bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of pouring temperature on the tensile strength and micro structure of Al alloys by centrifugal casting
Authors: Irfa’i M A , Ganda A N F
Published: March 2021

There are many ways to overcome the leaking pipes in pipe joining; one of them is by using centrifugal casting as method for its production. The goal of this study is to know the effect of pouring temperature on the tensile strength and microstructure of centrifugal casted pipe product. We tried to produce the pipe at temperature of 680°C, 700°C and 720°C, with the constant rotation speed of the centrifugal casting machine (1500 rpm). The tensile test was done based on standard of ASTM E8. The results show that the highest tensile strength is obtained from the product that was manufactured at 680°C (136.3 MPa) and the lowest is at 720°C (115.3 MPa). These data are supported with the result of microstructure test which revealed that the amount of Al dendrite structure is more homogenous and uniform when the pouring temperature is closed to melting point.
Conceptual design of Wau Bulan UAV
Authors: Kusumohadi C S , Basri S , Rafie A S M
Published: March 2021

This paper presents conceptual design of an UAV that using “Wau Bulan” shape as its planform. Wau Bulan is a one type of Malaysia’s kite. Wau bulan kite has wing and tail part. Wau Bulan wing is a lens shape wing with aspect ratio 3.48. Tail part shape likes crescent moon. Tail part area is 46.23% of wing area. Wau Bulan UAV was designed to perform surveillance mission. Initial weight sizing and performance sizing was done to assure the reasonable value of aerodynamics and propulsion parameter. Joined wing and blended wing body technology concepts were used to aim the requirement parameters that defined during initial sizing process. The aerodynamics characteristic was analyzed using experimental method. Experimental results show that wau bulan planform aerodynamics characteristics fulfill designed parameter that chosen during initial sizing.
Microwave assisted polyol process for time-saving synthesis of superparamagnetic nanoparticles and application in artificial mimic enzyme
Authors: Xiao Wangchuan , Su Zhizhong , Zhao Yan , Wang Chuanyuan
Published: March 2021

A microwave assisted polyol process accomplished within 10 min was developed for synthesis of superparamagnetic Fe3O4 nanoparticles (MNPs) with well controlled size between 2 and 6 nm. Effects of reaction time and temperature on the size of the MNPs were investigated through transmission electronic microscope, x-ray diffraction pattern, thermogravimetic and magnetic analysis. The results indicates that longer reaction time or higher temperature lead to formation of MNPs with larger size. As a proof-of-concept, the MNPs were utilized as peroxidase and their activity was also investigated. Oxidation of typical substrate, 3, 3’, 5, 5’ -tetramethylbenzidine, can be proceeded by using the MNPs as artificial mimic enzyme. The MNPs display the maximal catalyzed activity under the optimum condition as pH = 3.5, 40 °C and concentration of TMB and H2O2 with 120 and 110 mmol·l−1, respectively. This work provides a new way for fast synthesis of MNPs, which are of potential application in artificial mimic enzyme.
Invited Commentary: The Society for Epidemiologic Research’s Commitment to Diversity and Equity—Pathways to Filling the Glass
Authors: Ahern Jennifer , Kaufman Jay S , Werler Martha M
Published: March 2021

In the article by Nobles et al. (Am J Epidemiol. 2021;190(9):1710–1720), characteristics of those epidemiologists selected for various chair and presentation roles at the annual meetings of the Society for Epidemiologic Research (SER) from 2015 through 2017 were examined. Characteristics that were compared included inferred gender, institutional affiliation, subject area, and h-index. Important disparities were observed between session chairs, speakers, and poster presenters. SER leadership considers diversity and equity to be priorities and is committed to positive change. New programs and processes have been used to broaden participation and improve diversity since 2018, but the SER must continue its efforts to change processes and monitor of the experiences of SER members. A diversity of perspectives within the SER membership and at its meetings will improve all aspects of our practice of epidemiology.
Bayesian adaptive design for concurrent trials involving biologically related diseases
Authors: Psioda Matthew A , Xia H Amy , Jiang Xun , Xu Jiawei , Ibrahim Joseph G
Published: March 2021

We develop a Bayesian design method for a clinical program where an investigational product is to be studied concurrently in a set of clinical trials involving related diseases with the goal of demonstrating superiority to a control in each. The approach borrows information on treatment effectiveness using correlated mixture priors using an analysis procedure that is closely related Bayesian model averaging. Mixture priors are constructed by eliciting conjugate priors based on pessimistic and enthusiastic predictions for the data to be observed for each disease and then by eliciting mixture weights for all possible configurations of the pessimistic and enthusiastic priors across the diseases to be studied. The proposed approach provides a robust framework for information borrowing in settings where the diseases may have endpoints based on different data types. We show via simulation that operating characteristics based on the proposed design framework are favorable compared to those based on information borrowing designs using the Bayesian hierarchical model which is poorly suited for information borrowing when there are different data types underpinning the endpoints across which information is to be borrowed.
Locus coeruleus integrity and the effect of atomoxetine on response inhibition in Parkinson’s disease
Authors: O’Callaghan Claire , Hezemans Frank H , Ye Rong , Rua Catarina , Jones P Simon , Murley Alexander G , Holland Negin , Regenthal Ralf , Tsvetanov Kamen A , Wolpe Noham , Barker Roger A , Williams-Gray Caroline H , Robbins Trevor W , Passamonti Luca , Rowe James B
Published: March 2021

