Search

Quinolines are ubiquitous heterocyclic aromatic scaffolds, which can be found in many natural and synthetic products. They are highly valued for their pharmacological and electrochemical properties, encouraging the discovery of new routes for quinoline synthesis and diversification. In particular, polyaryl‐substituted quinolines have recently surged as useful substrates for a wide variety of applications, yet their synthetic routes remain difficult and inefficient. Herein, we report a rapid and novel mechanochemical Friedländer synthesis of polyaryl‐substituted quinolines under basic conditions using ball milling. The optimized reaction conditions resulted in moderate to excellent yields ranging from 48% to >95% and demonstrated broad functional group tolerance at 1 hour reaction times. We further show a new route for the synthesis of photocatalyst DPQN2,4−di−OMe and photo‐ligand PPQN2,4−di−OMe as well as OLED donor‐acceptor pCzPPQ, electron transport material oligoquinoline TQB and organic semiconductor DPA. A gram scale reaction was also achieved using Resonant Acoustic Mixing (RAM), providing an isolated yield of 87% after a simple recrystallization in ethanol. [ABSTRACT FROM AUTHOR]

A mechanochemical‐enabled Ru‐catalyzed regioselective synthesis of 3,4‐isoxazoles and 3,4,5‐isoxazoles from terminal and internal alkynes and hydroxyimidoyl chlorides is reported. This solid‐state and solvent‐free approach carefully examines the impact of the milling conditions on regiocontrol in 1,3‐dipolar cycloadditions using mechanochemical means. The study reveals that milling frequency, jar material, and the choice of liquid additive for liquid‐assisted grinding (LAG) significantly influence the catalytic activity of the Ru catalyst. Transmission electron microscope (TEM) analysis confirms the crucial role of coordinating liquid additives such as acetone and cyclopentyl methyl ether (CPME) in stabilizing and reducing the size of the in‐situ formed Ru nanoparticles, which is essential for catalytic activity. The applicability of this protocol is further demonstrated through the synthesis of a library of 3,4‐ and 3,4,5‐isoxazoles from a wide range of terminal and internal alkynes with varying physical states and electronic properties that highlights the potential of this method for the synthesis of more complex target molecules. [ABSTRACT FROM AUTHOR]

This study surveyed South Australian medical oncologists to capture their perceptions, willingness to participate and perceived barriers and motivations to participation in voluntary assisted dying (VAD) activities. Approximately 70% of surveyed medical oncologists reported familiarity with VAD legislation. Less than half of physicians (39.1%) reported willingness to participate in any VAD activities, and the rate of conscientious objection was 22%. The top barriers to participation were lack of time and uncertainty given no prior experience. These results demonstrate both a low rate of conscientious objection and a low rate of willingness to participate at the point of VAD implementation in South Australia, and identify barriers to participation that are largely logistical. [ABSTRACT FROM AUTHOR]

Molecular p‐dopants designed to undergo electron transfer with organic semiconductors are typically planar molecules with high electron affinity. However, their planarity can promote the formation of ground‐state charge transfer complexes with the semiconductor host and results in fractional instead of integer charge transfer, which is highly detrimental to doping efficiency. Here, we show this process can be readily overcome by targeted dopant design exploiting steric hindrance. To this end, we synthesize and characterize the remarkably stable p‐dopant 2,2′,2′′‐(cyclopropane‐1,2,3‐triylidene)tris(2‐(perfluorophenyl)acetonitrile) comprising pendant functional groups that sterically shield its central core while retaining high electron affinity. Finally, we demonstrate it outperforms a planar dopant of identical electron affinity and increases the thin film conductivity by up to an order of magnitude. We believe exploiting steric hindrance represents a promising design strategy towards molecular dopants of enhanced doping efficiency. [ABSTRACT FROM AUTHOR]

A mechanochemical desymmetrization of symmetrical bis‐ and tris‐alkynes by a controlled 1,3‐dipolar cycloaddition reaction using nitrile oxide dipoles (NOs). This operationally simple protocol allows access to 3,5‐isoxazole‐alkyne adducts from easily prepared or commercially available symmetrical bis‐ and tris‐alkynes in moderate to excellent yields. In addition, we have highlighted the synthetic utility of 3,5‐isoxazole‐alkyne by developing a route to access, for the first time, β‐ketoenamine‐alkyne derivatives, and unsymmetrical bis‐3,5‐isoxazoles. [ABSTRACT FROM AUTHOR]

This study examines the determinants of cooperative banks' diversification proclivity, with consideration of the spatial dependence effect. The empirical analysis demonstrates that Italian cooperative banks operate as a network with significant spillover effects that should not be ignored. Indeed, local banks compete in the same market segment, and any shift in their diversification strategy has a cascading effect on neighbouring cooperative banks as a result of customer migration. Finally, we observe that an increase in bank market power results in a decline in local bank lending activity. [ABSTRACT FROM AUTHOR]

