DS based 2-DOF PID controller for various integrating processes with time delay.

This study proposes a direct synthesis-based two-degree-of-freedom (2-DOF) controller for various types of integrating processes with time delays. This 2-DOF controller includes a proportional-integral-derivative (PID) controller to enhance load disturbance rejection performance and a set-point filter to improve servo response performance. The main PID controller parameters are expressed as process model parameters and a single adjustment variable, while the set-point filter is composed of PID controller parameters with weighted factors. The adjustment variable is tuned to achieve an optimal balance between response performance and robustness, based on the maximum magnitude of the sensitivity function (Ms). Controller parameters for various Ms values and guidelines for setting these parameters are provided in a consistent formulaic form using a curve-fitting method. These parameter-setting formulas facilitate the accurate implementation of PID controllers with specified Ms values and allow the controller design to be extended to processes with larger dimensionless time delays for a given Ms value. Although a 2-DOF controller was proposed, the adjustment variable for setting the parameters of the main PID controller and the set-point filter was solely the desired time constant. The proposed method was applied to various integrating processes with time delays, and its performance was compared with existing methods reported in the literature, based on performance indices such as settling time, overshoot, integral of absolute error, total variation in input usage, and global performance index. Simulations were conducted using six examples of various integrating processes with time delays to verify the effectiveness and applicability of the proposed controller.

Translational potential of mouse models of human metabolic disease.

Obesity causes significant morbidity and mortality globally. Research in the last three decades has delivered a step-change in our understanding of the fundamental mechanisms that regulate energy homeostasis, building on foundational discoveries in mouse models of metabolic disease. However, not all findings made in rodents have translated to humans, hampering drug discovery in this field. Here, we review how studies in mice and humans have informed our current framework for understanding energy homeostasis, discuss their challenges and limitations, and offer a perspective on how human studies may play an increasingly important role in the discovery of disease mechanisms and identification of therapeutic targets in the future.

Hybrid controller with neural network PID/FOPID operations for two-link rigid robot manipulator based on the zebra optimization algorithm.

The performance of the robotic manipulator is negatively impacted by outside disturbances and uncertain parameters. The system's variables are also highly coupled, complex, and nonlinear, indicating that it is a multi-input, multi-output system. Therefore, it is necessary to develop a controller that can control the variables in the system in order to handle these complications. This work proposes six control structures based on neural networks (NNs) with proportional integral derivative (PID) and fractional-order PID (FOPID) controllers to operate a 2-link rigid robot manipulator (2-LRRM) for trajectory tracking. These are named as set-point-weighted PID (W-PID), set-point weighted FOPID (W-FOPID), recurrent neural network (RNN)-like PID (RNNPID), RNN-like FOPID (RNN-FOPID), NN+PID, and NN+FOPID controllers. The zebra optimization algorithm (ZOA) was used to adjust the parameters of the proposed controllers while reducing the integral-time-square error (ITSE). A new objective function was proposed for tuning to generate controllers with minimal chattering in the control signal. After implementing the proposed controller designs, a comparative robustness study was conducted among these controllers by altering the initial conditions, disturbances, and model uncertainties. The simulation results demonstrate that the NN+FOPID controller has the best trajectory tracking performance with the minimum ITSE and best robustness against changes in the initial states, external disturbances, and parameter uncertainties compared to the other controllers.

Analysis of the relative frequencies of the multipartite BNYVV genomic RNAs in different plants and tissues.

Multipartite virus genomes are composed of two or more segments, each packaged into an independent viral particle. A potential advantage of multipartitism is the regulation of gene expression through changes in the segment copy number. Soil-borne beet necrotic yellow vein virus (BNYVV) is a typical example of multipartism, given its high number of genomic positive-sense RNAs (up to five). Here we analyse the relative frequencies of the four genomic RNAs of BNYVV type B during infection of different host plants (Chenopodium quinoa, Beta macrocarpa and Spinacia oleracea) and organs (leaves and roots). By successfully validating a two-step reverse-transcriptase digital droplet PCR protocol, we show that RNA1 and -2 genomic segments always replicate at low and comparable relative frequencies. In contrast, RNA3 and -4 accumulate with variable relative frequencies, resulting in distinct RNA1 : RNA2 : RNA3 : RNA4 ratios, depending on the infected host species and organ.

