectored bacterial plant pathogen with a wide host range, causing significant economic impact in the agricultural and horticultural industries. Once restricted to the Americas, severe European outbreaks have been discovered recently in Italy, Spain, France, and Portugal. The Italian outbreak, detected in Puglia in 2013, has spread over 100 km, killing millions of olive trees, and is still expanding. To date, quantified assessment of important epidemiological parameters useful for risk assessment and management, such as transmission rates, symptomless periods, and time to death in field populations, has been lacking. This is due to the emergent and novel nature of the outbreak and length of time needed to monitor the course of disease progression. To address this, we developed a Bayesian method to infer epidemiological parameters by fitting and comparing compartmental epidemiological models to short snapshots of disease progression observed in multiple field plots. We estimated that each infected tree with symptoms is able to infect around 19 trees per year (95% credible range 14–26). The symptomless stage was estimated to have low to negligible infectivity and to last an average of approximately 1.2 years (95% credible range 1.0–1.3 years). Tree desiccation was estimated to occur approximately 4.3 years (95% credible range 4.0–4.6 years) after symptom appearance. However, we were unable to estimate the infectiousness of desiccated trees from the data. Our method could be used to make early estimates of epidemiological parameters in other emerging disease outbreaks where symptom expression is slow.
EU climate law sans frontières: The extension of the 2030 Framework to the Energy Community contracting parties
Authors: Minas Stephen
Published: June 2020

As challenging as meeting the 2030 climate and energy targets will be for the European Union (EU), it is the decision to extend the 2030 Framework to the contracting parties of the Energy Community (EnC) which will arguably require a truly Herculean effort. In 2018, the contracting parties agreed to adapt the revised Energy Efficiency and Renewable Energy Directives, and the Energy Union Governance Regulation. However, the EnC parties face significant obstacles, while the Energy Community has limited compliance mechanisms. This article examines the Energy Community as a hybrid legal space in which the European Commission, EnC Secretariat and contracting parties co‐create legal order. It investigates major challenges to the extension of the 2030 Framework to the Energy Community, including the EnC’s structure and composition, weaknesses in national implementation and a limited dispute resolution regime. The article also reflects on the role of law in the external dimension of EU climate policy.
Serum Krebs von den Lungen‐6 level in the disease progression and treatment of Mycobacterium avium complex lung disease
Authors: Asakura Takanori , Kimizuka Yoshifumi , Nishimura Tomoyasu , Suzuki Shoji , Namkoong Ho , Masugi Yohei , Sato Yasunori , Ishii Makoto , Hasegawa Naoki
Published: June 2020

Background and objective

The lack of useful biomarkers reflecting the disease state limits the management of Mycobacterium avium complex lung disease (MAC‐LD). We clarified the associations between serum KL‐6 level, disease progression and treatment response.

Methods

Resected lung tissues from MAC‐LD patients were immunostained for KL‐6. We compared serum KL‐6 levels between MAC‐LD and healthy control or bronchiectasis patients without nontuberculous mycobacterial lung disease (NTM‐LD). Serum KL‐6 level was assessed in a prospective observational study at Keio University Hospital between May 2012 and May 2016. We investigated associations between serum KL‐6 level and disease progression and treatment response in patients untreated for MAC‐LD on registration (n = 187).

Results

The KL‐6+ alveolar type 2 cell population in the lung and serum KL‐6 level were significantly higher in MAC‐LD patients than in controls. Serum KL‐6 level in bronchiectasis patients without NTM‐LD showed no significant increase. Of the 187 patients who did not receive treatment on registration, 53 experienced disease progression requiring treatment. Multivariable Cox analysis revealed that the serum KL‐6 level (aHR: 1.18, P = 0.005), positive acid‐fast bacilli smear (aHR: 2.64, P = 0.001) and cavitary lesions (aHR: 3.01, P < 0.001) were significantly associated with disease progression. The change in serum KL‐6 (ΔKL‐6) was significantly higher in the disease progression group; it decreased post‐treatment, reflecting the negative sputum culture conversion.

Conclusion

Serum KL‐6 level is associated with disease progression and treatment response. Longitudinal assessment combined with AFB smear status and presence of cavitary lesions may aid MAC‐LD management.
Economic Development and South Africa: 25 Years Analysis (1994 to 2019)
Authors: Dhamija Pavitra
Published: June 2020

Economic Development highlights the growth and progression of every nation towards prosperity, and South Africa is not an exception to this phenomenon. Present article reviews economic progression in South Africa for last 25 years of time by applying systematic literature review and bibliometric analysis (1,241 articles) on Scopus extracted database (1994 to 2019; until 06 June). Inferences evidence significant work contributed by top universities, authors, funding sources, journals and citation statistics. Noticeably, implementation of a concept solely will not fetch real situation; however, a systematic review extends good to excellent understanding of the considered research agenda. Findings reveal the contradictory inter‐connectivity of Cluster 1 Economic Inequality and Poverty, Cluster 2 Developing Country and Corruption and Cluster 6 Economic Development and Economic Policy. It is very important to understand that if a nation is facing economic inequality, corruption, and poverty; how it can achieve the status of economically developed nation. Identification of Cluster 3 Industrialization and Industry 4.0, Cluster 4 Unemployment and Entrepreneurship Education and Cluster 5 Sustainable Development and Economic Growth signifies scope of improvement. Conclusively, the researcher has proposed a conceptual model to address above stated concerns.
Changes in facial moisture distribution and feelings of moisture/dryness among various environmental temperatures and humidities in summer and winter
Authors: Egawa Mariko , Koizumi Koyo , Hirao Tetsuji
Published: June 2020

Background

As environmental conditions vary depending on area of residence, consideration of environmental temperature and humidity conditions is crucial for detection of actual skin conditions in daily life. In this study, we determined changes in facial moisture and sensory evaluation distributions in various environmental temperature and humidity conditions.