Aim: Anthropogenic environmental modifications such as climate or land‐use change are causing species to move on their own beyond their native ranges. As this phenomenon will increase in the near future, it is crucial to determine whether range‐expanding species, or neonatives, are more or less likely than native and alien species to impact their recipient ecosystems. Here, we compared impact magnitudes of bark beetle species from their native, neonative and alien ranges, simultaneously. Location: Global. Methods: We formulated four general scenarios about the magnitude of environmental impacts in different ranges (native, neonative and alien) based on hypotheses commonly used in invasion biology. We tested these scenarios globally on Dendroctonus bark beetles, asking whether they have the most harmful impacts in their native, neonative or alien ranges. Impacts reported in the literature were assessed with the IUCN Environmental Impact Classification for Alien Taxa (EICAT). Results: We found that bark beetles cause the most harmful impacts in their native ranges, followed by the neonative ranges, while impacts in their alien ranges are the lowest. This indicates that the more dissimilar the environment is from that in the native range, the lower the probability of high‐impact magnitudes. Our results align with several non‐exclusive hypotheses, e.g. pre‐adaptation and habitat filtering, while they do not support others, e.g. enemy release or Darwin's naturalization. The results are also in contrast with previous studies on vertebrates and plants, which found no or mixed differences in impact magnitudes with biogeographic origin. Main conclusions: Our analysis suggests that bark beetles, like other species that are keystone and abundant in their native ranges, have generally lower impacts when introduced to novel environments due to biotic resistance or lack of pre‐adaptation. Research and management implications regarding the impacts of neonative and alien populations are also discussed. [ABSTRACT FROM AUTHOR]

This Review summarizes recent efforts to capitalize on 5‐hydroxymethylfurfural (HMF) and related furans as emerging building blocks for the synthesis of fine chemicals and materials, with a focus on advanced applications within medicinal and polymer chemistry, as well as nanomaterials. As with all chemical industries, these fields have historically relied heavily on petroleum‐derived starting materials, an unsustainable and polluting feedstock. Encouragingly, the emergent chemical versatility of biomass‐derived furans has been shown to facilitate derivatization towards valuable targets. Continued work on the synthetic manipulation of HMF, and related derivatives, for access to a wide range of target compounds and materials is crucial for further development. Increasingly, biomass‐derived furans are being utilized for a wide range of chemical applications, the continuation of which is paramount to accelerate the paradigm shift towards a sustainable chemical industry. [ABSTRACT FROM AUTHOR]

Human activities have caused massive losses of natural populations across the globe. Like many groups, amphibians have experienced substantial declines worldwide, driven by environmental changes such as habitat conversion, pollution, and disease emergence. Each of these drivers is often found in close association with the presence of roads.Here we report a novel consequence of roads affecting an amphibian native to much of North America, the wood frog (Rana sylvatica). Across 38 populations distributed from southern to central New England, we found that adult wood frogs living adjacent to roads had higher incidence and severity of oedema (indicated by obvious bloating caused by subcutaneous fluid accumulation) during the breeding season than frogs living away from the influence of roads. This effect was best explained by increased conductivity of breeding ponds, probably caused by runoff pollution from road salt used for de‐icing. Oedema severity was negatively correlated with locomotor performance in more northerly populations.Interestingly, northern populations experience more intense winters, which tends to result in more de‐icing salt runoff and increased energetic demands associated with overwintering cryoprotection needs. Thus, this emerging consequence of roads appears to impose potential fitness costs associated with locomotion, and these effects might be most impactful on populations living in regions where de‐icing is most intense.Together, our findings reveal a novel set of impacts of roads and runoff pollution on wood frog physiology and performance, which seem likely to contribute to population decline. Given the global prevalence of roads and increasing salinisation of freshwater habitats, oedema and related impacts could be widespread consequences faced by amphibian populations across much of the planet's temperate zones. [ABSTRACT FROM AUTHOR]

A new synthetic route utilizing biomass‐derived furans as a starting material for the production of bis(5‐arylfuran‐2‐yl)methane scaffolds was developed. Decarboxylative cross‐coupling of 5‐hydroxymethylfuroic acid (HMFA) was studied in detail with overall good yields. Acid‐catalyzed self‐condensation was optimized to produce the target structures in excellent yields. Overall, this report introduces a new expedient synthesis to obtain bis(furyl) methane scaffolds that avoids the use of protecting groups and highlights the utilization of renewable carbon sources as starting materials. [ABSTRACT FROM AUTHOR]

In this article we consider the effects of the inclusion of spatial dependence in the empirical model measuring small cooperative banks' risk performance. In the presence of cross‐sectional dependence, spatial analysis deals with co‐movement among geographical units, allowing for the evaluation of spillover effects and improving econometric models. The article makes several contributions to the literature. First, we support the hypothesis that the inclusion of spatial terms improves small bank soundness models. Second, with the Z Score used as a proxy for bank soundness, we indirectly test the impacts of relationship lending on small firms, which is a classic tool adopted by small banks to assess the creditworthiness of small firms. Third, since we control for banks' market power, we expand the literature on the relationship between bank risk and market competitive pressure. Finally, we find empirical evidence that bank size does affect the financial standing of small banks. [ABSTRACT FROM AUTHOR]

