bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-Car Convex Feasible Set Algorithm in Trajectory Planning
Authors: Huang Jing , Liu Changliu
Published: January 2021

Trajectory planning is an essential module for autonomous driving. To deal with multi-vehicle interactions, existing methods follow the prediction-then-plan approaches which first predict the trajectories of others then plan the trajectory for the ego vehicle given the predictions. However, since the true trajectories of others may deviate from the predictions, frequent re-planning for the ego vehicle is needed, which may cause many issues such as instability or deadlock. These issues can be overcome if all vehicles can form a consensus by solving the same multi-vehicle trajectory planning problem. Then the major challenge is how to efficiently solve the multi-vehicle trajectory planning problem in real time under the curse of dimensionality. We introduce a novel planner for multi-vehicle trajectory planning based on the convex feasible set (CFS) algorithm. The planning problem is formulated as a non-convex optimization. A novel convexification method to obtain the maximal convex feasible set is proposed, which transforms the problem into a quadratic programming. Simulations in multiple typical on-road driving situations are conducted to demonstrate the effectiveness of the proposed planning algorithm in terms of completeness and optimality.
An Online Transfer Learning Approach for Identification and Predictive Control Design With Application to RCCI Engines
Authors: Bao Yajie , Mohammadpour Velni Javad , Shahbakhti Mahdi
Published: January 2021

This paper presents a framework to refine identified artificial neural networks (ANN) based state-space linear parameter-varying (LPV-SS) models with closed-loop data using online transfer learning. An LPV-SS model is assumed to be first identified offline using inputs/outputs data and a model predictive controller (MPC) designed based on this model. Using collected closed-loop batch data, the model is further refined using online transfer learning and thus the control performance is improved. Specifically, fine-tuning, a transfer learning technique, is employed to improve the model. Furthermore, the scenario where the offline identified model and the online controlled system are “similar but not identitical” is discussed. The proposed method is verified by testing on an experimentally validated high-fidelity reactivity controlled compression ignition (RCCI) engine model. The verification results show that the new online transfer learning technique combined with an adaptive MPC law improves the engine control performance to track requested engine loads and desired combustion phasing with minimum errors.
Application of MIMO Data Driven Feedback Control Design to Dual Stage Hard Disk Drives
Authors: Shah Prateek , Chen Zhi , Horowitz Roberto
Published: January 2021

With increasing data density on hard disk drives, there is need to develop more robust and better performing track following control systems. We present a multi-input multi-output (MIMO) data driven feedback control design methodology. The design considers multiple frequency response measurements of all actuators, simultaneously, ensuring robustness of the control design system. A mixed H2 – H∞ norm locally convex optimization algorithm is used to synthesize the feedback controllers for MIMO systems.

Feedback controllers are developed for dual stage hard disk drives using the MIMO data driven control design technique. A dual stage hard disk drive comprises of two actuators in series, controlling a read/write head onto a rotating disk. Our objective is to stabilize the closed loop of the actuators and minimize the error position signal of the read/write head. H2 norm and H∞ norm control objectives are used to formulate the MIMO data driven control problem. The design is based on a set of five frequency response measurements of the two actuators. We also compare the MIMO design methodology to a single-input multi-output (SIMO) design methodology presented earlier [1].
Constrained Control of Input Delayed Systems With Partially Compensated Input Delays
Authors: Abel Imoleayo , Janković Mrdjan , Krstić Miroslav
Published: January 2021

Control Barrier Functions (CBFs) have become popular for enforcing — via barrier constraints — the safe operation of nonlinear systems within an admissible set. For systems with input delay(s) of the same length, constrained control has been achieved by combining a CBF for the delay free system with a state predictor that compensates the single input delay. Recently, this approach was extended to multi input systems with input delays of different lengths. One limitation of this extension is that barrier constraint adherence can only be guaranteed after the longest input delay has been compensated and all input channels become available for control. In this paper, we consider the problem of enforcing constraint adherence when only a subset of input delays have been compensated. In particular, we propose a new barrier constraint formulation that ensures that when possible, a subset of input channels with shorter delays will be utilized for keeping the system in the admissible set even before longer input delays have been compensated. We include a numerical example to demonstrate the effectiveness of the proposed approach.
Passivity-Based Disturbance Observer Design
Authors: Chen Ying-Chun , Woolsey Craig
Published: January 2021

A design method is proposed for a nonlinear disturbance observer based on the notion of passivity. As an initial application, we consider here systems whose structure comprises a set of integrator cascades, though the proposed approach can be extended to a larger class of systems. We describe an explicit procedure to choose the output of the system and to design the nonlinear feedback law used by the observer, provided the system satisfies a sufficient condition for output feedback semi-passification. The output injection term in the observer scales the measurement residual with a nonlinear gain that depends on the output and a set of static design parameters. We provide guidance for parameter tuning such that the disturbance tracking performance and the transient response of the estimation error can be intuitively adjusted. Example applications to two nonlinear mechanical systems illustrate that the proposed nonlinear observer design method is quite effective, producing an observer that can estimate a wide range of disturbances without any need to know or assume the disturbance dynamics.
A feature-based data association method for multiple acoustic source localization in a distributed microphone array
Authors: Dang Xudong , Zhu Hongyan
Published: January 2021

