Optimal Control of a Single Queue with Retransmissions: Delay-Dropping Tradeoffs

A single queue incorporating a retransmission protocol is investigated, assuming that the sequence of per effort success probabilities in the Automatic Retransmission reQuest (ARQ) chain is a priori defined and no channel state information at the transmitter is available. A Markov Decision Problem with an average cost criterion is formulated where the possible actions are to either continue the retransmission process of an erroneous packet at the next time slot or to drop the packet and move on to the next packet awaiting for transmission. The cost per slot is a linear combination of the current queue length and a penalty term in case dropping is chosen as action. The investigation seeks policies that provide the best possible average packet delay-dropping trade-off for Quality of Service guarantees. An optimal deterministic stationary policy is shown to exist, several structural properties of which are obtained. Based on that, a class of suboptimal -policies is introduced. These suggest that it is almost optimal to use a K-truncated ARQ protocol as long as the queue length is lower than L, else send all packets in one shot. The work concludes with an evaluation of the optimal delay-dropping tradeoff using dynamic programming and a comparison between the optimal and suboptimal policies.Comment: 29 pages, 8 figures, submitted to IEEE Transactions on Wireless Communication

Protocolised early de-resuscitation in septic shock (REDUCE): protocol for a randomised controlled multicentre feasibility trial.

BACKGROUND Fluid overload is associated with excess mortality in septic shock. Current approaches to reduce fluid overload include restrictive administration of fluid or active removal of accumulated fluid. However, evidence on active fluid removal is scarce. The aim of this study is to assess the efficacy and feasibility of an early de-resuscitation protocol in patients with septic shock. METHODS All patients admitted to the intensive care unit (ICU) with a septic shock are screened, and eligible patients will be randomised in a 1:1 ratio to intervention or standard of care. INTERVENTION Fluid management will be performed according to the REDUCE protocol, where resuscitation fluid will be restricted to patients showing signs of poor tissue perfusion. After the lactate has peaked, the patient is deemed stable and assessed for active de-resuscitation (signs of fluid overload). The primary objective of this study is the proportion of patients with a negative cumulative fluid balance at day 3 after ICU. Secondary objectives are cumulative fluid balances throughout the ICU stay, number of patients with fluid overload, feasibility and safety outcomes and patient-centred outcomes. The primary outcome will be assessed by a logistic regression model adjusting for the stratification variables (trial site and chronic renal failure) in the intention-to-treat population. ETHICS AND DISSEMINATION The study was approved by the respective ethical committees (No 2020-02197). The results of the REDUCE trial will be published in an international peer-reviewed medical journal regardless of the results. TRIAL REGISTRATION NUMBER ClinicalTrials.gov, NCT04931485

Development of a GEM-TPC prototype

The use of GEM foils for the amplification stage of a TPC instead of a con- ventional MWPC allows one to bypass the necessity of gating, as the backdrift is suppressed thanks to the asymmetric field configuration. This way, a novel continuously running TPC, which represents one option for the PANDA central tracker, can be realized. A medium sized prototype with a diameter of 300 mm and a length of 600 mm will be tested inside the FOPI spectrometer at GSI using a carbon or lithium beam at intermediate energies (E = 1-3AGeV). This detector test under realistic experimental conditions should allow us to verify the spatial resolution for single tracks and the reconstruction capability for displaced vertexes. A series of physics measurement implying pion beams is scheduled with the FOPI spectrometer together with the GEM-TPC as well.Comment: 5 pages, 4 figures, Proceedings for 11th ICATTP conference in como (italy

Development and validation of a prognostic model for the early identification of COVID-19 patients at risk of developing common long COVID symptoms

