bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of a single‐tablet regimen containing tenofovir disoproxil fumarate 300 mg, lamivudine 300 mg and efavirenz 400 mg as a switch strategy in virologically suppressed HIV‐1‐infected subjects on nonnucleoside reverse transcriptase inhibitor‐containing first‐line antiretroviral therapy in Pune, India
Authors: Dravid A , Betha TP , Sharma AK , Gawali R , Mahajan U , Kulkarni M , Saraf C , Kore S , Dravid M , Rathod N
Published: July 2020

Objectives

As per National AIDS Control Organization (NACO) estimates, there are 2.1 million people living with HIV (PWH) in India, of whom 1.2 million are on first‐line antiretroviral therapy (ART). This study explored the use of a single‐tablet regimen containing tenofovir disoproxil fumarate 300 mg + lamivudine 300 mg + efavirenz 400 mg (TLE400 STR) as a first‐line switch strategy in PWH in Pune, India.

Methods

This retrospective cohort study was conducted in private sector ART clinics in three tertiary‐level hospitals in Pune, India. PWH > 12 years of age (n = 502) who initiated first‐line ART (predominantly TLE600 STR), completed ≥ 6 months of follow‐up and achieved virological suppression [plasma viral load (VL) < 1000 HIV‐1 RNA copies/mL] were identified and switched to TLE400 STR. The virological and immunological efficacy of TLE400 STR at 6 and 12 months of follow‐up were noted. Grade 3/4 adverse events (especially efavirenz‐related neuropsychiatric adverse events) leading to regimen discontinuation were also noted.

Results

Of 502 PWH who switched to TLE400 STR, complete virological suppression (VL < 20 copies/mL) was maintained in more than 97% of patients at follow‐up. TLE400 STR was successful in maintaining CD4 counts within the range observed at the start of the regimen. Grade 3/4 adverse events leading to TLE400 STR discontinuation were seen in 11 (2.2%) patients. Virological failure (VL > 1000 copies/mL) and treatment regimen failure were seen in six (1.2%) and 49 (9.8%) subjects, respectively.

Conclusions

TLE400 STR exhibits excellent efficacy and safety as a switch strategy and should be introduced in the Indian National ART Program, especially for PWH who are virologically suppressed on TLE600 STR.
Stratum corneum occlusion induces water transformation towards lower bonding state: a molecular level in vivo study by confocal Raman microspectroscopy
Authors: Choe C. , Schleusener J. , Choe S. , Ri J. , Lademann J. , Darvin M. E.
Published: July 2020

Objective

It is conventionally understood that occlusive effects are the retention of excessive water in the stratum corneum (SC), the increase of SC thickness (swelling) and a decrease of the transepidermal water loss. However, the influence of occlusion on water binding properties in the SC is unknown.

Methods

The action of plant‐derived jojoba and almond oils, as well as mineral‐derived paraffin oil and petrolatum topically applied on human skin, is investigated in vivo using confocal Raman microspectroscopy. To understand the oils’ influence on the SC on the molecular level, the depth‐dependent hydrogen bonding states of water in the SC and their relationship to the conformation of keratin, concentration of natural moisturizing factor (NMF) molecules and lipid organization were investigated.

Results

A significant SC swelling was observed only in petrolatum‐treated skin. The water concentration was increased in oil‐treated skin in the intermediate SC region (40–70% SC depth). Meanwhile, the amount of free, weakly and tightly bound water increased, and strongly bound water decreased in the uppermost SC region (0–30% SC depth). The NMF concentration of oil‐treated skin was significantly lower at 50–70% SC depth. The lateral organization of lipids in oil‐treated skin was lower at 0–30% SC depth. The secondary structure of keratin was changed towards an increase of β‐sheet content in mineral‐derived oil‐treated skin and changed towards an increase of α‐helix content in plant‐derived oil‐treated skin.

Conclusion

The occlusive properties can be summarized as the increase of free water and the transformation of water from a more strongly to a more weakly hydrogen bonding state in the uppermost SC, although some oils cause insignificant changes of the SC thickness. The accompanied changes in the keratin conformation at the intermediate swelling region of the SC also emphasize the role of keratin in the SC’s water‐transporting system, that is the water in the SC transports intercellularly and intracellularly in the intermediate swelling region and only intercellularly in the uppermost non‐swelling region. Bearing this in mind, almond, jojoba and paraffin oils, which are not occlusive from the conventional viewpoint, have an occlusion effect similar to petrolatum on the SC.
Venus Re‐Defined Resource Pack: An Evaluation
Authors: Hiett Sandra , Orbach Catherine
Published: July 2020

Within the history of Western European art the nude is a central subject. For schools, this can be a problematic area for study. The Venus Re‐Defined resource pack was produced to accompany a display at Tate Gallery Liverpool which included sculptures by Rodin, Matisse, Renoir and Maillol. It aims to actively engage young people in discussions of these works and the debates which surround them. Drawing upon a feminist critique, the pack identifies three themes for exploration: sculpture and the body, the relationship between artist and model and the representation of women. This paper examines how teachers used the pack in six secondary schools and explores the opportunities and demands presented by this issue based approach.
From a Word Picture to a Painting: The Use of Marion Richardson's Visualisation Technique with Key Stage 1 Children
Authors: Brigstock Dee
Published: July 2020

This study uses a method of visualisation propounded by the art educator Marion Richardson (1892‐1946), to discover if I, a non‐specialist teacher, could use this process to increase the technical and compositional skills of young children. The programme involved a series of five painting lessons, the first used to assess ability, after which the children involved were split into Control and Experimental Groups.

