Real-world evidence from Germany and the United States: Treatment initiation on low-efficacy versus high-efficacy therapies in patients with multiple sclerosis.

BACKGROUND: The hit-hard-and-early (HHAE) strategy where treatment is initiated with high-efficacy therapies opposed to low-efficacy therapies presents a potential paradigm shift in multiple sclerosis (MS) management. This study aimed to assess the adoption of the HHAE strategy in Germany and the United States (US) from 2020 to 2022 based on real-world data. METHODS: The analysis was based on longitudinal, patient-level data from Germany and the US. For Germany, data was extracted from the Permea platform covering approximately 44 % of all German community pharmacy dispensing. For the US, data from the Komodo Healthcare Map™ was utilized, covering medical benefit data from around 88 % of the US patient population. Patients ≥18 years old and who had at least 2 prescriptions for MS-related disease-modifying drugs (DMDs) between January 2020 and December 2022 were included. To approximate therapy beginners, a washout period of one year before treatment start was applied, excluding all patients who had an MS-related DMD prescription or claim in 2019. Cohort entry date was the day of the first MS-related DMD dispense or claim. DMDs were classified as high-efficacy and low-efficacy based on the Multiple Sclerosis Therapy Consensus Group (MSTCG). Group differences were assessed with two-sided χ2-square and t-tests. RESULTS: 29,604 MS therapy beginners were identified in the German and 49,791 MS therapy beginners were identified in the US dataset. 29.6 % of MS therapy beginners in Germany and 61.6 % in the US followed the HHAE strategy. Between 2020 and 2022, a significant 14 % increase in the HHAE strategy was observed in both countries (p < 0.0001). High-efficacy therapy beginners switched from their initially prescribed therapy less frequently than low-efficacy therapy beginners: 6.9 % of high-efficacy vs. 19.5 % of low-efficacy therapy beginners in Germany (p < 0.0001) and 5.5 % of high-efficacy vs. 25.0 % low-efficacy therapy beginners in the US (p < 0.0001) switched from their first prescribed DMD. CONCLUSION: Between 2020 and 2022, the adoption of the HHAE strategy increased in both countries, with the US exhibiting nearly double the adoption rates. High-efficacy therapy beginners were less likely to switch from their initially prescribed medication than low-efficacy therapy beginners. Real world evidence can provide valuable insights into rapidly changing treatment patterns in patients with MS.

Manipulating the functionality and structures of π-conjugated polymers utilizing intramolecular noncovalent interactions towards efficient organic photovoltaics.

Careful control of electronic properties, structural order, and solubility of π-conjugated polymers is central to the improvement of organic photovoltaic (OPV) performance. In this work, we designed and synthesized a series of naphthobisthiadiazole-quaterthiophene copolymers by systematically replacing the alkyl groups with ester groups and changing the position of the fluorine groups in the quaterthiophene moiety. These alterations lowered the HOMO and LUMO energy levels and systematically varied the combination of intramolecular noncovalent interactions such as O⋯S and F⋯S interactions in the backbone. More importantly, although the introduction of such noncovalent interactions often lowers the solubility owing to the interlocking of backbone linkages, we found that careful design of the noncovalent interactions afforded polymers with relatively high solubility and high crystallinity at the same time. As a result, the power conversion efficiency of OPV cells that used fullerene (PC61BM) and nonfullerene (Y12) as the acceptor was improved. Our work offers important information for the development of high-performance π-conjugated polymers for OPVs.

Halogen-Free π $\upi$ -Conjugated Polymers Based on Thienobenzobisthiazole for Efficient Nonfullerene Organic Solar Cells: Rational Design for Achieving High Backbone Order and High Solubility.

In π $\upi$ -conjugated polymers, a highly ordered backbone structure and solubility are always in a trade-off relationship that must be overcome to realize highly efficient and solution-processable organic photovoltaics (OPVs). Here, it is shown that a π $\upi$ -conjugated polymer based on a novel thiazole-fused ring, thieno[2',3':5,6]benzo[1,2-d:4,3-d']bisthiazole (TBTz) achieves both high backbone order and high solubility due to the structural feature of TBTz such as the noncovalent interlocking of the thiazole moiety, the rigid and bent-shaped structure, and the fused alkylthiophene ring. Furthermore, based on the electron-deficient nature of these thiazole-fused rings, the polymer exhibits deep HOMO energy levels, which lead to high open-circuit voltages (VOC s) in OPV cells, even without halogen substituents that are commonly introduced into high-performance polymers. As a result, when the polymer is combined with a typical nonfullerene acceptor Y6, power conversion efficiencies of reaching 16% and VOC s of more than 0.84 V are observed, both of which are among the top values reported so far for "halogen-free" polymers. This study will serve as an important reference for designing π $\upi$ -conjugated polymers to achieve highly efficient and solution-processable OPVs.

