Kinetics of ventilation-induced changes in diaphragmatic metabolism by bilateral phrenic pacing in a piglet model

Citation: Breuer, T., Hatam, N., Grabiger, B., Marx, G., Behnke, B. J., Weis, J., . . . Bruells, C. S. (2016). Kinetics of ventilation-induced changes in diaphragmatic metabolism by bilateral phrenic pacing in a piglet model. Scientific Reports, 6, 10. doi:10.1038/srep35725Perioperative necessity of deep sedation is inevitably associated with diaphragmatic inactivation. This study investigated 1) the feasibility of a new phrenic nerve stimulation method allowing early diaphragmatic activation even in deep sedation and, 2) metabolic changes within the diaphragm during mechanical ventilation compared to artificial activity. 12 piglets were separated into 2 groups. One group was mechanically ventilated for 12 hrs (CMV) and in the second group both phrenic nerves were stimulated via pacer wires inserted near the phrenic nerves to mimic spontaneous breathing (STIM). Lactate, pyruvate and glucose levels were measured continuously using microdialysis. Oxygen delivery and blood gases were measured during both conditions. Diaphragmatic stimulation generated sufficient tidal volumes in all STIM animals. Diaphragm lactate release increased in CMV transiently whereas in STIM lactate dropped during this same time point (2.6 vs. 0.9 mmol L-1 after 5:20 hrs; p < 0.001). CMV increased diaphragmatic pyruvate (40 vs. 146 mu mol L-1 after 5:20 hrs between CMV and STIM; p < 0.0001), but not the lactate/pyruvate ratio. Diaphragmatic stimulation via regular electrodes is feasible to generate sufficient ventilation, even in deep sedation. Mechanical ventilation alters the metabolic state of the diaphragm, which might be one pathophysiologic origin of ventilator-induced diaphragmatic dysfunction. Occurrence of hypoxia was unlikely

Shaping the spectral correlation of bi-photon quantum frequency combs by multi-frequency excitation of an SOI integrated nonlinear resonator

: We reveal the generation of a broadband (&gt; 1.9 THz) bi-photon quantum frequency comb (QFC) in a silicon-on-insulator (SOI) Fabry-Pérot micro-cavity and the control of its spectral correlation properties. Correlated photon pairs are generated through three spontaneous four-wave mixing (SFWM) processes by using a co-polarized bi-chromatic coherent input with power P1 and P2 on adjacent resonances of the nonlinear cavity. Adjusting the spectral power ratio r = P1/(P1 + P2) allows control over the influence of each process leading to an enhancement of the overall photon pair generation rate (PGR) μ(r) by a maximal factor of μ(r = 0.5)/μ(r = 0) ≈ 1.5, compared to the overall PGR provided by a single-pump configuration with the same power budget. We demonstrate that the efficiency aND of the non-degenerate excitation SFWM process (NDP) doubles the efficiency a1 ≈ a2 of the degenerate excitation SFWM processes (DP), showing a good agreement with the provided model

Immune Dysregulation in Patients Persistently Infected with Human Papillomaviruses 6 and 11

Human Papillomaviruses (HPVs) 6 and 11 are part of a large family of small DNA viruses, some of which are commensal. Although much of the population can contain or clear infection with these viruses, there is a subset of individuals who develop persistent infection that can cause significant morbidity and on occasion mortality. Depending on the site of infection, patients chronically infected with these viruses develop either recurrent, and on occasion, severe genital warts or recurrent respiratory papillomas that can obstruct the upper airway. The HPV-induced diseases described are likely the result of a complex and localized immune suppressive milieu that is characteristic of patients with persistent HPV infection. We review data that documents impaired Langerhans cell responses and maturation, describes the polarized adaptive T-cell immune responses made to these viruses, and the expression of class select II MHC and KIR genes that associate with severe HPV6 and 11 induced disease. Finally, we review evidence that documents the polarization of functional TH2 and T-regulatory T-cells in tissues persistently infected with HPV6 and 11, and we review evidence that there is suppression of natural killer cell function. Together, these altered innate and adaptive immune responses contribute to the cellular and humoral microenvironment that supports HPV 6 and 11-induced disease

Fully on-chip photonic turnkey quantum source for entangled qubit/qudit state generation

Integrated photonics has recently become a leading platform for the realization and processing of optical entangled quantum states in compact, robust and scalable chip formats, with applications in long-distance quantum-secured communication, quantum-accelerated information processing and nonclassical metrology. However, the quantum light sources developed so far have relied on external bulky excitation lasers, making them impractical prototype devices that are not reproducible, hindering their scalability and transfer out of the laboratory into real-world applications. Here we demonstrate a fully integrated quantum light source that overcomes these challenges through the integration of a laser cavity, a highly efficient tunable noise suppression filter (>55 dB) exploiting the Vernier effect, and a nonlinear microring for entangled photon-pair generation through spontaneous four-wave mixing. The hybrid quantum source employs an electrically pumped InP gain section and a Si3N4 low-loss microring filter system, and demonstrates high performance parameters, that is, pair emission over four resonant modes in the telecom band (bandwidth of ~1 THz) and a remarkable pair detection rate of ~620 Hz at a high coincidence-to-accidental ratio of ~80. The source directly creates high-dimensional frequency-bin entangled quantum states (qubits/qudits), as verified by quantum interference measurements with visibilities up to 96% (violating Bell’s inequality) and by density matrix reconstruction through state tomography, showing fidelities of up to 99%. Our approach, leveraging a hybrid photonic platform, enables scalable, commercially viable, low-cost, compact, lightweight and field-deployable entangled quantum sources, quintessential for practical, out-of-laboratory applications such as in quantum processors and quantum satellite communications systems