The Experimental Group practised ‘visualising’ their pictures, before beginning to draw or paint. The completed pictures were marked separately by three independent assessors, used to making judgements on the quality of children's art work. I had no part in the marking, but supplied relevant details about the content of the lessons. At no time did any one except myself know the membership of either the Control or the Experimental Groups.

It was predicted that there would be a small improvement in the quality of work produced by the children from the Experimental group over and above that of the Control group.

The results show that the Experimental group made significant progress over the Control group.
Art and World View: Escaping the Formalist Labyrinth
Authors: Cunliffe Leslie
Published: July 2020

This paper attempts to identify the theoretical and practical issues for developing the secondary art curriculum for dealing with the meaning of works of art in relationship to the demands of teaching attainment target 2 of the English National Curriculum for ait and the new GCSE syllabuses to be introduced in September, 1996.

The first section deals with the theoretical issues related to art, meaning and life. Formalism is considered inadequate for understanding and responding to works of art and is rejected in favour of an approach that gives greater priority to the multidimensional and relational features that give works of art meaning. This places art back again as an irreducible feature of wider cultural processes. In advocating this approach I will criticise collectivist and historicist explanations that are ultimately rooted in Hegel's idea of the ‘spirit of the age’. The more dynamic understanding of culture as a product of an elaborate ‘conversation’ that is open but constrained, based on the available symbolic codes of a given form of life, will be preferred as an explanation for art and cultural change.

The second section models some classroom strategies that can be used to teach art on the basis of considerations related to meaning that emerge from the previous theoretical discussion. Searle's [19831 distinction in the ‘direction of fit’ of perception between ‘mind‐to‐world’ and ‘world‐to‐mind’ is used to establish a methodological principle for understanding and dealing with meaning in works of art. The former starts with the pupils' existing schemata and deals in ambiguities and conjectured interpretation. The latter gives priority to the art object in context, and attempts to develop in pupils an empathy for and understanding of the multi‐dimensional factors that influence the making of art.

The paper argues for the need for both approaches to be used in a complementary way so that a knowledge‐seeking rather than a self‐seeking attitude to the meaning of works of art is nurtured in pupils.
Do foreign institutional investors drive corporate social responsibility? Evidence from listed firms in China
Authors: Li Zhe , Wang Ping , Wu Tianlong
Published: July 2020

This paper investigates the effect of qualified foreign institutional investors (QFIIs) on corporate social responsibility (CSR) within the context of listed firms in China. We find that QFIIs offer an incisive channel for improving socially responsible practices. In addition, we find that firms with QFIIs are more likely to comply with the Global Reporting Initiative (GRI) guidelines, and that their sustainability reports tend to be longer. We also find that this positive effect is more pronounced in firms with low initial CSR scores than those with high CSR scores at the time when QFIIs enter the sample. Our empirical evidence further confirms that this positive impact is driven by QFIIs from countries with high social awareness, or QFIIs from geographically distant countries, consistent with their motives, and is linked to the ownership of QFIIs, especially when the QFII is among the top ten of the largest shareholders. Finally, our extended analysis reveals that the increase in CSR performance associated with the presence of QFIIs results in greater firm performance and easier access to finance.
Considerations for working with youth with socially complex needs
Authors: Bounds Dawn T. , Winiarski Dominka A. , Otwell Caitlin H. , Tobin Valerie , Glover Angela C. , Melendez Adrian , Karnik Niranjan S.
Published: July 2020

Topic

The presence of adverse childhood experiences offers a glimpse into the social complexity in the lives of youth. Thus far, youth have been categorized as “at‐risk” or “vulnerable,”—identifiers which highlight a deficits‐based framework and continue to stigmatize youth. To combat this systemic marginalization, we propose using the term youth with socially complex needs. These youth, often minority ethnic/racial and/or sexual/gender minorities, experience repeated adversity and discrimination.

Purpose

The purpose of this paper is to conceptualize the unique considerations of working with youth with socially complex needs—who have an increased vulnerability for social marginalization.

Sources Used

Given the adversity experienced and challenges inherent in working with youth with socially complex needs, ethical principles, and relevant care delivery models were explored.

