Carotid Blood Flow as a Surrogate for Pulse Contour Analysis in Assessment of Fluid Responsiveness: A Prospective, Observational, Single-Centre Study (Contour Study).

Background and objectives The quest for an accurate and reliable non-invasive method of assessing cardiac output in critically ill patients is still ongoing. Carotid artery Doppler is a promising non-invasive, reproducible, and feasible bedside monitor. So we compared the change in cardiac output derived from arterial pressure waveforms (pulse contour analysis) with that from carotid artery Doppler-derived measurements, in post-major elective abdominal surgery patients. Materials and methods We conducted a prospective observational study in 30 adult post-major elective abdominal surgery patients admitted to the Gastroenterology and Liver Transplant intensive care unit postoperatively on mechanical ventilator support, who were found to be fluid responsive clinically on passive leg raise (PLR) test. Demographics and vasopressor support were recorded. Hemodynamic parameters including heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), cardiac output (CO) using arterial pulse contour analysis (Vigileo monitor/FloTrac® sensor; Edwards Lifesciences, Irvine, California, United States), and carotid blood flow (CBF) were recorded on the baseline, pre- and post- PLR, and post fluid bolus administration. Balanced salt solution at the rate of 6ml/kg over 20 minutes was given as a fluid bolus. Results Of the 30 patients who were included in the study, 16 patients (53.3%) were on vasopressor support, mean (± SD) age of the patients was 52.93 (± 8.13) years. There was a significant increase in the SBP (mmHg) pre- to post-PLR, that is, 112.2±15.57 and 118.7±14.96, respectively (p-value = 0.001). Also from pre-PLR to post-fluid bolus administration, the increase in SBP was significant, 112.2±15.57 and 121.93±13.96, respectively (p-value = 0.001). The change in cardiac output measured using Vigileo and CBF from pre- to post-PLR (7.66±1.45 to 9.14±1.76, p< 0.001 for Vigileo and 8.10±1.66 to 9.72±1.99, p<0.001 for CBF) and pre-PLR to post fluid administration (7.66±1.45 to 9.39±1.77, p< 0.001 for Vigileo and 8.10±1.66 to 10.31±2.26, p< 0.001 for CBF) were significant. There was a positive correlation between the change in cardiac output as measured from arterial pulse contour analysis technique (Vigileo) and that measured from CBF (r=0.884) pre- and post-PLR. There was a significant correlation between cardiac output measurements derived from two techniques, before PLR, after PLR, and after fluid expansion (p< 0.001 for each variable). The change in cardiac output before PLR and after fluid expansion was also correlated by both the techniques (correlation coefficient being, r=0.781). Conclusion There was a significant positive correlation of the CO (absolute and change) measurements pre- and post-interventions (that is, PLR and fluid bolus administration) as made by pulse contour analysis (Vigileo) and by CBF in post-surgical patients. Pulse wave Doppler of CBF could be used as a surrogate for invasive measures of CO measurement for prediction of fluid responsiveness in this subgroup. Further larger studies can be performed to validate the same.

Targeted learning in observational studies with multi-valued treatments: An evaluation of antipsychotic drug treatment safety.

We investigate estimation of causal effects of multiple competing (multi-valued) treatments in the absence of randomization. Our work is motivated by an intention-to-treat study of the relative cardiometabolic risk of assignment to one of six commonly prescribed antipsychotic drugs in a cohort of nearly 39 000 adults with serious mental illnesses. Doubly-robust estimators, such as targeted minimum loss-based estimation (TMLE), require correct specification of either the treatment model or outcome model to ensure consistent estimation; however, common TMLE implementations estimate treatment probabilities using multiple binomial regressions rather than multinomial regression. We implement a TMLE estimator that uses multinomial treatment assignment and ensemble machine learning to estimate average treatment effects. Our multinomial implementation improves coverage, but does not necessarily reduce bias, relative to the binomial implementation in simulation experiments with varying treatment propensity overlap and event rates. Evaluating the causal effects of the antipsychotics on 3-year diabetes risk or death, we find a safety benefit of moving from a second-generation drug considered among the safest of the second-generation drugs to an infrequently prescribed first-generation drug known for having low cardiometabolic risk.

