Cancer immune therapy has shown remarkable benefit in the treatment of a range of cancer types, although it may initiate autoimmune-related disorders in some patients. We have attempted to establish ...whether the incidence of irAEs after the use of anti–PD-1 antibodies nivolumab or pembrolizumab in advanced malignancies is associated with anti–PD-1 treatment efficacy.
We studied patients treated with single-agent nivolumab or pembrolizumab for advanced cancer. irAEs (immune-related adverse events) were identified clinically and graded as per the Common Terminology Criteria for Adverse Events version 4.0. Efficacy was evaluated with objective response rate (ORR, immune-Response Evaluation Criteria in Solid Tumours RECIST criteria) progression-free survival (PFS) and overall survival (OS). Tests were performed to determine the association between irAEs and ORR, PFS or OS.
We identified 106 patients. Primary diagnoses were lung cancer (n = 77), melanoma (n = 8), head and neck carcinoma (n = 7), renal carcinoma (n = 5), Hodgkin's lymphoma (n = 3), urothelial carcinoma (n = 3) and gallbladder adenocarcinoma, hepatocellular carcinoma and Merkel cell carcinoma (n = 1 each). IrAEs were observed in 40 patients (37.7%). The most frequent irAEs were hypothyroidism (n = 15), nephritis (n = 5) and hyperthyroidism (n = 4). Objective response was observed in 44 patients (41.5%), and median PFS was 5.5 months (0.5–31 months). Thirty-three of the 40 patients with irAEs had objective response (82.5%) in contrast with 11 of the 66 cases without irAEs (16.6%) (OR 23.5, P < 0.000001). PFS in patients with irAEs was 10 months and 3 months in those without irAEs (HR 2.2, P = 0.016). OS in patients with irAEs was 32 months and 22 in those without irAEs, without statistically significant differences.
In advanced cancer treated with single-agent anti–PD-1 antibodies, patients with irAEs showed a markedly improved efficacy over patients without irAEs (ORR of 82.5% and PFS of 10 months vs ORR of 16.6% and PFS of 3 months). Future studies of anti–PD-1 immune-therapy should address this association to explore the underlying biological mechanisms of efficacy.
•In advanced cancer treated with anti–PD-1 antibodies nivolumab or pembrolizumab, incidence of irAEs was associated with a marked efficacy.•Response rate increased significantly from 16.6% to 82.5% when an irAE was present.•The follow-up showed an increase of PFS from 3 to 10 months when an irAE was present.•The follow-up showed an increase of OS from 22 to 32 months when an irAE was present.
Abstract
Motivated by recent advances in neuroscience, in this work, we explore the emergent behaviour of quantum systems with a dynamical biologically-inspired qubits interaction. We use a minimal ...model of two interacting qubits with an activity-dependent dynamic interplay as in classical dynamic synapses that induces the so-called synaptic depression, that is, synapses that present synaptic fatigue after heavy presynaptic stimulation. Our study shows that in absence of synaptic depression the two-qubits quantum system shows typical Rabi oscillations whose frequency decreases when synaptic depression is introduced, so one can trap excitations for a large period of time. This creates a population imbalance between the qubits even though the Hamiltonian is Hermitian. This imbalance can be sustained in time by introducing a small energy shift between the qubits. In addition, we report that long time entanglement between the two qubits raises naturally in the presence of synaptic depression. Moreover, we propose and analyse a plausible experimental setup of our two-qubits system which demonstrates that these results are robust and can be experimentally obtained in a laboratory.
•SAM system and HPA axis reactivity predict future health and disease outcomes.•Exaggerated and blunted responses predict different health and disease outcomes.•Reactivity-related health and disease ...outcomes are both physical and mental.•Intermediate stress responses (“Goldilocks” responses) may be the most adaptive.•A “bidirectional multi-system reactivity hypothesis” is proposed.
Acute psychological stress activates the sympatho-adrenal medullary (SAM) system and hypothalamo-pituitary adrenal (HPA) axis. The relevance of this stress reactivity to long-term health and disease outcomes is of great importance. We examined prospective studies in apparently healthy adults to test the hypothesis that the magnitude of the response to acute psychological stress in healthy adults is related to future health and disease outcomes.