Conclusions

Delivering mental health care and/or conducting research in collaboration with youth with socially complex needs requires thoughtful consideration of ethical principles and models of care. In conclusion, we propose a strengths‐based, individualized approach to working with youth with socially complex needs that requires a dynamic, fluid, multisystemic approach to care and research.
The Japanese Multidimensional Attitudes Scale Toward Persons With Autism Spectrum Disorders1
Authors: Tsujita Masaki , Ban Mutsuhisa , Kumagaya Shin‐Ichiro
Published: July 2020

This study aimed to develop a Japanese Multidimensional Attitudes Scale (J‐MAS) as a useful instrument to assess negative attitudes toward persons with autism spectrum disorder among typical Japanese persons. Five hundred and fifty‐two Japanese participants completed the Japanese translation of the original version of the MAS, which was derived via the translation/back‐translation method. An exploratory factor analysis revealed four factors (Cognitions, Negative Affects, Behaviors, and Calm) that corresponded to the factor model of the original version of the MAS. Nine items were statistically negligible, accordingly. A confirmatory factor analysis revealed that the factor model of the J‐MAS is fairly good, and preferable to the factor models of the English, Spanish, French, Korean, and German versions for a sample of typical Japanese persons. These results indicate that the J‐MAS provides a valid assessment of attitudes toward persons with autism spectrum disorder among typical Japanese persons.
Free verse, historical poetics, and settler time
Authors: Kappeler Erin Joyce
Published: July 2020

This article pushes back against the ongoing literary historical tendency to narrate the emergence of free verse forms in the modernist era as a salutary break with the poetic practices of the nineteenth century. Using the methods of historical poetics, I read key texts by the modernist poet and activist Mary Austin, who helped to invent Native American poetry as a field, to show that the concept of free verse was a tool of settler cultural domination as much as it was a democratization of poetic language or a formal innovation. Austin framed free verse poetry as a technology for managing time—specifically, for integrating Native Americans into the relentlessly linear march of what Mark Rifkin has recently theorized as settler time. Austin's theories of free verse had significant, distorting effects on the way Native American oral expressions were presented as poetry in modernist anthologies. Remembering that debates about rhythm, meter, and poetic form were also debates about temporality, space, and identity fundamentally challenges our critical assumptions about the hierarchies of form and genre that implicitly structure our literary historical narratives.
Central place foraging drives niche partitioning in seabirds
Authors: Jessopp Mark , Arneill Gavin E. , Nykänen Milaja , Bennison Ashley , Rogan Emer
Published: July 2020

When species coexist, it is expected that they will reduce competition through niche partitioning or spatial segregation. We investigated the importance of niche partitioning versus spatial segregation across a seabird community where food and foraging constraints vary seasonally. Spatial clustering of seabird density in the western Irish Sea occurred in both seasons, with hotspots of seabird occurrence significantly higher in summer (Moran's I: 0.29) than winter (Moran's I: 0.19). A positive correlation between seabird density and feeding guild richness suggested a role for niche partitioning in reducing competition. This correlation was significantly stronger in summer than winter (Z‐test, p < 0.05), suggesting that when foraging range is constrained during the breeding season, interspecific competition is reduced through increased niche partitioning. Reduced spatial clustering and weaker correlations between density and feeding guild richness in winter suggests that spatial segregation plays a greater role in reducing interspecific competition outside the breeding season. This study demonstrates the relative importance of niche partitioning and spatial segregation, highlighting niche partitioning as a response to constraints on foraging range during the breeding season.
The blue light dose from white light emitting diodes (LEDs) and other white light sources
Authors: Dain Stephen J.
Published: July 2020

Purpose

This study was carried out to determine if light emitting diodes (LEDs) represented a special case in exposing the retina to blue light, when compared with other methods of backlighting television and computer screens and with fluorescent tube lighting.

Method

The spectral distribution of light from computer and television screens (cathode ray tube, plasma screen, organic LEDs, and screens backlit by cold cathode tubes and/or LEDs), domestic type spotlights (LED and fluorescent tube) and objects in the outdoor sunlit environment were measured with a telespectroradiometer. The spectral data were analysed for the proportion of blue light and luminance. The results were also presented as time to reach the occupational safety limit, without regard to the normal 10 000 s time limit by which time there is no summation of exposure.

Results

The amount of blue light in a source is essentially independent of the technology of the light source, but closely related to the correlated colour temperature.

Conclusions

Fluorescent lamps show essentially the same proportions of blue light and LEDs do not represent a special case, given the same correlated colour temperature. Blue‐blocking lenses are no more needed with LED sources than with other screen illumination methods or with fluorescent lighting. There is no evidence base on which to recommend blue‐blocking lenses for indoor applications.
Presence of intralesional melanocytes as a histopathological feature of actinic keratosis based on in vivo harmonic generation microscopy in Asians
Authors: Ho Yi‐Hsin , Pan Yi , Sun Chi‐Kuang , Liao Yi‐Hua
Published: July 2020

Background

Most patients with actinic keratosis (AK) present with more than one lesion. Although histopathological examination is the gold standard for diagnosing this condition, performing an invasive skin biopsy for each AK is impractical. Thus, this study aimed to identify AK’s morphological characteristics based on harmonic generation microscopy (HGM). Moreover, the correlation between features observed using HGM and histopathological grading of AK was examined.

Methods

Lesions of seven patients were examined using HGM (n = 1, ex vivo and n = 6, in vivo), and histopathological examinations of the biopsy specimens were also performed. The features of each AK, based on HGM, were assessed and compared with corresponding standard histopathological findings.

