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Background and aims: E‐cigarette and other electronic nicotine delivery systems (ENDS) use has grown considerably over the past decade, with notable increases among young people. US state policy contexts for ENDS and tobacco may shape initiation into ENDS use among adolescents as they age into early adulthood. We aimed to determine whether state‐level comprehensive vaping ban policies reduce the odds of youth initiation into ENDS use, net of additional state‐level ENDS and tobacco policies, as well as the youth's cigarette smoking status. Design: Longitudinal data from the Population Assessment of Tobacco and Health study were merged with a state‐year database on tobacco and ENDS policies. Multivariable discrete‐time event history models of ENDS initiation were estimated. Setting: United States. Participants: Twenty thousand twelve youth assessed over six waves from 2013 to 2019 (n = 53 974 observations). Measurement We examined comprehensive indoor vaping bans (i.e. 100% vape‐free workplaces, restaurants and bars) as a key factor in initiation into ENDS use (i.e. first instance of vaping) from age 13 to 22. Findings Among young people, residing in a state with a comprehensive vaping ban was associated with 18% lower odds of ENDS initiation (odds ratio = 0.82; 95% confidence interval =[0.71, 0.94]), even after controlling for other state ENDS and tobacco policies, the youth's cigarette smoking and socio‐demographic background and state‐level covariates. Conclusions: In the United States, state‐level vaping bans (i.e. 100% vape‐free workplaces, restaurants and bars) are associated with reduced odds of youth initiation into electronic nicotine delivery systems use. [ABSTRACT FROM AUTHOR]

The involvement of endothelial barrier function in abdominal aortic aneurysm (AAA) and its upstream regulators remains unknown. Single‐cell RNA sequencing shows that disrupted endothelial focal junction is an early (3 days) and persistent (28 days) event during Angiotensin II (Ang II)‐induced AAA progression. Consistently, mRNA sequencing on human aortic dissection tissues confirmed downregulated expression of endothelial barrier‐related genes. Aldehyde dehydrogenase 2 (ALDH2), a negative regulator of AAA, is found to be upregulated in the intimal media of AAA samples, leading to testing its role in early‐stage AAA. ALDH2 knockdown/knockout specifically in endothelial cells (ECs) significantly increases expression of EC barrier markers related to focal adhesion and tight junction, restores endothelial barrier integrity, and suppresses early aortic dilation of AAA (7 and 14 days post‐Ang II). Mechanically, ELK3 acts as an ALDH2 downstream regulator for endothelial barrier function preservation. At the molecular level, ALDH2 directly binds to LIN28B, a regulator of ELK3 mRNA stability, hindering LIN28B binding to ELK3 mRNA, thereby depressing ELK3 expression and impairing endothelial barrier function. Therefore, preserving vascular endothelial barrier integrity via ALDH2‐specific knockdown in ECs holds therapeutic potential in the early management of AAAs. [ABSTRACT FROM AUTHOR]

DONSON is one of 13 genes mutated in a form of primordial microcephalic dwarfism known as Meier‐Gorlin syndrome. The other 12 encode components of the CDC45‐MCM‐GINS helicase, around which the eukaryotic replisome forms, or are factors required for helicase assembly during DNA replication initiation. A role for DONSON in CDC45‐MCM‐GINS assembly was unanticipated, since DNA replication initiation can be reconstituted in vitro with purified proteins from budding yeast, which lacks DONSON. Using mouse embryonic stem cells as a model for the mammalian helicase, we show that DONSON binds directly but transiently to CDC45‐MCM‐GINS during S‐phase and is essential for chromosome duplication. Rapid depletion of DONSON leads to the disappearance of the CDC45‐MCM‐GINS helicase from S‐phase cells and our data indicate that DONSON is dispensable for loading of the MCM2‐7 helicase core onto chromatin during G1‐phase, but instead is essential for CDC45‐MCM‐GINS assembly during S‐phase. These data identify DONSON as a missing link in our understanding of mammalian chromosome duplication and provide a molecular explanation for why mutations in human DONSON are associated with Meier‐Gorlin syndrome. Synopsis: DONSON is required for assembly of the CMG helicase in mammalian cells. This explains why hypomorphic mutations in human DONSON cause Meier‐Gorlin Syndrome, which is associated with defects in CMG helicase assembly or function. DONSON binds directly to the CMG helicase but is not a stable component of the replisome.DONSON is essential for DNA replication in mouse embryonic stem cells.DONSON is essential for assembly of the CMG helicase.DONSON is dispensable for loading of the MCM2‐7 helicase core but is required for stable association of GINS and CDC45 with loaded MCM2‐7. [ABSTRACT FROM AUTHOR]

Proteolytic reactions on the phospholipid membrane surface, so‐called "membrane‐dependent" reactions, play central role in the process of blood clotting. One particularly important example is FX activation by the extrinsic tenase (VIIa/TF). Here we constructed three mathematical models of FX activation by VIIa/TF: (A) a homogeneous "well‐mixed" model, (B) a two‐compartment "well‐mixed" model, (C) a heterogeneous model with diffusion, to investigate the impact and importance of inclusion of each complexity level. All models provided good description of the reported experimental data and were equivalently applicable for <40 μM of phospholipids. Model C provided better predictions than A, B in the presence of TF‐negative phospholipid microparticles. Models predicted that for high TF surface density (STF) and FX deficiency the FX activation rate was limited by the rate of FX binding to the membrane. For low STF and excess of FX the reaction rate was limited by the tenase formation rate. The analysis of the substrate delivery pathways revealed that FX bound to VIIa/TF predominantly from solution for STF >2.8 × 10−3 nmol/cm2 and from the membrane for lower STF. We proposed the experimental setting to distinguish between the collision‐limited and non‐collision‐limited binding. The analysis of models in flow and non‐flow conditions revealed that the model of a vesicle in flow might be substituted by model C in the absence of the substrate depletion. Together, this study was the first which provided the direct comparison of more simple and more complex models. The reaction mechanisms were studied in a wide range of conditions. [ABSTRACT FROM AUTHOR]

Aims: To investigate whether a heart failure (HF) hospitalization is associated with initiation/discontinuation of guideline‐directed medical HF therapy (GDMT) and consequent outcomes. Methods and results: Among patients in the Swedish HF registry with an ejection fraction <50% enrolled in 2009–2018, initiation/discontinuation of GDMT was investigated by assessing dispensations of GDMT in those with versus without a HF hospitalization. Of 14 737 patients, 6893 (47%) were enrolled when hospitalized for HF. Initiation of GDMT was more likely than discontinuation following a HF hospitalization compared to a control group of patients without a HF hospitalization (odds ratio range 2.1–4.0 vs. 1.4–1.6 for the individual medications), although the proportion of patients not on GDMT was still high (8.1–44.0%). Key patient characteristics triggering less use of GDMT (i.e. less initiation or more discontinuation) were older age and worse renal function. Following a HF hospitalization, initiation of renin–angiotensin system inhibitors/angiotensin receptor–neprilysin inhibitors or beta‐blockers was associated with lower and their discontinuation with higher mortality risk, but no association with mortality was observed for initiation/discontinuation of mineralocorticoid receptor antagonists. Conclusions: Following a HF hospitalization, initiation of GDMT was more likely than discontinuation, although still limited. Perceived or actual low tolerance were barriers to GDMT implementation. Early re‐/initiation of GDMT was associated with better survival. Our findings represent a call for further implementing the current guideline recommendation for an early re‐/initiation of GDMT following a HF hospitalization. [ABSTRACT FROM AUTHOR]

Continental‐scale strike‐slip shear zones often record significant tectono‐magmatism and dynamic deformation processes of the crustal lithosphere. However, the genetic relationships and timing among the anatexis, deformation, and initial shearing along a strike‐slip shear zone have not been well defined. Here, we carried out detailed field, microstructural, zircon U–Pb geochronology, geochemical and EBSD texture analyses of leucogranites and migmatites in the Chongshan shear zone (CS‐SZ). The results indicate that most migmatites and leucogranites exhibit strong shear deformation and well‐developed high‐temperature mylonitic microstructures. The quartz aggregated from foliated leucogranites developed dominant high‐temperature prism and prism slip systems. The pre‐ and syn‐kinematic crustal anatexis and localized weak zone mainly occurred from 35 to 29 Ma along the CS‐SZ, which is closely related to the post‐collisional extension and collapse of overthickened crust. Biotite dehydration melting formed pre‐ and syn‐kinematic melts and leucogranites that further experienced fractional crystallization of plagioclase and K‐feldspar during melting and subsequent melt migration and emplacement upward along the tectonic weak zone. The thinning and weakening of lithospheric crust further facilitated the initial and formation strike‐slip displacement along the CS‐SZ, which occurred from 29 to 20 Ma or much later to 18 Ma. Finally, we propose that crustal anatexis and upward migrating melts play a key role in controlling the thermal state and rheological strength of the crust, resulting in nucleation and initiation of the localized deep‐seated shear zone that accommodates significant displacement for the India–Asia continental forward collision and intracontinental deformation. Key Points: The Chongshan shear zone experienced large‐scale crustal anatexis from 35 to 18 MaThe anatexis of the migmatites is controlled by biotite dehydration meltingAnatexis plays a key role in nucleation and initiation of the localized deep‐seated shear zone [ABSTRACT FROM AUTHOR]

