Why are Young Adults Using E-cigarettes? A Survey of Vermont Undergraduate Students

While rates of conventional cigarette smoking having steadily decreased over the past several decades, more and more individuals are beginning to use alternative nicotine products such as e-cigarettes. Chief among these users are young adults, who use the devices at rates higher than any other population. While e-cigarettes have demonstrated the potential to act as tools to aid in the process of conventional cigarette cessation among adult smokers, young adults do not often indicate cessation to be a motivation driving their e-cigarette use. In addition, research has demonstrated that among younger users, e-cigarettes have the potential to lead to future conventional cigarette use. As such, it is important to better understand the motivations underlying e-cigarette use that young adults do identify with. Previous research has indicated the relative importance of both affective and social motivations for use. The current study included these categories as well as categories based on analytical and biological motivations in order to assess participants on a wide range of possible motivations. Consistent with previous research, the results of the current study indicated the importance of affective motivations in driving e-cigarette use. However, participants did not demonstrate the same level of agreement with the social, analytical, and biological motivations. Interventions aimed at reducing the rates of e-cigarette use among young adults would therefore likely benefit from targeting these affective motivations underlying use

Investigating a domain adaptation approach for integrating different measurement instruments in a longitudinal clinical registry

In a longitudinal clinical registry, different measurement instruments might have been used for assessing individuals at different time points. To combine them, we investigate deep learning techniques for obtaining a joint latent representation, to which the items of different measurement instruments are mapped. This corresponds to domain adaptation, an established concept in computer science for image data. Using the proposed approach as an example, we evaluate the potential of domain adaptation in a longitudinal cohort setting with a rather small number of time points, motivated by an application with different motor function measurement instruments in a registry of spinal muscular atrophy (SMA) patients. There, we model trajectories in the latent representation by ordinary differential equations (ODEs), where person-specific ODE parameters are inferred from baseline characteristics. The goodness of fit and complexity of the ODE solutions then allows to judge the measurement instrument mappings. We subsequently explore how alignment can be improved by incorporating corresponding penalty terms into model fitting. To systematically investigate the effect of differences between measurement instruments, we consider several scenarios based on modified SMA data, including scenarios where a mapping should be feasible in principle and scenarios where no perfect mapping is available. While misalignment increases in more complex scenarios, some structure is still recovered, even if the availability of measurement instruments depends on patient state. A reasonable mapping is feasible also in the more complex real SMA dataset. These results indicate that domain adaptation might be more generally useful in statistical modeling for longitudinal registry data.Comment: 18 pages, 4 figure

Redox cycling of straw-amended soil simultaneously increases iron oxide crystallinity and the content of highly disordered organo-iron(III) solids