Marked improvements in glycaemic outcomes following insulin pump therapy initiation in people with type 1 diabetes:a nationwide observational study in Scotland

This study was supported by funding from Diabetes UK (17/0005627) and the Chief Scientist Office (ref. ETM/47).Aims/hypothesis Our aim was to assess the use of continuous subcutaneous insulin infusion (CSII) in people with type 1 diabetes in Scotland and its association with glycaemic control, as measured by HbA1c levels, frequency of diabetic ketoacidosis (DKA) and severe hospitalised hypoglycaemia (SHH), overall and stratified by baseline HbA1c. Methods We included 4684 individuals with type 1 diabetes from the national Scottish register, who commenced CSII between 2004 and 2019. We presented crude within-person differences from baseline HbA1c over time since initiation, crude DKA and SHH event-rates pre-/post-CSII exposure. We then used mixed models to assess the significance of CSII exposure, taking into account: (1) the diffuse nature of the intervention (i.e. structured education often precedes initiation); (2) repeated within-person measurements; and (3) background time-trends occurring pre-intervention. Results HbA1c decreased after CSII initiation, with a median within-person change of −5.5 mmol/mol (IQR −12.0, 0.0) (−0.5% [IQR −1.1, 0.0]). Within-person changes were most substantial in those with the highest baseline HbA1c, with median −21.0 mmol/mol (−30.0, −11.0) (−1.9% [−2.7, −1.0]) change in those with a baseline >84 mmol/mol (9.8%) within a year of exposure, that was sustained: −19.0 mmol/mol (−27.6, −6.5) (−1.7% [−2.5, −0.6]) at ≥5 years. Statistical significance and magnitude of change were supported by the mixed models results. The crude DKA event-rate was significantly lower in post-CSII person-time compared with pre-CSII person-time: 49.6 events (95% CI 46.3, 53.1) per 1000 person-years vs 67.9 (64.1, 71.9); rate ratio from Bayesian mixed models adjusting for pre-exposure trend: 0.61 (95% credible interval [CrI] 0.47, 0.77; posterior probability of reduction pp = 1.00). The crude overall SHH event-rate in post-CSII vs pre-CSII person-time was also lower: 17.8 events (95% CI 15.8, 19.9) per 1000 person-years post-exposure vs 25.8 (23.5, 28.3) pre-exposure; rate ratio from Bayesian mixed models adjusting for pre-exposure trend: 0.67 (95% CrI 0.45, 1.01; pp = 0.97). Conclusions/interpretation CSII therapy was associated with marked falls in HbA1c especially in those with high baseline HbA1c. CSII was independently associated with reduced DKA and SHH rates. CSII appears to be an effective option for intensive insulin therapy in people with diabetes for improving suboptimal glycaemic control.Publisher PDFPeer reviewe

Flash monitor initiation is associated with improvements in HbA1c levels and DKA rates among people with Type 1 Diabetes in Scotland:a retrospective nationwide observational study

Funding Information: This study was supported by funding from the Diabetes UK (17/0005627) and the Chief Scientist Office (Ref. ETM/47).Peer reviewedPublisher PD

Feasibility and efficacy of bypassing the right ventricle and pulmonary circulation to treat right ventricular failure: an experimental study

<p>Abstract</p> <p>Background</p> <p>Right ventricular failure (RVF) and -support is associated with poor results. We aimed for a new approach of right - sided assistance bypassing the right ventricle and pulmonary circulation in order to better decompress the right ventricle and optimize left ventricular filling.</p> <p>Methods</p> <p>From a microaxial pump (Abiomed), a low resistance oxygenator (Maquet and Novalung) and two cannulas (28 and 27 Fr) a system was set up and evaluated in an ovine model (n = 7). Connection with the heart was the right and left atrium. One hour the system was operated without RVF and turned of again. Then a RVF was induced and the course with the system running was evaluated. Complete hemodynamic monitoring was performed as well as echocardiography, flow measurement and blood gas analysis.</p> <p>Results</p> <p>The overall performance of the system was reliable. Without RVF no relevant changes of hemodynamics occurred; blood gases were supra normal. In RVF a cardiogenic shock developed (MAP 35 ± 13 mmHg, CO 1,1 ± 0,7 l/min). Immediately after starting the system the circulation normalized (significant increase of MAP to 85 ± 13 mmHg, of CO to 4,5 ± 1,9). Echocardiography also revealed right ventricular recovery. After stopping the system, RVF returned.</p> <p>Conclusions</p> <p>Bypassing the right ventricle and pulmonary circulation with an oxygenating assist device, which may offer the advantages of enhanced right ventricular decompression and augmented left atrial filling, is feasible and effective in the treatment of acute RVF. Long time experiments are needed.</p