[The Immune System of the Critically Ill Patient]. / Das Immunsystem des kritisch Kranken.

Critically ill patients often experience a dysregulated immune response, leading to immune dysfunction. Sepsis, trauma, severe infections, and certain medical conditions can trigger a state of systemic inflammation, known as the cytokine storm. This hyperactive immune response can cause collateral damage to healthy tissues and organs, exacerbating the patient's condition. On the other hand, some critically ill patients may suffer from immune paralysis which can increase the risk of nosocomial infections.Fever is an evolutionary adaptation that evolved as an effective defense mechanism to fight invading pathogens. By raising body temperature, fever enhances the immune response, inhibits pathogen growth, promotes recovery, and aids in the formation of immune memory. Understanding the role of fever in the context of immune defense is crucial for optimizing medical interventions and supporting the body's natural ability to combat infections.Future Directions: Advancements in immunology research and technology hold promise for better understanding the immune system's complexities in critically ill patients. Personalized medicine approaches may be developed to tailor therapies to individual patients based on their immune profile, optimizing treatment outcomes. Based on recent studies prognostic parameters such as lymphocyte count, IL-10 concentration and mHLA-DR expression can be used to stratify the immunological response pattern in septic patients.Conclusion: The immune system's response in critically ill patients is a multifaceted process, involving intricate interactions between various immune cells, cytokines, and organs. Striking the delicate balance between immune activation and suppression remains a significant challenge in clinical practice. Continued research and therapeutic innovations are vital to improve patient outcomes and reduce the burden of critical illness on healthcare systems.

International Round Robin Test of Thermoelectric Generator Modules.

The status of metrology for the characterization of thermoelectric generator modules (TEM) is investigated in this work by an international round robin (RR) test including twelve laboratories from nine countries on three continents. Measurements have been performed with three samples of a Bi2Te3-based commercial TEM type, which has prevailed over three competing types during previous tests on the short- and long-term stability. A comparison of temperature-dependent results is provided up to 200 °C hot side temperature for the maximum power output Pmax, the incident heat flow Q˙In (at maximum efficiency conditions), and the maximum efficiency ηmax. Data evaluation from all RR participants reveals maximum standard deviations for these measurands of 27.2% (Pmax), 59.2% (Q˙In), and 25.9% (ηmax). A comparison between RR data sets and reference data from manufacturer specifications shows high deviations of up to 46%, too. These deviations reflect the absence of measurement guidelines and reference samples and confirm the need for improvements in the standardization of TEM metrology. Accordingly, the results of the RR are presented against the background of our own investigations on the uncertainty budgets for the determination of the abovementioned TEM properties using inhouse-developed characterization facilities, which comprise reference and absolute measurement techniques for the determination of heat flow.

Impact of the Dopant Species on the Thermomechanical Material Properties of Thermoelectric Mg2Si0.3Sn0.7.

Thermoelectric generators are an excellent option for waste heat reuse. Materials for such devices have seen their thermoelectric properties improving constantly. The functioning of a generator, however, does not only depend on thermoelectric properties. Thermal and mechanical properties play a decisive role in the feasibility of any thermoelectric generator. To shed light on the properties exhibited by thermoelectric materials, we present the temperature dependent characterization of Young's modulus and coefficient of thermal expansion for Mg2Si0.3Sn0.7. Comparing undoped to Bi-doped n-type and Li-doped p-type material, we investigated the influence of doping in the relevant temperature regime and found the influences to be minor, proving similar properties for n- and p-type. We found a Young's modulus of 84 GPa for the p-type and 83 GPa for the n-type, similar to that of the undoped compound with 85 GPa. The thermal expansion coefficients of undoped, as well as n- and p-type were equally similar with values ranging from 16.5 to 17.5 × 10-6 1/K. A phase analysis was performed to further compare the two materials, finding a similar phase distribution and microstructure. Finally, using the gathered data, estimations on the possible thermally induced stresses under a temperature difference are provided to evaluate the relevance of knowing temperature dependent thermal and mechanical properties.

Overcoming Asymmetric Contact Resistances in Al-Contacted Mg2(Si,Sn) Thermoelectric Legs.

