The magnitude and sustainability of treatment benefit of zuranolone on function and well-being as assessed by the SF-36 in adult patients with MDD and PPD: An integrated analysis of 4 randomized clinical trials.

BACKGROUND: Major depressive disorder (MDD) and postpartum depression (PPD) are disabling conditions. This integrated analysis of MDD and PPD clinical trials investigated the impact of zuranolone-a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors and neuroactive steroid under investigation for adults with MDD and approved as an oral, once-daily, 14-day treatment course for adults with PPD in the US-on health-related quality of life, including functioning and well-being, as assessed using the 36-item Short Form Health Survey V2 (SF-36). METHODS: Integrated data from 3 MDD (201B, MOUNTAIN, WATERFALL) and 1 PPD trial (ROBIN) for individual SF-36 domains were compared for zuranolone (30- and 50-mg) vs placebo at Day (D)15 and D42. Comparisons between zuranolone responders (≥50 % reduction from baseline in 17-item Hamilton Depression Rating Scale total score) and nonresponders were assessed. RESULTS: Overall, 1003 patients were included (zuranolone, n = 504; placebo, n = 499). Significant differences in change from baseline (CFB) to D15 for patients in zuranolone vs placebo groups were observed in 6/8 domains; changes were sustained or improved at D42, with significant CFB differences for all 8 domains. Zuranolone responders had significantly higher CFB scores vs nonresponders for all domains at D15 and D42 (p < 0.001). LIMITATIONS: Two zuranolone doses were integrated across populations of 2 disease states with potential differences in functioning, comorbidities, and patient demographics. All p-values presented are nominal. CONCLUSIONS: Integrated data across 4 zuranolone clinical trials showed improvements in functioning and well-being across all SF-36 domains. Benefits persisted after completion of treatment course at D42.

Effect of Zuranolone on Concurrent Anxiety and Insomnia Symptoms in Women With Postpartum Depression.

Objective: Concurrent anxiety and/or insomnia symptoms in women with postpartum depression (PPD) are common and associated with more severe PPD. The effects of zuranolone on concurrent anxiety and/or insomnia symptoms and on patient-perceived functional health in women with PPD in the ROBIN study are reported.Methods: The phase 3, double-blind, randomized, placebo-controlled trial (conducted January 2017-December 2018) included women aged 18-45 years, ≤ 6 months postpartum, with PPD (onset of DSM-5-defined major depressive episode in the third trimester or ≤ 4 weeks postpartum) and baseline 17-item Hamilton Depression Rating Scale (HDRS-17) total score ≥ 26. Women were randomized 1:1 to once-daily oral zuranolone 30 mg (n = 77) or placebo (n = 76) for 14 days with follow-up through day 45. Concurrent remission of depressive and anxiety symptoms (Hamilton Anxiety Rating Scale total score ≤ 7 plus HDRS-17 total score ≤ 7 or Montgomery-Asberg Depression Rating Scale total score ≤ 10), improvement in insomnia symptoms, patient-perceived functional health, and treatment effect sizes described by number needed to treat (NNT) were assessed. Analyses were exploratory; P values are nominal.Results: Rates of concurrent remission of depressive and anxiety symptoms were higher with zuranolone versus placebo (P < .05) at days 3, 15, and 45; the rate of sustained concurrent remission (ie, at both days 15 and 45) was also higher with zuranolone (P < .05). Anxiety symptoms (assessed by HDRS-17 anxiety/somatization subscale and Edinburgh Postnatal Depression Scale anxiety subscale) improved with zuranolone versus placebo (P < .05) at days 3 through 45. Potential benefits on insomnia symptoms and patient-perceived functional health were observed. Day 15 NNTs were 5 for both HDRS-17 response and remission.Conclusions: Zuranolone was associated with concurrent improvements in depressive and anxiety symptoms, with beneficial effects on insomnia symptoms and patient-perceived functional health in adults with PPD.Trial Registration: ClinicalTrials.gov identifier: NCT02978326.

Effect of brexanolone on depressive symptoms, anxiety, and insomnia in women with postpartum depression: Pooled analyses from 3 double-blind, randomized, placebo-controlled clinical trials in the HUMMINGBIRD clinical program.

