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The reliability and durability of integrated circuits (ICs), present in almost every electronic system, from consumer electronics to the automotive or aerospace industries, have been and will continue to be critical concerns for IC chip makers, especially in scaled nanometer technologies. In this context, ICs are expected to deliver optimal performance and reliability throughout their projected lifetime. However, real-time reliability assessment and remaining lifetime projections during in-field IC operation remain unknown due to the absence of trustworthy on-chip reliability monitors. The integration of such on-chip monitors has recently gained significant importance because they can provide real-time IC reliability extraction by exploiting the fundamental physics of two of the major reliability degradation phenomena: bias temperature instability (BTI) and hot carrier degradation (HCD). In this work, we present an extensive study of ring oscillator (RO)-based degradation and annealing monitors designed on our latest 28 nm versatile array chip. This test vehicle, along with a dedicated test setup, enabled the reliable statistical characterization of BTI- and HCD-stressed as well as annealed RO monitor circuits. The versatility of the test vehicle presented in this work permits the execution of accelerated degradation tests together with annealing experiments conducted on RO-based reliability monitor circuits. From these experiments, we have constructed precise annealing maps that provide detailed insights into the annealing behavior of our monitors as a function of temperature and time, ultimately revealing the usage history of the IC.

We develop a compact physics model for hot-carrier degradation (HCD) that is valid over a wide range of gate and drain voltages (Vgs and Vds, respectively). Special attention is paid to the contribution of secondary carriers (generated by impact ionization) to HCD, which was shown to be significant under stress conditions with low Vgs and relatively high Vds. Implementation of this contribution is based on refined modeling of carrier transport for both primary and secondary carriers. To validate the model, we employ foundry-quality n-channel transistors and a broad range of stress voltages {Vgs,Vds}.

Liquid metal polymer composites (LMPCs) are formed by dispersing eutectic gallium-indium-tin (galinstan) droplets within a soft polymer matrix, such as polydimethylsiloxane (PDMS), resulting in an insulating composite that is suitable for dielectric applications, including wearable sensors and actuators. LMPCs offer a unique combination of robust mechanical performance and desirable electrical properties. While much research has focused on the effects of rigid fillers in polymer composites, the behavior of liquid metal fillers, particularly the impact of homogeneity, has received limited attention. The density disparity between galinstan and the polymer matrix (6.44 g cm -3 compared to 0.97 g cm -3 ) results in the settling of galinstan droplets before curing, especially in matrices with low viscosity, leading to an inhomogeneous composition that may affect material performance. To address this, an innovative approach was introduced that enabled a spatially uniform (homogeneous) dispersion of galinstan droplets in PDMS while preserving the non-conductive nature of the composites. Work described herein evaluates the influence of homogeneity on electrical and mechanical properties as well as performance of LMPCs as pressure sensors. It was found that homogeneity has minimal effect on permittivity and dielectric loss but exhibits a complex behavior with respect to other parameters, including dielectric strength, which is often exacerbated at higher concentrations (≥50 vol%). These findings provide valuable insight that contributes to improved control over the material properties of LMPCs and expands their potential applications in soft robotics and stretchable electronics.

Efficient encapsulation and sustained release of small hydrophilic molecules from traditional hydrogel systems have been challenging due to the large mesh size of 3D networks and high water content. Furthermore, the encapsulated molecules are prone to early release from the hydrogel prior to use, resulting in a short shelf life of the formulation. Here, we present a hydration-induced void-containing hydrogel (HVH) based on hyperbranched polyglycerol-poly(propylene oxide)-hyperbranched polyglycerol (HPG-PPG-HPG) as a robust and efficient delivery system for small hydrophilic molecules. Specifically, after the HPG-PPG-HPG is incubated overnight at 4 °C in the drug solution, it is hydrated into a hydrogel containing micron-sized voids, which could encapsulate hydrophilic drugs and achieve 100% drug encapsulation efficiency. In addition, the voids are surrounded by a densely packed polymer matrix, which restricts drug transport to achieve sustained drug release. The hydrogel/drug formulation can be stored for several months without changing the drug encapsulation and release properties. HVH hydrogels are injectable due to shear thinning properties. In rats, a single injection of the HPG-PPG-HPG hydrogel containing 8 μg of tetrodotoxin (TTX) produced sciatic nerve block lasting up to 10 hours without any TTX-related systemic toxicity nor local toxicity to nerves and muscles., Competing Interests: Conflict of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. U.W. reports research grants from the US National Institutes of Health. She serves on the External Consultant Board for the “NIH Preclinical Screening Platform for Pain”, a novel pre-clinical pain therapy screening platform that has been launched at the National Institute for Neurological Disorders and Stroke in the U.S. In her capacity as a special government employee of the US Food and Drug Administration (FDA), she has served as a voting member of the FDA Anesthetic and Analgesic Drug Products Advisory Committee. In the past 3 years she has received compensation for serving on advisory boards or for consulting activities for Aphrodite Health Inc., Wilmington, DE, Avenue Therapeutics Inc., New York, NY, Bayer Aktiengesellschaft, Leverkusen, Germany, and Biohaven Pharmaceuticals, New Haven, CT, all unrelated to the submitted work

