The neurobiology of insulin-like growth factor I: From neuroprotection to modulation of brain states.

After decades of research in the neurobiology of IGF-I, its role as a prototypical neurotrophic factor is undisputed. However, many of its actions in the adult brain indicate that this growth factor is not only involved in brain development or in the response to injury. Following a three-layer assessment of its role in the central nervous system, we consider that at the cellular level, IGF-I is indeed a bona fide neurotrophic factor, modulating along ontogeny the generation and function of all the major types of brain cells, contributing to sculpt brain architecture and adaptive responses to damage. At the circuit level, IGF-I modulates neuronal excitability and synaptic plasticity at multiple sites, whereas at the system level, IGF-I intervenes in energy allocation, proteostasis, circadian cycles, mood, and cognition. Local and peripheral sources of brain IGF-I input contribute to a spatially restricted, compartmentalized, and timed modulation of brain activity. To better define these variety of actions, we consider IGF-I a modulator of brain states. This definition aims to reconcile all aspects of IGF-I neurobiology, and may provide a new conceptual framework in the design of future research on the actions of this multitasking neuromodulator in the brain.

Anti-alignment driven dynamics in the excited states of molecules under strong fields.

We develop two novel models of the H2+ molecule and its isotopes from which we assess quantum-mechanically and semi-classically whether the molecule anti-aligns with the field in the first excited electronic state. The results from both models allow us to predict anti-alignment dynamics even for the HD+ isotope, which possesses a permanent dipole moment. The molecule dissociates at angles perpendicular to the field polarization in both the excited and the ground electronic state, as the population is exchanged through a conical intersection. The quantum mechanical dispersion of the initial state is sufficient to cause full dissociation. We conclude that the stabilization of these molecules in the excited state through bond-hardening under a strong field is highly unlikely.

Simulating the city traffic complexity induced by traffic light periods.

We revisited the global traffic light optimization problem through a cellular automata model, which allows us to address the relationship between the traffic lights and car routing. We conclude that both aspects are not separable. Our results show that a good routing strategy weakens the importance of the traffic light period for mid-densities, thus limiting the parameter space where such optimization is relevant. This is confirmed by analyzing the travel time normalized by the shortest path between the origin and destination. As an unforeseen result, we report what seems to be a power-law distribution for such quantities, indicating that the travel time distribution slowly decreases for long travel times. The power-law exponent depends on the density, traffic light period, and routing strategy, which in this case is parametrized by the tendency of agents to abandon a route if it becomes stagnant. These results could have relevant consequences on how to improve the overall traffic efficiency in a particular city, thus providing insight into useful measurements, which are often counter-intuitive, which may be valuable to traffic controllers that operate through traffic light periods and phases.

Does following optimized routes for single cars improve car routing?

We study the impact of deserting a pre-established path, determined by a navigation software, on the overall city traffic. To do so, we consider a cellular automaton model for vehicular traffic, where the cars travel between two randomly assigned points in the city following three different navigation strategies based on the minimization of the individual paths or travel times. We found, in general, that, above a critical car density, the transport improves in all strategies if we decrease the time that the vehicles persist in trying to follow a particular strategy when a route is blocked, namely, the mean flux increases, the individual travel times decrease, and the fluctuations of density in the streets decrease; consequently, deserting helps prevent traffic jams.

The Game Between a Biased Reviewer and His Editor.

This paper shows that, for a large range of parameters, the journal editor prefers to delegate the choice to review the manuscript to the biased referee. If the peer review process is informative and the review reports are costly for the reviewers, even biased referees with extreme scientific preferences may choose to become informed about the manuscript's quality. On the contrary, if the review process is potentially informative but the reviewer reports are not costly for the referees, the biased reviewer has no incentive to become informed about the manuscript. Furthermore, if the reports are costly for referees but the peer review processes are not potentially informative, the biased reviewers will never become informed. In this paper, we also present a web resource that helps editors to experiment with the review process as a device for information transmission.

Solar wind thermally induced magnetic fluctuations.

A kinetic description of Alfvén-cyclotron magnetic fluctuations for anisotropic electron-proton quasistable plasmas is studied. An analytical treatment, based on the fluctuation-dissipation theorem, consistently shows that spontaneous fluctuations in plasmas with stable distributions significantly contribute to the observed magnetic fluctuations in the solar wind, as seen, for example, in [S. D. Bale et al., Phys. Rev. Lett. 103, 211101 (2009)], even far below from the instability thresholds. Furthermore, these results, which do not require any adjustable parameters or wave excitations, are consistent with the results provided by hybrid simulations. It is expected that this analysis contributes to our understanding of the nature of magnetic fluctuations in the solar wind.