Purpose: To assess the effects of delayed versus early renal replacement therapy (RRT) initiation for patients with AKI. Methods: Related RCTs of RRT initiated at different times published on PubMed, Web of Science, Embase, and Cochrane Library were searched. Results: Fifteen RCTs studies with 5395 patients were included. The results showed that the 28‐day mortality (RR 1.01; 95% CI 0.94 ~ 1.08; p = 0.80), 60‐day mortality (RR 1.00; 95% CI 0.91 ~ 1.11; p = 0.93), 90‐day mortality (RR 1.01; 95% CI 0.94 ~ 1.08; p = 0.80), dialysis dependence among survivors (RR 0.67; 95% CI 0.40 ~ 1.13; p = 0.13), length of ICU stay (RR −1.32; 95% CI −3.26 ~ 0.62; p = 0.18) and length of hospital stay among survivors(RR −0.98; 95% CI −2.89 ~ 0.92; p = 0.31) were not significantly different between the two groups. In addition, early initiation of RRT increases the incidence of hypotension (RR 1.42, 95% CI 1.23 ~ 1.63; p < 0.00001) and infectious (RR 1.36; 95% CI 1.03 ~ 1.80; p = 0.03) events. Conclusion: Early initiation of RRT cannot improve the prognosis and benefit patients. [ABSTRACT FROM AUTHOR]

Summary: The evolutionary history of complement suggests that the alternative pathway arose prior to the arrival of the classical and lectin pathways. In these pathways, target specificity is provided by antibodies and sugar specific lectins. While these efficient initiation systems dominate activation on most targets, the alternative pathway produces most of the C3b and 80%‐90% of the C5b‐9. While the tickover process, originally proposed by Peter Lachmann, provided ancient hosts with a crude self/non‐self‐discriminatory system that initiated complement attack on everything foreign, tickover clearly plays a more minor role in complement activation in modern organisms possessing classical and lectin pathways. Spontaneous activation of the alternative pathway via tickover may play a major role in human pathologies where tissue damage is complement‐mediated. The molecular mechanism of tickover is still not convincingly proven. Prevailing hypotheses include (a) spontaneous hydrolysis of the thioester in C3 forming the C3b‐like C3(H2O) in solution and (b) "enhanced tickover" in which surfaces cause specific or non‐specific contact activated conformational changes in C3. Theoretical considerations, including computer simulations, suggest that the latter mechanism is more likely and that more research needs to be devoted to understanding interactions between biological surfaces and C3. [ABSTRACT FROM AUTHOR]

Introduction: Since its inception >50 years ago, clean intermittent catheterization (CIC) has become ubiquitous in managing lower urinary tract dysfunction in children. Emphasis has been on its impact on daily life, but little on its implementation and adjustment in families. The aim of the current study was to discover how families learned to implement and manage their child's CIC needs by interviewing caregivers, adolescents, and young adults about their experiences. Interviews were designed to uncover facilitators and barriers to beginning CIC to initiate potential improvements in a multidisciplinary approach. Methods: A semi‐structured interview guide was developed and piloted initially to 12 families for validation. Between August 2018 and October 2019, 40 families (52 interviews of caregivers and patients >12 years) were then interviewed with open‐ended questions interspersed with more specific ones to generate discussion. Transcripts were coded using Dedoose software to create a base list with emergent codes. Inductive and deductive methods were employed to generate themes. Consensus was reached during successive team meetings. Results: Five major and several subthemes emerged regarding implementation of CIC by caregivers and patients learning CIC for the first time. Theme 1: Parental reaction to CIC: Caregivers described benefits of an adjustment period on learning their child's need for CIC. Prenatal information to caregivers of spina bifida children gave them time to mentally process the need for CIC. Theme 2: Ease of learning CIC: impact of age and gender: caregivers identified advantages of initiating CIC in infancy. Caregivers speculated CIC was physically easier in boys than girls due to meatus location. Developmentally ready children expressed a desire for independence and privacy as they learned to initiate CIC. Theme 3: The impact of additional caregiver support in learning and performing CIC: presence of multiple caregivers optimized learning and implementation of CIC. Having secondary caregivers available provided peace of mind and more flexibility in maintaining reliable CIC care. Patients learning CIC found it helpful to have a parent present at the teaching session. Occasionally, female caregivers reported feelings of anger and frustration when male caregivers were reluctant to be involved in catheterization, irrespective of their child's gender. Theme 4: Satisfaction with healthcare team's approach: The healthcare team's responsiveness to their learning needs affected how they mastered CIC. The healthcare team's teaching and reassurance helped build caregiver confidence. Developmentally appropriate children were able to learn self‐catheterization when supported by the healthcare team. Patients learning self‐CIC articulated having a supportive healthcare team was helpful with implementation. Theme 5: Effect of CIC on employment status relative to job changes, insurance, and daycare: implementing and performing CIC presented a spectrum of issues related to employment. Educating employers regarding CIC facilitated a caregiver's ability to both remain at work and administer to their child. Caregivers underscored the importance of adequate insurance when considering employment choices. Concerns about daycare availability affected caregivers' work schedules. Conclusions: It is anticipated this information will aid healthcare personnel to more effectively teach and initiate CIC in families, and in individuals learning for the first time. The findings should serve as the basis for conducting future patient satisfaction studies, which would determine the effectiveness and reproducibility of these approaches. [ABSTRACT FROM AUTHOR]

We report on ultra‐slowly propagating discharge events with speeds in the range 1–13 km/s, much lower than any known lightning process. The propagation speeds of these discharges are orders of magnitude slower than leader or streamer speeds, but faster than the ion drift speed. For one particular event, a lightning leader forms about 40 ms later within 50 m of the discharge, likely within the same high field region. A second slow event forms 9 ms prior to the initiation, and leads into the negative leader. Most slow events appear to not be directly involved with lightning initiation. This suggests that the classic streamer cascade model of initiation is not always a definitive process. In this work we describe these discharge events displaying unique behavior, their relation to common lightning discharges, and their implications for lightning initiation. Plain Language Summary: While lightning is generally a very fast process, here we report on ultra‐slow discharges which may be a new and unexpected method of lightning initiation. These discharges travel at uncharacteristically low speeds and are observed in conjunction with lightning initiation in two cases, while in three different cases they are not. This indicates that these events are also evidence of failed lightning leader formation, which complicates the current understanding of how lightning initiates. Additionally, the velocity of these events is slow enough that in principle the propagation can be observed by the unaided eye ‐ challenging the colloquial notion of "fast as lightning." Key Points: The ultra‐slowly propagating events travel at speeds at least an order of magnitude slower than the slowest positive leadersIn one observed case, the slow propagation led directly into the formation of a lightning leaderIn most cases, these discharges are not connected with lightning initiation [ABSTRACT FROM AUTHOR]

We introduce a gold nanorod (AuNR) driven methodology to induce free radical polymerization in water with near infrared light (800 nm). The process exploits photothermal conversion in AuNR and subsequent heat transfer to a radical initiator (here azobisisobutyronitrile) for primary radical generation. A broad range of reaction conditions were investigated, demonstrating control over molecular weight and reaction conversion of dimethylacrylamide polymers, using nuclear magnetic resonance spectroscopy. We underpin our experimental data with finite element simulation of the spatio‐temporal temperature profile surrounding the AuNR directly after femtosecond laser pulse excitation. Critically, we evidence that polymerization can be induced through biological tissues given the enhanced penetration depth of the near infrared light. We submit that the presented initiation mechanism in aqueous systems holds promise for radical polymerization in biological environments, including cells. [ABSTRACT FROM AUTHOR]

Introduction: The impact of timing of hemodialysis (HD) for end‐stage renal disease (ESRD) patients treated with twice‐weekly HD remains unclear. We aimed to determine the effects of late initiation of HD on short‐term mortality and hospitalization. Methods: A multicenter cohort study was conducted in 11 HD centers in Northeastern Thailand (HEmodialysis Network of the NorthEastern Thailand study group). We recruited adult ESRD patients who were treated with twice‐weekly HD for more than 3 months and had data on eGFR at HD initiation. Clinical and laboratory values at the time of recruitment were recorded. Late and early (eGFR at start <5 and >5 ml/min/1.73 m2) initiations were defined. Outcomes were disease‐related death (excluding any accidental deaths) and first hospitalization. Data analysis was performed by multivariable cox‐regression analysis. Findings: A total of 407 patients who had data on eGFR at HD initiation (303 in late group and 104 in early group) were included for analysis. There were 56.8% male with a mean age of 55 years. During the 15.1 months of follow‐up, there were 27 (6.6%) disease‐related deaths. The 1‐year survival rate was similar among late and early initiation groups. The incidence density of first hospitalization in the late group was significantly lower than those in the early group (HR adjusted, 0.63; 95% CI, 0.40–0.99, p = 0.047). Among 303 patients who were in the late start group, patients with diabetes had a higher mortality rate (HR, 3.49; 95% CI, 1.40–8.70, p = 0.007) when compared to non‐diabetic patients. Discussion: Early initiation of HD at eGFR >5 ml/min/1.73 m2 had no short‐term survival benefit compared to the late group in ESRD patients treated with twice‐weekly HD for at least 3 months in a resource‐limited setting. A survival benefit from an early start of HD was found among diabetic patients. [ABSTRACT FROM AUTHOR]