Physical activity is an important factor for primary and secondary stroke prevention. The process of stroke rehabilitation includes early and late physical activity and exercise, which prevents further stoke and improve patients' quality of life. MY WAY project, an ERASMUS+ SPORT program, is aimed at analyzing and developing or transferring best innovative practices related to physical activity and exercise enhancing health in poststroke patients. The aim of the study was to identify, analyze, and present the good practices and strategies to encourage participation in sport and physical activity and engage and motivate chronic stroke patients to perform physical activity changing their lifestyle and to maintain a high adherence to long-term exercise-based rehabilitation programs. Our results demonstrated that unified European stroke long-term exercise-based rehabilitation guidelines do not exist. It seems that low training frequency with high aerobic exercise intensity may be optimal for improved physical performance and quality of life in combination with a high adherence. It is important to optimize the training protocols suitable for each patient. The continuous education and training of the specialized professionals in this field and the presence of adequate structures and cooperation between different healthcare centers are important contributors. The clear objective for each country should be to systematically make the necessary steps to enhance overall exercise-based stroke rehabilitation attendance in the long term. Long-term interventions to support the importance of physical exercise and lifelong exercise-based rehabilitation in chronic stroke patients should be created, what coincides with the goal of the MY WAY project. [ABSTRACT FROM AUTHOR]

We examine the lowballing fee strategy of industry specialist auditors and their related audit quality, for engagements with affiliated business groups (ABGs) in Taiwan. Taiwanese auditors must sign their audit reports. This enables us to identify specialist audit engagement partners and examine their association with fee strategies and audit quality for specific clients. ABGs are generally large and complex and have extensive related‐party transactions. This elevates the levels of audit risk and audit effort and suggests a need for higher fees. Industry specialist auditors generally do not need to lower their fees to compete for clients. Yet, for new ABG clients, we find they are associated with lowballing, especially for ABGs with high business‐relatedness. We do not find evidence of lower audit quality for these new ABG clients. We thus conclude that industry specialist auditors evidently anticipate higher future value from increasing their market share among certain ABG clients. [ABSTRACT FROM AUTHOR]

Aim: A link has been established between malnutrition, immunological status, and hepatocellular carcinoma (HCC). The prognostic nutritional index (PNI) has been recognized as a prognostic indicator in early‐stage HCC and in patients treated with first‐line therapy. However, to date, the role of the PNI in HCC patients treated with regorafenib has not been reported. Methods: We undertook a multicentric analysis on a cohort of 284 patients affected by advanced HCC treated with regorafenib. The PNI was calculated as follows: 10 × serum albumin concentration (g/dl) + 0.005 × peripheral lymphocyte count (number/mm3). Univariate and multivariate analyses were used to investigate the association between PNI and survival outcomes. Results: A PNI cut‐off value of 44.45 was calculated by a receiver operating characteristic analysis. The median overall survival was 12.8 and 7.8 months for patients with high (>44.45) and low (≤44.45) PNI, respectively (hazard ratio, 0.58; 95% confidence interval, 0.43–0.77; p = 0.0002). In the univariate and multivariate analyses, low PNI value and increased serum bilirubin level emerged as independent prognostic factors for overall survival. No differences were found between high and low PNI in terms of progression‐free survival (p = 0.14). Conclusion: If validated, the PNI could represent an easy‐to‐use prognostic tool able to guide the clinical decision‐making process in HCC patients treated with regorafenib. [ABSTRACT FROM AUTHOR]

Summary: This article introduces a network architecture, called dynoNet, utilizing linear dynamical operators as elementary building blocks. Owing to the dynamical nature of these blocks, dynoNet networks are tailored for sequence modeling and system identification purposes. The back‐propagation behavior of the linear dynamical operator with respect to both its parameters and its input sequence is defined. This enables end‐to‐end training of structured networks containing linear dynamical operators and other differentiable units, exploiting existing deep learning software. Examples show the effectiveness of the proposed approach on well‐known system identification benchmarks. [ABSTRACT FROM AUTHOR]

We evaluated the effect of phytic acid on matrix metalloproteinase (MMP)‐ or cysteine cathepsin (CC)‐mediated dentin degradation. Demineralized dentin beams were divided into five groups (n = 12) and treated with 1%, 2%, or 3% phytic acid or with 37% phosphoric acid. Untreated demineralized beams served as controls. After incubation for 1 or 3 wk, dry mass loss was determined and aliquots of incubation media were analysed for cross‐linked telopeptide of type I collagen (ICTP) fragments for MMP‐mediated and c‐terminal telopeptide of type I collagen (CTX) for cathepsin‐k‐mediated degradation. The direct effect of phytic acid was evaluated using MMP activity assay. Data were analysed using repeated‐measures anova. ICTP releases with 1% and 2% phytic acid treatment were statistically significantly lower than those following phosphoric acid treatment at 3 wk. The CTX release for phytic acid‐treated beams at 3 wk was not significantly different from that of untreated control beams, but it was significantly lower than that of phosphoric acid‐treated beams. Their MMP activities at 3 wk were not significantly different from those of the controls but they were significantly lower than those seen for phosphoric acid‐treated beams. Compared to phosphoric acid, phytic acid treatment resulted in a reduced dentinal host‐derived endogenous enzymatic activity and collagen degradation. [ABSTRACT FROM AUTHOR]

