Hybrid TiO2 Solar Cells Produced from Aerosolized Nanoparticles of Water-Soluble Polythiophene Electron Donor Layer

Hybrid solar cells (HSCs) with water soluble polythiophene sodium poly[2-(3-thienyl)-ethyloxy-4-butylsulfonate] (PTEBS) thin films produced using electrospray deposition (ESD) were fabricated, tested, and modeled and compared to devices produced using conventional spin coating. A single device structure of FTO/TiO2/PTEBS/Au was used to study the effects of ESD of the PTEBS layer on device performance. ESD was found to increase the short circuit current density (Jsc) by a factor of 2 while decreasing the open circuit voltage (Voc) by half compared to spin coated PTEBS films. Comparable efficiencies of 0.009% were achieved from both device construction types. Current-voltage curves were modeled using the characteristic solar cell equation and showed a similar increase in generated photocurrent with an increase by two orders of magnitude in the saturation current in devices from ESD films. Increases in Jsc are attributed to an increase in the interfacial contact area between the TiO2 and PTEBS layers, while decreases in Voc are attributed to incomplete film formation from ESD

Mutual Control of Cholinergic and Low-Threshold Spike Interneurons in the Striatum

The striatum is the largest nucleus of the basal ganglia and is crucially involved in action selection and reward processing. Cortical and thalamic inputs to the striatum are processed by local networks in which several classes of interneurons play an important, but still poorly understood role. Here we investigated the interactions between cholinergic and low-threshold spike (LTS) interneurons. LTS interneurons were hyperpolarized by co-application of muscarinic and nicotinic receptor antagonists (atropine and mecamylamine, respectively). Mecamylamine alone also caused hyperpolarizations, while atropine alone caused depolarizations and increased firing. LTS interneurons were also under control of tonic GABA, as application of the GABAA receptor antagonist picrotoxin caused depolarizations and increased firing. Frequency of spontaneous GABAergic events in LTS interneurons was increased by co-application of atropine and mecamylamine or by atropine alone, but reduced by mecamylamine alone. In the presence of picrotoxin and tetrodotoxin (TTX), atropine and mecamylamine depolarized the LTS interneurons. We concluded that part of the excitatory effects of tonic acetylcholine (ACh) on LTS interneurons were due to cholinergic modulation of tonic GABA. We then studied the influence of LTS interneurons on cholinergic interneurons. Application of antagonists of somatostatin or neuropeptide Y (NPY) receptors or of an inhibitor of nitric oxide synthase (L-NAME) did not cause detectable effects in cholinergic interneurons. However, prolonged synchronized depolarizations of LTS interneurons (elicited with optogenetics tools) caused slow-onset depolarizations in cholinergic interneurons, which were often accompanied by strong action potential firing and were fully abolished by L-NAME. Thus, a mutual excitatory influence exists between LTS and cholinergic interneurons in the striatum, providing an opportunity for sustained activation of the two cell types. This activation may endow the striatal microcircuits with the ability to enter a high ACh/high nitric oxide regime when adequately triggered by external excitatory stimuli to these interneurons

Surgical techniques for evacuation of chronic subdural hematoma: a mini-review

Chronic subdural hematoma is one of the most common neurosurgical pathologies with over 160,000 cases in the United States and Europe each year. The current standard of care involves surgically evacuating the hematoma through a cranial opening, however, varied patient risk profiles, a significant recurrence rate, and increasing financial burden have sparked innovation in the field. This mini-review provides a brief overview of currently used evacuation techniques, including emerging adjuncts such as endoscopic assistance and middle meningeal artery embolization. This review synthesizes the body of available evidence on efficacy and risk profiles for each critical aspect of surgical technique in cSDH evacuation and provides insight into trends in the field and promising new technologies

Estimating the clinical effectiveness and value-based price range of erenumab for the prevention of migraine in patients with prior treatment failures: a US societal perspective

