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Habitat loss and fragmentation is the largest contributing factor to species extinction and declining biodiversity. Landscapes are becoming highly spatially heterogeneous with varying degrees of human modification. Much theoretical study of habitat fragmentation has historically focused on a simple theoretical landscape with patches of habitat surrounded by a spatially homogeneous hostile matrix. However, terrestrial habitat patches are often surrounded by complex mosaics of many different land cover types, which are rarely ecologically neutral or completely inhospitable environments. We employ an extension of a reaction diffusion model to explore effects of heterogeneity in the matrix immediately surrounding a patch in a one-dimensional theoretical landscape. Exact dynamics of a population exhibiting logistic growth, an unbiased random walk in the patch and matrix, habitat preference at the patch/matrix interface, and two functionally different matrix types for the one-dimensional landscape is obtained. These results show existence of a minimum patch size (MPS), below which population persistence is not possible. This MPS can be estimated via empirically derived estimates of patch intrinsic growth rate and diffusion rate, habitat preference, and matrix death and diffusion rates. We conclude that local matrix heterogeneity can greatly change model predictions, and argue that conservation strategies should not only consider patch size, configuration, and quality, but also quality and spatial structure of the surrounding matrix.

We will analyze the symmetric positive solutions to the two-point steady state reaction-diffusion equation: \begin{equation*} \begin{split} -&u^{\prime \prime}= \begin{cases} \lambda\left[ u-\dfrac{1}{K}u^2-\dfrac{cu^2}{1+u^2}\right];& x\in [L,1-L] ,\\ \lambda \left[u-\dfrac{1}{K}u^2\right];& x\in (0,L)\cup(1-L,1), \end{cases} \\ -&u^{\prime}(0) + \sqrt{\lambda}\gamma u(0) = 0,\\ &u^{\prime}(1) + \sqrt{\lambda}\gamma u(1) = 0,\\ \end{split} \end{equation*} where $\lambda$, $c$, $K$, and $\gamma$ are positive parameters and the parameter $L\in(0,\frac{1}{2})$. The steady state reaction-diffusion equation above occurs in ecological systems and population dynamics. The above model exhibits logistic growth in the one-dimensional habitat $\Omega_0=(0,1)$, where grazing (type of predation) is occurring on the subregion $[L,1-L]$. In this model, $u$ is the population density and $c$ is the maximum grazing rate. $\lambda$ is a parameter which influences the equation as well as the boundary conditions, and $\gamma$ represents the hostility factor of the surrounding matrix. Previous studies have shown the occurrence of S-shaped bifurcation curves for positive solutions for certain parameter ranges when the boundary condition is Dirichlet ($\gamma \longrightarrow \infty$). Here we discuss the occurrence of S-shaped bifurcation curves for certain parameter ranges, when $\gamma$ is finite, and their evolutions as $\gamma$ and $L$ vary.

The relationship between conspecific density and the probability of emigrating from a patch can play an essential role in determining the population-dynamic consequences of an Allee effect. In this paper, we model a population that inside a patch is diffusing and growing according to a weak Allee effect per-capita growth rate, but the emigration probability is dependent on conspecific density. The habitat patch is one-dimensional and is surrounded by a tuneable hostile matrix. We consider five different forms of density dependent emigration (DDE) that have been noted in previous empirical studies. Our models predict that at the patch-level, DDE forms that have a positive slope will counteract Allee effects, whereas, DDE forms with a negative slope will enhance them. Also, DDE can have profound effects on the dynamics of a population, including producing very complicated population dynamics with multiple steady states whose density profile can be either symmetric or asymmetric about the center of the patch. Our results are obtained mathematically through the method of subsuper solutions, time map analysis, and numerical computations using Wolfram Mathematica.

A tecnologia de identificação por radiofrequência (RFID) tem se destacado como uma ferramenta para automação, segurança e gestão de acervos de bibliotecas. O presente artigo descreve o processo inicial de implantação da tecnologia RFID no acervo da Biblioteca do Centro Universitário Univates (UNIVATES), evidenciando os recursos humanos e de informática envolvidos. O tempo entre planejamento e execução da gravação e etiquetagem ocorreu no período de novembro de 2013 a março de 2014. Conclui-se que processo de preparação do acervo para receber esta tecnologia é demorado e custoso, entretanto, o adequado planejamento, assim como a utilização de recursos da tecnologia da informação que possibilitem gerenciar todo o processo, permitem maior confiabilidade e agilidade.

