Beyond the microcirculation: sequestration of infected red blood cells and reduced flow in large draining veins in experimental cerebral malaria.

Sequestration of infected red blood cells (iRBCs) in the microcirculation is a hallmark of cerebral malaria (CM) in post-mortem human brains. It remains controversial how this might be linked to the different disease manifestations, in particular brain swelling leading to brain herniation and death. The main hypotheses focus on iRBC-triggered inflammation and mechanical obstruction of blood flow. Here, we test these hypotheses using murine models of experimental CM (ECM), SPECT-imaging of radiolabeled iRBCs and cerebral perfusion, MR-angiography, q-PCR, and immunohistochemistry. We show that iRBC accumulation and reduced flow precede inflammation. Unexpectedly, we find that iRBCs accumulate not only in the microcirculation but also in large draining veins and sinuses, particularly at the rostral confluence. We identify two parallel venous streams from the superior sagittal sinus that open into the rostral rhinal veins and are partially connected to infected skull bone marrow. The flow in these vessels is reduced early, and the spatial patterns of pathology correspond to venous drainage territories. Our data suggest that venous efflux reductions downstream of the microcirculation are causally linked to ECM pathology, and that the different spatiotemporal patterns of edema development in mice and humans could be related to anatomical differences in venous anatomy.

Peroral endoscopic myotomy: a two-center retrospective study of practice and adverse events.

Background and study aims: Peroral endoscopic myotomy (POEM) is the preferred technique for the treatment of esophageal motility disorders and is less invasive than surgery. This study was performed to compare two university centers in the practice of POEM, in terms of efficacy and adverse events, for the treatment of esophageal motility disorder. Patients and methods: Retrospective comparative study of patients undergoing a POEM between September 2020 and December 2022 from the University Hospital of Liège (Belgium) and Besançon (France). The clinical success was defined by an Eckardt score ≤ 3 after the procedure. Results: Fifty-five patients were included. In both centers, 87,3% of the patients had achalasia (mostly type II), and 12,7% had another esophageal motility disorder. The use of antibiotic prophylaxis was systematic in Liège center but not in Besançon center (100% and 9.1% respectively). The mean value of the post-operative Eckardt score was 1.55± 2.48 in both center with 93.2% of patients with a score ≤ 3 (92% in Besançon and 94.74% in Liège). The rate of adverse event was generally low. There were two minor adverse events more frequent in Liège, clinical capnomediastinum and pain at day one, but they were managed with conservative treatment. Only 7.3% of the total patients had an infectious phenomenon that did not correlate with the use of antibiotic prophylaxis. Conclusion: The post-operative Eckardt score and the adverse event rate were comparable between the university centers. This study confirmed that POEM is a safe and effective technique. It also showed that using an antibiotic prophylaxis does not influence the development of infectious adverse events.

Evaluation of a machine learning tool for the early identification of patients with undiagnosed psoriatic arthritis - A retrospective population-based study.

Background: Psoriatic arthritis (PsA), an immune-mediated chronic inflammatory skin and joint disease, affects approximately 0.27% of the adult population, and 20% of patients with psoriasis. Up to 10% of psoriasis patients are estimated for having undiagnosed PsA. Early diagnosis and treatment can prevent irreversible joint damage, disability and deformity. Questionnaires for screening to identify undiagnosed PsA patients require patient and physician involvement. Objective: To evaluate a proprietary machine learning tool (PredictAI™) developed for identification of undiagnosed PsA patients 1-4 years prior to the first time that they were suspected of having PsA (reference event). Methods: This retrospective study analyzed data of the adult population from Maccabi Healthcare Service between 2008 and 2020. We created 2 cohorts: The general adult population ("GP Cohort") including patients with and without psoriasis and the Psoriasis cohort ("PsO Cohort") including psoriasis patients only. Each cohort was divided into two non-overlapping train and test sets. The PredictAI™ model was trained and evaluated with 3 years of data predating the reference event by at least one year. Receiver operating characteristic (ROC) analysis was used to investigate the performance of the model, built using gradient boosted trees, at different specificity levels. Results: Overall, 2096 patients met the criteria for PsA. Undiagnosed PsA patients in the PsO cohort were identified with a specificity of 90% one and four years before the reference event, with a sensitivity of 51% and 38%, and a PPV of 36.1% and 29.6%, respectively. In the GP cohort and with a specificity of 99% and for the same time windows, the model achieved a sensitivity of 43% and 32% and a PPV of 10.6% and 8.1%, respectively. Conclusions: The presented machine learning tool may aid in the early identification of undiagnosed PsA patients, and thereby promote earlier intervention and improve patient outcomes.