Interaction of Corynebacterium pseudotuberculosis with ovine cells in vitro.

Caseous lymphadenitis is an infectious and contagious disease caused by Corynebacterium pseudotuberculosis, with a worldwide distribution and high prevalence in small ruminant populations. This disease causes significant economic loss in small ruminants through reduced meat, wool, and milk production. C. pseudotuberculosis can also affect horses, domestic and wild large ruminants, swine, and man. It is considered an occupational zoonosis for humans. As part of in vitro investigations of the pathogenesis of C. pseudotuberculosis, this study analyzed its capacity to adhere to and invade the FLK-BLV-044 cell line, derived from ovine embryonic kidney cells. C. pseudotuberculosis showed a measurable capacity to adhere to and invade this cell line with no significant differences between the four strains assessed. The incubation of the cell line at 4ºC, pre-incubation with sugars, complete and heat inactivated antiserum, and heat-killed and ultraviolet-killed bacteria produced a significant (P < 0.05) decrease in the invasion efficiency or inability to invade the cell line. Plate counting and fluorescence studies showed intracellular bacteria for up to 6 days. Non-phagocytic cells may therefore act as a suitable environment for C. pseudotuberculosis survival and play a role in the spread of infection and/or maintenance of a carrier state.

[Do anesthetic techniques influence postoperative outcomes? Part II]. / ¿Influyen las técnicas anestésicas en los resultados postoperatorios? Parte II.

The knowledge of the influence of anesthetic techniques in postoperative outcomes has opened a large field of research in recent years. In this second part, we review some of the major controversies arising from the literature on the impact of anesthetic techniques on postoperative outcomes in 6 areas: postoperative cognitive dysfunction, chronic postoperative pain, cancer recurrence, postoperative nausea/vomiting, surgical outcomes, and resources utilization. The development of protective and preventive anesthetic strategies against short and long-term postoperative complications will probably occupy an important role in our daily anesthetic practice. Dynamic postoperative pain control has been confirmed as one of the basic requirements of accelerated postoperative recovery programs ("fast-track surgery"), and it is also a preventive factor for development of chronic postoperative pain. The weight of anesthetic technique on postoperative immunosuppression is to be defined. The potential influence of anesthesia on cancer recurrence, is a highly controversial area of research. The classic pattern of perioperative fluid therapy may increase postoperative complications. On the other hand, the maintenance of normoglycemia and normothermia was associated with a decreased postoperative morbidity. The high volume of surgical procedures means that the adequacy of human, organizational and technological resources have a major impact on overall costs.

[Do anesthetic techniques influence postoperative outcomes? Part I]. / ¿Influyen las técnicas anestésicas en los resultados postoperatorios? Parte I.

The influence of anesthetic technique on postoperative outcomes has opened a wide field of research in recent years. High-risk patients undergoing non-cardiac surgery are those who have higher incidence of postoperative complications and mortality. A proper definition of this group of patients should focus maximal efforts and resources to improve the results. In view of the significant reduction in postoperative mortality and morbidity in last 20 years, perioperative research should take into account new indicators to investigate the role of anesthetic techniques on postoperative outcomes. Studies focused on the evaluation of intermediate outcomes would probably discriminate better effectiveness differences between anesthetic techniques. We review some of the major controversies arising in the literature about the impact of anesthetic techniques on postoperative outcomes. We have grouped the impact of these techniques into 9 major investigation areas: mortality, cardiovascular complications, respiratory complications, postoperative cognitive dysfunction, chronic postoperative pain, cancer recurrence, postoperative nausea/vomiting, surgical outcomes and resources utilization. In this first part of the review, we discuss the basis on postoperative outcomes research, mortality, cardiovascular and respiratory complications.

[Identifying and prioritising adverse episodes and failures related to patient safety in Pain Treatment Units]. / Identificación y priorización de episodios adversos y fallos relacionados con la seguridad del paciente en las Unidades de Tratamiento del Dolor.