Multisource localization using time difference of arrival (TDOA) is challenging because the correct combination of TDOA estimates across different microphone pairs, corresponding to the same source, is usually unknown, which is termed as the data association problem. Moreover, many existing multisource localization techniques are originally demonstrated in two dimensions, and their extensions to three dimensions (3D) are not straightforward and would lead to much higher computational complexity. In this paper, we propose an efficient, feature-based approach to tackle the data association problem and achieve multisource localization in 3D in a distributed microphone array. The features are generated by using interchannel phase difference (IPD) information, which indicates the number of times each frequency bin across all time frames has been assigned to sources. Based on such features, the data association problem is addressed by correlating most similar features across different microphone pairs, which is executed by solving a two-dimensional assignment problem successively. Thereafter, the locations of multiple sources can be obtained by imposing a single-source location estimator on the resulting TDOA combinations. The proposed approach is evaluated using both simulated data and real-world recordings.
Fixed gain multichannel active noise control with disturbance dependent objectives and iterative solution
Authors: Berkhoff Arthur P.
Published: January 2021

This paper presents a solution method for a fixed multichannel frequency domain feedforward controller, which is optimized for different sound field disturbances, each corresponding to a different control objective. A controller determined on the basis of identical control objectives for different disturbances can be solved efficiently by using the inverse of two relatively small matrices, the Hermitian square of the secondary path and the cross-spectral density matrix of all combinations between the reference signals. In contrast, the dependence between the disturbance and the control objective results in a large matrix, which may not fit in the memory of a computer. To design the controller for systems with relatively large numbers of sensors and sources, an iterative method based on the conjugate gradient technique is used. A preconditioner based on a disturbance-independent control objective is proposed. This preconditioner improves the convergence rate for some applications. A numerical example of the iterative method is given for active control of the acoustic field inside a room in which a disturbance dependent weighting function is applied to the cost function. It is shown that the iterative method efficiently finds the solution for the disturbance dependent active noise control problem.
Probability of detection of electric vehicles with and without added warning sounds
Authors: Roan Michael J. , Neurauter Luke , Song Miao , Miller Marty
Published: January 2021

Detection performance as a function of distance was measured for 16 subjects who pressed a button upon aurally detecting the approach of an electric vehicle. The vehicle was equipped with loudspeakers that broadcast one of four additive warning sounds. Other test conditions included two vehicle approach speeds [10 and 20 km/h (kph)] and two background noise conditions (55 and 60 dBA). All of the test warning sounds were designed to be compliant with FMVSS 141 proposed regulations in regard to the overall sound pressure levels around the vehicle and in 1/3 octave band levels. Previous work has provided detection results as average vehicle detection distance. This work provides the results as probability of detection (Pd) as a function of distance. The curves provide insight into the false alarm rate when the vehicle is far away from the listeners as well and the Pd at the mean detection distance. Results suggest that, although the test sounds provide an average detection distance that exceeds the National Highway Traffic Safety Administration minimum at the two test speeds, Pd is not always 100% at those distances, particularly at the 10 kph. At the higher speed of 20 kph, the tire-road interaction noise becomes dominant, and the detection range is greatly extended.
PERK inhibition attenuates vascular remodeling in pulmonary arterial hypertension caused by
BMPR2
mutation
Authors: Shimizu Takashi , Higashijima Yoshiki , Kanki Yasuharu , Nakaki Ryo , Kawamura Takeshi , Urade Yoshihiro , Wada Youichiro
Published: January 2021

Inhibiting the PERK arm of the unfolded protein response may alleviate pulmonary arterial hypertension.
Reprogramming CD8
+
T cells
Authors: Foley John F.
Published: January 2021

MEK1/2 inhibition enhances both the persistence and antitumor activity of CD8
+
T cells in vivo.
Revisiting Ediacaran sulfur isotope chemostratigraphy with in situ nanoSIMS analysis of sedimentary pyrite
Authors: Wang Wei , Hu Yongliang , Muscente A. Drew , Cui Huan , Guan Chengguo , Hao Jialong , Zhou Chuanming
Published: January 2021