Fluid injection stimulates seismicity far from active tectonic regions. However, the details of how fluids modify on‐fault stresses and initiate seismic events remain poorly understood. We conducted laboratory experiments using a biaxial loading apparatus with a 3 m saw‐cut granite fault and compared events induced at different levels of background shear stress. Water was injected at 10 mL/min and normal stress was constant at 4 MPa. In all experiments, aseismic slip initiated on the fault near the location of fluid injection and dynamic rupture eventually initiated from within the aseismic slipping patch. When the fault was near critically stressed, seismic slip initiated only seconds after MPa‐level injection pressures were reached and the dynamic rupture propagated beyond the fluid pressure perturbed region. At lower stress levels, dynamic rupture initiated hundreds of seconds later and was limited to regions where aseismic slip had significantly redistributed stress from within the pressurized region to neighboring locked patches. We found that the initiation of slow slip was broadly consistent with a Coulomb failure stress, but that initiation of dynamic rupture required additional criteria to be met. Even high background stress levels required aseismic slip to modify on‐fault stress to meet initiation criteria. We also observed slow slip events prior to dynamic rupture. Overall, our experiments suggest that initial fault stress, relative to fault strength, is a critical factor in determining whether a fluid‐induced rupture will "runaway" or whether a fluid‐induced rupture will remain localized to the fluid pressurized region. Plain Language Summary: Humans can create earthquakes on natural faults by injecting fluids underground. However, details regarding what factors affect these earthquakes are not fully understood. We conducted laboratory experiments on 3 m blocks of rock that slip similar to a natural fault. Our experiments investigated how the initiation and overall size of earthquakes differed when fluid was pumped into a critically loaded fault (nearly ready to host an earthquake) versus a fault that was less critical. In the near‐critical case, earthquakes occurred quickly and ruptured the entire fault. These earthquakes required fluid pressure to start the earthquake, but then were sustained by energy already present in the rock rather than due to fluid pressure. However, when the fault was not critical, earthquakes could only initiate after fluid pressure caused silent slip to redistribute significant amounts of shear stress from within the fluid pressurized area to the surrounding areas. When stress had redistributed enough that the surrounding areas reached a critical state, an earthquake initiated, but it did not rupture very far and remained small. Our experiments agree with recently published computer simulations that illustrate how induced earthquakes are strongly affected by the levels of preexisting stress in the rock. Key Points: Slip under high stress levels is driven by elastic stress transfer from induced aseismic slip, ruptured beyond the fluid pressurized regionSlip under low stress levels was primarily driven by fluid injection and was limited by the extent of the fluid pressurized regionRegardless of background stress level, fluid injection first produced aseismic slip and slow slip events, then dynamic rupture [ABSTRACT FROM AUTHOR]

Highly energetic 1‐(azidomethyl)‐5H‐tetrazole (AzMT, 3) has been synthesized and characterized. This completes the series of 1‐(azidoalkyl)‐5H‐tetrazoles represented by 1‐(azidoethyl)‐5H‐tetrazole (AET) and 1‐(azidopropyl)‐5H‐tetrazole (APT). AzMT was thoroughly analyzed by single‐crystal X‐ray diffraction experiments, elemental analysis, IR spectroscopy and multinuclear (1H, 13C, 14N, 15N) NMR measurements. Several energetic coordination compounds (ECCs) of 3d metals (Mn, Fe, Cu, Zn) and silver in combination with anions such as (per)chlorate, mono‐ and dihydroxy‐trinitrophenolate were prepared, giving insight into the coordination behavior of AzMT as a ligand. The synthesized ECCs were also analyzed by X‐ray diffraction experiments, elemental analysis, and IR spectroscopy. Differential thermal analysis for all compounds was conducted, and the sensitivity towards external stimuli (impact, friction, and ESD) was measured. Due to the high enthalpy of formation of AzMT (+654.5 kJ mol−1), some of the resulting coordination compounds are extremely sensitive, yet are able to undergo deflagration‐to‐detonation transition (DDT) and initiate pentaerythritol tetranitrate (PETN). Therefore, they are to be ranked as primary explosives. [ABSTRACT FROM AUTHOR]

Buprenorphine possesses many unique attributes that make it a practical agent for adults and adolescents with opioid use disorder (OUD) and/or acute or chronic pain. Sublingual buprenorphine has been the standard of care for treating OUD, but its use in pain management is not as clearly defined. Current practice guidelines recommend a period of mild‐to‐moderate withdrawal from opioids before transitioning to buprenorphine due to its ability to displace full agonists from the μ‐opioid receptor. However, this strategy can lead to negative physical and psychological outcomes for patients. Novel initiation strategies suggest that concomitant administration of small doses of buprenorphine with opioids can avoid the unwanted withdrawal associated with buprenorphine initiation. We aim to systematically review the buprenorphine initiation strategies that have emerged in the last decade. Embase, PubMed, and Cochrane Databases were searched for relevant literature. Studies were included if they were published in the English language and described the transition to buprenorphine from opioids. Data were collected from each study and synthesized using descriptive statistics. This review included 7 observational studies, 1 feasibility study, and 39 case reports/series which included 924 patients. The strategies utilized between the literature included traditional initiation (47.9%), microdosing with various buprenorphine formulations (16%), and miscellaneous methods (36.1%). Traditional initiation and microdosing initiation were compared in the data synthesis and analysis; miscellaneous methods were omitted given the high variability between methods. Overall, 95.6% of patients in the traditional initiation group and 96% of patients in the microdosing group successfully rotated to sublingual buprenorphine. Initiation regimens can vary widely depending on patient‐specific factors and buprenorphine formulation. A variety of buprenorphine transition strategies are published in the literature, many of which were effective for patients with OUD, pain, or both. [ABSTRACT FROM AUTHOR]

Structural Reactive Materials (RMs) are multi‐material composites that provide adequate structural strength and large exothermic yield. Combining the thermal energy output with kinetic energy, RMs fulfill a role in increasing the overall performance and energetic release of military weapon systems. The goal of this current research is to enhance the understanding of the thermomechanical conditions that are responsible for Al/PTFE RM ignition under dynamic loading. Two mechanisms of initiation commonly reported in the literature are shear‐induced and crack‐induced. To investigate the propensity of shear‐induced initiation a Shear Compression Specimen (SCS), combined with Kolsky Bar experimentation, was utilized to predominately load the RM specimen in dynamic shear. COMSOL Multiphysics simulations were conducted in conjunction with the experiments to obtain an equivalent stress‐strain response of the RM so that the work done on the gauge section of the SCS could be quantified. With the implementation of high‐speed cameras, the gauge section of the SCS was monitored to observe if RM ignition occurred from the dynamic shear loading. The results of the experiments conducted here indicate that fracture precedes ignition despite severe shear‐induced plastic deformation (and associated heating) occurring in the gauge section of the specimen, indicating that a crack‐induced ignition mechanism is likely active in this materials system under the studied loading rates. [ABSTRACT FROM AUTHOR]

Background: The number of new dialysis patients, particularly among the elderly population, has been globally increasing. In Japan, patients aged ≥65 years and ≥75 years comprised 72% and 45% of patients on dialysis in 2018, respectively. Few studies have reported seasonal variations in the initiation of dialysis. We investigated the seasonal prevalence of the emergent hemodialysis initiation in the elderly. Methods: We reviewed 479 elderly patients who initiated hemodialysis between January 2006 and December 2018. Early elderly patients were defined as patients aged between 65 and 74 years, and late elderly patients were defined as those aged ≥75 years. Emergent hemodialysis initiation was defined as initiation with a temporary vascular catheter without elective permanent vascular access or unplanned hemodialysis initiation due to patients requiring critical care regardless of elective permanent vascular access. The information collected included age, sex, and details of the initiation of hemodialysis. Results: The early elderly group consisted of 199 patients, and the late elderly group consisted of 279 patients. In the late elderly group, hemodialysis initiation was most frequent in winter, followed by spring, autumn, and summer (p = 0.018). Moreover, emergent hemodialysis initiation was most frequent in winter, followed by spring, autumn, and summer (p = 0.009). Emergent hemodialysis initiation due to fluid overload was most frequent in winter, followed by autumn, spring, and summer (p < 0.001). Among late elderly patients who initiated hemodialysis, 78% did not have permanent hemodialysis access at the time of the initiation of hemodialysis. Conclusion: In the late elderly group, hemodialysis initiation and emergent hemodialysis initiation were significantly more frequent in the winter than in the remaining seasons. In addition, emergent hemodialysis initiation due to fluid overload was most frequent in winter in the late elderly group. [ABSTRACT FROM AUTHOR]