Results

Using the histopathological findings as a standard reference, HGM’s accuracy in detecting features of AK lesions, such as hyperkeratosis, epidermal thinning, abnormal architecture, and atypical honeycomb pattern, was 100%. Approximately five (72%) patients had similar histopathological grades. Moreover, based on HGM, except for one patient with grade 1 AK, six (85.71%) patients had lesions with intraepidermal dendritic cell‐like cells, representing melanocytes.

Conclusion

Harmonic generation microscopy can be used in vivo to provide critical diagnostic information with a resolution comparable to histopathological examination. In addition, intralesional melanocytes in AK, which may be correlated with disease severity, can be specifically enhanced using HGM.
Salmonella Prevalence Alone Is Not a Good Indicator of Poultry Food Safety
Authors: Oscar Thomas
Published: July 2020

Salmonella is a leading cause of foodborne illness (i.e., salmonellosis) outbreaks, which on occasion are attributed to ground turkey. The poultry industry uses Salmonella prevalence as an indicator of food safety. However, Salmonella prevalence is only one of several factors that determine risk of salmonellosis. Consequently, a model for predicting risk of salmonellosis from individual lots of ground turkey as a function of Salmonella prevalence and other risk factors was developed. Data for Salmonella contamination (prevalence, number, and serotype) of ground turkey were collected at meal preparation. Scenario analysis was used to evaluate effects of model variables on risk of salmonellosis. Epidemiological data were used to simulate Salmonella serotype virulence in a dose‐response model that was based on human outbreak and feeding trial data. Salmonella prevalence was 26% (n = 100) per 25 g of ground turkey, whereas Salmonella number ranged from 0 to 1.603 with a median of 0.185 log per 25 g. Risk of salmonellosis (total arbitrary units (AU) per lot) was affected (p ≤ 0.05) by Salmonella prevalence, number, and virulence, by incidence and extent of undercooking, and by food consumption behavior and host resistance but was not (p > 0.05) affected by serving size, serving size distribution, or total bacterial load of ground turkey when all other risk factors were held constant. When other risk factors were not held constant, Salmonella prevalence was not correlated (r = −0.39; p = 0.21) with risk of salmonellosis. Thus, Salmonella prevalence alone was not a good indicator of poultry food safety because other factors were found to alter risk of salmonellosis. In conclusion, a more holistic approach to poultry food safety, such as the process risk model developed in the present study, is needed to better protect public health from foodborne pathogens like Salmonella.
“I Really Belong Here”: Civic Capacity‐Building among Returning Citizens
Authors: Cossyleon Jennifer E. , Flores Edward O.
Published: July 2020

This article focuses on unlikely movement actors whose civic engagement has been understudied: people with criminal records (“returning citizens”). We present findings from 18 months of ethnographic research with members (leaders) of Fighting to Overcome Records and Create Equality (FORCE), a civic group led by returning citizens. FORCE leaders received institutional support from Community Renewal Society (CRS), a larger faith and community‐based organization, to lead a rights reform movement in Chicago. Findings suggest that FORCE leaders constructed notions of kinship, recognition, and power through civic capacity‐building efforts—and that social belonging was core to such capacity‐building efforts. While bonding social belonging occurred as FORCE leaders formed kinship with people facing similar social and economic marginality, bridging social belonging emerged as leaders felt recognized by CRS staff organizers, affiliates, and elected officials. Bonding and bridging social belonging enabled FORCE leaders, who faced constant social exclusion in society, to experience much needed kinship, recognition, and power. Future studies should continue to uncover how local capacity‐building processes have life‐changing relational effects on movement participants from socially and economically marginalized groups.
Inference method for cultural diffusion patterns using a field model
Authors: Zhang Haiping , Zhou Xingxing , Tang Guoan , Ji Genlin , Zhang Xueying , Xiong Liyang
Published: July 2020

Cultural diffusion is one of the core concepts in the field of traditional cultural geography. Understanding the spatial diffusion patterns and coupling relationships of specific cultural phenomena is an effective means to explore the formation mechanism and development trend of culture. However, the quantitative analyses of cultural diffusion patterns from the perspective of classical cultural geography, particularly in the automatic detection of cultural regions and the identification of cultural diffusion types, and the internal diffusion structure of culture, are lacking. This study proposes a method called field model‐based cultural diffusion patterns (FM‐CDP). By using the point data of a cultural event, FM‐CDP can detect different levels of cultural regions, automatically identify their spatial diffusion types, and calculate the spatial diffusion relationship among cultural regions. The spatial diffusion pattern of the place names of Chinese villages was analyzed in this work to verify the effectiveness of FM‐CDP. Results showed that FM‐CDP can effectively identify existing cultural diffusion patterns from the point data of specific cultural features. This method can also be applied to the analysis of other cultural diffusion patterns that represent a certain cultural phenomenon in the form of point features.
Prolonged (post‐thaw) shelf life of −80°C frozen AB apheresis plasma
Authors: Rijnhout Tim W.H. , Noorman Femke , De Kort Bob , Zoodsma Margreet , Hoencamp Rigo
Published: July 2020

BACKGROUND

Early plasma transfusion is important in the treatment of patients with major hemorrhage. Prolonged shelf life of AB type frozen −80°C and cold‐stored (4°C) deep frozen plasma (DFP) will improve strategic stock management, minimize need for resupply, and make pre‐hospital implementation more feasible.