We searched Medline Complete, PsycINFO, CINAHL Complete and Embase up to 15 Aug 2019. Included studies were peer-reviewed, English-language, prospective studies in apparently healthy adults. The exposure was acute psychological stress reactivity (SAM system or HPA axis) at baseline. The outcome was any health or disease outcome at follow-up after ≥1 year.
We identified 1719 papers through database searching and 1 additional paper through other sources. Forty-seven papers met our criteria including 32,866 participants (range 30–4100) with 1−23 years of follow-up. Overall, one third (32 %; 83/263) of all reported findings were significant and two thirds (68 %; 180/263) were null. With regard to the significant findings, both exaggerated (i.e. high) and blunted (i.e. low) stress reactivity of both the SAM system and the HPA axis at baseline were related to health and disease outcomes at follow-up. Exaggerated stress reactivity at baseline predicted an increase in risk factors for cardiovascular disease and decreased telomere length at follow-up. In contrast, blunted stress reactivity predicted future increased adiposity and obesity, more depression, anxiety and PTSD symptoms, greater illness frequency, musculoskeletal pain and regulatory T-Cell percentage, poorer cognitive ability, poorer self-reported health and physical disability and lower bone mass.
Exaggerated and blunted SAM system and HPA axis stress reactivity predicted distinct physical and mental health and disease outcomes over time. Results from prospective studies consistently indicate stress reactivity as a predictor for future health and disease outcomes. Dysregulation of stress reactivity may represent a mechanism by which psychological stress contributes to the development of future health and disease outcomes.
Due to the appeal and recent technological advances of video games, the games have gained interest as an intervention tool for active aging. The aim of this systematic literature review and ...meta-analysis was to determine the efficacy of video games for active aging and to examine the influence of potential moderator variables.
A systematic search was done using the following databases: Medline, PsycINFO, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials. In addition, previous reviews and meta-analyses were used to identify randomized controlled trials (RCT) of video game-based interventions for active aging published through February 28, 2018. An evaluation of the methodological quality of the articles and a meta-analysis and moderator analysis was conducted.
A total of 22 articles depicting 21 RCT with 1125 participants were included. The results indicated that video game-based interventions produced positive effects on objectively measured physical health, negative affect and social health, with small effect sizes (d = 0.41, d = 0.26 and d = 0.40, respectively). The magnitude of this effect was moderated by the presence of subclinical conditions of participants, the type of game (exergames), the presence of physical activity, the type of prevention (indicated), non-blinded assignation, and older age of participants. The methodological quality of the studies was acceptable, the weakest area being external validity.
These finding indicate that video game-based interventions may assist adults in leading active aging processes and preventing secondary aging. Although more research is needed, video game-based interventions are a promising and accessible tool for active aging promotion.
The degree to which children and adolescents are infected by and transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. The role of children and adolescents in transmission ...of SARS-CoV-2 is dependent on susceptibility, symptoms, viral load, social contact patterns, and behavior.
To systematically review the susceptibility to and transmission of SARS-CoV-2 among children and adolescents compared with adults.
PubMed and medRxiv were searched from database inception to July 28, 2020, and a total of 13 926 studies were identified, with additional studies identified through hand searching of cited references and professional contacts.
Studies that provided data on the prevalence of SARS-CoV-2 in children and adolescents (younger than 20 years) compared with adults (20 years and older) derived from contact tracing or population screening were included. Single-household studies were excluded.
PRISMA guidelines for abstracting data were followed, which was performed independently by 2 reviewers. Quality was assessed using a critical appraisal checklist for prevalence studies. Random-effects meta-analysis was undertaken.
Secondary infection rate (contact-tracing studies) or prevalence or seroprevalence (population screening studies) among children and adolescents compared with adults.
A total of 32 studies comprising 41 640 children and adolescents and 268 945 adults met inclusion criteria, including 18 contact-tracing studies and 14 population screening studies. The pooled odds ratio of being an infected contact in children compared with adults was 0.56 (95% CI, 0.37-0.85), with substantial heterogeneity (I2 = 94.6%). Three school-based contact-tracing studies found minimal transmission from child or teacher index cases. Findings from population screening studies were heterogenous and were not suitable for meta-analysis. Most studies were consistent with lower seroprevalence in children compared with adults, although seroprevalence in adolescents appeared similar to adults.