The COVID-19 pandemic raised concerns about the potential for co-infection or over-infection with other respiratory infections, as they can complicate the diagnosis, treatment and prognosis of the disease. This is also a challenge for forensic pathologists, who may come across cases where the presence of co-infection or over-infection is suspected or confirmed, and it is important that they take this into account when determining the cause of death. The aim of this systematic review is to analyse the prevalence of each specific pathogen co-infecting or over-infecting patients with SARS-CoV-2 infection. In total, 575 studies were selected from the Scopus and Pub-Med online databases and 8 studies were included in a meta-analysis. Male gender, advanced age and nursing home care are risk factors associated with the development of co-infection, whereas age, tachypnoea, hypoxaemia and bacterial infection are predictors of mortality. Overall, however, having a SARS-CoV-2 infection does not represent a real risk for the development of co-infections/super-infections.

The research on substance use disorders is ongoing in the quest to find anti-addiction vaccines to treat drug abuse. This article provides a systematic review of clinical trials that have been conducted on humans to evaluate the efficacy, safety, and abstinence rates of anti-addiction vaccines for different drugs, with useful results regarding cocaine and nicotine vaccines in particular; this study includes also a meta-analysis to establish the antibody-titer production following the nicotine vaccination, while a meta-analysis of cocaine vaccines was not performed due to the small number of included trials. The articles taken into consideration were published between 2002 and 2015, including searches through 2022. Overall, 13 articles were selected with 2,266 participants from different ethnic groups. The meta-analysis of nicotine vaccines showed that vaccinated groups were 50 times more likely to create specific antibodies compared to the non-vaccinated. These results demonstrated how the nicotine vaccine has good immunogenicity.

This study aimed to investigate the detection of morphine in fingernails from forensic autopsies using immunohistochemistry (IHC), with confirmation by ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS). A primary antibody specific to morphine and a secondary antibody conjugated to horseradish peroxidase (HRP) was used. IHC on specimens of Subjects A and B (both drug addicts) resulted in the detection of morphine on a cell layer of the nail plate matrix. UHPLC-HRMS and GC-MS analysis showed that Subject A had a morphine concentration of 0.35 ng/mg in the fingernail and 472 ng/mL in the blood, while Subject B reached 1.23 ng/mg in the fingernail and 360 ng/ml in the blood. Most of those matrices were positive for codeine, methadone, EDDP, and 6-MAM. The use of IHC in Subject C (a former addict) showed no positivity for morphine in the fingernail, while the UHPLC-HRMS analysis confirmed its absence in the fingernail and blood. Additionally, an analysis of the scalp or pubic hair of the subjects was carried out using UHPLC-HRMS. The results suggest that IHC can be used to establish the site of accumulation of morphine in the nail matrix; for postmortem diagnosis; and that basic substances can be detected by UHPLC-HRMS. There are no previous studies on the use of IHC as a technique for forensic purposes in unconventional matrices, such as nails.

Traditional electronic devices are composed of rigid materials and components that tend to be unsuitable for soft robotic and stretchable electronic applications, such as wearable or continuous pressure sensing. However, deformable materials have the potential to improve upon traditional devices through enhanced sensitivity and responsiveness, better conformability and biocompatibility at the human-machine interface, and greater durability. This work presents deformable composite materials composed of the gallium-indium-tin alloy galinstan (GaInSn) that combines the conductivity of a metal and the intrinsic deformability of a liquid. Dispersing galinstan in an elastomer allows for the formation of deformable dielectric materials that have tunable mechanical and electrical behavior, for example, modulus and relative permittivity. Galinstan composites have been shown previously to have a minimal modulus impact on the elastomer but concurrently achieve impressive dielectric performance. However, galinstan dispersions can be costly and face challenges of mechanical and electrical reliability. Thereby, this work investigates multimaterial composites composed of galinstan and a rigid filler, either iron or barium titanate, with respect to morphology, mechanical behavior, dielectric behavior, and pressure sensing performance for the purpose of achieving a balance between a low modulus and superior electrical performance. By combining galinstan and rigid fillers, it was found that the mechanical and electrical properties, such as modulus, permittivity, loss behavior, sensitivity, and linearity of the multimaterial composites can be improved by tuning filler formulation. This suggests that these dielectric materials can be used for sensing applications that can be precisely calibrated to specific material properties and the needs of the user. These deformable multimaterial composites, found to be stretchable and highly responsive in sensing applications, will expand the current mechanical abilities of deformable dielectric materials to improve soft robotic and stretchable electronic devices.