Reconstructions of ancient sulfur cycling and redox conditions commonly rely on sulfur isotope measurements of sedimentary rocks and minerals. Ediacaran strata (635–541 Ma) record a large range of values in bulk sulfur isotope difference (Δ34S) between carbonate-associated sulfate (δ34SCAS) and sedimentary pyrite (δ34Spy), which has been interpreted as evidence of marine sulfate reservoir size change in space and time. However, bulk δ34Spy measurements could be misleading because pyrite forms under syngenetic, diagenetic, and metamorphic conditions, which differentially affect its isotope signature. Fortunately, these processes also impart recognizable changes in pyrite morphology. To tease apart the complexity of Ediacaran bulk δ34Spy measurements, we used scanning electron microscopy and nanoscale secondary ion mass spectrometry to probe the morphology and geochemistry of sedimentary pyrite in an Ediacaran drill core of the South China block. Pyrite occurs as both framboidal and euhedral to subhedral crystals, which show largely distinct negative and positive δ34Spy values, respectively. Bulk δ34Spy measurements, therefore, reflect mixed signals derived from a combination of syndepositional and diagenetic processes. Whereas euhedral to subhedral crystals originated during diagenesis, the framboids likely formed in a euxinic seawater column or in shallow marine sediment. Although none of the forms of pyrite precisely record seawater chemistry, in situ framboid measurements may provide a more faithful record of the maximum isotope fractionation from seawater sulfate. Based on data from in situ measurements, the early Ediacaran ocean likely contained a larger seawater sulfate reservoir than suggested by bulk analyses.
Surgical repair of an obstetric cloaca with review of the literature
Authors: Gehrich Alan Paul , McClellan Edward , Gillern Suzanne
Published: January 2021

A complete perineal wound breakdown of a fourth degree laceration leading to a cloaca is a rare but devastating complication of vaginal childbirth. A 32-year-old primiparous woman presented with an obstetric cloaca 4 months following delivery. She underwent preoperative evaluation and, following extensive counselling, elected to proceed with operative repair. The procedure is presented in 15 well-defined steps with photos. The repair was performed in standard fashion with three supplementary steps. These included: (1) division of the rectovaginal tissue into three distinct layers; (2) attachment of these layers individually to the reconstructed perineal body and sphincter and (3) incorporation of the levator muscles into the repair. The wound healed well within 6 weeks of repair. Now 3½ years postoperatively, the patient has no faecal incontinence or sexual dysfunction and only minimal defecatory dysfunction. The discussion describes our surgical approach in the context of a review of the literature.
Pneumococcal induced thrombotic thrombocytopenic purpura with features of purpura fulminans
Authors: Walsh Laura Frances , Sherbuk Jacqueline E , Wispelwey Brian
Published: January 2021

A 42-year-old woman with a history of acute myeloid leukaemia status postallogeneic stem cell transplant presented with fevers, altered mental status, pulmonary infiltrates and septic shock that further progressed to thrombocytopenia and purpura fulminans. Laboratory studies were consistent with a diagnosis of thrombotic thrombocytopenic purpura (TTP). Blood cultures grewStreptococcus pneumoniae. On chart review, our patient had a history of low immunoglobulin levels following stem cell transplant, which may have predisposed her to pneumococcal infection. The patient responded to therapy with ceftriaxone, plasma exchange, rituximab and caplacizumab. This is the fourth-documented case of pneumococcal induced TTP and, to the best of our knowledge, the first-describing pneumococcal induced TTP with purpura fulminans. We conclude that patients with TTP should be evaluated for infectious aetiologies and empiric antibiotics should be considered. Clinicians should be aware of the possibility for TTP to lead to purpura fulminans.
Ruptured salpingitis isthmica nodosa: a rare cause for spontaneous haemoperitoneum
Authors: Huang Dora , Lowe Sandon , Kumaran Pravena , Choy Kay Tai
Published: January 2021

Salpingitis isthmica nodosa (SIN) is the nodular swelling or diverticulum of the isthmus of the fallopian tube. It is most commonly identified when investigating female infertility or in association with ruptured ectopic pregnancies. We experienced a rare and atypical presentation of SIN. A 33-year-old woman presented with a 1-hour history of acute lower abdominal pain associated with nausea and vomiting. CT and pelvic ultrasound revealed haemoperitoneum with no radiological evidence for its aetiology. Initial beta-human chorionic gonadotropin excluded ectopic pregnancy. A diagnostic laparoscopy was performed following clinical deterioration of the patient. Active bleeding of the right fallopian tube was identified and managed with a right partial salpingectomy, with subsequent histopathology revealing ruptured SIN. There have been no reported cases of SIN being a primary cause for an acute abdomen or haemoperitoneum in the absence of an ectopic pregnancy, making this case a surgical novelty.
Successful rescue treatment of right posterior inferior cerebellar artery (PICA) vascular stasis with tirofiban following endovascular coil implantation
Authors: Houle Christopher , Reddy Varun
Published: January 2021

This report describes a patient who developed intraprocedural vascular stasis immediately following elective endovascular coil emboliation. Urgent antiplatelet treatment with the GpIIb/IIIa agent tirofiban was used. It was infused intra-arterially during the procedure, followed by a fixed rate intravenous continuous infusion, and successfully restored normal circulation. There were no reports of further bleeding or haemodynamic compromise during the hospital stay. The patient’s condition returned to baseline and he was discharged the following day with no neurological deficits.
Co-designing organisational improvements and interventions to increase inpatient activity in four stroke units in England: a mixed-methods process evaluation using normalisation process theory
Authors: Clarke David , Gombert-Waldron Karolina , Honey Stephanie , Cloud Geoffrey , Harris Ruth , Macdonald Alastair , McKevitt Christopher , Robert Glenn , Jones Fiona
Published: January 2021

Objective

To explore facilitators and barriers to using experience-based co-design (EBCD) and accelerated EBCD (AEBCD) in the development and implementation of interventions to increase activity opportunities for inpatient stroke survivors.

