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Though widely used, resting heart rate (RHR), as measured by a wearable device, has not been previously evaluated in a large cohort against a variety of important baseline characteristics. This study aimed to assess the validity of the RHR measured by a wearable device compared against the gold standard of ECG (electrocardiography), and assess the relationships between device-measured RHR and a broad range of clinical characteristics. The Project Baseline Health Study (PHBS) captured detailed demographic, occupational, social, lifestyle, and clinical data to generate a deeply phenotyped cohort. We selected an analysis cohort within it, which included participants who had RHR determined by both ECG and the Verily Study Watch (VSW). We examined the correlation between these simultaneous RHR measures and assessed the relationship between VSW RHR and a range of baseline characteristics, including demographic, clinical, laboratory, and functional assessments. From the overall PBHS cohort (N=2502), 875 (35%) participants entered the analysis cohort (mean age 50.9, SD 16.5 years; n=519, 59% female and n=356, 41% male). The mean and SD of VSW RHR was 66.6 (SD 11.2) beats per minute (bpm) for female participants and 64.4 (SD 12.3) bpm for male participants. There was excellent reliability between the two measures of RHR (ECG and VSW) with an intraclass correlation coefficient of 0.946. On univariate analyses, female and male participants had similar baseline characteristics that trended with higher VSW RHR: lack of health care insurance (both P<.05), higher BMI (both P<.001), higher C-reactive protein (both P<.001), presence of type 2 diabetes mellitus (both P<.001) and higher World Health Organization Disability Assessment Schedule (WHODAS) 2.0 score (both P<.001) were associated with higher RHR. On regression analyses, within each domain of baseline characteristics (demographics and socioeconomic status, medical conditions, vitals, physical function, laboratory assessments, and patient-reported outcomes), different characteristics were associated with VSW RHR in female and male participants. RHR determined by the VSW had an excellent correlation with that determined by ECG. Participants with higher VSW RHR had similar trends in socioeconomic status, medical conditions, vitals, laboratory assessments, physical function, and patient-reported outcomes irrespective of sex. However, within each domain of baseline characteristics, different characteristics were most associated with VSW RHR in female and male participants. ClinicalTrials.gov NCT03154346; https://clinicaltrials.gov/study/NCT03154346.

To evaluate remote participant engagement in a clinical study over time, based on data from the Project Baseline Health Study (PBHS), a hybrid in-person and virtual study. The PBHS enrolled 2,502 adult US residents from March 3, 2017 to April 26, 2019, with a ≤5-year follow-up. We summarized 4-year retention and rates of longitudinal patient-reported outcome survey completion. We investigated participant characteristics for their associations with quarterly remote survey completion using regression models. Of the total participants (  = 2,502), 94% remained enrolled after 4 years and 60% completed all annual visits; 2,490 participants stayed enrolled for at least one quarter. The median (IQR) number of remote electronic survey sets completed was 8 (3-12), of a possible 16. Age [odds ratio (OR), >70 vs. ≤30 years: 2.56; 95% CI: 2.24-2.94] and education (OR, advanced degree vs. ≤high school: 1.36; 95% CI: 1.22-1.52) were positively associated with remote survey completion. Participants with lower odds of completion were Black (OR vs. White: 0.73; 95% CI: 0.67-0.80), Hispanic (OR vs. non-Hispanic: 0.84; 95% CI: 0.77-0.93), or had at least mild symptoms of depression (OR vs. without: 0.90; 95% CI: 0.84-0.96) or anxiety (OR vs. without: 0.84; 95% CI: 0.78-0.90). Overall, 94% of PBHS participants remained enrolled after four years. Age, race, ethnicity, income, education, and symptomatic depression/anxiety were significantly associated with longitudinal remote questionnaire completion. These findings on engagement over time may inform future longitudinal study design. Clinicaltrials.gov, identifier (NCT03154346).

