Inclusion Of Phase Research Articles

Inclusion of phase III clinical trial costs in health economic evaluations

IntroductionProtocol-driven trial activities contribute to the utility gain demonstrated in the phase III clinical trial of a new drug. If this utility gain cannot be distinguished from the effects of the new drug itself, protocol-driven trial costs cannot be easily dismissed for consistency reasons. This study aims to estimate the impact of including per-patient costs of phase III clinical trials on the incremental cost-effectiveness ratio (ICER).MethodsThe analysis utilized a modeling approach with secondary data from an ad-hoc literature review, considering both societal and payer perspectives. While the costs of phase III clinical trials may cancel out during the period of “normal” life-years due to the incremental cost calculation, they do not cancel out when differential early treatment termination occurs (e.g., due to differential mortality). Assuming the presence of differential mortality, per-patient phase III trial costs were calculated for the period of added life-years. These costs were then included in the ICER of a new drug, under the assumption that direct patient-related costs constitute 30–70% of the total trial costs. Capital costs were also incorporated from a societal perspective.ResultsBased on assumptions of $40,000 out-of-pocket expenses per patient enrolled in a phase III trial and a life expectancy gain of three months, incremental costs increased by $27,000 from a societal perspective. From a payer perspective, the estimate was $12,000.ConclusionsThe costs of phase III trials are a relevant component of the ICER, and excluding it is generally not appropriate for consistency reasons. Properly considering these trial costs is essential for a comprehensive evaluation of a new drug’s cost-effectiveness.

Monte‐Carlo based algorithm for reconstruction of oriented microstructure

AbstractDespite the development of three‐dimensional imaging techniques in materials science, most of the microstructural data is taken from two‐dimensional sections. It includes images produced by optical, scanning, and transmission electron microscopy. Due to the stochastic indefinite characteristics of such sections, it is a challenge to reproduce three‐dimensional microstructure characteristics quantitatively. Several analytical techniques were developed in stereology to overcome such limitations. Nevertheless, available analytical techniques are restricted to limiting cases of entirely random or fully coaxial orientation of microstructural features. On the other hand, achieving ideal coaxiality of such inclusions in actual technological conditions is not achievable. In this work, the Monte‐Carlo‐based optimization algorithm is constructed to overcome the limitations of existing stereometric models. This algorithm considers information from longitudinal and transverse sets of images. Orientations, as well as size distributions, are taken into account. The model operates under the assumption of log‐normal distribution of 3d size characteristics and von Mises distributions of angles. Then, a derivation‐free optimization algorithm is used to match histograms of simulated and observed sections. The method for estimating the initial values of optimized variables is proposed, based on the existing analytic solutions. The reconstruction algorithm is then applied to estimate three‐dimensional angle and size distributions of inclusion of phase in near‐eutectic alloy, produced by directional solidification technique. Finally, the algorithm's convergence is discussed, as well as its limitations and future developments.

Exploring the effect of exchange coupling in (SrFe9.8Al2La0.2O19)1-x/(Co0.7Zn0.3Fe2O4)x nanocomposites synthesised by sol–gel auto combustion method

Extensive research has been conducted over the last decade to develop permanent magnets utilizing less rare earth materials. Exchange-coupled nanocomposite magnets are a fascinating development in the field of permanent magnets. They involve the combination of hard and soft ferrites, resulting in a unique and evolving magnet. Here we present an in-depth structural, morphological and magnetic characterization of ferrite-based nanostructures obtained through a bottom-up sol−gel approach. The combination of high coercivity of a hard phase SrFe9.8Al2La0.2O19 (SFALO) and high saturation magnetization of a soft phase, Co0.7Zn0.3Fe2O4 (CZFO), allowed us to develop exchange-coupled bi-magnetic nanocomposites by varying the mass percentage (x = 0, 0.1, 0.2, 0.3, 0.4, 1). Thermogravimetric analysis (TGA) up to 1200 °C was used to investigate the material’s thermal properties with the phase formation temperature. Detailed atomic/nano-scale structural characterizations of these nanocomposites were performed by X-ray diffraction and Transmission Electron Microscopy. The average particle size was calculated from the SEM analysis and it was observed that most of the composites with ratio x = 0.1, 0.3 & 0.4 was 145 nm and x = 0.2 was 165 nm. The Switching Field Distribution (SFD) curve revealed the exchange coupling between soft and hard magnetic particles. The findings indicate that the inclusion of a soft magnetic phase has a considerable impact on the exchange coupling between the hard and soft ferrite phases. As the spinel concentration increased, in the composite the saturation magnetization increased from 18 emu/g to 48 emu/g. From the stroner-wholfrathmodel, the decrease in the remanence ratio below 0.5 concludes the crystallites are randomly oriented. The nanocomposite with the ratio x = 0.1 was observed with the high magneto crystalline anisotropy of 2183.23 × 102 (J/m3) and a high energy product (BH)max of 5.5 kJ/m3. The aforementioned features of nanocomposites demonstrate their potential for use in permanent magnet applications.