Thermoelectric generators are a reliable and environmentally friendly source of electrical energy. A crucial step for their development is the maximization of their efficiency. The efficiency of a TEG is inversely related to its electrical contact resistance, which it is therefore essential to minimize. In this paper, we investigate the contacting of an Al electrode on Mg2(Si,Sn) thermoelectric material and find that samples can show highly asymmetric electrical contact resistivities on both sides of a leg (e.g., 10 µΩ·cm2 and 200 µΩ·cm2). Differential contacting experiments allow one to identify the oxide layer on the Al foil as well as the dicing of the pellets into legs are identified as the main origins of this behavior. In order to avoid any oxidation of the foil, a thin layer of Zn is sputtered after etching the Al surface; this method proves itself effective in keeping the contact resistivities of both interfaces equally low (<10 µΩ·cm2) after dicing. A slight gradient is observed in the n-type leg's Seebeck coefficient after the contacting with the Zn-coated electrode and the role of Zn in this change is confirmed by comparing the experimental results to hybrid-density functional calculations of Zn point defects.

Discrepancy between Constant Properties Model and Temperature-Dependent Material Properties for Performance Estimation of Thermoelectric Generators.

The efficiency of a thermoelectric (TE) generator for the conversion of thermal energy into electrical energy can be easily but roughly estimated using a constant properties model (CPM) developed by Ioffe. However, material properties are, in general, temperature (T)-dependent and the CPM yields meaningful estimates only if physically appropriate averages, i.e., spatial averages for thermal and electrical resistivities and the temperature average (TAv) for the Seebeck coefficient (α), are used. Even though the use of αTAv compensates for the absence of Thomson heat in the CPM in the overall heat balance, we find that the CPM still overestimates performance (e.g., by up to 6% for PbTe) for many materials. The deviation originates from an asymmetric distribution of internally released Joule heat to either side of the TE leg and the distribution of internally released Thomson heat between the hot and cold side. The Thomson heat distribution differs from a complete compensation of the corresponding Peltier heat balance in the CPM. Both effects are estimated quantitatively here, showing that both may reach the same order of magnitude, but which one dominates varies from case to case, depending on the specific temperature characteristics of the thermoelectric properties. The role of the Thomson heat distribution is illustrated by a discussion of the transport entropy flow based on the α(T) plot. The changes in the lateral distribution of the internal heat lead to a difference in the heat input, the optimum current and thus of the efficiency of the CPM compared to the real case, while the estimate of generated power at maximum efficiency remains less affected as it is bound to the deviation of the optimum current, which is mostly <1%. This deviation can be corrected to a large extent by estimating the lateral Thomson heat distribution and the asymmetry of the Joule heat distribution. A simple guiding rule for the former is found.

Best-practice IgM- and IgA-enriched immunoglobulin use in patients with sepsis.

BACKGROUND: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Despite treatment being in line with current guidelines, mortality remains high in those with septic shock. Intravenous immunoglobulins represent a promising therapy to modulate both the pro- and anti-inflammatory processes and can contribute to the elimination of pathogens. In this context, there is evidence of the benefits of immunoglobulin M (IgM)- and immunoglobulin A (IgA)-enriched immunoglobulin therapy for sepsis. This manuscript aims to summarize current relevant data to provide expert opinions on best practice for the use of an IgM- and IgA-enriched immunoglobulin (Pentaglobin) in adult patients with sepsis. MAIN TEXT: Sepsis patients with hyperinflammation and patients with immunosuppression may benefit most from treatment with IgM- and IgA-enriched immunoglobulin (Pentaglobin). Patients with hyperinflammation present with phenotypes that manifest throughout the body, whilst the clinical characteristics of immunosuppression are less clear. Potential biomarkers for hyperinflammation include elevated procalcitonin, interleukin-6, endotoxin activity and C-reactive protein, although thresholds for these are not well-defined. Convenient biomarkers for identifying patients in a stage of immune-paralysis are still matter of debate, though human leukocyte antigen-antigen D related expression on monocytes, lymphocyte count and viral reactivation have been proposed. The timing of treatment is potentially more critical for treatment efficacy in patients with hyperinflammation compared with patients who are in an immunosuppressed stage. Due to the lack of evidence, definitive dosage recommendations for either population cannot be made, though we suggest that patients with hyperinflammation should receive an initial bolus at a rate of up to 0.6 mL (30 mg)/kg/h for 6 h followed by a continuous maintenance rate of 0.2 mL (10 mg)/kg/hour for ≥ 72 h (total dose ≥ 0.9 g/kg). For immunosuppressed patients, dosage is more conservative (0.2 mL [10 mg]/kg/h) for ≥ 72 h, without an initial bolus (total dose ≥ 0.72 g/kg). CONCLUSIONS: Two distinct populations that may benefit most from Pentaglobin therapy are described in this review. However, further clinical evidence is required to strengthen support for the recommendations given here regarding timing, duration and dosage of treatment.