Pronounced Backbone Coplanarization by π-Extension in a Sterically Hindered Conjugated Polymer System Leads to Higher Photovoltaic Performance in Non-Fullerene Solar Cells.

Achieving both the backbone order and solubility of π-conjugated polymers, which are often in a trade-off relationship, is imperative for maximizing the performance of organic solar cells. Here, we studied three different π-conjugated polymers based on thiazolothiazole (PSTz1 and POTz1) and benzobisthiazole (PNBTz1) that were combined with a benzodithiophene unit in the backbone, where PNBTz1 was newly synthesized. Because of the steric hindrance between the side chains located on neighboring heteroaromatic rings, POTz1 had a much less coplanar backbone than PSTz1 in which such a steric hindrance is absent. However, POTz1 showed higher photovoltaic performance in solar cells that used Y6 as the acceptor material. This was likely due to the significantly higher solubility of POTz1 than PSTz1, resulting in a better morphology. Interestingly, PNBTz1 was found to have markedly higher backbone coplanarity than POTz1, despite having similar steric hindrance between the side chains, most likely owing to the more extended π-electron system, whereas PNBTz1 had good solubility comparable to POTz1. As a result, PNBTz1 exhibited higher photovoltaic performance than POTz1 in the Y6-based cells: specifically, the fill factor was significantly enhanced. Our results indicate that the backbone order and solubility can be achieved by the careful molecular design, which indeed leads to higher photovoltaic performance.

Immediate and Temporal Enhancement of Power Conversion Efficiency in Surface-Passivated Perovskite Solar Cells.

This work reports strategies for improving the power conversion efficiency (PCE) by capitalizing on temporal changes through the storage effect and immediate improvements by interface passivation. It is demonstrated that both strategies can be combined as shown by PCE improvement in passivated perovskite solar cells (PSCs) upon ambient storage because of trap density reduction. By analyzing the dominant charge recombination process, we find that lead-related traps in perovskite bulk, rather than at the surface, are the recombination centers in both as-fabricated and ambient-stored passivated PSCs. This emphasizes the necessity to reduce intrinsic defects in the perovskite bulk. Furthermore, storage causes temporal changes in band alignment even in passivated PSCs, contributing to PCE improvement. Building on these findings, composition engineering was employed to produce further immediate PCE improvements because of defect reduction in the bulk, achieving a PCE of 22.2%. These results show that understanding the dominant recombination mechanisms within a PSC is important to inform strategies for producing immediate and temporal PCE enhancements either by interface passivation, storage, composition engineering, or a combination of them all to fabricate highly efficient PSCs.

Nongeminate Recombination in All-Polymer Solar Cells with Different Crystallinities.

One of the most challenging issues facing the organic photovoltaic community is to realize a high fill factor (FF) even with thick active layers. This is because the thick active layer is beneficial for photon absorption but makes charge collection difficult, which is primarily restricted by nongeminate recombination in solar cells. In this work, we have studied nongeminate recombination in four kinds of polymer solar cells based on blends of donor-conjugated polymers with different crystallinities and acceptor-conjugated polymers with a naphthalene diimide unit by using transient photovoltage and photocurrent techniques. As a result, we find that nongeminate recombination is considerably suppressed with an increasing degree of crystallinity of donor polymers, leading to a high FF of more than 0.6 even with an active layer thickness of 300 nm. The origin of such a phenomenon is further discussed in terms of variations in the states of mixed phases with a cascaded energy structure between crystalline domains and amorphous domains evaluated by conductive atomic force microscopy.

Semi-Circumferential Decompression: Total En-Bloc Ligamentum Flavectomy to Treat Lumbar Spinal Stenosis with Two-Level Degenerative Spondylolisthesis.

