Cost-Effectiveness of Poly ADP-Ribose Polymerase Inhibitors in Cancer Treatment: A Systematic Review

Background: PARP inhibitors have shown significant improvement in progression-free survival, but their costs cast a considerable financial burden. In line with value-based oncology, it is important to evaluate whether drug prices justify the outcomes. / Objectives: The aim of the study was to systematically evaluate PARP inhibitors on 1) cost-effectiveness against the standard care, 2) impact on cost-effectiveness upon stratification for genetic characteristics, and 3) identify factors determining their cost-effectiveness, in four cancer types. / Methods: We systematically searched PubMed, EMBASE, Web of Science, and Cochrane Library using designated search terms, updated to 31 August 2021. Trial-based or modeling cost-effectiveness analyses of four FDA-approved PARP inhibitors were eligible. Other studies known to authors were included. Reference lists of selected articles were screened. Eligible studies were assessed for methodological and reporting quality before review. / Results: A total of 20 original articles proceeded to final review. PARP inhibitors were not cost-effective as recurrence maintenance in advanced ovarian cancer despite improved performance upon genetic stratification. Cost-effectiveness was achieved when moved to upfront maintenance in a new diagnosis setting. Limited evidence indicated non–cost-effectiveness in metastatic breast cancer, mixed conclusions in metastatic pancreatic cancer, and cost-effectiveness in metastatic prostate cancer. Stratification by genetic testing displayed an effect on cost-effectiveness, given the plummeting ICER values when compared to the “treat-all” strategy. Drug cost was a strong determinant for cost-effectiveness in most models. / Conclusions: In advanced ovarian cancer, drug use should be prioritized for upfront maintenance and for patients with BRCA mutation or BRCAness at recurrence. Additional economic evaluations are anticipated for novel indications

Optical Slot-Waveguide Based Biochemical Sensors

Slot-waveguides allow light to be guided and strongly confined inside a nanometer-scale region of low refractive index. Thus stronger light-analyte interaction can be obtained as compared to that achievable by a conventional waveguide, in which the propagating beam is confined to the high-refractive-index core of the waveguide. In addition, slot-waveguides can be fabricated by employing CMOS compatible materials and technology, enabling miniaturization, integration with electronic, photonic and fluidic components in a chip, and mass production. These advantages have made the use of slot-waveguides for highly sensitive biochemical optical integrated sensors an emerging field. In this paper, recent achievements in slot-waveguide based biochemical sensing will be reviewed. These include slot-waveguide ring resonator based refractometric label-free biosensors, label-based optical sensing, and nano-opto-mechanical sensors

Exoplanet phase curves: observations and theory

Phase curves are the best technique to probe the three dimensional structure of exoplanets' atmospheres. In this chapter we first review current exoplanets phase curve observations and the particular challenges they face. We then describe the different physical mechanisms shaping the atmospheric phase curves of highly irradiated tidally locked exoplanets. Finally, we discuss the potential for future missions to further advance our understanding of these new worlds.Comment: Fig.5 has been updated. Table 1 and corresponding figures have been updated with new values for WASP-103b and WASP-18b. Contains a table sumarizing phase curve observation

New evidence of marine fauna tropicalization off the Southwestern Iberian Peninsula (Southwest Europe)

Climate change and the overall increase of seawater temperature are causing a poleward shift in species distribution, which includes a phenomenon described as the tropicalization of temperate regions. This work aims to report the first records of four species off the southwestern Iberian Peninsula, namely, the oceanic puffer Lagocephalus lagocephalus (Linnaeus, 1758), the Madeira rockfish Scorpaena maderensis Valenciennes, 1833, the ornate wrasse Thalassoma pavo (Linnaeus, 1758), and the bearded fireworm Hermodice carunculata (Pallas, 1766). These last three species, along with other occurrences of aquatic fauna and flora along the Portuguese coast, reveal an ongoing process of poleward expansion of several species, which urgently necessitates a comprehensive survey along the entire Iberian Peninsula. The putative origins of these subtropical and tropical species off continental Portugal are discussed, as well as the potential public health problems that two of the four reported species may cause.Agência financiadora Fundação para a Ciencia e a Tecnologia (FCT) SFRH/BD/140556/2018 SFRH/BD/104209/2014 Delta Stewardship Council 1167 Delta Science Program 1167 Fundação para a Ciencia e a Tecnologia (FCT) UID/Multi/04326/2013 European Regional Development Fund (COMPETE Program, Operational Competitiveness Program)info:eu-repo/semantics/publishedVersio