BACKGROUND: Frequent migraine with four or more headache days per month is a common, disabling neurovascular disease. From a US societal perspective, this analysis models the clinical efficacy and estimates the value-based price (VBP) for erenumab, a fully human monoclonal antibody that inhibits the calcitonin gene-related peptide receptor. METHODS: A Markov health state transition model was developed to estimate the incremental costs, quality-adjusted life-years (QALYs), and value-based price range for erenumab in migraine prevention. The model comprises "on preventive treatment", "off preventive treatment", and "death" health states across a 10-year time horizon. The evaluation compared erenumab to no preventive treatment in episodic and chronic migraine patients that have failed at least one preventive therapy. Therapeutic benefits are based on estimated changes in monthly migraine days (MMD) from erenumab pivotal clinical trials and a network meta-analysis of migraine studies. Utilities were estimated using previously published mapping algorithms. A VBP analysis was performed to identify maximum erenumab annual prices at willingness-to-pay (WTP) thresholds of $100,000-$200,000 per QALY. Estimates of VBP under different scenarios such as choice of different comparators, assumptions around inclusion of placebo effect, and exclusion of work productivity losses were also generated. RESULTS: Erenumab resulted in incremental QALYs of 0.185 vs supportive care (SC) and estimated cost offsets due to reduced MMD of $8,482 over 10 years, with an average duration of treatment of 2.01 years. The estimated VBP at WTP thresholds of$100,000-$200,000 for erenumab compared to SC ranged from$14,238-$23,998. VBP estimates including the placebo effect and excluding work productivity ranged from$7,445-$13,809; increasing to$12,151-$18,589 with onabotulinumtoxinA as a comparator in chronic migraine. CONCLUSION: Erenumab is predicted to reduce migraine-related direct and indirect costs, and increase QALYs compared to SC

Physician Characteristics Associated With Ordering 4 Low-Value Screening Tests in Primary Care

Importance: Efforts to reduce low-value tests and treatments in primary care are often ineffective. These efforts typically target physicians broadly, most of whom order low-value care infrequently. Objectives: To measure physician-level use rates of 4 low-value screening tests in primary care to investigate the presence and characteristics of primary care physicians who frequently order low-value care. Design, Setting, and Participants: A retrospective cohort study was conducted using administrative health care claims collected between April 1, 2012, and March 31, 2016, in Ontario, Canada. This study measured use of 4 low-value screening tests-repeated dual-energy x-ray absorptiometry (DXA) scans, electrocardiograms (ECGs), Papanicolaou (Pap) tests, and chest radiographs (CXRs)-among low-risk outpatients rostered to a common cohort of primary care physicians. Exposures: Physician sex, years since medical school graduation, and primary care model. Main Outcomes and Measures: This study measured the number of tests to which a given physician ranked in the top quintile by ordering rate. The resulting cross-test score (range, 0-4) reflects a physician's propensity to order low-value care across screening tests. Physicians were then dichotomized into infrequent or isolated frequent users (score, 0 or 1, respectively) or generalized frequent users for 2 or more tests (score, ≥2). Results: The final sample consisted of 2394 primary care physicians (mean [SD] age, 51.3 [10.0] years; 50.2% female), who were predominantly Canadian medical school graduates (1701 [71.1%]), far removed from medical school graduation (median, 25.3 years; interquartile range, 17.3-32.3 years), and reimbursed via fee-for-service in a family health group (1130 [47.2%]), far removed from medical school graduation (median, 25.3 years; interquartile range, 17.3-32.3 years), and reimbursed via fee-for-service in a family health group (1130 [47.2%). They ordered 302 509 low-value screening tests (74 167 DXA scans, 179 855 ECGs, 19 906 Pap tests, and 28 581 CXRs) after 3 428 557 ordering opportunities. Within the cohort, generalized frequent users represented 18.4% (441 of 2394) of physicians but ordered 39.2% (118 665 of 302 509) of all low-value screening tests. Physicians who were male (odds ratio, 1.29; 95% CI, 1.01-1.64), further removed from medical school graduation (odds ratio, 1.03; 95% CI, 1.02-1.04), or in an enhanced fee-for-service payment model (family health group) vs a capitated payment model (family health team) (odds ratio, 2.04; 95% CI, 1.42-2.94) had increased odds of being generalized frequent users. Conclusions and Relevance: This study identified a group of primary care physicians who frequently ordered low-value screening tests. Tailoring future interventions to these generalized frequent users might be an effective approach to reducing low-value care

Identification of Functional Differences in Metabolic Networks Using Comparative Genomics and Constraint-Based Models