Iron speciation in soils is influenced largely by its redox state, but the extent of and controls on Fe speciation during recurrent reduction and oxidation events are not fully understood. To investigate the effects of organic matter (OM) inputs and the frequency and duration of redox oscillations on soil Fe speciation, we conducted redox-oscillation experiments with topsoil from a Fluvisol mixed with rice straw (0, 10, 50 g/kg organic carbon, OC). The soil was initially dominated by short-range ordered (SRO) Fe(III) solids and subjected to 14- and 28-day reduction–oxidation cycles for 112 days, with the time spent under anoxic and oxic conditions maintained at 6:1. Reduction was initiated by flooding reactors with artificial river water. To simulate leaching conditions, soil re-oxidation was achieved by air-drying soil after removal of reacted solutions. Fresh river water was then added for each new redox cycle. We monitored changes in solution composition (Eh, pH, Fe(II), total Fe, OC, and Si) and assessed changes of solid-phase Fe speciation by selective extractions, X-ray absorption spectroscopy, and 57Fe Mössbauer spectroscopy. Dissolved OC and Fe increased with increasing straw addition, but decreased in each treatment through consecutive reduction intervals. Release rates of dissolved Fe and OC were highly correlated, implying that microbial reduction of soil Fe(III) solids was fostered by straw amendments. Reduction-induced losses of OC and Fe from straw amended soil were amplified at high redox frequency. Ferrous Fe did not detectably accumulate in the solid phase upon repeated soil oxidation. Although Fe(III)-poor phyllosilicates gained in relative importance in redox-cycled soils, their fraction was hardly affected during redox cycling. Instead, straw additions led to an enhanced depletion of ferrihydrite during soil redox cycling and a relative enrichment of highly disordered Fe(III) species [‘very SRO (vSRO) Fe(III) solids’], which remained only partially ordered in 5-K Mössbauer spectra and likely consisted predominantly of polynuclear organic Fe complexes. The depletion of ferrihydrite in straw-amended soils after 112 days was greater in the 14-day cycle than in the 28-day cycle experiment and accompanied by a less pronounced enrichment of vSRO Fe(III) solids. The crystallinity of distinct Fe oxides (ferrihydrite, lepidocrocite, and hematite) increased during soil redox cycling especially in straw-amended soils, but without noticeable ferrihydrite conversion into crystalline Fe oxides. The increase in the crystallinity of distinct Fe oxides after 112 days was greater at low redox frequency in straw-free soil, however this frequency effect was suppressed by straw additions. Longer soil redox cycling (112 vs. 56 days) increased the crystallinity of distinct Fe oxides, which was most pronounced at high straw levels and low redox frequency. Our results imply that redox changes in SRO Fe oxide- and OM-rich soils can cause a relative enrichment of more crystalline Fe oxides, while still maintaining a pool of vSRO Fe(III) solids. We conclude that soil redox oscillations can lead to divergent transformation pathways of Fe oxides, which concomitantly increase bulk Fe-oxide crystallinity and generate increasing fractions of highly disordered Fe(III) solids on comparatively short time scales. In addition, our study suggests that faster redox cycling in soils with ample electron donor supply and water leaching leads to higher element exports (e.g., OC, metal(loid)s) from soil due to weekly redox pulsing than more slowly alternating redox conditions

Tailoring Soft Local Zones in Quenched Blanks of the Steel 22MnB5 by Partial Pre-cooling with Compressed Air

The high-strength boron steel 22MnB5 steel is widely used for automotive lightweight constructions. A novel approach is promising to tailor strength and ductility in the hardened condition using locally pre-tempered sheets for the hot stamping process. It results in the formation of locally soft spots where mechanical joining is subsequently intended. A slow pre-cooling of the later joining zones with cooling rates below a certain critical cooling rate for obtaining a decreased strength in these regions is required. A tubular air cooling system suited for this task is presented and tested in a process where the subsequent quenching of the overall sheet is realized by rapid cooling in a water bath. Varying the air pressure and cooling duration allows controlling the size of the softened local spot in a wide range and still obtaining a bainitic microstructure. Using two-stage cooling with point jet nozzles and a subsequent hot stamping process with water-cooled dies resulted in a main sheet hardness of about 470 HV5 and of 260 HV5 in the pre-cooled spots, respectively

Combined deep drawing and fusion bonding of structural FRP-metal hybrid parts

This research describes the development of a combined process of forming and thermal joining without adhesives of high strength steels and organosheets. In order to achieve cycle times below 20 s the temperature of the forming tool remains constant at 110 °C throughout the process. Thus, the removal of the component can take place immediately after the forming process without cooling of the forming tool. The thermal energy required to assure the thermal joining process at 280 °C at the beginning of the intermediate forming step is applied by means of heating the steel in a furnace before the transfer to the forming tool. By choosing certain coating depended heat treatment parameters during the heating step, galvannealed rough surfaces of the steel blanks can be generated in order to increase the joint strength. The paper includes a surface analysis and lap-shear testing results to quantify the respective joint strength to be achieved with the proposed surface treatment. In addition tensile test results of the heated DP800 steel to characterize the thermal influence on the mechanical properties of the heated high-strength steels will be shown. Furthermore the paper presents a tool concept with a graded blank holder to perform stretching of the metal on the one hand and draping of the organosheet on the other hand as well as preliminary forming results

Structure-Guided Redesign Improves NFL HIV Env Trimer Integrity and Identifies an Inter-Protomer Disulfide Permitting Post-Expression Cleavage