An ultra-stable single-chain insulin analog resists thermal inactivation and exhibits biological signaling duration equivalent to the native protein

Thermal degradation of insulin complicates its delivery and use. Previous efforts to engineer ultra-stable analogs were confounded by prolonged cellular signaling in vivo, of unclear safety and complicating mealtime therapy. We therefore sought an ultra-stable analog whose potency and duration of action on intravenous bolus injection in diabetic rats are indistinguishable from wild-type (WT) insulin. Here, we describe the structure, function, and stability of such an analog, a 57-residue single-chain insulin (SCI) with multiple acidic substitutions. Cell-based studies revealed native-like signaling properties with negligible mitogenic activity. Its crystal structure, determined as a novel zinc-free hexamer at 2.8 Å, revealed a native insulin fold with incomplete or absent electron density in the C domain; complementary NMR studies are described in the accompanying article. The stability of the analog (ΔGU 5.0(±0.1) kcal/mol at 25 °C) was greater than that of WT insulin (3.3(±0.1) kcal/mol). On gentle agitation, the SCI retained full activity for >140 days at 45 °C and >48 h at 75 °C. These findings indicate that marked resistance to thermal inactivation in vitro is compatible with native duration of activity in vivo Further, whereas WT insulin forms large and heterogeneous aggregates above the standard 0.6 mm pharmaceutical strength, perturbing the pharmacokinetic properties of concentrated formulations, dynamic light scattering, and size-exclusion chromatography revealed only limited SCI self-assembly and aggregation in the concentration range 1-7 mm Such a combination of favorable biophysical and biological properties suggests that SCIs could provide a global therapeutic platform without a cold chain

Projecting the 10-year costs of care and mortality burden of depression until 2032: a Markov modelling study developed from real-world data

Background Based on real-world data, we developed a 10-year prediction model to estimate the burden among patients with depression from the public healthcare system payer's perspective to inform early resource planning in Hong Kong. Methods We developed a Markov cohort model with yearly cycles specifically capturing the pathway of treatment-resistant depression (TRD) and comorbidity development along the disease course. Projected from 2023 to 2032, primary outcomes included costs of all-cause and psychiatric care, and secondary outcomes were all-cause deaths, years of life lived, and quality-adjusted life-years. Using the territory-wide electronic medical records, we identified 25,190 patients aged ≥10 years with newly diagnosed depression from 2014 to 2016 with follow-up until 2020 to observe the real-world time-to-event pattern, based on which costs and time-varying transition inputs were derived using negative binomial modelling and parametric survival analysis. We applied the model as both closed cohort, which studied a fixed cohort of incident patients in 2023, and open cohort, which introduced incident patients by year from 2014 to 2032. Utilities and annual new patients were from published sources. Findings With 9217 new patients in 2023, our closed cohort model projected the 10-year cumulative costs of all-cause and psychiatric care to reach US$309.0 million and US$58.3 million, respectively, with 899 deaths (case fatality rate: 9.8%) by 2032. In our open cohort model, 55,849–57,896 active prevalent cases would cost more than US$322.3 million and US$60.7 million, respectively, with more than 943 deaths annually from 2023 to 2032. Fewer than 20% of cases would live with TRD or comorbidities but contribute 31–54% of the costs. The greatest collective burden would occur in women aged above 40, but men aged above 65 and below 25 with medical history would have the highest costs per patient-year. The key cost drivers were relevant to the early disease stages. Interpretation A limited proportion of patients would develop TRD and comorbidities but contribute to a high proportion of costs, which necessitates appropriate attention and resource allocation. Our projection also demonstrates the application of real-world data to model long-term costs and mortality, which aid policymakers anticipate foreseeable burden and undertake budget planning to prepare for the care need in alternative scenarios

