bluuebunny/crossref_metadata_2025 huggingface dataset:
A Review of Robust Operations Management under Model Uncertainty
Authors: Lu Mengshi , Shen Zuo‐Jun Max
Published: July 2020

Over the past two decades, there has been explosive growth in the application of robust optimization in operations management (robust OM), fueled by both significant advances in optimization theory and a volatile business environment that has led to rising concerns about model uncertainty. We review some common modeling frameworks in robust OM, including the representation of uncertainty and the decision‐making criteria, and sources of model uncertainty that have arisen in the literature, such as demand, supply, and preference. We discuss the successes of robust OM in addressing model uncertainty, enriching decision criteria, generating structural results, and facilitating computation. We also discuss several future research opportunities and challenges.
T cell receptor therapy against melanoma—Immunotherapy for the future?
Authors: Winge‐Main Anna K. , Wälchli Sébastien , Inderberg Else Marit
Published: July 2020

Malignant melanoma has seen monumental changes in treatment options the last decade from the very poor results of dacarbazine treatment to the modern‐day use of targeted therapies and immune checkpoint inhibitors. Melanoma has a high mutational burden making it more capable of evoking immune responses than many other tumours. Even when considering double immune checkpoint blockade with anti‐CTLA‐4 and anti‐PD‐1, we still have far to go in melanoma treatment as 50% of patients with metastatic disease do not respond to current treatment. Alternative immunotherapy should therefore be considered. Since melanoma has a high mutational burden, it is considered more immunogenic than many other tumours. T cell receptor (TCR) therapy could be a possible way forward, either alone or in combination, to improve the response rates of this deadly disease. Melanoma is one of the cancers where TCR therapy has been frequently applied. However, the number of antigens targeted remains fairly limited, although advanced personalized therapies aim at also targeting private mutations. In this review, we look at possible aspects of targeting TCR therapy towards melanoma and provide an implication of its use in the future.
Detection of community‐acquired respiratory viruses in allogeneic stem‐cell transplant recipients and controls—A prospective cohort study
Authors: Rachow Tobias , Lamik Toni , Kalkreuth Jana , Kurze Stephanie , Wagner Kathleen , Stier Pia , Hammersen Friedrich J. , Rüthrich Maria Madeleine , Winkelmann Nils , Klink Anne , Hilgendorf Inken , Hermann Beate , Lang Susanne , Hochhaus Andreas , von Lilienfeld‐Toal Marie
Published: July 2020

Background

Community‐acquired respiratory viruses (CARV) cause upper and lower respiratory tract infections (URTI/LRTI) and may be life‐threatening for recipients of an allogeneic stem cell transplantation (allo‐SCT).

Methods

In a prospective study encompassing 4 winter‐seasons, we collected throat gargles (TG) at random time points from allo‐SCT recipients (patients) and controls and followed them up for at least 3 weeks including repetitive sampling and documentation of symptoms. A Multiplex‐PCR system to identify 20 CARV and Mycoplasma pneumoniae was used to detect CARV.

Results

One hundred ninety‐four patients with 426 TG and 273 controls with 549 TG were included. There were more patients with a positive test result (25% vs 11% in the controls), and the patients had a higher number of positive TG (70 = 16%) compared to controls (32 = 6%) (P < .001). Altogether, 115 viruses were detected. Multiple viruses in one TG (11/48, 34%) and prolonged shedding were only observed in patients (13/48, 27%). Patients had more RSV (18/83, 26%) and adenovirus (15/83, 21%) than controls (both viruses 2/32, 6%). Independent risk factors for the detection of CARV included age >40 years (OR 3.38, 95% CI 1.8‐6.4, P < .001) and presence of URTI‐symptoms (OR 3.22, 95% CI 1.9‐5.5, P < .001). No controls developed a LRTI or died whereas 4/48 (8%) patients developed a LRTI (coronavirus in 2, RSV in 1 and influenza A H1N1 in 1 patient). One patient died of CARV (influenza A H1N1).

Conclusion

Allo‐SCT‐recipients have more CARV‐infections, exhibit a different epidemiology, have more cases of co‐infection or prolonged shedding and have a higher rate of LRTI and mortality.
A novel mutation in PDE6B in Spanish Water Dogs with early‐onset progressive retinal atrophy
Authors: Winkler Paige A. , Ramsey Harrison D. , Petersen‐Jones Simon M.
Published: July 2020

Objective

To identify the underlying mutation in a recently identified early‐onset progressive retinal atrophy (PRA) in the Spanish Water Dog (SWD) breed.

Animal Studied

Eighteen SWDs were used in this study. Six SWDs diagnosed with PRA and 12 phenotypically normal SWDs.

Procedures

An exclusion analysis using an established microsatellite panel to screen PRA candidate genes was combined with whole genome sequencing of two affected SWD siblings and two phenotypically normal SWDs (a sibling and the dam).

Results

A 6‐bp deletion was identified in exon 19 of PDE6B removing two highly conserved amino acids from the enzymatic domain of the PDE6B protein (c.2218‐2223del; p.Phe740_Phe741del). This segregated with the disease status in the small study pedigree.

