bluuebunny/crossref_metadata_2025 huggingface dataset:
A high molecular weight hyaluronic acid biphasic dispersion as potential therapeutics for interstitial cystitis
Authors: Rooney Peadar R. , Kannala Vijaya Krishna , Kotla Niranjan G. , Benito Ana , Dupin Damien , Loinaz Iraida , Quinlan Leo R. , Rochev Yury , Pandit Abhay
Published: October 2020

Interstitial cystitis (IC) is a progressive bladder disease characterized by increased urothelial permeability, inflammation of the bladder with abdominal pain. While there is no consensus on the etiology of the disease, it was believed that restoring the barrier between urinary solutes and (GAG) urothelium would interrupt the progression of this disease. Currently, several treatment options include intravesical delivery of hyaluronic acid (HA) and/or chondroitin sulfate solutions, through a catheter to restore the urothelial barrier, but have shown limited success in preclinical, clinical trials. Herein we report for the first time successful engineering and characterization of biphasic system developed by combining cross‐linked hyaluronic acid and naïve HA solution to decrease inflammation and permeability in an in vitro model of interstitial cystitis. The cross‐linking of HA was performed by 4‐arm‐polyethyeleneamine chemistry. The HA formulations were tested for their viscoelastic properties and the effects on cell metabolism, inflammatory markers, and permeability. Our study demonstrates the therapeutic effects of different ratios of the biphasic system and reports their ability to increase the barrier effect by decreasing the permeability and alteration of cell metabolism with respect to relative controls. Restoring the barrier by using biphasic system of HA therapy may be a promising approach to IC.
Cationic contrast‐enhanced computed tomography distinguishes between reparative, degenerative, and healthy equine articular cartilage
Authors: Nelson Brad B. , Mäkelä Janne T. A. , Lawson Taylor B. , Patwa Amit N. , Snyder Brian D. , McIlwraith C. Wayne , Grinstaff Mark W. , Goodrich Laurie R. , Kawcak Chris E.
Published: October 2020

Cationic contrast‐enhanced computed tomography (CECT) is a quantitative imaging technique that characterizes articular cartilage, though its efficacy in differentiating repair tissue from other disease states is undetermined. We hypothesized that cationic CECT attenuation will distinguish between reparative, degenerative, and healthy equine articular cartilage and will reflect biochemical, mechanical, and histologic properties. Chondral defects were created in vivo on equine femoropatellar joint surfaces. Within defects, calcified cartilage was retained (Repair 1) or removed (Repair 2). At sacrifice, plugs were collected from within defects, and at locations bordering (adjacent site) and remote to defects along with site‐matched controls. Articular cartilage was analyzed via CECT using CA4+ to assess glycosaminoglycan (GAG) content, compressive modulus (E
eq), and International Cartilage Repair Society (ICRS) II histologic score. Comparisons of variables were made between sites using mixed model analysis and between variables with correlations. Cationic CECT attenuation was significantly lower in Repair 1 (1478 ± 333 Hounsfield units [HUs]), Repair 2 (1229 ± 191 HUs), and adjacent (2139 ± 336 HUs) sites when compared with site‐matched controls (2587 ± 298, 2505 ± 184, and 2563 ± 538 HUs, respectively; all p < .0001). Cationic CECT attenuation was significantly higher at remote sites (2928 ± 420 HUs) compared with Repair 1, Repair 2, and adjacent sites (all p < .0001). Cationic CECT attenuation correlated with ICRS II score (r = .79), GAG (r = .76), and E
eq (r = .71; all p < .0001). Cationic CECT distinguishes between reparative, degenerative, and healthy articular cartilage and highly correlates with biochemical, mechanical, and histological tissue properties.
Glycerol chlorination reaction mechanism
Authors: Nogueira Diogo , Oliveira Ricardo R. , Rocha Alexandre B.
Published: October 2020

A new reaction mechanism for the glycerol chlorination is proposed. This mechanism is based on theoretical calculations within density functional theory combined with polarizable continuum model . Two possibilities were investigated, the first is the SN2 chlorination forming mono‐ and dichlorinated products and the second one is through an ester intermediate formed by glycerol esterification in the presence of acetic acid as catalyst. Our results indicate that the first chlorination reaction can occur in the absence of the catalyst and the main product is 3‐monochloropropane‐1,2‐diol (1‐MCP). The inhibitory role of water in the second chlorination is also revealed, that is, water formation suppresses the second chlorination when reaction is conducted in the absence of a carboxylic acid. In the presence of the catalyst, oxonium species are formed as reaction intermediates and the main products are 1‐MCP and 1,3‐dichloropropan‐2‐ol (1,3‐DCP). Our results are in agreement with the experimental data, which indicate that the 1,3‐DCP is the main product when an acid catalyst is employed and, also, there is no significant formation of 2‐monochloropropane‐1,2‐diol and 1,2‐dichloropropan‐3‐ol .
High‐resolution distribution pattern of surface water nitrous oxide along a cruise track from the Okhotsk Sea to the western Arctic Ocean
Authors: Zhan Liyang , Zhang Jiexia , Ouyang Zhangxian , Lei Ruibo , Xu Suqing , Qi Di , Gao Zhongyong , Sun Heng , Li Yuhong , Wu Man , Liu Jian , Chen Liqi
Published: October 2020