Enhancing the thermoelectric performance of Sr0.6La0.4Nb2O6-δ-based ceramics through composite effects

Donor-doped SrNb2O6-based materials are regarded as highly promising candidates for high-temperature thermoelectric applications. The Sr0.6La0.4Nb2O6-δ/x wt% Ti (x = 1, 5, 10, 15) composite ceramics thermoelectric materials were prepared and the mechanism for enhancing their thermoelectric properties was investigated. The experimental results demonstrate that during sintering, nano-additive titanium powder undergoes oxidation to form TiO2. The inclusion of a secondary phase ultimately leads to successful reduction in electrical resistivity within the composite oxides. Due to crystal defects, complex structure and phonon scattering at grain boundaries, the samples consistently exhibit low thermal conductivity values below 3.0 W m−1K−1. Among them, the sample doped with 10 wt% Ti shows the highest PF value (470.0 μW/mK2 at 1073 K), demonstrating a significant increase in power factor of 280 % compared to Sr0.6La0.4Nb2O6 without the Ti composite. Consequently, the Sr0.6La0.4Nb2O6-δ/10 wt% Ti composite material achieved a maximum ZT value of 0.20, representing a fifty-three percent enhancement compared to the undoped sample.

The influence of mineral inclusion on the effective strength of rock-like geomaterials

The influences of microstructure on the macroscopic mechanical behavior of a composite with a porous matrix reinforced by mineral inclusions are investigated in the present work by both numerical and theoretical methods. The mineral inclusions are embedded at the mesoscopic scale and much bigger than the pores which are located at the microscopic scale. In order to consider the properties of the studied rock-like geomaterials, such as the dissymmetry between tension and compression, the solid phase at the microscopic scale is assumed to obey to a Drucker–Prager criterion. Based on the studied microstructure, the Fast Fourier Transform (FFT) based numerical method is firstly adopted to investigate the macroscopic plastic yield stress of the studied composite. Different microstructure having different volume fraction of inclusion, micro-porosity and frictional coefficient of the solid phase are considered. Based on these numerical results, the existing theoretical yield criterion is estimated. One finds that it should be improved for the case of a microstructure having a high inclusion content. Then, a new macroscopic yield criterion is constructed in the present work by using the modified secant method. This criterion ameliorates fundamentally the one proposed in Shen et al. (2013), specially for the case of a deviatoric loading. It is then estimated and validated by comparing with the FFT based numerical results which were carried out in this work with different volume fractions of heterogeneous phase.

Electrically‐Driven Light Source Embedded in a GaP Nanowaveguide for Visible‐Range Photonics on Chip

AbstractThe key components of photonic integrated circuits are nanoscale optica emitters and nanowaveguides. III‐V semiconductor nanostructures are considered as the most promising material platform for these components due to highly efficient luminescence and high refractive index, but the problem of emission coupling with waveguide is to be solved. In this work, the use of GaP nanowires (NWs) with different types of doping (GaP:Si or GaP:Be) is proposed as optical waveguides with directly integrated electrically‐driven light sources, solving the problem of emission‐to‐waveguide coupling. Single NWs are integrated with electrodes and pump electroluminescence by a tunnel junction allowing to study emission properties with nanoscale spatial resolution. Basing on the experiments on scanning tunnelling microscopy (STM), electron microscopy, time‐resolved photoluminescence micro‐spectroscopy, X‐ray diffraction, and STM‐induced electroluminescence, it is proven that GaP NWs exhibit different integrated light‐source on doping type of NWs. GaP:Be NWs contain inclusion of the crystalline wurtzite phase with a direct bandgap, and, thus, these NW regions can be considered as electrically‐driven nanoscale sources of light monolithically integrated into GaP NW‐based waveguides. Meanwhile, GaP:Si NWs work as optical waveguides capable of efficient light generation over the entire length of NW. The developed designs are promising for construction of integrated photonic circuits.