Kinetic studies of the uptake of iron by transferrin from iron-pyrophosphate indicate that the reaction proceeds via an intermediate mixed ligand complex of the type PP(,i)-Fe-transferrin-CO(,3)('2-). The EPR spectrum of the \"intermediate\" complex was determined by computer modelling of the kinetic data and deconvolution of the experimental spectra. The distinct spectral characteristics of the intermediate indicate that the coordination environment of the iron is different from that of either of the reactants, consistent with formation of a complex in which iron is coordinated to both transferrin and pyrophosphate. Studies of the interaction of sodium cyanide with iron(III)-transferrin demonstrate that a low-spin cyanide adduct of transferrin is produced which exhibits a rhombic EPR spectrum with principal components at g = 1.92, 2.15 and 2.34. The stoichiometry of adduct formation is: Fe(,c)-Tf-HCO(,3) + 2 CN('-) (--->) Fe(,c)-Tf-(CN)(,3) + HCO(,3)('-) where adduct formation only occurs at the C-terminal domain and the subscript \"c\" designates this half of the protein. This is the first example of an inorganic anion substituting for bicarbonate in transferrin. The results also show that ligands in the first coordination sphere of iron bound at the specific iron binding site in transferrin are susceptible to displacement by chelators in solution. Nitrate binding to transferrin was studied using N-15 paramagnetic relaxation enhancement. Significant relaxation enhancement of the N-15 nucleus in the presence of bound paramagnetic iron was observed, indicating that the anion binding site is close to the metal on the protein. The metal anion distance was estimated to be in the range of eight to fifteen Angstroms.

Whoever thought the day would come when NBC and CBS would fight a ratings war with competing specials of \"The Nutcracker\"? And did anyone expect that even Public Television would air a different dance program per week for two straight months, beginning with a new look at the ballets of George Balanchine?

We determined the variability in enteral feeding practices in mechanically ventilated patients in four adult intensive care units of a tertiary-care, referral hospital. Patients who had been mechanically ventilated for at least 48 h and received enteral nutrition were prospectively followed. Fifty-five of 101 consecutive mechanically ventilated patients received enteral nutrition; in 93% of patients, feedings were infused into the stomach. Patients who were cared for in the medical intensive care unit, where a nutritional protocol was operational, received enteral nutrition earlier in their ventilatory course ( P = 0.004) and feedings were advanced to target rates faster ( P = 0.043) than those who received care in other units. The number ( P = 0.243) and duration ( P = 0.668) of interruptions in feeding did not differ by patient location. On average, patients received only 50% to 70% of their targeted caloric goals during the first 6 days of enteral nutrition. Most feeding discontinuations (41%) were secondary to procedures. Gastrointestinal intolerances, including vomiting, aspiration, abdominal distention, and increased gastric residuals, were uncommon despite allowing gastric residuals up to 300 mL. The practice of providing enteral feeds to mechanically ventilated patients varies widely, even within one hospital. A protocol enhanced early initiation of enteral feeds and advancement to target feeding rates but did not alter the number or duration of interruptions in enteral feedings. Procedures represented the most common reason for stopping enteral feeds, and gastrointestinal intolerances (vomiting, aspiration, and increased gastric residuals) caused few feeding interruptions. The gastric route was safe and well tolerated for early enteral feeding in most mechanically ventilated patients.

Nitrogen oxide (NO) species are markers for oxidative stress that may be pathogenic in acute lung injury (ALI). We tested two hypotheses in patients with ALI: (1) higher levels of urine NO would be associated with worse clinical outcomes, and (2) ventilation with lower VT would reduce urine NO as a result of less stretch injury. Urine NO levels were measured by chemiluminescence in 566 patients enrolled in the National Heart Lung and Blood Institute Acute Respiratory Distress Syndrome Network trial of 6 ml/kg versus 12 ml/kg VT ventilation. The data were expressed corrected and uncorrected for urine creatinine (Cr). Higher baseline levels of urine NO to Cr were associated with lower mortality (odds ratio, 0.43 per log(10) increase in the ratio), more ventilator-free days (mean increase, 1.9 d), and more organ-failure-free days (mean increase, 2.3 d) on multivariate analysis (p < 0.05 for all analyses). Similar results were obtained using urine NO alone. NO to Cr levels were higher on Day 3 in the 6 ml/kg than in the 12 ml/kg VT group (p = 0.04). Contrary to our hypothesis, higher urine NO was associated with improved outcomes in ALI at baseline and after treatment with the 6 ml/kg VT strategy. Higher endogenous NO may reflect less severe lung injury and better preservation of the pulmonary and systemic endothelium or may serve a protective function in patients with ALI.

While seemingly straightforward in principle, the reliable estimation of rate constants is seldom easy in practice. Numerous issues, such as the complication of poor reaction coordinates, cause obvious approaches to yield unreliable estimates. When a reliable order parameter is available, the reactive flux theory of Chandler allows the rate constant to be extracted from the plateau region of an appropriate reactive flux function. However, when applied to real data from single-molecule experiments or molecular dynamics simulations, the rate can sometimes be difficult to extract due to the numerical differentiation of a noisy empirical correlation function or difficulty in locating the plateau region at low sampling frequencies. We present a modified version of this theory which does not require numerical derivatives, allowing rate constants to be robustly estimated from the time-correlation function directly. We compare these approaches using single-molecule force spectroscopy measurements of an RNA hairpin.