Nitrous oxide in the surface water was measured using an automatic underway system, along with measurements of surface water pCO2, dissolved oxygen, salinity, temperature, and sea ice coverage, along a cruise track through the Bering Sea and Chukchi Sea to the Canadian Basin during the 7th Chinese National Arctic Research Expedition. The results show that, overall, the regions along the cruise track are net sources of N2O to the atmosphere. Several N2O oversaturation maxima were observed along the cruise track, with an absolute maximum of approximately 60%. According to the hydrographic setting and the distribution patterns of pCO2, dissolved oxygen, and sea ice coverage in the study area, it was concluded that the N2O oversaturation maxima may result from hydrographic processes, such as mixing of different water masses, upwelling or convection, and possible production beneath the sea ice. Additionally, the lowest value of approximately 90% may result from dilution related to the melting of sea ice. An evaluation of the air–sea flux along the cruise track shows that the continental shelf and upwelling region are N2O sources, whereas the study area in the open Arctic Ocean does not show obvious source or sink characteristics.
Long‐term changes in trophic ecology of blue mussels in a rapidly changing ecosystem
Authors: Liénart Camilla , Garbaras Andrius , Qvarfordt Susanne , Sysoev Anton Öberg , Höglander Helena , Walve Jakob , Schagerström Ellen , Eklöf Johan , Karlson Agnes ML
Published: October 2020

Ocean climate change strongly affects organisms and ecosystems, and the causes, consequences, and underlying mechanisms need to be documented. In the Baltic Sea, a marginal sea under severe eutrophication stress, a longer productive season, and changes in the phytoplankton community over the last few decades have likely impacted diet and condition of keystone species, from individual to population level. This study uses stable isotopes (δ13C, δ15N, and derived isotope niche metrics) to trace energy and nutrient flows in archived samples of blue mussel (Mytilus edulis trossulus) spanning 24 yr (1993–2016). We test if long‐term changes in isotope and elemental composition in mussels, as well as population abundance and biomass, can be explained by changes in abiotic and biotic variables, using partial least square regressions and structural equation modeling. We found decreasing trends in δ13C and δ15N as well as in mean size and total biomass of mussels, but no unidirectional changes in their stoichiometry or condition index. Changes in isotope composition were best explained by nitrogen‐fixing cyanobacteria, by increased terrestrial organic carbon from land runoff (reflecting precipitation) and by decreases in dissolved inorganic nitrogen (indicative of successful eutrophication mitigation) and in biomass of a mixotrophic ciliate species. The trophic niche (assessed from isotope niche) was included as the best predictor for both mussel body condition and the observed decline in their total biomass. This study reveals that altered trophic relationships from climate‐induced changes in the productivity base may strongly impact keystone species, with potential knock‐on effects on ecosystem functions.
Correlates of Psychological Distress in Patients with Parkinson's Disease During the COVID‐19 Outbreak
Authors: De Micco Rosa , Siciliano Mattia , Sant'Elia Valeria , Giordano Alfonso , Russo Antonio , Tedeschi Gioacchino , Tessitore Alessandro
Published: October 2020

Background

Following the severe consequences of the COVID‐19 outbreak, on March 9, 2020, the Italian government implemented extraordinary measures to limit viral transmission, including restrictive quarantine measures. This resulted in a rapid and profound change of people's daily lives.

Objective

We assessed the psychological impact of the 40‐day quarantine in a large cohort of patients with Parkinson's disease (PD) and caregivers. Moreover, we analyzed whether prelockdown clinical features may be associated with subjective response of patients with PD to this traumatic event.

Methods

A total of 94 patients with PD were enrolled in the study. The Impact of Event Scale‐Revised, the Kessler Psychological Distress Scale, and the 12‐item Zarit Burden Inventory were obtained from patients and caregivers by email. A multivariate regression analysis was performed to determine whether prelockdown clinical motor and nonmotor features were associated with the psychological impact of lockdown.

Results

Regression analyses showed that prelockdown levels of anxiety, treatment‐related motor complications, patients' quality of life, and lockdown hours per day were significantly associated with psychological impact measures of the 40‐day quarantine. In addition, we showed that caregiver burden was correlated with overall patient autonomy and attention/memory impairment.

