Small Peak Research Articles

In-person, virtual visiting and telephone calls in Australia and New Zealand intensive care units: A point prevalence multicentre study mapping daytime and nighttime interactions

BackgroundFamily presence, in-person and via virtual visiting (video calls) and the telephone, is an integral part of patient- and family-centred critical care. Previous studies focussed on visiting policies and their effects. Data mapping the frequency and timing of these interactions are not available. ObjectivesThe aims of this study were to describe the prevalence of in-person visiting and the use of telephone or video conferencing in Australia and New Zealand intensive care units (ICUs). DesignA point prevalence survey was conducted to map visiting policies, hourly family presence at the bedside, telephone or video calls, and reasons for each interaction. SettingThe research was conducted in a 24-h study period in October 2020, corresponding to the end of the 2nd COVID-19 pandemic wave in 40 Australia and New Zealand ICUs. Measurements and main resultsAt the time of survey, 77% of ICUs had restrictions to visiting, median (interquartile range [IQR]) time of 9 (2; 24) hours with permitted visiting per day, a mean of 8 hours less than before the COVID-19 pandemic. There were 532 patients, a median (IQR) of 13 (6; 25) patients per ICU. Two patients had COVID-19. Over 24 h, 65% of patients had at least one in-person visit, median (IQR) of 1 (0; 3) hours with visitors. Telephone calls were received for 52% patients, median (IQR) of 1 (0; 2) calls. Video calls were received for 6% of the patients. In-person visits peaked between 10:00 and 12:00, with a second smaller peak between 16:00 and 17:00. Visiting continued through the evening, and 2% of the patients had visitors overnight. Telephone calls peaked at 10:00, continued through the day and evening, with few calls received overnight. In-person visits were predominantly motivated by family interactions (81%) and telephone calls by clinical updates (51%) and family interactions (47%). ConclusionsIn a low COVID-19 prevalence period, Australia and New Zealand ICUs had partially reopened to visitors. Most visits happened during the day and evening but persisted overnight. ICU resourcing and visiting policies should take these data into account to facilitate family presence at the bedside, virtual visiting, and obtaining clinical updates via telephone.

Study of Some Structural and Optical Properties for Synthesized Graphene/Polyaniline/Zns Nanocomposite

Hybrid graphene (GR)/ polyaniline (PANI) based composites incorporating zinc sulfide (ZnS) nanoparticles were synthesized using the drop-casting method. The weight percentage of ZnS was varied from 0.01 to 0.05%. The optical, structural, and morphological characteristics of the nanocomposite were examined utilizing X-ray diffraction (XRD), Scanning Electron Microscopy (SEM), Atomic Force Microscopic (AFM), and UV-Vis spectroscopy. The qualities and dimensions of the GR, PANI, and ZnS NPs and nanoparticle morphology resulting from the nanocomposite process were examined. Utilizing energy dispersive energy X-ray dispersive (EDX), the weight percentage of each element can be verified. The widening sharp peaks in the XRD patterns suggested the creation of a nanocrystalline phase of ZnS with a crystallite size of less than 50 nm. SEM demonstrated the interaction between ZnS nanoparticles and graphene/polyaniline. Surface topography examination using AFM shows that ZnS NPs may be effectively dispersed on top of GR/PANI structures. The ultraviolet-visible absorption spectrum (UV-Vis) showed a small absorption peak at the wavelength of 459.34nm and a broad absorption peak at 652nm.

Seasonal variation in suicide: age group and summer effects in the United States (2015–2020)

BackgroundSuicide is a global public health concern that affects more than 700,000 people globally every year. Seasonal variation in suicide rates is a phenomenon that has been well-documented, but recent data on the seasonality of suicide within specific age groups and sex in the United States remains less well understood.MethodsPublicly available data on monthly suicides was obtained from the Underlying Cause of Death database, CDC WONDER, from 2015–2020. The incidence of summer suicides, from June, July and August, for two groups, 15–24 and ages 25 + , was calculated and a two-sided test was performed. Seasonal Decomposition analysis was performed and time series created from 2015–2020 for every age group then converted into Trend, Seasonality, and Residual respectively.ResultsFor Americans ages 15–24, the highest spike in suicides was in autumn, September–October, with a trough in June. This is the only age group in which this occurred, differing from previous understanding of the seasonality of suicide in the literature. With all other age groups (25–34, 35–44, 45–54, 55–64, 65–74, 75 +) there was a consistent pattern of a peak in late spring/early summer, a small peak in fall, and a trough in late winter.ConclusionsThere is a seasonal variation in suicide deaths in the United States with the youngest group, ages 15–24, presenting a different pattern compared to other ages. There were no significant differences in suicide seasonality by sex.