METHODS AND MATERIALS

Plasma products type AB of different age and origin (−30°C Fresh Frozen [(FFP], −80°C DFP [short (±1 year) and long (±7 year)] stored) were thawed (Day 0), stored at 4°C, and sampled on Days 7 and 14. Additionally, samples of plasma containing blood products (Octaplas LG®, whole blood and platelets) were compared for coagulation factor activity, phospholipid clotting time (PPL), and kaolin TEG during 4°C or 22°C storage.

RESULTS

Coagulation profiles of FFP, short‐ and long‐stored −80°C DFP were not significantly different after thaw. Cold storage did not affect fibrinogen, Protein C, and Antithrombin III activities whereas factor V, VII, VIII, and Protein S decreased in all blood products. After 14 days DFP still meets the guidelines for clinical use, except for Protein S (0.4 IU/mL). With exception of Octaplas LG®, phospholipid activity and TEG coagulation were similar between plasma containing blood components during storage.

CONCLUSION

AB DFP quality was unaffected by almost 7 years of frozen storage. Quality of thawed 14‐day stored AB DFP met, with exception of Protein S, all minimal guidelines which implies that its quality is sufficient for use in the (pre)‐hospital (military) environment for treatment of major hemorrhage.
Improved long‐term time‐series predictions of total blood use data from England
Authors: Nandi Anita K. , Roberts David J. , Nandi Asoke K.
Published: July 2020

Background

Red blood cells are essential for modern medicine but managing their collection and supply to cope with fluctuating demands represents a major challenge. As deterministic models based on predicted population changes have been problematic, there remains a need for more precise and reliable prediction of use. Here, we develop three new time‐series methods to predict red cell use 4 to 52 weeks ahead.

Study Design and Methods

From daily aggregates of red blood cell (RBC) units issued from 2005 to 2011 from the NHS Blood and Transplant, we generated a new set of non‐overlapping weekly data by summing the daily data over 7 days and derived the average blood use per week over 4‐week and 52‐week periods. We used three new methods for linear prediction of blood use by computing the coefficients using Minimum Mean Squared Error (MMSE) algorithm.

Results

We optimized the time‐window size, order of the prediction, and order of the polynomial fit for our data set. By exploiting the annual periodicity of the data, we achieved significant improvements in long‐term predictions, as well as modest improvements in short‐term predictions. The new methods predicted mean RBC use with a standard deviation of the percentage error of 2.5% for 4 weeks ahead and 3.4% for 52 weeks ahead.

Conclusion

This paradigm allows short‐ and long‐term prediction of RBC use and could provide reliable and precise prediction up to 52 weeks ahead to improve the efficiency of blood services and sufficiency of blood supply with reduced costs.
Pulsed Eddy Current Response to General Corrosion in Concrete Rebar
Authors: Eddy Ian , Underhill P. R. , Morelli J. , Krause T. W.
Published: July 2020

Corrosion of carbon steel rebar in concrete structures, such as highway bridges and buildings, has a direct impact on their structural integrity since the rebar provides the tensile strength within the structure. Rebar strength depends on the remaining effective radius of a given rod. Long-time decay up to 0.1 s, in the transient response of pulsed eddy current (PEC), was examined as a potential method to quantify general corrosion in ferromagnetic rebar. The transient response of a coaxial solenoidal drive–receive coil pair, oriented parallel to the rebar axis, was analyzed over a range of distances into the concrete (liftoff) and rebar radii. At long times, the single exponential decay constant was largely independent of liftoff. A power law relationship for the characteristic decay time, consistent with long-time diffusion of electromagnetic fields into a rod, was observed. The intercept of a best-fit line to measured voltage decay decreased exponentially with liftoff and maintained a measurable response up to 110 mm distance for a 25 mm (1 in.) diameter rebar. This exponential decay was present in 22 mm (7/8 in.), 19 mm (3/4 in.), and 15 mm (5/8 in.) samples as well. Reported results demonstrate the potential for PEC to quantify remaining cross-sectional area of rebar in concrete structures.
A Single-Loop Reliability-Based MDSDO Formulation for Combined Design and Control Optimization of Stochastic Dynamic Systems
Authors: Azad Saeed , Alexander-Ramos Michael J.
Published: July 2020