Conclusions

We identified specific PD motor and nonmotor features potentially predisposing to higher psychological impact of stressful situations, such as quarantine. This may help guide postpandemic interventions and preventive strategies to avoid further impairment of psychological well‐being in patients with PD.
Structure and therapeutic uses of butyrylcholinesterase: Application in detoxification, Alzheimer's disease, and fat metabolism
Authors: Xing Shuaishuai , Li Qi , Xiong Baichen , Chen Yao , Feng Feng , Liu Wenyuan , Sun Haopeng
Published: October 2020

Structural information of butyrylcholinesterase (BChE) and its variants associated with several diseases are discussed here. Pure human BChE has been proved safe and effective in treating organophosphorus (OPs) poisoning and has completed Phase 1 and 2 pharmacokinetic (PK) and safety studies. The introduction of specific mutations into native BChE to endow it a self‐reactivating property has gained much progress in producing effective OPs hydrolases. The hydrolysis ability of native BChE on cocaine has been confirmed but was blocked to clinical application due to poor PK properties. Several BChE mutants with elevated cocaine hydrolysis activity were published, some of which have shown safety and efficiency in treating cocaine addiction of human. The increased level of BChE in progressed Alzheimer's disease patients made it a promising target to elevate acetylcholine level and attenuate cognitive status. A variety of selective BChE inhibitors with high inhibitory activity published in recent years are reviewed here. BChE could influence the weight and insulin secretion and resistance of BChE knockout (KO) mice through hydrolyzing ghrelin. The BChE‐ghrelin pathway could also regulate aggressive behaviors of BChE‐KO mice.
One stage microvascular mandible reconstruction by using scapula chimeric flap combined with computer‐aided‐design and computer‐aided‐manufacturing plate including bilateral alloplastic TMJ prosthesis: A case report
Authors: Chauvel‐Picard Julie , Kreutzer Kilian , Heiland Max , Kreusch Thomas , Ebker Tobias , Beck‐Broichsitter Benedicta
Published: October 2020

This report focuses a defect comprising the complete mandible due to osteonecrosis, including both condyles, that required bilateral temporomandibular joint (TMJ) reconstruction with complete mandibular corpus using a computer‐aided‐design and computer‐aided‐manufacturing(CAD‐CAM) planning to harvest a scapula chimeric free flap combined with plate including bilateral alloplastic TMJ prosthesis. This procedure was realized in one and the same surgery. A 73 year‐old‐man developed an osteoradionecrosis of the total mandible including both condyles after radiation therapy for a squamous cell carcinoma of the tongue base(cT4aN2bM0G3). A CAD‐CAM reconstruction was planned with a plate extended by bilateral individual TMJ prosthesis, individual fossa components and combined with a composite free flap originating from the subscapular vessel system including scapula(circumflex subscapular artery) for reconstruction of the mandibular corpus which was osteotomized in three segments with a resection guide, the parascapular skin paddle (descending branch of circumflex subscapular artery) for compensation of the soft tissue deficiency of the cervical skin and latissimus dorsi muscle(thoracodorsal artery) for the inner mucosal lining and intraoral reconstruction. The subscapular artery was anastomosed to the external carotid artery and two concomitant veins were sutured end‐to‐side to the internal jugular vein. The patient was discharged without feeding tube and tracheostomy. No complications have been observed after 6 months follow‐up. The patient was able to tolerate soft diet and had comprehensible speech. Thus, a total mandibular reconstruction including both condyles using alloplastic and autoplastic reconstruction in one and the same stage is a valid option and may be considered in comparably severe cases.
Operations strategies with snobbish and strategic consumers
Authors: Lee Chang Hwan , Choi Tsan‐Ming , Edwin Cheng T. C.
Published: October 2020

Studying the optimal production and pricing strategies of a luxury brand manufacturer (in this paper, the “manufacturer” is in fact also the “retailer”), we consider the following situation. First, consumers exhibit a prestige‐seeking (snobbish) behavior that values product exclusivity. Their utility decreases as more consumers possess the product. Second, consumers show a forward‐looking (strategic) behavior. They make shop visit decisions based on predicted product availability. Third, the manufacturer's production policy is unobservable to consumers. Given these basic premises, we consider a traditional newsvendor inventory system and analytically derive the equilibrium production and pricing strategies within the rational expectation framework. We then propose two improvement strategies, each using a well‐established channel policy, to steer the game participants to reach a better equilibrium than the one for the traditional system. First, under the limited edition strategy with consumer returns, the firm uses the consumer return policy as a proxy for the limited edition strategy that aims to increase product exclusivity. Second, under the product line extension strategy, the firm applies product line extension as a means to guide the game participants to simultaneously increase product availability and product exclusivity. Finally, we extend the study by incorporating a variety of modeling variations and examine robustness of the research findings.
A fast implicit difference scheme for solving the generalized time–space fractional diffusion equations with variable coefficients
Authors: Gu Xian‐Ming , Huang Ting‐Zhu , Zhao Yong‐Liang , Lyu Pin , Carpentieri Bruno
Published: October 2020

In this article, we first propose an unconditionally stable implicit difference scheme for solving generalized time–space fractional diffusion equations (GTSFDEs) with variable coefficients. The numerical scheme utilizes theL1‐type formula for the generalized Caputo fractional derivative in time discretization and the second‐order weighted and shifted Grünwald difference (WSGD) formula in spatial discretization, respectively. Theoretical results and numerical tests are conducted to verify the(2 − γ)‐order and 2‐order of temporal and spatial convergence withγ ∈ (0, 1)the order of Caputo fractional derivative, respectively. The fast sum‐of‐exponential approximation of the generalized Caputo fractional derivative and Toeplitz‐like coefficient matrices are also developed to accelerate the proposed implicit difference scheme. Numerical experiments show the effectiveness of the proposed numerical scheme and its good potential for large‐scale simulation of GTSFDEs.
The final outcome of charitable bequest gift intentions: Findings and implications for legacy fundraising
Authors: Wishart Roewen , James Russell N.
Published: October 2020