Background: A score to predict the association between unexplained osteoporosis and an underlying systemic Mastocytosis (SM) is lacking., Objective: This study aimed at identifying criteria able to predict the diagnosis of SM without skin involvement and provide an indication for bone marrow (BM) assessment., Methods: We included 139 adult patients with unexplained osteoporosis and suspected SM. After BM evaluation, 63 patients (45.3 %) were diagnosed with SM, while the remaining 76 patients (54.7 %) negative for clonal mast cell (MC) disorders, constituted our control group. Univariate and multivariate analysis identified three independent predictive factors: age (<54 years: +1 point, >64 years: -1 point), serum basal tryptase (sBT) levels >19 ng/mL (+2 points) and vertebral fractures (+2 points)., Results: These variables were used to build the OSTEO-score, able to predict the diagnosis of SM before BM assessment with a sensitivity of 73.5 % and a specificity of 67.1 %. Patients with a score < 3 had a lower probability of having SM compared to patients with a score ≥ 3 (28.5 % and 71.4 %, respectively, p < 0.0001). When sBT levels were corrected for the presence of hereditary alpha-tryptasemia (HαT) using the BST calculater (https://bst-calculater.niaid.nih.gov/) recently published [1,2], the sensitivity of ΗαT-adjusted OSTEO-score increased to 87.8 %, and the specificity reached 76.1 %. Also, the positive predictive value of a score ≥ 3 increased to 85.2 %., Conclusions: Further studies are needed to validate these results and characterize the role of tryptase genotyping in patients with unexplained osteoporosis in reducing the risk of misdiagnosing patients with SM. Our proposed scoring model allows the identification of patients with the highest probability of having SM, avoiding unnecessary BM studies., Competing Interests: Declaration of competing interest All the authors have approved this manuscript and declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose of Review: Patients with mast cell disorders frequently experience symptoms from excessive mediator release like histamine and tryptase, ranging from mild flushing to severe anaphylactic responses. Hypersensitivity reactions (HRs) to drugs are a major cause of anaphylaxis in these patients, who often worry about triggering mast cell degranulation when taking medications. The aim of this review is to explore the complex interactions between mast cell disorders and drug HRs, focusing on the clinical challenges of managing these conditions effectively to enhance understanding and guide safer clinical practices., Recent Findings: Among the drugs most commonly associated with hypersensitivity reactions in patients with mast cell disorders are non-steroidal anti-inflammatory drugs, antibiotics, and perioperative agents. Recent studies have highlighted the role of Mas-related G-protein coupled receptor member X2 (MRGPRX2) - a receptor involved in non-immunoglobulin E mediated mast cell degranulation - in exacerbating HRs. Investigations reveal varied drug tolerance among patients, underscoring the need for individual risk assessments., Summary: Tailored diagnostic approaches are crucial for confirming drug allergies and assessing tolerance in patients with mastocytosis, preventing unnecessary medication avoidance and ensuring safety before acute situations arise., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Delayed anaphylaxis after ingestion of red meat because of galactose-alpha-1,3-galactose (alpha-gal) syndrome has increased in recent years. The mechanism involves an immunoglobulin E reaction to alpha-gal, a molecule found in mammalian meat, dairy products, medications and excipients containing mammalian-derived components, and tick salivary glycans. Sensitization occurs due to the bite of a lone star tick and the transmission of alpha-gal molecules into person's bloodstream. We describe a case of alpha-gal syndrome with severe food, drug, and perioperative allergy in which anaphylaxis with hypovolemic shock occurred immediately after an emergency surgical procedure, when a gelatin-containing drug was injected. This case study confirms that the clinical manifestations of alpha-gal syndrome could be different depending on the route of administration, with immediate reactions if an alpha-gal-containing drug is injected and delayed type allergic manifestations occurring several hours after oral intake. The purpose of this report is to highlight the importance of risk communication in case of exposure to medical products and surgical procedures of patients with alpha-gal syndrome and to encourage drug manufacturers to indicate clearly the origin of excipients in product literature., Competing Interests: The authors declared no conflict of interest.