Molecular Oxygen (O2) Artifacts in Tandem Mass Spectra.

Peak annotation plays an important role in mass spectral evaluation of the NIST 2023 tandem mass spectral library. While most fragment ions are formed by neutral losses, there are peaks that represent adduct ions from these fragments. Previously, we have reported two main types of addition reactions in the collision cell, namely addition of H2O and N2. Here we report a different reaction in the collision cell, with addition of O2 leading to a small peak that could only be assigned to a peroxyl radical ion. For example, some protonated iodoaromatics lose an iodine atom to form a radical cation [M+H-I]+•, which reacts with O2 to generate a peroxyl radical ion [M+H-I+O2]+•. Higher concentrations of O2 result in higher peroxyl radical peaks, which become dominant while the precursor ions are consumed, as examined by five compounds under different concentrations of O2. The correlation of the peroxyl radical peak intensities to the concentration of O2 provides a tool to estimate trace amounts of O2 within the instrument. In the NIST 2023 tandem mass spectral library, the peaks for [M+H-X+O2]+· are most abundant in numbers and in intensity for X = NO2 or I, are much less abundant for X = Br, and are rare for X = Cl. Other leaving groups in this library are SO3H, SO2NH2, CSNH2, CO2C6F5, SO2CH3, and COCH3. The O2 addition reaction is also observed with negative ions in this library. While adducts of H2O and N2 often constitute major peaks, the peaks of the peroxyl radicals under standard conditions are mostly very small and may be mistaken for noise, but their correct annotation improves the quality of the spectra and is important when comparing spectra from different instruments or conditions.

PEAKO and peakTree: tools for detecting and interpreting peaks in cloud radar Doppler spectra – capabilities and limitations

Abstract. Cloud radar Doppler spectra are of particular interest for investigating cloud microphysical processes, such as ice formation, riming and ice multiplication. When hydrometeor types within a cloud radar observation volume have different terminal fall velocities, they can produce individual Doppler spectrum peaks. The peaks of different particle types can overlap and be further broadened and blended by turbulence and other dynamical effects. If these (sub-)peaks can be separated, properties of the underlying hydrometeor populations can potentially be estimated, such as their fall velocity, number, size and to some extent their shape. However, this task is complex and dependent on the operation settings of the specific cloud radar, as well as atmospheric dynamics and hydrometeor characteristics. As a consequence, there is a need for adjustable tools that are able to detect peaks in cloud radar Doppler spectra to extract the valuable information contained in them. This paper presents the synergistic use of two algorithms used for analyzing the peaks in Doppler spectra: PEAKO and peakTree. PEAKO is a supervised machine learning tool that can be trained to obtain the optimal parameters for detecting peaks in Doppler spectra for specific cloud radar instrument settings. The learned parameters can then be applied by peakTree, which is used to detect, organize and interpret Doppler spectrum peaks. The application of the improved PEAKO–peakTree toolkit is demonstrated in two case studies. The interpretation is supported by forward-simulated cloud radar Doppler spectra by the Passive and Active Microwave TRAnsfer tool (PAMTRA), which are also used to explore the limitations of the algorithm toolkit posed by turbulence and the number of spectral averages chosen in the radar settings. From the PAMTRA simulations, we can conclude that a minimum number of n = 20–40 spectral averages is desirable for Doppler spectrum peak discrimination. Furthermore, small liquid peaks can only be reliably separated for eddy dissipation rate values up to approximately 0.0002 m2 s−3 in the simulation setup which we tested here. The first case study demonstrates that the methods work for different radar systems and settings by comparing the results for two cloud radar systems which were operated simultaneously at a site in Punta Arenas, Chile. Detected peaks which can be attributed to liquid droplets agree well between the two systems, as well as with an independent liquid-predicting neural network. The second case study compares PEAKO–peakTree-detected cloud radar Doppler spectrum peaks to in situ observations collected by a balloon-based holographic imager during a campaign in Ny-Ålesund, Svalbard. This case demonstrates the algorithm toolkit's ability to identify different hydrometeor types but also reveals its limitations posed by strong turbulence and a low n. Despite these challenges, the algorithm toolkit offers a powerful means of extracting comprehensive information from cloud radar observations. In the future, we envision PEAKO–peakTree applications on the one hand for interpreting cloud microphysics in case studies. The identification of liquid cloud peaks emerges as a valuable asset, e.g., in studies on cloud radiative effects, in seeder–feeder processes, or for tracing vertical air motions. Furthermore, the computation of the moments for each subpeak enables the tracking of hydrometeor populations and the observation of growth processes along fallstreaks. On the other hand, PEAKO–peakTree applications could be extended to statistical evaluations of longer data sets. Both algorithms are openly available on GitHub, offering accessibility for the scientific community.