Data-driven set-point learning control with ESO and RBFNN for nonlinear batch processes subject to nonrepetitive uncertainties.

This paper proposes an extended state observer (ESO) based data-driven set-point learning control (DDSPLC) scheme for a class of nonlinear batch processes with a priori P-type feedback control structure subject to nonrepetitive uncertainties, by only using the process input and output data available in practice. Firstly, the unknown process dynamics is equivalently transformed into an iterative dynamic linearization data model (IDLDM) with a residual term. A radial basis function neural network is adopted to estimate the pseudo partial derivative information related to IDLDM, and meanwhile, a data-driven iterative ESO is constructed to estimate the unknown residual term along the batch direction. Then, an adaptive set-point learning control law is designed to merely regulate the set-point command of the closed-loop control structure for realizing batch optimization. Robust convergence of the output tracking error along the batch direction is rigorously analyzed by using the contraction mapping approach and mathematical induction. Finally, two illustrative examples from the literature are used to validate the effectiveness and advantage of the proposed design.

IGT/LAZY genes are differentially influenced by light and required for light-induced change to organ angle.

BACKGROUND: Plants adjust their growth orientations primarily in response to light and gravity signals. Considering that the gravity vector is fixed and the angle of light incidence is constantly changing, plants must somehow integrate these signals to establish organ orientation, commonly referred to as gravitropic set-point angle (GSA). The IGT gene family contains known regulators of GSA, including the gene clades LAZY, DEEPER ROOTING (DRO), and TILLER ANGLE CONTROL (TAC). RESULTS: Here, we investigated the influence of light on different aspects of GSA phenotypes in LAZY and DRO mutants, as well as the influence of known light signaling pathways on IGT gene expression. Phenotypic analysis revealed that LAZY and DRO genes are collectively required for changes in the angle of shoot branch tip and root growth in response to light. Single lazy1 mutant branch tips turn upward in the absence of light and in low light, similar to wild-type, and mimic triple and quadruple IGT mutants in constant light and high-light conditions, while triple and quadruple IGT/LAZY mutants show little to no response to changing light regimes. Further, the expression of IGT/LAZY genes is differentially influenced by daylength, circadian clock, and light signaling. CONCLUSIONS: Collectively, the data show that differential expression of LAZY and DRO genes are required to enable plants to alter organ angles in response to light-mediated signals.

The functional maturity of grafted human pluripotent stem cell derived-islets (hSC-Islets) evaluated by the glycemic set point during blood glucose normalizing process in diabetic mice.

Human pluripotent stem cell (hPSCs) derived-pancreatic islets (hSC-islets) are good candidates for cell replacement therapy for patients with diabetes as substitutes for deceased donor-derived islets, because they are pluripotent and have infinite proliferation potential. Grafted hSC-islets ameliorate hyperglycemia in diabetic mice; however, several weeks are needed to normalize the hyperglycemia. These data suggest hSC-islets require maturation, but their maturation process in vivo is not yet fully understood. In this study, we utilized two kinds of streptozotocin (STZ)-induced diabetes model mice by changing the administration timing in order to examine the time course of maturation of hSC-islets and the effects of hyperglycemia on their maturation. We found no hyperglycemia in immune-compromised mice when hSC-islets had been transplanted under their kidney capsules in advance, and STZ was administered 4 weeks after transplantation. Of note, the blood glucose levels of those mice were stably maintained under 100 mg/dl 10 weeks after transplantation; this is lower than the mouse glycemic set point (120-150 mg/dl), suggesting that hSC-islets control blood glucose levels to the human glycemic set point. We confirmed that gene expression of maturation markers of pancreatic beta cells tended to upregulate during 4 weeks after transplantation. Periodical histological analysis revealed that revascularization was observed as early as 1 week after transplantation, but reinnervation in the grafted hSC-islets was not detected at all, even 15 weeks after transplantation. In conclusion, our hSC-islets need at least 4 weeks to mature, and the human glycemic set point is a good index for evaluating ultimate maturity for hSC-islets in vivo.