SUMMARY: Homogalacturonan (HG), the most abundant pectic glycan, functions as a cell wall structural and signaling molecule essential for plant growth, development and response to pathogens. HG exists as a component of pectic homoglycans, heteroglycans and glycoconjugates. HG is synthesized by members of the GALACTURONOSYLTRANSFERASE (GAUT) family. UDP‐GalA‐dependent homogalacturonan:galacturonosyltransferase (HG:GalAT) activity has previously been demonstrated for GAUTs 1, 4 and 11, as well as the GAUT1:GAUT7 complex. Here, we show that GAUTs 10, 13 and 14 are also HG:GalATs and that GAUTs 1, 10, 11, 13, 14 and 1:7 synthesize polymeric HG in vitro. Comparison of the in vitro HG:GalAT specific activities of the heterologously‐expressed proteins demonstrates GAUTs 10 and 11 with the lowest, GAUT1 and GAUT13 with moderate, and GAUT14 and the GAUT1:GAUT7 complex with the highest HG:GalAT activity. GAUT13 and GAUT14 are also shown to de novo synthesize (initiate) HG synthesis in the absence of exogenous HG acceptors, an activity previously demonstrated for GAUT1:GAUT7. The rate of de novo HG synthesis by GAUT13 and GAUT14 is similar to their acceptor dependent HG synthesis, in contrast to GAUT1:GAUT7 for which de novo synthesis occurred at much lower rates than acceptor‐dependent synthesis. The results suggest a unique role for de novo HG synthesis by GAUTs 13 and 14. The reducing end of GAUT13‐de novo‐synthesized HG has covalently attached UDP, indicating that UDP‐GalA serves as both a donor and acceptor substrate during de novo HG synthesis. The functional significance of unique GAUT HG:GalAT catalytic properties in the synthesis of different pectin glycan or glycoconjugate structures is discussed. Significance Statement: Three new GAUTs (10, 13 and 14) are shown to be HG:GalATs. Comparison of products synthesized in vitro by GAUTs 1, 1:7, 10, 11, 13 and 14 under identical reaction conditions shows that all can synthesize polymeric HG. GAUTs 13 and 14 also de novo synthesize HG at rates comparable to their acceptor‐dependent activities. The results support the hypothesis that different GAUTs synthesize homogalacturonan with unique structural and/or functional roles in vivo. [ABSTRACT FROM AUTHOR]

Adolescence is the peak period for the emergence of substance use, which can lead to long-term psychosocial, occupational and interpersonal complications. Ongoing large-scale, longitudinal, consortium initiatives, such as the Adolescent Brain and Cognitive Development (ABCD) study, offer unprecedented opportunities to elucidate key risk factors for problematic substance use in a well-powered sample and to examine how changes in risk factors relate to symptoms across time. Delay discounting has been proposed as a putative risk marker for early substance-use initiation and other forms of psychopathology. However, the extent to which other factors (e.g., socio-economic status and cognitive ability) influence discounting behaviour in young adolescents is not well established. The present study leverages data from the ABCD study (n = 11 045) to assess associations between core demographic and familial variables and delay discounting in youth-operationalized using hyperbolic discounting rates (k)-before the onset of significant psychopathology. Model estimates revealed significant effects of individual difference factors (e.g., sex and socio-economic status) and alcohol risk status (based on family history) on delay discounting. No significant differences were observed in the primary sample when comparing the presence of parent drug problems or prenatal drug exposures. These effects will require replication in later waves of ABCD. Nonetheless, these results provide support for delay discounting as a potential risk marker for problematic alcohol use and demonstrate a relationship between key demographic variables and adolescent discounting behaviour. Further, these results provide an empirical baseline from which developmental trajectories of delay discounting and substance use may be tracked throughout future waves of ABCD. [ABSTRACT FROM AUTHOR]

Summary: In this article, I examine the blurred lines between my own experience of violence in South Africa and that of the women I encountered while doing fieldwork in Pafuri, Mozambique. I centralize the importance of personal insight to deal with violent sexuality and rape and argue that reflection provides meaning to the process of ethnographic fieldwork. I examine the similarities between my own experience of violence in South Africa and that of my interlocutors in Mozambique, set within a regional political system that marginalizes women's experiences in both countries. While negative experiences of rape stem from a prejudiced history, I argue that these experiences can be overcome through rebirth or initiation. In my case, this was achieved through the personal level of transformation that fieldwork produced, while for women in Pafuri, the initiation (vukhomba) of young girls translates violence into empowerment. [ABSTRACT FROM AUTHOR]

Background: Alcohol use shows age‐graded patterning, with normative use progressing through characteristic milestones of escalating use or severity. Despite some knowledge about the timing of milestone attainment and sequencing across milestones, there is a gap in our understanding of the earliest stages of use. This study characterizes the timing, sequencing, and speed of progression through milestones beginning with the first sip of alcohol. Methods: Sixth through eighth graders (N = 1023; 52% female; 76% White; M = 12.23 years old) completed web surveys through the end of high school. Participants reported on alcohol experiences including the first sip, full drink, consumption of 3+ drinks/occasion (heavy drinking), being drunk, and experiencing acute consequences, from which milestone age and speed of progression (duration) were calculated. Milestone prevalence, sequencing, and timing were characterized, and associations between age of attainment and speed of progression were examined. We also examined whether milestone timing and progression varied by sex and racial/ethnic group. Results: Overall, milestones followed the expected ordering with the exception of heavy drinking (3+ drinks/occasion) and being drunk, which appear to index similar experiences. An earlier age of attainment was associated with an increased likelihood of attaining each of the milestones. In contrast, once a milestone was achieved, there was reduced risk of initiation of subsequent adjacent milestones for individuals with an earlier first sip and full drink, and earlier initiation was associated with a longer duration to subsequent milestones. Girls were more likely to attain all milestones than boys, but there was no sex difference in the age of attainment. In contrast, Hispanic youth reported earlier ages of initiation than White non‐Hispanic youth, but the likelihood of attainment did not vary by race/ethnicity. Rapid progression was observed in females but did not vary by race/ethnicity. Discussion: Risks associated with early drinking are complex, with little support for normative ordering of milestones beyond the first sip. Although early drinking is associated with an increased risk of subsequent drinking, it does not appear to place the drinker on an accelerated course to heavier use. A nuanced understanding of risks associated with milestone timing may inform intervention efforts. [ABSTRACT FROM AUTHOR]

Background: Improving oral anticancer agent (OAA) initiation and adherence is the important quality‐of‐care issues, particularly since one fourth of anticancer agents being developed will be administered orally. Our objective was to identify provider‐ and patient‐level characteristics associated with OAA initiation and adherence among individuals with metastatic renal cell carcinoma (mRCC). Methods: We used state cancer registry data linked to multi‐payer claims data to identify patients with mRCC diagnosed in 2004–2015. Provider data were obtained from North Carolina Health Professions Data System and the National Plan & Provider Enumeration System. We estimated risk ratios (RRs) and corresponding 95% confidence limits (CLs) using modified Poisson regression to evaluate factors associated with OAA initiation and adherence. Results: Among the 207 (out of 687) patients who initiated an OAA following mRCC diagnosis and survived 90 days, median proportion of days covered was 0.91. Patients with a modal provider specializing in hematology/medical oncology were much more likely to initiate OAAs than those seen by other specialties. Additionally, patients with a female provider were more likely to initiate OAAs than those with a male provider. Compared to patients treated by providers practicing in both urban and rural areas, patients with providers practicing solely in urban areas were more likely to initiate OAAs, after controlling for patient‐level factors (RR = 1.37; 95% CL: 1.09–1.73). Medicare patients were less likely to be adherent than those with private insurance (RR = 0.61; 95% CL: 0.42–0.87). Conclusions: Our results suggest that provider‐ and patient‐level factors influence OAA initiation in patients with mRCC but only insurance type was associated with adherence. [ABSTRACT FROM AUTHOR]

The corrosion of a 75Sn–25Pb coating on low‐carbon steel exposed to a vapor/condensate phase over a 1 mol/L HCl solution has been studied. The corrosion mechanism initiation was based on several steps. The presence of CO2 and lead involves the precipitation of cerussite PbCO3 crystals. Overtime, the cerussite evolved and transformed into PbCl2. This transformation was not direct and involved the creation of reaction intermediates whose chemical composition was variable. In parallel, tin formed oxides that were not stable in the HCl solution. These oxides dissolved and led to the formation of an electrolyte concentrated in Sn2+. When tin ions' saturation was reached, tin precipitated to form abhurite, Sn21Cl16(OH)14O6, or hydrated tin chloride, SnCl2.2H2O. This study highlighted the particularity of the corrosion mechanism. It also showed that the presence of tin promoted the oxidation of lead and consequently the formation of cerussite. [ABSTRACT FROM AUTHOR]

Recent debate about raising federal minimum wage to $15 per hour receives substantial public attention. Yet the minimum wage literature has been focusing on the labor market outcomes, with the health implications rarely being discussed. This paper investigates the impact of minimum wage increases on multiple dimensions of cigarette smoking behaviors for the low‐skilled population using the Current Population Survey‐Tobacco Use Supplement over a long time period (1998–2015). Results show that a $1 increase in the minimum wage raises the prevalence of smoking by about 2.3% and reduces cessation by about 13.7% among the low‐skilled workers. With further examinations, we find evidence of an income effect as one potential mechanism that leads to more smoking. The impacts on all low‐skilled adults, however, are somewhat smaller, which are most likely driven by the null effects among those who are out of the labor force. We additionally conduct a series of sensitivity tests and confirm the robustness of these results. [ABSTRACT FROM AUTHOR]

Initiating insulin therapy with a basal insulin analogue has become a standard of care in the treatment of type 2 diabetes mellitus (T2DM). Despite increasing choices in pharmacological approaches, intensified glucose monitoring and improvements in quality of care, many patients do not achieve the desired level of glycaemic control. Although insulin therapy, when optimized, can help patients reach their glycaemic goals, there are barriers to treatment initiation on both the side of the patient and provider. Providers experience barriers based on their perceptions of patients' capabilities and concerns. They may lack the confidence to solve the practical problems of insulin therapy and avoid decisions they perceive as risky for their patients. In this study, we review recommendations for basal insulin initiation, focussing on glycaemic targets, titration, monitoring, and combination therapy with non‐insulin anti‐hyperglycaemic medications. We provide practical advice on how to address some of the key problems encountered in everyday clinical practice and give recommendations where there are gaps in knowledge or guidelines. We also discuss common challenges faced by people with T2DM, such as weight gain and hypoglycaemia, and how providers can address and overcome them. [ABSTRACT FROM AUTHOR]