Background & Aims: According to the Barcelona Clinic Liver Cancer (BCLC) staging system, monofocal hepatocellular carcinoma (HCC) is classified as early (BCLC A) irrespective of its size, even though controversies still exist regarding staging and treatment of large tumours. We aimed at evaluating the appropriate staging and treatment for large (>5 cm) monofocal (HCC). Methods: From the Italian Liver Cancer database, we selected 924 patients with small early monofocal HCC (2‐5 cm; SEM‐HCC), 163 patients with larger tumours (>5 cm; LEM‐HCC) and 1048 intermediate stage patients (BCLC B). Results: LEM‐HCC patients had a worse overall survival (OS) than SEM‐HCC (31.0 vs 49.0 months; P <.0001), and this was confirmed at multivariate analysis (HR 1.63, 95% CI 1.29‐2.05; P <.0001). The small difference in OS between LEM‐HCC and BCLC B patients (31.0 vs 27.0 months; P =.03) disappeared in the multivariate model (HR 0.98, 95% CI 0.77‐1.25; P =.89). In all monofocal tumours, treatment was the strongest independent predictor of survival, with a progressively decreasing survival benefit moving from "curative" to "palliative" therapies. The survival of resected patients with LEM‐HCC was significantly shorter than that of SEM‐HCC (44.0 vs 78.0 months; P =.002), but liver resection provided the highest survival benefit in both groups compared to other treatments. Conclusions: Monofocal HCC larger than 5 cm should not be staged as BCLC A and either a different staging system or a different subgrouping of patients (e.g. BCLC AB) should be used. Liver resection, if feasible, remains the recommended treatment for all these patients. [ABSTRACT FROM AUTHOR]

Aim: Transanal total mesorectal excision is a promising novel sphincter‐saving procedure for low rectal cancer. However, the transanal bottom‐up dissection is associated with increased rates of iatrogenic urethral injuries. Near‐infrared fluorescence (NIRF) imaging, given its deeper tissue penetration, has been explored in a limited number of studies for enhanced intra‐operative urethral visualization. In this study, we explored the feasibility of a novel, ultrabright, biocompatible fluorescent polymer to coat urinary catheters for the purpose of intra‐operative urethral visualization. Methods: In an ex vivo experiment, using a near‐infrared laparoscope, the fluorescent signal of a coated catheter (near‐infrared coating of equipment, NICE) was qualitatively and quantitatively compared to the signal of indocyanine green (ICG)/Instillagel® mixtures and ICG‐filled catheters at several concentrations. Also, in three male human torsos, using fluorescent urinary catheters, NIRF‐guided perineal dissections and a transanal total mesorectal excision were performed. Intra‐operative NIRF‐based urethral visualization was performed systematically. Results: During the qualitative and quantitative fluorescence signal assessment, NICE‐coated catheters were clearly superior to the ICG‐based solutions. In the cadaveric experiments, enhanced urethral visualization was possible even at early stages of dissection, when the organ was covered by several tissue layers. Conclusions: NICE‐coated catheters represent a promising potential to allow for NIRF‐based intra‐operative urethral visualization. [ABSTRACT FROM AUTHOR]

This paper examines how corporate social responsibility (CSR) affects bank efficiency in a sample of large commercial banks across 22 countries over the 2013–2017 period. We used a one‐step model of stochastic frontier analysis for panel data to estimate bank profit efficiency and found that the greater the activities in the social and environmental dimensions of CSR, the lower the level of efficiency, whereas activities in the corporate governance dimension are generally not relevant. This result supports the relevance of agent perspectives for these firms. However, we also found that institutional context moderates this baseline result. Specifically, all CSR activities have a positive impact on bank efficiency in common law countries and countries where the effectiveness of stakeholder protection is high. This supports the view that contexts that favor firms' sustainable behavior also increase bank efficiency. [ABSTRACT FROM AUTHOR]

Oligothiophenes are important organic molecules in a number of burgeoning industries as semi‐conducting materials due to their extensive π‐conjugation and charge transport properties. Typically, non‐symmetric, di‐aryl‐substituted thiophenes are prepared by the successive formation of Grignards, organotin, and/or boronic acid intermediates that can be subsequently employed in cross‐coupling reactions. While reliable, these approaches present synthetic difficulties due to the reactivity of organo‐metallic/pseudo‐metallic species, and produce considerable amounts of waste due to necessary pre‐functionalization. We have developed a decarboxylative cross‐coupling route as an effective strategy for the modular and less wasteful synthesis of a wide range of non‐symmetric, di‐arylthiophenes. This method uses a thiophene ester building block for successive decarboxylative palladium‐catalyzed couplings that allows for the efficient synthesis and evaluation of the opto‐electronic properties of a library of candidate semi‐conductors with functional groups that could be challenging to access using previous routes. [ABSTRACT FROM AUTHOR]

A library of symmetrical linear oligothiophene was prepared employing decarboxylative cross‐coupling reaction as the key transformation. Thiophene potassium carboxylate salts were used as cross‐coupling partners without the need of co‐catalyst, base, or additives. This method demonstrates complete chemoselectivity and is a comprehensive greener approach compared to the existing methods. The modularity of this approach is demonstrated with the preparation of discreet oligothiophenes with up to 10 thiophene repeat units. Symmetrical oligothiophenes are prototypical organic semiconductors where their molecular electrical doping as a function of the chain length can be assessed spectroscopically. An oligothiophene critical length for integer charge transfer was observed to be 10 thiophene units, highlighting the potential use of discrete oligothiophenes as doped conduction or injection layers in organic electronics applications. [ABSTRACT FROM AUTHOR]