Pattern formation from homogeneous states for an elliptic system with mixed interactions

In this paper, we are interested in the asymptotic behavior of a ground state vector solution for the following coupled nonlinear Schrödinger system { Δ u 1 − λ 1 u 1 + β 11 ( u 1 ) 3 + α β 12 u 1 ( u 2 ) 2 − β β 13 u 1 ( u 3 ) 2 = 0 Δ u 2 − λ 2 u 2 + α β 21 ( u 1 ) 2 u 2 + β 22 ( u 2 ) 3 − β β 23 u 2 ( u 3 ) 2 = 0 Δ u 3 − λ 3 u 3 − β β 31 ( u 1 ) 2 u 3 − β β 32 ( u 2 ) 2 u 3 + β 33 ( u 3 ) 3 = 0 in Ω and ∂ u i ∂ n = 0 on ∂Ω when α , β > 0 are very large. The existence of a ground state vector solution for (1) was proved in Byeon et al. [Pattern formation via mixed interactions for coupled Schrödinger equations under Neumann boundary condition. J Fixed Point Theory Appl. 2017;19:559–583] when α , β , α / β 2 − n 2 are large. We prove that if λ 3 is small, as α , β , α / β 2 − n 2 → ∞ , u 3 converges to a constant, u 1 and u 2 develop a small peak on ∂Ω . Under an additional condition α / β 2 − n 2 + δ → ∞ for some δ > 1 , we show that the peak point converges to a maximum point of the mean curvature of ∂Ω .

Impact of Al3+ substitution on structural, Raman, transport electromagnetic properties of LiFe2O4 nanoparticles

Nanocrystalline Li0.5AlxFe2.5-xO4(x = 0.0 to 0.8 in steps, x = 0.2) compounds were prepared using the sol-gel auto-combustion technique. X-ray diffraction (XRD) analysis confirmed the single-phase cubic spinel structure, which showed that the lattice constant changed significantly, especially in the x = 0.6 sample, where it decreased clearly. The crystallite size decreased with increasing Aluminium content, reaching a small value of about 5 nm for the composition x = 0.8 sample. Raman peaks of pure LiFe2O4 were determined in both phases (alpha and beta), while smaller peaks at 198 and 236 cm−1 that related to the alpha phase were distinguished. All peaks diminished in intensity after Al3+ ions were doped to LiFe2O4 except for the peak at 700, where it became predominantly. The bandgap of the samples was deduced and analyzed from Tauc's plot according to UV–Vis spectra. The change in the electronic structure of the Li-Al ferrites, at which the size of the ferrite becomes close to the de Broglie wavelength, results in a band gap for the Al replaced by LiFe2O4 with different electronic configurations. The variation of the fundamental part of the dielectric constant (ε′), loss tangent (tan δ), and AC conductivity with frequency has been discussed with composition. The increase in Al3+ ion content affected the coercive force, as it decreased, while the saturation magnetism increased when adding Aluminium (x = 0.2) and then began to decline gradually.

Green Synthesis, Characterization and Pharmaceutical Applications of Biocompatible Zinc Oxide Nanoparticles Using Heliotropium rariflorum Stocks.

Background: Zinc oxide nanoparticles are safe, non-toxic, and biocompatible. These NPs are used in food packaging materials, self-cleaning glass, ceramics, deodorants, sunscreens, paints, coatings, ointments, lotions, and as preservatives. This study explored the biological potential of ZnO nanoparticles synthesized using H. rariflorum. Methods: In vitro antibacterial and antifungal activities against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, Candida albicans, Penicillium notatum, Aspergillus flavus, Aspergillus niger and Aspergillus solani were determined. Antioxidant activity was explored using the DPPH radical scavenging method. In vivo analgesic, antipyretic and sedative potential of synthesized nanoparticles was investigated using a mouse model. Results: SEM with various magnification powers showed that some particles were spherical while some were aggregated, flake-shaped, and hexagonal with rough and irregular surfaces. The EDX analysis revealed Zn (12.63%), O (22.83%) and C (63.11%) with trace quantities of Si (0.40%), Ca (0.54%) and P (0.49%). The XRD pattern indicated an amorphous state, with no peaks observed throughout the spectrum. The UV-visible spectrophotometry revealed a characteristic absorption peak at 375 nm, indicating the presence of ZnO nanoparticles. Fourier Transform Infrared Spectroscopy (FTIR) displayed several small peaks between 1793 and 2370 cm-1, providing evidence of the presence of different kinds of organic compounds with different functional groups. ZnO-NPs showed dose-dependent antibacterial and antifungal potential against all strains. Staphylococcus aureus and Candida albicans were the most susceptible strains. The nanoparticles exhibited a maximum antioxidant effect of 85.28% at 100 μg/mL. In this study, the acute toxicity test showed no mortality, and normal behavior was observed in mice at ZnO-NP doses of 5, 10, and 20 mg/kg. For analgesic and antipyretic activities, a two-way ANOVA revealed that dose, time, and the interaction between dose and time were significant. In contrast, the samples had a non-significant effect on sedative activity. Conclusions: This innovative study suggests a potential use of plant resources for managing microbes and treating various diseases, providing a scientific basis for the traditional use of H. rariflorum.

