The measurement of the optical absorption cross section of photosystem 1 and photosystem 2 from whole live cells of porphyridium cruentum, in light state 1 and light state 2

The optical cross section of PS I in whole cells of Porphyridium cruentum (UTEX 161), held in either state 1 or state 2, was determined by measuring the change in absorbance at 820nm, an indication of P700+; the X-section of PS2 was determined by measuring the variable fluorescence, (Fv-Fo)/Fo, from PS2. Both cross-sections were 7 determined by fitting Poisson distribution equations to the light saturation curves obtained with single turnover laser flashes which varied in intensity from zero to a level where maximum yield occurred. Flash wavelengths of 574nm, 626nm, and 668nm were used, energy absorbed by PBS, by PBS and chla, and by chla respectively. There were two populations of both PSi and PS2. A fraction of PSi is associated with PBS, and a fraction of PS2 is free from PBS. On the transition S1->S2, only with PBS-absorbed energy (574nm) did the average X-section of PSi increase (27%), and that of PS2 decrease (40%). The fraction of PSi associated with PBS decreased, from 0.65 to 0.35, and the Xsection of this associated PS 1 increased, from 135±65 A2 to 400±300A2. The cross section of PS2 associated with PBS decreased from 150±50 A2 to 85±45 A2, but the fraction of PS2 associated with PBS, approximately 0.75, did not change significantly. The increase in PSi cross section could not be completely accounted for by postulating that several PSi are associated with a single PBS and that in the transition to state2, fewer PSi share the same number of PBS, resulting in a larger X-section. It is postulated that small changes occur in the attachment of PS2 to PBS causing energy to be diverted to the attached PSi. These experiments support neither the mobile-PBS model of state transitions nor that of spillover. From cross section changes there was no evidence of energy transfer from PS2 to PSi with 668nm light. The decrease in PS2 fluorescence which occurred at this wavelength cannot be explained by energy transfer; another explanation must be sought. No explanation was found for an observed decrease in PSi yield at high flash intensities

Cost effectiveness of school-located influenza vaccination programs for elementary and secondary school children.

BackgroundStudies have noted variations in the cost-effectiveness of school-located influenza vaccination (SLIV), but little is known about how SLIV's cost-effectiveness may vary by targeted age group (e.g., elementary or secondary school students), or vaccine consent process (paper-based or web-based). Further, SLIV's cost-effectiveness may be impacted by its spillover effect on practice-based vaccination; prior studies have not addressed this issue.MethodsWe performed a cost-effectiveness analysis on two SLIV programs in upstate New York in 2015-2016: (a) elementary school SLIV using a stepped wedge design with schools as clusters (24 suburban and 18 urban schools) and (b) secondary school SLIV using a cluster randomized trial (16 suburban and 4 urban schools). The cost-per-additionally-vaccinated child (i.e., incremental cost-effectiveness ratio (ICER)) was estimated by dividing the incremental SLIV intervention cost by the incremental effectiveness (i.e., the additional number of vaccinated students in intervention schools compared to control schools). We performed deterministic analyses, one-way sensitivity analyses, and probabilistic analyses.ResultsThe overall effectiveness measure (proportion of children vaccinated) was 5.7 and 5.5 percentage points higher, respectively, in intervention elementary (52.8%) and secondary schools (48.2%) than grade-matched control schools. SLIV programs vaccinated a small proportion of children in intervention elementary (5.2%) and secondary schools (2.5%). In elementary and secondary schools, the ICER excluding vaccine purchase was $85.71 and$86.51 per-additionally-vaccinated-child, respectively. When additionally accounting for observed spillover impact on practice-based vaccination, the ICER decreased to $80.53 in elementary schools -- decreasing substantially in secondary schools. (to$53.40). These estimates were higher than the published practice-based vaccination cost (median = $25.50, mean =$45.48). Also, these estimates were higher than our 2009-2011 urban SLIV program mean costs ($65) due to additional costs for use of a new web-based consent system ($12.97 per-additionally-vaccinated-child) and higher project coordination costs in 2015-2016. One-way sensitivity analyses showed that ICER estimates were most sensitive to the SLIV effectiveness.ConclusionsSLIV raises vaccination rates and may increase practice-based vaccination in primary care practices. While these SLIV programs are effective, to be as cost-effective as practice-based vaccination our SLIV programs would need to vaccinate more students and/or lower the costs for consent systems and project coordination.Trial registrationClinicalTrials.gov NCT02227186 (August 25, 2014), updated NCT03137667 (May 2, 2017)