Background and purpose Methods Results Conclusions Post‐COVID‐19 condition (PCC) is a prevalent and high‐burden sequela of SARS‐CoV‐2 infection. Because of the complexity of its manifestations, PCC case definition currently lacks standardisation and reproducibility. We aimed to devise a simple screening tool to boost reproducibility and comparability of PCC case definition across PCC studies, and to provide a framework in which to reliably identify suspected PCC cases. We also developed a comprehensive assessment protocol based on the most frequently reported PCC characteristics.Within a European multi‐centre study and based on the conclusions of a previous systematic review, we devised a checklist to assess the presence of PCC‐associated symptoms and their temporal relationship with COVID‐19.The checklist was developed to include three symptom cores (cognitive, psychiatric, and general). For each symptom, onset is assessed within 3 months after COVID‐19 resolution and persistence for at least 2 months. Any symptom fulfilling this criterion is sufficient to prompt suspicion of PCC. At least one symptom is required in the cognitive or psychiatric domains to suspect PCC with neuropsychiatric involvement. Our protocol features an extensive neuropsychological evaluation and self‐administered scales for mood, anxiety, stress‐related symptoms, sleep disorders, quality of life, disability, mental health, and personality traits; scales for quantitative assessment of fatigue and headache are also included.Consistent identification of PCC cases is crucial to correctly include patients in research and clinical studies. We propose a simple, reproducible, and flexible screening tool and a proposal for a comprehensive assessment that could be employed to enhance standardisation and comparability. [ABSTRACT FROM AUTHOR]

Abstract: Publications in high quality journals often serve to indicate research productivity. However, many top‐rated journals infrequently publish cross‐disciplinary topics such as healthcare financial management (HFM). So, academic administrators and HFM researchers find it challenging to evaluate the quality of the work. Journals open to publishing HFM articles are distributed across multiple disciplines. Each field has its own journal rankings typically focused on their primary subject area. Starting with prior literature, we form a cross‐disciplinary journal list and solicit preliminary input from editors, associated editors, reviewers, and authors. We then solicit confirmatory ranking input from independent researchers in a holdout sample. [ABSTRACT FROM AUTHOR]

In a recent meta-analysis, the average estimated recurrences were 5.0% for wide excisions and 26.0% for partial excisions,[3] although radical surgery is associated with a longer recovery time that can influence the therapeutic choice depending on the patients' needing. Surgical procedures are mentioned in almost all international guidelines, nevertheless, patients' compliance could be not always high due to the fear of wide excisions and reconstructive surgeries. Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease affecting ~1% of the population, with a female prevalence.[1] Management of HS may be challenging since the lack of effective treatments. [Extracted from the article]

New client acceptance decisions are critical for auditors. Audit quality can be negatively affected by limited knowledge of the new client's operations and finances. This may be mitigated for auditors with industry specialization. We examine whether new clientele negatively affect audit quality at the individual level and how the association with audit quality varies across auditors with different levels of industry specialization. Our study fills a gap in the literature by directly addressing the effects of new clients on audit quality for specialist and non-specialist auditors, as well as portfolio-concentration experts, and sheds light on the nature of risks associated with new client acceptance decisions. We find both industry specialists and portfolio-concentration experts can maintain their audit quality when accepting new clients, while there is a decline in quality for auditors who are neither industry specialists nor portfolio-concentration experts. [ABSTRACT FROM AUTHOR]

This work describes the coupling methodology between a modified version of RELAP5/Mod3.3 and ANSYS Fluent CFD code developed at the University of Pisa. The described coupling procedure can be classified as “two-way,” nonoverlapping, “online” coupling. In this work, a semi-implicit numerical scheme has been implemented, giving greater stability to the simulations. A MATLAB script manages both the codes, oversees the reading and writing of the boundary conditions at the interfaces, and handles the exchange of data. A new tool was used to control the Fluent session, allowing a reduction of the time required for the exchange of data. The coupling tool was used to simulate a loop system (NACIE facility) and a pool system (CIRCE facility), both working with Lead Bismuth Eutectic and located at ENEA Brasimone Research Centre. Some modifications in the coupling procedure turned out to be necessary to apply the methodology in the pool system. In this paper, the comparison between the obtained coupled numerical results and the experimental data is presented. The good agreement between experiments and calculations evinces the capability of the coupled calculation to model correctly the involved phenomena. [ABSTRACT FROM AUTHOR]