Porous silicon with sodium perchlorate oxidizer is hypothesized to be a detonable explosive, which is atypical for heterogenous fuel/oxidizer composites. The existence of detonation in energetic porous silicon remains contested and would theoretically feature several unique behaviors illustrated by this study. Calculations to predict detonation performance are performed using CHEETAH thermochemical code for silicon porosities of 45–85 % surrounding 69 %, which represents an experimentally typical case. Uniquely, e‐PS detonation is predicted to produce low gas volume. At 69 % porosity, condensed detonation products comprise 78 % of the mass (varying from 86 % to 46 % for 45–85 % porosity), and therefore a low TNT equivalent mechanical energy of 0.429 (but 1.32 when comparing total detonation energy). The calculated pressure of detonation for 69 % porosity is 1.065 GPa, only about 4 % of that of typical military explosives but over 50 times greater than compression wave amplitudes estimated for fast‐burning nanothermites, which are comparable heterogenous fuel/oxidizer composites. At porosities above 67 %, computed detonation velocities are shown to exceed estimates for the unreacted speed of sound and therefore a detonation structure consistent with classical CJ theory is proposed. Indeed, published maximum experimental propagation speeds for energetic porous silicon in this upper porosity range when pore size is optimal agree well with CHEETAH computations of detonation velocity, thereby supporting that detonation is possible. Below 66 % porosity, sound speed in unreacted material overtakes the calculated detonation velocities. Traditionally this precludes formation of a detonation wave since the shockwave would decay as energy propagates ahead acoustically into unreacted material. However, experimental agreement is still observed between 60–67 % porosity. By comparing computed detonation pressure with estimates for the strength of unreacted porous silicon, this range is proposed to be a transition zone in which a detonation‐like structure could be maintained, despite the inverted sound speed comparison, by rapid catastrophic fracture of porous silicon at the detonation front. This hypothesis implies that a sonic precompression wave must precede the detonation wave since at least a minor fraction of shock energy would propagate ahead in unreacted material. Finally, comparisons are made with baseline primary explosives and nanothermites showing that among metal‐based composite energetics on the basis of reaction rate and detonation pressure, energetic porous silicon currently exhibits the most promise for replacing primary explosives at reasonable densities in igniters and augmenting initiator formulations. [ABSTRACT FROM AUTHOR]

Background and aims: No previous studies have examined the prospective association between disposable income and binge‐drinking initiation among adolescents. We aimed to examine whether there is such an association and, if so, whether it is robust to confounders, uniform across individual characteristics and linear versus non‐linear. Design Prospective study of adolescents from 32 middle schools, stratified according to geographic location, urban and rural locations and standard of living. Adolescents were assessed in 2017 (T1) and 1 year later (T2). Setting: Norway. Participants: A nation‐wide sample of 1845 adolescents (mean age 13.5 years, 44% boys) with no binge‐drinking experience at T1. Measurements Data were collected on binge drinking at T1 and T2. Data on disposable income and on a range of demographic, individual and family factors were collected at T1. Findings Overall, 7.2% initiated binge drinking between T1 and T2. Logistic regression showed that the crude linear effect of disposable income on binge drinking initiation was substantial, and only slightly attenuated in the fully adjusted model including all putative confounders [odds ratio (OR) = 1.19, 95% confidence interval (CI) = 1.08, 1.31, P < 0.001]. However, interaction analyses showed disposable income to be negatively related to binge drinking initiation for adolescents who had experienced light drinking at T1 (OR = 0.66, 95% CI = 0.49, 0.89, P = 0.006) or who had seen their mothers intoxicated [OR = 0.62, 95% CI = 0.39, 0.99, P = 0.043). Conclusion: Norwegian adolescents with higher disposable income have a greater risk of subsequent binge drinking initiation than those with lower disposable income. Each additional 100 NOK (≈ €10) of weekly income increased the risk of binge drinking initiation in the following year by approximately 20%. [ABSTRACT FROM AUTHOR]

Background: Adherence to ADHD medication is a complex phenomenon as the decision to adhere is influenced by a range of factors. To design tailored interventions to promote adherence, it is important to understand the factors that influence adherence in the context of its three phases: initiation, implementation and discontinuation. Objective: The objective of this study was to explore the phase‐specific factors that influence adherence to medication in adults who have a diagnosis of ADHD. Methods: Three focus groups (FGs) were conducted with twenty adults with ADHD in different metropolitan areas of Sydney, Australia. FGs were transcribed verbatim and thematically analysed. Results: Participants' decision to initiate medication (the initiation phase) was influenced by their perceived needs (desire to improve academic and social functioning) and concerns (fear of side‐effects) about medication following a similar process as defined by the Necessity‐Concerns Framework (NCF). The balance between benefits of medication (needs) and side‐effects (concerns) continued to determine participants' daily medication‐taking (the implementation phase) and persistence (or discontinuation) with their medication. Forgetfulness and stigma were reported as concerns negatively impacting the implementation phase, while medication cost and dependence influenced the discontinuation phase of adherence. Conclusions: Adults' decision to initiate, continue or discontinue medication is influenced by a range of factors; some are unique to each phase while some are common across the phases. Participants balanced the needs for the medication against their concerns in determining whether to adhere to medication at each phase. It appears that the NCF has applicability when decision making about medication is explored at the three phases of adherence. [ABSTRACT FROM AUTHOR]

In steep landscapes, wildfire‐induced changes to soil and vegetation can lead to extreme and hazardous geomorphic responses, including debris flows. The wildfire‐induced mechanisms that lead to heightened geomorphic responses, however, depend on many site‐specific factors including regional climate, vegetation, soil texture, and soil burn severity. As climate and land use change drive changes in fire regime, there is an increasing need to understand how fire alters geomorphic responses, particularly in areas where fire has been historically infrequent. Here, we examine differences in the initiation, magnitude, and particle‐size distribution of debris flows that initiated within the area burned by the 2019 Woodbury Fire in central Arizona, USA, and those that initiated in a nearby unburned area. Despite similar rainfall intensities, unburned watersheds were less likely to produce debris flows. Debris flows in unburned areas initiated from both runoff and shallow landslides, while debris flows only initiated from runoff‐related processes in the burned area. The grain‐size distribution making up the matrix of debris‐flow deposits within the burned area generally had a lower ratio of sand to silt relative to debris flows that initiated in the unburned area, though there were no systematic differences in the coarse fraction of debris‐flow sediment between burned and unburned areas. Results help expand our ability to predict postwildfire debris‐flow activity in a wider range of settings, specifically the Sonoran Desert ecoregion, and provide general insight into the impact of wildfire on geomorphic processes in steep terrain. Key Points: Even low severity fires can increase debris flow likelihood and volumeDebris flows initiated from runoff and shallow landslides in unburned areas but were only generated by runoff in burned areasDebris flows initiating in the burned area had greater fractions of silt relative to those initiating in the unburned area [ABSTRACT FROM AUTHOR]

Upward lightning occurs generally from tall structures. The mechanism of the initiation of upward lightning is not yet fully understood. Upward lightning can be classified into two categories based on either the absence or the presence of other lightning activity prior to the upward flash. This work proposes an explanation of how upward lightning flashes can be triggered by nearby lightning activity. It is generally thought that the lightning activity prior to the flash will intensify the electric field at the tip of the tall structures. However, to the best of our knowledge, no attempt has been made to evaluate theoretically this hypothesis. In this paper, we derive analytically the electric field enhancement on the ground (or at the top of tall structures) based on different triggering scenarios. These fields are later used in a simplified corona model to evaluate if they are able to trigger upward lightning. It is shown that both slow processes such as leader propagation and faster return strokes can trigger an upward negative flash from relatively short structures of a few tens of meters, even without any slowly varying background electric field. This study confirms theoretically experimental observations and it provides new insights into the mechanisms of initiation of upward flashes from tall structures. Key Points: Analytical formulas are derived to describe the electrostatic field changes associated with horizontal and vertical leadersThe derived formulas are used to evaluate the electric fields in different scenarios leading to the triggering of an upward flashUpward lightning can be triggered by nearby lightning activity, either during leader propagation phase, or after the return stroke phase [ABSTRACT FROM AUTHOR]

Aims: To examine the association between alcohol prices and age of initiation of alcohol use and the association between age of alcohol use initiation and heavy episodic drinking (HED) among adolescents in Chile. Design We estimated discrete‐time hazard models using retrospective data and generalized ordered probit models with repeated cross‐sectional data. Setting: Chile. Participants: A total of 248 336 urban youth who attended secondary school between 2003 and 2015 and self‐reported ever having tried alcohol. Measurements We created drinking histories from self‐reported responses of age, age of alcohol use initiation and year/month of survey. From two self‐reported responses, we created a four‐category ordinal variable of heavy episodic drinking: none, one to two, three to nine and more than 10 HED episodes in the past 30 days. We constructed a monthly measure of real alcohol prices using the all‐items and alcohol component of the Consumer Price Index compiled by Chile's statistical agency, the Instituto Nacional de Estadísticas. Findings First, we found negative, statistically significant and policy‐meaningful associations between alcohol prices and the age of alcohol use initiation. The estimated price elasticity of delay was −0.99 [95% confidence interval (CI) = –1.30, −0.69]. A 10% increase in real alcohol prices was associated with delayed alcohol use initiation of approximately 6.6 months. Secondly, we found that youth who had started drinking alcohol at a later age had statistically significant and substantially lower probabilities of having reported HED during the previous month. For example, youth who started drinking at 16 were 4.9 (95% CI = 4.2–5.6) percentage points more likely to have reported no HED in the previous month relative to youth who started drinking alcohol when aged 12 years or younger. Conclusions: Increasing the price of alcohol products may delay alcohol initiation among young people in Chile. Chilean youth who start drinking alcohol later may engage in less harmful drinking practices. [ABSTRACT FROM AUTHOR]