Identifying content to improve risk assessment communications within the Risk Profile: Literature reviews and focus groups with expert and non-expert stakeholders.

OBJECTIVE: To improve consumer decision making, the results of risk assessments on food, feed, consumer products or chemicals need to be communicated not only to experts but also to non-expert audiences. The present study draws on evidence from literature reviews and focus groups with diverse stakeholders to identify content to integrate into an existing risk assessment communication (Risk Profile). METHODS: A combination of rapid literature reviews and focus groups with experts (risk assessors (n = 15), risk managers (n = 8)), and non-experts (general public (n = 18)) were used to identify content and strategies for including information about risk assessment results in the "Risk Profile" from the German Federal Institute for Risk Assessment. Feedback from initial focus groups was used to develop communication prototypes that informed subsequent feedback rounds in an iterative process. A final prototype was validated in usability tests with experts. RESULTS: Focus group feedback and suggestions from risk assessors were largely in line with findings from the literature. Risk managers and lay persons offered similar suggestions on how to improve the existing communication of risk assessment results (e.g., including more explanatory detail, reporting probabilities for individual health impairments, and specifying risks for subgroups in additional sections). Risk managers found information about quality of evidence important to communicate, whereas people from the general public found this information less relevant. Participants from lower educational backgrounds had difficulties understanding the purpose of risk assessments. User tests found that the final prototype was appropriate and feasible to implement by risk assessors. CONCLUSION: An iterative and evidence-based process was used to develop content to improve the communication of risk assessments to the general public while being feasible to use by risk assessors. Remaining challenges include how to communicate dose-response relationships and standardise quality of evidence ratings across disciplines.

Amorphization and nanocrystal formation in a Pd-Ni-Cu-P alloy after cooling under different conditions.

Structure formation during solidification of a Pd-Ni-Cu-P melt is studied. It is demonstrated that changes in the heat transfer conditions lead to a nonlinear change in the characteristics of the structure. The article presents the regimes of cooling the samples and the results of their structure and composition studies. It is found that a decrease in the cooling rate of the alloy leads to an increase in the size, proportion and composition of nanoinclusions in an amorphous matrix. X-ray diffraction method, electron probe microanalysis, transmission microscopy and scanning calorimetry are used for samples characterization. This article is part of the theme issue 'Transport phenomena in complex systems (part 2)'.

The descending pain modulation system predicts short term efficacy of multimodal pain therapy: an observational prospective cohort study.

OBJECTIVES: Treating chronic pain patients with multimodal pain therapy (MMPT) alters perception, awareness, and processing of pain at multiple therapeutic levels. Several clinical observations suggest that the effects of therapy may go beyond the possible sum of each level of therapy and may be due to a central descending inhibitory effect measurable by conditioned pain modulation (CPM). Thus, we investigated whether CPM is able to identify a group of patients that benefit particularly from MMPT. METHODS: This was an observational prospective cohort study. Patients were hospitalized on a special pain medicine ward with specially trained staff for 10 days. The patients were questioned and had investigations before and shortly after MMPT and were followed-up on 3 months post discharge. Before and after treatment, subjects were investigated via CPM and quantitative sensory testing (QST) as well as completing questionnaires. The study was registered in the German Clinical Trials Register (DRKS00006850). RESULTS: During the study period of 24 months, 224 chronic pain patients were recruited. 51 percent of patients completed the study period. There was an improvement in overall groups regarding all domains assessed, lasting beyond the end of the intervention. Patients with a sufficient CPM effect, defined as a reduction in pain during the conditioning stimulus, at baseline did show a more pronounced reduction in mean pain ratings than those without. This was not the case 3 months after therapy. Furthermore, sufficient CPM was identified as a predictor for pain reduction using a linear regression model. CONCLUSION: In conclusion, this study shows that while a heterogeneous group of patients with chronic pain disorders does sustainably benefit from MMPT in general, patients with a sufficient CPM effect do show a more pronounced decrease in pain ratings directly after therapy in comparison to those without.