Outcomes of patients with metastatic solid cancers treated on early phase clinical trials in western Australia.

e23094 Background: Cancer drug development is flourishing with novel immunotherapy combinations, antibody drug conjugates and increasingly molecularly targeted therapies that have pushed the inclusion of phase I clinical trials into earlier lines of systemic treatment. Linear Clinical Research is a dedicated Phase I centre with a catchment area of over 3 million people. We conducted a retrospective review into the outcomes of our centre. Methods: We included patients between 01/01/2020 to 30/04/2023, with advanced/metastatic or rare cancers with no available or suitable standard of care treatment. Data were extracted from our internal database with minimum follow up of 6 months. The primary endpoint was overall survival (OS). Other endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), time to response (TTR), duration of response (DOR), duration of treatment (DOT), post-treatment survival (PTS), and 90-day mortality. Subgroup analyses based on treatment type were performed. Multivariate cox regression analysis was performed as part of tertiary endpoints. Results: 251 patients were recruited to 53 trials. Median age : 61 years (range: 21-83 years), 54.6% female, 74.1% Caucasian, ECOG 0-1: 90.8%, 26.7% rare cancers, 52.2% had 0-1 line of previous treatment, 47.8% had ≥ 2 lines. Trial treatments were: 51.4% immunotherapy (IO), 30.7% targeted therapy matched to molecular findings (TT), 2.8% antibody drug conjugate (ADC), 12.7% combination therapy (IO/TT/ADC/chemotherapy), 2.0% endocrine therapy alone, and < 1% chemotherapy. At data cut-off, 129 OS events had occurred (56.0%, median follow up of 22.0 months).The median OS was 16.0 months (95% CI 11.1 - 20.9), median PFS: 3.0 months (95% CI 2.2 - 3.8), ORR: 23.6%, DCR: 67.3%, median TTR: 2.0 months (IQR: 1.0-3.0), median DOR: 14.0 months (IQR: 6.0-38.0), median DOT: 3.0 months (IQR 1.0-10.0), median PTS: 7.0 months (IQR 2.0-27.0), 90-day mortality: 17.7%. Median OS based on treatment type: 11.0 months (95% CI 5.7-16.3) (IO), 12.0 months (95% CI 1.6-22.4) (TT), median not reached (range :1.0-28.0) (ADC), and 19.0 months (95% CI 13.6-24.4) (combination therapy). Median PFS based on treatment type: 2.0 months (95% CI 1.2-2.8) (IO), 5.0 months (95% CI 2.5-7.5) (TT), 10.0 months (95% CI: 0.0-28.0) (ADC), 6.0 months (95% CI 2.2 - 9.8) (combination therapy). Multivariate Cox analysis showed that higher number of lines of previous treatment was negatively associated with PFS and OS when adjusted for age, gender, type of treatment, and baseline sum of diameter (SOD). Conclusions: Our overall OS, ORR, and DCR are better than historical data of phase 1 during chemotherapy era , and are comparable to other centers nationally and internationally. Further work needs to be done to improve survival outcomes including algorithms to better match patients and trials earlier in their disease course.

Re: "A Novel Randomized Trial Protocol for Evaluating Wound Healing Interventions" by Bull et al.

This response critically evaluates the study "A Novel Randomized Trial Protocol for Evaluating Wound Healing Interventions," highlighting key concerns and proposing improvements. The study's departure from standard analytical principles, characterized by inadequate power and a lack of cohort comparisons, raises questions about the reliability of its conclusions. Rigorous adherence to established randomized controlled trial methodologies is crucial for valid evidence in wound healing research. Additionally, the inclusion of a run-in phase presents challenges in subject recruitment, resulting in a significant loss of eligible participants. Streamlining study designs to minimize such barriers is imperative for ensuring feasibility and achieving sufficient statistical power. The use of a laser-assisted wound measurement (LAWM) device, though validated for area measurement, overlooks wound depth, introducing potential bias. This limitation underscores the need for meticulous consideration of measurement tools to ensure comprehensive and accurate data collection. The study's proposed outcome protocol neglects crucial wound healing parameters like wound bed quality and tunnelling/undermining. Advocating for customized scoring systems based on wound etiology could address these oversights, enhancing the study's clinical relevance. This critical response emphasizes the importance of methodological rigor and comprehensive outcome assessments in advancing wound healing research. Addressing these concerns will contribute to a more robust evidence base, fostering improved translational outcomes in wound healing interventions. On behalf of Bull et al, Harding & Clements categorically respond to the concerns raised.