Cognitive decline is a common feature of Parkinson’s disease, and many of these cognitive deficits fail to respond to dopaminergic therapy. Therefore, targeting other neuromodulatory systems represents an important therapeutic strategy. Among these, the locus coeruleus-noradrenaline system has been extensively implicated in response inhibition deficits. Restoring noradrenaline levels using the noradrenergic reuptake inhibitor atomoxetine can improve response inhibition in some patients with Parkinson’s disease, but there is considerable heterogeneity in treatment response. Accurately predicting the patients who would benefit from therapies targeting this neurotransmitter system remains a critical goal, in order to design the necessary clinical trials with stratified patient selection to establish the therapeutic potential of atomoxetine. Here, we test the hypothesis that integrity of the noradrenergic locus coeruleus explains the variation in improvement of response inhibition following atomoxetine. In a double-blind placebo-controlled randomized crossover design, 19 patients with Parkinson’s disease completed an acute psychopharmacological challenge with 40 mg of oral atomoxetine or placebo. A stop-signal task was used to measure response inhibition, with stop-signal reaction times obtained through hierarchical Bayesian estimation of an ex-Gaussian race model. Twenty-six control subjects completed the same task without undergoing the drug manipulation. In a separate session, patients and controls underwent ultra-high field 7 T imaging of the locus coeruleus using a neuromelanin-sensitive magnetization transfer sequence. The principal result was that atomoxetine improved stop-signal reaction times in those patients with lower locus coeruleus integrity. This was in the context of a general impairment in response inhibition, as patients on placebo had longer stop-signal reaction times compared to controls. We also found that the caudal portion of the locus coeruleus showed the largest neuromelanin signal decrease in the patients compared to controls. Our results highlight a link between the integrity of the noradrenergic locus coeruleus and response inhibition in patients with Parkinson’s disease. Furthermore, they demonstrate the importance of baseline noradrenergic state in determining the response to atomoxetine. We suggest that locus coeruleus neuromelanin imaging offers a marker of noradrenergic capacity that could be used to stratify patients in trials of noradrenergic therapy and to ultimately inform personalized treatment approaches.
Early diagnosis of brain tumours using a novel spectroscopic liquid biopsy
Authors: Brennan Paul M , Butler Holly J , Christie Loren , Hegarty Mark G , Jenkinson Michael D , Keerie Catriona , Norrie John , O’Brien Rachel , Palmer David S , Smith Benjamin R , Baker Matthew J
Published: March 2021

Early diagnosis of brain tumours is challenging and a major unmet need. Patients with brain tumours most often present with non-specific symptoms more commonly associated with less serious diagnoses, making it difficult to determine which patients to prioritize for brain imaging. Delays in diagnosis affect timely access to treatment, with potential impacts on quality of life and survival. A test to help identify which patients with non-specific symptoms are most likely to have a brain tumour at an earlier stage would dramatically impact on patients by prioritizing demand on diagnostic imaging facilities. This clinical feasibility study of brain tumour early diagnosis was aimed at determining the accuracy of our novel spectroscopic liquid biopsy test for the triage of patients with non-specific symptoms that might be indicative of a brain tumour, for brain imaging. Patients with a suspected brain tumour based on assessment of their symptoms in primary care can be referred for open access CT scanning. Blood samples were prospectively obtained from 385 of such patients, or patients with a new brain tumour diagnosis. Samples were analysed using our spectroscopic liquid biopsy test to predict presence of disease, blinded to the brain imaging findings. The results were compared to the patient’s index brain imaging delivered as per standard care. Our test predicted the presence of glioblastoma, the most common and aggressive brain tumour, with 91% sensitivity, and all brain tumours with 81% sensitivity, and 80% specificity. Negative predictive value was 95% and positive predictive value 45%. The reported levels of diagnostic accuracy presented here have the potential to improve current symptom-based referral guidelines, and streamline assessment and diagnosis of symptomatic patients with a suspected brain tumour.
Structural Plastic Changes of Cortical Gray Matter Revealed by Voxel-Based Morphometry and Histological Analyses in a Monkey Model of Central Post-Stroke Pain
Authors: Nagasaka Kazuaki , Nemoto Kiyotaka , Takashima Ichiro , Bando Daigo , Matsuda Keiji , Higo Noriyuki
Published: March 2021