A single center observational study on emergency department clinician non-adherence to clinical practice guidelines for treatment of uncomplicated urinary tract infections

Background The Emergency Department (ED) is a frequent site of antibiotic use; poor adherence with evidence-based guidelines and broad-spectrum antibiotic overuse is common. Our objective was to determine rates and predictors of inappropriate antimicrobial use in patients with uncomplicated urinary tract infections (UTI) compared to the 2010 International Clinical Practice Guidelines (ICPG). Methods A single center, prospective, observational study of patients with uncomplicated UTI presenting to an urban ED between September 2012 and February 2014 that examined ED physician adherence to ICPG when treating uncomplicated UTIs. Clinician-directed antibiotic treatment was compared to the ICPG using a standardized case definition for non-adherence. Binomial confidence intervals and student’s t-tests were performed to evaluate differences in demographic characteristics and management between patients with pyelonephritis versus cystitis. Regression models were used to analyze the significance of various predictors to non-adherent treatment. Results 103 cases met the inclusion and exclusion criteria, with 63.1 % receiving non-adherent treatment, most commonly use of a fluoroquinolone (FQ) in cases with cystitis (97.6 %). In cases with pyelonephritis, inappropriate antibiotic choice (39.1 %) and no initial IV antibiotic for pyelonephritis (39.1 %) where recommended were the most common characterizations of non-adherence. Overall, cases of cystitis were no more/less likely to receive non-adherent treatment than cases of pyelonephritis (OR 0.9, 95 % confidence interval 0.4–2.2, P = 0.90). In multivariable analysis, patients more likely to receive non-adherent treatment included those without a recent history of a UTI (OR 3.8, 95 % CI 1.3–11.4, P = 0.02) and cystitis cases with back or abdominal pain only (OR 11.4, 95 % CI 2.1–63.0, P = 0.01). Conclusions Patients with cystitis with back or abdominal pain only were most likely to receive non-adherent treatment, potentially suggesting diagnostic inaccuracy. Physician education on evidence-based guidelines regarding the treatment of uncomplicated UTI will decrease broad-spectrum use and drug resistance in uropathogens

Inhaler technique mastery and maintenance in healthcare professionals trained on different devices

Peer reviewedPostprin

A Prospective, Controlled Trial of a Protocol-based Strategy to Discontinue Mechanical Ventilation

Weaning protocols can improve outcomes, but their efficacy may vary with patient and staff characteristics. In this prospective, controlled trial, we compared protocol-based weaning to usual, physiciandirected weaning in a closed medical intensive care unit (ICU) with high physician staffing levels and structured, system-based rounds. Adult patients requiring mechanical ventilation for more than 24 hours were assigned to usual care (UC) or protocol weaning based on their hospital identification number. Patients assigned to UC (n ϭ 145) were managed at their physicians' discretion. Patients assigned to protocol (n ϭ 154) underwent daily screening and a spontaneous breathing trial by respiratory and nursing staff without physician intervention. There were no significant baseline differences in patient characteristics between groups

The Relationship Between Real-World Inhaled Corticosteroid Adherence and Asthma Outcomes:A Multilevel Approach