Developing Contacting Solutions for Mg2Si1-xSnx-Based Thermoelectric Generators: Cu and Ni45Cu55 as Potential Contacting Electrodes.

Magnesium silicides can be used for thermoelectric energy conversion as high values of figure of merit zT were obtained for n-type (1.4 at 500 °C) and p-type (0.55 at 350 °C) materials. This, however, needs to be complemented by low resistive and stable contacting to ensure long-term thermogenerator operation and minimize losses. In this study, we selected Cu and Ni45Cu55 as contacting electrodes for their high electrical conductivity, similar coefficient of thermal expansion (CTE), and good adhesion to Mg2(Si,Sn). Both electrodes were joined to Mg2Si0.3Sn0.7 pellets by hot pressing in a current-assisted press. Microstructural changes near the interface were analyzed using SEM/EDX analysis, and the specific electrical contact resistance rc was estimated using a traveling potential probe combined with local Seebeck scanning. Good contacting was observed with both electrode materials. Results show low rc with Cu, suitable for applications, for both n- and p-type silicides (<10 µΩ·cm2), with the occurrence of wide, highly conductive diffusion regions. Ni45Cu55 joining also showed relatively low rc values (∼30 µΩ·cm2) for n- and p-type but had a less inhomogeneous reaction layer. We also performed annealing experiments with Cu-joined samples at 450 °C for 1 week to investigate the evolution of the contact regions under working temperatures. rc values increased (up to ∼100 µΩ·cm2) for annealed n-type samples but remained low (<10 µΩ·cm2) for p-type. Therefore, Cu is a good contacting solution for p-type Mg2(Si,Sn) and a potential one for n-type if the diffusion causing contact property degradation can be prevented.

Structural and Functional Properties of the Thin Film System Ti-Ni-Si.

The thin film system Ti-Ni-Si was investigated using methods of combinatorial materials science. A thin film composition spread library of the system was fabricated using combinatorial magnetron sputtering. The functional properties Seebeck coefficient, electrical resistivity, and luminance were determined using high-throughput characterization techniques. A thin-film phase diagram was established by the assessment of high-throughput X-ray diffraction results. Correlations between composition, phase constitution, and functional properties with focus on the binary composition space are discussed.

High efficiency Mg2(Si,Sn)-based thermoelectric materials: scale-up synthesis, functional homogeneity, and thermal stability.

Considering the need for large quantities of high efficiency thermoelectric materials for industrial applications, a scalable synthesis method for high performance magnesium silicide based materials is proposed. The synthesis procedure consists of a melting step followed by high energy ball milling. All the materials synthesized via this method demonstrated not only high functional homogeneity but also high electrical conductivity and Seebeck coefficients of around 1000 Ω-1 cm-1 and -200 µV K-1 at 773 K, respectively. The measured values were similar for all the samples extracted from the ∅50 mm and ∅70 mm compacted pellets and were stable upon thermal cycling. Thermal stability experiments from 168 hours to 720 hours at 723 K revealed no significant change in the material properties. The low thermal conductivity of ∼2.5 W m-1 K-1 at 773 K led to a maximum figure of merit, zT max, of 1.3 at the same temperature and an average value, zT avg, of 0.9 between 300 K and 773 K, which enables high efficiency in future silicide-based thermoelectric generators.

Predictors of Outcomes in Patients with Prolonged Weaning with Focus on Respiratory Tract Pathogens and Infection.