Fluid Responsiveness in Critically Ill Patients Using Carotid Peak Systolic Velocity Variability: A New Frontier.

Background and objectives A fluid responder is a patient who can increase his stroke volume/ cardiac output by more than 10%-15% after a fluid bolus. Left ventricular outflow tract (LVOT) velocity time integral (VTI) variability is widely used as an adynamic parameter of fluid responsiveness, but a transthoracic echo view of LVOT VTI is often time-consuming and, at times, difficult to achieve. So, in the quest for another parameter that might equally be a good surrogate marker of stroke volume variation, carotid peak systolic velocity (CPSV) variation has been studied. The objective was to assess CPSV variation in patients who are already fluid responders. Methods The sample size was calculated considering a minimum correlation coefficient of 0.5. Adult patients in whom the physician wanted to give a fluid bolus and whose average LVOT VTI was more than 15% over 3 respiratory cycles were included in the study. Demographic variables, along with hemodynamic parameters such as heart rate, blood pressure, the need for vasopressors, mode of breathing (spontaneous or mechanical ventilation), and CPSV variation,were noted and averaged over three respiratory cycles. Fluid bolus (Plasmalyte) 6 ml/kg bolus over 10-15 minutes. Post-fluid hemodynamic variables, along with averaged LVOT VTI over three respiratory cycles and averaged CPSV variation over three respiratory cycles, are noted. Results Thirty adult patients were evaluated in the study. In spontaneously breathing patients (n=12), the average CPSV variation expressed as mean + standard deviation before and after fluid administration of 6ml/kg of ideal body weight was 14.1 ± 3.4 and 5.4 ± 2.6, respectively (p < 0.05). In mechanically ventilated patients (n=18), the average CPSV variation expressed as mean + standard deviation before and after fluid administration of 6ml/kg of ideal body weight fluid was 15 ± 5.3 and 6.5 ± 3.1, respectively (p <0.005). Overall, there was a statistically significant positive correlation between LVOT VTI variation and CPSV variation before fluid therapy (correlation coefficient 0.56 and p-value 0.001) and a statistically significant moderate positive correlation post-fluid therapy (correlation coefficient 0.37 and p-value 0.043). Conclusion We found a significant decrease in CPSV variation post-fluid administration in patients who are fluid responders, which mimics a decrease in stroke volume variation after fluid administration in patients who are fluid responsive.

Mental health of health care workers during the hour of crisis - A study from tertiary care hospital in North India.

Background and Aims: This cross-sectional study aimed to analyze the psychosocial, behavioral, and sleep impact of coronavirus disease-19 (COVID-19) pandemic on healthcare workers (HCWs) at a tertiary-care hospital in Northern India. Materials and Methods: An online questionnaire including three psychological scales - peritraumatic distress inventory (PDI), insomnia Severity Index (ISI), and Depression anxiety stress scale was circulated among the HCWs at a tertiary-care hospital in Northern India. Results: Three hundred and ninety-six HCWs (Mean age standard deviation: 34.8 [8.1%] years; 181 females) responded. Place of posting was active COVID area (27.2%), reserve active COVID team (23.2%), trained reserve pool (29.5%), and non-COVID areas (19.9%). More than half of all the respondents (51%) had abnormal PDI score (>14) with a propensity to develop posttraumatic stress disorder. Furthermore, there was a significantly higher prevalence of abnormal PDI scores in those involved in active COVID care units (74%) versus non-COVID care unit (24%, P = 0.001). More than 60% of all the respondents had abnormal ISI score suggesting significant insomnia. Stress was seen in 71% of all the respondents while 82% were anxious and 77% participants had depressive symptoms. Hence, the psychological morbidity among the HCWs was high. Conclusion: Our study found a much higher prevalence of peritraumatic distress, insomnia, anxiety, stress, and depression among the HCWs, more so in those working in COVID areas. Factors indigenous to Indian population in terms of psychological health must be studied and addressed to reduce this psychological morbidity since the battle with COVID is long.

An Enhanced User Authentication and Key Agreement Scheme for Wireless Sensor Networks Tailored for IoT.