Conclusions

Identification of this novel PDE6B mutation adds to the already described PDE6B mutations responsible for PRA in the Irish Setter, Sloughi, and American Staffordshire Terrier dog breeds. A DNA‐based test was designed to allow breeders to genotype their animals and make informed breeding decisions in the effort to eradicate PRA from the SWD breed.
Acute reductions in haematocrit increase flow‐mediated dilatation independent of resting nitric oxide bioavailability in humans
Authors: Hoiland Ryan L. , Tremblay Joshua C. , Stacey Benjamin S. , Coombs Geoff B. , Nowak‐Flück Daniela , Tymko Michael M. , Patrician Alexander , Stembridge Mike , Howe Connor A. , Bailey Damian M. , Green Daniel J. , MacLeod David B. , Ainslie Philip N.
Published: July 2020

Key points

Changes in haematocrit influence nitric oxide signalling through alterations in shear stress stimuli and haemoglobin scavenging of nitric oxide; these two regulatory factors have not been assessed simultaneously

Isovolumic haemodilution led to a marked increase in brachial artery flow‐mediated dilatation in humans

The increase in flow‐mediated dilatation occurred in the face of an unaltered shear stress stimulus for vasodilatation and reduced resting steady‐state nitric oxide levels in the blood

Collectively, our data point towards haemoglobin scavenging of nitric oxide as a key regulatory factor of brachial flow‐mediated dilatation and highlight the importance of the simultaneous consideration of nitric oxide production and inactivation when investigating vascular function in humans

Haemoglobin (Hb) may impact the transduction of endothelium‐dependent and nitric oxide (NO)‐mediated vasodilator activity, given its contribution to shear stress stimuli and diverse biochemical reactions with NO. We hypothesized that an acute reduction in [Hb] and haematocrit (Hct) would increase brachial artery flow‐mediated dilatation (FMD). In 11 healthy males (28 ± 7 years; 23 ± 2 kg m−2), FMD (Duplex ultrasound), arterial blood gases, Hct and [Hb], blood viscosity, and NO metabolites (ozone‐based chemiluminescence) were measured before and after isovolumic haemodilution, where ∼20% of whole blood was removed and replaced with 5% human serum albumin. Haemodilution reduced Hct by 18 ± 2% (P < 0.001) and whole blood viscosity by 22 ± 5% (P < 0.001). Plasma nitrite (P = 0.01), S‐nitrosothiols (P = 0.03) and total red blood cell NO (P = 0.001) were collectively reduced by ∼15–40%. Brachial artery FMD increased by ∼160% from 3.8 ± 2.1 to 9.7 ± 4.5% (P = 0.004). Statistical covariation for the shear stress stimulus did not alter FMD, indicating that the increase in FMD was not directly related to alterations in whole blood viscosity and the shear stimulus. Collectively, these findings indicate that haemoglobin scavenging of NO appears to be an important factor in the regulation of FMD under normal conditions through constraint of endothelium‐dependent NO‐mediated vasodilatation in healthy humans.
Photoheterotrophic Assimilation of Valerate and Associated Polyhydroxyalkanoate Production by
Rhodospirillum rubrum
Authors: Bayon-Vicente Guillaume , Zarbo Sarah , Deutschbauer Adam , Wattiez Ruddy , Leroy Baptiste
Published: July 2020

The use and the littering of plastics represent major issues that humanity has to face. Polyhydroxyalkanoates (PHAs) are good candidates for the replacement of oil-based plastics, as they exhibit comparable physicochemical properties but are biobased and biodegradable. However, the current industrial production of PHAs is curbed by the production costs, which are mainly linked to the carbon source. Volatile fatty acids issued from the fermentation processes constitute interesting carbon sources, since they are inexpensive and readily available. Among them, valerate is gaining interest regarding the ability of many bacteria to produce a copolymer of PHAs. Here, we describe the photoheterotrophic assimilation of valerate by
Rhodospirillum rubrum
, a purple nonsulfur bacterium mainly known for its metabolic versatility. Using a knowledge-based optimization process, we present a new strategy for the improvement of PHA production, paving the way for the use of
R. rubrum
in industrial processes.
Free Fatty Acids Interfere with the DNA Binding Activity of the Virulence Regulator PrfA of Listeria monocytogenes
Authors: dos Santos Patrícia T. , Thomasen Rikke S. S. , Green Mathias S. , Færgeman Nils J. , Kallipolitis Birgitte H.
Published: July 2020

Listeria monocytogenes
is a Gram-positive pathogen able to cause foodborne infections in humans and animals. Key virulence genes in
L. monocytogenes
are activated by the transcription regulator PrfA, a DNA binding protein belonging to the CRP/FNR family. Various signals from the environment are known to affect the activity of PrfA, either positively or negatively. Recently, we found that specific medium- and long-chain free fatty acids act as antimicrobial agents as well as signaling compounds in
L. monocytogenes
. Here, we show that both antimicrobial and nonantimicrobial free fatty acids inhibit PrfA-dependent activation of virulence gene transcription by interfering with the DNA binding activity of PrfA. Our findings suggest that free fatty acids could be candidates for alternative therapies against
L. monocytogenes
.
Broad and Differential Animal Angiotensin-Converting Enzyme 2 Receptor Usage by SARS-CoV-2
Authors: Zhao Xuesen , Chen Danying , Szabla Robert , Zheng Mei , Li Guoli , Du Pengcheng , Zheng Shuangli , Li Xinglin , Song Chuan , Li Rui , Guo Ju-Tao , Junop Murray , Zeng Hui , Lin Hanxin
Published: July 2020