BACKGROUND: The impact of respiratory tract pathogens and infection on outcomes in patients with prolonged weaning is largely unknown. OBJECTIVE: We studied predictors of weaning outcomes (death and failure to achieve spontaneous ventilation) in a population treated during a 3.5-year period in a specialized and certified weaning centre. METHODS: Patient data were retrieved retrospectively from the clinical charts. Complete datasets were available in 173 patients. The following parameters were investigated as potential predictors of both endpoints: age; comorbidities; tracheobronchial pathogens; bacteraemia, pneumonia and number of pneumonias; and number of inhouse treatment cycles (none vs. ≥1). RESULTS: Tracheobronchial pathogens, pneumonia, bacteraemia and the number of antibiotic cycles all significantly increased weaning duration and hospitalisation times. Independent predictors of death were atrial fibrillation (OR 2.6, 95% CI 1.2-5.8, p = 0.02) and tracheobronchial multiresistant Pseudomonas aeruginosa (OR 3.9, 95% CI 1.4-11.0, p = 0.01). Independent predictors of failure to achieve spontaneous ventilation included chronic obstructive pulmonary disease (OR 2.8, 95% CI 1.0-7.8, p = 0.045); neuromuscular disease (OR 8.3, 95% CI 1.2-27.2, p = 0.02); tracheobronchial P. aeruginosa (OR 3.3, 95% CI 1.3-9.3, p = 0.01); Stenotrophomonas maltophilia (OR 7.9, 95% CI 1.4-51.6, p = 0.02); and pneumonia (OR 4.4, 95% CI 1.5-10.9, p = 0.003). CONCLUSIONS: The impact of respiratory tract pathogens and infection on weaning outcomes was remarkable. Predictors of death and failure to achieve spontaneous ventilation differed considerably. A priority may be to investigate preventive strategies against colonisation and infection with respiratory pathogens, particularly P. aeruginosa.

Nanostructured Composites of Bi1-xSbx Nanoparticles and Carbon Nanotubes and the Characterization of Their Thermoelectric Properties.

The impact of inclusions of carbon nanotubes (CNT) on the thermoelectric properties of nanostructured Bi1-xSbx alloys with an Sb content between 10 and 20% was investigated for varying amounts of CNT. Three series of Bi1-xSbx pellets with 0, 0.3, and 0.5 wt % CNT were synthesized by mechanical alloying followed by uniaxial pressing. The resistivity was investigated in the temperature range from 30 to 500 K, revealing an enlargement of the band gap due to nanostructuring of the Bi1-xSbx alloy, which is even more pronounced for alloys including CNT. This enlargement is attributed to a modification of the interface between the Bi1-xSbx nanoparticles by a graphene-like coating, which is formed during the fabrication process due to the addition of CNT. Measurements of the Seebeck coefficient and the thermal conductivity were also performed to determine the thermoelectric properties. In total, the CNT-containing samples show a significant improvement of the figure of merit up to 250% for the Bi0.88Sb0.12 composition with 0.3 wt % CNT due to the interface modification between the nanoparticles, demonstrating the beneficial effect of CNT on the thermoelectric properties.

Dispersion of Multi-Walled Carbon Nanotubes in Skutterudites and Its Effect on Thermoelectric and Mechanical Properties.

Filled cobalt-antimony based skutterudites have proven themselves as very promising thermoelectric materials for generator applications in an intermediate temperature range between 400 and 800 K due to their high figure of merit. Besides the functional thermoelectric properties also the skutterudites' mechanical properties play an important role to withstand external mechanical and internal thermomechanical loads during operation. Properties of interest are hardness as well as fracture toughness and resistance to fatigue. Carbon nano tubes are well known for their high tensile strength and may therefore be used to increase the mechanical strength of composite materials. Additionally, the thermoelectric properties of the composite material might benefit from the high electrical conductivity of carbon nano tubes and increased phonon scattering at interfaces between matrix and carbon nano tube. A main precondition for benefiting from embedded nano-tubes is to achieve a homogeneous distribution of the CNTs and good adhesion between carbon nano tube and matrix material. In this work we present the influence of the introduction of multi-walled carbon nano tubes on the thermoelectric and mechanical properties of p-type skutterudites Ce(0.14)La(0.06)Co(2)Fe(2)Sb(12). The influence of different carbon nano tube concentrations and preparation routes on the resulting composite material's thermoelectric, mechanical and microstructural properties is studied. A reduction of electrical and thermal conductivity as well as fracture strength is observed with increasing carbon nano tube content which is attributed to strong agglomeration of the nano tubes. The results underline the pivotal role of a homogeneous distribution of the carbon nano tubes for improving the mechanical properties of skutterudites.

Novel solution route synthesis of low thermal conductivity nanocrystalline bismuth telluride.

A novel synthesis approach based on a solution route has been developed for the fabrication of nanocrystalline bismuth telluride. The method consists of dissolving both bismuth and tellurium into the same organic solvent with the assistance of complexing agents and one-step coprecipitation of bismuth telluride. The synthesized nanocrystalline bismuth telluride powders possess rhombohedral crystal structure and are nanosheet/nanorod-like with an average size of between 30 and 40 nm. The thermal conductivity of the hot-pressed compact consolidated from the as-synthesized nanopowders is 0.39-0.45 Wm(-1)K(-1) in the temperature range of 323 to 523 K, which is at most one third of that of bulk bismuth telluride-based materials reported in the literature. Such low thermal conductivity of the investigated bismuth telluride is mainly attributed to substantially high concentration of grain boundaries provided by nanostructuring to scatter phonons intensively.

Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: Part II. Treatment.

BACKGROUND: Invasive candidiasis and candidemia are frequently encountered in the nosocomial setting particularly in the intensive care unit (ICU). OBJECTIVE AND METHODS: To review the current management of invasive candidiasis and candidemia in non-neutropenic adult ICU patients based on a review of the literature and an European expert panel discussion. RESULTS AND CONCLUSIONS: Empiric and directed treatment for invasive candidiasis are predicated on the hemodynamic status of the patient. Unstable patients may benefit from broad-spectrum antifungal agents, which can be narrowed once the patient has stabilized and the identity of the infecting species is established. In stable patients, a more classical approach using fluconazole may be satisfactory provided that the patient is not colonized with fluconazole resistant strains or there has been recent past exposure to an azole (<30 days). In contrast, pre-emptive therapy is based on the presence of surrogate markers.

Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: Part I. Epidemiology and diagnosis.

BACKGROUND: Invasive candidiasis and candidemia are frequently encountered in the nosocomial setting, particularly in the intensive care unit (ICU). OBJECTIVES AND METHODS: To review the current management of invasive candidiasis and candidemia in non-neutropenic adult ICU patients based on a review of the literature and a European expert panel discussion. RESULTS AND CONCLUSIONS: Candida albicans remains the most frequently isolated fungal species followed by C. glabrata. The diagnosis of invasive candidiasis involves both clinical and laboratory parameters, but neither of these are specific. One of the main features in diagnosis is the evaluation of risk factor for infection which will identify patients in need of pre-emptive or empiric treatment. Clinical scores were built from those risk factors. Among laboratory diagnosis, a positive blood culture from a normally sterile site provides positive evidence. Surrogate markers have also been proposed like 1,3 beta-D: glucan level, mannans, or PCR testing. Invasive candidiasis and candidemia is a growing concern in the ICU, apart from cases with positive blood cultures or fluid/tissue biopsy, diagnosis is neither sensitive nor specific. The diagnosis remains difficult and is usually based on the evaluation of risk factors.

Susceptible, intermediate, and resistant - the intensity of antibiotic action.

INTRODUCTION: To date, the resistance of infectious agents has been assessed by widely varying criteria in different countries. Therefore, published data on resistance often cannot be meaningfully compared. In Germany, different laboratories can potentially report different results for identical microorganisms, since there is no uniform system for categorization. This situation is unsatisfactory. METHODS: Selective literature review and evaluation of committee reports. RESULTS: The new ISO standard 20776 for determination of the resistance of infectious agents and the harmonized evaluation system of the European Society for Clinical Microbiology and Infectious Diseases provide a new basis for susceptibility testing. The categorization of infectious agents as "susceptible," "intermediate," or "resistant" to particular antibiotics will become more reliable and will be consistent throughout Europe. DISCUSSION: For a number of antibiotics, the criteria for evaluation of infectious agents as "susceptible," "intermediate", or "resistant" will change. Comparability with earlier resistance data will be compromised. However, the new evaluation criteria reflect current knowledge on the pharmacokinetics and pharmacodynamics of antimicrobial substances.

Acute respiratory distress syndrome and pneumonia: a comprehensive review of clinical data.

Acute respiratory distress syndrome (ARDS) and pneumonia are closely correlated in the critically ill patient. Whereas ARDS is often complicated by nosocomial pneumonia, pulmonary infection is also the most frequent single cause of ARDS. The prevalence of pneumonia during the course of ARDS seems to be particularly high, but whether persons with ARDS are more susceptible to pneumonia or simply have more risk factors remains unknown because of methodological limitations. Recent research suggests that host factors have a major bearing on the development of ARDS. To date, sepsis seems to be the principal link between pneumonia and ARDS. However, prospective observational data on this supposed sequence are not available. The individual role of specific pathogens for the development of ARDS is difficult to assess, because prospective studies are missing. Respiratory viruses have received particular attention, but this review suggests that infections with coronavirus and avian influenza virus (H5N1) are associated with a high incidence of ARDS.