Materials and Methods

An original near‐infrared (NIR) imaging system was used to obtain moisture distributions. Sensory evaluations of feelings of moisture/dryness were graded, and changes were compared among 10 healthy Japanese female subjects in four different environmental temperature and humidity conditions (28°C, 60% RH; 28°C, 20% RH; 15°C, 60% RH; 15°C, 20% RH) in summer and winter.

Results

Skin moisture was lower at high temperatures and higher at low temperatures. Feelings of dryness on bare skin were high in low humidity. Sensitivity of feelings of moisture and dryness was high around the center of the cheekbones between side of the eyes and the mouth, but the same was not true of the moisture distribution. Moisture level was lower in winter at high temperatures, especially under the eyes near the side of the nose ridge, while the sense of dryness was not strong. These divergences between sensory evaluation and moisture level indicate the presence of a “hidden dry situation.”

Conclusion

Changes in moisture level and sensory evaluation scores in facial skin varied among environmental conditions, which differed between summer and winter, even under the same environmental temperature and humidity.
Modelo estructural de competencia profesional didáctica para profesores técnicos no pedagogos
Authors: Romero-Jeldres Marcela Rosa , Faouzi-Nadim Tarik
Published: June 2020

Este artículo indaga sobre las competencias pedagógicas de los profesores técnicos sin formación pedagógica que apoyan las trayectorias laborales y educativas de los estudiantes que eligen la educación media técnico profesional (EMTP) en Chile.Utilizando un cuestionario sobre las percepciones acerca del dominio de competencias pedagógicas y la técnica de modelos estructurales, se estudió el dominio asociado con las competencias profesionales didácticas en una muestra estratificada de 151 docentes. Los resultados señalan que el modelo es sensible a los contextos con vulnerabilidad social y al actuar competencial de docentes sin formación, por lo que resulta un aporte para determinar perfeccionamientos focalizados.
Analysis of Shroud Cavity Leakage in a Radial Turbine for Optimal Operation in Compressed Air Energy Storage System
Authors: Shao Ziyi , Li Wen , Wang Xing , Zhang Xuehui , Chen Haisheng
Published: June 2020

As an important energy generation device of the compressed air energy storage (CAES) system, the radial-inflow turbine with shrouded impeller is employed to avoid the leakage flow in the rotor, especially in the high-pressure stages. However, a lack of clarity in the leakage characteristics and their drivers still prevents a systematic approach to the efficient performance and proper design of the shrouded radial turbine. In the present work, the shroud cavity leakage of the shrouded radial turbine has been studied numerically. The physical quantity synergy is innovatively employed to research the internal flow field of the shroud cavity. It is found that the influence of high rotating speed on the seal leakage cannot be neglected, and the average reduced rate of seal leakage is found to be about 9.9% for the designed clearance. The leakage mass flow rate could be reduced by increasing the rotating speed or decreasing the seal clearance. The synergy angle is able to predict the flow resistance in shroud cavity very well. According to the volume-averaged synergy angle in the seal, the dimensionless seal clearance smaller than 1.5% in the shrouded radial turbine is recommended. Compared with the seal clearance in other high-pressure shrouded turbomachines, the current recommended clearance should be within a reasonable field.
The Influence of Anterior Cruciate Ligament Matrix Mechanical Properties on Simulated Whole-Knee Biomechanics
Authors: Rosario Ryan , Marchi Benjamin C. , Arruda Ellen M. , Coleman Rhima M.
Published: June 2020

Knee finite element (FE) models are used to study tissue deformation in response to complex loads. Typically, ligaments are modeled using transversely isotropic, hyperelastic material models fitted to tension data along the predominant fiber direction (longitudinal) and, less commonly, to tension data orthogonal to the fiber direction (transverse). Currently, the shear and bulk responses of the anterior cruciate ligament (ACL) are not fitted to experimental data. In this study, a newly proposed material model was fitted to longitudinal tension, transverse tension, and shear experimental data. The matrix transverse tensile, shear, and bulk stiffnesses were then varied independently to determine the impact of each property on knee kinematics and tissue deformation in a whole-knee FE model. The range of values for each parameter was chosen based on published FE studies of the knee. For a knee at full extension under 134 N anterior tibial force (ATF), increasing matrix transverse tensile stiffness, shear stiffness, or bulk stiffness decreased anterior tibial translation (ATT), ACL longitudinal strain, and ACL shear strain. For a knee under 134 N ATF and 1600 N compression, changing the ACL matrix mechanical properties caused variations in ATT and thus changed cartilage deformation contours by changing the point of contact between the femoral and the tibial cartilage. These findings indicate that material models for the ACL must describe matrix material properties to best predict the in vivo response to applied loads.
The Effect of the Loading Rate on the Full-Field Strain Distribution on the Surface on the Intervertebral Discs
Authors: Maria Luisa Ruspi , Luca Cristofolini
Published: June 2020