SARS-CoV-2 uses human ACE2 as a primary receptor for host cell entry. Viral entry mediated by the interaction of ACE2 with spike protein largely determines host range and is the major constraint to interspecies transmission. We examined the receptor activity of 14 ACE2 orthologs and found that wild-type and mutant SARS-CoV-2 lacking the furin cleavage site in S protein could utilize ACE2 from a broad range of animal species to enter host cells. These results have important implications in the natural hosts, interspecies transmission, animal models, and molecular basis of receptor binding for SARS-CoV-2.
Supplemental Material: Metamorphic evolution of Proterozoic ultramafic rocks from the Oaxacan Complex (Oaxaca State, southern Mexico): Tectonic implications
Authors: Culí Laura , al. et
Published: July 2020

Composition of rocks organized by samples
‘Barrier dysfunction in Atopic newBorns studY’ (BABY): protocol of a Danish prospective birth cohort study
Authors: Gerner Trine , Halling Anne-Sofie , Rasmussen Rinnov Maria , Haarup Ravn Nina , Hjorslev Knudgaard Mette , Menné Bonefeld Charlotte , Ewertsen Caroline , Trautner Simon , Jakaša Ivone , Kezic Sanja , Skov Lone , Thyssen Jacob P
Published: July 2020

Introduction

Skin barrier development and dysfunction in premature and mature newborns is important for the risk of atopic dermatitis (AD).

Methods and analysis

The Barrier dysfunction in Atopic newBorns studY (BABY) Cohort is a prospective birth cohort study of 150 preterm children (gestational age (GA) below 37+0) and 300 term children (GA 37+0 to 41+6). Skin barrier is assessed through transepidermal water loss, tape stripping, Raman-spectroscopy and microbiome sampling. Clinical examinations are done and DNA from buccal swabs is collected for genetic analyses. Thymus size is assessed by ultrasound examination. Information on pregnancy, delivery, parental exposures and diseases are collected, and structured telephone interviews are conducted at 18 and 24 months to assess exogenous exposures in the child and onset of AD. Hanifin and Rajka criteria as well as The UK Working Party's Diagnostic Criteria for Atopic Dermatitis are used to diagnose AD. Severity of AD is assessed using the Eczema Area and Severity Index (EASI) and Patient Oriented Eczema Measure (POEM).

Ethics and dissemination

The study is approved by the scientific Ethical Committee of the Capital Region (H-16042289 and H-16042294).

Outcomes will be presented at national and international conferences and in peer-reviewed publications.
Balloon versus Amplatz for tract dilation in fluoroscopically guided percutaneous nephrolithotomy: a systematic review and meta-analysis
Authors: Peng Pan-xin , Lai Shi-cong , Seery Samuel , He Yu-hui , Zhao Hang , Wang Xu-ming , Zhang Guan
Published: July 2020

Objective

To compare the safety and efficacy of balloon and Amplatz for tract dilation in fluoroscopically guided percutaneous nephrolithotomy (PCNL).

Method

EMBASE, PUBMED, MEDLINE and the Cochrane Central Register of Controlled Trials were searched for pertinent studies up until 30 October 2019. Pooled effects were calculated as ORs with 95% CIs or mean differences (MD) with 95% CIs. Endpoints included postoperative decrease in haemoglobin, transfusion rate, complication rate, successful dilation rate, stone-free rate, fluoroscopy time, access time, total operation time and length of postoperative hospitalisation (LPH). Bonferroni’s correction was intercalated to reduce the likelihood of making a meta-analytical false positive.

Results

One randomised controlled trial and five controlled clinical trials were included, which involved 1317 patients in total. We found a lower drop in postoperative haemoglobin for patients receiving balloon dilation compared with those in the Amplatz group (MD=−0.21, 95% CI −0.33 to 0.09, p=0.0005; Bonferroni correction a=0.005). Access time in the balloon group was also, on average, 2.61 min shorter than the Amplatz group (MD=−2.61, 95% CI −4.20 to 1.01, p=0.001; Bonferroni correction a=0.005). No significant differences were identified between the two dilation methods in terms of transfusion rate, complication rate, successful dilation rate, stone-free rate, fluoroscopy time, total operation time and LPH.

Conclusion

Balloon dilation is a safe and effective tract dilation technique for access creation during fluoroscopically guided PCNL. Both of methods have similar success rates although balloon dilation is associated with significantly less postoperative haemoglobin decline and shorter access time. Therefore, balloon dilation appears to be the superior tract dilation technique, but further confirmatory research is required to confirm these findings.
Catalonia Suicide Risk Code Epidemiology (CSRC-Epi) study: protocol for a population-representative nested case–control study of suicide attempts in Catalonia, Spain
Authors: Mortier Philippe , Vilagut Gemma , Puértolas Gracia Beatriz , De Inés Trujillo Ana , Alayo Bueno Itxaso , Ballester Coma Laura , Blasco Cubedo María Jesús , Cardoner Narcís , Colls Cristina , Elices Matilde , Garcia-Altes Anna , Gené Badia Manel , Gómez Sánchez Javier , Martín Sánchez Mario , Morros Rosa , Prat Pubill Bibiana , Qin Ping , Mehlum Lars , Kessler Ronald C , Palao Diego , Pérez Sola Víctor , Alonso Jordi
Published: July 2020

Introduction

Suicide attempts represent an important public health burden. Centralised electronic health record (EHR) systems have high potential to provide suicide attempt surveillance, to inform public health action aimed at reducing risk for suicide attempt in the population, and to provide data-driven clinical decision support for suicide risk assessment across healthcare settings. To exploit this potential, we designed the Catalonia Suicide Risk Code Epidemiology (CSRC-Epi) study. Using centralised EHR data from the entire public healthcare system of Catalonia, Spain, the CSRC-Epi study aims to estimate reliable suicide attempt incidence rates, identify suicide attempt risk factors and develop validated suicide attempt risk prediction tools.