Mechanisms and predictors of menses resumption once normal weight is reached in anorexia nervosa.

BACKGROUND: In cases of Anorexia Nervosa (AN), achieving weight gain recovery beyond the lower limits set by the World Health Organization and normalizing classical nutritional markers appears to be essential for most patients. However, this is not always adequate to restore menstrual cycles. This discrepancy can cause concern for both patients and healthcare providers, and can impact the medical management of these individuals. Thus, the purpose of this study was to assess the ability of anthropometric and hormonal factors to predict the resumption of menstrual cycles in individuals with anorexia nervosa upon reaching a normal body weight. METHOD: Patients with AN who had achieved a normal Body Mass Index but had not yet resumed their menstrual cycles (referred to as ANRec) were evaluated on two occasions: first at visit 1 and then again 6 months later, provided their body weight remained stable over this period (visit 2). Among the 46 ANRec patients who reached visit 2, they were categorized into two groups: 20 with persistent amenorrhea (PA-ANRec) and 26 who had regained their menstrual cycles (RM-ANRec). Anthropometric measurements, several hormone levels, Luteinizing Hormone (LH) pulsatility over a 4-h period, and LH response to gonadotropin-releasing hormone injection (LH/GnRH) were then compared between the two groups at visit 1. RESULTS: Patients in the RM-ANRec group exhibited higher levels of follicular stimulating hormone, estradiol, inhibin B, LH/GnRH, and lower levels of ghrelin compared to those in the PA-ANRec group. Analysis of Receiver Operating Characteristic curves indicated that having ≥ 2 LH pulses over a 4-h period, LH/GnRH levels ≥ 33 IU/l, and inhibin B levels > 63 pg/ml predicted the resumption of menstrual cycles with a high degree of specificity (87%, 100%, and 100%, respectively) and sensitivity (82%, 80%, and 79%, respectively). CONCLUSIONS: These three hormonal tests, of which two are straightforward to perform, demonstrated a high predictive accuracy for the resumption of menstrual cycles. They could offer valuable support for the management of individuals with AN upon achieving normalized weight. Negative results from these tests could assist clinicians and patients in maintaining their efforts to attain individualized metabolic targets. TRIAL REGISTRATION: IORG0004981.

Once a minimally normal weight has been reached during eating disorder recovery for female patients with anorexia nervosa (AN), the persistence of amenorrhea can be a cause for concern both patient and practitioner. In our study, we have discovered that positive results in biological blood tests, which can be conveniently conducted in an ambulatory setting, offer valuable predictive insights. Specifically, parameters such as LH pulse numbers exceeding 2, LH response to GnRH injection surpassing 33 UI/L, or Inhibin B levels in the blood exceeding 63 pg/mL, can accurately predict the resumption of menstrual cycles in the upcoming months, provided that the patient does not experience weight loss or engage in intense exercise. Conversely, negative results from these tests at this critical juncture in the recovery process can serve as valuable tools to encourage and motivate both the healthcare provider and the patient. By maintaining their efforts and continuing to increase their weight, patients can work towards a more comprehensive restoration of their menstrual cycles.

The Recent Dangers for European Happiness: Is Homeostatic Resilience Sufficient?