Background: The coronavirus disease 2019 (COVID-19) pandemic demands reliable prognostic models for estimating the risk of long COVID. We developed and validated a prediction model to estimate the probability of known common long COVID symptoms at least 60 days after acute COVID-19. Methods: The prognostic model was built based on data from a multicentre prospective Swiss cohort study. Included were adult patients diagnosed with COVID-19 between February and December 2020 and treated as outpatients, at ward or intensive/intermediate care unit. Perceived long-term health impairments, including reduced exercise tolerance/reduced resilience, shortness of breath and/or tiredness (REST), were assessed after a follow-up time between 60 and 425 days. The data set was split into a derivation and a geographical validation cohort. Predictors were selected out of twelve candidate predictors based on three methods, namely the augmented backward elimination (ABE) method, the adaptive best-subset selection (ABESS) method and model-based recursive partitioning (MBRP) approach. Model performance was assessed with the scaled Brier score, concordance c statistic and calibration plot. The final prognostic model was determined based on best model performance. Results: In total, 2799 patients were included in the analysis, of which 1588 patients were in the derivation cohort and 1211 patients in the validation cohort. The REST prevalence was similar between the cohorts with 21.6% (n = 343) in the derivation cohort and 22.1% (n = 268) in the validation cohort. The same predictors were selected with the ABE and ABESS approach. The final prognostic model was based on the ABE and ABESS selected predictors. The corresponding scaled Brier score in the validation cohort was 18.74%, model discrimination was 0.78 (95% CI: 0.75 to 0.81), calibration slope was 0.92 (95% CI: 0.78 to 1.06) and calibration intercept was -0.06 (95% CI: -0.22 to 0.09). Conclusion: The proposed model was validated to identify COVID-19-infected patients at high risk for REST symptoms. Before implementing the prognostic model in daily clinical practice, the conduct of an impact study is recommended. Keywords: Clinical prediction model; Long COVID; Prognostic factors; Stratified medicin

The in vivo respiratory phenotype of the adenosine A1 receptor knockout mouse

The nucleoside adenosine has been implicated in the regulation of respiration, especially during hypoxia in the newborn. In this study the role of adenosine A1 receptors for the control of respiration was investigated in vivo. To this end, respiration of unrestrained adult and neonatal adenosine A1 receptor knockout mice (A1R(-/-)) was measured in a plethysmographic device. Under control conditions (21% O2) and mild hypoxia (12-15% O2) no difference of respiratory parameters was observed between adult wildtype (A1R(+/+)) and A1R(-/-) mice. Under more severe hypoxia (6-10% O2) A1R(+/+) mice showed, after a transient increase of respiration, a decrease of respiration frequency (fR) and tidal volume (VT) leading to a decrease of minute volume (MV). This depression of respiration during severe hypoxia was absent in A1R(-/-) mice which displayed a stimulated respiration as indicated by the enhancement of MV by some 50-60%. During hypercapnia-hyperoxia (3-10% CO2/97-90 % O2), no obvious differences in respiration of A1R(-/-) and A1R(+/+) was observed. In neonatal mice, the respiratory response to hypoxia was surprisingly similar in both genotypes. However, neonatal A1R(-/-) mice appeared to have more frequently periods of apnea during hypoxia and in the post-hypoxic control period. In conclusion, these data indicate that the adenosine A1 receptor is an important molecular component mediating hypoxic depression in adult mice and it appears to stabilize respiration of neonatal mice

