In the HPLC analysis, EA, rutin, (+) catechin and quercetin (3007.26, 490.74, 117.72 and 13.85 mg/100 g extract, respectively) were detected. Phytochemical group test of ASE indicated the presence of reducing sugars, Mizoribine DNA Damage inhibitor steroids, terpenoids, saponins,

tannins and flavonoids. Thus, high level of EA in ASE, along with other phytochemical constituents might be responsible for the observed activity of the extract. (C) 2014 PVJ. All rights reserved”
“Inhibition of the non-receptor tyrosine kinase ITK, a component of the T-cell receptor signalling cascade, may represent a novel treatment for allergic asthma. Here we report the structure-based optimization of a series of benzothiazole amides that demonstrate sub-nanomolar inhibitory potency against ITK with good cellular activity and kinase selectivity. We also elucidate the binding mode of these inhibitors by solving the X-ray crystal structures of several inhibitor-ITK complexes. (C) 2013 Elsevier Ltd. All rights reserved.”
“Introduction: Pulmonary arterial hypertension (PAH) is a major cause of mortality in connective tissue disease (CTD). We sought to quantify survival and determine factors predictive of mortality in a cohort of patients with CTD-associated PAH (CTD-PAH) in the current era of advanced PAH therapy.\n\nMethods: Patients with right heart catheter proven CTD-PAH were recruited

from six specialised PAH treatment centres across Australia and followed prospectively. Using survival methods including Cox proportional FK228 mw hazards regression, we modelled for all-cause mortality. Independent variables included demographic, clinical and hemodynamic data.\n\nResults: Among

117 patients (104 (94.9%) with systemic sclerosis), during 2.6 +/- 1.8 (mean +/- SD) years of follow-up from PAH diagnosis, there were 32 (27.4%) deaths. One-, two-and three-year survivals were 94%, 89% and 73%, respectively. In multiple regression analysis, higher mean right atrial pressure (mRAP) at diagnosis (hazard ratio (HR) = 1.13, 95% CI: 1.04 to 1.24, P = 0.007), lower baseline six-minute walk distance (HR = 0.64, 95% CI: 0.43 to 0.97, P = 0.04), higher baseline World Health Organization functional GSK1838705A solubility dmso class (HR = 3.42, 95% CI: 1.25 to 9.36, P = 0.04) and presence of a pericardial effusion (HR = 3.39, 95% CI: 1.07 to 10.68, P = 0.04) were predictive of mortality. Warfarin (HR = 0.20, 95% CI: 0.05 to 0.78, P = 0.02) and combination PAH therapy (HR = 0.20, 95% CI: 0.05 to 0.83, P = 0.03) were protective.\n\nConclusions: In this cohort of CTD-PAH patients, three-year survival was 73%. Independent therapeutic predictors of survival included warfarin and combination PAH therapy. Our findings suggest that anticoagulation and combination PAH therapy may improve survival in CTD-PAH. This observation merits further evaluation in randomised controlled trials.

(C) 2008 Elsevier B.V. All rights reserved.”
“The tumor necrosis factor superfamily (TNFSF) consists of more than 20 members that can modulate cellular and immunological functions, including cell survival and the stimulation of an inflammatory response. Y 27632 Many TNF superfamily members display potent anticancer activity when used as recombinant proteins in vitro and in vivo. While TNF, TRAIL and FasL have already been used as payloads in antibodybased

pharmacodelivery strategies, most TNF superfamily members have not yet been investigated as antibody payloads. Here, we report the cloning, production and characterization of eight novel antibody fusion proteins based on CD4OL, FasL, TRAIL, LiGHT, VEGI, lymphotoxin alpha, lymphotoxin beta and lymphotoxin alphal /beta2. The monoclonal antibody F8 was chosen as fusion partner of proven tumor targeting performance, which recognizes the alternatively-spliced EDA domain of fibronectin, a marker of angiogenesis. A quantitative biodistribution analysis performed with radioiodinated protein preparations in tumor-bearing mice revealed that TRAIL and lymphotoxin

alphal /beta2 were able to selectively accumulate at the tumor site, while all other members of the TNF superfamily abrogated www.selleckchem.com/products/VX-680(MK-0457).html the selective tumor targeting performance of the parental antibody or accumulated also in healthy tissues. The study indicates that even cytokines, which are closely related in terms of structure and function, may have a substantially different impact on the biodistribution and functional check details properties of the corresponding fusions with disease-homing antibodies. (C) 2013 Elsevier B.V. All rights reserved.”
“Background: Our study objective was to describe the frequency, indications, and outcomes after inferior vena cava (IVC) filter placement in a population-based sample of residents of the Worcester, Massachusetts, metropolitan area who had been diagnosed as having acute venous thromboembolism