Central post-stroke pain (CPSP) is a chronic pain caused by stroke lesions of somatosensory pathways. Several brain imaging studies among patients with CPSP demonstrate that the pathophysiological mechanism underlying this condition is the maladaptive plasticity of pain-related brain regions. However, the temporal profile of the regional plastic changes, as suggested by brain imaging of CPSP patients, as well as their cellular basis, is unknown. To investigate these issues, we performed voxel-based morphometry (VBM) using T1-weighted magnetic resonance imaging and immunohistochemical analysis with our established CPSP monkey model. From 8 weeks after a hemorrhagic lesion to the unilateral ventral posterolateral nucleus of the thalamus, the monkeys exhibited significant behavioral changes that were interpreted as reflecting allodynia. The present VBM results revealed a decrease in gray matter volume in the pain-related areas after several weeks following the lesion. Furthermore, immunohistochemical staining in the ipsilesional posterior insular cortex (ipsi-PIC) and secondary somatosensory cortex (ipsi-SII), where the significant reduction in gray matter volume was observed in the VBM result, displayed a significant reduction in both excitatory and inhibitory synaptic terminals compared to intact monkeys. Our results suggest that progressive changes in neuronal morphology, including synaptic loss in the ipsi-PIC/SII, are involved in theCPSP.
Prevalence of Severe Acute Respiratory Syndrome Coronavirus 2 Among Healthcare Workers—Zambia, July 2020
Authors: Fwoloshi Sombo , Hines Jonas Z , Barradas Danielle T , Yingst Samuel , Siwingwa Mpanji , Chirwa Lameck , Zulu James E , Banda Dabwitso , Wolkon Adam , Nikoi Kotey I , Chirwa Bob , Kampamba Davies , Shibemba Aaron , Sivile Suilanji , Zyambo Khozya D , Chanda Duncan , Mupeta Francis , Kapina Muzala , Sinyange Nyambe , Kapata Nathan , Zulu Paul M , Makupe Alex , Mweemba Aggrey , Mbewe Nyuma , Ziko Luunga , Mukonka Victor , Mulenga Lloyd B , Malama Kennedy , Agolory Simon
Published: March 2021

Background

Healthcare workers (HCWs) in Zambia have become infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19). However, SARS-CoV-2 prevalence among HCWs is not known in Zambia.

Methods

We conducted a cross-sectional SARS-CoV-2 prevalence survey among Zambian HCWs in 20 health facilities in 6 districts in July 2020. Participants were tested for SARS-CoV-2 infection using polymerase chain reaction (PCR) and for SARS-CoV-2 antibodies using enzyme-linked immunosorbent assay (ELISA). Prevalence estimates and 95% confidence intervals (CIs), adjusted for health facility clustering, were calculated for each test separately, and a combined measure for those who had PCR and ELISA was performed.

Results

In total, 660 HCWs participated in the study, with 450 (68.2%) providing a nasopharyngeal swab for PCR and 575 (87.1%) providing a blood specimen for ELISA. Sixty-six percent of participants were females, and median age was 31.5 years (interquartile range, 26.2–39.8). The overall prevalence of the combined measure was 9.3% (95% CI, 3.8%–14.7%). PCR-positive prevalence of SARS-CoV-2 was 6.6% (95% CI, 2.0%–11.1%), and ELISA-positive prevalence was 2.2% (95% CI, .5%–3.9%).

Conclusions

SARS-CoV-2 prevalence among HCWs was similar to a population-based estimate (10.6%) during a period of community transmission in Zambia. Public health measures such as establishing COVID-19 treatment centers before the first cases, screening for COVID-19 symptoms among patients who access health facilities, infection prevention and control trainings, and targeted distribution of personal protective equipment based on exposure risk might have prevented increased SARS-CoV-2 transmission among Zambian HCWs.
Concurrent diabetes and heart failure: interplay and novel therapeutic approaches
Authors: Karwi Qutuba G , Ho Kim L , Pherwani Simran , Ketema Ezra B , Sun Qiuyu , Lopaschuk Gary D
Published: March 2021

Diabetes mellitus increases the risk of developing heart failure, and the co-existence of both diseases worsens cardiovascular outcomes, hospitalization, and the progression of heart failure. Despite current advancements on therapeutic strategies to manage hyperglycaemia, the likelihood of developing diabetes-induced heart failure is still significant, especially with the accelerating global prevalence of diabetes and an ageing population. This raises the likelihood of other contributing mechanisms beyond hyperglycaemia in predisposing diabetic patients to cardiovascular disease risk. There has been considerable interest in understanding the alterations in cardiac structure and function in diabetic patients, collectively termed as ‘diabetic cardiomyopathy’. However, the factors that contribute to the development of diabetic cardiomyopathies are not fully understood. This review summarizes the main characteristics of diabetic cardiomyopathies, and the basic mechanisms that contribute to its occurrence. This includes perturbations in insulin resistance, fuel preference, reactive oxygen species generation, inflammation, cell death pathways, neurohormonal mechanisms, advanced glycated end-products accumulation, lipotoxicity, glucotoxicity, and post-translational modifications in the heart of the diabetic. This review also discusses the impact of antihyperglycaemic therapies on the development of heart failure, as well as how current heart failure therapies influence glycaemic control in diabetic patients. We also highlight the current knowledge gaps in understanding how diabetes induces heart failure.
Cardioprotective shock management: monitoring and supportive therapies
Authors: Schibilsky David , Delmas Clement , Bonello Laurent , Hunziker Patrick
Published: March 2021

Cardiogenic shock is a highly lethal syndrome, leading to rapid death or secondary multiorgan damage, but current shock therapies, including mechanical support devices, also have a significant side effect profile. The overarching goal of shock therapy is ensuring long-term survival with good quality of life. This implies averting death, modifying the disease course by promoting heart recovery and avoiding additional cardiac damage, protecting other organs, and circumventing complications. Monitoring and supportive therapies are subordinate to these goals. Rather than merely following preconceived notions, the rapid evolution in mechanical support technology requires iterative and critical review of the benefits of current procedures, protocols and drugs in view of their overall contribution to the therapeutic goals. This article discusses various monitoring and supportive pharmaceutical modalities typically used in patients with cardiogenic shock requiring mechanical support.
Managing vascular access and closure for percutaneous mechanical circulatory support
Authors: Karatolios Konstantinos , Hunziker Patrick , Schibilsky David
Published: March 2021