Design

Mixed-methods process evaluation underpinned by normalisation process theory (NPT).

Setting

Four post-acute rehabilitation stroke units in England.

Participants

Stroke survivors, family members, stroke unit staff, hospital managers, support staff and volunteers. Data informing our NPT analysis comprised: ethnographic observations, n=366 hours; semistructured interviews with 76 staff, 53 stroke survivors and 27 family members pre-EBCD/AEBCD implementation or post-EBCD/AEBCD implementation; and observation of 43 co-design meetings involving 23 stroke survivors, 21 family carers and 54 staff.

Results

Former patients and families valued participation in EBCD/AEBCD perceiving they were equal partners in co-design. Staff engaged with EBCD/AEBCD, reporting it as a valuable improvement approach leading to increased activity opportunities. The structured EBCD/AEBCD approach was influential in enabling coherence and cognitive participation and legitimated staff involvement in the change process. Researcher facilitation of EBCD/AEBCD supported cognitive participation, collective action and reflexive monitoring; these were important in implementing and sustaining co-design activities. Observations and interviews post-EBCD/AEBCD cycles confirmed creation and use of new social spaces and increased activity opportunities in all units. EBCD/AEBCD facilitated engagement with wider hospital resources and local communities, further enhancing activity opportunities. However, outside of structured group activity, many individual staff–patient interactions remained task focused.

Conclusions

EBCD/AEBCD facilitated the development and implementation of environmental changes and revisions to work routines which supported increased activity opportunities in stroke units providing post-acute and rehabilitation care. Former stroke patients and carers contributed to improvements. NPT’s generative mechanisms were instrumental in analysis and interpretation of facilitators and barriers at the individual, group and organisational level, and can help inform future implementations of similar approaches.
Students’ top 10 priorities of research uncertainties on students’ sleep: a pragmatic James Lind Alliance approach
Authors: Holmen Heidi , Riiser Kirsti , Løyland Borghild , Sandbekken Ida Hellum , Almendingen Kari , Andenæs Randi , Bjørnnes Ann Kristin , Fagerlund Bettina Holmberg , Früh Elena Albertini , Helseth Sølvi , Kvarme Lisbeth Gravdal , Leegaard Marit , Misvær Nina , Pallesen Ståle , Rasalingam Anurajee , Ravn Ingrid , Ribu Lis , Rostad Hanne Marie , Sparboe-Nilsen Bente , Sæterstrand Torill Margaret , Torbjørnsen Astrid , Utne Inger , Valeberg Berit Taraldsen , Valla Lisbeth , Winger Anette , Grov Ellen Karine
Published: January 2021

Objectives

Inspired by the James Lind Alliance (JLA) user involvement approach, the aim of the present study was to identify the top 10 uncertainties for sleep research raised by students in higher education, and to discuss our experiences with adapting the JLA method to a student population.

Design

The study design is a pragmatic JLA approach, including a priority setting partnership within the field of sleep, collection of sleep-related research uncertainties as reported by students in higher education, sorting of the uncertainties and a final identification of the top 10 uncertainties through collaborative work between researchers, students, stakeholders and experts in the field. Uncertainties were collected using a one-question online survey: ‘as a student, which question(s) do you consider to be important with regards to sleep?’. A variety of approaches were applied to promote the survey to the students, including social media, radio, the university website, stands in university cafeterias and a sleep stunt. NVivo V.12 was used to code and sort the questions.

Setting

A higher education institution in Norway.

Participants

555 students.

Results

The data collection provided 608 uncertainties, and the following prioritised top 10: (1) screen time, (2) stress, (3) educational achievements, (4) social relations, (5) mental health, (6) physical activity, (7) indoor environment, (8) substance abuse, (9) shift work and (10) sleep quality. Despite successful data collection, we found sleep to be a broad topic, and defining specific questions throughout the sorting and verification process proved difficult.

Conclusions

We identified the prioritised top 10 research uncertainties as reported by students in higher education, ranking screen time first. However, the process was time and resource consuming. The research uncertainties addressed by the students showed great diversity, characterised by heterogeneity and a lack of specificity, making verification of the uncertainties challenging.
Cardiac Arrest Nurse Leadership (CANLEAD) trial: a simulation-based randomised controlled trial implementation of a new cardiac arrest role to facilitate cognitive offload for medical team leaders
Authors: Pallas Jeremy David , Smiles John Paul , Zhang Michael
Published: January 2021

Background

Medical team leaders in cardiac arrest teams are routinely subjected to disproportionately high levels of cognitive burden. This simulation-based study explored whether the introduction of a dedicated ‘nursing team leader’ is an effective way of cognitively offloading medical team leaders of cardiac arrest teams. It was hypothesised that reduced cognitive load may allow medical team leaders to focus on high-level tasks resulting in improved team performance.