Charitable bequest gifts are important to charities but evaluating legacy fundraising activities is problematic. These activities may not generate bequest income until many years later. Thus, many charities focus on generating reports of current plans or intentions for bequest gifts. Such approaches depend on the link between these reports and ultimate bequest transfers. However, this link is not well documented. This study presents the first multi‐organisational results linking ultimate estate distributions with lifetime legacy giving plans or intentions reported to charities. Ten Australian charities provided data from those dying in 2014–2017. Among 700 decedents who had confirmed the presence of a planned bequest gift to the charity, 35% generated no estate gift. This lost gift rate varied from 17 to 60% across different organisations. The average loss rate was 24% when the charity had at least one communication with the decedent within 2 years of death, and 48% otherwise. Among 264 people reporting to the charity that they were “intending” or “considering” an estate gift but not confirming it, 89% left no gift at death. Among 507 people only requesting information about making a bequest gift, 95% left no gift at death. These results suggest the importance of moving donors to the point of planned gift confirmation and then maintaining relationships until the end of life. However, marketing remains challenging given that 58% of the 2,682 total bequest gifts received by these organisations came from decedents who were not donors during life.
Fracture behavior and mechanical, thermal, and rheological properties of biodegradable films extruded by flat die and calender
Authors: Gigante Vito , Aliotta Laura , Coltelli Maria Beatrice , Cinelli Patrizia , Botta Luigi , La Mantia Francesco Paolo , Lazzeri Andrea
Published: October 2020

The development of biodegradable materials for tailored applications, particularly in the field of polymeric films and sheets, is a challenging technological goal as well as a contribution to help protect the environment. Poly(lactic) acid (PLA) is a promising substitute for several oil‐based polymers; however, to overcome its thermal and mechanical drawbacks, researchers have developed solutions such as blending PLA with polybutylene adipate terephthalate (PBAT), which is capable of increasing the ductility of the final material. In this study, PLA/PBAT binary blends, with minimum possible content of nonrenewable materials, were examined from processing, thermal, morphological, and rheological perspective. An optimized PLA/PBAT ratio was chosen as the polymeric basis to obtain a biodegradable formulation by adding a biobased plasticizer and appropriate fillers to produce a micrometer film with tailored flexibility and tear resistance. The processing technology involved flat‐die extrusion, followed by calendering. The tearing resistance of the produced film was investigated, and the results were compared with literature data. A study on the essential work of fracture was implemented to explore the mode III out‐of‐plane fracture resistance starting from a trouser tear test.
Interventional therapy via flexible bronchoscopy in the management of foreign body‐related occlusive endobronchial granulation tissue formation in children
Authors: Li Shuxian , Wu Lei , Zhou Junfen , Wang Yingshuo , Jin Fang , Chen Xiaoyang , Liu Jinling , Chen Zhimin
Published: October 2020

Background

Occlusive granulation tissue formation, as one of the most common sequelae of chronic foreign body aspiration, can cause tracheobronchial obstruction and delayed fixed airway stenosis necessitating interventions. The aim of this study was to explore the clinical efficacy and safety of interventional therapy via flexible bronchoscopy for treatment of granulation tissue related airway obstruction secondary to foreign body aspiration in children.

Method

Patients with long‐term foreign body related granulation tissue were treated with flexible bronchoscopy therapeutic modalities, including forceps, cryotherapy, holmium laser, and balloon dilatation. Clinical efficacy was evaluated by clinical symptoms and endoscopic manifestations.

Results

A total of eight patients with granulation tissue hyperplasia caused by foreign body in bronchus, with a median age of 29.5 (range, 18–54) months, underwent interventional therapy between January 2016 and December 2019. Four patients received forceps and CO2 cryotherapy and one patient required forceps only. The remaining three patients received holmium laser combined with CO2 cryotherapy, and one of them required additional balloon dilatation. Four cases required a second cryotherapy procedure, and one case received three cryotherapy procedures for extensive granulation tissue. The treatment efficacy was 100% without complications.