Aims: To identify prototypical developmental patterns of tobacco product and cannabis use and co‐use initiation during adolescence, and determine risk factors for and consequences of these initiation patterns. Design Prospective repeated‐measures cohort with eight semi‐annual assessments during high school. Multiple‐event process survival mixture modeling identified latent initiation classes with distinct patterns of variation in timing of use initiation of tobacco products and cannabis. We then estimated: (1) associations of baseline risk factors with membership in initiation classes and (2) differences between initiation classes in frequency of cannabis and tobacco product use at the final assessment. Setting: Ten high schools in the Los Angeles, CA, USA metropolitan area, 2013–17. Participants: Students [1031 (45.4%) males; mean (standard deviation) age at baseline = 14.6 (0.39) years] who had never used any tobacco products or cannabis at baseline 9th grade assessment (n = 2272). Measurements: Self‐report measures of electronic cigarette (e‐cigarette), combustible cigarette, hookah, cigar/cigarillos and cannabis use were collected at each assessment. Findings Four distinct tobacco and cannabis use initiation classes were identified: (1) early and high‐risk cannabis and polytobacco initiators (n = 116; 5.1%); (2) early cannabis and polytobacco initiators (n = 172; 7.6%); (3) late cannabis and e‐cigarette initiators (n = 431; 19.0%); and (4) abstainers (n = 1553; 68.4%). At baseline, older age for the early and high‐risk cannabis and polytobacco initiators [odds ratio (OR) = 1.22, 95% confidence interval (CI) = 1.10, 1.35, P < 0.001], peer cannabis use (OR = 1.60, 95% CI = 1.23, 2.08, P < 0.001) and delinquent behavior (OR = 1.30, 95% CI = 1.08, 1.55, P = 0.004) were associated with membership in the three initiation classes (versus abstainers). Membership in the early and high‐risk cannabis and polytobacco initiators class (versus three other classes) was significantly associated with increased past 30‐day frequency and daily intensity of use at the final assessment (P‐values < 0.001). Conclusions: Older age, peer cannabis use and delinquent behavior appear to be risk factors for the initiation of tobacco/cannabis product use among high school students in the Los Angeles metropolitan region. Early and higher‐risk polyproduct use initiation appears to be associated with greater escalation of past 30‐day and daily tobacco and cannabis use at the end of the high school. [ABSTRACT FROM AUTHOR]

Introduction and Aim: Evidence regarding the association between e‐cigarette use and subsequent initiation of smoking mostly relates to the US population. In Australia, no studies are available investigating the association between the uses of e‐cigarettes and smoking initiation among young adults who have never smoked. This study aimed to determine the association between lifetime e‐cigarette use and subsequent initiation of cigarette smoking among tobacco‐naïve Australian women aged 20–27. Design and Methods: The current study used data (n = 5398) from the third (2015) and fourth (2016) surveys collected from a cohort of Australian women born in 1989–1995 who participated in the Australian Longitudinal Study on Women's Health. Multivariable logistic regression was used to identify the association between lifetime e‐cigarette use at the baseline survey and initiation of cigarette smoking (smoked 100 cigarettes or more in the last year) at the follow up adjusting for possible confounders. Effects were expressed as odds ratios with 95% confidence interval. Results: The mean (± SD) age of the study participants at baseline (third survey) was 22.5 (±1.7). Ever e‐cigarette use at baseline was positively associated with smoking initiation at follow up (adjusted odds ratio 3.71; 95% confidence interval 2.33, 5.93). History of depression, binge drinking and higher childhood adversity score were also risk factors for subsequent smoking initiation in the follow up. Discussion and Conclusions: This study identified a strong association between e‐cigarette use and subsequent initiation of smoking. Enforcing the existing restriction of sale and supply of e‐liquid containing nicotine is essential to prevent never smokers from nicotine addiction via e‐cigarettes. [ABSTRACT FROM AUTHOR]

A mild, metal‐free, atmospheric oxygen‐mediated radical hydrothiolation of alkenes (and alkyne) is reported. A variety of sulfur containing motifs including alkanethiols, thiophenols and thioacids undergo an atmospheric oxygen‐mediated radical hydrothiolation reaction with a plethora of alkenes in good yield with excellent functional group compatibility, typically with short reaction times to furnish a range of functionalized products. Biomolecules proved tolerant to the conditions and the procedure is robust and easily executable requiring no specialized equipment. Concise mechanistic studies confirm the process proceeds through radical intermediates in a thiol‐ene reaction manifold. The methodology offers an efficient "green" approach for thiol‐ene mediated "click" ligation and a milder alternative to thermally initiated hydrothiolation processes. [ABSTRACT FROM AUTHOR]

Objective: Due to the possibility of serious adverse events (AE), patients are commonly admitted to hospital for 3‐5 days for ketogenic diet (KD) initiation. This study examined the incidence of potential AE during admission for KD initiation to investigate the possibility of safely initiating a KD at home. Methods: Children with drug‐resistant epilepsy (DRE) who were admitted to hospital for 5 days for KD initiation were retrospectively studied. Results: A total of 66 children (59% female) were analyzed. The mean age at the initiation of the KD was 48.0 ± 38.4 months, and the mean weight was 14.6 ± 6.3 kg. The median number of anticonvulsant medications used at the time of KD initiation was 3. The etiology of the DRE was structural in 4.5%, hypoxic ischemic encephalopathy in 10.6%, genetic/metabolic in 31.8%, acquired in 10.6%, and unknown in 42.2%. The potential AE occurred in 28.7% of patients, including hypoglycemia (20%), hypoactivity (6.1%), somnolence (3%), and vomiting (7.6%). A univariate analysis of the clinical characteristics of the AE and no AE groups showed a statistically significant difference in weight (P = 0.003) and age (P = 0.033). The concurrent use of topiramate was found to have a near‐significant association (P = 0.097) between the groups. The groups' urine ketone levels on all 5 days were compared, and a statistically significant difference was found on day 3 (P = 0.026). A statistically significant difference in the serum bicarbonate levels (P = 0.038) was found between the patients taking topiramate and those not taking it. Significance: The incidence of AE during admission for KD initiation was found to be low. The AE either required no intervention or were easily managed with simple interventions. Thus, in carefully selected patients, it may be possible to initiate a KD at home if the parents are adequately prepared and monitored. [ABSTRACT FROM AUTHOR]

Low‐velocity, shock‐free impact is one of the accidental loads that can lead to a thermal explosion, the latter being the consequence of a chain of mechanisms depending on the microstructure of the material. To investigate the causes, the predictive capability of numerical tools depends on the physics embedded in the models. While a consensus has developed around the concept of hot spots, the exact nature of the thermo‐mechanical heat‐generating processes that preceded them remains to be clarified. We are studying a composition similar to the PBX 9501. HMX crystals are mixed with a few percent of a polymer binder. Recent experiments (reverse edge‐on impact test) have revealed the influence of the plasticity of HMX grains even at low strain rates and low confinement. The heat released by the plastic dissipation has been identified as a potential candidate for the formation of hot spots. In this study, a numerical representation based on a polycrystalline β‐HMX material subjected to intense shear is presented. Due to the high pressure generated by the impact, the intergranular slip is ignored. Emphasis is placed on the heterogeneity resulting from the micro‐structural characteristics and the interaction between the anisotropic single crystals. The behavior of the binder and the influence of other heterogeneities such as friction or micro cracks are set aside. Finally, the mechanical dissipation is calculated in the models and the maximum temperature is deduced. [ABSTRACT FROM AUTHOR]

Ten impact experiments are presented that probe the initiation behavior of an RDX‐based explosive. The explosive pellets were impacted by thin aluminum impactors supported by low‐impedance polymers, thereby subjecting the pellets to short duration shocks. Impact conditions were used to determine impact tilt, pulse pressure and duration, sample transit time, and whether or not a detonation occurred. Exploding Foil Initiator (EFI) launchers were used as a baseline for evaluating the technique, and it was found that the present technique addresses multiple shortcomings of EFI‐based systems. The aluminum foil allowed impacts with pressure durations of 70–80 ns, resulting in input conditions closely matching those of EFI‐based systems. The thicker aluminum plate impactors resulted in pulse durations of approximately 600 ns and allowed access to a previously inaccessible region of the initiation curve. Initiation thresholds were bracketed using both impactors, and the data is compared with complementary initiation data from EFI‐based systems with good agreement. Based on the results and closely related work, a novel, physically‐based criterion is proposed to allow the initiation curve to be predicted based on the explosive's unreacted equation of state and sustained‐pulse, shock‐to‐detonation run distance (the "Pop‐plot"), giving a physical basis for previously published observations. Finally, the criterion is applied to the data available to propose a relationship between pressure, pulse duration, and run distance, suggesting that input pulse durations of 50–100 % higher than the critical condition should be applied to approximate the run distance of a sustained pulse. [ABSTRACT FROM AUTHOR]