We present tuna-step, a novel microfluidic module based on step emulsification that allows for reliable generation of droplets of different sizes. Until now, sizes of droplets generated with step emulsification were hard-wired into the geometry of the step emulsification nozzle. To overcome this, we incorporate a thin membrane underneath the step nozzle that can be actuated by pressure, enabling the tuning of the nozzle size on-demand. By controllably reducing the height of the nozzle, we successfully achieved a three-order-of-magnitude variation in droplet volume without adjusting the flow rates of the two phases. We developed and applied a new hydrophilic surface modification, that ensured long-term stability and prevented swelling of the device when generating oil-in-water droplets. Our system produced functionally graded soft materials with adjustable porosity and material content. By combining our microfluidic device with a custom 3D printer, we generated and extruded oil-in-water emulsions in an agarose gel bath, creating unique self-standing 3D hydrogel structures with porosity decoupled from flow rate and with composition gradients of external phases. We upscaled tuna-step by setting 14 actuatable nozzles in parallel, offering a step-emulsification-based single chip solution that can accommodate various requirements in terms of throughput, droplet volumes, flow rates, and surface chemistry.

Diagnostic testing of patients who present for evaluation of insect venom allergy can involve many levels of investigation. A detailed initial history is critical for diagnosis and prognosis. The severity of previous sting reactions and the presence or absence of urticaria or hypotension predict severe future sting reactions and underlying mast cell disorders. Venom skin tests and specific IgE measurement can confirm the diagnosis but have limited positive predictive value for the frequency and severity of future sting reactions. Testing for serum IgE to recombinant venom component allergens can distinguish true allergy from cross-reactivity to honey bee and yellowjacket venoms. Basophil activation tests can improve the detection of venom allergy and predict the severity of reactions and the efficacy of venom immunotherapy but are limited in availability. An elevated basal serum tryptase level is an important marker for severe sting anaphylaxis and underlying mast cell disorders (eg, hereditary α-tryptasemia and clonal mast cell disease). When there is high suspicion (eg, using the Red Espanola de Mastocytosis score), bone marrow biopsy is the definitive tool to characterize mast cell disorders that are associated with the most severe outcomes in patients with insect sting allergy., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Anaphylaxis is a well-known feature of mastocytosis, particularly in relation to hymenoptera venom stings. It is therefore hypothesized that mastocytosis patients may also be predisposed to severe hypersensitivity reactions to certain medications including non-steroidal anti-inflammatory drugs (NSAIDs). For this reason, these patients are usually discouraged from using these drugs. The current study aimed to determine the prevalence and evaluate the severity of NSAID-related hypersensitivity reactions among patients with mastocytosis., Methods: A retrospective study was conducted among a total of 388 (≥18 years old) consecutive patients from two independent European mastocytosis centers, in Sweden and Italy. Patients underwent a thorough allergy work-up where self-reported NSAID-hypersensitivity reactions were re-evaluated by an allergist in the first cohort (202 patients) and results were validated in the second cohort (186 patients)., Results: Overall frequency of NSAID-hypersensitivity was 11.3% in the total study cohort. Most patients reacted with cutaneous symptoms (89%), whereas severe hypersensitivity reactions were infrequent with only 11 patients (2.8%) experiencing anaphylaxis. All NSAID-related hypersensitivity reactions had occurred before mastocytosis was diagnosed. There was no difference between the groups regarding gender, baseline tryptase levels or presence of atopy, asthma/rhinitis., Conclusion: Our study indicates an approximate 4-fold increased prevalence of NSAID hypersensitivity among mastocytosis patients compared to the general population. However, most NSAID reactions were limited to the skin as the prevalence of overall anaphylaxis was infrequent. Our results support that mastocytosis patients with a known tolerance to NSAIDs can continue using these medications without special precautions, whereas those with a prior reaction to NSAIDs should undergo thorough allergy work-up, including drug challenges., Competing Interests: 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., (© 2022 Bonadonna, Olivieri, Jarkvist, Nalin, Zanotti, Maclachlan and Gulen.)