Monoterpenes, source of the distinctive odor of conifers, are generally considered plant defensive compounds. However, they are also known to act as long-range insect attractants, as they are volatile and permeate forest airspaces. Moreover, they are lipid soluble and can be absorbed into plant epicuticular waxes. We test their role in short-range host plant choice by both adult females and larvae of a folivorous forest pest ( Choristoneura fumiferana). We conducted laboratory assays testing the responses of Eastern spruce budworm to an artificial monoterpene mix (α-pinene, β-pinene, limonene, myrcene) and to white spruce ( Picea glauca) epicuticular waxes in closed arenas. Ovipositing females preferred filter paper discs treated with P. glauca waxes to controls, and preferred the waxes + monoterpenes treatment to waxes alone. However, females showed no preference between the monoterpene-treated disc and the control when presented without waxes. Feeding larvae prefered wax discs to control discs. They also consumed discs treated with realistic monoterpene concentrations and wax preferentially over wax-only discs, but showed no preference between extremely high monoterpene concentrations and wax-only controls. In an insect-free assay, P. glauca epicuticular wax decreased monoterpene volatilization. These results suggest that P. glauca waxes and realistic concentrations of monoterpenes are stimulatory to both egg-laying females and feeding larvae, and that their effects are synergistic. [ABSTRACT FROM AUTHOR]

As carbon-carbon bonds are an essential bond type in Nature, reactions that form C-C bonds are of great interest in organic chemistry. Among the most popular C-C bond formation methods with aromatic systems are palladium-catalyzed coupling reactions, such as the Heck, Suzuki, Negishi and Stille reactions. Even though these methods are efficient, they produce stoichiometric amounts of high molecular weight byproducts, placing them in conflict with the increasingly important ideas of sustainable reactions and green chemistry. In contrast, palladium-catalyzed desulfinative coupling reactions produce minimal waste; in general, only hydrogen halides or alkali halides are formed as byproducts in addition to SO2 gas, which can potentially be recycled. This microreview provides a brief historic overview on palladium-catalyzed coupling reactions with organosulfur compounds, with the main focus on the use of sulfinate salts as nucleophilic or electrophilic reaction partners. Various methods to access the sulfinate salts, and the coupling reactions of sulfonyl precursors that proceed through sulfinic acid/salt intermediates generated in situ are also discussed. [ABSTRACT FROM AUTHOR]

Background and objective There appears to be two distinct clinical phenotypes of obese patients with asthma-those with early-onset asthma and high serum IgE ( TH2-high), and those with late-onset asthma and low serum IgE ( TH2-low). The aim of the present study was to determine in the two phenotypes of obese asthma the effect of weight loss on small airway function. Methods TH2-low ( n = 8) and TH2-high ( n = 5) obese asthmatics underwent methacholine challenge before and 12 months following bariatric surgery. Dose-response slopes as measures of sensitivity to airway closure and narrowing were measured as maximum % fall forced vital capacity ( FVC) and forced expiratory volume in 1 s/ FVC, respectively, divided by dose. Resting airway mechanics were measured by forced oscillation technique. Results Weight loss reduced sensitivity to airway closure in TH2-low but not TH2-high obese asthmatics (pre-post mean change ± 95% confidence interval: 1.8 ± 0.8 doubling doses vs −0.3 ± 1.7 doubling doses, P = 0.04). However, there was no effect of weight loss on the sensitivity to airway narrowing in either group ( P = 0.8, TH2-low: 0.8 ± 1.0 doubling doses, TH2-high: −1.1 ± 2.5 doubling doses). In contrast, respiratory resistance (20 Hz) improved in TH2-high but not in TH2-low obese asthmatics (pre-post change median interquartile range: 1.5 (1.3-2.8) cmH2O/L/s vs 0.6 (−1.8-0.8) cmH2O/L/s, P = 0.03). Conclusions TH2-low obese asthmatics appear to be characterized by increased small airway responsiveness and abnormalities in resting airway function that may persist following weight loss. However, this was not the case for TH2-high obese asthmatics, highlighting the complex interplay between IgE status and asthma pathophysiology in obesity. [ABSTRACT FROM AUTHOR]

A range of aryl sulfinates can be oxidatively dimerized to generate substituted biphenyls with concomitant extrusion of sulfur dioxide with a palladium catalyst. Catalytic amounts of TEMPO and excess oxygen are utilized as oxidants to regenerate the palladium catalyst. [ABSTRACT FROM AUTHOR]

Two experimental approaches to the synthesis of a scarcely reported biologically active thienoisoquinoline system are demonstrated. A 5-step linear synthesis employing a palladium-catalyzed decarboxylative cross-coupling and functionalization sequence allowed for the preparation of a diverse range of substituted thienoisoquinoline systems. Alternatively the palladium-catalyzed decarboxylative cross-coupling and CH activation steps can be telescoped to produce a one-pot reaction sequence that provides efficient access to aryl-substituted thienoisoquinolines. [ABSTRACT FROM AUTHOR]

A range of 2,5-diarylated thiophenes were synthesised as small molecule mimetics of the α-helix to modulate the amyloidogenesis and cytotoxic effect of islet amyloid polypeptide (IAPP). 3-Substituted thiophene-2-carboxylic acids were used as key intermediates and functionalised by palladium decarboxylative cross-coupling and direct CH activation successively with overall yields ranging from 23 to 95 %. The effect of the ligands on IAPP amyloid fibril formation was evaluated with the thioflavin T (ThT) fluorescence-based assay. Furthermore, the capacity of these compounds to inhibit the cytotoxic effect of IAPP was assessed using β-pancreatic cells. [ABSTRACT FROM AUTHOR]