Hydrogen peroxide and hydroperoxides with substituents of different size are combined with ferrous sulfate to form redox initiation systems, which are used to initiate the polymerization of styrene in emulsion. Gas chromatography and size‐exclusion chromatography are used to measure the monomer conversion and the molecular weight of the polystyrene. Nuclear magnetic resonance is used to identify the characteristic structures, quantitative information is used to understand the polymerization. The results suggest that the initiation of the primary radicals directly depend on the size of the substitute, hydroxyl radical shows almost no selectivity between head‐addition and tail‐addition during initiation (Fhi = 47.4%). But for primary radicals with big substitute groups, for example, t‐butyl and cumyl hydroperoxides, tail‐addition takes advantages over head‐addition during initiation (Fhi ≈80%). As for the termination mechanism, it mainly depends on the solubility of the peroxide in water, the interfacial area of the particle as well as the diffusion rate of the primary radical in aqueous phase. Primary termination dominates in the polymerization initiated by hydroperoxide with poor solubility in water, for example, Fpt = 75–80% for t‐butyl and cumyl hydroperoxides. But Fpt is only 18.3% in the polymerization initiated by hydrogen peroxide (H2O2), indicating coupling termination predominately occurred because H2O2 has excellent solubility in water. [ABSTRACT FROM AUTHOR]

The sensitivity of energetic materials to initiating stimuli is one of the tests with binary response. Usually, there is not a single sharp boundary between energy levels causing initiation and not causing initiation. Instead, there is an interval of energies causing the initiation with certain probability, called the sensitivity curve. In the past, various methods were developed to determine the whole sensitivity curve, or its important points (e. g. Bruceton staircase, Robbins‐Monroe, Langlie, Probit analysis, or Neyer's D‐optimal test, 3pod). All these methods, despite frequently used, have their limitations. We would like to introduce the new method/algorithm, called FEST (Fast and Efficient Sensitivity Testing), for the determination of a sensitivity curve. The sensitivity curve is represented by the cumulative distribution function for a lognormal distribution. The calculation of the level for the next shot is similar to Neyer's approach in the beginning of the test procedure. Later, after the overlap is reached and therefore unique maximum likelihood estimates for μ and σ exist, the next shot level is calculated from these parameters using two user‐defined constants. These constants can be used to shift the levels of testing into the area of interest of the sensitivity curve. In this article, the algorithm is introduced, its convergence to real values is supported by simple Monte Carlo simulations, and a real life example (determination of sensitivity to electrostatic discharge for a pyrotechnic mixture) is presented. [ABSTRACT FROM AUTHOR]

The initiation and organization of a long‐duration hail‐producing mesoscale convective system (MCS) in eastern China are investigated using convection‐allowing simulations at 3‐km grid spacing with the Advanced Regional Prediction System. The lifecycle of this MCS is characterized by two stages. In the first stage, a series of convective storms are initiated along the northwest border of Jiangsu Provinces. These storms organize into a northwest southeast line as they moved southeastward, eventually organizing into an eastward moving bow‐echo structure during the second stage. Our analyses show that the storms initiate along a northwest‐southeast oriented convergence boundary set up between two low‐level mesoscale vortices, one to the northwest of Jiangsu Province and one over the East China Sea. Comparisons between the fake‐dry and control simulations show that the rearward (westward) spreading of a cold pool from another MCS proceeding the hail‐producing MCS plays a key role in generating and enhancing the vortex over Eastern China Sea. The tilting of baroclinically generated horizontal vorticity along the edge of the cold outflow creates a cyclonic and anticyclonic vortex couplet. The cyclonic vortex becomes the dominant East China Sea vortex as it is superposed onto the background cyclonic circulation. This cold outflow‐induced vortex also has strong impacts on the later organization of the hail‐producing MCS, leading to the eventual establishment of a bow‐echo structure. Finally, a three‐stage conceptual model for the initiation and organization of the long‐lasting multicellular MCS is proposed, and the understanding on the complex interactions between two MCSs will be helpful to operational forecasters. Key Points: Storm initiation occurred along a northwest‐southeast oriented convergence zone and finally organized into an MCS with a bow‐echoTwo low‐level mesoscale vortices, one overland and one over the East China Sea, set up the strong convergence zoneAn earlier MCS plays key roles in generating and enhancing the vortex over sea via baroclinic vorticity generation at the edge of its rearward spreading cold pool [ABSTRACT FROM AUTHOR]

Following the 2013 public subsidy of pregabalin in Australia for neuropathic pain not responding to other medicines, use and misuse increased substantially. We used pharmaceutical dispensing claims for a 10% sample of Australians to quantify initiation, discontinuation and dispensing of other analgesics before and after initiation. We identified 130 770 people initiating pregabalin between 2013/14 and 2017/18 (median age: 61 years; 56.8% female). Discontinuation rates at 1‐year increased from 77.0% in 2013/14 to 85.9% in 2017/18; 38% only had 1 dispensing. Approximately 1/3 (37.5%) initiated on the lowest strength capsule (25 mg) with only 31.2% later up‐titrating to a higher strength. 47.4% and 53.0% were dispensed opioids within 180 days before and after pregabalin initiation, respectively. Many individuals are using pregabalin for short treatment durations and low dose ranges not consistent with treatment of neuropathic pain, which is generally a chronic condition. This may suggest poorer tolerability than observed in clinical trials, or use for other conditions, some of which may be for indications where the balance of benefits and risk is less clear. [ABSTRACT FROM AUTHOR]

Carcinogenesis is a process of somatic evolution. Previous models of stem and transient amplifying cells in epithelial proliferating units like colonic crypts showed that intermediate numbers of stem cells in a crypt should optimally prevent progression to cancer. If a stem cell population is too small, it is easy for a mutator mutation to drift to fixation. If it is too large, it is easy for selection to drive cell fitness enhancing carcinogenic mutations to fixation. Here, we show that a multiscale microsimulation, that captures both within‐crypt and between‐crypt evolutionary dynamics, leads to a different conclusion. Epithelial tissues are metapopulations of crypts. We measured time to initiation of a neoplasm, implemented as inactivation of both alleles of a tumor suppressor gene. In our model, time to initiation is dependent on the spread of mutator clones in the crypts. The proportion of selectively beneficial and deleterious mutations in somatic cells is unknown and so was explored with a parameter. When the majority of non‐neutral mutations are deleterious, the fitness of mutator clones tends to decline. When crypts are maintained by few stem cells, intercrypt competition tends to remove crypts with fixed mutators. When there are many stem cells within a crypt, there is virtually no crypt turnover, but mutator clones are suppressed by within‐crypt competition. If the majority of non‐neutral mutations are beneficial to the clone, then these results are reversed and intermediate‐sized crypts provide the most protection against initiation. These results highlight the need to understand the dynamics of turnover and the mechanisms that control homeostasis, both at the level of stem cells within proliferative units and at the tissue level of competing proliferative units. Determining the distribution of fitness effects of somatic mutations will also be crucial to understanding the dynamics of tumor initiation and progression. [ABSTRACT FROM AUTHOR]

New Findings: Whatis the topic of this review?This review explores the modulatory role of lung vagal afferents and intra‐neuraxial and carotid body chemoreceptors upon hypoglossal pre‐inspiratory activity.What advances does it highlight?Pre‐inspiratory activity manifesting in hypoglossal neural efferent discharge may be potentiated by mechanical interruption of vagal continuity and challenge with administration of a hypoxic and/or hypercapnic gas mixture and attenuated by static and/or dynamic pulmonary stretch. Differential excitability of, or premotoneuronal volleys exhibiting distinct spatiotemporal patterns of discharge arriving at, motoneurons residing within the hypoglossal motor nucleus may emergently generate phase‐spanning pre‐inspiratory inspiratory activity of hypoglossal neural efferent discharge manifest at the population level. The hypoglossal nerve (XII) innervates muscles mediating excursive movements of the tongue. The population discharge of hypoglossalmotoneuronal axons constituting the hypoglossal nerve precedes and extends through the inspiratory epoch. The epoch subtended between the onsets of hypoglossal and phrenic neural discharge constitutes so‐called pre‐inspiration. Hypoglossal pre‐inspiratory neural discharge serendipitously displaces the tongue along a tensor reducing upper airway resistance anticipative of succeeding inspiratory efforts. Hypoglossal motoneurons exhibiting discharge onset during pre‐inspiration experience successive hyperpolarization of membrane voltage and attenuation of unitary spiking frequency, although a subset may, paradoxically and state‐dependently, exhibit depolarization of membrane voltage and augmentation of neuronal spiking frequency, by dynamic stretch placed upon the alveolar walls and interstitium. Marked static elevation of positive‐end expiratory pressure may induce hypoglossal bursting decoupled from phasic rhythmic phrenic discharge. Augmentation of the amplitude and/or duration of hypoglossal inspiratory discharge during successive pre‐inspiratory and inspiratory epochs by inhalation of a hypoxic and/or hypercapnic gas mixture remains restrained in the presence of intact vagal inputs and is potentiated by interruptions of vagal continuity. Unravelling the mechanisms underlying the genesis of pre‐inspiratory activity will inform our understanding of respiratory rhythm generation and pattern shaping. In the present work, I seek to explore the mechanisms underlying modulation of hypoglossal pre‐inspiratory discharge by hypercapnia, hypoxia and static and dynamic lung stretch placed upon hypoglossal pre‐inspiratory activity, the mechanisms underlying the generation of hypoglossal pre‐inspiratory activity, and the extent of microanatomical and functional overlap between propriobulbar interneuronal microcircuits generating hypoglossal pre‐inspiratory activity and propriobulbar interneuronal microcircuit oscillators generating pre‐inspiratory activity inaugurally inducing respiratory rhythmic activity and thus use experimental data from previous work and that developed by other investigators to explore the modulatory role of lung vagal afferents and intra‐neuraxial and carotid body chemoreceptors upon hypoglossal pre‐inspiratory activity. [ABSTRACT FROM AUTHOR]