Background: Low inhaled corticosteroid (ICS) adherence is associated with increased asthma burden. This relationship is likely bidirectional, and may vary across adherence stages (initiation, implementation, and persistence). Studies rarely examine reciprocal influences. Objective: To investigate the relationship between ICS implementation and asthma-related outcomes over 2 years, considering bidirectionality and temporal sequence. Methods: Primary care records (1987-2012) from the Optimum Patient Care Research Database, United Kingdom, were used. Eligible patients were 6 years or older and had 3 or more years of continuous registration starting 1 year before ICS initiation (index date), physician-diagnosed asthma, 2 or more ICS and/or short-acting β-agonist prescriptions each follow-up year, and no long-acting β-agonists, leukotriene receptor antagonists, or maintenance oral corticosteroids in the preceding year. ICS implementation (percentage of days covered) and risk domain asthma control (RDAC; no asthma-related hospitalizations, emergency visits, or outpatient visits and no oral corticosteroid or antibiotic prescriptions with evidence of respiratory review) were estimated for each prescription interval (period between 2 successive prescriptions). Multilevel analyses modeled bidirectional relationships between ICS implementation and RDAC (and its components), controlling for sociodemographic and clinical characteristics. Results: In prescription data from 10,472 patients, ICS implementation in the preceding interval did not predict RDAC, but was weakly positively associated with simultaneous RDAC. Being male, non–current smoker, without chronic obstructive pulmonary disease diagnosis, and with fewer than 4 comorbidities significantly increased odds of RDAC. Asthma-related antibiotics and outpatient visits in the same interval and short-acting β-agonist overuse in the preceding and same interval predicted lower ICS implementation. Conclusions: Patients may adapt their ICS use to their current needs without this impacting later RDAC.</p

Asthma routinization, family asthma management, caregiver depressive symptoms, and medication adherence in Head Start preschool children

IntroductionMedication adherence is suboptimal in childhood asthma. Children rely on caregivers to manage medication administration. It is important to detect families who are at risk for poor adherence or to identify potential areas that can assist families with better adherence to asthma medications in order to improve asthma outcomes. We investigated the association between asthma routines, family asthma management knowledge and skills, and caregiver depressive symptoms with daily controller medication adherence among Head Start preschool children in Baltimore City.MethodsOur study included 256 low-income urban preschool children who were prescribed a daily controller medication. Asthma routinization (by the Asthma Routines Questionnaire), family asthma management [by the Family Asthma Management System Scale (FAMSS)], and caregiver depressive symptoms (by the Center for Epidemiological Studies – Depression) were assessed at baseline. The medication possession ratio (MPR) to measure adherence to daily controller medications was calculated at baseline and 12 months from pharmacy fill records. Multiple regression models evaluated the relationship between asthma routinization, the FAMSS, the CES-D, and MPR.ResultsResults indicated that only 7% of families had an MPR above 80% at baseline, and 24% of caregivers had clinically significant depressive symptoms. Higher asthma medication routines were associated with higher MPR at baseline (b = 0.05, p = 0.03). Higher family asthma management was associated with higher MPR at both baseline (b = 0.04, p &lt; 0.01) and 12 months (b = 0.05, p &lt; 0.01).DiscussionOur findings highlight the importance of family asthma management and maintaining medication routines over time to improve asthma controller medication adherence

Improved adherence with once-daily versus twice-daily dosing of mometasone furoate administered via a dry powder inhaler: a randomized open-label study

Background Poor adherence with prescribed asthma medication is a major barrier to positive treatment outcomes. This study was designed to determine the effect of a once-daily administration of mometasone furoate administered via a dry powder inhaler (MF-DPI) on treatment adherence compared with a twice-daily administration. Methods This was a 12-week open-label study designed to mimic an actual clinical setting in patients ≥12 years old with mild-to-moderate persistent asthma. Patients were randomized to receive MF-DPI 400 μg once-daily in the evening or MF-DPI 200 μg twice-daily. Adherence was assessed primarily using the number of actual administered doses reported from the device counter divided by the number of scheduled doses. Self-reports were also used to determine adherence. Health-related quality of life, healthcare resource utilization, and days missed from work or school were also reported. Results 1233 patients were randomized. The mean adherence rates, as measured by the automatic dose counter, were significantly better (P < 0.001) with MF-DPI 400 μg once-daily in the evening (93.3%) than with MF-DPI 200 μg twice-daily (89.5%). Mean adherence rates based on self-reports were also significantly better (P < 0.001) with MF-DPI 400 μg QD PM (97.2%) than with MF-DPI 200 μg twice-daily (95.3%). Adherence rates were lower in adolescents (12-17 years old). Health-related quality of life improved by 20% in patients using MF-DPI once-daily in the evening and by 14% in patients using MF-DPI twice-daily. Very few (<8%) patients missed work/school. Conclusion Mean adherence rates were greater with a once-daily dosing regimen of MF-DPI than with a twice-daily dosing regimen. This trial was completed prior to the ISMJE requirements for trial registration