Circularity of new composites from recycled high density polyethylene and leather waste for automotive bumpers. Testing performance and environmental impact

New composite materials (suitable for automotive bumpers), composed of recycled high-density polyethylene (rHDPE) and leather buffing dust waste (BF) ranging from 20 to 50 wt%, were produced and investigated for mechanical properties. Optimal mechanical performance was achieved with composites containing 30 % wt BF. The environmental performance of automotive bumper production from both virgin and recycled HDPE reinforced with 30 % wt BF (HDPE-BF, rHDPE-BF) composites was compared to that of conventional polypropylene (PP) by performing a cradle to gate life cycle assessment.A component-based approach, instead of a comprehensive LCA assessment for the entire car was adopted using various functional units (FU) such as mass (FU1), volume (FU2), and volume of raw material fulfilling a specific impact strength requirement (FU3), thus enriching the paper with methodological discussions.The rHDPE-BF system provided better environmental performance compared to the virgin PP system, when considering both mass and volume-related functional units, mainly due to the avoidance of virgin polymer production. Even with the inclusion of the use phase in FU2 and a slightly higher density (+1.7 %) of composites than PP-based bumpers, the rHDPE system still provides better environmental performance (10 % less impact). The sensitivity analysis highlighted the significance of car type and final density of the bumper on the impact results. Finally, when using FU3, due to its higher impact strength, HDPE-BF system is clearly the best environmental alternative (50 % less impact) followed by rHDPE-BF system. In all cases, rising the content of recycled materials in the bumpers increases its circularity.The paper illustrates the importance of selecting a suitable functional unit, based on a specific application (i.e., automotive bumpers), to evaluate the environmental impact of new composite materials in comparison to traditional options. Expanding the assessment to encompass multiple functions provides a more accurate portrayal of reality but also introduces greater result uncertainty.

Observational studies to emulate randomized trials: Some real-world barriers.

The randomized controlled trial (RCT) forms the basis for drug approval by regulatory agencies. Observational studies using existing data from healthcare databases now also provide real-world evidence (RWE) in regulatory decision-making. Several initiatives are assessing the value of RWE by conducting observational studies that emulate published RCTs. While many RCTs are straightforward to emulate, others are challenging. We describe three RCT design aspects that pose challenges for observational studies. First are trials that enrol already treated subjects who must discontinue these treatments at the time of randomization, which can distort the comparison with observational studies. Second is the inclusion of a run-in phase, especially to exclude non-compliant subjects from the trial. Third are trials that evaluate the effect of weaning off treatment. In conclusion, future randomized trials that aim to be emulated by observational studies could consider study designs that allow emulation and thus provide valid and complementary RWE.

Impact of the Hexagonal Phase on Multiphoton‐Absorption Properties of Mixed‐Cation Halide Perovskite: FA0.8MA0.2PbI3

AbstractRecently, mixed‐cation halide perovskites have gained significant attention for developing stable, high‐performance solar cells. However, their nonlinear optical (NLO) properties are much less explored. Herein, this study reports on intriguing NLO properties observed from FA0.8MA0.2PbI3 single crystals, having an ideal bandgap of 1.52 eV for photovoltaic performance. Contrary to a simple prediction, the perovskite exhibits higher‐order multiphoton absorption (MPA) over a broad wavelength range from 1300 to 1710 nm as evidenced by wavelength‐ and intensity‐dependent photoluminescence measurements. The corresponding MPA coefficients are very large to dominate lower‐order ordinary MPA across the bandgap. The hexagonal phase present in the perovskite is responsible for the observed higher‐order transition as confirmed by the recovery of ordinary MPA in the absence of the hexagonal phase. Although the perovskite is known to crystallize into the cubic phase at room temperature, these results indicate that minor inclusion of the hexagonal phase (≈4.0% at room temperature) can drastically alter the nature of the multiphoton process by double resonance uniquely offered by the mixed phases.