Methods and analysis

The CSRC-Epi study is registry-based study, specifically, a two-stage exposure-enriched nested case–control study of suicide attempts during the period 2014–2019 in Catalonia, Spain. The primary study outcome consists of first and repeat attempts during the observation period. Cases will come from a case register linked to a suicide attempt surveillance programme, which offers in-depth psychiatric evaluations to all Catalan residents who present to clinical care with any suspected risk for suicide. Predictor variables will come from centralised EHR systems representing all relevant healthcare settings. The study’s sampling frame will be constructed using population-representative administrative lists of Catalan residents. Inverse probability weights will restore representativeness of the original population. Analysis will include the calculation of age-standardised and sex-standardised suicide attempt incidence rates. Logistic regression will identify suicide attempt risk factors on the individual level (ie, relative risk) and the population level (ie, population attributable risk proportions). Machine learning techniques will be used to develop suicide attempt risk prediction tools.

Ethics and dissemination

This protocol is approved by the Parc de Salut Mar Clinical Research Ethics Committee (2017/7431/I). Dissemination will include peer-reviewed scientific publications, scientific reports for hospital and government authorities, and updated clinical guidelines.

Trial registration number

NCT04235127.
Relationship between high-density lipoprotein cholesterol levels and endothelial function in women: a cross-sectional study
Authors: Takaeko Yuji , Matsui Shogo , Kajikawa Masato , Maruhashi Tatsuya , Yamaji Takayuki , Harada Takahiro , Han Yiming , Hashimoto Haruki , Kihara Yasuki , Hida Eisuke , Chayama Kazuaki , Goto Chikara , Aibara Yoshiki , Yusoff Farina Mohamad , Kishimoto Shinji , Nakashima Ayumu , Higashi Yukihito
Published: July 2020

Objectives

The purpose of this study was to evaluate the relationship between high-density lipoprotein cholesterol (HDL-C) levels and endothelial function in women.

Design

Cross-sectional study.

Setting

22 university hospitals and affiliated clinics in Japan.

Participants

1719 Japanese women aged 17–90 years who were not receiving lipid-lowering therapy.

Measures

We evaluated flow-mediated vasodilation (FMD) and serum levels of HDL-C. All participants were divided into four groups by HDL-C level: low HDL-C (<40 mg/dL), moderate HDL-C (40–59 mg/dL), high HDL-C (60–79 md/dL) and extremely high HDL-C (≥80 mg/dL).

Results

Univariate regression analysis revealed a significant relationship between FMD and HDL-C (r=0.12, p<0.001). FMD values were significantly smaller in the low HDL-C group (5.2%±3.8%) and moderate HDL-C group (5.2%±3.8%) than in the extremely high HDL-C group (6.7%±3.4%) (p=0.024 and p=0.003, respectively), while there was no significant difference in FMD between the high HDL-C group and the extremely high HDL-C group. Multiple logistic regression analysis did not show a significant association between HDL-C levels and FMD.

Conclusions

Endothelial function increased in relation to HDL-C levels. However, there was no association of HDL-C levels with endothelial function after adjustment of traditional cardiovascular risk factors in women.

Trial registration number

UMIN000012950; Results.
Injection Molded Autoclavable, Scalable, Conformable (iMASC) system for aerosol-based protection: a prospective single-arm feasibility study
Authors: Byrne James D , Wentworth Adam J , Chai Peter R , Huang Hen-Wei , Babaee Sahab , Li Canchen , Becker Sarah L , Tov Caitlynn , Min Seokkee , Traverso Giovanni
Published: July 2020

Objective

To develop and test a new reusable, sterilisable N95 filtering facepiece respirator (FFR)-comparable face mask, known as the Injection Molded Autoclavable, Scalable, Conformable (iMASC) system, given the dire need for personal protective equipment within healthcare settings during the COVID-19 pandemic.

Design

Single-arm feasibility study.

Setting

Emergency department and outpatient oncology clinic.

Participants

Healthcare workers who have previously undergone N95 fit testing.

Interventions

Fit testing of new iMASC system.

Primary and secondary outcome measures

Primary outcome is success of fit testing using an Occupational Safety and Health Administration (OSHA)-approved testing method, and secondary outcomes are user experience with fit, breathability and filter replacement.

Results

Twenty-four subjects were recruited to undergo fit testing, and the average age of subjects was 41 years (range of 21–65 years) with an average body mass index of 26.5 kg/m2. The breakdown of participants by profession was 46% nurses (n=11), 21% attending physicians (n=5), 21% resident physicians (n=5) and 12% technicians (n=3). Of these participants, four did not perform the fit testing due to the inability to detect saccharin solution on premask placement sensitivity test, lack of time and inability to place mask over hair. All participants (n=20) who performed the fit test were successfully fitted for the iMASC system using an OSHA-approved testing method. User experience with the iMASC system, as evaluated using a Likert scale with a score of 1 indicating excellent and a score of 5 indicating very poor, demonstrated an average fit score of 1.75, breathability of 1.6, and ease of replacing the filter on the mask was scored on average as 2.05.