BACKGROUND: Brexanolone is currently the only treatment specifically approved for postpartum depression (PPD) in the United States, based on the results from one Phase 2 and two Phase 3 double-blind, randomized, controlled trials in the HUMMINGBIRD program. METHODS: Adults with PPD randomized to a 60-h infusion of brexanolone 90 µg/kg/h (BRX90) or placebo from the 3 trials were included in these post hoc analyses. Data on change from baseline (CFB) in the 17-item Hamilton Rating Scale for Depression (HAMD-17) total score, HAMD-17 Anxiety/Somatization and Insomnia subscales, and Clinical Global Impression of Improvement (CGI-I) scale were pooled. Response rates for HAMD-17 (≥50 % reduction from baseline) and CGI-I (score of 1 or 2) scales and time to response were analyzed. RESULTS: Patients receiving BRX90 (n = 102) versus placebo (n = 107) achieved a more rapid HAMD-17 response (median, 24 vs 36 h; p = 0.0265), with an Hour-60 cumulative response rate of 81.4 % versus 67.3 %; results were similar for time to CGI-I response (median, 24 vs 36 h; p = 0.0058), with an Hour-60 cumulative response rate of 81.4 % versus 61.7 %. CFB in HAMD-17 Anxiety/Somatization and Insomnia subscales also favored BRX90 versus placebo, starting at Hour 24 through Day 30 (all p < 0.05), and response rates for both subscales were higher with BRX90. LIMITATIONS: The study was not powered to assess exploratory outcomes. CONCLUSIONS: Brexanolone was associated with rapid improvement in depressive symptoms and symptoms of anxiety and insomnia compared with placebo in women with PPD. These data continue to support the use of brexanolone to treat adults with PPD.

Comparing survival and subsequent treatment of first-line tyrosine kinase inhibitors in patients of advanced lung adenocarcinoma with epidermal growth factor receptor mutation.

BACKGROUND/PURPOSE: Three first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are widely available to treat advanced lung adenocarcinoma harboring EGFR mutation. However, studies comparing efficacy or effectiveness of these EGFR TKIs came out with inconclusive results. METHODS: In this real-world data analysis with a nationwide retrospective cohort design, adult patients with newly diagnosed advanced lung adenocarcinoma with EGFR mutation between 2011 and 2016, who received a first-line EGFR TKI, were included. Overall survival (OS) and time to next treatment (TTNT) were compared between patients receiving different EGFR TKIs after overlap weighting. RESULTS: We enrolled 10,431 patients, including 6,230, 2,359, and 1842 in gefitinib, erlotinib, and afatinib groups, respectively. The median (95% confidence interval [CI]) OS were 24.2 (22.9-26.2), 25.7 (24.0-27.9), and 29.1 (25.8-32.1) months for those receiving gefitinib, erlotinib, and afatinib, respectively (p = 0.001). The hazard ratios (95% CI) for the afatinib group were 0.85 (0.74-0.98) and 0.91 (0.79-1.05) comparing with the gefitinib and erlotinib groups, respectively. The median (95% CI) TTNT were 10.9 (10.4-11.2), 11.7 (11.3-12.1), 13.4 (12.5-14.3) months for those receiving gefitinib, erlotinib, and afatinib, respectively (p < 0.001). The hazard ratios (95% CI) for the afatinib group were 0.79 (0.70-0.88) and 0.89 (0.79-1.00) comparing with the gefitinib and erlotinib groups, respectively. There were 6111 (59%) patients receiving subsequent therapies, and the majority of them received a second-line chemotherapy, particularly platinum-based chemotherapy. CONCLUSION: Afatinib, compared with gefitinib, might provide better effectiveness as the first-line targeted therapy for patients of advanced lung adenocarcinoma with EGFR mutation.

Development of neuroactive steroids for the treatment of postpartum depression.

Postpartum depression (PPD) is a common major depressive episode surrounding childbirth, with estimated rates ranging from 5.5% to 23.5% of all live births across Europe and the USA based on the presence of key symptoms. PPD has been associated with significant impairments in both maternal functioning and mother-infant attachment, and these impairments can have lasting effects on the emotional and cognitive development of children. Although the precise pathophysiology of PPD is unknown, preclinical findings suggest that large fluctuations in neurosteroid hormone levels can induce physiological plasticity in the expression of functional GABAA receptors during pregnancy and the postpartum period, and that deficits in this plasticity may underpin a biological mechanism that contributes to the manifestation of depressive symptoms. Here, we review the controlled clinical trials to date that have assessed the efficacy of pharmacological treatments for PPD, including oestradiol, selective serotonin reuptake inhibitors, brexanolone (an iv formulation of allopregnanolone) and an investigational neuroactive steroid and GABAA positive allosteric modulator, zuranolone. Coupled with the GABAergic deficits implicated in major depressive disorder, these findings highlight not only the potential role of GABAA receptor plasticity in the pathophysiology of PPD, but also the novel therapeutic approach of using positive allosteric modulators targeting GABAergic transmission to treat women affected by PPD.