Purpose of Review: To discuss our evolving knowledge about the genetic variations in human tryptase and recent advances in associated clinical phenotypes., Recent Findings: Hereditary alpha-tryptasemia (HAT) is an autosomal dominant genetic trait and a common cause of elevated basal serum tryptase (BST) in Western populations. It is a risk factor for severe anaphylaxis and an established modifier of mast cell mediator-associated symptoms among patients with systemic mastocytosis (SM)., Summary: The unique properties of naturally occurring alpha/beta-tryptase heterotetramers may explain certain elements of phenotypes associated with HAT. Understanding the physiology of tryptases and how this may relate to the clinical features associated with HAT is the first step in identifying optimal medical management and targets for novel therapeutics., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Chronic vascular wounds have a significant economic and social impact on our society, calling for the allocation of a great deal of attention and resources. The coronavirus disease (COVID-19) outbreak has represented a difficult challenge to face for health care providers and fragile patients, such as for outpatients and Day-Hospital patients needing continuous care at the Angiology Unit of the University Hospital of Padova in Italy, one of the most crucial areas worldwide. The project consisted of a critical revision of all the procedures from the patients' arrivals to their discharge after completing the entire course of treatment. The previous standard of practice was modified according to the current evidence-based guidelines and the national and local government's indications. The new standard of practice allowed our unit to protect every patient and staff member from the coronavirus infection, providing the same high standard of care as before the COVID-19 outbreak.

An interlaboratory comparison study was conducted by the Vitamin D Standardization Program (VDSP) to assess the performance of liquid chromatography - tandem mass spectrometry (LC-MS/MS) assays used for the determination of serum total 25-hydroxyvitamin D (25(OH)D), which is the sum of 25-hydroxyvitamin D 2 (25(OH)D 2 ) and 25-hydroxyvitamin D 3 (25(OH)D 3 ). A set of 50 single-donor samples was assigned target values for concentrations of 25(OH)D 2 , 25(OH)D 3 , 3-epi-25-hydroxyvitamin D 3 (3-epi-25(OH)D 3 ), and 24R,25-dihydroxyvitamin D 3 (24R,25(OH) 2 D 3 ) using isotope dilution liquid chromatography - tandem mass spectrometry (ID LC-MS/MS). VDSP Intercomparison Study 2 Part 1 includes results from 14 laboratories using 14 custom LC-MS/MS assays. Assay performance was evaluated using mean % bias compared to the assigned target values and using linear regression analysis of the test assay mean results and the target values. Only 53% of the LC-MS/MS assays met the VDSP criterion of mean % bias ≤ |±5%|. For the LC-MS/MS assays not meeting the ≤ |±5%| criterion, four assays had mean % bias of between 12 and 21%. Based on multivariable regression analysis using the concentrations of the four individual vitamin D metabolites in the 50 single-donor samples, the performance of several LC-MS/MS assays was found to be influenced by the presence of 3-epi-25(OH)D 3 . The results of this interlaboratory study represent the most comprehensive comparison of LC-MS/MS assay performance for serum total 25(OH)D and document the significant impact of the lack of separation of 3-epi-25(OH)D 3 and 25(OH)D 3 on assay performance, particularly with regard to mean % bias., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

An interlaboratory comparison study was conducted by the Vitamin D Standardization Program (VDSP) to assess the performance of ligand binding assays (Part 2) for the determination of serum total 25-hydroxyvitamin D [25(OH)D]. Fifty single-donor samples were assigned target values for concentrations of 25-hydroxyvitamin D 2 [25(OH)D 2 ], 25-hydroxyvitamin D 3 [25(OH)D 3 ], 3-epi-25-hydroxyvitamin D 3 [3-epi-25(OH)D 3 ], and 24R,25-dihydroxyvitamin D 3 [24R,25(OH) 2 D 3 ] using isotope dilution liquid chromatography-tandem mass spectrometry (ID LC-MS/MS). VDSP Intercomparison Study 2 Part 2 includes results from 17 laboratories using 32 ligand binding assays. Assay performance was evaluated using mean % bias compared to the assigned target values and using linear regression analysis of the test assay mean results and the target values. Only 50% of the ligand binding assays achieved the VDSP criterion of mean % bias ≤ |± 5%|. For the 13 unique ligand binding assays evaluated in this study, only 4 assays were consistently within ± 5% mean bias and 4 assays were consistently outside ± 5% mean bias regardless of the laboratory performing the assay. Based on multivariable regression analysis using the concentrations of individual vitamin D metabolites in the 50 single-donor samples, most assays underestimate 25(OH)D 2 and several assays (Abbott, bioMérieux, DiaSorin, IDS-EIA, and IDS-iSYS) may have cross-reactivity from 24R,25(OH) 2 D 3 . The results of this interlaboratory study represent the most comprehensive comparison of 25(OH)D ligand binding assays published to date and is the only study to assess the impact of 24R,25(OH) 2 D 3 content using results from a reference measurement procedure., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