(VTE) in 1999, 2001, and 2003.\n\nMethods: A retrospective chart review of inpatient and outpatient medical records was conducted. Recorded indication(s) for IVC filter placement was determined among a subset of cases from 3 Worcester tertiary care hospitals. Three thrombosis specialists assessed the appropriateness of IVC filter placement.\n\nResults: Of 1547 greater Worcester residents with validated acute VTE and without a prior IVC filter, 203 (13.1%) had an IVC filter placed after acute VTE. Patients with an IVC filter were older, had more comorbidities, and had a higher mortality rate during 3 years of follow-up. There was unanimous agreement by panel members that the use of an IVC filter was appropriate in 51% of cases and inappropriate in 26% of cases, with no consensus in the remaining 23%.\n\nConclusions: In this community-based study, IVC filters were frequently used in the treatment of patients with acute VIE.

The expressions were limited to only some Ro-3306 chemical structure of the effector cells within a population, disclosing disparities in numbers and location between naive colonies and their immune challenged counterparts. Administration of the immunosuppression drug Cyclosporine-A during ascidian’s allogeneic assays inhibited both fusion and rejection reactions,

probably through the inhibition of ascidian’s immunocytes (morula cells) movement and activation. Our results, together with previous published data, depict an immunophilins-based immune mechanism, which is similarly activated in allogeneic responses of distantly related animals from sponges to humans. (C) 2012 Elsevier GmbH. All rights reserved.”
“Mosquito infections with natural isolates

of Plasmodium falciparum are notoriously variable and pose a problem for reliable evaluation of efficiency of transmission-blocking agents for malaria control interventions. Here, we show that monoclonal P. falciparum isolates produce higher parasite loads than mixed ones. Induction of the mosquito immune responses by wounding efficiently decreases Plasmodium numbers in monoclonal infections but fails to do so in infections with two or more parasite genotypes. Our results point to the parasites genetic complexity as a potentially crucial component of mosquito-parasite interactions. (C) 2012 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.”
“The aim of this exploratory survey was to assess predictors for an selleck chemicals academic career in a population of physicians working full time (FT) or part time (PT) in the north-western part of Switzerland. We also asked for individual attitudes, influences and motivations towards PT work.\n\nMETHODS: In a cross-sectional study,

resident and senior physicians were asked via hyperlink to complete an anonymous 91-item questionnaire. The completed questionnaires were collected anonymously online.\n\nRESULTS: Overall, 389 of 1104 (35%) questionnaires were NU7441 in vivo returned for analysis. Of the respondents, 68.1% worked FT and 31.9% PT. More women than men (57.5% vs 42.5%) responded to the questionnaire and more women than men (68.2% vs 31.8%) were working as residents. Of the FT physicians, 88.9% favoured a work reduction to 60.0-90.0%; 82.9% FT and 97.0% PT physicians considered the introduction of PT work opportunities in their hospital as reasonable. A higher academic score was reached by men (mean 3.69, SD 3.39) than by women (mean 2.22, SD 2.77). Among senior physicians, PT work had a significant influence on the academic score. The possibility to do research, followed by male gender, were the two most significant factors positively influencing an academic career.\n\nCONCLUSION: The possibility to perform research remains the most important predictor for a successful academic career. Working PT diminishes the chance of academic success.