Achieving clinical response in postpartum depression leads to improvement in health-related quality of life.

OBJECTIVE: To evaluate the health-related quality of life (HRQoL) burden associated with postpartum depression (PPD), determine the extent to which clinical response impacts HRQoL, and estimate the impact of PPD and clinical response on healthcare resource utilization (HRU) and productivity. METHODS: Patient data (n = 127) from two multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trials evaluating the safety and efficacy of brexanolone injection in adults with PPD were employed for these posthoc analyses. HRQoL and health utility was assessed with the SF-36-v2 Health Survey (SF-36v2) acute version. The 17-item Hamilton Rating Scale for Depression (HAMD-17) total score was used to identify clinical response (≥50% reduction in HAMD-17 total score). Baseline HRQoL burden was assessed by comparison to age- and gender-adjusted population normative data from the 2009 QualityMetric PRO Norming study. The impact of clinical response was evaluated by comparing day 7 and day 30 SF-36v2 scores between clinical responders and non-responders. Interpretations of the meaningfulness of clinical response were indirectly estimated via 2017 National Health and Wellness Survey data linking SF-36v2 mental component summary (MCS) scores to (HRU) and productivity. RESULTS: Baseline HRQoL of patients with PPD was significantly below normative values. Day 7 and day 30 clinical response were associated with large and statistically significant improvements in HRQoL, greater likelihood of meeting SF-36v2 responder definitions, and reduced impairment. MCS levels corresponding to those observed in clinical responders were linked to lower HRU and productivity loss relative to non-responders. CONCLUSIONS: PPD places a substantial burden on HRQoL. Achievement of rapid clinical response (at day 7) and clinical response sustained several weeks following the end of treatment (day 30) led to significant improvement in HRQoL, suggesting the importance of identifying women with PPD and providing effective treatment options.

Healthcare resource utilization and costs associated with postpartum depression among commercially insured households.

OBJECTIVE: To quantify the economic burden of postpartum depression (PPD) that accrues to commercially insured households in the year following childbirth. METHODS: Administrative claims data from OptumHealth Care Solutions (2009-2016) were used to identify households that included women identified with PPD per the algorithm and propensity score-matched comparison households of women who were not identified with PPD or a history of depression after childbirth. Study outcomes included direct total all-cause medical and pharmaceutical costs during the first year following childbirth and number of outpatient visits at the household level stratified by household member. RESULTS: Households affected by PPD as identified by the algorithm (N = 7769) incurred 22% higher mean total all-cause medical and pharmaceutical spending than unaffected matched controls (N = 41,308) during the first year following childbirth ($36,049 versus $29,448, p < 0.01) and an average of 16 more outpatient visits than unaffected households (p < .01). Costs accrued by mothers comprised the largest share (>50%) of total all-cause spending. Mothers identified with PPD had significantly higher annual mean direct total all-cause medical and pharmaceutical spending than their matched controls without PPD ($19,611 versus $15,410, p < .01), driven primarily by an average of 11 more outpatient visits than unaffected mothers (p < .01). CONCLUSIONS: Households affected by PPD as identified by the algorithm incurred higher mean total all-cause medical and pharmaceutical spending during the first year following childbirth than did their matched controls identified without PPD, but not all costs were attributable to maternal treatment for PPD. These findings contribute to a better understanding of the potential economic burden associated with PPD and demonstrated costs may extend beyond the mother to members of the household.

Matched cohort study of healthcare resource utilization and costs in young children of mothers with postpartum depression in the United States.