Contrasting results are reported when the spine is tested at different strain rates. Tissue specimens from the ligaments or the intervertebral discs (IVD, including annulus fibrosus and nucleus pulposus) exhibit higher stiffness and lower dissipation at high strain rates. Counterintuitively, when spine segments are tested at high rates, the hysteresis area and loop width increase. It is unclear how the load is shared between the different structures at different loading rates. The hypotheses of this study were: (i) As the IVD stiffens at higher loading rates, the strain distribution around the disc would be different depending on the loading rate; (ii) Preconditioning attenuates the strain-rate dependency of the IVD, thus making differences in strain distribution smaller at the different rates. Six segments of three vertebrae (L4–L6) were extracted from porcine spines and tested in presso-flexion at different loading rates (reaching full load in 0.67, 6.7, and 67 s). The full-field strain maps were measured using digital image correlation on the surface of the IVDs from lateral. The posterior-to-anterior trends of the strain were computed in detail for each IVD, and compared between loading rates. The values and the direction of principal strain on the surface of the IVDs, vertebrae, and endplates remained unchanged at different rates. In the transition zone between IVD and vertebra, only slight differences due to the loading rate appeared but with no statistical significance. These findings will allow better understanding of the rate-dependent behavior and failure of the IVD.
Investigating the Effects of Demographics on Shoulder Morphology and Density Using Statistical Shape and Density Modeling
Authors: Soltanmohammadi Pendar , Elwell Josie , Veeraraghavan Vishnu , Athwal George S. , Willing Ryan
Published: June 2020

A better understanding of how the shape and density of the shoulder vary among members of a population can help design more effective population-based orthopedic implants. The main objective of this study was to develop statistical shape models (SSMs) and statistical density models (SDMs) of the shoulder to describe the main modes of variability in the shape and density distributions of shoulder bones within a population in terms of principal components (PCs). These PC scores were analyzed, and significant correlations were observed between the shape and density distributions of the shoulder and demographics of the population, such as sex and age. Our results demonstrated that when the overall body sizes of male and female donors were matched, males still had, on average, larger scapulae and thicker humeral cortical bones. Moreover, we concluded that age has a weak but significant inverse effect on the density within the entire shoulder. Weak and moderate, but significant, correlations were also found between many modes of shape and density variations in the shoulder. Our results suggested that donors with bigger humeri have bigger scapulae and higher bone density of humeri corresponds with higher bone density in the scapulae. Finally, asymmetry, to some extent, was noted in the shape and density distributions of the contralateral bones of the shoulder. These results can be used to help guide the designs of population-based prosthesis components and pre-operative surgical planning.
Improving Utilization of Maximal Oxygen Uptake and Work Economy in Recreational Cross-Country Skiers With High-Intensity Double-Poling Intervals
Authors: Johansen Jan-Michael , Eriksen Sondre , Sunde Arnstein , Slettemeås Øystein B. , Helgerud Jan , Støren Øyvind
Published: June 2020

Purpose:To investigate the effect of a double-poling (DP) high-intensity aerobic interval-training (HIT) intervention performed without increasing total HIT volume. This means that regular HIT training (eg, running) was replaced by HIT DP. The aim was to explore whether this intervention could improve peak oxygen uptake in DP, the fractional utilization of maximal oxygen uptake (VO2max) in DP, oxygen cost of DP, maximal aerobic speed, and a 3-km DP time trial.Methods:Nine non-specially-DP-trained cross-country skiers (intervention group) and 9 national-level cross-country skiers (control group) were recruited. All participants were tested for VO2max in running, peak oxygen uptake in DP, oxygen cost of DP, and time-trial performance before and after a 6-wk, 3-times-per-week HIT DP intervention. The intervention group omitted all regular HIT with HIT in DP, leaving the total weekly amount of HIT unchanged.Results:Seven participants in each group completed the study. VO2max in running remained unchanged in both groups, whereas peak oxygen uptake in DP improved by 7.1% (P = .005) in the intervention group. The fractional utilization of VO2max in DP thus increased by 7.3% (P = .019), oxygen cost of DP by 9.2% (P = .047), maximal aerobic speed by 16.5% (P = .009), and time trial by 19.5% (P = .004) in the intervention group but remained unchanged in the control group.Conclusions:The results indicate that a 6-wk HIT DP intervention could be an effective model to improve DP-specific capacities, with maintenance of VO2max in running.
S1 Domain RNA-Binding Protein CvfD Is a New Posttranscriptional Regulator That Mediates Cold Sensitivity, Phosphate Transport, and Virulence in Streptococcus pneumoniae D39
Authors: Sinha Dhriti , Zheng Jiaqi J. , Tsui Ho-Ching Tiffany , Richardson John D. , De Lay Nicholas R. , Winkler Malcolm E.
Published: June 2020