Polydrug use is a frequent pattern of consumption in Europe. This behavior has mainly been analyzed within restricted groups; more rarely in large populations. Current polydrug use is less studied than simultaneous use. This study focused on the concurrent assumption of polydrug among drivers using hair matrix. Hair matrix, for its biological characteristics, allows to identify illicit drug use more often than other matrices, i.e., urine, and it provides information on the long-term use of them. Hair samples of subjects positive for opiates, cocaine and delta-9-tetrahydrocannabinol (Δ 9 -THC) collected by the forensic toxicology laboratory of the University of Macerata in the period 2010-2020, were analyzed using a gas chromatography-mass spectrometry method. Our results evidenced that a significant part of the examined population (12.15%) used polydrug. A strong predominance of males over females was evident. Polydrug users were more frequently young people. The abuse of two substances was predominant. Cocaine and Δ 9 -THC was the most common combination, followed by cocaine and morphine, and morphine and Δ 9 -THC. The timeframe of polydrug use was also analyzed. Our study shows that polydrug use is a very frequent behavior, and that hair analysis may be a powerful tool to obtain objective biological information of this complex phenomenon.

We identify correlation between the drain currents in pristine n-channel FinFET transistors and changes in time-0 currents induced by hot-carrier stress. To achieve this goal, we employ our statistical simulation model for hot-carrier degradation (HCD), which considers the effect of random dopants (RDs) on HCD. For this analysis we generate a set of 200 device instantiations where each of them has its own unique configuration of RDs. For all "samples" in this ensemble we calculate time-0 currents (i.e. currents in undamaged FinFETs) and then degradation characteristics such as changes in the linear drain current and device lifetimes. The robust correlation analysis allows us to identify correlation between transistor lifetimes and drain currents in unstressed devices, which implies that FinFETs with initially higher currents degrade faster, i.e. have more prominent linear drain current changes and shorter lifetimes. Another important result is that although at stress conditions the distribution of drain currents becomes wider with stress time, in the operating regime drain current variability diminishes. Finally, we show that if random traps are also taken into account, all the obtained trends remain the same.

Well documented, persistent racial/ethnic health disparities in obesity and hypertension in the US demonstrate the continued need for interventions that focus on people of color who may be at higher risk. We evaluated a demonstration project funded by the CDC's Racial/Ethnic Approaches to Community Health (REACH) program at four federally qualified health centers (FQHC) and YMCA fitness and wellness centers in Boston. No-cost YMCA memberships were offered from June 2014 to June 2015 to non-Latino black and Latino adults with a diagnosis of hypertension. YMCA visit data were merged with health data for 224 participants ( n  = 1265 health center visits). We assessed associations between gym visit frequency and weight, body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP) using longitudinal time-varying linear fixed-effects models. The total number of gym visits over the entire program duration was 5.5, while the conditional total number of visits (after the first gym visit has been made) was 17.3. Having visited the gym at least 10 times before an FQHC exam was, on average, associated with lower weight (1.19 kg, p  = 0.01), lower BMI (0.43 kg/m 2 , p  = 0.01) and reductions in SBP (-3.20 mm Hg, p  = 0.01) and DBP (-2.06 mm Hg p  = 0.01). Having visited the gym an average of 1.4 times per month (study average) was associated with reductions in weight, BMI, and DBP. No-cost gym visits were associated with improved weight and blood pressure in hypertensive non-Latino black and Latino adults in this program. Additional evaluation is necessary to assess the sustainability of these effects.