Even with current generation mechanical circulatory support (MCS) devices, vascular complications are still considerable risks in MCS that influence patients’ recovery and survival. Hence, efforts are made to reduce vascular trauma and obtaining safe and adequate arterial access using state-of-the-art techniques is one of the most critical aspects for optimizing the outcomes and efficiency of percutaneous MCS. Femoral arterial access remains necessary for numerous large-bore access procedures and is most commonly used for MCS, whereas percutaneous axillary artery access is typically considered an alternative for the delivery of MCS, especially in patients with severe peripheral artery disease. This article will address the access, maintenance, closure and complication management of large-bore femoral access and concisely describe alternative access routes.
Evaluating the impact of a very low-cost intervention to increase practices’ engagement with data and change prescribing behaviour: a randomized trial in English primary care
Authors: Curtis Helen J , Bacon Seb , Croker Richard , Walker Alex J , Perera Rafael , Hallsworth Michael , Harper Hugo , Mahtani Kamal R , Heneghan Carl , Goldacre Ben
Published: March 2021

Background

Unsolicited feedback can solicit changes in prescribing.

Objectives

Determine whether a low-cost intervention increases clinicians’ engagement with data, and changes prescribing; with or without behavioural science techniques.

Methods

Randomized trial (ISRCTN86418238). The highest prescribing practices in England for broad-spectrum antibiotics were allocated to: feedback with behavioural impact optimization; plain feedback; or no intervention. Feedback was sent monthly for 3 months by letter, fax and email. Each included a link to a prescribing dashboard. The primary outcomes were dashboard usage and change in prescribing.

Results

A total of 1401 practices were randomized: 356 behavioural optimization, 347 plain feedback, and 698 control. For the primary engagement outcome, more intervention practices had their dashboards viewed compared with controls [65.7% versus 55.9%; RD 9.8%, 95% confidence intervals (CIs): 4.76% to 14.9%, P < 0.001]. More plain feedback practices had their dashboard viewed than behavioural feedback practices (69.1% versus 62.4%); but not meeting the P < 0.05 threshold (6.8%, 95% CI: −0.19% to 13.8%, P = 0.069). For the primary prescribing outcome, intervention practices possibly reduced broad-spectrum prescribing to a greater extent than controls (1.42% versus 1.12%); but again not meeting the P < 0.05 threshold (coefficient −0.31%, CI: −0.7% to 0.1%, P = 0.104). The behavioural impact group reduced broad-spectrum prescribing to a greater extent than plain feedback practices (1.63% versus 1.20%; coefficient 0.41%, CI: 0.007% to 0.8%, P = 0.046). No harms were detected.

Conclusions

Unsolicited feedback increased practices’ engagement with data, with possible slightly reduced antibiotic prescribing (P = 0.104). Behavioural science techniques gave greater prescribing effects. The modest effects on prescribing may reflect saturation from similar initiatives on antibiotic prescribing.

Clinical Trial Registration

ISRCTN86418238.
Glucose-induced internalization of the S. cerevisiae galactose permease Gal2 is dependent on phosphorylation and ubiquitination of its aminoterminal cytoplasmic tail
Authors: Tamayo Rojas Sebastian A , Schmidl Sina , Boles Eckhard , Oreb Mislav
Published: March 2021

The hexose permease Gal2 of Saccharomyces cerevisiae is expressed only in the presence of its physiological substrate galactose. Glucose tightly represses the GAL2 gene and also induces the clearance of the transporter from the plasma membrane by ubiquitination and subsequent degradation in the vacuole. Although many factors involved in this process, especially those responsible for the upstream signaling, have been elucidated, the mechanisms by which Gal2 is specifically targeted by the ubiquitination machinery have remained elusive. Here, we show that ubiquitination occurs within the N-terminal cytoplasmic tail and that the arrestin-like proteins Bul1 and Rod1 are likely acting as adaptors for docking of the ubiquitin E3-ligase Rsp5. We further demonstrate that phosphorylation on multiple residues within the tail is indispensable for the internalization and possibly represents a primary signal that might trigger the recruitment of arrestins to the transporter. In addition to these new fundamental insights, we describe Gal2 mutants with improved stability in the presence of glucose, which should prove valuable for engineering yeast strains utilizing complex carbohydrate mixtures present in hydrolysates of lignocellulosic or pectin-rich biomass.
Polypharmacy Results in Functional Impairment in Mice: Novel Insights Into Age and Sex Interactions
Authors: Wu Harry , Mach John , Gemikonakli Gizem , Tran Trang , Allore Heather , Gnjidic Danijela , Howlett Susan E , de Cabo Rafael , Le Couteur David G , Hilmer Sarah N
Published: March 2021