The Vitamin D External Quality Assessment Scheme (DEQAS) distributes human serum samples four times per year to over 1000 participants worldwide for the determination of total serum 25-hydroxyvitamin D [25(OH)D)]. These samples are stored at -40 °C prior to distribution and the participants are instructed to store the samples frozen at -20 °C or lower after receipt; however, the samples are shipped to participants at ambient conditions (i.e., no temperature control). To address the question of whether shipment at ambient conditions is sufficient for reliable performance of various 25(OH)D assays, the equivalence of DEQAS human serum samples shipped under frozen and ambient conditions was assessed. As part of a Vitamin D Standardization Program (VDSP) commutability study, two sets of the same nine DEQAS samples were shipped to participants at ambient temperature and frozen on dry ice. Twenty-eight laboratories participated in this study and provided 34 sets of results for the measurement of 25(OH)D using 20 ligand binding assays and 14 liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. Equivalence of the assay response for the frozen versus ambient DEQAS samples for each assay was evaluated using multi-level modeling, paired t-tests including a false discovery rate (FDR) approach, and ordinary least squares linear regression analysis of frozen versus ambient results. Using the paired t-test and confirmed by FDR testing, differences in the results for the ambient and frozen samples were found to be statistically significant at p < 0.05 for four assays (DiaSorin, DIAsource, Siemens, and SNIBE prototype). For all 14 LC-MS/MS assays, the differences in the results for the ambient- and frozen-shipped samples were not found to be significant at p < 0.05 indicating that these analytes were stable during shipment at ambient conditions. Even though assay results have been shown to vary considerably among different 25(OH)D assays in other studies, the results of this study also indicate that sample handling/transport conditions may influence 25(OH)D assay response for several assays., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

An intralaboratory study assessing assay variability and bias for determination of serum total 25-hydroxyvitamin D [25(OH)D] was conducted by the Vitamin D Standardization Program (VDSP). Thirteen assays for serum total 25(OH)D were evaluated in a single laboratory including 11 unique immunoassays and one liquid chromatography - tandem mass spectrometry (LC-MS/MS) assay. Fifty single-donor serum samples, including eight samples with high concentrations of 25(OH)D 2 (> 30 nmol/L), were assigned target values for 25(OH)D 2 and 25(OH)D 3 using reference measurement procedures (RMP). Using four replicate measurements for each sample, the mean total percent coefficient of variation (%CV) and mean % bias from the target values were determined for each assay using the 50 single-donor samples and a 42-sample subset, which excluded 8 high 25(OH)D 2 concentration samples, and compared with VDSP performance criteria of ≤ 10 % CV and ≤ ±5 % mean bias. All 12 assays achieved the performance criterion for % CV, and 9 of the 12 assays were within ≤ ±5 % mean bias. The Fujirebio Inc. assay exhibited the lowest %CV and highest percentage of individual measurements within ≤ ±5 % mean bias. Ten immunoassays exhibited changes in response due to the high 25(OH)D 2 samples with Abbott, Biomérieux, DiaSorin, DIAsource, and IDS-iSYS assays having the largest deviations. The Fujirebio Inc. and Beckman Coulter assays were only minimally affected by the presence of the high 25(OH)D 2 samples. Samples with high concentrations of 25(OH)D 2 provided a critical performance test for immunoassays indicating that some assays may not have equal response or recovery for 25(OH)D 2 and 25(OH)D 3 ., (Published by Elsevier Ltd.)