Ecological genetics in the North Atlantic: environmental gradients and adaptation at specific loci

The North Atlantic intertidal community provides a rich set of organismal and environmental material for the study of ecological genetics. Clearly defined environmental gradients exist at multiple spatial scales: there are broad latitudinal trends in temperature, meso-scale changes in salinity along estuaries, and smaller scale gradients in desiccation and temperature spanning the intertidal range. The geology and geography of the American and European coasts provide natural replication of these gradients, allowing for population genetic analyses of parallel adaptation to environmental stress and heterogeneity. Statistical methods have been developed that provide genomic neutrality tests of population differentiation and aid in the process of candidate gene identification. In this paper, we review studies of marine organisms that illustrate associations between an environmental gradient and specific genetic markers. Such highly differentiated markers become candidate genes for adaptation to the environmental factors in question, but the functional significance of genetic variants must be comprehensively evaluated. We present a set of predictions about locus-specific selection across latitudinal, estuarine, and intertidal gradients that are likely to exist in the North Atlantic. We further present new data and analyses that support and contradict these simple selection models. Some taxa show pronounced clinal variation at certain loci against a background of mild clinal variation at many loci. These cases illustrate the procedures necessary for distinguishing selection driven by internal genomic vs. external environmental factors. We suggest that the North Atlantic intertidal community provides a model system for identifying genes that matter in ecology due to the clarity of the environmental stresses and an extensive experimental literature on ecological function. While these organisms are typically poor genetic and genomic models, advances in comparative genomics have provided access to molecular tools that can now be applied to taxa with well-defined ecologies. As many of the organisms we discuss have tight physiological limits driven by climatic factors, this synthesis of molecular population genetics with marine ecology could provide a sensitive means of assessing evolutionary responses to climate change

Study design and participant characteristics of a randomized controlled trial of directly administered antiretroviral therapy in opioid treatment programs

<p>Abstract</p> <p>Background</p> <p>HIV-infected drug users are at higher risk of non-adherence and poor treatment outcomes than HIV-infected non-drug users. Prior work from our group and others suggests that directly administered antiretroviral therapy (DAART) delivered in opioid treatment programs (OTPs) may increase rates of viral suppression.</p> <p>Methods/Design</p> <p>We are conducting a randomized trial comparing DAART to self-administered therapy (SAT) in 5 OTPs in Baltimore, Maryland. Participants and investigators are aware of treatment assignments. The DAART intervention is 12 months. The primary outcome is HIV RNA < 50 copies/mL at 3, 6, and 12 months. To assess persistence of any study arm differences that emerge during the active intervention, we are conducting an 18-month visit (6 months after the intervention concludes). We are collecting electronic adherence data for 2 months in both study arms. Of 457 individuals screened, a total of 107 participants were enrolled, with 56 and 51 randomly assigned to DAART and SAT, respectively. Participants were predominantly African American, approximately half were women, and the median age was 47 years. Active use of cocaine and other drugs was common at baseline. HIV disease stage was advanced in most participants. The median CD4 count at enrollment was 207 cells/mm³, 66 (62%) had a history of an AIDS-defining opportunistic condition, and 21 (20%) were antiretroviral naïve.</p> <p>Conclusions</p> <p>This paper describes the rationale, methods, and baseline characteristics of subjects enrolled in a randomized clinical trial comparing DAART to SAT in opioid treatment programs.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00279110">NCT00279110</a></p