OBJECTIVES: An expert group coordinated by the Andalusian School of Public Health identified the most serious and frequent adverse events in Pain Treatment Units (PTU), as well the failures and underlying causes, as a prior step to preparing preventive actions. The aims of the project were to identify potential adverse events in Pain Treatment Units, identify failures and their underlying causes, and prioritise these failures according to a failure modes and effects analysis (FMEA) tool. MATERIAL AND METHODS: The method employed consisted of a literature search, the selection of an expert group with experience in PTU, creating a catalogue of adverse events using the generation of ideas technique, and putting the FMEA and Risk Priority Index tools into practice. RESULTS: Up to 66 types of adverse events were identified associated with; medication (30), invasive techniques (15), care process (10), patient information and education (6), and clinical practice (5). It was found that up to 101 failures could be triggered by these adverse events, and that 242 causes could lead to these failures. CONCLUSIONS: The results indicated the need to work principally in two directions, improving the care process in the PTU (the health care organisation), and the professional work, this latter having two aspects, improving the clinical practice, and increase professional skills by means of specific training. Communication, whether inter-professional or inter-department, or with the patient and their family, is identified as a key aspect for improvement.

What is the sensitivity and specificity of the peer review process?

In this paper, we introduce the concepts of sensitivity and specificity to mathematically describe the accuracy of the peer review process. Sensitivity refers to the probability that the final decision for a manuscript would be acceptance, provided the manuscript meets the journal standards required for publication (i.e., true positive rate). Specificity refers to the probability that the final decision would be rejection, provided the work does not meet the standards required for publication (i.e., true negative rate). Therefore, in the peer review process, sensitivity measures the ability to correctly accept manuscripts that meet the required standards (true positives) and specificity measures the ability to correctly reject manuscripts that do not meet those quality standards required for publication (true negatives). Sensitivity and specificity values can inform the editor under what conditions the outcome of a peer review process becomes more precise and, therefore, if this does not occur, when the editor must improve the analysis involved in processing the information received from reviewers' reports. Sensitivity and specificity understood in this way can promote the ethical conduct of peer review processes and improve the validity of manuscript editorial decisions.

Pedestrian flow in two dimensions: Optimal psychological stress leads to less evacuation time and decongestion.

Collective motion is an innate ability of all living systems, which depends on physiological and psychosocial factors in the case of humans. Such a collective organization is becoming of great interest in collective motion in human crowds. Using a cellular automaton (CA) simulation model, we demonstrate that emergency egress from a two-dimensional corridor with optimal stress leads to less evacuation time and efficient mass evacuations. We study how three types of stress (i.e., mild stress, optimal stress, and anxiety) described in the literature have a significant impact on the collective dynamics. We found that low-stress levels could decrease the evacuation time in an entire occupied room since agents choose alternative routes rather than the shortest path to the exit and display cooperative behavior. Therefore, the combination of mild and optimal stress can lead to efficient evacuations. Also CA simulations may be used to find safer and more efficient ways to conduct mass evacuation procedures.

Spread of the fascioliasis endemic area assessed by seasonal follow-up of rDNA ITS-2 sequenced lymnaeid populations in Cajamarca, Peru.

Fascioliasis is a worldwide emerging snail-borne zoonotic trematodiasis with a great spreading capacity linked to animal and human movements, climate change, and anthropogenic modifications of freshwater environments. South America is the continent with more human endemic areas caused by Fasciola hepatica, mainly in high altitude areas of Andean regions. The Peruvian Cajamarca area presents the highest human prevalences reported, only lower than those in the Bolivian Altiplano. Sequencing of the complete rDNA ITS-2 allowed for the specific and haplotype classification of lymnaeid snails collected in seasonal field surveys along a transect including 2007-3473 m altitudes. The species Galba truncatula (one haplotype preferentially in higher altitudes) and Pseudosuccinea columella (one haplotype in an isolated population), and the non-transmitting species Lymnaea schirazensis (two haplotypes mainly in lower altitudes) were found. Climatic seasonality proved to influence G. truncatula populations in temporarily dried habitats, whereas L. schirazensis appeared to be more climatologically independent due to its extreme amphibious ecology. Along the southeastern transect from Cajamarca city, G. truncatula and L. schirazensis shared the same site in 7 localities (46.7% of the water collections studied). The detection of G. truncatula in 11 new foci (73.3%), predominantly in northern localities closer to the city, demonstrate that the Cajamarca transmission risk area is markedly wider than previously considered. Lymnaea schirazensis progressively increases its presence when moving away from the city. Results highlight the usefulness of lymnaeid surveys to assess borders of the endemic area and inner distribution of transmission foci. Similar lymnaeid surveys are still in need to be performed in the wide northern and western zones of the Cajamarca city. The coexistence of more than one lymnaeid transmitting species, together with a morphologically indistinguishable non-transmitting species and livestock movements inside the area, conform a complex scenario which poses difficulties for the needed One Health control intervention.