Pain at one body site can be reduced, when another painful stimulus occurs at the same time. This mechanism is referred to as conditioned pain modulation (CPM).Some patients with chronic pain are treated using different methods such as medication, physiotherapy, and patient education in an in-patient setting, referred to as multimodal pain therapy (MMST). To improve pain therapy, it is vital to identify whether patients who respond especially well to a certain treatment show specific characteristics (i.e. mechanism-based therapy). We investigated whether the prospect of success of MMST is related to how well CPM works in patients. We assessed the CPM effect and sensory function of 224 patients with chronic pain before and after therapy to answer this question. Additionally, patients completed questionnaires about their pain, mood, quality of life, and sleep directly after therapy and three months later. All patients showed improvement after therapy, but in those in which CPM worked well, pain was reduced stronger than in those in which CPM did not. Three months after treatment, the difference disappeared.

Peri- and intraoperative EEG signatures in newborns and infants.

OBJECTIVE: The electroencephalographic derived indices have been developed for adult patients, however these monitors have not been validated for infants. METHODS: Frontal EEGs were recorded in 115 infants aged <1 year [0-3-months (N = 27), 4-6-months (N = 30), 7-9-months (N = 29) and 10-12-months (N = 29)] who received general anaesthesia with sevoflurane. Total power (µV2) and relative ß-, α-, θ-, δ-power (%) were analyzed. Additionally, in 20 EEGs event marker were added (baseline, loss of consciousness, intraoperative situation, extubation) to assess perioperative EEG dynamics. RESULTS: Newborns show a mean relative δ-power at 80% in intraoperative EEG compared to infants (10-12 months) showing 47.5%. Relative ß-power and α-power are low in newborns (mean 3.2% and 4.6%; respectively), with a marked increase in the older infants (4-6 months) (mean 10.9% and 14.4%; respectively). EEG dynamic in newborns from baseline (relative δ-power of 88%) to the intraoperative situation (80.5%) are discrete. In contrast infants >6-months have a strong reduction of relative δ-power from baseline to the intraoperative situation, which corresponds to an increase of faster frequencies. CONCLUSIONS: Age dependent perioperative EEG signatures can be demonstrated in infants younger than one year. SIGNIFICANCE: We demonstrate significant differences in EEG readouts between newborns and infants which questions our monitoring systems in paediatric anaesthesia.

Immuno-regenerative biomaterials for in situ cardiovascular tissue engineering - Do patient characteristics warrant precision engineering?

In situ tissue engineering using bioresorbable material implants - or scaffolds - that harness the patient's immune response while guiding neotissue formation at the site of implantation is emerging as a novel therapy to regenerate human tissues. For the cardiovascular system, the use of such implants, like blood vessels and heart valves, is gradually entering the stage of clinical translation. This opens up the question if and to what extent patient characteristics influence tissue outcomes, necessitating the precision engineering of scaffolds to guide patient-specific neo-tissue formation. Because of the current scarcity of human in vivo data, herein we review and evaluate in vitro and preclinical investigations to predict the potential role of patient-specific parameters like sex, age, ethnicity, hemodynamics, and a multifactorial disease profile, with special emphasis on their contribution to the inflammation-driven processes of in situ tissue engineering. We conclude that patient-specific conditions have a strong impact on key aspects of in situ cardiovascular tissue engineering, including inflammation, hemodynamic conditions, scaffold resorption, and tissue remodeling capacity, suggesting that a tailored approach may be required to engineer immuno-regenerative biomaterials for safe and predictive clinical applicability.

Demonstration of the effect of stirring on nucleation from experiments on the International Space Station using the ISS-EML facility.

The effect of fluid flow on crystal nucleation in supercooled liquids is not well understood. The variable density and temperature gradients in the liquid make it difficult to study this under terrestrial gravity conditions. Nucleation experiments were therefore made in a microgravity environment using the Electromagnetic Levitation Facility on the International Space Station on a bulk glass-forming Zr57Cu15.4Ni12.6Al10Nb5 (Vit106), as well as Cu50Zr50 and the quasicrystal-forming Ti39.5Zr39.5Ni21 liquids. The maximum supercooling temperatures for each alloy were measured as a function of controlled stirring by applying various combinations of radio-frequency positioner and heater voltages to the water-cooled copper coils. The flow patterns were simulated from the known parameters for the coil and the levitated samples. The maximum nucleation temperatures increased systematically with increased fluid flow in the liquids for Vit106, but stayed nearly unchanged for the other two. These results are consistent with the predictions from the Coupled-Flux model for nucleation.