Males and females may respond differently to medications, yet knowledge about sexual dimorphisms in the effects of polypharmacy remains limited, particularly in aging. This study aimed to assess the effect of high Drug Burden Index (DBI) polypharmacy treatment compared to control on physical function and behavior in young and old, male and female mice. We studied whether age and sex play a role in physical function and behavior following polypharmacy treatment and whether they are paralleled by differences in serum drug levels. Young (2.5 months) and old (21.5 months), C57BL/6 mice were randomized to control or high DBI polypharmacy treatment (simvastatin, metoprolol, oxybutynin, oxycodone, and citalopram; n = 6–8/group) for 4–6 weeks. Compared to control, polypharmacy reduced physical function (grip strength, rotarod latency, gait speed, and total distance), middle zone distance (increased anxiety), and nesting score (reduced activities of daily living) in mice of both ages and sexes (p < .001). Old animals had a greater decline in nesting score (p < .05) and midzone distance (p < .001) than young animals. Grip strength declined more in males than females (p < .05). Drug levels at steady state were not significantly different between polypharmacy-treated animals of both ages and sexes. We observed polypharmacy-induced functional impairment in both age and sex groups, with age and sex interactions in the degree of impairment, which were not explained by serum drug levels. Studies of the pathogenesis of functional impairment from polypharmacy may improve management strategies in both sexes.
Cellular Immune Phenotypes and Worsening Scores of Frailty-Associated Parameters Over an 18-Month Period in the Very Old
Authors: Goldeck David , Adriaensen Wim , Oettinger Lilly , Vaes Bert , van Pottelbergh Gijs , Degryse Jean-Marie , Hamprecht Klaus , Matheï Catharina , Pawelec Graham
Published: March 2021

Frailty has been related to inflammaging and certain immune parameters. In previous analyses of participants older than 80 years of age in the longitudinal BELFRAIL cohort study, the main focus was on T-cell phenotypes and the association with cytomegalovirus (CMV) serostatus and survival, finding that a CD4:CD8 ratio greater than 5 was associated with frailty, impaired activities of daily living (ADLs), and mortality (but only in women). Here, we phenotyped peripheral blood immune cells via multicolor flow cytometry and correlated these with the dynamics of changes in ADL, geriatric depression score, Mini-Mental State Examination, and Short Physical Performance Battery from baseline values over 18 months follow-up. We found that higher frequencies of B cells and late-differentiated CD8+ T cells at 18 months from baseline were associated with ADL impairment that had worsened over the preceding 18 months. There were no significant associations with monocyte, dendritic cell, or natural killer (NK) cell phenotypes. No associations with the Geriatric Depression Scale, the Mini-Mental State Examination, or the Short Physical Performance Battery were found. Thus, while these results do not establish causality, they suggest that certain adaptive immune, but not innate immune, parameters are associated with a worsened ADL in the very old.
Finding opportunity in the COVID-19 crisis: prioritizing gender in the design of social protection policies
Authors: Perri Melissa , Metheny Nick , Matheson Flora I , Potvin Kelly , O’Campo Patricia
Published: March 2021

The COVID-19 pandemic is highlighting the harm perpetuated by gender-blind programs for marginalized citizens, including sexual and gender minorities (SGMs) and cisgender women. Gender-blind programs are known to augment harms associated with violence and structural stigmatization by reinforcing rather than challenging unequal systems of power. The intersecting marginalization of these populations with systems of class, race, and settler-colonialism is exacerbating the impact that policies such as physical distancing, school closures, and a realignment of healthcare priorities are having on the wellbeing of these populations. The overarching reasons why women and SGM are marginalized are well known and stem from a hegemonic, patriarchal system that fails to fully integrate these groups into planning and decision making regarding public health programming—including the response to COVID-19. In this perspective, we aim to highlight how the exclusion of cisgender women and SGM, and failure to use a gender redistributive/transformative approach, has (i) hampered the recovery from the pandemic and (ii) further entrenched the existing power structures that lead to the marginalization of these groups. We also argue that COVID-19 represents a once-in-a-century opportunity to realign priorities regarding health promotion for cisgender women and SGM by using gender redistributive/transformative approaches to the recovery from the pandemic. We apply this framework, which aims to challenge the existing power structures and distribution of resources, to exemplars from programs in health, housing, employment, and incarceration to envision how a gender redistributive/transformative approach could harness the COVID-19 recovery to advance health equity for cisgender women and SGM.
Characterization of Klebsiella pneumoniae complex isolates from pigs and humans in farms in Thailand: population genomic structure, antibiotic resistance and virulence genes
Authors: Leangapichart Thongpan , Lunha Kamonwan , Jiwakanon Jatesada , Angkititrakul Sunpetch , Järhult Josef D , Magnusson Ulf , Sunde Marianne
Published: March 2021

Objectives

To define characteristics of Klebsiella pneumoniae complex (hereafter KP) isolates from healthy pigs, farm workers and their household members in Thailand.

Methods

A total of 839 individual rectal swabs from pigs on 164 farms and 271 faecal samples of humans working on pig farms and persons living in the same household in Khon Kaen, Thailand were screened for gut colonization by KP. Genomic sequences were investigated for antibiotic resistance and virulence genes. Phylogenetic analyses were performed in addition to comparison with isolates from previous studies from Thailand.

Results

KP was detected in approximately 50% of pig and human samples. In total, 253 KP isolates were obtained: 39% from pigs, 34% from farmers and 26% from individuals living on the same farm but without animal contact. MLST revealed high genetic diversity with 196 different STs distributed over four phylogroups (Kp1 to Kp4). Low prevalence of ESBL-KP (7.5%) and colistin-resistant KP (3.2%) was observed among pigs and humans. Remarkably, four convergent MDR and hypervirulent strains were observed: one from pigs (ST290) and three from humans [ST35, ST3415 (strain 90CP1), ST17 (strain 90CM2)]. Sharing of KP clones among pigs and humans was identified for some STs including ST4788, ST661, ST3541 and ST29.