An interlaboratory study was conducted through the Vitamin D Standardization Program (VDSP) to assess commutability of Standard Reference Materials® (SRMs) and proficiency testing/external quality assessment (PT/EQA) samples for determination of serum total 25-hydroxyvitamin D [25(OH)D] using ligand binding assays and liquid chromatography-tandem mass spectrometry (LC-MS/MS). A set of 50 single-donor serum samples were assigned target values for 25-hydroxyvitamin D 2 [25(OH)D 2 ] and 25-hydroxyvitamin D 3 [25(OH)D 3 ] using reference measurement procedures (RMPs). SRM and PT/EQA samples evaluated included SRM 972a (four levels), SRM 2973, six College of American Pathologists (CAP) Accuracy-Based Vitamin D (ABVD) samples, and nine Vitamin D External Quality Assessment Scheme (DEQAS) samples. Results were received from 28 different laboratories using 20 ligand binding assays and 14 LC-MS/MS methods. Using the test assay results for total serum 25(OH)D (i.e., the sum of 25(OH)D 2 and 25(OH)D 3 ) determined for the single-donor samples and the RMP target values, the linear regression and 95% prediction intervals (PIs) were calculated. Using a subset of 42 samples that had concentrations of 25(OH)D 2 below 30 nmol/L, one or more of the SRM and PT/EQA samples with high concentrations of 25(OH)D 2 were deemed non-commutable using 5 of 11 unique ligand binding assays. SRM 972a (level 4), which has high exogenous concentration of 3-epi-25(OH)D 3 , was deemed non-commutable for 50% of the LC-MS/MS assays., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Secondary organic aerosol (SOA) accounts for a significant fraction of particulate matter (PM) in the atmosphere. Source identification, including the SOA fraction, is critical for the effective management of air pollution. Molecular SOA markers (tracers) are key compounds allowing the source apportionment of SOA using different methodologies. Therefore, accurate SOA marker measurements in ambient air PM are important. This study determined the concentrations of 12 key SOA markers (biogenic and anthropogenic) in the urban dust standard reference material available from the National Institute of Standards and Technology (NIST) (SRM 1649b). Two extraction procedures, sonication and QuEChERS-like (quick easy cheap effective rugged and safe), have been compared. Three research laboratories/institutes using two analytical techniques (gas chromatography/mass spectrometry (GC/MS) and ultra-high-pressure liquid chromatography/tandem mass spectrometry (HPLC/MS-MS)) carried out the analyses. The results obtained were all in good agreement, except for 2-methylerythritol. The analysis of this compound still seems to be challenging by both GC/MS (large injection repeatability) and HPLC/MS-MS (separation issues of both 2-methyltetrols: 2-methylthreitol and 2-methylerythritol). Possible inhomogeneity in the SRM for this compound could also explain the large discrepancies observed. Sonication and QuEChERS-like procedures gave comparable results for the extraction of the SOA markers showing that QuEChERS-like extraction is suitable for the analysis of SOA markers in ambient air PM. As this study provides, for the first time, indicative values in a reference material for typical SOA markers, the analysis of SRM 1649b (urban dust) could be used for quality control/assurance purposes. Graphical abstract.

Retention indices (I) for 45 polycyclic aromatic hydrocarbons (PAHs) and 63 methyl-substituted PAHs were determined by gas chromatography - mass spectrometry (GC-MS) using two different stationary phases: a Rxi-PAH phase (a "higher phenyl-content stationary phase") and a 50% (mole fraction) liquid crystalline dimethylpolysiloxane phase. Retention data were obtained for parent PAHs from molecular mass (MM) 128 g/mol (naphthalene) to 328 g/mol (benzo[c]picene) and for 12 sets of methyl-PAHs (methylfluorenes, methylanthracenes, methylphenanthrenes, methylfluoranthenes, methylpyrenes, methylbenz[a]anthracenes, methylbenzo[c]phenanthrenes, methylchrysenes, methyltriphenylenes, methylbenzo[a]pyrenes, methylperylenes, and methylpicenes). Molecular shape descriptors such as length-to-breath ratio (L/B) and thickness (T) were determined for all the PAHs studied. Correlation between I and L/B ratio was evaluated for both stationary phases with a better correlation observed for the 50% liquid crystalline phase (correlation coefficients ranging from 0.22 to 1.00). Graphical Abstract GC separation of six methylchrysene isomers (m/z 242) on two different stationary phases: 50 % phenyl-like methylpolysiloxane phase and 50 % liquid crystalline phase. Retention indices (I) are plotted as a function of L/B for both phases. The data marker numbers identify each isomer based on methyl-substitution position.