Non-dynamic graciloplasty is an effective treatment for patients with passive fecal incontinence.

BACKGROUND: Fecal incontinence is a multifactorial problem and its etiology is complex. Various therapies are available and different success rates have been described. The aim of this study was to assess the effectiveness and safety of non-dynamic graciloplasty in patients with passive fecal incontinence. METHODS: We retrospectively studied charts of patients with fecal incontinence treated with graciloplasty at our institution from November 2015 until June 2018. Patients were included according to the following criteria: (1) presence of predominantly passive fecal incontinence and (2) presence of a lax perineal body. Primary outcome was the effectiveness, defined as a significant reduction or absence of the complaints of passive fecal incontinence at 3, 6 and 12 months after surgery. Second, we studied the safety of the procedure evaluating the complications within 30 days after surgery. RESULTS: Thirty-one patients met the inclusion criteria. Twenty-six of them, in addition to passive incontinence as the main symptom, had some degree of fecal urgency. The median age at the first visit to the outpatient clinic was 64.0 years (IQR 52-68). Most patients were female (n = 29, 94%). At 3 months after graciloplasty, 71% (22 of 31) of patients were successfully treated for their passive fecal incontinence. At 6 months, the success rate of the graciloplasty increased to 77%. At 12 months among the patients who were still seen in the clinic, the success rate was 58% (18/31). Two patients cancelled follow-up visits after 3 months, because of failure to control symptoms in 1 case. After 6 months, 9 patients were given the choice to do telephone follow-up only. Of these 11 patients without in-person follow-up, 10 were contacted 1 year after surgery and in 7 of them, the graciloplasty was effective in controlling their passive fecal incontinence for an overall success rate of 80% (25/31). Of the 26 patients with mixed passive and urge incontinence, 6 (23%) still complained of urge incontinence at 1 year. Of these patients with persistent urge incontinence, 6 underwent sacral nerve stimulation which was successful in 4. Two serious complications occurred within 30 days. A rectal perforation requiring temporary colostomy and a recto-vaginal fistula which was successfully repaired. CONCLUSION: Non-dynamic graciloplasty is an effective treatment for passive fecal incontinence. Differentiation based on subtypes of fecal incontinence might be important for a pattern-specific approach to treatment. More research is necessary to determine the right indications for more invasive treatments of fecal incontinence.

Super-resolution lightwave tomography of electronic bands in quantum materials.

Searching for quantum functionalities requires access to the electronic structure, constituting the foundation of exquisite spin-valley-electronic, topological, and many-body effects. All-optical band-structure reconstruction could directly connect electronic structure with the coveted quantum phenomena if strong lightwaves transported localized electrons within preselected bands. Here, we demonstrate that harmonic sideband (HSB) generation in monolayer tungsten diselenide creates distinct electronic interference combs in momentum space. Locating these momentum combs in spectroscopy enables super-resolution tomography of key band-structure details in situ. We experimentally tuned the optical-driver frequency by a full octave and show that the predicted super-resolution manifests in a critical intensity and frequency dependence of HSBs. Our concept offers a practical, all-optical, fully three-dimensional tomography of electronic structure even in microscopically small quantum materials, band by band.

Microscopic Coulomb interaction in transition-metal dichalcogenides.

The quasi-two dimensional Coulomb interaction potential in transition metal dichalcogenides is determined using the Kohn-Sham wave functions obtained fromab initiocalculations. An effective form factor is derived that accounts for the finite extension of the wave functions in the direction perpendicular to the material layer. The resulting Coulomb matrix elements are used in microscopic calculations based on the Dirac Bloch equations yielding an efficient method to calculate the band gap and the opto-electronic material properties in different environments and under various excitation conditions.

What is the Preferred Screening Tool for COVID-19 in Asymptomatic Patients Undergoing a Surgical or Diagnostic Procedure?