Recent advances have led to the identification of numerous sRNAs in the major human respiratory pathogen
S. pneumoniae
. However, little is known about the functions of most sRNAs or RNA-binding proteins involved in RNA biology in pneumococcus. In this paper, we characterize the phenotypes and one target of the S1 domain RNA-binding protein CvfD, a homolog of general stress protein 13 identified, but not extensively characterized, in other
Firmicutes
species. Pneumococcal CvfD is a broadly pleiotropic regulator, whose absence results in misregulation of divalent cation homeostasis, reduced translation of the PhoU2 master regulator of phosphate uptake, altered metabolism and sRNA amounts, cold sensitivity, and attenuation of virulence. These findings underscore the critical roles of RNA biology in pneumococcal physiology and virulence.
Light and Primary Production Shape Bacterial Activity and Community Composition of Aerobic Anoxygenic Phototrophic Bacteria in a Microcosm Experiment
Authors: Piwosz Kasia , Vrdoljak Ana , Frenken Thijs , González-Olalla Juan Manuel , Šantić Danijela , McKay R. Michael , Spilling Kristian , Guttman Lior , Znachor Petr , Mujakić Izabela , Fecskeová Lívia Kolesár , Zoccarato Luca , Hanusová Martina , Pessina Andrea , Reich Tom , Grossart Hans-Peter , Koblížek Michal
Published: June 2020

Metabolic coupling between phytoplankton and bacteria determines the fate of dissolved organic carbon in aquatic environments, and yet how changes in the rate of primary production affect the bacterial activity and community composition remains understudied. Here, we experimentally limited the rate of primary production either by lowering light intensity or by adding a photosynthesis inhibitor. The induced decrease had a greater influence on bacterial respiration than on bacterial production and growth rate, especially at an optimal light intensity. This suggests that changes in primary production drive bacterial activity, but the effect on carbon flow may be mitigated by increased bacterial growth efficiencies, especially of light-dependent AAP bacteria. Bacterial activities were independent of changes in bacterial community composition, which were driven by light availability and AAP bacteria. This direct effect of light on composition of bacterial communities has not been documented previously.
A Mouse Model for Infection with Enterovirus A71 in Small Extracellular Vesicles
Authors: Gu Jiaqi , Wu Jing , Cao Yuwen , Zou Xinran , Jia Xiaonan , Yin Yiqian , Shen Li , Fang Daihua , Mao Lingxiang
Published: June 2020

EV-A71 was supposed to infect the CNS through the neural pathway and the circulation of the blood in previous studies. Reverse axon transport had been confirmed as an important pathway for EV-A71 to infect the CNS; however, it is still unknown how EV-A71 infects the CNS through the circulation of the blood. Combined with the infectivity of sEVs secreted from EV-A71-infected cells and the characteristic that sEVs could cross the blood-brain barrier, we considered that sEVs may play a vital role in EV-A71 pathogenesis of the CNS.
​False-positive paracetamol levels in a patient with hyperbilirubinaemia: clinical perspectives
Authors: James Joel , Stauss Madelena , Ponnusamy Arvind , Myers Martin
Published: June 2020

​Serum concentrations of paracetamol are measured to investigate the cause of acute hepatitis, monitor the clearance of paracetamol from the body and to determine if supratherapeutic levels warrant treatment with N-acetylcysteine (NAC). ​A 49-year-old man treated for ischaemic colitis developed worsening renal and liver function tests. As part of the investigation of hepatorenal failure, paracetamol levels were requested, which were elevated at 14 mg/L (normal <4 mg/L) resulting in treatment with NAC. Despite treatment, levels of paracetamol remained elevated and the link between hyperbilirubinemia and false-positive paracetamol levels was identified. ​Bilirubin and its by-products have intense absorbance in the ultraviolet and visible regions of the electromagnetic spectrum, causing interference in the enzymatic colorimetric assay most commonly used to measure paracetamol concentration, resulting in false-positive paracetamol levels. Laboratories correct for this interference above a predetermined bilirubin concentration, termed the Icteric Index; however, in our case this interference occurred at a lower level of hyperbilirubinaemia than previously identified as significant. This interaction was found to be more significant at lower bilirubin levels when low or no paracetamol levels were present in the serum, resulting in a change to laboratory practice and development of a ‘Sliding Scale’ approach to analysis. ​Concurrent bilirubin or Icteric Index measurement is recommended for all laboratories that use the enzymatic colorimetric assay for paracetamol measurement. Lower Icteric Index or bilirubin thresholds are required when low or no paracetamol levels are present in the serum to prevent false-positive paracetamol results. We describe a new ‘Sliding Scale’ approach to analysis, and highlight an important interaction for clinicians to be aware of.
Colon capsule endoscopy in colorectal cancer screening: a randomised controlled trial
Authors: Kaalby Lasse , Deding Ulrik , Kobaek-Larsen Morten , Havshoi Anne-Line Volden , Zimmermann-Nielsen Erik , Thygesen Marianne Kirstine , Kroijer Rasmus , Bjørsum-Meyer Thomas , Baatrup Gunnar
Published: June 2020

Introduction

The use of capsule endoscopy has become an approved method in small bowel diagnostics, but the same level of integration is not seen in large bowel diagnostics. We will use colon capsule endoscopy (CCE) as a filter test in colorectal cancer (CRC) screening between the faecal immunochemical test (FIT) and colonoscopy. We aim to investigate the clinical performance, population acceptability, and economic implications of the procedure in a large-scale clinical trial.