Reproductive biology of fringescale sardinella (Sardinella fimbriata Valenciennes, 1847) from Malampaya Sound, Palawan, Philippines

Reproduction is a fundamental biological process that is essential for the continuous survival of fish species. Understanding their early life history and reproductive biology can explain how the population behave over time. A total of 1,238 fish samples were examined to determine the reproductive patterns and period of fringescale sardinella (Sardinella fimbriata) from Malampaya Sound, Palawan, Philippines. Monthly sampling from April 2023 to March 2024 revealed a 1:1 sex ratio. Gonadal examination of the fish revealed the presence of spawning individuals throughout the study period. The minimum size of matured fish observed was 11.0 cm and 11.1 cm for male and female S. fimbriata, respectively. The peak of spawning was April as indicated by the highest calculated GSI of 7.62% and fecundity of 18,465. A smaller peak was again observed in the month of September. The length at maturity was estimated to be 11.4 and 8.8 cm for males and females, respectively. Fecundity ranged between 2,700 to 36,067 eggs per spawn for size class between 11.1-14.8 cm and weight 13.07-31.93 g. Regression analysis between fecundity and morphometric characteristics such as body length, weight, eviscerated weight, and gonad weight revealed a positive correlation. Very low coefficients of determination were computed, ranging between 0.0028-0.1233. A significant association between fecundity and the morphometric variable gonadal weight was observed, as shown by the p-value of 0.0000. These outcomes are valuable data in the formulation of conservation and management strategies for the area. Implementation of appropriate conservation measures, monitoring of environmental parameters, strict enforcement of fishery regulation, coupled with increased environmental awareness and community participation will guarantee the long-term sustainability of the fringescale sardinella population and the preservation and sustainable use of marine biodiversity in Malampaya Sound.

Case Report: Hemoglobin Hasharon with Concurrent Alpha Thalassemia in a Patient with Maple Syrup Urine Disease

Abstract Hemoglobin Hasharon (Hb Hasharon) is an unstable hemoglobin variant stemming from a mutation in the alpha globin gene. This mutation involves the replacement of aspartic acid with histidine at position 47 of the alpha globin chain. Initially identified in 1967 in Israel, Hb Hasharon has since been sporadically reported in various populations, including in Italy, Greece, Germany, and among Latin Americans of Mediterranean descent. Only three English articles have reported several cases of the combined alpha thalassemia deletion and Hasharon mutation, all between 1978-1980. Notably, there has been no prior report of Hb Hasharon with concurrent alpha thalassemia in patients with maple syrup urine disease (MSUD). We hereby present the first case of Hb Hasharon with alpha thalassemia in a patient diagnosed with MSUD. This patient, a 16-month-old female, received a prenatal diagnosis of MSUD through amniocentesis, confirming homozygosity for a known pathogenic variant in DBT (c.75_76delAT, p.C26wfsX2). Prompt initiation of formula feeding has effectively controlled her MSUD. The patient was referred for further evaluation due to hemoglobin newborn screen showing hemoglobin A, Hb F and “variant hemoglobin”. Her parents denied any family history of hemoglobinopathy. Her complete blood count was predominantly normal except for mild microcytosis, with a mean corpuscular volume of 69.1 fl (normal range 70.0-86.0 fl). The patient didn’t exhibit neonatal jaundice or any other signs or symptoms of hemolysis. The reticulocyte count was also within normal limits. The hemoglobin electrophoresis results revealed a complex pattern, with 28.8% of an unknown hemoglobin between zone 4 and 5 on capillary zone electrophoresis (CZE) as well as a possible A2 variant in zone 1. High-performance liquid chromatography (HPLC) indicated a 29.1% peak at a retention time of 4.72 minutes, along with several smaller peaks, that were indicative of the degradation of the unstable unknown hemoglobin. Although the zones and retention time aligned with Hb Hasharon, the percentage differed from the expected range of 19-20% in CZE and 18-21% in HPLC for this variant, prompting the team to order alpha and beta globin sequencing tests. Beta globin gene complete sequencing yielded negative results, while the sequencing of alpha globin gene revealed that the patient carries one copy of the -alpha3.7 alpha-globin deletion and one copy of the c.142G>C (p.Asp48His) variant in the alpha2-globin (HBA2) gene, resulting in an -alpha/alpha2alpha1 genotype with Hb Hasharon. While Hb Hasharon is generally not clinically significant, its co-occurrence with alpha-thalassemia can lead to hemolytic anemia. In our patient, clinic and chemical parameters were predominantly within normal ranges, except for mild microcytosis. The potential interaction between MSUD and Hb Hasharon with concurrent alpha thalassemia remains unknown. Continued patient monitoring will enable us to evaluate whether these conditions may influence each other’s clinical and biochemical profiles.