Unsaturated lipids are prone to get oxidized through a sequence of reactions known as lipid oxidation. From a phenomenon considered at the beginning as a mere chemical process and described by the triptych of initiation, propagation, and termination, the vision of lipid oxidation has progressively evolved to further integrate the physical dimension of the phenomenon. Despite tremendous research efforts, however, this sequence of reactions is not yet well understood, especially in lipid dispersions where many facts are still inexplicable and unpredictable under the current paradigm. Here, the aim is to suggest that the main reason why a better understanding has not already been achieved is that the reactional network is not yet organized in a coherent spatiotemporal framework. The novel concepts and hypotheses proposed in this article may help redirecting a significant part of research efforts toward the establishment of a spatially and temporally resolved model of oxidation in dispersed lipids. Practical Application: Predicting how oxidation spreads in lipid dispersions represents a goal of crucial importance for academia but also for industry. Such prediction models would indeed greatly help food manufacturers prevent oxidation by using the most adapted antioxidative strategies for their specific products. To achieve such an objective, it is proposed that the first thing to do is to go beyond the extremely reductive and narrow framework in which this chemical process has been locked in. Indeed, while lipid dispersions are composed of a multitude of lipid colloids, researchers usually consider oxidation at the sole level of an individual droplet or membrane. Instead, lipid oxidation is advocated as a dynamic trafficking of chemical species within large communities of different colloidal objects such as droplets, membranes, or micelles dispersed in water—a system that dubbed "colloidal ecosystem". This might represent a scale complementary to the scales of individual colloids or molecules that were the sole consideration so far to try to represent lipid oxidation. Only then can one hope to effectively apply modeling and "omics" approaches, as is explained in more details in this article. [ABSTRACT FROM AUTHOR]

The influence of microstructural variation on the initiation of octahydro‐1,3,5,7‐tetranitro‐1,3,5,7‐tetrazocine (HMX) has been evaluated. These evaluations encompass two classes of fine‐grain HMX, Class 5 and Fluid Energy Milled (FEM). Initiation data of HMX using thick Polyimide flyers (203 μm) near the power flux (Πc) limiting condition (2.26 GPa to 4.63 GPa) as a function of density are presented. The initiation results depict decreasing threshold velocities as density decreases for both materials. The Class 5 has a lower threshold velocity value than the FEM at comparable density values. Microstructure evaluations based solely on the total specific interface area (SIA) are inconsistent with the initiation results. Further evaluation resulted in the requirement of calculating cumulative SIA as a function of feature size to match the trends observed in threshold behavior. The results support the concept of an activated hot spot size as a function of pressure as formulated by Khasainov et al. [1]. Analysis of the microstructure indicates the distinguishing features between Class 5 and FEM are the large particle size tails of the distributions. [ABSTRACT FROM AUTHOR]

All‐atom molecular dynamics (MD) and Eulerian continuum simulations, performed using the LAMMPS and SCIMITAR3D codes, respectively, were used to study thermo‐mechanical aspects of the shock‐induced collapse of an initially cylindrical 50 nm diameter pore in single crystals of 1,3,5‐triamino‐2,4,6‐trinitrobenzene (TATB). Three impact speeds, 0.5 km s−1, 1.0 km s−1 and 2.0 km s−1, were used to generate the shocks. These impact conditions are expected to yield collapse mechanisms ranging from predominantly visco‐plastic to hydrodynamic. For the MD studies, three crystal orientations (relative to shock‐propagation direction) were examined that span the limiting cases with respect to the crystalline anisotropy in TATB. An isotropic constitutive model was used for the continuum simulations, thus crystal anisotropy is absent. The evolution of spatiotemporally resolved quantities during collapse is reported including local pressure, temperature, pore size and shape, and material flow. Multiple models for the melting curve and specific heat were studied. Within the isotropic elastic/perfectly plastic continuum framework and for the range of impact conditions studied, the specific heat and melting curve sub‐models are shown to have modest effects on the continuum hotspot predictions in the present inert calculation. Treating the MD predictions as 'ground truth', albeit with a classical rather than quantum‐like heat capacity, it is clear that – at a minimum – an extension of the constitutive model to account for crystal plasticity and anisotropic strength will be required for a high‐fidelity continuum description. [ABSTRACT FROM AUTHOR]

Initiating antiretroviral therapy (ART) as early as the day of HIV diagnosis is a strategy of increasing global interest to control the HIV epidemic and optimize the health of people living with HIV (PLWH). No detrimental effects of rapid‐start ART have been identified in randomized controlled trials undertaken in low‐ or middle‐income countries, or in cohort studies performed in high‐income countries. Rapid‐start ART may be a key approach in reaching the 2020 Joint United Nations Programme on HIV/AIDS goal of 90% of all PLWH knowing their status, 90% of those diagnosed receiving sustained ART, and 90% of those receiving ART achieving viral suppression; it may also be important for achieving the suggested fourth "90%" goal: improving health‐related quality‐of‐life in PLWH. Presently there is insufficient broad evidence for guidelines to recommend universal test‐and‐treat strategies for all people, in all settings, at HIV diagnosis; consequently, there is a pressing need to conduct high‐quality studies that investigate immediate ART initiation. This article evaluates global evidence regarding rapid‐start ART, including same‐day start, with particular focus on the implementation of this strategy in high‐income countries. [ABSTRACT FROM AUTHOR]

Aim: A recent, growing concern regarding haemodialysis in Japan is a sustained increase in the elderly population. Among very elderly people who start haemodialysis, the prognosis is considered to be poor; however, this has not been fully elucidated. This study aimed to discover the short‐term prognosis and related factors in very elderly patients who commence haemodialysis. Methods: Between January 2008 and December 2013, 122 patients aged ≥85 years at haemodialysis initiation were documented in our hospital. Predictors of 90‐day and 1‐year mortality after haemodialysis initiation were assessed with Cox proportional hazards regression analysis. Selection of covariates for the multivariate model was based on forward stepwise selection using the probability of a likelihood ratio statistics. Results: The subjects' mean age was 87.4 ± 2.5 years, and 48% were female. The most common cause of death was infection (38% of patients) and the leading cause of infectious death was pneumonia. The 90‐day and 1‐year survival rates were 81% and 62%, respectively. Suboptimal initiation was a significant prognostic factor for 90‐day [hazard ratio (HR) 3.98, 95% confidence interval (CI) 1.18–13.43] and 1‐year [HR 3.19, 95% CI 1.51–6.76] mortality after adjusting for confounders in multivariate analysis. Conclusion: Very elderly patients who started haemodialysis had a poor prognosis, and suboptimal initiation significantly predicted outcome. Shared decision‐making with patients and their families is needed for initiating haemodialysis on the conditions that appropriate information on the expected prognosis is provided. Summary at a Glance: In very elderly patients commencing dialysis in Japan, 46 of 122 patients studied died over the next 12 months, 22 of these within 3 months. More than half started haemodialysis with a temporary catheter and this group, called 'suboptimal initiation', were notable for their poorer performance status and greater mortality risk. This manuscript raises important issues about the management of end‐stage kidney disease in the very elderly in Japan. [ABSTRACT FROM AUTHOR]

Abstract: A continuous supply of radical species is a key requirement for activating chain growth and accessing quantitative monomer conversions in reversible addition‐fragmentation chain transfer (RAFT) polymerization. In Fenton‐RAFT, activation is provided by hydroxyl radicals, whose indiscriminate reactivity and short‐lived nature poses a challenge to accessing extended polymerization times and quantitative monomer conversions. Here, an alternative Fenton‐RAFT procedure is presented, whereby radical generation can be finely controlled via metered dosing of a component of the Fenton redox reaction (H2O2) using an external pumping system. By limiting the instantaneous flux of radicals and ensuring sustained radical generation over tunable time periods, metered reagent addition reduces unwanted radical “wasting” reactions and provides access to consistent quantitative monomer conversions with high chain‐end fidelity. Fine tuning of radical concentration during polymerization is achieved simply via adjustment of reagent dose rate, offering significant potential for automation. This modular strategy holds promise for extending traditional RAFT initiation toward more tightly regulated radical concentration profiles and affords excellent prospects for the automation of Fenton‐RAFT polymerization. [ABSTRACT FROM AUTHOR]

Experimental results on pulsed dielectric barrier discharge (DBD) initiation stages in air are given in the present work. Pictures of discharge afterglow and current traces from a sectioned electrode were collected and analyzed. The qualitative model of volume nanosecond DBD formation based on combination of well‐known model of self‐sustained gas discharge development together with surface charge spreading from electroscopic data is proposed. Represented qualitative explanation of observed phenomena involve summarized conclusions from cross‐correlation spectroscopy researches, well‐known streamer theory, model of self‐sustained gas discharge development, and dielectric surface charge spreading behavior from electroscopic measurements. [ABSTRACT FROM AUTHOR]