Methods and analysis

We will randomly allocate 124 214 Danish citizens eligible for participation in the national CRC screening programme within the Region of Southern Denmark to either an intervention group or a control group. Prior to submitting a FIT, citizens randomised to the intervention group will be informed about their opportunity to undergo CCE, instead of colonoscopy, if the FIT is positive. Suspected cancers; >3 adenomas <10 mm in size, 1 adenoma >10 mm in size or >4 adenomas regardless of size, detected during CCE will generate an invitation to colonoscopy as per regular screening guidelines, whereas citizens with suspected low risk polyps will re-enter the biennial screening programme. Citizens with no CCE findings will be excluded from screening for 8 years. In the control group, citizens will follow standard screening procedures.

Ethics and dissemination

All participants must consent prior to capsule ingestion. All collected data will be handled and stored in accordance with current data protection legislation. Approvals from the regional ethics committee (ref. S-20190100) and the Danish data protection agency have been obtained (ref. 19/29858).

Trial registration details

The study has been registered with ClinicalTrials.gov under:NCT04049357.
Spatial and epidemiological drivers ofPlasmodium falciparummalaria among adults in the Democratic Republic of the Congo
Authors: Deutsch-Feldman Molly , Brazeau Nicholas F , Parr Jonathan B , Thwai Kyaw L , Muwonga Jeremie , Kashamuka Melchior , Tshefu Kitoto Antoinette , Aydemir Ozkan , Bailey Jeffrey A , Edwards Jessie K , Verity Robert , Emch Michael , Gower Emily W , Juliano Jonathan J , Meshnick Steven R
Published: June 2020

Background

Adults are frequently infected with malaria and may serve as a reservoir for further transmission, yet we know relatively little about risk factors for adult infections. In this study, we assessed malaria risk factors among adults using samples from the nationally representative, cross-sectional 2013–2014 Demographic and Health Survey (DHS) conducted in the Democratic Republic of the Congo (DRC). We further explored differences in risk factors by urbanicity.

Methods

Plasmodium falciparuminfection was determined by PCR. Covariates were drawn from the DHS to model individual, community and environmental-level risk factors for infection. Additionally, we used deep sequencing data to estimate the community-level proportions of drug-resistant infections and included these estimates as potential risk factors. All identified factors were assessed for differences in associations by urbanicity.

Results

A total of 16 126 adults were included. Overall prevalence of malaria was 30.3% (SE=1.1) by PCR; province-level prevalence ranged from 6.7% to 58.3%. Only 17% of individuals lived in households with at least one bed-net for every two people, as recommended by the WHO. Protective factors included increasing within-household bed-net coverage (Prevalence Ratio=0.85, 95% CI=0.76–0.95) and modern housing (PR=0.58, 95% CI=0.49–0.69). Community-level protective factors included increased median wealth (PR=0.87, 95% CI=0.83–0.92). Education, wealth, and modern housing showed protective associations in cities but not in rural areas.

Conclusions

The DRC continues to suffer from a high burden of malaria; interventions that target high-risk groups and sustained investment in malaria control are sorely needed. Areas of high prevalence should be prioritised for interventions to target the largest reservoirs for further transmission.
MEDLINK: a low-cost, portable, verbally interactive and programmable remote patient monitoring (RPM) device
Authors: Ejofodomi O'tega , Zara Jason , Ofualagba Godswill
Published: June 2020

Remote patient monitoring (RPM) devices are a novel method for physicians to monitor their patients after discharge and long after they have gone home. Usually RPM devices are bulky, relatively expensive, restricted in the physiological parameters they measure and are hard to operate.

MEDLINK is a low cost (~$C1500), verbally interactive, programmable and portable RPM device that possesses the ability to verbally interact with a physician to obtain his or her information as well as the patient’s key statistics, and then to obtain the physician’s selection of physiological parameters he or she wishes to remotely monitor from that particular patient. When the patient switches on the unit, MEDLINK also verbally interacts with the patient to measure and acquire the physician’s selected physiological parameter and sends this information to the physician’s phone, via text messages and emails. Security and privacy of patient’s medical data can be preserved by using the patient’s ID instead of patient name.

Physiological parameters that can be acquired by MEDLINK include: ECG, blood pressure, heart rate, blood glucose, pulse rate, blood oxygen saturation, electromyography, body temperature, spirometer, respiratory rate and much more. Future work involves the integration of more biomedical sensors to the existing MEDLINK product to expand its range of measurable physiological parameters to its maximum, and to conduct a short clinical trial on the product prior to commercialisation.
Lessons learned: using adverse incident reports to investigate the characteristics and causes of prescribing errors
Authors: Lane Natalie , Hunter Ian
Published: June 2020

Introduction

Prescribing errors are a principal cause of preventable harm in healthcare. This study aims to establish a systematic approach to analysing prescribing-related adverse incident reports, in order to elucidate the characteristics and contributing factors of common prescribing errors and target multifaceted quality improvement initiatives.

Methods

All prescribing-related adverse incident reports submitted across one NHS board over 12 months were selected. Incidents involving commonly implicated drugs (involved in ≥10 incidents) underwent analysis to establish likely underlying causes using Reason’s Model of Accident Causation.