Objective: To assess healthcare resource utilization (HRU) and costs in children of mothers with and without postpartum depression (PPD).Methods: Administrative claims data from the IBM Watson Health MarketScan Databases (2010-2016) were used. Women with live births (index date = delivery date) were identified and linked to their newborns. The mother-child pairs were divided into PPD and non-PPD exposure cohorts based on claims for depression, mood or adjustment disorders, or anxiety identified in the mother between 15 and 365 days after delivery. Mother-child pairs with PPD exposure were propensity score matched 1:3 to mother-child pairs without PPD exposure. Children were required to have 24 months of continuous health plan enrolment following delivery. Additional comparisons were performed between mother-child pairs with and without preterm delivery.Results: Overall, 33,314 mother-child pairs with PPD exposure were propensity score matched to 102,364 mother-child pairs without PPD exposure. During the 24-month follow-up period, HRU across most service categories was significantly higher among children in the PPD exposure cohort than non-PPD exposure cohort. Among outpatient services, the percentages of children with a physician specialist service (68% versus 64%), early-intervention screening (40% versus 37%), and an emergency room visit (48% versus 42%) were greater in children of mothers with PPD (all p < .001). Furthermore, children of mothers with PPD incurred 12% higher total healthcare costs in the first 24 months of life compared to children of mothers without PPD ($24,572 versus $21,946; p < .001). After excluding mothers with preterm delivery, the proportion of children with ER visits, physician specialist services, and outpatient pharmacy claims was significantly higher in the PPD exposure cohort than non-PPD exposure cohort (all p < .001).Conclusion: The results of this analysis suggest that HRU and costs over the first 24 months of life in children of mothers with PPD exceeded that of children of mothers without evidence of PPD.

The humanistic burden of postpartum depression: a systematic literature review.

OBJECTIVE: Postpartum depression (PPD) is the most common medical complication of childbirth. PPD can be disabling, with potential negative effects on maternal health-related quality-of-life (HRQoL) as well as on children and partners. The objective of this study was to systematically review and summarize recently published literature describing the humanistic burden of PPD on affected women, their children, and partners. METHODS: Databases including Embase, MEDLINE, and PsycINFO, as well as conference proceedings were searched for keywords related to PPD. Searches were initially conducted in February 2017 and restricted to the prior 5 years for databases and the prior 2 years for conference proceedings. Searches were updated in February 2018. Two researchers independently reviewed 1154 unique records according to pre-defined inclusion and exclusion screening criteria. RESULTS: Forty-eight studies were identified; over 40 studies assessed the effects of PPD on children of affected mothers, with many demonstrating a negative association with elements of parenting and childhood development. Furthermore, five studies that evaluated the effects of PPD symptoms on partners suggested that certain aspects of their relationships were negatively affected. Partners of affected women also experienced greater levels of their own stress, anxiety, and depression compared with partners of women without PPD symptoms. Despite limited data on HRQoL among women with PPD symptoms (four studies), a negative impact on physical and mental sub-scales was observed. CONCLUSIONS: Findings suggest that PPD symptoms have a substantial humanistic burden on affected mothers as well as on their children and partners.

Comparison of Disease-Modifying Therapies for the Management of Multiple Sclerosis: Analysis of Healthcare Resource Utilization and Relapse Rates from US Insurance Claims Data.

BACKGROUND: Data on comparative healthcare resource utilization and costs associated with the newer oral disease-modifying therapies (DMTs) for managing relapsing-remitting multiple sclerosis (MS) in routine clinical practice are limited. The purpose of this study was to estimate healthcare resource utilization, costs, and relapse rates in the year after initiating treatment with dimethyl fumarate (DMF), interferon (IFN)-ß, glatiramer acetate (GA), teriflunomide, or fingolimod in routine clinical practice for patients with MS who did not receive a DMT in the previous year. METHODS: Patients initiating DMF, IFNß, GA, teriflunomide, or fingolimod were identified based on claims data from 2012 to 2015 in the Truven MarketScan Commercial Claims Databases (n = 4194). Healthcare resource utilization assessment included the proportion of patients who were hospitalized, or had emergency room (ER) or urgent care (UC) visits. Healthcare costs were estimated for 1 year before and 1 year after DMT initiation. Relapse episodes were identified based on a published claims-based algorithm and clinical input from the research investigators. RESULTS: After DMT initiation, significant reductions in the proportions of patients who were hospitalized or requiring ER/UC visits were observed in all patient cohorts (p < 0.001 and p < 0.05, respectively). Non-prescription medical costs decreased after DMT initiation, with the largest decrease observed in the DMF cohort (US$5761 reduction, p < 0.0001). Reductions in non-prescription medical costs were associated with decreased use of outpatient services and inpatient hospital stays, and have the potential to partially offset DMT costs. CONCLUSIONS: DMT initiation is associated with reductions in healthcare resource utilization and non-prescription medical costs in routine clinical practice.