Conclusion

Interventional procedure via flexible bronchoscopy is a safe, reliable, and effective method in the management of tracheobronchial obstruction and stenosis caused by foreign body‐related granulation tissue hyperplasia. It is worthy of clinical application.
Reaction mechanism of tetrathionate hydrolysis based on the crystal structure of tetrathionate hydrolase from Acidithiobacillus ferrooxidans
Authors: Kanao Tadayoshi , Hase Naruki , Nakayama Hisayuki , Yoshida Kyoya , Nishiura Kazumi , Kosaka Megumi , Kamimura Kazuo , Hirano Yu , Tamada Taro
Published: October 2020

Tetrathionate hydrolase (4THase) plays an important role in dissimilatory sulfur oxidation in the acidophilic iron‐ and sulfur‐oxidizing bacterium Acidithiobacillus ferrooxidans. The structure of recombinant 4THase from A. ferrooxidans (Af‐Tth) was determined by X‐ray crystallography to a resolution of 1.95 Å. Af‐Tth is a homodimer, and its monomer structure exhibits an eight‐bladed β‐propeller motif. Two insertion loops participate in dimerization, and one loop forms a cavity with the β‐propeller region. We observed unexplained electron densities in this cavity of the substrate‐soaked structure. The anomalous difference map generated using diffraction data collected at a wavelength of 1.9 Å indicated the presence of polymerized sulfur atoms. Asp325, a highly conserved residue among 4THases, was located near the polymerized sulfur atoms. 4THase activity was completely abolished in the site‐specific Af‐Tth D325N variant, suggesting that Asp325 plays a crucial role in the first step of tetrathionate hydrolysis. Considering that the Af‐Tth reaction occurs only under acidic pH, Asp325 acts as an acid for the tetrathionate hydrolysis reaction. The polymerized sulfur atoms in the active site cavity may represent the intermediate product in the subsequent step.
Quantum Fluctuations and New Instantons I: Linear Unbounded Potential
Authors: Mukhanov V. F. , Rabinovici E. , Sorin A. S.
Published: October 2020

We consider the decay of a false vacuum in circumstances where the methods suggested by Coleman run into difficulties. We find that in these cases quantum fluctuations play a crucial role. Namely, they naturally induce both ultraviolet and infrared cutoff scales, determined by the parameters of the classical solution, beyond which this solution cannot be trusted anymore. This leads to the appearance of a broad class of new O(4) invariant instantons, which would have been singular in the absence of an ultraviolet cutoff. We apply our results to a case where the potential is unbounded from below in a linear way and in particular show how the problem of small instantons is resolved by taking into account the inevitable quantum fluctuations.
Organizing pneumonia associated with T‐cell lymphoma
Authors: Chan Chrystal , Fagarasanu Andrei D. , Reid Andre , Sadowski Daniel C. , Gillson Ashley‐Mae E.
Published: October 2020

A 61‐year‐old male with a history of coeliac disease was diagnosed with organizing pneumonia (OP) on transbronchial and transthoracic lung biopsies. He then developed refractory coeliac disease type II and haemophagocytic lymphohistiocytosis. Nine months after his initial diagnosis of OP and after multiple biopsies of the lung, duodenum, and bone marrow, he was diagnosed with enteropathy‐associated T‐cell lymphoma (EATL). Although OP in patients with lymphoma is most commonly attributed to chemotherapeutic agents or bone marrow transplant, it may be seen in the absence of prior anticancer treatment. The mechanism linking OP and lymphoma is unclear but OP could represent a syndrome of T‐cell dysfunction or develop as a direct reaction to malignant infiltration of the lung. In patients with atypical presentations, exclusion of an alternate diagnosis must be pursued using surgical lung biopsy, wherever possible. This is the first reported case of OP associated with EATL.
A novel robotic system for flexible ureteroscopy
Authors: Shu Xiongpeng , Chen Qi , Xie Le
Published: October 2020

Background

Interventional robots currently exist for flexible ureteroscopy (fURS). However, force feedback and intra‐renal pressure, which are important in fURS, were rarely considered when designing these robots.

Methods

We propose a novel robotic system for fURS integrated with partial force feedback function that is the bending knob's torque feedback of the flexible ureteroscope, and intra‐renal pressure monitoring. The proposed robotic system adopts commercial haptic device to realize torque feedback. In addition, we further propose a neural network‐based method to optimize the operation of above haptic device.

Results

Experimental results show that the slave robot can capture the variation of bending conditions and feedback to the operator, and can also accurately monitor the intra‐renal pressure. Besides, the neural network‐based method shows its potential in improving the operation.

Conclusions

The results confirm the feasibility of proposed robot's functions. In vivo experiments are needed to further evaluate this system in future work.
Output feedback stabilization within prescribed finite time of asymmetric time‐varying constrained nonholonomic systems
Authors: Gao Fangzheng , Wu Yuqiang , Huang Jiacai , Liu Yanhong
Published: October 2020

In this article, the fixed‐time stabilization problem is investigated for a category of nonholonomic chained‐form systems. Notably, the study possess two important features: the system under investigation is subject to asymmetric time‐varying output constraints (that are equal to the space constraints of mobile robot or other nonholonomic mechanical systems), and only output is available for feedback. A novel universal barrier Lyapunov function (UBLF), which is equivalent to the classical Lyapunov function for unconstrained systems, is introduced to address asymmetric time‐varying output constraint requirements. Under the universal framework in the sense that the proposed scheme can work for system with symmetric/asymmetric constraints or without constraint requirements, an output feedback controller is developed by employing the barrier function and the bi‐limit control techniques. It is shown that the suggested controller ensures the states of the closed‐loop system (CLS) to zero in a prescribed finite time, while the asymmetric time‐varying constraints on system output are not violated. Finally, simulation results are given to confirm the efficacy of the presented control scheme.
A Markov chain approach for ranking treatments in network meta‐analysis
Authors: Chaimani Anna , Porcher Raphaël , Sbidian Émilie , Mavridis Dimitris
Published: October 2020