Results

330 prescribing-related adverse incident reports were identified. Commonly implicated drugs were insulin (10% of incidents), gentamicin (7%), co-amoxiclav (5%) and amoxicillin (5%). The most prevalent error types were prescribing amoxicillin when contraindicated due to allergy (5%); prescribing co-amoxiclav when contraindicated due to allergy (5%); prescribing the incorrect type of insulin (3%); and omitting to prescribe insulin (3%). Error-producing factors were identified in 86% of incidents involving commonly implicated drugs. 53% of incidents involved error-producing factors related to the working environment; 38% involved factors related to the healthcare team; and 37% involved factors related to the prescriber.

Discussion

This study establishes that systematic analysis of adverse incident reports can efficiently identify the characteristics and contributing factors of common prescribing errors, in a manner useful for targeting quality improvement. Furthermore, this study produced a number of salient findings. First, a narrow range of drugs were implicated in the majority of incidents. Second, a small number of error types were highly recurrent. Lastly, a range of contributing factors were evident, with those related to the working environment contributing to the majority of prescribing errors analysed.
Acute kidney injury associated with immune checkpoint inhibitor therapy: incidence, risk factors and outcomes
Authors: Meraz-Muñoz Alejandro , Amir Eitan , Ng Pamela , Avila-Casado Carmen , Ragobar Claire , Chan Christopher , Kim Joseph , Wald Ron , Kitchlu Abhijat
Published: June 2020

Background

Immune checkpoint inhibitors (ICPi) are a novel and promising anti-cancer therapy. There are limited data on the incidence, risk factors and outcomes of acute kidney injury (AKI) in patients receiving ICPi.

Methods

We conducted a cohort study of patients receiving ICPi at our center between 2010 and 2017 via electronic health record. The primary outcome was AKI (increase of >50% from baseline serum creatinine (sCr)). Risk factors for AKI were assessed using logistic regression. Survival among those with and without AKI was compared using the Kaplan-Meier method.

Results

Among 309 patients on ICPi, 51 (16.5%) developed AKI (Kidney Disease Improving Global Outcomes (KDIGO) stages 1: 53%, 2: 22%, 3: 25%). AKI was associated with other immune-related adverse events (IRAE) (OR 3.2, 95% CI 1.6 to 6; p<0.001), hypertension (OR 4.3, 95% CI 1.8 to 6.1; p<0.001) and cerebrovascular disease (OR 9.2; 95% CI 2.1 to 40; p<0.001). Baseline sCr, cancer, and ICPi type was not associated with AKI. Use of angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (OR 2.9; 95% CI 1.5 to 5.7; p=0.002), diuretics (OR 4.3; 95% CI 1.9 to 9.8; p<0.001), and corticosteroid treatment (OR 1.9; 95% CI 1.1 to 3.6; p=0.03) were associated with AKI. In the multivariable analysis, AKI was associated only with other IRAE (OR 2.82; 95% CI 1.45 to 5.48; p=0.002) and hypertension (OR 2.96; 95% CI 1.33 to 6.59; p=0.008). AKI was not associated with increased risk of mortality (HR 1.1; 95% CI: 0.8 to 1.6; p=0.67). ICPi nephrotoxicity was attributed via biopsy or nephrologist assessment in 12 patients (six interstitial nephritis, two membranous nephropathy, two minimal change disease, and two thrombotic microangiopathy). Subsequent doses of ICPi were administered to 12 patients with prior AKI, with one (8.3%) having recurrent AKI.

Conclusion

AKI is a common complication in patients receiving ICPi treatment. The development of other IRAE and previous diagnosis of hypertension were associated with increased AKI risk. AKI was not associated with worse survival. Distinguishing kidney IRAE from other causes of AKI will present a frequent challenge to oncology and nephrology practitioners. Kidney biopsy should be considered to characterize kidney lesions and guide potential therapy.
Tim-3 finds its place in the cancer immunotherapy landscape
Authors: Acharya Nandini , Sabatos-Peyton Catherine , Anderson Ana Carrizosa
Published: June 2020

The blockade of immune checkpoint receptors has made great strides in the treatment of major cancers, including melanoma, Hodgkin’s lymphoma, renal, and lung cancer. However, the success rate of immune checkpoint blockade is still low and some cancers, such as microsatellite‐stable colorectal cancer, remain refractory to these treatments. This has prompted investigation into additional checkpoint receptors. T-cell immunoglobulin and mucin domain 3 (Tim-3) is a checkpoint receptor expressed by a wide variety of immune cells as well as leukemic stem cells. Coblockade of Tim-3 and PD-1 can result in reduced tumor progression in preclinical models and can improve antitumor T-cell responses in cancer patients. In this review, we will discuss the basic biology of Tim-3, its role in the tumor microenvironment, and the emerging clinical trial data that point to its future application in the field of immune-oncology.
Research priorities in advanced heart failure: James Lind alliance priority setting partnership
Authors: Taylor Clare J , Huntley Alyson L , Burden John , Gadoud Amy , Gronlund Toto , Jones Nicholas Robert , Wicks Eleanor , McKelvie Sara , Byatt Kit , Lehman Richard , King Anna , Mumford Bev , Feder Gene , Mant Jonathan , Hobbs Richard , Johnson Rachel
Published: June 2020

Objective

To determine research priorities in advanced heart failure (HF) for patients, carers and healthcare professionals.