Homology Modeling and Molecular Dynamics Simulation Combined with X-ray Solution Scattering Defining Protein Structures of Thromboxane and Prostacyclin Synthases.

A combination of molecular dynamics (MD) simulations and X-ray scattering (SAXS) has emerged as the approach of choice for studying protein structures and dynamics in solution. This approach has potential applications for membrane proteins that neither are soluble nor form crystals easily. We explore the water-coupled dynamic structures of thromboxane synthase (TXAS) and prostacyclin synthase (PGIS) from scanning HPLC-SAXS measurements combined with MD ensemble analyses. Both proteins are heme-containing enzymes in the cytochrome P450 family, known as prostaglandin H2 (PGH2) isomerase, with counter-functions in regulation of platelet aggregation. Currently, the X-ray crystallographic structures of PGIS are available, but those for TXAS are not. The use of homology modeling of the TXAS structure with ns-µs explicit water solvation MD simulations allows much more accurate estimation of the configuration space with loop motion and origin of the protein behaviors in solution. In contrast to the stability of the conserved PGIS structure in solution, the pronounced TXAS flexibility has been revealed to have unstructured loop regions in connection with the characteristic P450 structural elements. The MD-derived and experimental-solution SAXS results are in excellent agreement. The significant protein internal motions, whole-molecule structures, and potential problems with protein folding, crystallization, and functionality are examined.

Healthcare resource use and costs of multiple sclerosis patients in Germany before and during fampridine treatment.

BACKGROUND: Multiple sclerosis (MS) patients often suffer from gait impairment and fampridine is indicated to medically improve walking ability in this population. Patient characteristics, healthcare resource use, and costs of MS patients on fampridine treatment for 12 months in Germany were analyzed. METHODS: A retrospective claims database analysis was conducted including MS patients who initiated fampridine treatment (index date) between July 2011 and December 2013. Continuous insurance enrollment during 12 months pre- and post-index date was required, as was at least 1 additional fampridine prescription in the fourth quarter after the index date. Patient characteristics were evaluated and pre- vs post-index MS-related healthcare utilization and costs were compared. RESULTS: A total of 562 patients were included in this study. The mean (standard deviation [SD]) age was 50.5 (9.8) years and 63% were female. In the treatment period, almost every patient had at least 1 MS-related outpatient visit, 24% were hospitalized due to MS, and 79% utilized MS-specific physical therapy in addition to the fampridine treatment. Total MS-related healthcare costs were significantly higher in the fampridine treatment period than in the period prior to fampridine initiation (€17,392 vs €10,960, P < 0.001). While this difference was driven primarily by prescription costs, MS-related inpatient costs were lower during fampridine treatment (€1,333 vs €1,565, P < 0.001). CONCLUSIONS: Physical therapy is mainly used concomitant to fampridine treatment. While healthcare costs were higher during fampridine treatment compared to the pre-treatment period, inpatient costs were lower. Further research is necessary to better understand the fampridine influence.

Comparative Effectiveness Research of Disease-Modifying Therapies for the Management of Multiple Sclerosis: Analysis of a Large Health Insurance Claims Database.

INTRODUCTION: Limited data are available on the real-world effectiveness of newer oral disease-modifying therapies (DMTs) in multiple sclerosis. The purpose of this study was to retrospectively compare the real-world effectiveness of dimethyl fumarate (DMF), fingolimod, teriflunomide, and injectable DMTs in routine clinical practice based on US claims data. METHODS: Patients newly-initiating DMF, interferon beta (IFNß), glatiramer acetate (GA), teriflunomide, or fingolimod in 2013 were identified in the Truven MarketScan Commercial Claims Databases (N = 6372). Relapse episodes were identified based on a published claim-based algorithm and used to determine the annualized relapse rate (ARR) for the year before and after initiating therapy. Poisson and negative binomial regression was used to determine the adjusted incidence rate ratio (IRR) for each therapy relative to DMF. RESULTS: Significant ARR reductions in the year after initiating therapy were reported for DMF and fingolimod (P < 0.0001). Compared with DMF, the adjusted IRR (95% CI) for relapse in the year after initiating therapy was 1.27 (1.10-1.46) for IFNß, 1.34 (1.17-1.53) for GA, 1.23 (1.05-1.45) for teriflunomide, and 1.03 (0.88-1.21) for fingolimod. Results were consistent across subgroup and sensitivity analyses. CONCLUSION: These real-world data suggest DMF and fingolimod have similar effectiveness and demonstrate superior effectiveness to IFNß, GA, and teriflunomide. FUNDING: Biogen, Cambridge, MA, USA.