Impact of magnetic spinel ferrite content on the structure, morphology, optical, and magneto-dielectric properties of BaTiO3 materials

Abstract In this study, the influence of magnetic content of NiFe1.93Dy0.07O4 spinel ferrite on the structural, morphological, optical, and magneto-dielectric properties of BaTiO3 materials was investigated. NiFe1.93Dy0.07O4 magnetic nanoparticles and BaTiO3 dielectric materials were firstly synthesized using the hydrothermal method and sol–gel auto-combustion route, respectively. Then, different contents of the magnetic nanoparticles were added to BaTiO3 to form a series of BaTiO3/(NiFe1.93Dy0.07O4) x samples (abbreviated as BTO/(NDFO) x ) with x = 0, 2, 5, 10, 20, and 100 %. The analysis of the structure via X-ray diffraction (XRD) technique revealed a transformation from a tetragonal structure for the pristine BTO sample to a cubic structure upon the inclusion of magnetic nanoparticles. The morphological observations and chemical composition analyses via scanning electron microscope (SEM) coupled with EDX system showed the successful formulation of biphasic products. The optical properties were investigated, and it was found that the inclusion of the magnetic phase diminishes the bandgap energy (E g ) of final BTO/(NDFO) x samples. Furthermore, vibrating sample magnetometer (VSM) was used to investigate the magnetization properties. The values of saturation magnetization (M S ) and remanent (M r ) magnetization are rising with the increase of magnetic phase content. However, the coercivity (H c ) does not show a regular variation with the increase of NDFO content. The dielectric properties were also investigated for different BaTiO3/(NiFe1.93Dy0.07O4) x samples. The obtained results showed that the real permittivity (ε′) and dielectric tangent loss (tan δ) increased with increasing temperature. Remarkably, the addition of magnetic content provokes a reduction in tan δ values compared to the pristine BTO sample. The lowest values of tan δ and highest frequency stability were noticed in the sample added with 10 % of magnetic phase. The impedance and modulus were also determined and discussed.

Environmental Impacts in the Textile Sector: A Life Cycle Assessment Case Study of a Woolen Undershirt

The textile industry, known for its significant contribution to global greenhouse gas emissions, is increasingly active in exploring techniques and technologies to improve its environmental performance. The main tool to calculate environmental impacts is the Life Cycle Assessment (LCA) methodology, which is standardized and internationally recognized. Specific guidelines for the impact calculation of textile products are under development (Product Environmental Footprint Category Rules (PEFCRs) for the category of Apparel and Footwear). In this context, this study contributes to the knowledge in the textile sector through the development of a cradle-to-gate LCA of a woolen undershirt produced in Italy. This study shares robust and recent (2021) primary data for the phases of weaving, cutting, and sewing, obtained from an Italian company. Data from previous studies of the authors, as well as secondary data, are also used to complete the inventory. A further analysis is developed to include the use phase as well. The impact on climate change of one undershirt results in 11.7 kg CO2 eq, primarily due to the farming phase of sheep, which accounts for 88% of the total emissions. The impact on climate change of energy used in the wool transformation process has a relatively low impact (11%), also thanks to the partial use of electricity produced by photovoltaic panels, while materials (e.g., chemicals) and transportation have negligible contributions. The farming phase, despite relying on secondary data, is identified as the primary contributor for most of the other indicators. Additionally, it has been found that user habits play a key role in the impact related to one wearing of the undershirt. The findings suggest that further work is necessary in the textile sector and emphasize (i) the need for guidelines, enabling the inclusion of the use phase without compromising the comparability between different LCAs of similar textile products; (ii) the need for improved traceability practices in the textile sector, to enhance inventory data collection on the raw material production (wool fibers in the case under analysis).