In the literature on life satisfaction the author came across the hypothesis that happiness oscillates around a set point given by nurture and nature. This assumption implicitly supposes a homeostatic mechanism, which implies resilience against unhappiness. The present paper aims at the exploration and quantitative description of this resilience at the national level, which may be challenged by military conflicts, pandemics, energy crises, etc. In particular, the researcher would like to know, for which European countries the postulated resilience really exists, where the related national set points are, and whether there are limits of unhappiness below which the homeostatic set points cannot be reached anymore. In order to tackle these research questions, country-specific time series of annual happiness between 2007 and 2019 are analyzed by linear and quadratic regressions, where the current national happiness is the independent and the related following level of happiness the dependent variable. By analyzing the resulting regression equations, it is possible to identify and analyze its mathematical fixed points. Depending on whether they are stable or not, they are either homeostatic set points (equilibria) or critical limits, where homeostasis is destroyed. The present empirical analysis reveals that more than 50% of the analyzed European countries have no homeostasis of happiness. Consequently, these countries are psychologically vulnerable with regard to depressing developments like energy crises or pandemics. The remaining cases do often not display the classical form of homeostasis: they have either a shifting set point or only a narrow range, within which the homeostasis of happiness is maintained. Thus, there are only a few European countries with unlimited resilience against unhappiness and a set point that is stable over time.

Per-pathogen virulence of HIV-1 subtypes A, C and D.

HIV-1 subtypes differ in their clinical manifestations and the speed in which they spread. In particular, the frequency of subtype C is increasing relative to subtypes A and D. We investigate whether HIV-1 subtypes A, C and D differ in their per-pathogen virulence and to what extend this explains the difference in spread between these subtypes. We use data from the hormonal contraception and HIV-1 genital shedding and disease progression among women with primary HIV infection study. For each study participant, we determine the set-point viral load value, CD4+ T cell level after primary infection and CD4+ T cell decline. Based on both the CD4+ T cell count after primary infection and CD4+ T cell decline, we estimate the time until AIDS. We then obtain our newly introduced measure of virulence as the inverse of the estimated time until AIDS. After fitting a model to the measured virulence and set-point viral load values, we tested if this relation varies per subtype. We found that subtype C has a significantly higher per-pathogen virulence than subtype A. Based on an evolutionary model, we then hypothesize that differences in the primary length of infection period cause the observed variation in the speed of spread of the subtypes.

Self-Regulating Adaptive Controller for Oxygen Support to Severe Respiratory Distress Patients and Human Respiratory System Modeling.

Uncontrolled breathing is the most critical and challenging situation for a healthcare person to patients. It may be due to simple cough/cold/critical disease to severe respiratory infection of the patients and resulting directly impacts the lungs and damages the alveoli which leads to shortness of breath and also impairs the oxygen exchange. The prolonged respiratory failure in such patients may cause death. In this condition, supportive care of the patients by medicine and a controlled oxygen supply is only the emergency treatment. In this paper, as a part of emergency support, the intelligent set-point modulated fuzzy PI-based model reference adaptive controller (SFPIMRAC) is delineated to control the oxygen supply to uncomforted breathing or respiratory infected patients. The effectiveness of the model reference adaptive controller (MRAC) is enhanced by assimilating the worthiness of fuzzy-based tuning and set-point modulation strategies. Since then, different conventional and intelligent controllers have attempted to regulate the supply of oxygen to respiratory distress patients. To overcome the limitations of previous techniques, researchers created the set-point modulated fuzzy PI-based model reference adaptive controller, which can react instantly to changes in oxygen demand in patients. Nonlinear mathematical formulations of the respiratory system and the exchange of oxygen with time delay are modeled and simulated for study. The efficacy of the proposed SFPIMRAC is tested, with transport delay and set-point variations in the devised respiratory model.

Fast Track Treatment of Hypothyroidism with Levothyroxine: Reaching Homeostasis within Four Weeks.

With the current clinical method for the treatment of hypothyroidism the target for the optimum individual values for free thyroxine concentrations [FT4] and thyrotropine concentrations [TSH] of the specific patient are unknown. This situation leads to unnecessary long experimental medication administration that can take a period of sometimes one year. In this article a method will be described where hypothyroid patients are characterized with weekly measured FT4 and TSH concentrations during the first three weeks of synthetic thyroxine or levothyroxine (L-T4) treatment to predict their optimum [FT4] and belonging [TSH] endpoint for a euthyroid homeostatic state. The treatment with levothyroxine will start for all patients with a reference dose of 100 µg, which can be adjusted by the treating physician to a more safe and appropriate dose for the individual which is monitored with weekly thyroid function tests to observe the progress. After three weeks all characteristics of the patient can be inferred from the measured data. The final titration target together with the individual thyroxine half life can be calculated. With the known characteristics and the L-T4 titration target the clinician or treating physician has an instrument to reduce the experimental treatment burden for the patient from one year to a maximum of four weeks.