Conclusions

The study indicated a low prevalence of ESBL and mcr genes among KP isolated from pigs and healthy humans in Thailand and suggested the possibility of zoonotic transmission for a subset of circulating KP clones.
The Impact of a Two-Step Choice Process on Trade-Off Decisions
Authors: Lei Jing , Zhang Ying
Published: March 2021

Trade-offs between attributes are common when making product choices. Prior research suggests that consumers tend to avoid the extremes and opt for the middle options when they make a trade-off decision between two key product attributes (e.g., tastiness and healthiness of food items) in one step. In this research, we examine how consumers make such trade-off decisions in a two-step choice process in which consumers first choose between product categories competing on two key attributes and then make a final choice within the chosen category. In three studies, we show that when holding the actual choice options unchanged, consumers are more likely to make a more extreme final choice, prioritizing a single attribute rather than compromising when they follow a two-step choice process instead of a one-step process.
Alterations in the Expression of the Genes Responsible for the Synthesis of Heparan Sulfate in Brains With Alzheimer Disease
Authors: Pérez-López Natalia , Martín Carla , García Beatriz , Solís-Hernández Maria Pilar , Rodríguez David , Alcalde Ignacio , Merayo Jesús , Fernández-Vega Iván , Quirós Luis M
Published: March 2021

The saccharide chains of heparan sulfate appear to be involved in several aspects Alzheimer disease (AD) pathogenesis. Their structural complexity is due to the expression of different isoenzymes. We studied the differential transcription of heparan sulfate chain biosynthesis in AD brains, analyzing different brain regions in patients with different extents of AD pathology. The transcriptomic study was performed by RT-PCR using samples of amygdala, anterior hippocampus, posterior hippocampus, claustrum, calcarine fissure, globus pallidus and cerebellum from patients with mild, moderate, or severe AD, as well as healthy individuals. Certain heparan sulfate epitopes were also detected by immunohistochemistry. Several genes, across all stages of heparan sulfate synthesis, showed altered transcription in different brain regions of AD patients. The numbers of alterations were greater in in moderate versus mild AD patients. In severe patients, there were fewer alterations in genes related to early stages of biosynthesis, and overexpression of genes involved in late stages. The alterations correlated with progressive brain atrophy, although alterations were more common in the cerebellum. Detection of some heparan sulfate epitopes by immunohistochemistry was consistent with previous studies. In conclusion, transcriptional alterations in the biosynthetic genes of heparan sulfate depend on the brain region and the degree of AD pathology.
High-altitude tree growth responses to climate change across the Hindu Kush Himalaya
Authors: Zheng Lili , Gaire Narayan Prasad , Shi Peili
Published: March 2021

Aims

Rapid warming at high altitudes may lead to a higher sensitivity in tree growth to temperature. The key factors constraining tree radial growth and to what extent regional tree growth has suffered from climatic changes are unclear.

Methods

Tree-ring width data were collected from 73 sites across the Hindu Kush Himalaya (HKH), including three dominant genera (Abies, Juniperus and Picea) at high altitudes over 3000 m. Dynamic time warping was introduced to develop subregional chronologies by considering the synchrony of annual tree growth among different sites. We quantified the contribution of the climate variables, and analyzed the spatiotemporal variation of the growth–climate relationship.

Important Findings

The site chronologies were grouped into three clusters, corresponding to the three distinct bioclimatic zones, i.e. the western HKH, central-eastern HKH and southeastern Tibetan Plateau (TP). Tree growth was positively correlated to winter and spring precipitation in the drier western HKH, and to winter temperature and spring precipitation in the humid southeastern TP. Tree growth was markedly constrained by the minimum temperature, especially in winter, with its importance increasing from the west toward the east. As shown by moving correlation analysis, the signal of winter temperature in tree growth was weakened in the western and central-eastern HKH, while it was enhanced in the southeastern TP following rapid warming since the 1980s. Our results highlight that continuous warming may cause forest recession due to warming-induced moisture deficit in the western HKH, but forest expansion in the southeastern TP.
Validation of dose distribution for liver tumors treated with real-time-image gated spot-scanning proton therapy by log data based dose reconstruction
Authors: Yamada Takahiro , Takao Seishin , Koyano Hidenori , Nihongi Hideaki , Fujii Yusuke , Hirayama Shusuke , Miyamoto Naoki , Matsuura Taeko , Umegaki Kikuo , Katoh Norio , Yokota Isao , Shirato Hiroki , Shimizu Shinichi
Published: March 2021

In spot scanning proton therapy (SSPT), the spot position relative to the target may fluctuate through tumor motion even when gating the radiation by utilizing a fiducial marker. We have established a procedure that evaluates the delivered dose distribution by utilizing log data on tumor motion and spot information. The purpose of this study is to show the reliability of the dose distributions for liver tumors treated with real-time-image gated SSPT (RGPT). In the evaluation procedure, the delivered spot information and the marker position are synchronized on the basis of log data on the timing of the spot irradiation and fluoroscopic X-ray irradiation. Then a treatment planning system reconstructs the delivered dose distribution. Dose distributions accumulated for all fractions were reconstructed for eight liver cases. The log data were acquired in all 168 fractions for all eight cases. The evaluation was performed for the values of maximum dose, minimum dose, D99, and D5–D95 for the clinical target volumes (CTVs) and mean liver dose (MLD) scaled by the prescribed dose. These dosimetric parameters were statistically compared between the planned dose distribution and the reconstructed dose distribution. The mean difference of the maximum dose was 1.3% (95% confidence interval [CI]: 0.6%—2.1%). Regarding the minimum dose, the mean difference was 0.1% (95% CI: −0.5%—0.7%). The mean differences of D99, D5–D95 and MLD were below 1%. The reliability of dose distributions for liver tumors treated with RGPT-SSPT was shown by the evaluation of the accumulated dose distributions.
The Foundations of European Union Competition Law
Authors: Renato Nazzini
Published: March 2021