The diagnostic value of the MAT single acute or convalescent blood sample was determined in dogs in which leptospirosis status could be classified. The diagnostic value of a commercially available genus-specific PCR assay was evaluated by use of 36 blood samples and 20 urine samples.\n\nResults-Serologic acute testing of an acute blood sample had a specificity of 100% (95% Cl, 76% to 100%),

a sensitivity of 50% (33% to 67%), and an accuracy of 64% (49% to 77%). Serologic testing of a convalescent blood sample had a specificity of 92% PU-H71 concentration (65% to 99%), a sensitivity of 100% (87% to 100%), and an accuracy of 98% (88% to 100%). Results of the Leptospira PCR assay were negative for all samples from dogs for which leptospirosis status could selleck screening library be classified.\n\nConclusions

and Clinical Relevance-Serologic MAT results were highly accurate for diagnosis of leptospirosis in dogs, despite a low sensitivity for early diagnosis. In this referral setting of dogs pretreated with antimicrobials, testing of blood and urine samples with a commercially available genus-specific PCR assay did not improve early diagnosis.”
“The main pathological change of radiation-induced heart disease is fibrosis. Emerging evidence has indicated that Astragalus membranaceus and its extractant, Astragalus saponin (AST), were used for treating fibrosis diseases. In the present study, the effects of AST on fibrosis damage induced by irradiation were determined. LY2090314 inhibitor After being irradiated with 1 or 2-Gy X-rays, obvious changes of endoplasmic reticulum morphology were observed in cardiac fibroblasts (CFs), suggesting that its protein processing function was imbalanced, which indirectly indicated that fibrosis damage was caused by irradiating CFs. The expression levels of TGF-beta 1 and collagen I (Col-1)

were increased at 48-h post-irradiation. Administration of 20 mu g/ml AST reduced the production of reactive oxygen species in irradiated CFs and decreased the expression of Col-1, TGF-beta 1, and p-Smad2/3. Polymerase chain reaction (PCR)-array analysis showed that there were similar to 30 genes which were mainly classified into extracellular matrix, remodeling enzymes, inflammatory cytokines/chemokines, and TGF-beta superfamily, were up-regulated after treatment with 1-Gy X-ray, whereas most of these genes were down-regulated when pretreated with 20 mu g/ml of AST. In addition, TIMP1 and Smad7 genes that were down-regulated after treatment with 1-Gy X-ray were up-regulated when pretreated with 20 mu g/ml of AST. In conclusion, radiation-induced fibrosis damage was observed at a cellular level. AST attenuated this fibrosis damage effect in irradiated CFs and this anti-fibrosis effect may be closely related to its antioxidant action. The involvement of fibrosis-related molecules in irradiated CFs was systematically demonstrated by a PCR array for the first time.

“
“Cell therapy BI 2536 in vitro aiming at the replacement of degenerated neurons is a very attractive approach. By using an established in vitro organotypic brain stem (BS) slice culture we screen for candidate donor

cells, some of them being further functionally assessed in in vivo models of sensorineural hearing loss. Both in vitro and in vivo systems show that implanted cells face challenges of survival, targeted migration, differentiation and functional integration with the host tissue. Low success rates are possibly due to the lack of necessary neurotrophic factors, adhesion molecules and guiding cues. Olfactory ensheathing cells (OECs) have been shown to express a number of neurotrophic factors and to promote axonal growth through cell to cell interactions. In the present study we co-cultured OECs with Cl-amidine price organotypic BS slice in order to see if OECs can serve as a facilitator when screening candidate donor cells in an organotypic culture setup. Here we show that OECs

when co-cultured with the auditory BS slice not only promote neurite outgrowth from the cochlear nucleus (CN) region of the BS slice but also support cells by having BS slice axons growing along their processes. These findings further suggest that OECs may enhance survival and targeted migration of candidate donor cells suitable for cell therapy in vitro and in vivo. This article is part of a Special Issue entitled: Understanding olfactory ensheathing glia Selleckchem YM155 and their prospect for nervous system repair. (C) 2010 Elsevier Inc. All rights reserved.”
“In this article we will discuss the integration of developmental

patterning mechanisms with waves of competency that control the ability of a homogeneous field of cells to react to pattern forming cues and generate spatially heterogeneous patterns. We base our discussion around two well known patterning events that take place in the early embryo: somitogenesis and feather bud formation. We outline mathematical models to describe each patterning mechanism, present the results of numerical simulations and discuss the validity of each model in relation to our example patterning processes.”
“Scabies remains a significant public health problem worldwide. Research into aspects of Sarcoptes scabiei biology and host parasite interactions has been impeded by an inability to maintain mites in vitro and by limited access to parasite material and infected subjects. The generation of comprehensive expressed sequence tag libraries has enabled the initial characterisation of molecules of interest to diagnostics, vaccines, and drug resistance. The recent development and utilisation of animal models, combined with next-generation technologies, is anticipated to lead to new strategies to prevent, diagnose, and treat scabies, ultimately improving skin health in both human and veterinary settings.