Genome-scale network reconstructions are useful tools for understanding cellular metabolism, and comparisons of such reconstructions can provide insight into metabolic differences between organisms. Recent efforts toward comparing genome-scale models have focused primarily on aligning metabolic networks at the reaction level and then looking at differences and similarities in reaction and gene content. However, these reaction comparison approaches are time-consuming and do not identify the effect network differences have on the functional states of the network. We have developed a bilevel mixed-integer programming approach, CONGA, to identify functional differences between metabolic networks by comparing network reconstructions aligned at the gene level. We first identify orthologous genes across two reconstructions and then use CONGA to identify conditions under which differences in gene content give rise to differences in metabolic capabilities. By seeking genes whose deletion in one or both models disproportionately changes flux through a selected reaction (e.g., growth or by-product secretion) in one model over another, we are able to identify structural metabolic network differences enabling unique metabolic capabilities. Using CONGA, we explore functional differences between two metabolic reconstructions of Escherichia coli and identify a set of reactions responsible for chemical production differences between the two models. We also use this approach to aid in the development of a genome-scale model of Synechococcus sp. PCC 7002. Finally, we propose potential antimicrobial targets in Mycobacterium tuberculosis and Staphylococcus aureus based on differences in their metabolic capabilities. Through these examples, we demonstrate that a gene-centric approach to comparing metabolic networks allows for a rapid comparison of metabolic models at a functional level. Using CONGA, we can identify differences in reaction and gene content which give rise to different functional predictions. Because CONGA provides a general framework, it can be applied to find functional differences across models and biological systems beyond those presented here

Creative destruction in science

Drawing on the concept of a gale of creative destruction in a capitalistic economy, we argue that initiatives to assess the robustness of findings in the organizational literature should aim to simultaneously test competing ideas operating in the same theoretical space. In other words, replication efforts should seek not just to support or question the original findings, but also to replace them with revised, stronger theories with greater explanatory power. Achieving this will typically require adding new measures, conditions, and subject populations to research designs, in order to carry out conceptual tests of multiple theories in addition to directly replicating the original findings. To illustrate the value of the creative destruction approach for theory pruning in organizational scholarship, we describe recent replication initiatives re-examining culture and work morality, working parents\u2019 reasoning about day care options, and gender discrimination in hiring decisions. Significance statement It is becoming increasingly clear that many, if not most, published research findings across scientific fields are not readily replicable when the same method is repeated. Although extremely valuable, failed replications risk leaving a theoretical void\u2014 reducing confidence the original theoretical prediction is true, but not replacing it with positive evidence in favor of an alternative theory. We introduce the creative destruction approach to replication, which combines theory pruning methods from the field of management with emerging best practices from the open science movement, with the aim of making replications as generative as possible. In effect, we advocate for a Replication 2.0 movement in which the goal shifts from checking on the reliability of past findings to actively engaging in competitive theory testing and theory building. Scientific transparency statement The materials, code, and data for this article are posted publicly on the Open Science Framework, with links provided in the article

Migraine day frequency in migraine prevention: longitudinal modelling approaches

Background Health economic models are critical tools to inform reimbursement agencies on health care interventions. Many clinical trials report outcomes using the frequency of an event over a set period of time, for example, the primary efficacy outcome in most clinical trials of migraine prevention is mean change in the frequency of migraine days (MDs) per 28 days (monthly MDs [MMD]) relative to baseline for active treatment versus placebo. Using these cohort-level endpoints in economic models, accounting for variation among patients is challenging. In this analysis, parametric models of change in MMD for migraine preventives were assessed using data from erenumab clinical studies. Methods MMD observations from the double-blind phases of two studies of erenumab were used: one in episodic migraine (EM) (NCT02456740) and one in chronic migraine (CM) (NCT02066415). For each trial, two longitudinal regression models were fitted: negative binomial and beta binomial. For a thorough comparison we also present the fitting from the standard multilevel Poisson and the zero inflated negative binomial. Results Using the erenumab study data, both the negative binomial and beta-binomial models provided unbiased estimates relative to observed trial data with well-fitting distribution at various time points. Conclusions This proposed methodology, which has not been previously applied in migraine, has shown that these models may be suitable for estimating MMD frequency. Modelling MMD using negative binomial and beta-binomial distributions can be advantageous because these models can capture intra- and inter-patient variability so that trial observations can be modelled parametrically for the purposes of economic evaluation of migraine prevention. Such models have implications for use in a wide range of disease areas when assessing repeated measured utility values