Pädiatrische Notfallmedizin nach Mass – eine digitale Option

Hintergrund Pädiatrische Notfallbänder (PNB) unterstützen medizinisches Notfallpersonal bei der Versorgung von pädiatrischen Notfallpatienten. Ein kürzlich veröffentlichter digitaler Algorithmus zur längenbasierten Gewichtsschätzung war im Vergleich zu den auf dem Markt erhältlichen Bändern präziser. Um diesen digitalen Algorithmus klinisch zu testen, wurde ein Prototyp eines elektronischen PNB (ePER) entwickelt. Ziel Das Ziel dieser Studie war es, das ePER mit zwei bekannten papierbasierten, analogen PNB hinsichtlich Zeitbedarf und Präzision in einem pädiatrischen Notfallszenario zu vergleichen. Methoden Mitarbeiter der Anästhesieabteilung des Universitäts-Kinderspitals Zürich wurden gebeten, in randomisierter Reihenfolge mittels der beiden PNB und des ePER in einem simulierten Notfallszenario an pädiatrischen Notfallpuppen die Parameter Gewicht, Defibrillationsenergie, Adrenalindosis und Größe des endotrachealen Tubus zu bestimmen. Jeder Ablauf wurde mit einem digitalen Rekorder aufgezeichnet. Aus diesen Aufzeichnungen wurden die Zeit bis zur Nennung der jeweiligen Parameter und deren Korrektheit ermittelt. Ergebnisse Das Auffinden der definierten Parameter war mit dem ePER schneller als mit den konventionellen PNB (30 s vs. 47 s bzw. 51 s; beide p < 0,001). Die zu erfassenden Parameter wurden mit dem ePER in 85 % der Fälle korrekt erfasst, während mit den konventionellen PNB nur in 44 % bzw. 70 % der Fälle korrekte Werte ermittelt wurden. Schlussfolgerung Mit dem ePER stand die Information über die zu erfassenden Parameter schneller und präziser zur Verfügung. Das ePER stellt einen modernen Ansatz zur Unterstützung von Notfallpersonal während pädiatrischer Notfälle dar, insbesondere hinsichtlich Gewichtsschätzung, Medikamentendosierung und der richtigen Auswahl von medizinischem Equipment

Multi-photon excitation of intrinsic protein fluorescence and its application to pharmaceutical drug screening.

The majority of proteins contain intrinsic fluorophores as natural sensors of molecular structures, dynamics, and interactions. The intrinsic protein fluorescence signal allows for the label-free and, hence, undisturbed and rapid study of protein-ligand interactions. Ultraviolet-based drug screening is hampered by the background, photobleaching, light scattering, inner filter effects, and interfering assay compounds. Such problems can be overcome by means of molecular three-photon excitation (3PE) with infrared femtosecond light pulses since longer excitation wavelengths result in less Raleigh scattering, and the subfemtoliter (confocal-like) 3PE volume minimizes out-of-focus photobleaching, background generation, and inner filter effects. We demonstrate the general feasibility of 3PE for protein spectroscopy and illustrate the technique's excellent potential for high-throughput screening. By using the intrinsic fluorescence intensity of a protein-substrate, we were able to discriminate between ligands of different affinities in binding assays

Quantitative proteomic landscapes of primary and recurrent glioblastoma reveal a protumorigeneic role for FBXO2-dependent glioma-microenvironment interactions

Background: Recent efforts have described the evolution of glioblastoma from initial diagnosis to post-treatment recurrence on a genomic and transcriptomic level. However, the evolution of the proteomic landscape is largely unknown. Methods: Sequential window acquisition of all theoretical mass spectra mass spectrometry (SWATH-MS) was used to characterize the quantitative proteomes of two independent cohorts of paired newly diagnosed and recurrent glioblastomas. Recurrence-associated proteins were validated using immunohistochemistry and further studied in human glioma cell lines, orthotopic xenograft models and human organotypic brain slice cultures. External spatial transcriptomics, single-cell- and bulk RNA sequencing data was analyzed to gain mechanistical insights. Results: Although overall proteomic changes were heterogeneous across patients, we identified BCAS1, INF2 and FBXO2 as consistently upregulated proteins at recurrence and validated these using immunohistochemistry. Knockout of FBXO2 in human glioma cells conferred a strong survival benefit in orthotopic xenograft mouse models and reduced invasive growth in organotypic brain slice cultures. In glioblastoma patient samples, FBXO2 expression was enriched in the tumor infiltration zone and FBXO2-positive cancer cells were associated with synaptic signaling processes. Conclusions: These findings demonstrate a potential role of FBXO2-dependent glioma-microenvironment interactions to promote tumor growth. Furthermore, the published datasets provide a valuable resource for further studies. Keywords: Glioblastoma; PCT-SWATH; microenviroment; proteome