The functional DNA markers for lcyE were associated with lutein, and with the ratio of carotenoids in the alpha and beta branches, but not with provitamin A levels. However, the combined effects of the two genes were stronger than their individual effects on all carotenoids.\n\nConclusions: Tropical maize inbred lines harbouring the favourable alleles of the crtRB1-5′TE and 3′TE functional markers produce higher levels of provitamin A. Salubrinal price Such maize lines can be used

as donor parents to speed up the development of provitamin A biofortified tropical maize varieties adapted to growing conditions and consumer preferences, providing a route towards mitigation of vitamin A malnutrition in Sub-Saharan Africa.”
“Introduction: Maximal

oxygen uptake VO(2max) has an important place in the assessment of cardiopulmonary fitness. Currently there is insufficient normative data for Iranian adolescents. With this preliminary study, we aimed to set up the first normative data for our laboratory which may also serve as a basis for future large population-based studies in Iran.\n\nMaterial and methods: We assessed the peak oxygen consumption of 95 healthy Iranian adolescents, aged 13-17 years, and examined the cardiopulmonary responses to exercise test in relation to their age, sex and body size. Between June and September 2007, the level of aerobic capacity was evaluated by maximal oxygen consumption VO(2max)), which was calculated GDC-0994 using the exercise test on a bicycle ergometer.\n\nResults: During a four-month period, the cardiopulmonary exercise test was conducted on a population-based sample of 95 adolescents (44 boys and 51 girls). The mean age and body mass index were 15.59 +/- 1.85 years and 23.46 +/- 5.05 kg/m(2), respectively. The VO(2max) of boys was significantly higher in boys than in girls (16.71 +/- 8.72/12.48 +/- 6.25 ml/kg/min respectively, p = 0.001).\n\nConclusions: The current study presents normal data for a small representative sample of healthy Iranian adolescents. VO(2max) in our study was in the poor to average range when compared to the standard values of other populations. This information should prompt policy makers and medical

educators to address this problem, and to consider promoting exercise and integrating physical fitness into the school selleck chemical curriculum.”
“Numerous members of the Brassicaceae possess non-photoconvertible water-soluble chlorophyll (Chl)-binding proteins (Class II WSCPs), which function as Chl scavengers during cell disruption caused by wounding, pest/pathogen attacks, and/or environmental stress. Class II WSCPs have two extension peptides, one at the N-terminus and one at the C-terminus. The N-terminal peptide acts as a signal peptide, targeting the protein to the endoplasmic reticulum body, a unique defensive organelle found only in the Brassicaceae. However, the physiological and biochemical functions of the C-terminal extension peptide had not been characterized previously.

0-Tmagnetic resonance scanner. Two neuroradiologists learn more independently assessed images for anatomical delineation (infundibulum, optic apparatus, and cavernous sinus), degree of artifact, and confidence in lesion definition or exclusion using a 5-point scale. In addition, the readers were asked to rank overall preference. Results: Readers A and B found 3D Cube to be better or equal to 2D FSE in 84% and 86% of the cases. Three-dimensional Cube provided significantly better images than 2D FSE with

respect to delineation of the infundibulum (P smaller than 0.0001), cavernous sinus (P smaller than 0.0001), optic apparatus (P = 0.002 for reader A and P = 0.265 for reader B), and fewer artifacts at the sellar floor (P smaller than 0.0001). Three-dimensional Cube provided greater lesion conspicuity or confidence in lesion exclusion (P smaller than 0.0001). Conclusions: Three-dimensional Cube provides superior quality with thinner slices as well as diminished artifact and can replace conventional click here 2D FSE sequences for routine evaluations of the pituitary and parasellar region.”
“Background Unplanned pregnancy is a key public health indicator. We describe the prevalence of unplanned pregnancy, and associated factors, in a general population sample in Britain (England, Scotland, and Wales).\n\nMethod We did a probability sample survey, the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3), of