Beauty lies in simplicity: An efficient and environmentally benign palladium‐catalyzed protocol has been developed using a sulfinate as a nucleophilic coupling partner. The sulfinate position is arylated chemoselectively in very good yields. The bench‐stable, non‐hygroscopic heteroaromatic sulfinate salts rapidly undergo cross‐coupling without the need of a co‐catalyst, base, or additives (see scheme; mw=microwave). [ABSTRACT FROM AUTHOR]

Introduction Nonalcoholic fatty liver disease (NAFLD) has been described in adult GH deficiency syndrome. Furthermore, chronic liver disease can be associated with significant changes in levels of IGF-I, GH-binding protein (GHBP), IGF-binding proteins (IGFBPs) and acid-labile subunit (ALS). However, the effect of liver steatosis on the GHBP production has not been investigated yet. Aim of the study To explore whether GH secretion and/or levels of IGF-I, IGFBP-3, ALS and GHBP could be altered in obese patients in relation to the presence of liver steatosis. Materials and methods A total of 115 obese patients (BMI > 30) were enrolled in the protocol (65 patients with liver steatosis and 50 age- and BMI-matched controls). In all patients, the following parameters were studied: serum levels of glucose, insulin, the HOMA index, IGF-I, GHBP, IGFBP-3, ALS and GH after GHRH and arginine stimulation test. Results As expected, patients with NAFLD had blood glucose, insulin, HOMA-R significantly higher than controls, indicating a more severe insulin-resistance state in NAFLD. Furthermore, patients with NAFLD had higher levels of GHBP and IGFBP-3 and lower GH peak and IGF-I levels as compared to controls. No difference was found in ALS levels between the groups. In a multivariate analysis, GHBP was positively associated with hepatic steatosis while IGF-1 was negatively associated with hepatic steatosis. Conclusions This study demonstrates that in patients with NAFLD, the GHBP levels are increased, and that the GH/IGF-I axis is significantly altered probably leading to reduced IGF-I bioavailability at tissue level. [ABSTRACT FROM AUTHOR]

To develop in vitro models of cells, tissues and organs we have designed and realized a series of cell culture chambers. Each chamber is purpose designed to simulate a particular feature of the in vivo environment. The bioreactor system is user friendly, and the chambers are easy to produce, sterilize and assemble. In addition they can be connected together to simulate inter-organ or tissue cross-talk. Here we discuss the design philosophy of the bioreactor system and then describe its construction. Preliminary results of validation tests obtained with hepatocytes and endothelial cells are also reported. The results show that endothelial cells are extremely sensitive to small levels of shear stress and that the presence of heterotypic signals from endothelial cells enhances the endogenous metabolic function of hepatocytes. Biotechnol. Bioeng. 2011;108:2129-2140. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background: Although interpersonal psychotherapy (IPT) is an efficacious treatment for acute depression, the relative efficacy of treatment in each of the four IPT problem areas (grief, role transitions, role disputes, interpersonal deficits) has received little attention. We evaluated the specificity of IPT by comparing treatment success among patients whose psychotherapy focused on each problem area. Moreover, we sought to understand how the patient characteristics and interpersonal problems most closely linked to the onset of a patient's current depression contributed to IPT success. Methods: Patients meeting DSM-IV criteria for an episode of major depressive disorder (n=182) were treated with weekly IPT. Remission was defined as an average Hamilton Rating Scale for Depression 17-item score of 7 or below over 3 weeks. Personality disorders were diagnosed using the Structured Clinical Interview for DSM-IV Personality Disorders. Results: Contrary to our prediction that patients whose treatment was focused on interpersonal deficits would take longer to remit, survival analyses indicated that patients receiving treatment focused on each of the four problem areas did not differ in their times to remission. Nor were patients in the interpersonal deficits group more likely to have an Axis II diagnosis. Patients whose treatment focused on role transitions remitted faster than those whose treatment focused on role disputes, after controlling for covariates. Conclusion: With skillful use of IPT strategies and tactics and with careful medication management where appropriate, patients in this study whose treatment focused on each problem area were treated with equal success by trained IPT clinicians. Depression and Anxiety, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The purpose of this study was to characterize escitalopram population pharmacokinetics (PK) in patients treated for major depression in a cross-national, US-Italian clinical trial. Data from the 2 sites participating in this trial, conducted at Pittsburgh (United States) and Pisa (Italy), were used. Patients received 5, 10, 15, or 20 mg of escitalopram daily for a minimum of 32 weeks. Nonlinear mixed effects modeling was used to model the PK characteristics of escitalopram. One- and 2-compartment models with various random effect implementations were evaluated during model development. Objective function values and goodness-of-fit plots were used as model selection criteria. CYP2C19 genotype, age, weight, body mass index, sex, race, and clinical site were evaluated as possible covariates. In total, 320 plasma concentrations from 105 Pittsburgh patients and 153 plasma concentrations from 67 Pisa patients were available for the PK model development. A 1-compartmental model with linear elimination and proportional error best described the data. Apparent clearance (CL/F) and volume of distribution (V/F) for escitalopram without including any covariates in the patient population were 23.5 L/h and 884 L, respectively. CYP2C19 genotype, weight, and age had a significant effect on CL/F, and patient body mass index affected estimated V/F. Patients from Pisa, Italy, had significantly lower clearances than patients from Pittsburgh that disappeared after controlling for patient CYP2C19 genotype, age, and weight. Postprocessed individual empirical Bayes estimates on clearance for the 172 patients show that patients without allele CYP2C19*2 or *3 (n = 82) cleared escitalopram 33.7% faster than patients with heterogeneous or homogeneous *2 or *3 (*17/*2, *17/*3, *1/*2, *1/*3, *2/*2, *2/*3, and *3/*3, n = 46). CL/F significantly decreased with increasing patient age. Patients younger than 30 years (n = 45) cleared escitalopram 20.7% and 42.7% faster than patients aged 30 to 50 years (n = 84) and older than 50 years of age (n = 43), respectively. CYP2C19 genotype, age, and weight strongly influenced the CL/F of escitalopram. These variables may affect patient tolerance of this antidepressant and may provide important information in the effort to tailor treatments to patients' individual needs. [ABSTRACT FROM AUTHOR]