Evolution of Antibody Responses in HIV-1 CRF01_AE Acute Infection: Founder Envelope V1V2 Impacts the Timing and Magnitude of Autologous Neutralizing Antibodies.

Understanding the dynamics of early immune responses to HIV-1 infection, including the evolution of initial neutralizing and antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies, will inform HIV vaccine design. In this study, we assess the development of autologous neutralizing antibodies (ANAbs) against founder envelopes (Envs) from 18 participants with HIV-1 CRF01_AE acute infection. The timing of ANAb development directly associated with the magnitude of the longitudinal ANAb response. Participants that developed ANAbs within 6 months of infection had significantly higher ANAb responses at 1 year (50% inhibitory concentration [IC50] geometric mean titer [GMT] = 2,010 versus 184; P = 0.001) and 2 years (GMT = 3,479 versus 340; P = 0.015), compared to participants that developed ANAb responses after 6 months. Participants with later development of ANAb tended to develop an earlier, potent heterologous tier 1 (92TH023) neutralizing antibody (NAb) response (P = 0.049). CRF01_AE founder Env V1V2 loop lengths correlated indirectly with the timing (P = 0.002, r = -0.675) and directly with magnitude (P = 0.005, r = 0.635) of ANAb responses; Envs with longer V1V2 loop lengths elicited earlier and more potent ANAb responses. While ANAb responses did not associate with viral load, the viral load set point correlated directly with neutralization of the heterologous 92TH023 strain (P = 0.007, r = 0.638). In contrast, a striking inverse correlation was observed between viral load set point and peak ADCC against heterologous 92TH023 Env strain (P = 0.0005, r = -0.738). These data indicate that specific antibody functions can be differentially related to viral load set point and may affect HIV-1 pathogenesis. Exploiting Env properties, such as V1V2 length, could facilitate development of subtype-specific vaccines that elicit more effective immune responses and improved protection. IMPORTANCE Development of an effective HIV-1 vaccine will be facilitated by better understanding the dynamics between the founder virus and the early humoral responses. Variations between subtypes may influence the evolution of immune responses and should be considered as we strive to understand these dynamics. In this study, autologous founder envelope neutralization and heterologous functional humoral responses were evaluated after acute infection by HIV-1 CRF01_AE, a subtype that has not been thoroughly characterized. The evolution of these humoral responses was assessed in relation to envelope characteristics, magnitude of elicited immune responses, and viral load. Understanding immune parameters in natural infection will improve our understanding of protective responses and aid in the development of immunogens that elicit protective functional antibodies. Advancing our knowledge of correlates of positive clinical outcomes should lead to the design of more efficacious vaccines.

Immune-metabolic adaptations in pregnancy: A potential stepping-stone to sepsis.

Physiological shifts during pregnancy predispose women to a higher risk of developing sepsis resulting from a maladapted host-response to infection. Insightful studies have delineated subtle point-changes to the immune system during pregnancy. Here, we present an overlay of these point-changes, asking what changes and when, at a physiological, cellular, and molecular systems-level in the context of sepsis. We identify distinct immune phases in pregnancy delineated by placental hormone-driven changes in homeostasis setpoints of the immune and metabolic systems that subtly mirrors changes observed in sepsis. We propose that pregnancy immune-metabolic setpoint changes impact feedback thresholds that increase risk for a maladapted host-response to infection and thus act as a stepping-stone to sepsis. Defining maternal immune-metabolic setpoint changes is not only vital for tailoring the right diagnostic tools for early management of maternal sepsis but will facilitate an unravelling of the pathophysiological pathways that predispose an individual to sepsis.