Optimization of dynamic engineering systems requires an integrated approach that accounts for the coupling between embodiment design and control system design, simultaneously. Generally known as combined design and control optimization (co-design), these methods offer superior system’s performance and reduced costs. Despite the widespread use of co-design approaches in the literature, not much work has been done to address the issue of uncertainty in co-design problem formulations. This is problematic as all engineering models contain some level of uncertainty that might negatively affect the system’s performance, if overlooked. While in our previous study we developed a robust co-design approach, a more rigorous evaluation of probabilistic constraints is required to obtain the targeted reliability levels for probabilistic constraints. Therefore, we propose and implement a novel stochastic co-design approach based on the principles of reliability-based design optimization (RBDO) to explicitly account for uncertainties from design decision variables and problem parameters. In particular, a reliability-based, multidisciplinary dynamic system design optimization (RB-MDSDO) formulation is developed using the sequential optimization and reliability assessment (SORA) algorithm, such that the analysis-type dynamic equality constraints are satisfied at the mean values of random variables, as well as their most probable points (MPPs). The proposed approach is then implemented for two case studies, and the results were benchmarked through Monte Carlo simulation (MCS) to indicate the impact of including reliability measures in co-design formulations.
Diffusion as a first model of spread of viral infection
Authors: Acioli Paulo H.
Published: July 2020

The appearance of the coronavirus (COVID-19) in late 2019 has dominated the news in the last few months as it developed into a pandemic. In many mathematics and physics classrooms, instructors are using the time series of the number of cases to show exponential growth of the infection. In this manuscript, we propose a simple diffusion process as the mode of spreading infections. This model is less sophisticated than other models in the literature, but it can capture the exponential growth and it can explain it in terms of mobility (diffusion constant), population density, and probability of transmission. Students can change the parameters and determine the growth rate and predict the total number of cases as a function of time. Students are also given the opportunity to add other factors that are not considered in the simple diffusion model.
New connections: Redox regulation of kinases
Authors: Ferrarelli Leslie K.
Published: July 2020

Several studies glean insight into how kinases are structurally regulated by reversible oxidation.
RNA Sequencing Identifies a Common Physiology in Vancomycin- and Ciprofloxacin-Tolerant Staphylococcus aureus Induced by
ileS
Mutations
Authors: Singh Madhuri , Matsuo Miki , Sasaki Takashi , Hishinuma Tomomi , Yamamoto Norio , Morimoto Yuh , Kirikae Teruo , Hiramatsu Keiichi
Published: July 2020

Little is known about the mechanisms by which
ileS
mutations induce vancomycin tolerance in
Staphylococcus aureus
. This study showed that transcriptome profiles were similar in vancomycin-tolerant mutants and the IleRS-inhibitor-treated parent. Notably,
ileS
and
relA
, which induce a stringent response, were upregulated. The same mechanism was responsible for cross-tolerance to vancomycin and ciprofloxacin. These findings suggest that the accumulation of uncharged isoleucyl-tRNA following
ileS
mutations in
S. aureus
was responsible for drug tolerance.
Evaluation of MALDI Biotyper Interpretation Criteria for Accurate Identification of Nontuberculous Mycobacteria
Authors: Rodriguez-Temporal David , Rodríguez-Sánchez Belén , Alcaide Fernando
Published: July 2020

Identification of mycobacteria by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) requires not only a good protein extraction protocol but also an adequate cutoff score in order to provide reliable results. The aim of this study was to assess the cutoff scores proposed by the MALDI-TOF MS system for mycobacterial identification. A total of 693 clinical isolates from a liquid medium and 760 from a solid medium were analyzed, encompassing 67 different species of nontuberculous mycobacteria (NTM).
Enterobacterales
Infection after Intestinal Dominance in Hospitalized Patients
Authors: Rao Krishna , Seekatz Anna , Bassis Christine , Sun Yuang , Mantlo Emily , Bachman Michael A.
Published: July 2020

Increasing antibiotic resistance has resulted in infections that are life-threatening and difficult to treat. Interventions that prevent these infections, particularly without using antibiotics, could save lives. Intestinal colonization by pathogens, including vancomycin-resistant
Enterococcus
and carbapenem-resistant
Enterobacteriaceae
(part of the order
Enterobacterales
) is associated with subsequent infection, and increased colonization density is associated with increased infection risk. Therefore, colonization offers a window of opportunity for infection prevention if (i) there are rapid and inexpensive assays to detect colonization, (ii) there are safe and effective interventions, and (iii) the risk of infection outweighs the risk of the treatment. Fecal transplants are proof of principle that manipulating the microbiome can reduce such colonization and prevent infections. This study demonstrates the feasibility of implementing rapid and inexpensive assays to quantify colonization and measures the strength of association between
Enterobacterales
dominance and subsequent infection. The approach described here could be a valuable tool in the prevention of antibiotic-resistant infections.
An Important Role for CD4
+
T Cells in Adaptive Immunity to Toxoplasma gondii in Mice Lacking the Transcription Factor Batf3
Authors: Tussiwand Roxane , Behnke Michael S. , Kretzer Nicole M. , Grajales-Reyes Gary E. , Murphy Theresa L. , Schreiber Robert D. , Murphy Kenneth M. , Sibley L. David
Published: July 2020