In Vitro Activity of Oral Antimicrobial Agents against Pathogens Associated with Community-Acquired Upper Respiratory Tract and Urinary Tract Infections: A Five Country Surveillance Study.

INTRODUCTION: Bacterial infections that cause community-acquired urinary tract infections (CA-UTI) and upper respiratory tract infections (CA-URTI) are most frequently treated empirically. However, an increase in antimicrobial resistance has become a problem when treating outpatients. METHODS: This study determined the in vitro activities of oral antibiotics among 1501 pathogens from outpatients with CA-UTI and CA-URTI in medical centers during 2012 and 2013 from Argentina, Mexico, Venezuela, Russia, and the Philippines. Minimal inhibitory concentrations (MICs) were determined using broth microdilution and susceptibility defined by Clinical Laboratory Standards Institute (CLSI) and European Committee for Antimicrobial Susceptibility Testing (EUCAST) criteria. RESULTS: Ceftibuten (MIC50, ≤0.25 mg/L) was more potent in vitro compared to other ß-lactams against Enterobacteriaceae from CA-UTI. Susceptibility to fluoroquinolones using CLSI criteria varied: Argentina and Mexico (50%), the Philippines (60%), Venezuela (70%), and Russia (80%). Fosfomycin susceptibility was >90% against Enterobacteriaceae in each country. Susceptibility among Enterobacteriaceae to trimethoprim-sulfamethoxazole was 30.6-75.6% and nitrofurantoin susceptibility also varied among the countries and was higher when EUCAST breakpoints were applied (65->90%) compared to CLSI (52-84%). All Haemophilus influenzae isolates from CA-URTI were susceptible to ceftibuten, cefixime, cefpodoxime, and cefuroxime using CLSI breakpoint criteria. EUCAST criteria produced intermediate and resistant MIC values for these oral cephalosporins. Country-specific susceptibility variation for fluoroquinolones, macrolides, and trimethoprim-sulfamethoxazole was observed among Streptococcus pneumoniae and Streptococcus pyogenes from CA-URTI. CONCLUSION: This study demonstrated that antimicrobial susceptibility patterns varied in the five countries investigated among pathogens from CA-UTI and CA-URTI. FUNDING: Merck & Co. Inc., Kenilworth, New Jersey, USA.

High-Performance a-Si/c-Si Heterojunction Photoelectrodes for Photoelectrochemical Oxygen and Hydrogen Evolution.

Amorphous Si (a-Si)/crystalline Si (c-Si) heterojunction (SiHJ) can serve as highly efficient and robust photoelectrodes for solar fuel generation. Low carrier recombination in the photoelectrodes leads to high photocurrents and photovoltages. The SiHJ was designed and fabricated into both photoanode and photocathode with high oxygen and hydrogen evolution efficiency, respectively, by simply coating of a thin layer of catalytic materials. The SiHJ photoanode with sol-gel NiOx as the catalyst shows a current density of 21.48 mA/cm(2) at the equilibrium water oxidation potential. The SiHJ photocathode with 2 nm sputter-coated Pt catalyst displays excellent hydrogen evolution performance with an onset potential of 0.640 V and a solar to hydrogen conversion efficiency of 13.26%, which is the highest ever reported for Si-based photocathodes.

Toward efficient and omnidirectional n-type Si solar cells: concurrent improvement in optical and electrical characteristics by employing microscale hierarchical structures.