Characterization of the nontrivial and chaotic behavior that occurs in a simple city traffic model.

We explore in detail the nontrivial and chaotic behavior of the traffic model proposed by Toledo et al. [Phys. Rev. E 70, 016107 (2004)] due to the richness of behavior present in the model, in spite of the fact that it is a minimalistic representation of basic city traffic dynamics. The chaotic behavior, previously shown for a given lower bound in acceleration/brake ratio, is examined more carefully and the region in parameter space for which we observe this nontrivial behavior is found. This parameter region may be related to the high sensitivity of traffic flow that eventually leads to traffic jams. Approximate scaling laws are proposed.

Magnetostatic interaction between two bubble skyrmions.

A detailed analytic and numerical analysis of the interaction between two bubble skyrmions has been carried out. The results from the micromagnetic calculations show that when the skyrmions are in the same plane, the magnetic parameters vary weakly as a function of the separation between them. On the other hand, when the skyrmions are located in the same vertical axis, the magnetic parameters show a strong variation as a function of the separation of the skyrmions. In particular, when a magnetic disk is over another, there is a transition from a Bloch-like skyrmion configuration to a Néel-like skyrmion configuration as the distance between the disks decreases, as a consequence of the magnetostatic interaction. Therefore, it is possible to stabilize a bubble skyrmion with a Néel configuration without the Dzyaloshinskii-Moriya interaction. Thus, these results can be used for the control of the skyrmion parameters in magnetic spintronic devices that need to use these configurations.

Knowledge, attitude, and practice regarding COVID-19 outbreak in Bangladesh: An online-based cross-sectional study.

In Bangladesh, an array of measures have been adopted to control the rapid spread of the COVID-19 epidemic. Such general population control measures could significantly influence perception, knowledge, attitudes, and practices (KAP) towards COVID-19. Here, we assessed KAP towards COVID-19 immediately after the lock-down measures were implemented and during the rapid rise period of the outbreak. Online-based cross-sectional study conducted from March 29 to April 19, 2020, involving Bangladeshi residents aged 12-64 years, recruited via social media. After consenting, participants completed an online survey assessing socio-demographic variables, perception, and KAP towards COVID-19. Of the 2017 survey participants, 59.8% were male, the majority were students (71.2%), aged 21-30 years (57.9%), having a bachelor's degree (61.0%), having family income >30,000 BDT (50.0%), and living in urban areas (69.8). The survey revealed that 48.3% of participants had more accurate knowledge, 62.3% had more positive attitudes, and 55.1% had more frequent practices regarding COVID-19 prevention. Majority (96.7%) of the participants agreed 'COVID-19 is a dangerous disease', almost all (98.7%) participants wore a face mask in crowded places, 98.8% agreed to report a suspected case to health authorities, and 93.8% implemented washing hands with soap and water. In multiple logistic regression analyses, COVID-19 more accurate knowledge was associated with age and residence. Sociodemographic factors such as being older, higher education, employment, monthly family income >30,000 BDT, and having more frequent prevention practices were the more positive attitude factors. More frequent prevention practice factors were associated with female sex, older age, higher education, family income > 30,000 BDT, urban area residence, and having more positive attitudes. To improve KAP of general populations is crucial during the rapid rise period of a pandemic outbreak such as COVID-19. Therefore, development of effective health education programs that incorporate considerations of KAP-modifying factors is needed.

Impact of intestinal dysbiosis-related drugs on the efficacy of immune checkpoint inhibitors in clinical practice.