An enzyme-linked immunosorbent assay for detection of avian influenza virus subtypes H5 and H7 antibodies

BACKGROUND: Avian influenza virus (AIV) subtypes H5 and H7 attracts particular attention because of the risk of their potential pathogenicity in poultry. The haemagglutination inhibition (HI) test is widely used as subtype specific test for serological diagnostics despite the laborious nature of this method. However, enzyme-linked immunosorbent assays (ELISAs) are being explored as an alternative test method. H5 and H7 specific monoclonal antibodies were experimentally raised and used in the development of inhibition ELISAs for detection of serological response specifically directed against AIV subtypes H5 and H7. The ELISAs were evaluated with polyclonal chicken anti-AIV antibodies against AIV subtypes: H1N2, H5N2, H5N7, H7N1, H7N7, H9N9, H10N4 and H16N3. RESULTS: Both the H5 and H7 ELISA proved to have a high sensitivity and specificity and the ELISAs detected H5 and H7 antibodies earlier during experimental infection than the HI test did. The reproducibility of the ELISA’s performed at different times was high with Pearson correlation coefficients of 0.96-0.98. CONCLUSIONS: The ELISAs are a potential alternative to the HI test for screening of large amounts of avian sera, although only experimental sera were tested in this study

ALMA Survey of Orion Planck Galactic Cold Clumps (ALMASOP) : A Hot Corino Survey toward Protostellar Cores in the Orion Cloud

The presence of complex organic molecules (COMs) in the interstellar medium is of great interest since it may link to the origin and prevalence of life in the universe. Aiming to investigate the occurrence of COMs and their possible origins, we conducted a chemical census toward a sample of protostellar cores as part of the Atacama Large Millimeter/submillimeter Array Survey of Orion Planck Galactic Cold Clumps project. We report the detection of 11 hot corino sources, which exhibit compact emissions from warm and abundant COMs, among 56 Class 0/I protostellar cores. All of the hot corino sources discovered are likely Class 0, and their sizes of the warm region (>100 K) are comparable to 100 au. The luminosity of the hot corino sources exhibits positive correlations with the total number of methanol and the extent of its emissions. Such correlations are consistent with the thermal desorption picture for the presence of hot corinos and suggest that the lower-luminosity (Class 0) sources likely have a smaller region with COM emissions. With the same sample selection method and detection criteria being applied, the detection rates of the warm methanol in the Orion cloud (15/37) and the Perseus cloud (28/50) are statistically similar when the cloud distances and the limited sample size are considered. Observing the same set of COM transitions will bring a more informative comparison between the cloud properties.Peer reviewe

ALMA Survey of Orion Planck Galactic Cold Clumps (ALMASOP). I. Detection of New Hot Corinos with the ACA

We report the detection of four new hot corino sources, G211.47-19.27S, G208.68-19.20N1, G210.49-19.79W, and G192.12-11.10, from a survey study of Planck Galactic Cold Clumps in the Orion Molecular Cloud Complex with the Atacama Compact Array. Three sources had been identified as low-mass Class 0 protostars in the Herschel Orion Protostar Survey. One source in the lambda Orionis region is first reported as a protostellar core. We have observed abundant complex organic molecules (COMs), primarily methanol but also other oxygen-bearing COMs (in G211.47-19.27S and G208.68-19.20N1) and the molecule of prebiotic interest NH2CHO (in G211.47-19.27S), signifying the presence of hot corinos. While our spatial resolution is not sufficient to resolve most of the molecular emission structure, the large line width and high rotational temperature of COMs suggest that they likely reside in the hotter and innermost region immediately surrounding the protostar. In G211.47-19.27S, the D/H ratio of methanol ([CH2DOH]/[CH3OH]) and the(12)C/C-13 ratio of methanol ([CH3OH]/[(CH3OH)-C-13]) are comparable to those of other hot corinos. Hydrocarbons and long-carbon-chain molecules such as c-C(3)H(2)and HCCCN are also detected in the four sources, likely tracing the outer and cooler molecular envelopes.Peer reviewe