Conclusions

The iMASC system was shown to successfully fit multiple different face sizes and shapes using an OSHA-approved testing method. These data support further certification testing needed for use in the healthcare setting.
Patient-reported outcome measures in presbyopia: a literature review
Authors: Sharma Garima , Chiva-Razavi Sima , Viriato Daniel , Naujoks Christel , Patalano Francesco , Bentley Sarah , Findley Amy , Johnson Chloe , Arbuckle Rob , Wolffsohn James
Published: July 2020

Presbyopia is the age-related loss of near-distance focusing ability. The aim of this study was to identify patient-reported outcome measures (PROMs) used in clinical trials and quality-of-life studies conducted in individuals with presbyopia and to assess their suitability for use in individuals with phakic presbyopia. Literature searches were performed in Medline and Embase up until October 2017. Specific search terms were used to identify presbyopia studies that included a PROM. All clinical trials with PROM-supported endpoints in presbyopia were identified on ClinicalTrials.gov. Further searches were conducted to retrieve articles documenting the development and psychometric evaluation of the PROMs identified. A total of 703 records were identified; 120 were selected for full-text review. Twenty-one clinical trials employed PROMs to support a primary or secondary endpoint. In total, 13 PROMs were identified; a further 23 publications pertaining to the development and validation of these measures were retrieved. Most PROMs were developed prior to release of the Food and Drug Administration (FDA) 2009 patient-reported outcome guidance and did not satisfy regulatory standards. The Near Activity Visual Questionnaire (NAVQ) was identified as the most appropriate for assessing near-vision functioning in presbyopia. While the NAVQ was developed in line with the FDA guidance, the items do not reflect changes in technology that have occurred since the questionnaire was developed in 2008 (eg, the increase in smartphone use), and the measure was not validated in a purely phakic presbyopia sample. Further research is ongoing to refine the NAVQ to support trial endpoints related to changes in near-vision functioning associated with phakic presbyopia.
Identifying and encouraging high-quality healthcare: an analysis of the content and aims of patient letters of compliment
Authors: Gillespie Alex , Reader Tom W
Published: July 2020

Background

Although healthcare institutions receive many unsolicited compliment letters, these are not systematically conceptualised or analysed. We conceptualise compliment letters as simultaneously identifying and encouraging high-quality healthcare. We sought to identify the practices being complimented and the aims of writing these letters, and we test whether the aims vary when addressing front-line staff compared with senior management.

Methods

A national sample of 1267 compliment letters was obtained from 54 English hospitals. Manual classification examined the practices reported as praiseworthy, the aims being pursued and who the letter was addressed to.

Results

The practices being complimented were in the relationship (77% of letters), clinical (50%) and management (30%) domains. Across these domains, 39% of compliments focused on voluntary non-routine extra-role behaviours (eg, extra-emotional support, staying late to run an extra test). The aims of expressing gratitude were to acknowledge (80%), reward (44%) and promote (59%) the desired behaviour. Front-line staff tended to receive compliments acknowledging behaviour, while senior management received compliments asking them to reward individual staff and promoting the importance of relationship behaviours.

Conclusions

Compliment letters reveal that patients value extra-role behaviour in clinical, management and especially relationship domains. However, compliment letters do more than merely identify desirable healthcare practices. By acknowledging, rewarding and promoting these practices, compliment letters can potentially contribute to healthcare services through promoting desirable behaviours and giving staff social recognition.
Current challenges for assessing the long-term clinical benefit of cancer immunotherapy: a multi-stakeholder perspective
Authors: Quinn Casey , Garrison Louis P , Pownell Anja K , Atkins Michael B , de Pouvourville Gérard , Harrington Kevin , Ascierto Paolo Antonio , McEwan Phil , Wagner Samuel , Borrill John , Wu Elise
Published: July 2020

Immuno-oncologics (IOs) differ from chemotherapies as they prime the patient’s immune system to attack the tumor, rather than directly destroying cancer cells. The IO mechanism of action leads to durable responses and prolonged survival in some patients. However, providing robust evidence of the long-term benefits of IOs at health technology assessment (HTA) submission presents several challenges for manufacturers. The aim of this article was to identify, analyze, categorize, and further explore the key challenges that regulators, HTA agencies, and payers commonly encounter when assessing the long-term benefits of IO therapies. Insights were obtained from an international, multi-stakeholder steering committee (SC) and expert panels comprising of payers, economists, and clinicians. The selected individuals were tasked with developing a summary of challenges specific to IOs in demonstrating their long-term benefits at HTA submission. The SC and expert panels agreed that standard methods used to assess the long-term benefit of anticancer drugs may have limitations for IO therapies. Three key areas of challenges were identified: (1) lack of a disease model that fully captures the mechanism of action and subsequent patient responses; (2) estimation of longer-term outcomes, including a lack of agreement on ideal methods of survival analyses and extrapolation of survival curves; and (3) data limitations at the time of HTA submission, for which surrogate survival end points and real-world evidence could prove useful. A summary of the key challenges facing manufacturers when submitting evidence at HTA submission was developed, along with further recommendations for manufacturers in what evidence to produce. Despite almost a decade of use, there remain significant challenges around how best to demonstrate the long-term benefit of checkpoint inhibitor-based IOs to HTA agencies, clinicians, and payers. Manufacturers can potentially meet or mitigate these challenges with a focus on strengthening survival analysis methodology. Approaches to doing this include identifying reliable biomarkers, intermediate and surrogate end points, and the use of real-world data to inform and validate long-term survival projections. Wider education across all stakeholders—manufacturers, payers, and clinicians—in considering the long-term survival benefit with IOs is also important.
The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of multiple myeloma
Authors: Shah Nina , Aiello Jack , Avigan David E , Berdeja Jesus G , Borrello Ivan M , Chari Ajai , Cohen Adam D , Ganapathi Karthik , Gray Lissa , Green Damian , Krishnan Amrita , Lin Yi , Manasanch Elisabet , Munshi Nikhil C , Nooka Ajay K , Rapoport Aaron P , Smith Eric L , Vij Ravi , Dhodapkar Madhav
Published: July 2020