INTRODUCTION: Despite technical developments in decompression without fusion, many studies still assert that instability could be increased in patients with spinal stenosis and lumbar degenerative spondylolisthesis after spinal decompression surgery without fusion. Thus, this study aimed to describe and assess the clinical outcomes of the semi-circumferential decompression (SCD) technique used for microsurgical en-bloc total ligamentum flavectomy with preservation of the facet joint in treating patients who have lumbar spinal stenosis with two-level degenerative spondylolisthesis. METHODS: We retrospectively analyzed the clinical and radiologic outcomes of 14 patients who had spinal stenosis with two-level Meyerding grade I degenerative spondylolisthesis. We evaluated improvements in back pain and radiating pain using a visual analogue scale (VAS) and the Oswestry Disability Index (ODI). We have also examined the occurrence of spinal instability on a radiological exam using slip percentage and slip angle. RESULTS: The mean VAS score of back pain and radiating pain has been determined to decrease significantly from 6.7 to 3.3 and from 8.6 to 2.7, respectively. Meanwhile, the ODI score significantly improved from 27.3 preoperatively to 9.8 postoperatively. Statistically significant change was not observed in the slip percentage in both upper and lower levels. Dynamic slip percentage, which is defined as the difference in the slip percentage between flexion and extension, also did not significantly change. No statistically significant change was found in the slip angle and dynamic slip angle. CONCLUSIONS: SCD is a recommendable procedure that can improve clinical results. This procedure does not cause spinal instability when treating patients who have spinal stenosis with two-level degenerative spondylolisthesis.

Sn(IV)-free tin perovskite films realized by in situ Sn(0) nanoparticle treatment of the precursor solution.

The toxicity of lead perovskite hampers the commercialization of perovskite-based photovoltaics. While tin perovskite is a promising alternative, the facile oxidation of tin(II) to tin(IV) causes a high density of defects, resulting in lower solar cell efficiencies. Here, we show that tin(0) nanoparticles in the precursor solution can scavenge tin(IV) impurities, and demonstrate that this treatment leads to effectively tin(IV)-free perovskite films with strong photoluminescence and prolonged decay lifetimes. These nanoparticles are generated by the selective reaction of a dihydropyrazine derivative with the tin(II) fluoride additive already present in the precursor solution. Using this nanoparticle treatment, the power conversion efficiency of tin-based solar cells reaches 11.5%, with an open-circuit voltage of 0.76 V. Our nanoparticle treatment is a simple and broadly effective method that improves the purity and electrical performance of tin perovskite films.

Enhanced Charge Transport in a Conjugated Polymer Blended with an Insulating Polymer.

Herein, the hole transport in a quinoxaline-thiophene based conjugated polymer (PTQ1) mixed with an insulating polystyrene (PS) was studied by macroscopic and local current density-voltage characteristics measurements. As a result, we found that the hole conductivity in PTQ1 : PS blends increases as the weight ratio of PTQ1 is reduced down to 20 wt%. This is mainly ascribed to increases in mobility because the charge carrier density would be constant in the insulating PS matrix. With decreasing PTQ1 weight ratio in the blends, the absorption bandwidth of PTQ1 and additional emission due to excimer decreased, suggesting that interchain interactions are suppressed. By measuring the temperature-dependent conductivity, we also found that the activation energy for the hole conductivity is smaller in PTQ1 : PS blends than in PTQ1 neat films. These findings suggest that trap sites decrease because of the suppressed interaction between PTQ1 chains in blend films. We also measured conductive atomic force microscope images of the blend films to clarify the local conductive property. For PTQ1 neat films, a low conductive image was observed over the entire film. For PTQ1 : PS blends, on the other hand, many highly conductive spots were locally found. We thus conclude that the dilution of PTQ1 chains in the PS matrix leads to a lower formation of trap sites, resulting in more conductive transport in PTQ1 : PS blends than in PTQ1 neat films.

Improvement of Exciton Collection and Light-Harvesting Range in Ternary Blend Polymer Solar Cells Based on Two Non-Fullerene Acceptors.

Abstract: A non-fullerene molecule named Y6 was incorporated into a binary blend of PBDB-T and IT-M to further enhance photon harvesting in the near-infrared (near-IR) region. Compared with PBDB-T/IT-M binary blend devices, PBDB-T/IT-M/Y6 ternary blend devices exhibited an improved short-circuit current density (JSC) from 15.34 to 19.09 mA cm-2. As a result, the power conversion efficiency (PCE) increased from 10.65% to 12.50%. With an increasing weight ratio of Y6, the external quantum efficiency (EQE) was enhanced at around 825 nm, which is ascribed to the absorption of Y6. At the same time, EQE was also enhanced at around 600-700 nm, which is ascribed to the absorption of IT-M, although the optical absorption intensity of IT-M decreased with increasing weight ratio of Y6. This is because of the efficient energy transfer from IT-M to Y6, which can collect the IT-M exciton lost in the PBDB-T/IT-M binary blend. Interestingly, the EQE spectra of PBDB-T/IT-M/Y6 ternary blend devices were not only increased but also red-shifted in the near-IR region with increasing weight ratio of Y6. This finding suggests that the absorption spectrum of Y6 is dependent on the weight ratio of Y6, which is probably due to different aggregation states depending on the weight ratio. This aggregate property of Y6 was also studied in terms of surface energy.