Until recently, the Vitamin D External Quality Assessment Scheme (DEQAS) assessed the performance of various assays for the determination of serum total 25-hydroxyvitamin D [25(OH)D] by using a consensus mean based on the all-laboratory trimmed mean (ALTM) of the approximately 1000 participants' results. Since October 2012, the National Institute of Standards and Technology (NIST), as part of the Vitamin D Standardization Program, has participated in DEQAS by analyzing the quarterly serum sample sets using an isotope dilution LC-tandem MS (ID LC-MS/MS) reference measurement procedure to assign an accuracy-based target value for serum total 25(OH)D. NIST has analyzed 90 DEQAS samples (18 exercises × 5 samples/exercise) to assign target values. The NIST-assigned values are compared with the ALTM and the biases assessed for various assays used by the participants, e.g., LC-MS/MS, HPLC, and several ligand-binding assays. The NIST-value assignment process and the results of the analyses of the 90 DEQAS samples are summarized. The absolute mean bias between the NIST-assigned values and the ALTM was 5.6%, with 10% of the samples having biases >10%. Benefits of the accuracy-based target values are presented, including for sample sets with high concentrations of 25(OH)D2 and 3-epi-25(OH)D3.

Since 2005, the National Institute of Standards and Technology (NIST) has collaborated with the National Institutes of Health (NIH), Office of Dietary Supplements (ODS) to improve the quality of measurements related to human nutritional markers of vitamin D status. In support of the NIH-ODS Vitamin D Initiative, including the Vitamin D Standardization Program (VDSP), NIST efforts have focused on (1) development of validated analytical methods, including reference measurement procedures (RMPs); (2) development of Standard Reference Materials (SRMs); (3) value assignment of critical study samples using NIST RMPs; and (4) development and coordination of laboratory measurement QA programs. As a result of this collaboration, NIST has developed RMPs for 25-hydroxyvitamin D2 [25(OH)D2], 25(OH)D3, and 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3]; disseminated serum-based SRMs with values assigned for 25(OH)D2, 25(OH)D3, 3-epi-25(OH)D3, and 24R,25(OH)2D3; assigned values for critical samples for VDSP studies, including an extensive interlaboratory comparison and reference material commutability study; provided an accuracy basis for the Vitamin D External Quality Assurance Scheme; coordinated the first accuracy-based measurement QA program for the determination of 25(OH)D2, 25(OH)D3, and 3-epi-25(OH)D3 in human serum/plasma; and developed methods and SRMs for the determination of vitamin D and 25(OH)D in food and supplement matrix SRMs. The details of these activities and their benefit and impact to the NIH-ODS Vitamin D Initiative are described.

A link between the aromatic character of polycyclic aromatic hydrocarbons and gas chromatography elution order in columns with a polysiloxane backbone in the stationary phase is reported for the first time. The aromatic character was calculated using a method that combines the π-Sextet Rule and the Pauling Ring Bond Orders to allow the establishment of the location and migration of aromatic sextets in PAH structures. One GC column with a polysiloxane - like backbone (Rxi-PAH) and three GC columns with a polysiloxane backbone (DB-5, SE-52, and LC-50), were used for the analysis. According to the results of this study, within an isomer group, PAHs that contain a lower number of rings affected by the aromatic sextets tend to elute earlier than PAHs that contain a higher number of rings affected by the aromatic sextets. The PAHs that follow the calculated elution order are 88 % in the Rxi-PAH column, 88 % in the DB-5 column, 93 % in the SE-52 column, and 85% in the LC-50 column. It is expected that future analyses with other aromatic compounds in GC columns with a polysiloxane backbone in the stationary phase will follow a GC elution order that agrees with the aromatic character of the molecules., Competing Interests: The authors declare no competing financial interest. Certain commercial equipment, instruments, or materials (or suppliers, or software, ...) are identified in this paper to foster understanding. Such identification does not imply recommendation or endorsement by the National Institute of Standards and Technology, NIST, nor does it imply that the materials or equipment identified are necessarily the best available for the purpose.