INTRODUCTION: Since the outbreak of COVID-19, measures were taken to protect healthcare staff from infection, to prevent infection of patients admitted to the hospital and to distribute PPE according to need. To assure the proper protection without overuse of limited supply of these equipments, screening of patients before surgical or diagnostic procedure was implemented. This study evaluates the results of this screening. METHOD: All patients screened for COVID-19 before procedure warranting either general, locoregional anaesthesia or sedation were included. Screening included a symptom questionnaire by phone, PCR and HRCT chest testing. Surgical or procedural details were registered together with actions taken based on screening results. RESULTS: Three hundred ninety-eight screenings were performed on 386 patients. The symptom questionnaire was completed in 72% of screenings. In 371 screenings, PCR testing was performed and negative. HRCT chest found 18 cases where COVID-19 could not be excluded, with negative PCR testing. Three patients had their surgery postponed due to inconclusive screening, and additional measures were taken in three other patients. There were incidental findings in 14% of HRCT chest scans. DISCUSSION: Pre-operative screening will differentiate if PPE is needed for procedures and which patients can safely have elective surgery during this COVID-19 pandemic and in the times to come. HRCT chest has no additional value in the pre-operative screening of asymptomatic patients. Screening can be performed with a symptom questionnaire, and additional screening with PCR testing in high-risk patient groups should be considered.

[New challenges for anesthesia due to the climate change]. / Neue Herausforderungen für die Anästhesie durch den Klimawandel.

BACKGROUND: The climate crisis is the most serious threat to global health in the twenty-first century. In western countries 5-10% of all greenhouse gas emissions originate from the healthcare sector and the main contributing factors are energy-intense departments (intensive care units, operating suits and prehospital emergency services). OBJECTIVE: The aim of this review is to provide background knowledge and practical ideas to achieve climate-neutral hospitals. MATERIAL AND METHODS: Narrative review with information on the topics of (I) volatile anesthetics as greenhouse gases, (II) energy supply in hospitals and (III) solid waste management. RESULTS AND CONCLUSION: (I) Volatile anesthetics are highly potent greenhouse gases, especially desflurane has a major global warming potential. Total intravenous anesthesia (TIVA) with propofol or regional anesthetic techniques have a much lower impact on the climate. (II) Using sustainable energy sources as well as initiating energy sparing techniques, such as light-emitting diodes (LED) and motion sensors, can reduce CO2 emissions. (III) Waste can be managed by the reduce, reuse, recycle, rethink and research concept. Doctors should actively contribute to reach the climate goals.

Resistivity Saturation in Metallic Liquids Above a Dynamical Crossover Temperature Observed in Measurements Aboard the International Space Station.

Although a resistivity saturation (minimum conductivity) is often observed in disordered metallic solids, such phenomena in the corresponding liquids are not known. Here we report a saturation of the electrical resistivity in Zr_{64}Ni_{36} and Cu_{50}Zr_{50} liquids above a dynamical crossover temperature for the viscosity (T_{A}). The measurements were made for the levitated liquids under the microgravity conditions of the International Space Station. Based on recent molecular dynamics simulations, the saturation is likely due to the ineffectiveness of electron-phonon scattering above T_{A} when the phonon lifetime becomes too short compared to the electron relaxation time. This is different from the conventional resistivity saturation mechanisms in solids.

Control of the nonlinear response of bulk GaAs induced by long-wavelength infrared pulses.

The nonlinear optical response of GaAs is studied using extremely nonresonant 10 µm laser pulses with peak intensities greater than 2 GW/cm 2. We observe over an order of magnitude enhancement in the four-wave mixing efficiency by decreasing the CO 2 laser beat-wave frequency. This enhancement is attributed to currents of photoexcited unbound carriers modulated at the beat frequency, confirmed by measurements of nonlinear absorption at this long wavelength as well as a fully microscopic analysis of the excitation dynamics. Modeling of such nonperturbative semiconductor-laser interactions predicts that further decreasing the beat frequency can increase the nonlinear response and allow for its control over two orders of magnitude.

Perineal rectosigmoidectomy for rectal prolapse-the preferred procedure for the unfit elderly patient? 10 years experience from a UK tertiary centre.