When interpreting the relative effects from a network meta‐analysis (NMA), researchers are usually aware of the potential limitations that may render the results for some comparisons less useful or meaningless. In the presence of sufficient and appropriate data, some of these limitations (eg, risk of bias, small‐study effects, publication bias) can be taken into account in the statistical analysis. Very often, though, the necessary data for applying these methods are missing and data limitations cannot be formally integrated into ranking. In addition, there are other important characteristics of the treatment comparisons that cannot be addressed within a statistical model but only through qualitative judgments; for example, the relevance of data to the research question, the plausibility of the assumptions, and so on. Here, we propose a new measure for treatment ranking called the Probability of Selecting a Treatment to Recommend (POST‐R). We suggest that the order of treatments should represent the process of considering treatments for selection in clinical practice and we assign to each treatment a probability of being selected. This process can be considered as a Markov chain model that allows the end‐users of NMA to select the most appropriate treatments based not only on the NMA results but also to information external to the NMA. In this way, we obtain rankings that can inform decision‐making more efficiently as they represent not only the relative effects but also their potential limitations. We illustrate our approach using a NMA comparing treatments for chronic plaque psoriasis and we provide the Stata commands.
Spline‐based accelerated failure time model
Authors: Pang Menglan , Platt Robert W. , Schuster Tibor , Abrahamowicz Michal
Published: October 2020

The accelerated failure time (AFT) model has been suggested as an alternative to the Cox proportional hazards model. However, a parametric AFT model requires the specification of an appropriate distribution for the event time, which is often difficult to identify in real‐life studies and may limit applications. A semiparametric AFT model was developed by Komárek et al based on smoothed error distribution that does not require such specification. In this article, we develop a spline‐based AFT model that also does not require specification of the parametric family of event time distribution. The baseline hazard function is modeled by regression B‐splines, allowing for the estimation of a variety of smooth and flexible shapes. In comprehensive simulations, we validate the performance of our approach and compare with the results from parametric AFT models and the approach of Komárek. Both the proposed spline‐based AFT model and the approach of Komárek provided unbiased estimates of covariate effects and survival curves for a variety of scenarios in which the event time followed different distributions, including both simple and complex cases. Spline‐based estimates of the baseline hazard showed also a satisfactory numerical stability. As expected, the baseline hazard and survival probabilities estimated by the misspecified parametric AFT models deviated from the truth. We illustrated the application of the proposed model in a study of colon cancer.
Mixed‐Dimensional In‐Plane Heterostructures from 1D Mo6Te6 and 2D MoTe2 Synthesized by Te‐Flux‐Controlled Chemical Vapor Deposition
Authors: Kim Hyeonkyeong , Johns James E. , Yoo Youngdong
Published: October 2020

Mixed‐dimensional van der Waals heterostructures are scientifically important and practically useful because of their interesting exotic properties resulting from their novel hybrid structures. This study reports the composition‐ and phase‐selective fabrication of low‐dimensional molybdenum/tellurium (Mo/Te) compounds and the direct synthesis of mixed‐dimensional in‐plane 1D–2D Mo6Te6–MoTe2 heterostructures. The composition and phase of the Mo/Te compounds are controlled by changing the Te atomic flux that is adjusted by the Te temperature. Metallic 1D Mo6Te6 wires with an intrinsic 1D structure with a diameter of 3–8 nm and length of 100–300 nm are synthesized to form wire networks under low Te flux conditions, whereas the semiconducting few‐layer 2H MoTe2 films preferentially oriented along the <0001> direction are obtained under high Te flux. Under medium Te flux, the mixed‐dimensional in‐plane 1D–2D Mo6Te6–MoTe2 heterostructures are synthesized in which the semiconducting few‐layer 2H MoTe2 circular domains are edge‐contacted by the metallic 1D Mo6Te6 wire networks. Furthermore, the present Te‐flux‐controlled method reveals that the 1D Mo6Te6 networks change to few‐layer MoTe2 films as the Te flux increases. The in‐plane 1D–2D Mo6Te6–MoTe2 heterostructures synthesized by this method can be considered as advanced edge‐contacted 2D semiconductors for high‐performance 2D electronics.
Hydrogels: The Next Generation Body Materials for Microfluidic Chips?
Authors: Nie Jing , Fu Jianzhong , He Yong
Published: October 2020