Article 102 of the TFEU prohibits the abuse of a dominant position as incompatible with the common market. Its application in practice has been wide-ranging with goals as diverse as the preservation of an undistorted competitive process, the protection of economic freedom, the maximisation of consumer welfare, total welfare, or economic efficiency all cited as possible or desirable objectives. These conflicting aims have raised complex, conceptual questions such as how a dominant position should be defined, and how abuses can be assessed. This book addresses the conceptual questions underlying the test to be applied under Article 102 in light of the objectives of EU competition law. Adopting a comparative and interdisciplinary approach, the book covers all the main issues relating to Article 102, including the definition of dominance, the taxonomy of abuses, and the criteria for the assessment of individual abusive practices. It provides an in-depth doctrinal and normative commentary of the case law with the aim of establishing an intellectually robust and practically workable analytical framework for abuse of dominance.
Emergency Neurology
Authors: LaHue Sara , Levin Morris
Published: March 2021

Neurological emergencies, either presenting in the emergency department, arising in hospitalized patients, or presenting in the field are among the most worrisome of all medical situations. Neurologists are trained in best approaches to these emergencies, which include such diverse presentations as severe headache, transient neurologic deficits, altered consciousness and coma, severe vertigo and balance problems, uncontrolled seizures, radicular and facial pain, and posttraumatic conditions. However, as time is often “the enemy” as ER physicians commonly say, diagnostic and treatment dilemmas are particularly challenging in the field of emergency neurology. This volume attempts, as do all the offerings in Oxford University Press’s What Do I Do Now series, to present straightforward but thorough roadmaps for handling the most common and worrisome impasses faced by neurologists and other providers in the topic area. Illustrative cases in cerebrovascular, epileptic, infectious, inflammatory, metabolic, traumatic, neoplastic, and structural conditions are presented with recommendations for best approaches to differential diagnosis, diagnostic testing, and management decision-making in important challenges faced in both adult and pediatric cases. Each case contains a brief summary of key information. The reader is encouraged to imagine the case under discussion, formulate a differential diagnosis, plan diagnostic testing, and begin thinking about best management approaches. Then read Drs. LaHue’s and Levin’s approach to the situation. At the end of each chapter is a list of key points to remember in the topic and a selection of resources for further reading.
Hospital-Acquired Delirium
Authors: LaHue Sara C. , Levin Morris
Published: March 2021

Delirium is becoming increasingly recognized as a symptom of serious illness as well as a risk factor for poor clinical outcomes in its own right. This case provides a framework for these often nebulous presentations.
Coma with Fever
Authors: LaHue Sara C. , Levin Morris
Published: March 2021

Meningitis can be a life-threatening emergency that requires rapid identification and management. This case summarizes the workup for meningitis, including the appropriate timing of imaging studies and lumbar puncture.
Refractory Vertigo
Authors: LaHue Sara C. , Levin Morris
Published: March 2021

Vertigo is one of the most disturbing symptoms patients can experience and while generally a symptoms of vestibular dysfunction, cerebrovascular and other etiologies may be at play.
Intracranial Mass in a Person with HIV
Authors: LaHue Sara C. , Levin Morris
Published: March 2021

An immunosuppressed state, such as in the presence of HIV infection, can complicate the workup of brain lesions, and so several paradigms for diagnosis and initial treatment are reviewed here.
Acute Neuralgia
Authors: LaHue Sara C. , Levin Morris
Published: March 2021

Flares of trigeminal neuralgia pain will bring some patients to the emergency department and fortunately there are useful interventions.
Acute Cervical Radiculopathy
Authors: LaHue Sara C. , Levin Morris
Published: March 2021

The pain of acute cervical radiculopathy can be intense, but there are ways to buy time before choosing invasive approaches.
Myasthenic Crisis
Authors: LaHue Sara C. , Levin Morris
Published: March 2021

Acute respiratory failure can be due to a variety of causes, and neuromuscular weakness is an important consideration. Myasthenic crisis identification and management is reviewed.
Migraine in a Pregnant Patient
Authors: LaHue Sara C. , Levin Morris
Published: March 2021

The pregnant migraineur is often frustrated by the lack of safe therapies. Fortunately there are actually a number of good management options.
Acute coronary syndrome: STEMI and NSTEMI
Authors: Prasad Abhiram , Raphael Claire
Published: March 2021

