Quantum signatures in quadratic optomechanics

We analyze quantum effects occurring in optomechanical systems where the coupling between an optical mode and a mechanical mode is quadratic in displacement (membrane-in-the-middle geometry). We show that it is possible to observe quantum effects in these systems without achieving the single-photon strong coupling regime. We find that zero-point energy causes a mechanical frequency shift, and we propose an experimental way to measure it. Further, we show that it is possible to determine the phonon statistics from the cavity transmission, and propose a way to infer the resonator's temperature based on this feature. For completeness, we revisit the case of an isolated system and show that different types of mechanical quantum states can be created, depending on the initial cavity state. In this situation, mechanical motion undergoes collapse and revivals, and we compute the collapse and revival times, as well as the degree of squeezing.Comment: 7 pages, 6 figures, 2nd versio

Fluorescence perfusion assessment of vascular ligation during ileal pouch-anal anastomosis

Background: Intraoperative fluorescence angiography (FA) is of potential added value during ileal pouch-anal anastomosis (IPAA), especially after vascular ligation as part of lengthening measures. In this study, time to fluorescent enhancement during FA was evaluated in patients with or without vascular ligation during IPAA. Methods: This is a retrospective cohort study of all consecutive patients that underwent FA-guided IPAA between August 2018 and December 2019 in our tertiary referral centre. Vascular ligation was defined as disruption of the ileocolic arcade or ligation of interconnecting terminal ileal branches. FA was performed before and after ileoanal anastomotic reconstruction. During FA, time to fluorescent enhancement was recorded at different sites of the pouch. Results: Thirty-eight patients [55.3% male, median age 45 years (IQR 24–51 years)] were included, of whom the majority (89.5%) underwent a modified-2-stage restorative proctocolectomy. Vascular ligation was performed in 15 patients (39.5%), and concerned central ligation of the ileocolic arcade in 3 cases, interconnecting branches in 10, and a combination in 2. For the entire cohort, time between indocyanine green (ICG) injection and first fluorescent signal in the pouch was 20 s (IQR 15–31 s) before and 25 s (IQR 20–36 s) after anal anastomotic reconstruction. Time from ICG injection to the first fluorescent signal at the inlet, anvil and blind loop of the pouch were non-significantly prolonged in patients that received vascular ligation. Conclusions: Results from this study indicate that time to fluorescence enhancement during FA might be prolonged due to arterial rerouting through the arcade or venous outflow obstruction in case of vascular ligation.</p

Fluorescence perfusion assessment of vascular ligation during ileal pouch-anal anastomosis

Background: Intraoperative fluorescence angiography (FA) is of potential added value during ileal pouch-anal anastomosis (IPAA), especially after vascular ligation as part of lengthening measures. In this study, time to fluorescent enhancement during FA was evaluated in patients with or without vascular ligation during IPAA. Methods: This is a retrospective cohort study of all consecutive patients that underwent FA-guided IPAA between August 2018 and December 2019 in our tertiary referral centre. Vascular ligation was defined as disruption of the ileocolic arcade or ligation of interconnecting terminal ileal branches. FA was performed before and after ileoanal anastomotic reconstruction. During FA, time to fluorescent enhancement was recorded at different sites of the pouch. Results: Thirty-eight patients [55.3% male, median age 45 years (IQR 24–51 years)] were included, of whom the majority (89.5%) underwent a modified-2-stage restorative proctocolectomy. Vascular ligation was performed in 15 patients (39.5%), and concerned central ligation of the ileocolic arcade in 3 cases, interconnecting branches in 10, and a combination in 2. For the entire cohort, time between indocyanine green (ICG) injection and first fluorescent signal in the pouch was 20 s (IQR 15–31 s) before and 25 s (IQR 20–36 s) after anal anastomotic reconstruction. Time from ICG injection to the first fluorescent signal at the inlet, anvil and blind loop of the pouch were non-significantly prolonged in patients that received vascular ligation. Conclusions: Results from this study indicate that time to fluorescence enhancement during FA might be prolonged due to arterial rerouting through the arcade or venous outflow obstruction in case of vascular ligation.</p

Nanobody-targeted photodynamic therapy induces significant tumor regression of trastuzumab-resistant HER2-positive breast cancer, after a single treatment session

Rationale: A substantial number of breast cancer patients with an overexpression of the human epidermal growth factor receptor 2 (HER2) have residual disease after neoadjuvant therapy or become resistant to trastuzumab. Photodynamic therapy (PDT) using nanobodies targeted to HER2 is a promising treatment option for these patients. Here we investigate the in vitro and in vivo antitumor efficacy of HER2-targeted nanobody-photosensitizer (PS) conjugate PDT. Methods: Nanobodies targeting HER2 were obtained from phage display selections. Monovalent nanobodies were engineered into a biparatopic construct. The specificity of selected nanobodies was tested in immunofluorescence assays and their affinity was evaluated in binding studies, both performed in a panel of breast cancer cells varying in HER2 expression levels. The selected HER2-targeted nanobodies 1D5 and 1D5-18A12 were conjugated to the photosensitizer IRDye700DX and tested in in vitro PDT assays. Mice bearing orthotopic HCC1954 trastuzumab-resistant tumors with high HER2 expression or MCF-7 tumors with low HER2 expression were intravenously injected with nanobody-PS conjugates. Quantitative fluorescence spectroscopy was performed for the determination of the local pharmacokinetics of the fluorescence conjugates. After nanobody-PS administration, tumors were illuminated to a fluence of 100 J∙cm-2, with a fluence rate of 50 mW∙cm-2, and thereafter tumor growth was measured with a follow-up until 30 days. Results: The selected nanobodies remained functional after conjugation to the PS, binding specifically and with high affinity to HER2-positive cells. Both nanobody-PS conjugates potently and selectively induced cell death of HER2 overexpressing cells, either sensitive or resistant to trastuzumab, with low nanomolar LD50 values. In vivo, quantitative fluorescence spectroscopy showed specific accumulation of nanobody-PS conjugates in HCC1954 tumors and indicated 2 h post injection as the most suitable time point to apply light. Nanobody-targeted PDT with 1D5-PS and 1D5-18A12-PS induced significant tumor regression of trastuzumab-resistant high HER2 expressing tumors, whereas in low HER2 expressing tumors only a slight growth delay was observed. Conclusion: Nanobody-PS conjugates accumulated selectively in vivo and their fluorescence could be detected through optical imaging. Upon illumination, they selectively induced significant tumor regression of HER2 overexpressing tumors with a single treatment session. Nanobody-targeted PDT is therefore suggested as a new additional treatment for HER2-positive breast cancer, particularly of interest for trastuzumab-resistant HER2-positive breast cancer. Further studies are now needed to assess the value of this approach in c