A security protocol for wireless transmission is essential to defend sensitive information from malicious enemies by providing a variety of facilities such as privacy of the user's information, secure session key, associated authentication, and user-repeal facility when a person's authorizations are suddenly disclosed. Singh et al. proposed an improved user authentication and key agreement system for wireless sensor networks (WSNs). Authors are sure that their protocol is secure from various attacks. Here, we find several security pitfalls in their scheme, such as an offline password-guessing attack, failure to protect the session key, and a man-in-the-middle attack. To remove the identified pitfalls found in Singh et al.'s scheme, we design an enhanced authentication scheme for WSNs tailored for IoT. We prove the reliability of our proposed protocol using the real or random (RoR) model. We also evaluate the proposed scheme with the associated schemes and show its superior efficacy as compared to its counterparts.

Hindi Translation and Cross-cultural Validation of Child Version of Loneliness and Dissatisfaction, Parent-child Relationship and Conflict Behavior Questionnaires.

Objectives: We sought to translate the parallel forms (parent and child versions) of English versions of the Loneliness and Dissatisfaction Questionnaire (LSDQ-C), Parent Child Relationship (PCRQ-C), and Conflict Behavior Questionnaire (CBQ-C) into Hindi and evaluate their psychometric properties. Methods: Hindi translation and cross-language adaptation of LSDQ-C, PCRQ-C, and CBQ-C were done following WHO guidelines. Children aged 10-18 years old studying in either government or private schools of Chandigarh were enrolled through snowball convenient random sampling technique. Psychometric properties were assessed using intraclass correlation (ICC), Chronbach's alpha, test-retest reliability, paired t-test, and split-half reliability. Results: Item wise test-retest reliability of the Hindi version of all scales was assessed, and for most items, the ICC value was > 0.80, indicting good to excellent reliability. ICC value was in the acceptable range for a few items for the child version of the scales (0.70). Split half reliability was > 0.80. Our findings suggest good to excellent agreement between the English and Hindi version of all the scales. Conclusions: The internal consistency, split-half reliability, and test-retest reliability are good to excellent. Thus, the Hindi version of parallel forms (parent and child versions) LSDQ, PCR, and CBQ as translated in this study is a valid instrument.

Counterfactual time series analysis of short-term change in air pollution following the COVID-19 state of emergency in the United States.

Lockdown measures implemented in response to the COVID-19 pandemic produced sudden behavioral changes. We implement counterfactual time series analysis based on seasonal autoregressive integrated moving average models (SARIMA), to examine the extent of air pollution reduction attained following state-level emergency declarations. We also investigate whether these reductions occurred everywhere in the US, and the local factors (geography, population density, and sources of emission) that drove them. Following state-level emergency declarations, we found evidence of a statistically significant decrease in nitrogen dioxide (NO2) levels in 34 of the 36 states and in fine particulate matter (PM2.5) levels in 16 of the 48 states that were investigated. The lockdown produced a decrease of up to 3.4 µg/m3 in PM2.5 (observed in California) with range (- 2.3, 3.4) and up to 11.6 ppb in NO2 (observed in Nevada) with range (- 0.6, 11.6). The state of emergency was declared at different dates for different states, therefore the period "before" the state of emergency in our analysis ranged from 8 to 10 weeks and the corresponding "after" period ranged from 8 to 6 weeks. These changes in PM2.5 and NO2 represent a substantial fraction of the annual mean National Ambient Air Quality Standards (NAAQS) of 12 µg/m3 and 53 ppb, respectively. As expected, we also found evidence that states with a higher percentage of mobile source emissions (obtained from 2014) experienced a greater decline in NO2 levels after the lockdown. Although the socioeconomic restrictions are not sustainable, our results provide a benchmark to estimate the extent of achievable air pollution reductions. Identification of factors contributing to pollutant reduction can help guide state-level policies to sustainably reduce air pollution.

Identifying windows of susceptibility to endocrine disrupting chemicals in relation to gestational weight gain among pregnant women attending a fertility clinic.