The integration of microfluidics with biomedical research is confronted with considerable limitations due to its body materials. With high content of water, hydrogels own superior biocompatibility and degradability. Can hydrogels become another material choice for the construction of microfluidic chips, particularly biofluidics? The present review aims to systematically establish the concept of hydrogel‐based microfluidic chips (HMCs) and address three main concerns: i) why choosing hydrogels? ii) how to fabricate HMCs?, and iii) in which fields to apply HMCs? It is envisioned that hydrogels may be used increasingly as substitute for traditional materials and gradually act as the body material for microfluidic chips. The modifications of conventional process are highlighted to overcome issues arising from the incompatibility between the construction methods and hydrogel materials. Specifically targeting at the “soft and wet” hydrogels, an efficient flowchart of “i) high resolution template printing; ii) damage‐free demolding; iii) twice‐crosslinking bonding” is proposed. Accordingly, a broader microfluidic chip concept is proposed in terms of form and function. Potential biomedical applications of HMCs are discussed. This review also highlights the challenges arising from the material replacement, as well as the future directions of the proposed concept. Finally, the authors′ viewpoints and perspectives for this emerging field are discussed.
Surveillance and Control of Asymptomatic Carriers of Drug-Resistant Bacteria
Authors: Jamrozik Euzebiusz , Selgelid Michael J.
Published: October 2020

Drug-resistant bacterial infections constitute a major threat to global public health. Several key bacteria that are becoming increasingly resistant are among those that are ubiquitously carried by human beings and usually cause no symptoms (i.e. individuals are asymptomatic carriers) until a precipitating event leads to symptomatic infection (and thus disease). Carriers of drug-resistant bacteria can also transmit resistant pathogens to others, thus putting the latter at risk of infections that may be difficult or impossible to treat with currently available antibiotics. Accumulating evidence suggests that such transmission occurs not only in hospital settings but also in the general community, although much more data are needed to assess the extent of this problem. Asymptomatic carriage of drug-resistant bacteria raises important ethical questions regarding the appropriate public health response, including the degree to which it would be justified to impose burdens and costs on asymptomatic carriers (and others) in order to prevent transmission. In this paper, we (i) summarize current evidence regarding the carriage of key drug-resistant bacteria, noting important knowledge gaps and (ii) explore the implications of existing public health ethics frameworks for decision- and policy-making regarding asymptomatic carriers. Inter alia, we argue that the relative burdens imposed by public health measures on healthy carriers (as opposed to sick individuals) warrant careful consideration and should be proportionate to the expected public health benefits in terms of risks averted. We conclude that more surveillance and research regarding community transmission (and the effectiveness of available interventions) will be needed in order to clarify relevant risks and design proportionate policies, although extensive community surveillance itself would also require careful ethical consideration.
Conceptualizing the Impact of MDRO Control Measures Directed at Carriers: A Capability Approach
Authors: Byskov Morten Fibieger , Rump Babette Olga , Verweij Marcel
Published: October 2020

Many countries have implemented specific control measures directed at carriers of multidrug-resistant organisms (MDRO) in order to prevent further introduction and transmission of resistant organisms into hospitals and other healthcare related settings. These control measures may in many ways affect the lives and well-being of carriers of MDRO, resulting in complex ethical dilemmas that often remain largely implicit in practice. In this chapter, we propose to conceptualize the impact of MDRO control measures on the well-being of individual carriers in terms of capabilities and functionings. A capabilitarian framework for the ethical treatment of MDRO carriers commits us to conceptualize the harm done to carriers in terms of the impact that MDRO control measures have on what they are able to do or be. Adopting and adapting Nussbaum’s list of ten central human capabilities, we present a taxonomy of capabilities and functionings that are normatively relevant for the design and evaluation of MDRO control measures.
Fairness in the Use of Information About Carriers of Resistant Infections
Authors: Francis John G. , Francis Leslie P.
Published: October 2020

One standard menu of approaches to the prevalence of anti-microbial resistance diseases is to enhance surveillance, fund research to develop new antimicrobials, and educate providers and patients to reduce unnecessary antimicrobial use. The primarily utilitarian reasoning behind this menu is unstable, however, if it fails to take fairness into account. This chapter develops an account of the fair uses of information gained in public health surveillance. We begin by sketching information needs and gaps in surveillance. We then demonstrate how analysis of information uses is incomplete if viewed from the perspectives of likely vectors of disease who may be subjects of fear and stigma and likely victims who may be coerced into isolation or quarantine. Next, we consider aspects of fairness in the use of information in non-ideal circumstances: inclusive participation in decisions about information use, resource plans for those needing services, and assurances of reciprocal support. Fairness in information use recognizes the ineluctable twinning of victims and vectors in the face of serious pandemic disease.
Antimicrobial Resistance and Social Inequalities in Health: Considerations of Justice
Authors: Reid Lynette
Published: October 2020