In this meta-analysis, there is preliminary evidence that children and adolescents have lower susceptibility to SARS-CoV-2, with an odds ratio of 0.56 for being an infected contact compared with adults. There is weak evidence that children and adolescents play a lesser role than adults in transmission of SARS-CoV-2 at a population level. This study provides no information on the infectivity of children.
The dynamics of networks of neuronal cultures has been recently shown to be strongly dependent on the network geometry and in particular on their dimensionality. However, this phenomenon has been so ...far mostly unexplored from the theoretical point of view. Here we reveal the rich interplay between network geometry and synchronization of coupled oscillators in the context of a simplicial complex model of manifolds called Complex Network Manifold. The networks generated by this model combine small world properties (infinite Hausdorff dimension) and a high modular structure with finite and tunable spectral dimension. We show that the networks display frustrated synchronization for a wide range of the coupling strength of the oscillators, and that the synchronization properties are directly affected by the spectral dimension of the network.
Drug hypersensitivity reactions (DHRs) are a matter of great concern, both for outpatient and in hospital care. The evaluation of these patients is complex, because in vivo tests have a suboptimal ...sensitivity and can be time‐consuming, expensive and potentially risky, especially drug provocation tests. There are several currently available in vitro methods that can be classified into two main groups: those that help to characterize the active phase of the reaction and those that help to identify the culprit drug. The utility of these in vitro methods depends on the mechanisms involved, meaning that they cannot be used for the evaluation of all types of DHRs. Moreover, their effectiveness has not been defined by a consensus agreement between experts in the field. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology has organized a task force to provide data and recommendations regarding the available in vitro methods for DHR diagnosis. We have found that although there are many in vitro tests, few of them can be given a recommendation of grade B or above mainly because there is a lack of well‐controlled studies, most information comes from small studies with few subjects and results are not always confirmed in later studies. Therefore, it is necessary to validate the currently available in vitro tests in a large series of well‐characterized patients with DHR and to develop new tests for diagnosis.
Until a vaccine is developed, a test, trace and isolate strategy is the most effective method of controlling the COVID-19 outbreak. Contact tracing and case isolation are common methods for ...controlling infectious disease outbreaks. However, the effectiveness of any contact tracing system rests on public engagement. Numerous factors may influence an individual's willingness to engage with a contact tracing system. Understanding these factors has become urgent during the COVID-19 pandemic.
To identify facilitators and barriers to uptake of, and engagement with, contact tracing during infectious disease outbreaks.
A rapid systematic review was conducted to identify papers based on primary research, written in English, and that assessed facilitators, barriers, and other factors associated with the uptake of, and engagement with, a contact tracing system.
Four themes were identified as facilitators to the uptake of, and engagement with, contact tracing: collective responsibility; personal benefit; co-production of contact tracing systems; and the perception of the system as efficient, rigorous and reliable. Five themes were identified as barriers to the uptake of, and engagement with, contact tracing: privacy concerns; mistrust and/or apprehension; unmet need for more information and support; fear of stigmatization; and mode-specific challenges.
By focusing on the factors that have been identified, contact tracing services are more likely to get people to engage with them, identify more potentially ill contacts, and reduce transmission.
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•The accuracy of the proposed strategy of control is evaluated through simulations.•Results are compared with respect to vehicles equipped with different powertrains.•The modeled ...vehicle combines energy savings and greater autonomy.
This paper presents the development of an energy management strategy of a Plug-in Hybrid Electric Vehicle (PHEV). In this case, a rule-based optimal controller selects the appropriate operation mode. Furthermore, advantages and drawbacks of such vehicles are compared with respect to other vehicles powered by the most popular powertrain architectures. Simulations are carried out for three predefined drive cycles repeated over different geographic regions with varying CO2 intensities. The results reveal that the proposed controller is able to switch the vehicle’s operating mode according to previous established criteria.
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