Origin of Open-Circuit Voltage Loss in Polymer Solar Cells and Perovskite Solar Cells.

Herein, the open-circuit voltage (VOC) loss in both polymer solar cells and perovskite solar cells is quantitatively analyzed by measuring the temperature dependence of VOC to discuss the difference in the primary loss mechanism of VOC between them. As a result, the photon energy loss for polymer solar cells is in the range of about 0.7-1.4 eV, which is ascribed to temperature-independent and -dependent loss mechanisms, while that for perovskite solar cells is as small as about 0.5 eV, which is ascribed to a temperature-dependent loss mechanism. This difference is attributed to the different charge generation and recombination mechanisms between the two devices. The potential strategies for the improvement of VOC in both solar cells are further discussed on the basis of the experimental data.

Solving the Hierarchy Problem at Reheating with a Large Number of Degrees of Freedom.

We present a new solution to the electroweak hierarchy problem. We introduce N copies of the standard model with varying values of the Higgs mass parameter. This generically yields a sector whose weak scale is parametrically removed from the cutoff by a factor of 1/sqrt[N]. Ensuring that reheating deposits a majority of the total energy density into this lightest sector requires a modification of the standard cosmological history, providing a powerful probe of the mechanism. Current and near-future experiments can explore much of the natural parameter space. Furthermore, supersymmetric completions that preserve grand unification predict superpartners with mass below m_{W}M_{pl}/M_{GUT}∼10 TeV.

Gluons to Diphotons via New Particles with Half the Signal's Invariant Mass.

Any new particle charged under SU(3)_{C} and carrying an electric charge will leave an imprint in the diphoton invariant mass spectrum, as it can mediate the gg→γγ process through loops. The combination of properties of loop functions, threshold resummation, and gluon parton distribution functions can result in a peaklike feature in the diphoton invariant mass around twice the mass of a given particle even if the particle is short lived, and thus it does not form a narrow bound state. Using a recent ATLAS analysis, we set upper limits on the combined SU(3)_{C} and electric charge of new particles and indicate future prospects. We also discuss the possibility that the excess of events in the diphoton invariant mass spectrum around 750 GeV originates from loops of a particle with a mass of around 375 GeV.

Is a Price Increase Policy Enough for Adolescent Smokers?: Factors Affecting the Effectiveness of Increasing Cigarette Prices Among Korean Adolescent Smokers.

BACKGROUND: Cigarette pricing policy is one tool for controlling smoking behavior on a national scale. It is unclear, however, what effects such policy has on adolescents and which characteristic subgroups of adolescents are more or less sensitive to cigarette pricing policy. MATERIALS AND METHODS: Our data came from the 2013 Korea Youth Risk Behavior Web-based Survey. The dependent variable was whether or not a participant was classified as a "persistent smokers," defined as a smoker who would continue smoking despite any price increase. Other variables of interest were smoking days (quantity), previous attempts to stop smoking, and previous education on smoking cessation. The statistical analysis was performed using weighted data and the SURVEYFREQ and SURVEYLOGISTIC procedures in SAS 9.3. RESULTS: Among 7094 adolescent smokers (5349 males and 1745 females), 19.9% of males and 25.1% of females reported as persistent smokers. Compared with light smokers, heavy smokers are more likely to be persistent smokers (male: odds ratio [OR] = 2.45, 95% confidence interval [CI] = 2.04-2.95, P value < .001; female: OR = 3.23, 95% CI = 2.44-4.27, P value < .001). When we stratified the data by household income, previous attempts to stop smoking, and previous education on smoking cessation, that trend remained statistically significant. CONCLUSIONS: Because heavier smokers with higher risk of health-related consequences were less sensitive to pricing policy than mild smokers, pricing policy alone is not enough to reduce the societal burden caused by smoking. We suggest that additional cessation policy is needed along with pricing policy for adolescents with heavier smoking behavior in Korea. IMPLICATION: This study shows that heavy smokers are more likely to be persistent smokers despite the cigarette price increase policy, compared with light smokers in Korean adolescents. Because heavier smokers were less sensitive to pricing policy than mild smokers, pricing policy alone is not enough to reduce the societal burden caused by smoking. We suggest that additional tobacco control policies should be evaluated and effective ones implemented in addition to cigarette prices to reduce smoking among regular adolescent smokers.