We demonstrated that hierarchical structures combining different scales (i.e., pyramids from 1.5 to 7.5 µm in width on grooves from 40 to 50 µm in diameter) exhibit excellent broadband and omnidirectional light-trapping characteristics. These microscaled hierarchical structures could not only improve light absorption but prevent poor electrical properties typically observed from nanostructures (e.g., ultra-high-density surface defects and nonconformal deposition of following layers, causing low open-circuit voltages and fill factors). The microscaled hierarchical Si heterojunction solar cells fabricated with hydrogenated amorphous Si layers on as-cut Czochralski n-type substrates show a high short-circuit current density of 36.4 mA/cm(2), an open-circuit voltage of 607 mV, and a conversion efficiency of 15.2% due to excellent antireflection and light-scattering characteristics without sacrificing minority carrier lifetimes. Compared to cells with grooved structures, hierarchical heterojunction solar cells exhibit a daily power density enhancement (69%) much higher than the power density enhancement at normal angle of incidence (49%), demonstrating omnidirectional photovoltaic characteristics of hierarchical structures. Such a concept of hierarchical structures simultaneously improving light absorption and photocarrier collection efficiency opens avenues for developing large-area and cost-effective solar energy devices in the industry.

Consumer preferences for the predictive genetic test for Alzheimer disease.

The purpose of this study was to assess consumer preferences for predictive genetic testing for Alzheimer disease in the United States. A rating conjoint analysis was conducted using an anonymous online survey distributed by Qualtrics to a general population panel in April 2011 in the United States. The study design included three attributes: Accuracy (40%, 80%, and 100%), Treatment Availability (Cure is available/Drug for symptom relief but no cure), and Anonymity (Anonymous/Not anonymous). A total of 12 scenarios were used to elicit people's preference, assessed by an 11-point scale. The respondents also indicated their highest willingness-to-pay (WTP) for each scenario through open-ended questions. A total of 295 responses were collected over 4 days. The most important attribute for the aggregate model was Accuracy, contributing 64.73% to the preference rating. Treatment Availability and Anonymity contributed 20.72% and 14.59%, respectively, to the preference rating. The median WTP for the highest-rating scenario (Accuracy 100%, a cure is available, test result is anonymous) was $100 (mean = $276). The median WTP for the lowest-rating scenario (40% accuracy, no cure but drugs for symptom relief, not anonymous) was zero (mean = $34). The results of this study highlight attributes people find important when making the hypothetical decision to obtain an AD genetic test. These results should be of interests to policy makers, genetic test developers and health care providers.

Realizing high-efficiency omnidirectional n-type Si solar cells via the hierarchical architecture concept with radial junctions.

Hierarchical structures combining micropyramids and nanowires with appropriate control of surface carrier recombination represent a class of architectures for radial p-n junction solar cells that synergizes the advantageous features including excellent broad-band, omnidirectional light-harvesting and efficient separation/collection of photoexcited carriers. The heterojunction solar cells fabricated with hierarchical structures exhibit the efficiency of 15.14% using cost-effective as-cut Czochralski n-type Si substrates, which is the highest reported efficiency among all n-type Si nanostructured solar cells. We also demonstrate the omnidirectional solar cell that exhibits the daily generated power enhancement of 44.2% by using hierarchical structures, as compared to conventional micropyramid control cells. The concurrent improvement in optical and electrical properties for realizing high-efficiency omnidirectional solar cells using as-cut Czochralski n-type Si substrates demonstrated here makes a hierarchical architecture concept promising for large-area and cost-effective mass production.

U.S. publication trends in social and administrative pharmacy: implications for promotion and tenure.

BACKGROUND: There is no consensus on the preferred approach to assess journal quality. Procedures previously used include journal acceptance or rejection policies, impact factors, number of subscribers, citation counts, whether the articles were refereed or not, and journals cited in books within the discipline. This study built on the work of previous authors by using a novel approach to assess journal quality in social and administrative pharmacy (SAdP). OBJECTIVES: To determine U.S. SAdP faculty perceptions of prestigious journals for their research, SAdP faculty perceptions of prestigious journals by their promotion and tenure (P&T) committees, and current research trends in SAdP. METHODS: A census of U.S. colleges and schools of pharmacy was conducted using an e-mailed survey and an open-ended approach requiring respondents to list their preferred journals. RESULTS: Seventy-nine SAdP faculty reported that the 5 most prestigious journals were JAMA, New England Journal of Medicine, Health Affairs, Health Services Research, and Medical Care. These journals were selected because respondents wished to seek broad readership. CONCLUSIONS: Results of this study can be used as a guide by U.S. SAdP faculty and P&T committees to assess the quality of publications by pharmacy administration faculty with the caveat being that pharmacy versus nonpharmacy journals will be chosen based on the fit of the article with the audience.