Low-cost fabrication methods of ZnO nanorods and their physical and photoelectrochemical properties for optoelectronic applications

Zinc Oxide (ZnO) nanorods have great potential in several applications including gas sensors, light-emitting diodes, and solar cells because of their unique properties. Here, three low cost and ecofriendly techniques were used to produce ZnO nanorods on FTO substrates: hydrothermal, chemical bath deposition (CBD), and electrochemical deposition (ECD). This study explores the impact of such methods on the optical, structural, electrical, morphological, and photoelectrochemical properties of nanorods using various measurements. XRD analysis confirmed the hexagonal wurtzite structure of ZnO nanorods in all three methods, with hydrothermal showing a preferred orientation (002) and CBD and ECD samples showing multiple growth directions, with average particle sizes of 31 nm, 34 nm, and 33 nm, respectively. Raman spectra revealed hexagonal Wurtzite structure of ZnO, with hydrothermal method exhibiting higher E2 (high) peak at 438 cm−1 than CBD and ECD methods. SEM results revealed hexagonal ZnO nanorods became more regular and thicker for the hydrothermal method, while CBD and ECD led to less uniform with voids. UV-vis spectra showed absorption lines between 390 nm and 360 nm. Optical bandgap energies were calculated as 3.32 eV, 3.22 eV, and 3.23 eV for hydrothermal, CBD, and ECD samples, respectively. PL spectra revealed UV emission band with a small intensity peak around 389 nm and visible emission peaks at 580 nm. Temperature dependent PL measurements for ZnO nanorods indicated that the intensities ratio between bound exciton and free exciton decreases with temperature increases for the three methods. Photocurrent measurements revealed ZnO nanorod films as n-type semiconductors, with photocurrent values of 2.25 µA, 0.28 µA, and 0.3 µA for hydrothermal, CBD, and ECD samples, and photosensitivity values of 8.01, 2.79, and 3.56 respectively. Our results suggest that the hydrothermal method is the most effective approach for fabricating high-quality ZnO nanorods for optoelectronic applications.

Study on the effects of ultrasonic vibration-assisted wire-EDM machining parameters on material removal rate and surface roughness of NiTiV shape memory alloy

Nickel-titanium (NiTi)-based shape memory alloys (SMAs) exhibit remarkable properties, making them increasingly demanding in various engineering and medical applications especially when these SMAs are manufactured with intricate shapes and sizes. This present study examines the machining of Ni50Ti48V2 SMA using ultrasonic-assisted WEDM with input parameters of pulse ON time (TON), pulse OFF time (TOFF), peek current (I), and servo voltage (SV) along with 20 kHz constant ultrasonic vibration on the responses of material removal rate (MRR) and surface roughness (Ra). RSM-BBD response surface methodology was used to conduct the experiments. It was inferred from analysis of variance (ANOVA) analysis, that as the peak current (I) and pulse ON time (TON) increased, the MRR increased by 65.76% and Ra decreased by 54.44%. The confirmation was carried out in USV-WEDM under optimal conditions, which shows that both the predicted and actual MRR and Ra are close to each other. When compared with conventional WEDM, the USV-WEDM shows significant improvement in MRR by 8.6% and also improved surface quality by 6.3%. The surface characteristics of Ni50Ti48V2 after machining were examined using field-emitted scanning electron microscopy, showing small irreularisation peaks and wavy surface topography at optimised parameter conditions. USV-WEDM showed a lower-order micro-hardness variation due to effective flushing of molten layer re-accumulation as compared to WEDM. When comparing the base and machined samples, the temperatures of austenite and martensite are nearly the same, indicating that shape memory effects are unaffected by the USV-WEDM process.