Methods

Priority setting partnership using the systematic James Lind Alliance method for ranking and setting research priorities. An initial open survey of patients, carers and healthcare professionals identified respondents’ questions, which were categorised to produce a list of summary research questions; questions already answered in existing literature were removed. In a second survey of patients, carers and healthcare professionals, respondents ranked the summary research questions in order of priority. The top 25 unanswered research priorities were then considered at a face-to-face workshop using nominal group technique to agree on a ‘top 10’.

Results

192 respondents submitted 489 responses each containing one or more research uncertainty. Out-of-scope questions (35) were removed, and collating the responses produced 80 summary questions. Questions already answered in the literature (15) were removed. In the second survey, 65 questions were ranked by 128 respondents. The top 10 priorities were developed at a consensus meeting of stakeholders and included a focus on quality of life, psychological support, the impact on carers, role of the charity sector and managing prognostic uncertainty. Ranked priorities by physicians and patients were remarkably divergent.

Conclusions

Engaging stakeholders in setting research priorities led to a novel set of research questions that might not have otherwise been considered. These priorities can be used by researchers and funders to direct future research towards the areas which matter most to people living with advanced HF.
The effects of variable retention forestry on coarse woody debris dynamics and concomitant impacts on American marten habitat after 27 years
Authors: Farnell Ingrid , Elkin Ché , Lilles Erica , Roberts Anne-Marie , Venter Michelle
Published: June 2020

Coarse woody debris (CWD) in the form of logs, downed wood, stumps and large tree limbs is an important structural habitat feature for many small mammal species, including the American marten (Martes americana). At a long-term experimental trial in northern temperate hemlock-cedar forests of British Columbia, Canada, we analysed the impact of varying amounts of overstory basal area retention: 0% (clearcut), 40%, 70%, and 100% (unharvested) on CWD volume, decay class, and inputs from windthrow over 27 years. We used CWD attributes (diameter, length, decay class, and height above the ground) known to be favourable for martens to create an index for assessing the impact of harvesting intensity on CWD habitat features. Stands with 70% retention had CWD attributes that resulted in CWD habitat features similar to unharvested stands. Clearcuts contained pieces that were smaller, more decayed, and closer to the ground, which contributed to a habitat that was less valuable, compared with stands that had higher retention. Over the 27-year period, windthrown trees were the majority of CWD inputs, and volume change was positively related to percent retention. Our results highlight that forest management influences CWD size and input dynamics over multiple decades, and the need for consideration of these impacts when undertaking long-term multiple-use forestry planning.
An Adaptive Multi-Mode PWM Control PSR Flyback Converter
Authors: Chen Chang , Wang Lei , Chang Changyuan , Han Xiong
Published: June 2020

In this paper, an adaptive multi-mode PWM control PSR flyback converter is proposed. In constant voltage (CV) mode, the converter adopts primary-side regulate (PSR) scheme to detect load information through the auxiliary winding, which reflects the load information on the voltage of [Formula: see text]. The converter adjusts the switching frequency according to the voltage of [Formula: see text] under different load conditions, realizing adaptive multi-mode PWM control to significantly improve light- load efficiency and thus the overall average efficiency. Besides, it does not give compromise to other system performance, such as audible noise, standby power consumption, and regulation. To verify the feasibility and performance of the proposed circuit, the converter has been designed and fabricated in HHGRACE_0.35[Formula: see text][Formula: see text]m BCD process and verified in a 5V/1A circuit prototype. The experimental results show that 25% load power efficiency of the proposed converter is 78.1%, which is improved by up to 3.4% compared to the conventional converter.
Automatic Question Answering System Based on Convolutional Neural Network and Its Application to Waste Collection System
Authors: Jiang Chuan , Su Qianmin , Zhang Lele , Huang Bo
Published: June 2020

As a typical cyber-physical-social system (CPSS), the waste collection system profoundly changes the current waste processing mode and greatly relieves the dilemma of waste disposal. However, the existing waste collection system does not provide the function that guides people to deliver the waste into the correct trash bin. In order to improve the efficiency of waste collection system, we propose an automatic question answering system based on convolutional neural network (CNN) to help people classify waste correctly. The construction process of automatic question answering system is divided into the following steps. We first construct a question answering dataset about waste classification, in which question answering pairs from the four waste categories (recyclable waste, harmful waste, dry waste, and wet waste) are included. After the dataset is constructed, we perform text preprocessing on the dataset, which includes denoising, Chinese word segmentation, and removing stop words. After text preprocessing, we use the Word2vec model as feature representation. Then, we construct a CNN and utilize the word embeddings as an input to train model. Finally, we deploy the trained model to the waste collection system, which can answer the question of waste classification that people ask. We also present a comparative analysis of the proposed method and traditional machine learning methods. The experiment shows that the proposed method has higher accuracy of waste classification than that of traditional machine learning methods.
COMPARING METHODS FOR 3D INVERSE DYNAMICS ANALYSIS OF SQUAT LIFTING USING A FULL BODY LINKED SEGMENT MODEL
Authors: VAHDAT IMAN , PARNIANPOUR MOHAMAD , GHOMSHEH FARHAD TABATABAI , TOOSIZADEH NIMA , TANBAKOOSAZ ALI
Published: June 2020