Soluble HIV-1 envelope glycoprotein (Env) trimers are under active investigation as vaccine candidates in relevant pre-clinical models. Like SOSIPs, the cleavage-independent native flexibly linked (NFL) trimers are faithful mimics of the Env spike. Here, we analyzed multiple new designs to explore alternative modifications, informing tertiary interactions, while maintaining NFL trimer homogeneity and integrity. Accordingly, we performed a proline (P) substitution screen in the gp41 heptad repeat 1 region, identifying other trimer-enhancing Ps, including L555P. This P improved trimer integrity compared to I559P in selected properties. Next, we screened 15 structure-guided potential cysteine pairs in gp140 and found that A501C-L663C (“CC2”) forms an inter-protomer disulfide bond that demonstrably increased NFL trimer thermostability. We combined these two approaches with trimer-derived substitutions, coupled with glycine substitutions at helix-to-coil transitions, developed by our group. To increase the exposure of the fusion peptide (FP) N-terminus, we engineered an enterokinase (EK) cleavage site upstream of the FP for controlled post-expression cleavage. In combination, the redesigns resulted in highly stable and homogeneous NFL mimics derived from different clades. Following recombinant EK cleavage, the NFL trimers retained covalent linkage, maintaining a native-like structure while displaying enhanced stability and favorable antigenic features. These trimers also displayed increased exposure of neutralizing epitopes in the FP and gp120/gp41 interface, while retaining other neutralizing epitopes and occluding non-neutralizing elements. This array of Env-structure-guided designs reveals additional interactive regions in the prefusion state of the HIV Env spike, affording the development of novel antigens and immunogens

Lrmp/Jaw1 is Expressed in Sweet, Bitter, and Umami Receptor–Expressing Cells

Inositol 1,4,5-triphosphate–mediated calcium (IP3-Ca2+) signal cascade is an essential process in sweet, bitter, and umami taste signal transduction. Although the main components of this cascade have been identified, the candidate regulators of them in taste tissues are still unclear. In an effort to identify genes involved in taste signal transduction, we found that a gene encoding lymphoid-restricted membrane protein (Lrmp/Jaw1) was expressed in mouse taste tissues. Here we report that Lrmp/Jaw1 is specifically expressed in sweet, bitter, and umami taste receptor–expressing cells of mouse circumvallate, foliate, and fungiform papillae. In addition to this specific expression patterns, we found that Lrmp/Jaw1 is associated with type III IP3 receptor (IP3R3) via its coiled-coil domain in the COS7 heterologous expression system. These results raise the possibility that Lrmp/Jaw1 interacts with IP3R3 in taste cells and suggest an important role for Lrmp/Jaw1 in the IP3-Ca2+ signal cascade in sweet, bitter, and umami taste signal transduction

Learning Priors for Bayesian Computations in the Nervous System

Our nervous system continuously combines new information from our senses with information it has acquired throughout life. Numerous studies have found that human subjects manage this by integrating their observations with their previous experience (priors) in a way that is close to the statistical optimum. However, little is known about the way the nervous system acquires or learns priors. Here we present results from experiments where the underlying distribution of target locations in an estimation task was switched, manipulating the prior subjects should use. Our experimental design allowed us to measure a subject's evolving prior while they learned. We confirm that through extensive practice subjects learn the correct prior for the task. We found that subjects can rapidly learn the mean of a new prior while the variance is learned more slowly and with a variable learning rate. In addition, we found that a Bayesian inference model could predict the time course of the observed learning while offering an intuitive explanation for the findings. The evidence suggests the nervous system continuously updates its priors to enable efficient behavior

A Multicenter Evaluation of Different Chemotherapy Regimens in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Chemoradiation