Monitoring spirooxazine–merocyanine photoisomerization with ion-current rectifying quartz nanopipettes

The characterization and discrimination of chemical compounds is imperative in both academia and industry, but currently relies on expensive and/or bulky instrumentation. Herein, we demonstrate that the ion transport properties of bare quartz nanopipettes containing aprotic acetonitrile electrolyte can be used discriminate isomers based on polarization and solvation, through changes to interfacial solvent ordering at the nanopore wall. This is demonstrated by monitoring the photoinduced isomerization of spirooxazine to merocyanine using the ion-current rectification of a quartz-nanopipette containing acetonitrile electrolyte, which results in an increase in rectification ratio (RR) from 3.6 ± 0.3 to 5.1 ± 0.2. This change is comparable to traditional UV–Vis absorbance and fluorescence measurements of the same process, with the appearance of a small shoulder-like absorbance peak from 400 to 500 nm, and a strong fluorescence signal at 430 nm.

Quantitative Assessment of Conformational Heterogeneity in Apolipoprotein E4 Using Hydrogen-Deuterium Exchange Mass Spectrometry.

Apolipoprotein E4 (apoE4) is the strongest genetic risk factor for Alzheimer's disease (AD). However, structural differences between apoE4 and the AD-neutral isoform, apoE3, still remain unclear. Recent studies suggest that apoE4 harbors intermediates. However, the biophysical properties and isoform specificity of these intermediates are not known. Here, we use the kinetics of hydrogen-deuterium exchange by mass spectrometry (HDX-MS) to examine the conformational heterogeneities in apoE3 and apoE4. First, we use numerical simulations to compute the HDX-mass spectra of a protein following mixed EX1/EX2 kinetics. The results indicate that in the presence of EX1 kinetics, which is an indicator of conformational heterogeneity, time evolution of the standard deviation (σ(t)) of the spectra exhibits a clear peak, which is dependent on the number of residues (NEX1) and the rate constant of EX1 kinetics (kEX1). Then, we performed experiments with several variants of the apoE proteins and compared them with simulation to estimate NEX1 and kEX1. Kinetics of the mean deuteration is found to be faster for apoE4, consistent with its poorer stability than apoE3. Importantly, in the case of apoE4, σ(t) exhibits a clear peak at t ∼ 60 s, but apoE3 shows only a small peak at 1800 s. Therefore, both NEX1 and kEX1 are larger for apoE4, indicating greater conformational heterogeneity. Notably, the partial EX1 kinetics is observed in both the isolated N-terminal fragment and the full-length form of apoE4, although it is more pronounced in the full-length protein. Moreover, it is enhanced at higher pH and in the presence of bis-ANS. Mutations such as R61T and R112I diminish the EX1 kinetics, making apoE4 behave more like apoE3. Thus, the amino acid substitution at position 112 alters the structural dynamics of the N-terminal domain of apoE4; the changes are further propagated and amplified in the full-length protein. We conclude that HDX-MS is a label-free and robust methodology to characterize structural heterogeneities of proteins even under native conditions. This opens opportunities for screening of the "structure corrector" drug molecules that could convert apoE4 to apoE3-like.

B-206 Tick-borne disease molecular testing positivity and coinfection incidence in the northeastern united states: 2021-2023

Abstract Background The CDC estimates that Lyme disease affects hundreds of thousands of people each year in the United States. Tick-borne diseases caused by pathogens such as Anaplasma phagocytophilum, Babesia microti, Ehrlichia chaffeensis, and species of Borrelia follow a seasonal pattern due to the life cycle of disease-carrying ticks. In endemic areas, like the northeastern United States, the risk of coinfection by multiple tick-borne disease pathogens is higher and can complicate patient treatment. For example, while Anaplasma and Borrelia can be treated with doxycycline a Babesia coinfection would not be resolved with this medication. In this study, we performed a retrospective analysis of tick-borne disease molecular testing results to monitor positivity rates and incidence of coinfection. Methods This retrospective analysis included whole blood specimens submitted to a regional clinical laboratory in the northeastern United States for tick-borne disease molecular testing. Test results from 2021-2023 were analyzed for positivity rate trends and coinfection incidence. DNA was isolated from patient specimens and tested using laboratory developed real-time Taq polymerase PCR assays. Results Positivity rates for all tick-borne disease pathogens studied followed typical seasonal patterns (Table). Beginning in the early spring, as nymphs ended their dormancy and began to feed, infection rates of tick-borne disease climbed. Infections peaked in mid-summer and remained elevated through late autumn. For Anaplasma, a biphasic pattern was observed, with a smaller peak in late autumn when adult ticks are most active. Coinfections with Anaplasma and Babesia were observed in 136 specimens, while coinfections with Borrelia and Babesia were observed in 145 specimens. Conclusions Positivity rates for tick-borne disease pathogens followed expected seasonal patterns in the northeastern US. The incidence of coinfections involving Babesia microti highlights the importance of properly identifying tick-borne infections given the different treatment regimens indicated.