BACKGROUND: Rectal prolapse is a disease presentation with a prevalence of about 1%, mainly affecting older women. It usually presents with symptoms of rectal mass, rectal bleeding, fecal incontinence or constipation, with patients frequently feeling socially isolated as a result. Perineal rectosigmoidectomy is associated with lesser morbidity and mortality than the abdominal procedure, but with a much higher recurrence rate. Therefore, this technique is mainly suitable for the frail elderly patient. Specific outcomes in an elderly population have been described in only a few studies. We evaluated the morbidity, mortality, recurrence rate and functional results after this procedure related to age. METHODS: All patients who underwent a perineal rectosigmoidectomy over a 10-year period in two tertiary referral centers were included in the study. American Society of Anesthesiology (ASA) grade, pre- and postoperative symptoms, pathology-reported post-fixation specimen length, length of in-patient stay, 30-day morbidity/mortality, and recurrence were measured. RESULTS: A total of 45 patients underwent a perineal rectosigmoidectomy. Forty-three (95%) were female, with a median age of 82.0 years (IQR 70.5-86.5), ASA grade III and median follow-up of 20 months (range 8.5-45.5 months). Half of the cohort was over 80 years old. Significant symptomatic relief was achieved, predominantly the resolution of rectal mass (8.9% vs. 60.0% preoperatively), fecal incontinence (15.6% vs. 46.7%) and constipation (4.4% vs. 26.7%). The median length of stay was 6 days, while morbidity occurred in 14 patients (31.1%) and recurrence occurred in 6 patients (13%). There were no deaths within 30 days of the procedure and outcomes were comparable in the < 80 and ≥ 80 age group. CONCLUSIONS: Perineal rectosigmoidectomy is safe for older patients with greater comorbidities resulting in good functional results and is associated with low morbidity and mortality.

Memory effects in the long-wave infrared avalanche ionization of gases: a review of recent progress.

There are currently intense efforts being directed towards extending the range and energy of long distance nonlinear pulse propagation in the atmosphere by moving to longer infrared wavelengths, with the purpose of mitigating the effects of turbulence. In addition, picosecond and longer pulse durations are being used to increase the pulse energy. While both of these tacks promise improvements in applications, such as remote sensing and directed energy, they open up fundamental issues regarding the standard model used to calculate the nonlinear optical properties of dilute gases. Amongst these issues is that for longer wavelengths and longer pulse durations, exponential growth of the laser-generated electron density, the so-called avalanche ionization, can limit the propagation range via nonlinear absorption and plasma defocusing. It is therefore important for the continued development of the field to assess the theory and role of avalanche ionization in gases for longer wavelengths. Here, after an overview of the standard model, we present a microscopically motivated approach for the analysis of avalanche ionization in gases that extends beyond the standard model and we contend is key for deepening our understanding of long distance propagation at long infrared wavelengths. Our new approach involves the mean electron kinetic energy, the plasma temperature, and the free electron density as dynamic variables. The rate of avalanche ionization is shown to depend on the full time history of the pulsed excitation, as opposed to the standard model in which the rate is proportional to the instantaneous intensity. Furthermore, the new approach has the added benefit that it is no more computationally intensive than the standard one. The resulting memory effects and some of their measurable physical consequences are demonstrated for the example of long-wavelength infrared avalanche ionization and long distance high-intensity pulse propagation in air. Our hope is that this report in progress will stimulate further discussion that will elucidate the physics and simulation of avalanche ionization at long infrared wavelengths and advance the field.

Non-equilibrium dynamics in the dual-wavelength operation of vertical external-cavity surface-emitting lasers.

Microscopic many-body theory coupled with Maxwell's equation is used to study dual-wavelength operation in vertical external-cavity surface-emitting lasers. The intrinsically dynamic nature of coexisting emission wavelengths in semiconductor lasers is associated with characteristic non-equilibrium carrier dynamics, which causes significant deformations of the quasi-equilibrium gain and carrier inversion. Extended numerical simulations are employed to efficiently investigate the parameter space to identify the regime for dual-wavelength operation. Using a frequency selective intracavity etalon, two families of modes are stabilized with dynamical interchange of the strongest emission peaks. For this operation mode, anti-correlated intensity noise is observed in agreement with the experiment. A method using effective frequency selective filtering is suggested for stabilization of genuine dual-wavelength output.