The 'Nursing the Acute Medical Patient' level 8 continuing professional development (CPD) programme was developed to support the learning needs of staff nurses within an acute medical unit (AMU) in an Irish academic teaching hospital. Within this recently-established AMU, the nursing team was challenged by the complexity of clinical presentations. At the outset of the programme, over half of nurses employed in the AMU had less than 5 years' clinical experience. The 6-month CPD programme was developed collaboratively by the registered nurse tutor, advanced nurse practitioner candidate (trainee) in acute medicine and the clinical facilitator. The programme was accredited by University College Dublin, and awarded 10 European Credit Transfer System credits. Clinical competency assessment had to be completed in order to pass the programme and was facilitated by the development of the Comprehensive Clinical Learning Objective Performance Evaluation (CLOPE) document. The programme was positively evaluated by students and the wider multidisciplinary team. It has made a significant contribution to both staff development and the delivery of evidence-based care in the AMU.

Although endophytes of conifers have been extensively studied, few data are available on Cephalotaxaceae. We examined foliar and stem endophytes of Cephalotaxus harringtonia, within its natural range in Japan and outside its natural range in France to study the effect of geography on endophyte community composition. In Japan, rapidly growing endophytes were dominant and may have masked the real diversity, in comparison to France where most endophytes were growing slowly. Analyses of ITS rDNA revealed 104 different Blast Groups among 554 isolates. Almost no overlap between endophyte assemblages of C. harringtonia from the two countries was observed. It seems that Japanese C. harringtonia trees, which should be well adapted to their native site, would host a specific, endemic endophyte community, while trees that have been introduced recently to a foreign site, in France, should have captured existing cosmopolitan and more generalist taxa. In Japan the majority of xylariaceous taxa, which dominated the communities, were unknown and, although closely related to Asian taxa, may be new to science. Dothideomycetes were more prevalent in France. Locally, urban environment, particularly in Japan, may have introduced some perturbations in the native endophyte community of C. harringtonia, with an abundance of generalist fungi such as Nigrospora and Colletotrichum., (Copyright © 2013 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.)

Empfindlicher im Dunkelroten Licht 1 (EID1) is an F-box protein that functions as a negative regulator in phytochrome A (phyA)-specific light signalling. F-box proteins are components of SCF ubiquitin ligase complexes that target proteins for degradation in the proteasome. Here we present further characterization of EID1 at the expression level, and show that it regulates photomorphogenesis in seedlings, rosette leaf development and flowering. Data on transcript expression patterns indicate that EID1 is expressed during all stages of Arabidopsis development and exhibits no light response. Microscope studies demonstrate that EID1 is localized to the nucleus, where it can form speckles under continuous far-red light that resemble clastosomes. To characterize the composition and formation of SCF(EID1) complexes further, we used two-hybrid and bridge assays in yeast and in planta. EID1 interacts specifically with several Arabidopsis Skp1-like (ASK) proteins and Cullin1 to form stable dimeric and trimeric complexes. Our results support a two-step association process in which the F-box protein binds first to the ASK adaptor, forming a unit which then associates with the catalytic core of the SCF complex. Finally, our data indicate that the EID1 target interaction domain is composed of two independent modules.

The phytochrome family of red/far-red (R/FR)-responsive photoreceptors plays a key role throughout the life cycle of plants . Arabidopsis has five phytochromes, phyA-phyE, among which phyA and phyB play the most predominant functions . Light-regulated nuclear accumulation of the phytochromes is an important regulatory step of this pathway, but to this date no factor specifically required for this event has been identified . Among all phyA signaling mutants, fhy1 and fhy3 (far-red elongated hypocotyl 1 and 3) have the most severe hyposensitive phenotype, indicating that they play particularly important roles . FHY1 is a small plant-specific protein of unknown function localized both in the nucleus and the cytoplasm . Here we show that FHY1 is specifically required for the light-regulated nuclear accumulation of phyA but not phyB. Moreover, phyA accumulation is only slightly affected in fhy3, indicating that the diminished nuclear accumulation of phyA observed in fhy1 seedlings is not simply a general consequence of reduced phyA signaling. By in vitro pull-down and yeast two-hybrid analyses, we demonstrate that FHY1 physically interacts with phyA, preferentially in its active Pfr form. Furthermore, FHY1 and phyA colocalize in planta. We therefore identify the first component required for light-regulated phytochrome nuclear accumulation.