Effectiveness of Jacobson’s Relaxation Technique and Yoga in Insomnia among Shift Working Nurses

Background: Nurses are one of the main professions in the hospital to recover patients from their abnormal health conditions. The activity of nurses is intimately connected to shift work. Daily shift work results in increased workload and mental stress, which leads to sleep disorder and delayed adaptation for young nurses to shift work, this may cause the nurse’s difficulty falling asleep or insomnia. There is compelling evidence that shift work has a negative impact on sleep, alertness, and exhaustion, which may contribute to mental health issues and sleep issues. Aim: This study aims to find the effectiveness of Jacobson’s relaxation technique and yoga in insomnia among shift nurses. Methodology: In phase 1: The survey was conducted among 100 nurses through Google forms using ISI questionnaires. They were chosen with the help of the convenience sampling technique. Among 100 responded participants, 54% were diagnosed to have insomnia based on the total score range. 20% of selected nurses disagreed to participate in the experimental study (phase 2). Ultimately, 30 nurses were chosen to take part in the experimental trial based on the inclusion and exclusion criteria of phase 2. The participants in the study who had sleeplessness received two therapies. 30 selected nurses were randomly allocated into two groups, 15 in each group. One group was given yoga (Group Y) and another group was given Jacobson’s relaxation technique (Group J). It was given for a time period of 4 days per week for a duration of one month. Results: A statistically significant difference between Group Y (Yoga) and Group J (Jacobson's relaxation technique) was found by statistical analysis of the statistical data. In comparison to Group J, Group Y had lower PSQI values. As a result, group Y and group J differ statistically significantly from one another. Conclusion: It has been concluded that both yoga and Jacobson’s relaxation technique were more effective in improving sleep in nurses with insomnia, among them yoga is more effective than Jacobson’s relaxation technique.

Optimization of magnetoelectric coupling in BiFeO3-BaTiO3-MnFe2O4 tri-phase composites for ultra-sensitive devices

Multiferroic materials with coupled electric and magnetic orderings have astonished the scientific community by exhibiting magnetoelectric (ME) coupling, viable for multistate memory devices. Facile synthesis of multiferroic composites have further triggered these delightful attributes. Here we present a series of tri-phase composites of the form; (1–x)(0.7BiFeO3 + 0.3BaTiO3) + xMnFe2O4, synthesized by a facile two-step method. The phase-pure synthesis was confirmed using X-ray diffraction. For energy storage capability, a composition with x = 0.02, reveals the recoverable energy density of ∼0.22 mJ/cm3 followed by the highest efficiency of 64.02%, making such composition favourable for energy storage perspectives at minute inclusion of the spinel phase. The characteristic I-V curves were used to explain the leakage current of BiFeO3 (BFO). The positive up and negative down (PUND) sequence demonstrates the significant variation in switching charge density. The gradual increase in grain size resulted in a lowering of the coercivity values up to 301 Oe at x = 0.10 having 6.31 emu/g as saturation magnetization (MS) value along with MR/MS ratio of 0.33. The linear response shown by ME coupling at x = 0.06 along with the afore mentioned attributes make this composition a potential candidate for ultra-sensitive magnetoelectric devices.

Adverse events in MS patients fulfilling or not inclusion criteria of the respective clinical trial - The problem of generalizability.

The aim of this study was to evaluate how many MS patients treated with an approved DMD in routine care would have fulfilled the inclusion and exclusion criteria of phase III clinical trial and would therefore be eligible for the respective drug trial. Further, adverse events and disease progression for these patients were compared. A comparison of patients fulfilling phase III clinical trial inclusion and exclusion criteria and those who do not with regard to sociodemographic and clinical characteristics, adverse events and disease progression. Database was the REGIMS register, a national, prospective, observational, clinical multicentre registry. 1248 MS Patients were included. 27.2% patients would have been eligible for inclusion into a phase III clinical trial of their indication. Patients who did not meet the criterion age are more likely to have a serious adverse event (SAE), whereas patients who did not fulfil the criterion relapse had a significant lower occurrence of an adverse event (AE). Non-fulfilment of other inclusion criteria (EDSS Score; medication history and MS type) did not show any significant differences in drug safety variables, AE and SAE. Our results suggest that a low transferability of phase III clinical trial criteria, to patients in routine care with the exception of age, does not imply a higher risk with regard to adverse and serious adverse events.