Higher central set point of thyroid homeostasis in drug-naïve patients affected by first episode schizophrenia.

AIM: To assess central set point of thyroid homeostasis in drug-naïve patients affected by first episode schizophrenia. METHODS: This cross-sectional study was conducted in Xinxiang city, Henan, China. Patients were drug-naïve patients affected by first episode schizophrenia, aged 14-50 years old and admitted to the "Second Affiliated Hospital of Xinxiang Medical University" from January 2018 to December 2018. Controls were healthy individuals who underwent annual health from Xinxiang city, a community population of the same age and time period. The parameters of "central set point of thyroid homeostasis" were measured by "thyroid-stimulating hormone (TSH) index" and "thyroid feedback quantile-based index". The parameters were compared between schizophrenia patients and controls. Linear regression models adjusted by age and sex were used to assess the association of schizophrenia with the parameters. RESULTS: A total of 235 patients and 121 controls were included in this study. Patients affected by schizophrenia had significantly higher prevalence of hyperthyroxinemia and levels of free T4, "TSH index", and "thyroid feedback quantile-based index" than controls. After adjusting age and sex, schizophrenia was independently associated with the higher level of "TSH index" (adjusted ß 0.33, 95 % confidence interval 0.17, 0.49) and "thyroid feedback quantile-based index" (adjusted ß 0.21, 95 % confidence interval 0.12, 0.30). The results with age and sex matched patients and controls were similar to those observed in the overall study population. CONCLUSION: Higher central set point may be the underlying mechanism of thyroid allostatic load in drug-naïve patients affected first episode schizophrenia.

Obesity: an evolutionary context.

People completely lacking body fat (lipodystrophy/lipoatrophy) and those with severe obesity both show profound metabolic and other health issues. Regulating levels of body fat somewhere between these limits would, therefore, appear to be adaptive. Two different models might be contemplated. More traditional is a set point (SP) where the levels are regulated around a fixed level. Alternatively, dual-intervention point (DIP) is a system that tolerates fairly wide variation but is activated when critically high or low levels are breached. The DIP system seems to fit our experience much better than an SP, and models suggest that it is more likely to have evolved. A DIP system may have evolved because of two contrasting selection pressures. At the lower end, we may have been selected to avoid low levels of fat as a buffer against starvation, to avoid disease-induced anorexia, and to support reproduction. At the upper end, we may have been selected to avoid excess storage because of the elevated risks of predation. This upper limit of control seems to have malfunctioned because some of us deposit large fat stores, with important negative health effects. Why has evolution not protected us against this problem? One possibility is that the protective system slowly fell apart due to random mutations after we dramatically reduced the risk of being predated during our evolutionary history. By chance, it fell apart more in some people than others, and these people are now unable to effectively manage their weight in the face of the modern food glut. To understand the evolutionary context of obesity, it is important to separate the adaptive reason for storing some fat (i.e. the lower intervention point), from the nonadaptive reason for storing lots of fat (a broken upper intervention point). The DIP model has several consequences, showing how we understand the obesity problem and what happens when we attempt to treat it.

Trajectories in life satisfaction before and during COVID-19 with respect to perceived valence and self-efficacy.

Actions taken by governments to counteract the spread of the COVID-19 pandemic led to profound restrictions in daily lives, especially for adolescents and young adults, with closed schools and universities, travel restrictions, and reduction in social contacts. The purpose of the current study is to investigate the development of life satisfaction with assessments before and during the pandemic, including separate measurement occasions during a strict lockdown and when the implemented restrictions were relaxed again. Data are based on the German Personality Panel (GePP) with 1,920 young adults, assessed on four measurement occasions over a period of three years. Using latent change score modeling, we investigate the outbreak of the COVID-19 pandemic with respect to its perception as a critical life event over time. Further, we examine the influence of self-efficacy on change in life-satisfaction, as the belief in one's innate abilities has been shown to promote health related behavior and buffers against effects of negatively perceived critical life events. While average life satisfaction remained stable across time, we found a main effect of perceived positive valence and self-efficacy on latent change in life satisfaction at the within person level. Expressions of self-efficacy did not moderate the influence of the perception of the pandemic on self-reported life satisfaction. This study provides an important contribution to the recent COVID-19 literature as well as to the debate on stability and change of self-reported life satisfaction.