Screening of aerobic culturable hydrocarbon (HC)-degrading microorganisms isolated from petroleum-polluted soils and cyanobacterial mats from Indonesia resulted in the collection of 33 distinct species. Eight bacteria, 21 fungi and 4 yeasts were identified to the specific level by molecular and phenotypic techniques. Bacterial strains belonged to the genera Gordonia, Brevibacterium, Aeromicrobium, Dietzia, Burkholderia and Mycobacterium. Four species are new and not yet described. Fungi belonged to Aspergillus, Penicillium, Fusarium, Amorphoteca, Neosartorya, Paecilomyces, Talaromyces and Graphium. Yeasts were Candida, Yarrowia and Pichia. All strains were cultivated axenically in synthetic liquid media with crude oil as sole carbon and energy source. After incubation, the detailed chemical composition of the residual oil was studied by gravimetric and gas-chromatographic techniques. Thirteen parameters for assessing the biodegradation potential were defined and computed for each strain. Maximum degradation was observed on the saturated HCs (n- and isoalkanes, isoprenoids), whereas aromatic HC degradation was lower and was related to the structural composition of the molecules. A principal components analysis (PCA) permitted grouping and classifying the strains as a function of their degradative capacities. It was shown that the most active strains produced polar metabolites which accumulated in the resins and asphaltene fractions. These fractions are highly resistant to microbial metabolism. No taxonomic trend could be defined between microbial phyla in terms of HC biodegradation activity.

Photomorphogenesis of higher plants is regulated by photoreceptors including the red/far-red light-absorbing phytochromes, blue-UV/A sensing cryptochromes and as yet uncharacterized UV/B receptors. Specific phototransduction pathways that are controlled by either individual or interacting photoreceptors mediate regulation. Phytochrome B (phyB) is the major red light-sensing photoreceptor. Phototransduction mediated by this light sensor has been shown to include light-dependent nuclear import and interaction of phyB with transcription factor-like proteins in the nucleus. Here we report that nuclear import of phyB and physiological responses regulated by this photoreceptor exhibit very similar wavelength- and fluence rate-dependence. Nuclear import of phyB is insensitive to single red, blue and far-red light pulses. It is induced by continuous red light and to a lesser extent by continuous blue light, whereas far-red light is completely ineffective. The data presented indicate that light-dependent partitioning of phyB exhibits features characteristic of blue light responsiveness amplification, a phenomenon that is thought to be mediated by interaction of phyB with CRY1.

Strains of hydrocarbon-degrading microorganisms (bacteria and fungi) were isolated from an agricultural soil in France. In a field, a portion was treated with oily cuttings resulting from the drilling of an onshore well. The cuttings which were spread at the rate of 600 g HC m-2 contained 10% of fuel oil hydrocarbons (HC). Another part of the field was left untreated. Three months after HC spreading, HC adapted bacteria and fungi were isolated at different soil depths in the two plots and identified. The biodegradation potential of the isolated strains was monitored by measuring the degradation rate of total HC, saturated hydrocarbons, aromatic hydrocarbons and resins of the fuel. Bacteria of the genera Pseudomonas, Brevundimonas Sphingomonas, Acinetobacter, Rhodococcus, Arthrobacter, Corynebacterium and fungi belonging to Aspergillus, Penicillium, Beauveria, Acremonium, Cladosporium, Fusarium, and Trichoderma were identified. The most active strains in the assimilation of saturates and aromatics were Arthrobacter sp., Sphingomonas spiritivorum, Acinetobacter baumanii, Beauveria alba and Penicillum simplicissimum. The biodegradation potential of the hydrocarbon utilizing microorganisms isolated from polluted or unpolluted soils were similar. In laboratory pure cultures, saturated HC were more degraded than aromatic HC, whereas resins were resistant to microbial attack. On an average, individual bacterial strains were more active than fungi in HC biodegradation.

Obliteration of the fat plane surrounding the superior mesenteric artery has been described as characteristic of pancreatic carcinoma. To determine the specificity of this and other computed tomography findings in the pancreas and peripancreatic region, scans of 86 patients were reviewed without clinical history. Diagnoses included pancreatitis (26 patients); pancreatic adenocarcinoma (14 patients); lymphoma (17 patients); metastatic nonpancreatic carcinoma (14 patients); and normal findings (15 patients). Confluent adenopathy could not be reliably differentiated from a pancreatic mass except when adenopathy separated the common bile duct from the duodenum. Retrocrural adenopathy was unusual with pancreatic carcinoma. The fat plane surrounding the superior mesenteric artery was obliterated with pancreatic carcinoma (36%), nonpancreatic carcinoma (29%), and lymphoma (24%), but not with pancreatitis, although perivascular edema was seen in 19%. Evaluation of the celiac axis was less rewarding. Obliteration of the superior mesenteric artery fat plane is a sign of malignancy, but it is not specific for pancreatic carcinoma. We propose that the superior mesenteric artery origin be considered within a paraaortic space, separate from the anterior pararenal space. This explains its characteristic lack of involvement by pancreatitis.