Objective: The main objective of this study was to assess the accuracy of bottom-up solution for three-dimensional (3D) inverse dynamics analysis of squat lifting using a 3D full body linked segment model. Least squares solution was used in this study as reference for assessment of the accuracy of bottom-up solution. Findings of this study may clarify how much the bottom-up solution can be reliable for calculating the joint kinetics in 3D inverse dynamics problems. Methods: Ten healthy males volunteered to perform squat lifting of a box with a load of one-tenth of their body weights. The joint moments were calculated using 110 reflective passive markers (46 anatomical markers and 64 tracking markers) and a 3D full body linked segment model. Ground reaction forces and kinematics data were recorded using a Vicon system with two parallel Kistler force plates. Three-dimensional Newton–Euler equations of motion with bottom-up and least squares solutions were applied to calculate joint moments. The peak and mean values of the joint moments were determined to check the quantitative differences as well as the time-to-peak value of the moment curves was determined to check the temporal differences between the two inverse dynamics solutions. Results: Significant differences (all [Formula: see text]-[Formula: see text]) between the two inverse dynamics solutions were detected for the peak values of the hip (right and left sides) and L5–S1 joint moments in the lateral anatomical direction as well significant differences (all [Formula: see text]-[Formula: see text]) were detected for the peak and mean values of the L5–S1 joint moment in all anatomical directions. Moreover, small differences (all [Formula: see text]) were detected between the two inverse dynamic solutions for the calculated lower body joint moments. Conclusions: The findings of this study clarified the disadvantages of the straightforward solutions and demonstrated that the bottom-up solution may not be accurate for more distal measures from the force plate (for hip and S1–L5) but it may be accurate for more proximal joints (ankle and knee) in 3D inverse dynamics analysis.
In-silico analysis to identify the role of MEN1 missense mutations in breast cancer
Authors: Ganakammal Satishkumar Ranganathan , Koirala Mahesh , Wu Bohua , Alexov Emil
Published: June 2020

Background: The multiple endocrine neoplasia type 1 (MEN1) gene located on chromosome 11q13 encodes menin protein. Previously reported mutations were thought to result in loss of function of menin protein and that they are associated with multiple endocrine neoplasia 1 disorder. However, recently menin has also been characterized as an oncosuppressor protein and it was suggested that mutations in it are associated with various other tumors. Studies indicate that the menin protein stimulates the estrogen receptor (ER) that in turn increases the predisposition for inherited breast cancer.

Methods: Here, we used our supervised in-house combinatory in-silico predictor method to investigate the impact of unclassified missense mutations in MEN1 gene found in breast cancer tissue. We also examined the biophysical and biochemical properties to predict the effects of these missense variants on the menin protein stability and interactions. The results are compared with the effects of known pathogenic mutations in menin causing neoplasia.

Results: Our analysis indicates that some of the variants found in breast cancer tissue show similar pattern of destabilizing the menin protein and its interactions as the pathogenic variants associated with neoplasia. Taking together with the results of our in-silico consensus predictor, we classify missense mutations in menin protein found in breast cancer tissue into pathogenic and benign, and thus, suggesting as an indicator for early detection of elevated breast cancer risk.
The Age of FinTech: Implications for Research, Policy and Practice
Authors: Mention Anne-Laure
Published: June 2020

FinTech is inducing changes in how financial services (FS) are perceived, developed, promoted, delivered and consumed. Future of FinTech, however, is rooted in deliberate integrated actions to improve framework conditions related to consumer trust, regulation and scalability. Building on limited scholarship, this paper identifies the building blocks for the future of FinTech and provides prescriptive areas of focus to guide research, policy and practice. In sum, the purpose of the paper is to serve as a catalyst and a call for an integrative approach in developing a common understanding and interpretation of FinTech as a socially-constructed phenomenon at the intersection of research and technology management.
Isotopic and time series investigations of recent stalagmites (1945–2018), Schlossberg tunnels, Graz, Austria: implications for climate change in Central Europe
Authors: Bojar Ana-Voica , Lécuyer Christophe , Duliu Octavian G. , Bojar Hans-Peter , Fourel François
Published: June 2020

For the first time, we present a decadal-scale stable isotope record (δ
18
O, δ
13
C) of 67 speleothem calcite samples coming from an artificial tunnel network located in Graz, Austria. Stable isotope data are interpreted with the help of time series (TS) analysis of mean air temperatures (MAT) and mean annual precipitations (MAP) that have been monitored and recorded in a neighbouring meteorological station. Speleothem records have proved to be very useful in reconstructing changes of environmental conditions. For studied stalagmites, which grew between 1945 and 2018, the δ
18
O values average −18.64‰ and range from −23‰ to −17‰ (VPDB, Vienna Pee Dee Belemnite), suggesting variable climatic conditions. The δ
18
O values of calcite increase along the growth axis and are correlated with high temporal resolution MAT, MAP and weighted mean annual δ
18
O of precipitations. For the same time interval, while the temperature TS show an increasing trend, with a steeper gradient since the 1980s, the precipitation TS presents a weak decreasing tendency. Increase in the δ
13
C values of speleothems from −33‰ to −24‰ (VPDB) is correlated with increasing temperature and drought, associated CO
2
degassing and soil erosion over the tunnel system.