Hexagonal Enhanced Porous GaN with Delayed Integrated Pulse Electrochemical (iPEC) Etching

This present study investigates the effect of time delay (Td) on the formation of porous GaN (P-GaN) using integrated pulse electrochemical (iPEC) etching. Porous GaN (P-GaN) was formed by etching an N-type GaN wafer with a 4% KOH electrolyte for 60 minutes under an ultraviolet (UV) lamp at a current density of 80 mA/cm2. A Td of 120 minutes was applied before electrochemically etching the P-GaN sample. The top view image of the field emission scanning electron microscopy (FESEM) revealed a significant difference when a Td was applied. A dense and uniform hexagonal P-GaN was obtained from the Td iPEC sample, while the non-Td sample exhibited a multi-layered hexagonal porous structure with unfinished pore-etched areas. Higher porosity and deeper pores were observed in the Td sample. Intense high-resolution X-ray diffraction (HR-XRD) peak intensity was observed in the Td iPEC sample with a lower full width half maximum (FWHM), indicating that the sample had better crystallinity. The Raman spectra of the sample anodized with a Td exhibited higher Raman peak intensity and a slight shift to a higher frequency concerning as-grown GaN, indicating better crystallinity and a tensile stress relaxation of 0.24 GPa. Post etching, a blue shift of the photoluminescence (PL) peak, from 364 nm (as-grown GaN) to 363 nm (P-GaN), was observed, and a small PL peak started to form around 385 nm compared to the as-grown GaN due to the relaxation of the tensile stress, which modified the bandgap. The PL peak intensity of the Td sample was higher than the non-Td sample, indicating that the porosity and uniformity allowed more light interaction with the material, resulting in more efficient photon absorption and emission. The results indicated that potentially efficient optoelectronics devices can be fabricated on a P-GaN using a combination of electroless and electrochemical etching of the GaN epitaxial layer.

Time toxicity faced by patients with advanced cancer across primary cancer sites.

268 Background: Time toxicity, defined as the burden of time for patients interacting with the health care systems, is particularly important for patients with limited life expectancy. Little is known about the relative impact of time toxicity among different cancer types at the end of life. This study examines median contact days for inpatient, outpatient, and home health services among different primary cancer types for patients with advanced cancer with limited prognosis. Methods: A retrospective cohort analysis was performed on patients with advanced (stage 4) cancer who died within one year of diagnosis at Kaiser Permanente Northern California between January 1, 2015, and June 30, 2023. Time toxicity was defined as comprehensive contact days with healthcare system over the course of patients’ survival period between cancer diagnosis and death (i.e., contact days divided by survival or contact %). Types of contact included institutional stay (emergency department visit, hospitalization, skilled nursing facility, rehabilitation); outpatient visits (ambulatory care, labs, imaging); and in-home care (home-health, home hospice, telephone and virtual visit). The study quantified overall median contact % and contact % by specific care settings, stratified by cancer primary site. Results: The study included 10102 patients. The median age at diagnosis was 74 years with 47% female. Patients were predominantly white (65%), followed by Asian (12%), Hispanic (12%), and black (8%). The median Elixhauser comorbidity score was 4. With the exception of head and neck cancers, most cancers had higher contact % near diagnosis and at end of life (U-shaped curve). Head and neck cancers had the highest percent of patients undergoing surgery (36%) and radiation (52%), which may explain its sinuosity-like curve with a rapid increase of weekly contact % after diagnosis (a small peak), followed by rapid decrease and another increase by the end of their life. Survival days were comparatively long for head and neck cancers (158 days, IQR: 84-265) and short for thoracic (80 days, IQR: 35-166) and upper gastrointestinal cancers (80 days, IQR: 38-173). Malignant hematology patients had notably higher comprehensive contact % (74%, IQR: 47-100) which was driven primarily by emergency room department visits and hospital stays (p<0.001 for all contact types). Conclusions: The study highlights the high burden of time toxicity in patients with advanced cancer with limited prognosis. The significant variations in time toxicity among different cancer types, especially in malignant hematology and head and neck patients, emphasize the need to tailor goals of care discussions for patients with cancer at the end of life. By focusing on reducing unwanted time toxicity, healthcare providers can enhance the quality of life for patients with cancer, ensuring more efficient and patient-centered care delivery.