PURPOSE: Intestinal dysbiosis has emerged as a biomarker of response to immune checkpoint inhibitors (ICIs). It can be caused by antibiotics, although it may also result from the use of other drugs that have been studied to a lesser extent. The objective of our study was to analyze the association between the use of potentially dysbiosis-related drugs and survival in patients treated with ICIs in the clinical practice. MATERIALS AND METHODS: A retrospective, multicenter, cohort study was conducted. Clinicopathological variables were collected and the concomitant use of drugs was analyzed. A descriptive analysis of variables and overall survival, estimated by the Kaplan-Meier method, was performed, and association with various independent variables was assessed using Cox regression. RESULTS: We included 253 patients, mainly with non-small cell lung cancer and melanoma. The most commonly used drugs were acid reducers, prescribed to 55.3% of patients, followed by corticosteroids (37.9%), anxiolytic drugs (35.6%), and antibiotics (20.5%). The use of acid reducers (9 vs. 18 months, P < .0001), antibiotics (7 vs. 15 months, P < .017), anxiolytic drugs (8 vs. 16 months, P < .015), and corticosteroids (6 vs. 19 months, P < .00001) was associated with poorer overall survival. Furthermore, the greater the number of drugs used concomitantly with ICIs, the higher the risk of death (1 drug: hazard ratio, 1.88; CI 95%, 1.07-3.30; 4 drugs: hazard ratio, 4.19; CI9 5%, 1.77-9.92; P < .001). CONCLUSION: Response to ICIs may be influenced by the use of drugs that lead to intestinal dysbiosis. Although a confirmatory prospective controlled study is required, our findings should be taken into account when analyzing ICI efficacy.

Magnetic nanoparticles for local drug delivery using magnetic implants.

This chapter is a brief description of the state of the art of the field of targeted drug delivery using magnetic implants. It describes the advantages and drawbacks of the use of internal magnets to concentrate magnetic nanoparticles near tumor locations, and the different approaches to this task performed in vitro and in vivo reviewed in literature are presented.

Building a better methane generation model: Validating models with methane recovery rates from 35 Canadian landfills.

The German EPER, TNO, Belgium, LandGEM, and Scholl Canyon models for estimating methane production were compared to methane recovery rates for 35 Canadian landfills, assuming that 20% of emissions were not recovered. Two different fractions of degradable organic carbon (DOC(f)) were applied in all models. Most models performed better when the DOC(f) was 0.5 compared to 0.77. The Belgium, Scholl Canyon, and LandGEM version 2.01 models produced the best results of the existing models with respective mean absolute errors compared to methane generation rates (recovery rates + 20%) of 91%, 71%, and 89% at 0.50 DOC(f) and 171%, 115%, and 81% at 0.77 DOC(f). The Scholl Canyon model typically overestimated methane recovery rates and the LandGEM version 2.01 model, which modifies the Scholl Canyon model by dividing waste by 10, consistently underestimated methane recovery rates; this comparison suggested that modifying the divisor for waste in the Scholl Canyon model between one and ten could improve its accuracy. At 0.50 DOC(f) and 0.77 DOC(f) the modified model had the lowest absolute mean error when divided by 1.5 yielding 63 +/- 45% and 2.3 yielding 57 +/- 47%, respectively. These modified models reduced error and variability substantially and both have a strong correlation of r = 0.92.

Outcome of treating advanced neuroendocrine tumours with radiolabelled somatostatin analogues.

OBJECTIVES: To evaluate the initial response and outcomes (quality of life and presence of side effects) in patients with advanced neuroendocrine tumours (NET) after treatment with radiolabelled somatostatin analogues: (90)Y-DOTATyr3- octreotide ((90)Y-DOTATOC) and (177)Lu-DOTA-Tyr3- octreotate ((177)Lu-DOTATATE). MATERIAL AND METHODS: The study included 5 patients with advanced NET referred to European centres for treatment with (90)Y-DOTATOC and (177)Lu-DOTATATE after lack of response to conventional treatment. The mean age was 45.6 years (29-68 years). Response to therapy was assessed according to: (1) RECIST criteria, as complete response, partial response, stable disease or disease progression, (2) post-treatment survival time and (3) quality of life, using the Karnofsky performance index. RESULTS: All patients survived for >20 months after treatment; mean survival time was 28 months. At the time of writing, three of the patients are alive after 20, 26 and 37 months. Partial response was observed in one patient, stable disease in three and disease progression in the fifth patient. A good-to-excellent post-treatment quality of life was observed in all patients. CONCLUSION: Therapy with radiolabelled somatostatin analogues showed promising results in patients with advanced NET, with a partial response or disease stabilisation in four of the five patients, who have enjoyed an extended survival period and an improved quality of life.