Toxoplasma gondii
is a widespread parasite of animals that causes zoonotic infections in humans. Although healthy individuals generally control the infection with only moderate symptoms, it causes serious illness in newborns and those with compromised immune systems such as HIV-infected AIDS patients. Because rodents are natural hosts for
T. gondii
, laboratory mice provide an excellent model for studying immune responses. Here, we used a combination of an attenuated mutant strain of the parasite that effectively vaccinates mice, with a defect in a transcriptional factor that impairs a critical subset of dendritic cells, to studying the immune response to infection. The findings reveal that in BALB/c mice, CD4 memory T cells play a dominant role in producing IFN-γ needed to control chronic infection. Hence, BALB/c mice may provide a more appropriate model for declining immunity seen in HIV-AIDS patients where loss of CD4 cells is associated with emergence of opportunistic infections.
A test of the efficacy of sand saltation for silt production: Implications for the interpretation of loess
Authors: Adams Steven M. , Soreghan Gerilyn S.
Published: July 2020

Production of the silt that forms loess is attributed to processes operating in both glacial systems (glacial grinding) and sandy deserts (saltation-induced fracturing). However, the efficacy of saltation for significant silt production is controversial. Understanding the potential for silt production in deserts is essential for determining the paleoclimatic significance of loess. To better assess the significance of eolian abrasion for silt production, experimental abrasion was conducted in a device designed to simulate sand saltation at sustained storm-wind velocities (∼25 m/s). The design differs from previous work in (1) maintaining strong measured velocities for long duration, (2) removing preexisting silt and utilizing control samples, (3) and scaling results to estimate potential for loess accumulation. Scaling experimental rates of production to geologic proportions indicates that eolian abrasion of sand produces insufficient silt to create geologically significant loess deposits.
Effect of basic public health service project on neonatal health services and neonatal mortality in China: a longitudinal time-series study
Authors: Zhao Pengyu , Han Xueyan , You Lili , Zhao Yu , Yang Li , Liu Yuanli
Published: July 2020

Objective

To analyse the trend change and level change of neonatal health services and neonatal mortality before and after the introduction of the Basic Public Health Service (BPHS) project in 2009.

Design and setting

A national longitudinal study on neonatal mortality from 1991 to 2017 and neonatal health services from 2000 to 2017 was conducted based on data extracted from the National Neonatal Mortality Surveillance System and National Health Statistic Yearbook. The segmented linear regression model was used to assess the level changes and trend changes of the outcome variables before and after the introduction of BPHS project. Pearson correlation analysis as conducted to measure association between neonatal mortality rates (NMRs) and maternal health management rates (MMRs), neonatal visit rates, respectively.

Primary and secondary outcome measures

The outcome variables were national NMR, the gap of NMR between urban and rural areas, maternal health management rate and neonatal visit rate.

Results

The annual trend change coefficient of national NMR and the gap of NMR between urban and rural areas were −0.57 (p<0.01) and −0.49 (p<0.01) after the introduction of BPHS project, while the annual trend coefficient of the MMR and the neonatal visit rate were 1.21 (p<0.01) and 0.85 (p<0.01), respectively. The negative correlations were found between NMR and MMR (r=−0.79, p<0.01) and neonatal visit rate (r=−0.76, p<0.01).

Conclusion

The BPHS project was found to be associated with increased volume of neonatal health services and reduced NMR. The design and implementation of this project may provide references to other low-income and middle-income countries.
Validation of the diagnostic performance of ‘HeartMedi V.1.0’, a novel CT-derived fractional flow reserve measurement, for patients with coronary artery disease: a study protocol
Authors: Kim Soo-Hyun , Kang Si-Hyuck , Chung Woo-Young , Yoon Chang-Hwan , Park Sang-Don , Nam Chang-Wook , Kwon Ki-Hwan , Doh Joon-Hyung , Byun Young-Sup , Bae Jang-Whan , Youn Tae-Jin , Chae In-Ho
Published: July 2020

Introduction

Coronary CT angiography (CCTA) is widely used for non-invasive coronary artery evaluation, but it is limited in identifying the nature of functional characteristics that cause ischaemia. Recent computational fluid dynamic (CFD) techniques applied to CCTA images permit non-invasive computation of fractional flow reserve (FFR), a measure of lesion-specific ischaemia. However, this technology has limitations, such as long computational time and the need for expensive equipment, which hinder widespread use.

Methods and analysis

This study is a prospective, multicentre, comparative and confirmatory trial designed to evaluate the diagnostic performance of HeartMedi V.1.0, a novel CT-derived FFR measurement for the detection of haemodynamically significant coronary artery stenoses identified by CCTA, based on invasive FFR as a reference standard. The invasive FFR values ≤0.80 will be considered haemodynamically significant. The study will enrol 184 patients who underwent CCTA, invasive coronary angiography and invasive FFR. Computational FFR (c-FFR) will be analysed by CFD techniques using a lumped parameter model based on vessel length method. Blinded core laboratory interpretation will be performed for CCTA, invasive coronary angiography, invasive FFR and c-FFR. The primary objective of the study is to compare the area under the receiver–operator characteristic curve between c-FFR and CCTA to non-invasively detect the presence of haemodynamically significant coronary stenosis. The secondary endpoints include diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value and correlation of c-FFR with invasive FFR.

Ethics and dissemination

The study has ethic approval from the ethics committee of Seoul National University Bundang Hospital (E-1709/420-001) and informed consent will be obtained for all enrolled patients. The result will be published in a peer-reviewed journal.