Methods

This randomised controlled trial used a series of in situ simulations performed in two Australian emergency departments in 2018–2019. Teams balanced on experience were randomised to either control (traditional roles) or intervention (designated nursing team leader) groups. No crossover between groups occurred with each participant taking part in a single simulation. Debriefing data were collected for thematic analysis and quantitative evaluation of self-reported cognitive load and task efficiency was evaluated using the NASA Task Load Index (NTLX) and a ‘task time checklist’ which was developed for this trial.

Results

Twenty adult cardiac arrest simulations (120 participants) were evaluated. Intervention group medical team leaders had significantly lower NTLX scores (238.4, 95% CI 192.0 to 284.7) than those in control groups (306.3, 95% CI 254.9 to 357.6; p=0.02). Intervention group medical team leaders working alongside a designated nursing leader role had significantly lower cognitive loads than their control group counterparts (206.4 vs 270.5, p=0.02). Teams with a designated nurse leader role had improved time to defibrillator application (23.5 s vs 59 s, p=0.004), faster correction of ineffective compressions (7.5 s vs 14 s, p=0.04), improved compression fraction (91.3 vs 89.9, p=0.048), and shorter time to address reversible causes (107.1 s vs 209.5 s, p=0.002).

Conclusion

Dedicated nursing team leadership in simulation based cardiac arrest teams resulted in cognitive offload for medical leaders and improved team performance.
Prescription of analgesia in emergency medicine (POEM) secondary analysis: an observational multicentre comparison of pain relief provided to adults and children with an isolated limb fracture and/or dislocation
Authors: Wilson Sarah , Quinlan Jane , Beer Sally , Darwent Melanie , Dainty Jack R. , Sheehan James Robert , Keating Liza
Published: January 2021

Background

Acute pain is a common reason for emergency department (ED) attendance. Royal College of Emergency Medicine (RCEM) pain management audits have shown national variation and room for improvement. Previous evidence suggests that children receive less satisfactory pain management than adults.

Methods

Prescription of analgesia in emergency medicine is a cross-sectional observational study of consecutive patients presenting to 12 National Health Service EDs with an isolated long bone fracture and/or dislocation, and was carried out between 2015 and 2017. Using the recommendations in the RCEM Best Practice Guidelines, pain management in ED was assessed for differences of age (adults vs children) and hospital type (children’s vs all patients).

Results

From the total 8346 patients, 38% were children (median age 8 years). There was better adherence to the RCEM guidance for children than adults (24% (766/3196) vs 11% (579/5123)) for the combined outcome of timely assessment, pain score and appropriate analgesia. In addition, children were significantly more likely than adults to receive analgesia appropriate to the pain score (of those with a recorded pain score 67% (1168/1744) vs 52% (1238/2361)). Children’s hospitals performed much better across all reported outcomes compared with general hospitals.

Conclusions

In contrast to previous studies, children with a limb fracture/dislocation are more likely than adults to have a pain score documented and to receive appropriate analgesia. Unexpectedly, children’s EDs performed better than general EDs in relation to timely and appropriate analgesia but the reasons for this are not apparent from the present study.
Medication adherence in community-dwelling older people exposed to chronic polypharmacy
Authors: Franchi Carlotta , Ardoino Ilaria , Ludergnani Monica , Cukay Gjiliola , Merlino Luca , Nobili Alessandro
Published: January 2021

Background

To evaluate medication adherence and associated factors of seven of the most common drug classes prescribed to community-dwelling older people.

Methods

This is a retrospective cohort study on medication adherence in community-dwelling older people (65–94 years old) on chronic polypharmacy and recorded from 2013 to 2015 in the administrative database of the Lombardy region (Northern Italy). Adherence was assessed for diabetic drugs, antithrombotic agents, drugs acting on the renin–angiotensin system, statins, bisphosphonates, antidepressants and drugs for obstructive airway diseases by calculating the medication possession ratio (MPR). Patients were then divided in fully (MPR ≥80%), partially (40%≤MPR<80%) and poorly adherent (10%<MPR<40%).

Results

Among 140 537 patients included in the study, only 19.3% was fully adherent to all the therapies considered. Almost 40% of them were poorly adherent to at least one drug class, becoming 50% when patients exposed to four or more drug classes were considered. In adjusted regression model, being women (OR=1.14, 95% CI 1.13 to 1.16) and aged ≥80 years old (OR=1.22, 95% CI 1.20 to 1.24) were associated with an overall lower adherence. Instead, the participation to an experimental healthcare programme was associated with higher adherence (OR=0.92, 95% CI 0.87 to 0.96). Furthermore, being coprescribed with ≥10 drugs was associated with lower adherence to all the drug classes, with different effects (ORs from 0.42 to 0.73).

Conclusion

This study overall shows a low medication adherence in community-dwelling older people on chronic polypharmacy, especially in women and oldest old. The implementation and promotion of healthcare programmes for these patients could help improve overall adherence to chronic drug therapies.
Real-world experience with elective discontinuation of PD-1 inhibitors at 1 year in patients with metastatic melanoma
Authors: Pokorny Rebecca , McPherson Jordan P , Haaland Benjamin , Grossmann Kenneth F , Luckett Carolyn , Voorhies Benjamin Newell , Sageser Daniel S , Wallentine Jocelyn , Tolman Zachary , Hu-Lieskovan Siwen , Swami Umang
Published: January 2021

Background

Randomized trials evaluating programmed cell death protein 1 (PD-1) inhibitors in metastatic melanoma either permitted treatment for 2 years (pembrolizumab) or more (nivolumab). The optimal duration of therapy is currently unknown due to limited data, and shorter therapies may be effective.