BACKGROUND: Exposure to endocrine disrupting chemicals (EDC), such as phthalates and phenols, during pregnancy may be associated with excessive gestational weight gain (GWG), an important predictor of future health of the mother and the offspring. There is however a paucity of literature examining this association, and no study has accounted for the complex nature of EDCs exposure as a time-varying mixture of chemicals. OBJECTIVE: We examined the association between trimester-specific EDCs mixture and GWG in pregnant women attending a fertility clinic, to identify windows of susceptibility to such exposures, and assess the individual contribution of each chemical over pregnancy. METHODS: We included 243 pregnant women from the Environment and Reproductive Health (EARTH) Study, who provided up to 3 urine samples (one per trimester), and with available data on GWG. Urinary concentrations of 7 phthalate metabolites, bisphenol A, and 2 parabens, corrected for specific gravity, were included in the analysis. The association between trimester-specific EDCs mixture and GWG was evaluated using multiple regression models - categorizing exposures into concentration quartiles- and with Bayesian Kernel Machine Regression (BKMR), while adjusting for potential confounders. Hierarchical BKMR (hBKMR) was used to account for the time-varying nature of chemical concentrations over pregnancy, identifying the most important trimester and most important EDC within each trimester. RESULTS: During 1st trimester, higher GWG was observed at higher sum of metabolites of di (2-ethylhexyl) phthalate (ΣDEHP) from both multiple regression (e.g. comparing the 4th quartile with the 1st: ß = 2.36 kg, 95% CI: 0.47, 5.19) and BKMR. During 2nd and 3rd trimesters, positive associations with mono-n-butyl phthalate and propylparaben, and negative with ΣDEHP and methylparaben were observed. When evaluating exposures as a time-varying mixture with hBKMR, 1st trimester was the most important exposure window when evaluating prenatal urinary EDCs in relation to GWG. Within the 1st trimester, urinary ΣDEHP, mono-isobutyl phthalate and propylparaben had the highest contribution in the positive association between the mixture and GWG. CONCLUSION: We observed positive associations between urinary EDCs during pregnancy, especially DEHP metabolites, and GWG. Our results suggest the 1st trimester of pregnancy as the time window of highest susceptibility to the effects of EDCs on GWG, with potential indication for the design of public health interventions, informing prevention strategies for reducing sources of exposure at specific time points.

Colloidal Organohalide Perovskite Nanoplatelets Exhibiting Quantum Confinement.

We prepare colloidal nanoplatelets of methylammonium lead bromide (MAPbBr3) perovskite and compare the optical signatures of excitons in these two-dimensional systems to spherical perovskite nanocrystals and the corresponding bulk phase. We find that excitonic features that had previously been attributed to quantum confinement in MAPbBr3 nanocrystals are in fact a property of the bulk perovskite phase. Furthermore, we find that higher-energy absorption features originate from two-dimensional nanoplatelets, which are present in the nanocrystal reaction product. Upon further purification, we obtain colloidal nanoplatelets with predominantly single unit cell thickness and submicron lateral dimensions, which are stable in solution and exhibit a sharp excitonic absorption feature 0.5 eV blue-shifted from that of the three-dimensional bulk MAPbBr3 phase, representing a new addition to the growing family of colloidal two-dimensional nanostructures.

Photoluminescence of cerium fluoride and cerium-doped lanthanum fluoride nanoparticles and investigation of energy transfer to photosensitizer molecules.

CexLa1-xF3 nanoparticles have been proposed for use in nanoscintillator-photosensitizer systems, where excitation of nanoparticles by ionizing radiation would result in energy transfer to photosensitizer molecules, effectively combining the effects of radiotherapy and photodynamic therapy. Thus far, there have been few experimental investigations of such systems. This study reports novel synthesis methods for water-dispersible Ce0.1La0.9F3/LaF3 and CeF3/LaF3 core/shell nanoparticles and an investigation of energy transfer to photosensitizers. Unbound deuteroporphyrin IX 2,4-disulfonic acid was found to substantially quench the luminescence of large (>10 nm diameter) aminocaproic acid-stabilized nanoparticles at reasonable concentrations and loading amounts: up to 80% quenching at 6% w/w photosensitizer loading. Energy transfer was found to occur primarily through a cascade, with excitation of "regular" site Ce(3+) at 252 nm relayed to photosensitizer molecules at the nanoparticle surface through intermediate "perturbed" Ce(3+) sites. Smaller (<5 nm) citrate-stabilized nanoparticles were coated with the bisphosphonate alendronate, allowing covalent conjugation to chlorin e6 and resulting in static quenching of the nanoparticle luminescence: ∼50% at ∼0.44% w/w. These results provide insight into energy transfer mechanisms that may prove valuable for optimizing similar systems.