Evaluating the efficacy of uniformly designed square mesh resin 3D printed scaffolds in directing the orientation of electrospun PCL nanofibers

Replicating the architecture of extracellular matrices (ECM) is crucial in tissue engineering to support tissues’ natural structure and functionality. The ECM’s structure plays a significant role in directing cell alignment. Electrospinning is an effective technique for fabricating nanofibrous substrates that mimic the architecture of extracellular matrices (ECM). This study aims to evaluate the efficacy of resin 3D-printed scaffolds made from a low-conductivity material (i.e., a resin composed of methacrylated oligomers, monomers, and photoinitiators) in directing the alignment of electrospun polycaprolactone (PCL) nanofibers. Six 3D-printed scaffolds were fabricated using stereolithography (SLA) technology and strategically positioned on an aluminum foil collector plate during electrospinning. The structured geometry of the scaffolds, rather than the local electric field distribution, is hypothesized to guide nanofiber alignment. Images acquired through the scanning electron microscopy (SEM) were used to analyze and statistically quantify the nanofibrous scaffolds to evaluate the alignment of nanofibers over the scaffolds compared to a set of randomly deposited control nanofiber samples in the absence of the 3D printed scaffolds. SEM images also showed significant alignment of nanofibers within the pores of scaffolds, using histograms as a means for indicating the distribution of orientation angles. Statistical analysis revealed that this distribution deviates from normality due to the deviations in the tails and the existence of relatively smaller peaks at angles relative to 0°, particularly within a range of ± 50° and ± 40°. It is further found that the average peak orientation angle relative to 0° had a maximum probability of 0.014. Furthermore, the statistical analysis confirmed the distribution and significant differences in orientation between test samples with 3D-printed scaffolds and control samples. These findings demonstrate the effectiveness of resin 3D-printed scaffolds, particularly their geometric filtering effect, leading to controlled nanofiber alignment, which is proposed to be beneficial for enhancing cell adhesion, proliferation, and cell migration in tissue engineering applications.

Fourteen-year follow-up results of imatinib therapy in patients with unresectable and metastatic gastrointestinal stromal tumors.

Imatinib therapy is the gold standard for the treatment of unresectable and metastatic gastrointestinal stromal tumors (GISTs). However, few studies have reported the long-term outcomes of the treatment. Seventy patients who underwent imatinib therapy for unresectable and metastatic GISTs were enrolled between 2001 and 2009, and follow-up data were collected until October 2023. One hundred and sixty-eight months had passed since the final enrollment. The outcome measures were patient survival and the status of GIST and imatinib therapy. The cumulative incidence of disease progression (PD) and the chronological changes in PD hazard rate (HR) were also analyzed. The 5-, 10-, 15-, and 20-year overall survival rates were 64.3%, 30.0%, 16.8%, and 12.2%, respectively. Sixty of the 70 enrolled patients died before the data cutoff date: 47 (78.3%) patients died of GIST progression while the remaining 13 (21.7%) died of diseases other than GISTs. The cumulative incidence of PD logarithmically increased, and PD continued even after 10years of treatment. PD HR decreased over time to reach the lowest value at 9.6years after the initiation of treatment (HR 0.00027; 95% CI 0.00007-0.00174) and after that formed a small peak at 13years (HR 0.00144; 95% CI 0.00043-0.00436). Imatinib therapy showed high clinical efficacy in terms of long-term survival in GIST patients. However, patients undergoing imatinib therapy were at continuous risk of PD even after the 10-year treatment. Long-term treatment and follow-up beyond 10years are necessary for unresectable and metastatic GIST patients.

Insulating behaviour in room temperature rhombohedral LiNiO2 cathodes is driven by dynamic correlation

Abstract Inspired by the experimental finding of a paramagnetic insulating state in rhombohedral LiNiO2, a lithium-ion battery cathode of great interest, we calculate the electronic, magnetic, and optical properties of LiNiO2 employing a range of single-particle and many-body methods. Within density-functional theory (DFT) using the generalized-gradient approximation (GGA), meta-GGA, and hybrid functionals, we obtain a ferromagnetic half-metallic ground state for rhombohedral LiNiO2, as has been seen previously. Self-consistent GW calculations including self-interaction corrections beyond DFT for various flavours show an electronic band gap albeit with a small quasiparticle peak at the Fermi energy. Moving beyond this, room temperature state-of-the-art dynamical mean-field theory (DMFT) calculations on rhombohedral LiNiO2 show for the first time a gap of combined Mott and charge-transfer character. The paramagnetic insulating state has a band gap of ~0.6 eV, in excellent agreement with experiments and is in sharp contrast to DFT calculations that require the presence of an extra structural symmetry breaking in the form of Jahn–Teller distortions to open a gap. We observe Ni to be in a +2 state in a d 8L configuration, with a charge-transfer ligand hole in O p, and identify the ligand hole state from the DMFT DOS. We further show that whereas DFT shows the presence of an unphysical metallic Drude peak in the optical absorption spectra, DMFT calculations capture the correct form of the optical absorption spectra, and have an excellent match with the calculated band gap as well. Our results clarify that at room temperature, it is the charge transfer gap with a Mott character that causes rhombohedral LiNiO2’s insulating nature; a structural distortion is not required.