Single-channel qEEG characteristics distinguish delirium from no delirium, but not postoperative from non-postoperative delirium

OBJECTIVE: This exploratory study examined quantitative electroencephalography (qEEG) changes in delirium and the use of qEEG features to distinguish postoperative from non-postoperative delirium. METHODS: This project was part of the DeltaStudy, a cross-sectional,multicenterstudy in Intensive Care Units (ICUs) and non-ICU wards. Single-channel (Fp2-Pz) four-minutes resting-state EEG was analyzed in 456 patients. After calculating 98 qEEG features per epoch, random forest (RF) classification was used to analyze qEEG changes in delirium and to test whether postoperative and non-postoperative delirium could be distinguished. RESULTS: An area under the receiver operatingcharacteristic curve (AUC) of 0.76 (95% Confidence Interval (CI) 0.71-0.80) was found when classifying delirium with a sensitivity of 0.77 and a specificity of 0.63 at the optimal operating point. The classification of postoperative versus non-postoperative delirium resulted in an AUC of 0.50 (95%CI 0.38-0.61). CONCLUSIONS: RF classification was able to discriminate delirium from no delirium with reasonable accuracy, while also identifying new delirium qEEG markers like autocorrelation and theta peak frequency. RF classification could not distinguish postoperative from non-postoperative delirium. SIGNIFICANCE: Single-channel EEG differentiates between delirium and no delirium with reasonable accuracy. We found no distinct EEG profile for postoperative delirium, which may suggest that delirium is one entity, whether it develops postoperatively or not

Apolipoprotein E gene is related to mortality only in normal weight individuals: The Rotterdam study

Objective To investigate the relationship between the apolipoprotein E (APOE) gene and the risk of mortality in normal weight, overweight and obese individuals. Methods and Results In a population-based study of 7,983 individuals aged 55 years and older, we compared the risks of all-cause and coronary heart disease (CHD) mortality by APOE genotype, both overall and in subgroups defined by body mass index (BMI). We found significant evidence for interaction between APOE and BMI in relation to total cholesterol (p = 0.04) and HDL cholesterol (p < 0.001). Overall, APOE*2 carriers showed a decreased risk of all-cause mortality. Analyses within BMI strata showed a beneficial effect of APOE*2 only in normal weight persons (adjusted hazard ratio (HR) 0.7[95% CI 0.5–0.9]). APOE*2 was not associated with a lower risk of all-cause mortality in overweight or obese persons. The effect of APOE*2 in normal weight individuals tended to be due to the risk of CHD mortality (adjusted HR 0.5 [95% CI 0.2–1.2]). Conclusion The APOE*2 allele confers a lower risk of all-cause mortality only to normal weight individuals

Worldwide Survey of the "Assessing Pain, Both Spontaneous Awakening and Breathing Trials, Choice of Drugs, Delirium Monitoring/Management, Early Exercise/Mobility, and Family Empowerment" (ABCDEF) Bundle

OBJECTIVES: To assess the knowledge and use of the Assessment, prevention, and management of pain; spontaneous awakening and breathing trials; Choice of analgesia and sedation; Delirium assessment; Early mobility and exercise; and Family engagement and empowerment (ABCDEF) bundle to implement the Pain, Agitation, Delirium guidelines. DESIGN: Worldwide online survey. SETTING: Intensive care. INTERVENTION: A cross-sectional online survey using the Delphi method was administered to intensivists worldwide, to assess the knowledge and use of all aspects of the ABCDEF bundle. MEASUREMENT AND MAIN RESULTS: There were 1,521 respondents from 47 countries, 57% had implemented the ABCDEF bundle, with varying degrees of compliance across continents. Most of the respondents (83%) used a scale to evaluate pain. Spontaneous awakening trials and spontaneous breathing trials are performed in 66% and 67% of the responder ICUs, respectively. Sedation scale was used in 89% of ICUs. Delirium monitoring was implemented in 70% of ICUs, but only 42% used a validated delirium tool. Likewise, early mobilization was "prescribed" by most, but 69% had no mobility team and 79% used no formal mobility scale. Only 36% of the respondents assessed ICU-acquired weakness. Family members were actively involved in 67% of ICUs; however, only 33% used dedicated staff to support families and only 35% reported that their unit was open 24 hr/d for family visits. CONCLUSIONS: The current implementation of the ABCDEF bundle varies across individual components and regions. We identified specific targets for quality improvement and adoption of the ABCDEF bundle. Our data reflect a significant but incomplete shift toward patient- and family-centered ICU care in accordance with the Pain, Agitation, Delirium guidelines