Negative additive manufacturing of Al2O3-Al cermet material by fused deposition and Direct Ink Writing

Although additive manufacturing is an attractive alternative for the manufacturing of complex ceramic geometries, the manufactured parts have low mechanical properties due to low solid loading, high porosity, and geometrical distortions. Introducing ductile metal particles into the brittle ceramic matrix is an effective technique to enhance the geometrical accuracy and mechanical properties of the printed part. In the current research, the Direct Ink Writing technique is used to fabricate alumina-based matrix composite reinforced with Al particles by negative additive manufacturing. A homogenous cermet mixture in the form of Al 2 O 3 -Al with various Al compositions (5 vol.%, 10 vol.%, 15 vol.%, and 20. vol.%) was achieved by high-energy ball milling. A slurry was prepared by mixing the milled powder with the carboxymethyl cellulose binder and sodium silicate in the deionized water. Rheological measurements of all the slurries were carried out to investigate the shear-thinning behavior of the pastes. The slurry was cast into the polylactic acid mold as the mold was built up layer by layer simultaneously using a Mitsubishi robotic manipulator. The printed parts were dried, demolded by dissolving in Dichloromethane (DCM) solution, and sintered at 1400°C for 6 hours. X-ray diffraction results revealed two distinguished phases (ceramic and metal) in the finished part. It is possible to formulate printable alumina-aluminum cermet slurries with solid content as high as 50 vol.% and 97% density. It was found that by the inclusion of metallic Al phase, the micro-hardness reduces as compared to monolithic alumina ceramic.

New insights into the breathing physiology from transient respiratory nasal simulation

The flow characteristics and heat transfer during nasal breathing in the complete human upper airway were investigated through the respiratory cycle using transient numerical simulations. We postulate that the complete airway from the nasal cavity to the trachea most accurately represents dynamic airflow patterns during inhalation and exhalation as they are likely to be affected by downstream anatomical structures. A 3D model was constructed from a healthy adult computed tomography scan. Computational fluid dynamics simulations were performed with Ansys Fluent software [ANSYS Fluent, R1 User's Guide (ANSYS, Inc., 2020)] using the stress-blended eddy simulation turbulence model looking at airflow patterns, velocity, mucosal temperature, and humidity (H2O fraction). One and a half breathing cycles were simulated for a total of 5.65 s, where the first inhalation cycle was discarded to avoid start-up effects. The results demonstrated that airway geometry structures, including the turbinates, the soft palate, and the glottic region, affect the flow patterns differently during inspiration and expiration. It also demonstrated phenomena not seen in steady flow simulations or in those without the lower respiratory tract geometry, including the nasopharyngeal temperature imprint during inhalation, the nasopharyngeal jet during exhalation, and the flow structures of the larynx and laryngeal jet. The inclusion of the exhalation phase demonstrates airflow preconditioning before inhalation, which we postulate contributes to achieving alveolar conditions. Alveolar temperature and humidity conditions are not achieved by the nasal cavity alone, and we demonstrate the contribution of the nasopharynx and larynx to air conditioning. Including the complete airway with realistic anatomy and using transient airflow modeling provided new insights into the physiology of the respiratory cycle.

Defining soybean maturity group options for contrasting weather scenarios in the American Southern Cone

Soybean genotypes are grouped in maturity groups (MG) based on the response to photoperiod, and a genotype belonging to a particular MG is recommended according to latitude and planting date. From an agronomic viewpoint, an “optimum maturity group” (MG opt ) can be defined as the one that maximizes soybean yield in a particular environment, and not necessarily corresponds with the recommended MG based on thermo-photoperiod response. Our objectives were to (i) delineate spatial pattern of MG opt across contrasting environmental conditions for full-season soybean using geostatistics, and (ii) test whether the weather scenario change the spatial distribution of the MG opt . We hypothesized that, for the same region, the MG opt in dry years (i.e. La Niña phase) is larger than in humid years (i.e. El Niño phase). We analyzed multi-environment trials of full-season soybean (1675 site-years) using recent soybean genotypes and management practices across the Southern Cone of America. The MG opt ranged between 3.8 and 7.8 across regions and ENSO phases. The geostatistics approach indicated a spatial MG opt auto-correlation. The map for each ENSO phase indicates zones with contrasting MG opt and independently of ENSO phase, MG opt increased as latitude decreased. Also, for a particular latitude range, MG opt also varied according to longitude, suggesting that its variation can be associated with rainfall pattern and soil types in the region. Our approach delineated the distribution of MG opt for the American Southern Cone and highlighted that the inclusion of ENSO phase is important for guiding farmers MG options at regional scale. • Optimum maturity groups ranged from 3.8 to 7.8 in the Southern Cone of America. • Previous optimum maturity groups definition was improved using spatial analysis. • For a particular latitude, optimum maturity groups also varied according to longitude. • Optimum maturity groups varied with weather scenario in some areas of the Southern Cone.