Outcomes in multiple myeloma (MM) have improved dramatically in the last two decades with the advent of novel therapies including immunomodulatory agents (IMiDs), proteasome inhibitors and monoclonal antibodies. In recent years, immunotherapy for the treatment of MM has advanced rapidly, with the approval of new targeted agents and monoclonal antibodies directed against myeloma cell-surface antigens, as well as maturing data from late stage trials of chimeric antigen receptor (CAR) T cells. Therapies that engage the immune system to treat myeloma offer significant clinical benefits with durable responses and manageable toxicity profiles, however, the appropriate use of these immunotherapy agents can present unique challenges for practicing physicians. Therefore, the Society for Immunotherapy of Cancer convened an expert panel, which met to consider the current role of approved and emerging immunotherapy agents in MM and provide guidance to the oncology community by developing consensus recommendations. As immunotherapy evolves as a therapeutic option for the treatment of MM, these guidelines will be updated.
Are healthcare workers obligated to risk themselves during the COVID-19 pandemic according to Jewish law? A response to Solnicaet al
Authors: Gold Azgad
Published: July 2020

Solnicaet alargue that “Jewish law and modern secular approaches based on professional responsibilities obligate physicians to care for all patients even those with communicable diseases”. The authors base their viewpoint on the opinion of Rabbi Eliezer Waldenberg and apply it to suggest that physicians are obligated to endanger themselves during epidemics, such as COVID-19. It is argued that Solnicaet al’s analysis of Rabbi Waldenberg’s text and their conclusion that healthcare workers are obligated to endanger themselves while treating patient who suffer from contagious illness during epidemics according to Jewish law suffer from various shortcomings. Indeed, Jewish law looks favourably on healthcare workers who take a reasonable risk in treating their patients in the context of epidemics. However, it is considered a voluntary supererogatory act—not obligatory. Solnicaet almay express a legitimate ethical viewpoint. However, it does not seem to represent the mainstream approach of what Jewish law would demand as obligatory from its practitioners.
Study of external factors to minimize segregation of granular particles
Authors: Panda Saleema , Tan Danielle S
Published: July 2020

Segregation of granular particles affects the quality of end products in the pharmaceutical, chemical and food processing industries. Many researchers have worked on controlling the mechanical properties of granular particles to minimize segregation. In this paper, we studied different chute-related factors — inclination angle, friction, fill, channel geometry and base profile — and their effects on segregation. We conducted a small-scale experiment with chute inclined at different angles, and also numerical simulations performed using an open-source discrete element method (DEM) code — LIGGGHTS. We found the optimal condition for minimum segregation of a binary granular mixture. We concluded that segregation is minimized if the stream-wise velocity is low, for example, by keeping the chute at a low inclination [Formula: see text] and increasing the wall roughness to 0.14.
A pedestrian introduction to coherent and squeezed states
Authors: Bagchi Bijan , Ghosh Rupamanjari , Khare Avinash
Published: July 2020

This review is intended for readers who want to have a quick understanding on the theoretical underpinnings of coherent states and squeezed states which are conventionally generated from the prototype harmonic oscillator but not always restricting to it. Noting that the treatments of building up such states have a long history, we collected the important ingredients and reproduced them from a fresh perspective but refrained from delving into detailed derivation of each topic. By no means we claim a comprehensive presentation of the subject but have only tried to recapture some of the essential results and pointed out their interconnectivity.
HOW DO PARTIALLY HIDING BEHAVIOR AND COMPLETELY HIDING BEHAVIOR IMPACT INTERACTING POPULATIONS?
Authors: MA ZHIHUI , WANG SHUFAN , TANG HAOPENG
Published: July 2020

As the two main behaviors of prey populations in ecological systems, the partially hiding behavior (PHB) and the completely hiding behavior (CHB) play a significant role in determining the dynamics of predator–prey models. This work examines to the dynamical consequences of predator–prey systems with the PHB and the CHB. Previous research has independently studied the two behaviors, and the general conclusions are that the two behaviors can have positive and/or negative impacts on the considered population models. However, to our knowledge, no study has combined and compared the two behaviors in studying the dynamical consequences of predation interactions. Motivated by this, we investigated the dynamical consequences induced by the PHB and the CHB. From a mathematical point of view, the dynamical behaviors are studied and the corresponding sufficient conditions are given. Our findings are general and some published models are special cases of ours. From an ecological point of view, we find that the size of the ecological regions is mainly determined by the two behaviors, and which one is ecologically beneficial for the health coexistence of the interacting populations are primarily determined by the functional response and the attack coefficient of predators. Moreover, we conclude that the evolutionary and optimal choices of prey behavior (PHB or CHB) depend on the predators attack coefficient (large or small attack coefficient) and the resource level (abundant or pool resource level).
MODELING ZIKA TRANSMISSION DYNAMICS: PREVENTION AND CONTROL
Authors: ROY PARIMITA , UPADHYAY RANJIT KUMAR , CAUR JASMINE
Published: July 2020