Methods

Data of patients with metastatic cutaneous melanoma treated with single-agent PD-1 inhibitors at Huntsman Cancer Institute from January 1, 2015, to December 31, 2018, was reviewed to identify a continuous series of patients who made the joint decision with their provider to electively discontinue therapy at 1 year (>6 months and <18 months) in the setting of ongoing treatment response or disease stability. Patients were excluded if they received PD-1 inhibitors with other systemic therapy, had prior exposure to PD-1 therapy, or discontinued treatment due to disease progression or immune-related adverse event. Best objective response (BOR) per RECIST V.1.1 at treatment discontinuation, progression-free survival (PFS), and retreatment characteristics was analyzed.

Results

Of 480 patients who received PD-1 inhibitors, 52 met the inclusion criteria. The median treatment duration from first to the last dose was 11.1 months (95% CI 10.5 to 11.4). BOR was complete response in 13 (25%), partial response in 28 (53.8%), and stable disease in 11 (21.2%) patients. After a median follow-up of 20.5 months (range 3–49.2) from treatment discontinuation, 39 (75%) patients remained without disease progression, while 13 (25%) had progression (median PFS 3.9 months; range 0.7–30.9). On multivariable analysis, younger age, history of brain metastasis, and higher lactate dehydrogenase at the time of anti-PD-1 discontinuation were associated with recurrence. Patients with recurrent melanoma were managed with localized treatment, anti-PD-1 therapies, and BRAF-MEK inhibitors. All patients except one were alive at data cutoff.

Conclusion

In this large real-world, observational cohort study, the majority of patients with metastatic melanoma after 1 year of anti-PD-1 therapy remained without progression on long-term follow-up. The risk of disease progression even in patients with residual disease on imaging was low. After prospective validation, elective PD-1 discontinuation at 1 year may reduce financial and immunotherapy-related toxicity without sacrificing outcomes.
Revisiting the supersymmetric Pati–Salam models from intersecting D6-branes
Authors: Li Tianjun , Mansha Adeel , Sun Rui
Published: January 2021

Employing novel random and supervised scanning methods, we systematically revisit the construction of three-family $$N=1$$

N
=
1

supersymmetric Pati–Salam models in Type IIA orientifolds on $$\mathbf{T}^6/({\mathbb {Z}}_2\times {\mathbb {Z}}_2)$$

T

6

/

(

Z
2

×

Z
2

)

with intersecting D6-branes. Arising from the stacks of D6-branes with U(n) gauge symmetries, the Pati–Salam gauge symmetries $$SU(4)_C\times SU(2)_L \times SU(2)_R$$

S
U

(
4
)

C

×
S
U

(
2
)

L

×
S
U

(
2
)

R

can be broken down to the Standard Model via D-brane splitting as well as D- and F-flatness preserving Higgs mechanism. Also, the hidden sector contains USp(n) branes, which are parallel with the orientifold planes or their $${{\mathbb {Z}}_2}$$

Z
2

images. We find that the Type II T-duality in the previous study is not an equivalent relation in Pati–Salam model building if the model is not invariant under $$SU(2)_L$$

S
U

(
2
)

L

and $$SU(2)_R$$

S
U

(
2
)

R

exchange, and provides a way to obtain new models. We systematically construct the new models with three families, which usually do not have gauge coupling unification at the string scale. We for the first time construct the Pati–Salam models with at least one wrapping number whose absolute value reaching 5. In particular, for one large wrapping number equal to 5, we find that one kind of model carries more refined gauge couplings, and thus with more possibilities to have approximate gauge coupling unification.
Relation of Extra Edge Connectivity and Component Edge Connectivity for Regular Networks
Authors: Guo Litao , Zhang Mingzu , Zhai Shaohui , Xu Liqiong
Published: January 2021

Reliability of interconnection networks is important to design multiprocessor systems. The extra edge connectivity and component edge connectivity are two parameters for the reliability evaluation. The [Formula: see text]-extra edge connectivity [Formula: see text] is the cardinality of the minimum extra edge cut [Formula: see text] such that [Formula: see text] is not connected and each component of [Formula: see text] has at least [Formula: see text] vertices. The [Formula: see text]-component edge connectivity [Formula: see text] of a graph [Formula: see text] is the minimum edge number of a set [Formula: see text] such that [Formula: see text] is not connected and [Formula: see text] has at least [Formula: see text] components. In this paper, we find the relation of extra edge connectivity and component edge connectivity for regular networks. As an application, we determine the component edge connectivity of BC networks, [Formula: see text]-ary [Formula: see text]-cubes, enhanced hypercubes.
In–Out Intermittency with Nested Subspaces in a System of Globally Coupled, Complex Ginzburg–Landau Equations
Authors: Dangelmayr Gerhard , Oprea Iuliana
Published: January 2021