Hypertrophic cardiomyopathy (HCM) is the most frequent genetic cardiovascular disorder worldwide. It is the leading cause of sudden cardiac-related death in young people and a major cause of cardiac failure and death in elderly people. However, HCM frequently goes undiagnosed until the appearance of overt signs and symptoms, thereby delaying prophylactic and therapeutic measures. We screened patients for sarcomeric genes associated with HCM to obtain information that could be useful for an early diagnosis and so limit the severe consequences of silent HCM. We recruited 39 families with HCM from southern Italy and found mutations in 41% of families (12 with familial HCM and 4 with sporadic HCM). The remaining 23 families (59%) were negative for myofilament gene mutations. Of the 12 mutations identified, 8 were novel. Screening of the other family members available revealed that 27 had mutations; 11 of these individuals had no signs or symptoms suggestive of HCM. This study, besides characterizing the spectrum of mutations in another childhood population, and revealing an even greater genetic heterogeneity than formerly recognized, may increase genotype-phenotype correlations, and thus may help to identify asymptomatic candidates for early preventive or therapeutic measures. [ABSTRACT FROM AUTHOR]

The article discusses the lesson learned relative to experiments and modelling methodologies about heat and mass transfer, conducted at the University of Pisa in Pisa, Italy. It outlines the analysis of available techniques and theories used for the evaluation of evaporation and condensation rates in Light Water Reactors (LWR). Furthermore, it highlights the relevant conclusions obtained from the model development and assessment steps.

Veno-occlusive disease (VOD) of the liver is a severe complication of high-dose chemotherapy and allogeneic or autologous stem cell transplantation with potential fatal outcome. We report a case of severe VOD in a patient with a high-grade B-cell lymphoma. Liver-venule occlusion was confirmed by liver biopsy. Supportive care, fibrinolytic treatment with recombinant tissue plasminogen activator and defibrotide maintenance therapy led to complete resolution of VOD demonstrated at liver biopsy and with a follow-up of 44 months after autologous peripheral blood stem cell transplantation. The literature on VOD has been reviewed. [ABSTRACT FROM AUTHOR]

Acetaminophen (paracetamol) is used throughout the world for pain relief and antipyresis in both children and adults. In many countries, it can be purchased without a medical prescription and it is also a common component of a number of over-the-counter remedies for colds, influenza and the like. Fasting, malnutrition and use of alcohol and/or other drugs are thought to play causal roles in hepatotoxicity associated with recommended doses of acetaminophen although liver injury provoked by therapeutic doses has also been observed in the absence of these factors. We describe two patients who experienced subclinical hepatotoxic reactions after taking acetaminophen at therapeutic doses. The results of an antipyrine metabolism test suggest the presence of constitutional hyperactivity of the cytochrome P450-dependent mixed function oxidative system in both patients. We hypothesize that the latter contributed to the hepatotoxicity and that it may play a role in idiosyncratic reactions to this drug. [ABSTRACT FROM AUTHOR]

Objectives Surgical options for acute diverticulitis with peritonitis include Hartmann's procedure or resection and primary anastomosis with or without a stoma. Initial laparoscopic lavage and drainage can control the acute intra-abdominal sepsis to allow for a delayed definitive procedure in nonemergency conditions. Potential advantages include the avoidance of a laparotomy, stoma and local infections at the origin of dehiscence and incisional hernias. We evaluated this approach in a selected group of patients. Methods Patients with intra-abdominal pus secondary to diverticular perforation requiring surgery were included in the study. Patients with localized pus amenable to computerized tomography (CT)-guided drainage, faecal peritonitis, severe generalized peritonitis, and those in which the perforation was spontaneously visible were excluded. Standard demographic data, CT findings, intra-operative findings and postoperative outcomes were analysed. Results Ten patients were suitable for the approach. Mean patient age was 60.2 years. Mean body mass index was 28.2 m2/kg. Mean postoperative stay was 8.5 days and uneventful in all patients. One patient re-presented after 3 weeks with acute peritonitis requiring open sigmoidectomy. Six patients successfully underwent laparoscopic sigmoidectomy with primary anastomosis 2–3 months later. Two patients were not re-operated because of comorbidity and one refused surgery. Conclusions A two-stage totally minimally invasive approach may be a safe alternative strategy for selected cases of acute complicated diverticulitis. [ABSTRACT FROM AUTHOR]