Real-world clinical data analysis of PARPi as first-line maintenance therapy in newly diagnosed epithelial ovarian cancer patients

Objective: The real-world clinical data of patients with newly diagnosed ovarian cancer (including fallopian tube cancer and primary peritoneal cancer) who received first-line maintenance therapy with poly adenosine diphosphate ribose polymerase inhibitor (PARPi) were retrospectively analyzed, and the prognostic factors were preliminarily explored. Methods: (1) The clinicopathological data and follow-up data of ovarian cancer patients treated with PARPi first-line maintenance therapy from August 2018 (PARPi was launched in China) to December 31, 2021 in Sichuan Cancer Hospital were collected (real-world clinical data). (2) According to the different types of PARPi, real-world clinical data were divided into olaparib group and niraparib group, which were respectively compared with the inclusion and exclusion criteria of representative domestic and foreign phase Ⅲ randomized controlled trials (RCT), including olaparib as first-line maintenance therapy for advanced ovarian cancer patients with BRCA1/2 gene mutation (SOLO-1 study), niraparib as first-line maintenance therapy (PRIMA study), and niraparib as first-line maintenance therapy for Chinese advanced ovarian cancer patients (PRIME study). (3) The prognosis of the two groups and the prognostic factors were analyzed. Results: (1) A total of 83 patients were included in this study, with a median age of 51 years (47-57 years), including 75 cases of ovarian cancer, 5 cases of fallopian tube cancer, and 3 cases of primary peritoneal cancer; 5 cases of stage Ⅰ, 9 cases of stage Ⅱ, 55 cases of stage Ⅲ, 12 cases of stage Ⅳ, and 2 cases of unknown stage; neoadjuvant chemotherapy (NACT) was performed in 40 cases and non-NACT in 43 cases; 62 cases had no visible residual lesion after surgery (R0), 9 cases had residual disease lesions <1 cm (R1), 8 cases had residual disease lesions ≥1 cm (R2), and 4 cases with unknown postoperative residual disease. Thirty-two cases had PARPi treatment interruption, 40 cases had PARPi reduction, and 1 case terminated treatment due to acute leukemia. Of the 83 patients, 35 were in the olaparib group and 48 were in the niraparib group. The proportion of patients with high-grade serous carcinoma (100% and 75%, respectively) and the proportion of BRCA mutant patients (91% and 10%, respectively) in the olaparib group were higher than those in the niraparib group (all P<0.01). (2) Compared with the inclusion and exclusion criteria of the SOLO-1 study, the olaparib group had only 60% (21/35) coincidence rate; compared with the inclusion and exclusion criteria of PRIMA and PRIME studies, the coincidence rates of niraparib group were only 31% (15/48) and 69% (33/48). The most common reasons for non-compliance were number of chemotherapy courses, histopathological type, and surgical pathological stage. (3) Of the 83 cases received first-line maintenance therapy with PARPi, the median follow-up was 15.9 months (11.3-22.9 months), the median progression-free survival (PFS) was 29.7 months (95%CI: 25.9-33.6 months), and the median overall survival was 49.8 months (95%CI: 47.4-52.2 months). Univariate analysis showed that unilateral or bilateral ovarian cancer, efficacy after platinum-containing chemotherapy, presence or absence of measurable lesions at the end of chemotherapy, and total number of chemotherapy courses were significantly associated with PFS (all P<0.05). Multivariate analysis showed that unilateral or bilateral ovarian cancer, total number of chemotherapy courses, and efficacy after platinum-containing chemotherapy were independent factors affecting PFS in stage Ⅱ-Ⅳ patients with PARPi first-line maintenance therapy (all P<0.05). Conclusions: Unilateral ovarian cancer, the total number of chemotherapy courses no more than 9, and achieving complete response after platinum-containing chemotherapy before maintenance therapy are independent influencing factors of PFS benefit in patients with PARPi first-line maintenance therapy. Due to the large differences between the patients in real clinical practice and the research subjects of phase Ⅲ RCT, the results of representative retrospective studies still have important clinical reference significance.