The Zika virus (ZIKV) epidemic is depicted to have high spatial diversity and slow growth, attributable to the dynamics of the mosquito vector and mobility of the human populations. In an effort to understand the transmission dynamics of Zika virus, we formulate a new compartmental epidemic model with a system of seven differential equations and 11 parameters incorporating the decaying transmission rate and study the impact of protection measure on basic public health. We do not fit the model to the observed pattern of spread, rather we use parameter values estimated in the past and examine the extent to which the designed model prediction agrees with the pattern of spread seen in Brazil, via reaction–diffusion modeling. Our work includes estimation of key epidemiological parameters such as basic reproduction number ([Formula: see text], and gives a rough estimate of how many individuals can be typically infected during an outbreak if it occurs in India. We used partial rank correlation coefficient method for global sensitivity analysis to identify the most influential model parameters. Using optimal control theory and Pontryagin’s maximum principle, a control model has been proposed and conditions for the optimal control are determined for the deterministic model of Zika virus. The control functions for the strategies (i) vector-to-human contact reduction and (ii) vector elimination are introduced into the system. Numerical simulations are also performed. This work aimed at understanding the potential extent and timing of the ZIKV epidemic can be used as a template for the analysis of future mosquito-borne epidemics.
SPECTRALITY AND NON-SPECTRALITY OF PLANAR SELF-SIMILAR MEASURES WITH FOUR-ELEMENT DIGIT SETS
Authors: CHEN SI , TANG MIN-WEI
Published: July 2020

Let [Formula: see text] be the unit matrix and [Formula: see text]. In this paper, we consider the self-similar measure [Formula: see text] on [Formula: see text] generated by the iterated function system [Formula: see text] where [Formula: see text]. We prove that there exists [Formula: see text] such that [Formula: see text] is an orthonormal basis for [Formula: see text] if and only if [Formula: see text] for some integer [Formula: see text].
Critical groups and multiple solutions for Kirchhoff type equations with critical exponents
Authors: Sun Mingzheng , Su Jiabao , Zhang Binlin
Published: July 2020

In this paper, by Morse theory we will study the Kirchhoff type equation with an additional critical nonlinear term, and the main results are to compute the critical groups including the cases where zero is a mountain pass solution and the nonlinearity is resonant at zero. As an application, the multiplicity of nontrivial solutions for this equation with the parameter across the first eigenvalue is investigated under appropriate assumptions. To our best knowledge, estimates of our critical groups are new even for the Kirchhoff type equations with subcritical nonlinearities.
Experimental and Numerical Investigation of the Refined Zigzag Theory for Accurate Buckling Analysis of Highly Heterogeneous Sandwich Beams
Authors: Ascione Alessia , Orifici Adrian C. , Gherlone Marco
Published: July 2020

The Refined Zigzag Theory (RZT) is a structural theory developed for the analysis of composite multilayer and sandwich beams. However, the accuracy of RZT for buckling analysis of sandwich beams has not been experimentally investigated, and for RZT and Timoshenko Beam Theory (TBT) the effect of the degree of heterogeneity on their accuracy requires further study. The aim of this work was to validate the use of the RZT for predicting the critical buckling loads of sandwich beams, even with highly heterogeneous material properties, and to assess the use of the TBT for the same application. Buckling experiments were conducted on five foam-core sandwich beams, which varied in geometry and included highly heterogeneous configurations. For each beam, two finite element (FE) models were analyzed using RZT- and TBT-beam FEs. The comparison between the numerical and the experimental results highlighted a major capability of RZT to correctly predict the critical buckling load for all the beams considered. The dependence of the TBT results on the beam characteristics was further investigated through a parametric analysis, which showed the dominant effect to be a close to linear relationship between the TBT error and the beam face-to-core thickness ratio. The work demonstrated the outstanding accuracy of the RZT predictions, including the superior capabilities with respect to TBT, and has application for rapid and accurate analysis of industrial structures.
In-Plane Vibration of a Deployable Segmented Ring
Authors: Wang C. Y.
Published: July 2020

The in-plane vibrations of regular polygonal rings composed of rigid segments joined by torsional springs are studied for the first time. The nonlinear dynamical difference equations are formulated and solved by perturbation about the equilibrium state. As the number of segments increase, the frequencies, if aptly normalized, converge to the classical vibration frequencies of a continuous elastic ring. The vibration mode shapes are illustrated. The tiling of many identical polygons is discussed. Possible applications include the vibrations of space structures and graphene sheets.
Constructing an Efficient Machine Learning Model for Tornado Prediction
Authors: Aleskerov Fuad , Demin Sergey , Richman Michael B. , Shvydun Sergey , Trafalis Theodore B. , Yakuba Vyacheslav
Published: July 2020