Management of acute coronary syndrome (ACS) is dictated by clinical features and electrocardiographic findings. Morphine is used for pain relief. Sublingual or intravenous nitrates are administered to relieve ischaemia. Patients should be treated with dual antiplatelet medications, usually aspirin and one of clopidogrel, prasugrel, or ticagrelor. For ST-segment elevation myocardial infarction, reperfusion therapy is with primary percutaneous coronary intervention (PPCI) or thrombolysis for those presenting to non-PPCI centres who cannot have timely access to PPCI. For non-ST-segment elevation myocardial infarction and unstable angina, timing of angiography, and revascularization if indicated, is determined by the severity of ischaemia. All patients with ACS should be treated with secondary prevention medications, including antiplatelet therapy, statins, beta-blockers, and renin–angiotensin system inhibitors.
A novel approach to investigate chemical inhomogeneities in GRB host galaxies: theZabs–Zemiss relation
Authors: Metha Benjamin , Cameron Alex J , Trenti Michele
Published: March 2021

Models of chemical enrichment and inhomogeneity in high-redshift galaxies are challenging to constrain observationally. In this work, we discuss a novel approach to probe chemical inhomogeneities within long gamma-ray burst (GRB) host galaxies, by comparing the absorption metallicity, Zabs, from the GRB afterglow (which probes the environment along the line of sight) with the emission-line metallicity, Zemiss, measured via slit spectroscopy. Using the IllustrisTNG simulation, the theoretical relationship between these metallicity metrics is explored for a range of GRB formation models, varying the GRB progenitor metallicity threshold. For galaxies with fixed Zemiss, the median value of Zabs depends strongly on the GRB progenitor threshold metallicity, with Zabs significantly lower than Zemiss for high-metallicity hosts. Conversely, at fixed Zabs, the median value of Zemiss depends primarily on the metallicity distribution of galaxies in IllustrisTNG and their chemical inhomogeneities, offering a GRB model-independent way to constrain these processes observationally. Currently, only one host galaxy has data for both absorption and emission metallicities (GRB121014A). We re-analyse the emission spectrum and compare the inferred metallicity Zemiss to a recent Bayesian determination of Zabs, finding $\log (Z_{\rm emiss}/Z_{\odot }) = \log (Z_{\rm abs}/Z_{\odot }) +0.35^{+ 0.14}_{- 0.25}$, within ∼2 standard deviations of predictions from the IllustrisTNG simulation. Future observations with the James Webb Space Telescope will be able to measure Zemiss for four other GRB hosts with known Zabs values, using ∼2-h observations. While small, the sample will provide preliminary constraints on the Zabs–Zemiss relation to test chemical enrichment schemes in cosmological simulations.
The VMC Survey – XLII. Near-infrared period–luminosity relations for RR Lyrae stars and the structure of the Large Magellanic Cloud
Authors: Cusano F , Moretti M I , Clementini G , Ripepi V , Marconi M , Cioni M-R L , Rubele S , Garofalo A , de Grijs R , Groenewegen M A T , Oliveira J M , Subramanian S , Sun N-C , van Loon J Th
Published: March 2021

We present results from an analysis of ∼29 000 RR Lyrae stars located in the Large Magellanic Cloud (LMC). For these objects, near-infrared time-series photometry from the VISTA survey of the Magellanic Clouds system (VMC) and optical data from the Optical Gravitational Lensing Experiment (OGLE) IV survey and the Gaia Data Release 2 catalogue of confirmed RR Lyrae stars were exploited. Using VMC and OGLE IV magnitudes we derived period–luminosity (PL), period–luminosity–metallicity (PLZ), period–Wesenheit (PW), and period–Wesenheit–metallicity (PWZ) relations in all available bands. More that  7000 RR Lyrae were discarded from the analysis because they appear to be overluminous with respect to the PL relations. The $PL_{K_{\mathrm{s}}}$ relation was used to derive individual distance to ${\sim}22\, 000$ RR Lyrae stars, and study the three-dimensional structure of the LMC. The distribution of the LMC RR Lyrae stars is ellipsoidal with the three axis S1 = 6.5 kpc, S2 = 4.6 kpc, and S3 = 3.7 kpc, inclination i = 22 ± 4° relative to the plane of the sky and position angle of the line of nodes θ = 167 ± 7° (measured from north to east). The north-eastern part of the ellipsoid is closer to us and no particular associated substructures are detected and neither any metallicity gradient.
Modulated accretion in the T Tauri star RY Tau – a stable MHD propeller or a planet at 0.2 au?
Authors: Petrov P P , Romanova M M , Grankin K N , Artemenko S A , Babina E V , Gorda S Yu
Published: March 2021

Planets are thought to form at the early stage of stellar evolution when mass accretion is still ongoing. RY Tau is a T Tauri type star at the age of a few Myr, with an accretion disc seen at high inclination, so that the line of sight crosses both the wind and accretion gas flows. In a long series of spectroscopic monitoring of the star over the period 2013–2020, we detected variations in H$\, {\alpha }$ and Na i D absorptions at radial velocities of infall (accretion) and outflow (wind) with a period of about 22 d. The absorptions in the infalling and outflowing gas streams vary in antiphase: an increase of infall is accompanied by a decrease of outflow, and vice versa. These ‘flip-flop’ oscillations retain phase over several years of observations. We suggest that this may result from the magnetohydrodynamics processes at the disc–magnetosphere boundary in the propeller mode. Another possibility is that a massive planet is modulating some processes in the disc and is providing the observed effects. The period, if Keplerian, corresponds to a distance of 0.2 au, which is close to the dust sublimation radius in this star. The presence of the putative planet can be confirmed by radial velocity measurements: the expected amplitude is ≥90 m s−1 if the planet mass is ≥2 MJ.