Photovoltaic Performance of Perovskite Solar Cells with Different Grain Sizes.

Perovskite solar cells exhibit improved photovoltaic parameters with increasing perovskite grain size. The larger photocurrent is due to the enhanced absorption efficiency for thicker perovskite layers. The larger open-circuit voltage (VOC ) is ascribed to the reduced trap-assisted recombination for the larger grains. As a result, the power conversion efficiency exceeds 19% at best. Further improvement in VOC would be possible if the trap density were reduced.

Clinical Analysis of Lobular Keloid after Ear Piercing.

BACKGROUND: Lobular keloid appears to be a consequence of hypertrophic inflammation secondary to ear piercings performed under unsterile conditions. We wish to understand the pathogenesis of lobular keloids and report operative outcomes with a literature review. METHODS: A retrospective review identified 40 cases of lobular keloids between January, 2005 and December, 2010. Patient records were reviewed for preclinical factors such as presence of inflammation after ear piercing prior to keloid development, surgical management, and histopathologic correlation to recurrence. RESULTS: The operation had been performed by surgical core extirpation or simple excision, postoperative lobular compression, and scar ointments. Perivascular infiltration was noted in intra- and extra-keloid tissue in 70% of patients. The postoperative recurrence rate was 10%, and most of the patients satisfied with treatment outcomes. CONCLUSION: Histological perivascular inflammation is a prominent feature of lobular keloids. Proper surgical treatment, adjuvant treatments, and persistent follow-up observation were sufficient in maintaining a relatively low rates of recurrence.

Reduction of Nasal Bone Fracture using Ultrasound Imaging during Surgery.

BACKGROUND: Most nasal bone fractures are corrected using non-invasive methods. Often, patients are dissatisfied with surgical outcomes following such closed approach. In this study, we compare surgical outcomes following blind closed reduction to that of ultrasound-guided reduction. METHODS: A single-institutional prospective study was performed for all nasal fracture patients (n=28) presenting between May 2013 and November 2013. Upon research consent, patients were randomly assigned to either the control group (n=14, blind reduction) or the experimental group (n=14, ultrasound-guided reduction). Surgical outcomes were evaluated using preoperative and 3-month postoperative X-ray images by two independent surgeons. Patient satisfaction was evaluated using a questionnaire survey. RESULTS: The experimental group consisted of 4 patients with Plane I fracture and 10 patients with Plane II fracture. The control group consisted of 3 patients with Plane I fracture and 11 patients with Plane II fracture. The mean surgical outcomes score and the mean patient dissatisfaction score were found not to differ between the experimental and the control group in Plane I fracture (p=0.755, 0.578, respectively). In a subgroup analysis consisting of Plane II fractures only, surgeons graded outcomes for ultrasound-guided reduction higher than that for the control group (p=0.007). Likewise, among the Plane II fracture patients, those who underwent ultrasound-guided reduction were less dissatisfied than those who underwent blind reduction (p=0.043). CONCLUSION: Our study result suggests that ultrasound-guided closed reduction is superior to blind closed reduction in those patients with Plane II nasal fractures.

Improvement of Infraorbital Rim contour Using Medpor.

BACKGROUND: Asymmetry of the infraorbital rim can be caused by trauma, congenital or acquired disease, or insufficient reduction during a previous operation. Such asymmetry needs to be corrected because the shape of the infraorbital rim or midfacial skeleton defines the overall midfacial contour. METHODS: The study included 5 cases of retruded infraorbital rim. All of the patient underwent restoration of the deficient volume using polyethylene implants between June 2005 and June 2011. The infraorbital rim was accessed through a subciliary approach, and the implants were placed in subperiosteal space. Surgical outcomes were evaluated using preoperative and postoperative computed tomography studies. RESULTS: Implant based augmentation was associated with a mean projection of 4.6 mm enhancement. No postoperative complications were noted during the 30-month follow-up period. CONCLUSION: Because of the safeness, short recovery time, effectiveness, reliability, and potential application to a wide range of facial disproportion problems, this surgical technique can be applied to midfacial retrusion from a variety of etiologies, such as fracture involving infraorbital rim, congenital midfacial hypoplasia, lid malposition after blepharoplasty, and skeletal changes due to aging.