Within-country social inequalities in health have widened while global health inequalities have (with some exceptions) narrowed since the Second World War. On commonly accepted prioritarian and sufficientist views of justice and health, these two trends together would be acceptable: the wealthiest of the wealthy are pulling ahead, but the worst off are catching up and more are achieving sufficiency. Such commitments to priority or sufficiency are compatible with a common “development” narrative about economic and social changes that accompany changes (“transitions”) in population health. I set out a very simple version of health egalitarianism (without commitment to any particular current theory of justice) and focus on two common objections to egalitarianism. Priority and sufficiency both address the levelling down and formalism objections, but these objections are distinct: giving content to equality (I argue here) places in question the claimed normative superiority of priority and sufficiency. Using examples of the role of antimicrobials in both these trends – and the future role of AMR – I clarify (first) the multiple forms and dimensions of justice at play in health, and (second) the different mechanisms at work in generating the two current patterns (seen in life course narratives and narratives of political economy). The “accelerated transition” that narrowed global health inequalities is fed by anti-microbials (among other technology transfers). It did not accelerate but replaced the causal processes by which current HICs achieved the transition (growing and shared economic prosperity and widening political franchise). The impact of AMR on widening social inequalities in health in HICs will be complex: inequality has been fed in part by tertiary care enabled by antimicrobials; AMR might erode the solidarity underlying universal health systems as the well-off seek to maintain current expectations of curative and rehabilitative surgery and chemotherapy while AMR mounts. In light of both speculations about the impact of AMR on social and global health inequalities, I close with practical and with theoretical reflection. I briefly indicate the practical importance of understanding AMR from the perspective of health justice for policy response. Then, from a broader perspective, I argue that the content by which I meet the formalism objection demonstrates that the two trends (broadening within-country inequality and narrowing global inequality) are selective and biased samples of a centuries-long pattern of widening social inequalities in health. We are not in the midst of a process of “catching up”. In light of the long-term pattern described here, is the pursuit of sufficiency or priority morally superior to the pursuit of equality as a response to concrete suffering – or do they rationalize a process more objectively described as the best-off continuing to take the largest share of one of the most important benefits of economic development?
Solidarity and Antimicrobial Resistance
Authors: Holm Søren , Ploug Thomas
Published: October 2020

The concept of solidarity has received increasing attention in discussions about public health interventions, both as a possible justification for such interventions and as a possible motivating factors for individual action. This chapter provides an analysis of whether thinking through a lens of solidarity is likely to be helpful in devising strategies and policies to combat antimicrobial resistance. It first provides a critical overview of recent accounts of solidarity and argues that solidarity must be understood as a group based concept. It then applies this conception of solidarity to individual use of antibiotics through a case study of the antibiotic treatment of moderate and severe acne where it is argued that solidarity based thinking is valuable within a context of shared decision-making. Issues of policy making are then discussed and it is argued that basing a policy on solidarity on the one hand constrains the methods chosen to pursue public health goals, but that on the other hand solidarity may provide a strong and durable motivation to comply with such a policy. The limits of solidarity are explored in the final section and it is concluded that 1) the concept of solidarity does have an important role to play in thinking about public health, 2) considerations of solidarity can help us shape the goals and methods of public health policies in the area of antibiotics, and 3) that it is likely that solidarity may also be helpful in thinking through other contentious issues in public health.
Global Health Governance and Antimicrobial Resistance
Authors: Bennett Belinda , Iredell Jon
Published: October 2020

This chapter analyses the challenges and the adequacy of existing frameworks to provide a strong foundation to support global responses to antimicrobial resistance. Calls for global responses are indicative of a growing global commitment to seeking practical means of tackling the growing problem of antimicrobial resistance. While antimicrobial resistance is often conceptualised as an emergency, the application of the International Health Regulations, designed to govern responses to public health emergencies of international concern, remains unclear. Furthermore, there may be challenges for countries in developing and resourcing national approaches to address antimicrobial resistance. Clarity and agreement around definitions of key concepts related to antimicrobial resistance will also be essential to antibiotic stewardship and development of policy in this area. Finally, improvements to health systems as a result of the Sustainable Development Goals may help to support improvements in public health and may play a role in global strategies to address antimicrobial resistance.
Providing Universal Access While Avoiding Antiretroviral Resistance: Ethical Tensions in HIV Treatment
Authors: Haire Bridget
Published: October 2020

The provision of effective antiretroviral therapy is an ethical imperative, and global access to antiretroviral drugs is an important aspect of this. The other less recognised aspect of effective HIV management is in ensuring that HIV does not become resistant to the drugs used in treatment (and increasingly also in prevention), as multi-drug resistant HIV poses a major threat to the sustainability of current responses to HIV control. In resource-constrained environments, the rapid scale up of access to life-saving anti-HIV treatment was achieved using a public health approach that standardised antiretroviral regimens, minimised laboratory monitoring, and devolved responsibilities from clinicians where necessary. In recent years demand for antiretroviral treatment has increased due to new understandings of the clinical importance of early treatment, but global investment has declined. Exponential growth of the population using antiretrovirals without careful monitoring increases the risk of significant antiretroviral drug resistance. In this chapter, I consider the example of single-drug interventions to prevent parent-to-child HIV transmission, and how the implementation of that strategy increased health risks for mothers. I argue that while global antiretroviral scale up must continue, laboratory monitoring at individual and national levels needs to improve to maintain treatment effectiveness, and protocols for moving people from failing regimens need to be strengthened.