Tornado prediction variables are analyzed using machine learning and decision analysis techniques. A model based on several choice procedures and the superposition principle is applied for different methods of data analysis. The constructed model has been tested on a database of tornadic events. It is shown that the tornado prediction model developed herein is more efficient than a previous set of machine learning models, opening the way to more accurate decisions.
An Invasive Weed Optimization-Based Fuzzy Decision-making Framework for Bridge Intervention Prioritization in Element and Network Levels
Authors: Abdelkader Eslam Mohammed , Marzouk Mohamed , Zayed Tarek
Published: July 2020

Recently, the number of deteriorating bridges has drastically increased. Furthermore, tight maintenance budgets are cut down, imposing escalating adverse implications on the safety of bridges. This state of affairs entails the development of decision support systems for the effective management of bridges within the allocated budget. As such, this study introduces an invasive weed optimization-based fuzzy decision-making framework designated for bridge intervention prioritization in both element and network levels. The proposed decision-making platform encompasses three main tiers. The first tier is an optimized fuzzy analytical network process model that aims at computing the weighting vector of the bridge defects, namely corrosion, delamination, cracking, spalling and scaling. In this model, a genetic algorithm optimization model is formulated to improve the consistencies of judgment matrices through circumventing the imprecisions encountered by the classical judgment assignment. The second tier encompasses establishing an integrated bridge deck condition assessment model capitalizing on ground-penetrating radar and inspection reports. In it, the severities of the bridge defects are demonstrated in the form of fuzzy membership functions to address the inherent uncertainties of inspection. Subsequently, a variable-length invasive weed optimization model is structured to automatically calibrate the fuzzy membership functions. The third model is designed for structuring a bridge maintenance decision-making strategy stepping on the integrated condition index. The capabilities of the proposed framework were validated through several levels of comparisons. For instance, it significantly outperformed some of the current condition assessment models. Additionally, it inferred that the thresholds separating the four categories of the integrated bridge deck condition index are 75.651, 67.769 and 60.318.
Localized Lagrange Multipliers Mixed (u,p) Formulation Applied in Wind Turbine Analysis
Authors: Cardoso Onézimo Carlos Viana , da Silva Francisco Ilson
Published: July 2020

Fluid–structure analysis is frequently used to design offshore structures in a large range of engineering applications. In order to install wind turbines from the seashore, it is required that its towers must be attached at the sea floor or a system needs to be developed that allows the turbine to float. Therefore, the objective of this work is to develop a coupled structural finite element analysis using localized Lagrange multipliers (LLM) at idealized monopile wind turbines. This method enables us to model large structures like wind turbine towers submerged in the ocean and determine the influence of the fluid–structure interaction on the dynamic structural response of these equipments. In this work, the mixed formulation [Formula: see text] developed takes into account the condition of irrotationality of the acoustic fluid. The classical LLM method is modified, thus, a new mixed-formulation for the interface frame has fluid pressure and solid displacement as degree of freedom. In other words, a coupling frame is introduced as fictitious porous material with the aim of non-symmetrical coupling between elastic solid and potential fluid. The solution to the non-matching meshes domain problem is also achieved with this methodology by several numerical strategies. The equations of solid and fluid domains are obtained by classical finite element method and their interaction is modeled with Localized Lagrange Multipliers. The solutions of numerical equations are obtained by direct form in a monolithic approach. The new modeling by using a porous material interface frame algorithm is verified through examples.
Einstein–Maxwell tetrad grand unification
Authors: Garat Alcides
Published: July 2020

In this short note, we will prove in a few steps that the new tetrads introduced previously in Einstein–Maxwell four-dimensional Lorentzian spacetimes, where gravitational and non-null electromagnetic fields are present, contain both the necessary information to provide the gravitational field and the necessary information to provide the electromagnetic field as well. These new tools thus become grand unification objects.
KNOWLEDGE-ORIENTED LEADERSHIP AND OPEN INNOVATION: THE MEDIATING ROLE OF KNOWLEDGE PROCESS AND INFRASTRUCTURE CAPABILITY
Authors: SHEHZAD MUHAMMAD USMAN , DAVIS KATE , SHAKIL AHMAD MUHAMMAD
Published: July 2020

Purpose: The study aims to examine the causal relationships among knowledge-oriented leadership (KOL), open innovation (OI), knowledge infrastructure capability (KIC) and knowledge process capability (KPC). This study also explored the mediating role of knowledge infrastructure capability (KIC) and knowledge process capability (KPC) in the relationship between knowledge-oriented leadership and open innovation.

Design/methodology/approach: The study collected primary data via a standardized questionnaire comprising a sample of 305 pharmaceutical and health sector employees in Pakistan. Hypotheses were tested through structural equation modeling.

Findings: The results display the significant causal relationships among the variables and knowledge infrastructure and process capability and these significantly mediate the relationship between knowledge-oriented leadership and two-dimensional open innovation. Furthermore, this study found an insignificant effect of KOL on inbound open innovation.

Limitation: The findings of the paper are based on the data collected from the Pakistan pharmaceutical and health sector. In future, to accommodate the issue of generalizability, the framework can be used for samples from other countries.

Practical Implication: This study provides evidence that leadership is one of the most crucial sources that can aid in organizational effectiveness when dealing with knowledge by developing infrastructure and improving processes to enhance innovative outcomes.