A lead (II) 3D coordination polymer based on a marine cyclic peptide motif.

The crystal structure of a naturally occurring cyclic tetrapeptide cyclo(Gly-L-Ser-L-Pro-L-Glu) [cyclo(GSPE)] was obtained. The conformation of synthesized cyclo(GSPE) fixes the coordination to lead ion in a 1:1 ratio. This cyclo(GSPE)-Pb complex was constructed as an asymmetric 3D network in the crystalline state. The polymerization of a heavy metal ion with a rigid asymmetric cyclic tetrapeptide represents the first example of a new class of macrocyclic complexes.

Two-color two-dimensional electronic spectroscopy using dual acousto-optic pulse shapers for complete amplitude, phase, and polarization control of femtosecond laser pulses.

We demonstrate a dual pulse-shaper setup capable of independent polarization, phase, and amplitude control over each pulse. By using active phase stabilization, we achieve a phase stability of ~λ/314 between the two pulse shapers, making the dual-shaper setup suitable for both two-quantum and one-quantum measurements. The setup is compact and easily switchable between pump-probe and collinear geometries. We further illustrate the functionality of the dual-shaper setup by performing two-color 2D visible spectroscopy on colloidal CdSe quantum dots in pump-probe geometry.

False multiple exciton recombination and multiple exciton generation signals in semiconductor quantum dots arise from surface charge trapping.

Multiple exciton recombination (MER) and multiple exciton generation (MEG) are two of the main processes for assessing the usefulness of quantum dots (QDs) in photovoltaic devices. Recent experiments, however, have shown that a firm understanding of both processes is far from well established. By performing surface-dependent measurements on colloidal CdSe QDs, we find that surface-induced charge trapping processes lead to false MER and MEG signals resulting in an inaccurate measurement of these processes. Our results show that surface-induced processes create a significant contribution to the observed discrepancies in both MER and MEG experiments. Spectral signatures in the transient absorption signals reveal the physical origin of these false signals.

Controlling piezoelectric response in semiconductor quantum dots via impulsive charge localization.

By direct observation of coherent acoustic phonons, we demonstrate a novel extrinsic piezoelectric response in colloidal CdSe semiconductor quantum dots. This response is driven by the migration of charges to the surface of the quantum dot on a vibrationally impulsive time scale. Surface- and fluence-dependent studies reveal that the observed carrier capture based piezo response is controllable and is at least an order of magnitude larger than the intrinsic piezo response of wurtzite CdSe.

Magnetic frustration and spin disorder in isostructural M(mu-OH2)2[Au(CN)2]2 (M = Mn, Fe, Co) coordination polymers containing double aqua-bridged chains: SQUID and microSR studies.

A series of isostructural M(mu-OH(2))(2)[Au(CN)(2)](2) (M = Co, Fe, and Mn) coordination polymers was synthesized from the reaction of M(II) with [(n)Bu(4)N][Au(CN)(2)]. The basic structural motif for these polymers is analogous to that of previously reported Cu(II)- and Ni(II)-containing polymers and contains repeating double aqua bridges between metal centers that yield a chain structure with pendant [Au(CN)(2)](-) units. The aqueous reaction with Fe(III) yields Fe(mu-OH(2))(mu-OH)[Au(CN)(2)](2), which has a similar structure. The magnetic properties of these polymers were investigated by a combination of SQUID magnetometry and zero-field muon spin relaxation. The double aqua bridges were found to mediate ferromagnetic interactions along the chains in the Co(II)-containing polymer, whereas intrachain antiferromagnetic interactions are present in the Fe(II)-, Fe(III)-, and Mn(II)-containing polymers. Weak magnetic interchain interactions mediated through hydrogen bonds, involving the bridging water molecules and the pendant cyanide groups, are also present. In zero field, the interchain interactions yield a phase transition to a disordered spin-frozen magnetic state below 2-5 K for every polymer. However, the degree of spin disorder varies considerably, depending on the metal center.