Why does age at HIV infection correlate with set point viral load? An evolutionary hypothesis.

BACKGROUND: Set-point viral load (SPVL) correlates with the age at which people acquire HIV. Although immunosenescence may seem like a parsimonious explanation for this, it does not easily explain the observation that the relationship between age and SPVL attenuates when accounting for source partner SPVL. Here we propose an alternative explanation that encompasses this latter finding: that decreasing risk of acquisition with older age generates a selection bottleneck that selects for more virulent strains with age. METHODS: We adapted a previously published model of HIV transmission and evolution (EvoNetHIV), parameterized here for men who have sex with men (MSM). We conducted a series of simulation experiments that vary seven behavioral or clinical parameters that affect exposure risk as people age. We conducted regressions to determine the mean increase in SPVL per 10-year increase in seroconversion age, with and without source SPVL in the model. RESULTS: All runs generated significant relationships between seroconversion age and SPVL when not including source SPVL. All saw attenuated relationships, most to near 0, with source SPVL included. Four of our behavioral measures (relational duration, age-related homophily, coital frequency, and mean age at relationship formation) had clear effects on this relationship, all in the hypothesized direction. Combining multiple forms of behavioral heterogeneity yielded an increase of 0.056 log10 copies/mL SPVL per 10-year increase in seroconversion age, nearly as large as that seen in two empirical studies of age-SPVL correlations in MSM. CONCLUSION: The higher virulence of HIV among those infected later in life may be partly explained by a combination of selective bottlenecks and behavioral heterogeneity by age. Variation in the strength of this effect across populations may be in part due to different behavioral, epidemiological and clinical conditions, and not require assumptions about differences in patterns of immunosenescence among populations.

Antiobesity drugs before and after bariatric surgery - how to make the best use of them.

Obesity as a chronic, serious, and progressive lifelong disease requires an active approach to treatment. Treatment means necessary adjustment of lifestyle with suitable regular physical activity, including pharmacological or bariatric support. Current pharmacological treatment can be an effective helper in the preparation for the surgical treatment of obesity (bariatric and metabolic operations), and in greater adherence of the patient to the necessary regime changes in life and in preoperative weight reduction. With the lapse of time after surgical treatment, in many cases we indicate the start of pharmacological treatment if the weight increases again. We do not yet know the appropriate types of patients and the exact indications for specific therapeutic modalities - a suitable antiobesity drug or type of bariatric surgery. The best long-term results come from a combination of at least two of these options, along with a lifestyle change. Among modern antiobesity drugs, there are naltrexone-bupropion and liraglutide. Orlistat can be mentioned from older ones.

Improving the applicability of the thermo-physiological human simulator by correcting its local set point skin temperatures.

The thermo-physiological human simulator has been used in many regions for estimating thermal behavior of the locals. The applicability of the human simulator to populations from different regions is, however, questioned due to its lack of consideration for the ethnic diversities in thermoregulation. This study checked the potential of improving the applicability of the Newton human simulator, one of the most popular simulators, by correcting its local set point skin temperatures according to the target population (Chinese as an example). First, new set point skin temperatures were obtained by conducting tests with 101 Chinese under a thermal neutral condition. Then, simulator tests using the original and new set point skin temperatures were conducted separately for evaluating thermal responses of the Chinese under non-neutral conditions. The evaluated skin and core temperatures by the simulators were compared with those measured from the real human tests. It demonstrated that the evaluated skin temperatures are positively related with the set point skin temperatures of the simulator. Adjusting set point skin temperatures according to the Chinese improved the prediction performance of the local skin temperatures, with the root-mean-square-deviation being reduced for over 50% of the body segments. The proposed idea of correcting local set point skin temperatures would contribute to evaluating the thermal interaction between human body and its surroundings with a higher accuracy.