PURPOSE: The number of older adults with head-and-neck squamous cell carcinoma (HNSCC) is increasing, and treatment of these patients is challenging. Although cisplatin-based chemotherapy concomitantly with radiotherapy is considered standard regimen for patients with locoregionally advanced HNSCC, there is substantial real-world heterogeneity regarding concomitant chemotherapy in older HNSCC patients. METHODS: The XXX study is an international multicenter cohort study including older (≥65 years) HNSCC patients treated with definitive radiotherapy at 13 academic centers in the United States and Europe. Here, patients with concomitant chemoradiation were analyzed regarding overall survival (OS) and progression-free survival (PFS) using Kaplan-Meier analyses, while Fine-Gray competing risks regressions were performed regarding the incidence of locoregional failures (LRFs) and distant metastases (DMs). RESULTS: Six hundred ninety-seven patients with a median age of 71 years were included in this analysis. Single-agent cisplatin was the most common chemotherapy regimen (n=310; 44%), followed by cisplatin plus 5-fluorouracil (n=137; 20%), carboplatin (n=73; 10%), and mitomycin c plus 5-fluorouracil (n=64; 9%). Carboplatin-based regimens were associated with diminished PFS (HR=1.39 [1.03-1.89], p.05). Median cumulative dose of cisplatin was 180 mg/m2 (IQR, 120-200 mg/m2). Cumulative cisplatin doses ≥200 mg/m2 were associated with increased OS (HR=0.71 [0.53-0.95], p=.02), PFS (HR=0.66 [0.51-0.87], p=.003), and lower incidence of LRFs (SHR=0.50 [0.31-0.80], p=.004). Higher cumulative cisplatin doses remained an independent prognostic variable in the multivariate regression analysis for OS (HR=0.996 [0.993-0.999], p=.009). CONCLUSIONS: Single-agent cisplatin can be considered as the standard chemotherapy regimen for older HNSCC patients who can tolerate cisplatin. Cumulative cisplatin doses are prognostically relevant also in older HNSCC patients

Evaluation of Concomitant Systemic Treatment in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Radiotherapy

IMPORTANCE The number of older adults with head and neck squamous cell carcinoma (HNSCC) is increasing, and these patients are underrepresented in clinical trials. It is unclear whether the addition of chemotherapy or cetuximab to radiotherapy is associated with improved survival in older adults with HNSCC. OBJECTIVE To examine whether the addition of chemotherapy or cetuximab to definitive radiotherapy is associated with improved survival in patients with locoregionally advanced (LA) HNSCC. DESIGN, SETTING, AND PARTICIPANTS The Special Care Patterns for Elderly HNSCC Patients Undergoing Radiotherapy (SENIOR) study is an international, multicenter cohort study including older adults (≥65 years) with LA-HNSCCs of the oral cavity, oropharynx/hypopharynx, or larynx treated with definitive radiotherapy, either alone or with concomitant systemic treatment, between January 2005 and December 2019 at 12 academic centers in the US and Europe. Data analysis was conducted from June 4 to August 10, 2022. INTERVENTIONS All patients underwent definitive radiotherapy alone or with concomitant systemic treatment. MAIN OUTCOMES AND MEASURES The primary outcome was overall survival. Secondary outcomes included progression-free survival and locoregional failure rate. RESULTS Among the 1044 patients (734 men [70.3%]; median [IQR] age, 73 [69-78] years) included in this study, 234 patients (22.4%) were treated with radiotherapy alone and 810 patients (77.6%) received concomitant systemic treatment with chemotherapy (677 [64.8%]) or cetuximab (133 [12.7%]). Using inverse probability weighting to attribute for selection bias, chemoradiation was associated with longer overall survival than radiotherapy alone (hazard ratio [HR], 0.61; 95% CI, 0.48-0.77; P < .001), whereas cetuximab-based bioradiotherapy was not (HR, 0.94; 95% CI, 0.70-1.27; P = .70). Progression-free survival was also longer after the addition of chemotherapy (HR, 0.65; 95% CI, 0.52-0.81; P < .001), while the locoregional failure rate was not significantly different (subhazard ratio, 0.62; 95% CI, 0.30-1.26; P = .19). The survival benefit of the chemoradiation group was present in patients up to age 80 years (65-69 years: HR, 0.52; 95% CI, 0.33-0.82; 70-79 years: HR, 0.60; 95% CI, 0.43-0.85), but was absent in patients aged 80 years or older (HR, 0.89; 95% CI, 0.56-1.41). CONCLUSIONS AND RELEVANCE In this cohort study of older adults with LA- HNSCC, chemoradiation, but not cetuximab-based bioradiotherapy, was associated with longer survival compared with radiotherapy alone