In spite of recent progress in revascularization and anesthesiology procedures, in vascular centers today there are still patients with Critical Limb Ischemia (CLI) who are not considered suitable for revascularization. Most of these patients are elderly, with high co-morbidity factors, poor run off arterial limb vessels, and often with a salvageable limb. They are absent or neglected in the literature, and generally go untreated. We report details of 24- month amputations and mortality rates in 90 patients with CLI who were not considered suitable for revascularization, treated from 2005 to 2008 in a dedicated unit of our department. Patients with endstage general conditions or needing immediate primary amputation were excluded from our study. All patients received multidisciplinary assessment. Their median age was 78.4 years; 28 patients (31.1%) had rest pain only, and 62 (68.8%) had ischemic skin foot-leg wounds or gangrene <2 cm. Sixteen patients (37.7%) were assessed as not suitable for revascularization because of poor functional status, and 76 (64.4%) because of inadequate outflow limb vessels. Drugs to manage pain were administered to all patients (100%), prostanoid infusions were given to 80 (88%), anti-platelet drugs to 87 (96%), low molecular weight heparin or oral anticoagulants to 13 (14%), spinal cord stimulation to 3 (3%), hyperbaric oxygen treatment to 16 (17%) and wound treatment to 62 (68.8%). Toe or other foot-sparing amputations had a rate of 13%. After 24 months, the major amputation rate was 9.3% and the mortality rate 23.2%. Our observations show that, in spite of progress in revascularization procedures, there are still patients with CLI who are not considered suitable for revascularization and who could benefit from non-surgical treatment if a tailored approach is used.

Bergamot juice (BJ) contains different classes of flavonoids (e.g. flavanones and flavones) that can exert beneficial effects on human health. The aim of this study was to evaluate the qualitative and quantitative composition of a BJ obtained from fruits harvested in Southern Italy (Calabria) at the end of their maturation period. The identity of several flavonoids and furanocoumarins was assessed by co-chromatography, UV spectra and molecular weight comparison. The unknown compounds were dissociated by induced collision (CID-MS) and their identity established through the characteristic ions product. By this approach a complete profile of about twenty compounds (furano-coumarins, flavonoids C- and O-glycosides) present in BJ was obtained. Furthermore, three acylated flavanones, present in amounts of 20.1+/-1.1, 89.3+/-2.2 and 190.1+/-3.1 mg/L, respectively, and which seem to correspond to di-oxalate derivatives of neoeriocitrin, naringin and neohesperidin, were identified for the first time in BJ. The other main flavanones were naringin, neohesperidin and neoeriocitrin, and their content was 167.5+/-1.8, 123.9+/-1.7 and 73.3+/-1.6 mg/L, respectively. Concerning flavones, the total amount in BJ was about 160 mg/L and the main ones were vicenin-2, stellarin-2, rhoifolin and neodiosmin. Bergapten and bergamottin were the primary furanocoumarins in BJ and their amounts were 9.0+/-0.4 and 18.2+/-0.5 mg/L, respectively.

Continuing our investigations on inhibitors of ribonucleotide reductase (RNR), the crucial enzyme that catalyses the reduction of ribonucleotides to deoxyribonucleotides, we have now prepared and evaluated 5'-phosphonoacetic acid, amide and ester analogues of adenosine, uridine and cytidine with the aim to verify both substrate specificity and contribution to biological activity of diphosphate mimic moieties. A molecular modelling study has been conducted on the RNR R1 subunit, in order to verify the possible interaction of the proposed bioisosteric moieties. The study compounds were finally tested on the recombinant murine RNR showing a degree of inhibition that ranged from 350 microM for the UDP analogue 5'-deoxy-5'-N-(phosphon-acetyl)uridine sodium salt (amide) to 600 microM for the CDP analogue 5'-O-[(diethyl-phosphon)acetyl]cytidine (ester). None of the tested compounds displayed noteworthy cytostatic activity at 100-500 microM concentrations, whereas ADP analogue 5'-N-[(diethyl-phosphon) acetyl]adenosine (amide) and 5'-deoxy-5'-N-(phosphon-acetyl)adenosine sodium salt (amide) showed a moderate inhibitory activity (EC50: 48 microM) against HSV-2 and a modest inhibitory activity (EC50: 110 microM) against HIV-1, respectively.