Chaos and intermittency are studied for the system of globally coupled, complex Ginzburg–Landau equations governing the dynamics of extended, two-dimensional anisotropic systems near an oscillatory (Hopf) instability of a basic state with two pairs of counterpropagating, oblique traveling waves. Parameters are chosen such that the underlying normal form, which governs the dynamics of the spatially constant modes, has two symmetry-conjugated chaotic attractors. Two main states residing in nested invariant subspaces are identified, a state referred to as Spatial Intermittency ([Formula: see text]) and a state referred to as Spatial Persistence ([Formula: see text]). The [Formula: see text]-state consists of laminar phases where the dynamics is close to a normal form attractor, without spatial variation, and switching phases with spatiotemporal bursts during which the system switches from one normal form attractor to the conjugated normal form attractor. The [Formula: see text]-state also consists of two symmetry-conjugated states, with complex spatiotemporal dynamics, that reside in higher dimensional invariant subspaces whose intersection forms the 8D space of the spatially constant modes. We characterize the repeated appearance of these states as (generalized) in–out intermittency. The statistics of the lengths of the laminar phases is studied using an appropriate Poincaré map. Since the Ginzburg–Landau system studied in this paper can be derived from the governing equations for electroconvection in nematic liquid crystals, the occurrence of in–out intermittency may be of interest in understanding spatiotemporally complex dynamics in nematic electroconvection.
Complex Dynamics and Periodic Oscillation Mechanism in Two Novel Gene Expression Models with State-Dependent Delays
Authors: Wang Shuo , Pei Lijun
Published: January 2021

The reaction time delay in the transcription process depends on the concentration of the protein because the transportation of mRNA from the nucleus to the cytoplasm becomes saturated. Thus the gene regulatory network is a state-dependent delayed model. This study aims to provide some mathematical explanations for the dynamics of the system, such as the linear stability and periodic oscillation, using mathematical techniques, such as formal linearization, linear stability analysis, the method of multiple scale (MMS), and the normal form. First, Hopf bifurcation of the state-dependent delayed gene regulatory networks model in the gene expression is analyzed by the method of multiple scales (MMS). Mechanism of periodic oscillations is obtained by Hopf bifurcation. The findings show that when degradation effects of the mRNA and protein are very strong, the oscillatory gene expression disappears. Then, a more realistic version of the aforementioned model with both constant and state-dependent time delays is established due to the existence of the constant time delay in the protein degradation process. Its nonresonant double Hopf bifurcation is found and analyzed using MMS. Interesting complex dynamic phenomena, such as periodic, quasi-periodic, and global period-[Formula: see text] solutions, are also discovered. These observations indicate that both state-dependent delay and constant delay could induce richer dynamics of the system, and the modified model may potentially describe the real dynamical mechanism (both the transcription process and the degradation process) more accurately in the gene expression. The findings may provide important guidance or hints to understand the real dynamic mechanism of the gene expression process.
A Unified Chaotic System with Various Coexisting Attractors
Authors: Lai Qiang
Published: January 2021

This article presents a unified four-dimensional autonomous chaotic system with various coexisting attractors. The dynamic behaviors of the system are determined by its special nonlinearities with multiple zeros. Two cases of nonlinearities with sine function of the system are discussed. The symmetrical coexisting attractors, asymmetrical coexisting attractors and infinitely many coexisting attractors in the system are numerically demonstrated. This shows that such a system has an ability to produce abundant coexisting attractors, depending on the number of equilibrium points determined by nonlinearities.
Chaos Detection of the Chen System with Caputo–Hadamard Fractional Derivative
Authors: Yin Chuntao
Published: January 2021

In this paper, we investigate the chaotic behaviors of the Chen system with Caputo–Hadamard derivative. First, we construct some practical numerical schemes for the Chen system with Caputo–Hadamard derivative. Then, by means of the variational equation, we estimate the bounds of the Lyapunov exponents for the considered system. Furthermore, we analyze the dynamical evolution of the Chen system with Caputo–Hadamard derivative based on the Lyapunov exponents, and we found that chaos does exist in the considered system. Some phase diagrams and Lyapunov exponent spectra are displayed to verify our analysis.
A multifractal analysis for cuspidal windings on hyperbolic surfaces
Authors: Jaerisch Johannes , Kesseböhmer Marc , Munday Sara
Published: January 2021

In this paper, we investigate the multifractal decomposition of the limit set of a finitely generated, free Fuchsian group with respect to the mean cusp-winding number. We completely determine its multifractal spectrum by means of a certain free energy function and show that the Hausdorff dimension of sets consisting of limit points with the same scaling exponent coincides with the Legendre transform of this free energy function. As a by-product we generalize previously obtained results on the multifractal formalism for infinite iterated function systems to the setting of infinite graph directed Markov systems.
Who is Against Sino-African Relations? Evolving Perceptions on Chinese Engagement in Kenya
Authors: Waweru Sammy Mwangi
Published: January 2021