Trial registration number

KCT0002725; Pre-results.
How psychiatrists coordinate treatment for COVID-19: a retrospective study and experience from China
Authors: Yue Ling , Wang Jingyi , Ju Mingliang , Zhu Yi , Chen Lianghu , Shi Lin , Shi Bohai , Chen Jun , Shen Yifeng
Published: July 2020

Background

Patients with COVID-19 are at high risk of developing mental health problems; however, the prevalence and management of mental disorders and how psychiatrists coordinate the treatment are unclear.

Aims

We aimed to investigate the mental health problems of patients infected with COVID-19 and to identify the role of psychiatrists in the clinical treatment team during the pandemic. We also share the experience of psychiatric consultations of patients with COVID-19 in Shanghai, China.

Methods

We analysed data from the psychiatric medical records of 329 patients with COVID-19 in the Shanghai Public Health Clinical Center from 20 January to 8 March 2020. We collected information including sociodemographic characteristics, whether patients received psychiatric consultation, mental health symptoms, psychiatric diagnoses, psychiatric treatments and severity level of COVID-19.

Results

Psychiatric consultations were received by 84 (25.5%) patients with COVID-19. The most common symptoms of mental health problems were sleep disorders (75%), anxiety (58.3%) and depressive symptoms (11.9%). The psychiatric consultation rate was highest in critically ill patients (69.2%), with affective symptoms or disturbed behaviour as their main mental health problems. Psychiatric diagnoses for patients who received consultation included acute stress reaction (39.3%), sleep disorders (33.3%), anxiety (15.5%), depression (7.1%) and delirium (4.8%). In terms of psychiatric treatments, 86.9% of patients who received psychiatric consultation were treated with psychotropic medications, including non-benzodiazepine sedative-hypnotic agents (54.8%), antidepressants (26.2%), benzodiazepines (22.6%) and antipsychotics (10.7%). Among the 76 patients who were discharged from the hospital, 79% had recovered from mental health problems and were not prescribed any psychotropic medications. The symptoms of the remaining 21% of patients had improved and they were prescribed medications to continue the treatment.

Conclusions

This is the first study to report psychiatric consultations for patients with COVID-19. Our study indicated that a considerable proportion of patients with COVID-19, especially critically ill cases, experienced mental health problems. Given the remarkable effect of psychiatric treatments, we recommend that psychiatrists be timely and actively involved in the treatment of COVID-19.
Dendritic cell vaccination and CD40-agonist combination therapy licenses T cell-dependent antitumor immunity in a pancreatic carcinoma murine model
Authors: Lau Sai Ping , van Montfoort Nadine , Kinderman Priscilla , Lukkes Melanie , Klaase Larissa , van Nimwegen Menno , van Gulijk Mandy , Dumas Jasper , Mustafa Dana A M , Lievense Sanne L A , Groeneveldt Christianne , Stadhouders Ralph , Li Yunlei , Stubbs Andrew , Marijt Koen A , Vroman Heleen , van der Burg Sjoerd H , Aerts Joachim , van Hall Thorbald , Dammeijer Floris , van Eijck Casper H J
Published: July 2020

Background

Pancreatic ductal adenocarcinoma (PDAC) is notoriously resistant to treatment including checkpoint-blockade immunotherapy. We hypothesized that a bimodal treatment approach consisting of dendritic cell (DC) vaccination to prime tumor-specific T cells, and a strategy to reprogram the desmoplastic tumor microenvironment (TME) would be needed to break tolerance to these pancreatic cancers. As a proof-of-concept, we investigated the efficacy of combined DC vaccination with CD40-agonistic antibodies in a poorly immunogenic murine model of PDAC. Based on the rationale that mesothelioma and pancreatic cancer share a number of tumor associated antigens, the DCs were loaded with either pancreatic or mesothelioma tumor lysates.

Methods

Immune-competent mice with subcutaneously or orthotopically growing KrasG12D/+;Trp53R172H/+;Pdx-1-Cre (KPC) PDAC tumors were vaccinated with syngeneic bone marrow-derived DCs loaded with either pancreatic cancer (KPC) or mesothelioma (AE17) lysate and consequently treated with FGK45 (CD40 agonist). Tumor progression was monitored and immune responses in TME and lymphoid organs were analyzed using multicolor flow cytometry and NanoString analyzes.

Results

Mesothelioma-lysate loaded DCs generated cross-reactive tumor-antigen-specific T-cell responses to pancreatic cancer and induced delayed tumor outgrowth when provided as prophylactic vaccine. In established disease, combination with stimulating CD40 antibody was necessary to improve survival, while anti-CD40 alone was ineffective. Extensive analysis of the TME showed that anti-CD40 monotherapy did improve CD8 +T cell infiltration, but these essential effector cells displayed hallmarks of exhaustion, including PD-1, TIM-3 and NKG2A. Combination therapy induced a strong change in tumor transcriptome and mitigated the expression of inhibitory markers on CD8 +T cells.

Conclusion

These results demonstrate the potency of DC therapy in combination with CD40-stimulation for the treatment of pancreatic cancer and provide directions for near future clinical trials.