Rise of China and increased Chinese engagement across the globe, have attracted mixed and varied reactions of approval and disapproval in a number of host countries. Against this background, this study brings into perspective rise of anti-Chinese sentiments in Africa, with a Kenyan case study, examining who, why and where anti-Chinese sentiments are most prevalent. The study finds anti-Chinese sentiments being most prevalent among Kenya’s small scale traders who have been displaced by Chinese capital flow and trade in the country. The finding is contextualized within broader framework of globalization and its resultant effects on free movement of capital, trade and investment. More precisely, Chinese capital flow and trade have had distributional consequences of winners and losers with potential to displace Kenya’s small scale traders hence the rise of anti-Chinese sentiments. The anti-Chinese sentiments are equally evident among section of Kenya’s politicians and intelligentsia, who have questioned the viability of Chinese built infrastructure. Further, anti-Chinese sentiments have been found among ordinary citizens who have experienced, albeit isolated, incidences of Chinese misconducts in the country. Notwithstanding these negative reactions, Chinese engagement in Kenya is still pronounced and has popular support from government, general citizenry and among classes of Kenyan who have benefited from Chinese involvement in the country. The segmented nature of anti-Chinese sentiments has not been strong enough to undo general goodwill, attitude and perceptions, that ordinary citizen hold towards Chinese engagement in Kenya.
Early Childhood Adversity, Toxic Stress, and the Impacts of Racism on the Foundations of Health
Authors: Shonkoff Jack P. , Slopen Natalie , Williams David R.
Published: January 2021

Inequalities in health outcomes impose substantial human and economic costs on all societies—and the relation between early adversity and lifelong well-being presents a rich scientific framework for fresh thinking about health promotion and disease prevention broadly, augmented by a deeper focus on how racism influences disparities more specifically. This review begins with an overview of advances in the biology of adversity and resilience through an early childhood lens, followed by an overview of the unique effects of racism on health and a selective review of findings from related intervention research. This article presents a framework for addressing multiple dimensions of the public health challenge—including institutional/structural racism, cultural racism, and interpersonal discrimination—and concludes with the compelling need to protect the developing brain and other biological systems from the physiological disruptions of toxic stress that can undermine the building blocks of optimal health and development in the early childhood period.
Optimizing Electrodeposited Manganese Oxide at Carbon Cloth Electrodes for Harvesting Salinity-Gradient Energy
Authors: Fortunato Jenelle , Sassin Megan B. , Chervin Christopher N. , Parker Joseph F. , DeBlock Ryan H. , Gorski Christopher A. , Long Jeffrey W.
Published: January 2021

Electrical power can be generated from the controlled mixing of salinity gradients when solutions of differing salt concentration bathe opposing electrodes in a flow-cell configuration. The power density of such salinity-gradient cells is enhanced by moving beyond the double-layer capacitance of high-surface-area carbons to electrode materials that store charge via pseudocapacitance (e.g., manganese oxides; MnOx). We investigate the effects of MnOx loading on salinity-gradient power production, using anodic electrodeposition to coat carbon cloth (CC) electrodes with nanostructured Akhtenskite-type MnOx at controlled incremental mass loadings. Uniform MnOx deposition at exposed CC surfaces is confirmed by scanning electron microscopy with elemental mapping. Power-density measurements with the resulting MnOx@CC electrodes in a salinity-gradient cell fed by low (0.02 M NaCl) and high (0.5 M NaCl) concentration solutions show a positive correlation with MnOx loading, reaching a competitive peak average power density of 0.221 ± 0.001 mW cm–2 at 1.90 mg cm–2 MnOx. By comparing flow-cell data with results from half-cell electroanalytical characterization of individual electrodes, we show that salinity-gradient performance is ultimately limited by resistive losses in the modestly conductive MnOx coating at higher mass loading/thickness.
The Galvanic Protection of an Electrochemically Deposited Photocatalytic Au/FeAu Multilayered Nanowire—TiO2 Composite
Authors: Lucatero S. , Podlaha E. J.
Published: January 2021

Gold nanoparticles on the surface of TiO2 is a useful water splitting photocatalyst but its performance can degrade in an oxygenated environment. To deter this degradation a novel composite photocatalyst consisting of electrodeposited Au/FeAu nanowires dispersed onto electrochemically deposited TiO2 on top of a stainless steel substrate was shown to inhibit degradation effects observed during water oxidation in base. A step in illumination and impedance modulated photocurrent spectroscopy (IMPS) provided a quantitative measure of the photoactivity and fate of minority carriers (holes, h+) in fresh and aged composites. The photogenerated current and h+ flux to the electrode surface of fresh catalyst significantly decayed within a period of 120 d in the Au/TiO2 system, whereas in the Fe-containing composite, these performance parameters were maintained for an extended period of time. Composite photocatalysts with Au/FeAu nanowires exhibiting modulations in porosity and composition of the alloy segment were also investigated. The catalyst photoactivity was adversely affected by either decreasing porosity and/or increasing Fe content within the alloy layer of nanowires combined with TiO2.