15 162 men and women aged 16-74 years in Britain, including

5686 women of child-bearing age (16-44 years) who were included in the pregnancy analysis, between Sept 6, 2010, and Aug 31, 2012. We describe the planning status of pregnancies with known outcomes in the past year, and report the annual population prevalence of unplanned pregnancy, using a validated, multicriteria, multi-outcome measure (the London Measure of Unplanned Pregnancy). We set the findings in the context of secular trends in reproductive health-related events, and patterns across the life course.\n\nFindings 9.7% of women aged 16-44 years had pregnancies with known outcome in the year before interview, of which 16.2% (95% CI 13.1-19.9) https://www.selleckchem.com/products/pf299804.html scored as unplanned, 29.0% (25.2-33.2) as ambivalent, and 54.8% (50.3-59.2) as planned, giving an annual prevalence estimate for unplanned pregnancy of 1.5% (1.2-1.9). Pregnancies in women aged 16-19 years were most commonly unplanned (45.2% [30.8-60.5]). However, most unplanned pregnancies were in women aged 20-34 years (62.4% [50.2-73.2]). Factors strongly associated with unplanned pregnancy were first sexual intercourse before 16 years of age (age-adjusted odds ratio 2.85 [95% CI 1.77-4.57], current smoking (2.47 [1.46-4.18]), recent use of drugs other than cannabis (3.41 [1.64-7.11]), and lower educational attainment. Unplanned pregnancy was also associated with lack of sexual competence at first sexual intercourse (1.90 [1.14-3.08]), reporting higher frequency of sex (2.11 [1.25-3.

However, the peri-implant crestal bone change did not differ significantly among the 3 types of implant-abutment connections during the healing phase, loading phase 1, or loading phase 2. This retrospective clinical study reveals that the design of the implant-abutment connection appears to have no significant impact on short-term peri-implant crestal bone change.”
“Gastric bypass surgery

and exenatide therapy represent two relatively new methods in treating morbid VX-770 inhibitor obesity and type 2 diabetes, although there are many differences between them. With the data supported from our hospital, we just want to investigate the differences between bypass surgery and exenatide injection and want to answer the question: Which one is the best? And Why?\n\nData from January 2009 to January 2010 were summarized for comparison at Shengjing hospital, including weight loss, plasma glucose and insulin changes, glycosylated hemoglobin, and the subjective scores of patients themselves. Plasma lipoprotein and serum ions were measured to evaluate the nutrition status.\n\nPatients in the GB group received more weight loss and better glucose control compared with the EX group. At 6 months, feeding insulin level in the GB group was 18.1 +/- 3.2 mU/L, which was much lower than that in the EX group (64.5 +/- 13.2 mU/L, P < 0.01). The Hb1AC level in the GR group was 6.08 +/- 0.56 %, much

lower than that in the EX group (7.19 +/- 0.72 %, P < 0.01). We did not

find any statistical mTOR activation differences in lipoprotein, plasma ions, and subjective scores between the GB and EX groups.\n\nGastric bypass surgery is better in weight control and in the remission Dorsomorphin of insulin resistance compared with exenatide therapy. Both methods were safe and have no nutritional disorder in early stage, although the transferring in the GB group was higher than the EX group. The subjective scores from both groups declared that both methods could be accepted by patients.”
“Objectives: The aims of this study were to gain a better understanding of the motivations of pregnant women utilizing moxibustion for breech presentation and to measure the impact of research results on these patients’ treatment decisions regarding this alternative medicine technique.\n\nDesign: The study involved a statistical analysis of two self-administered questionnaires to 212 women who had previously participated in a randomized clinical trial on the efficacy of moxibustion; in addition, a qualitative thematic content analysis for open-ended questions was also performed.\n\nResults: Most women (69%) reported treating themselves at least once with complementary and alternative medicine (CAM). Higher use of CAM was associated with higher education and Caucasian origin. Pregnancy was associated with a significant reduction in utilization of CAMs.

Both methods showed meaningful results for the Epworth Sleepiness Scale and polysomnography variables

12 months after treatment compared with baseline measurements. The results were not significantly different in the posttreatment intergroup comparisons. Treatment success rates were 52.4% for click here nasal CPAP and 53.8% for TCRFTVR (P=.92).\n\nConclusion: Similar comparison results with nasal CPAP in objective and subjective variables make single-stage, multilevel TCRFTVR a good alternative in primary treatment of mild to moderate obstructive sleep apnea.”
“We report the case of an 8-days-old patient with linear rows of vesiculobullous lesions from birth. Along with these lesions, the neonate had eosinophilia, which made us arrive to the clinical diagnosis of Incontinentia Pigmenti.\n\nIncontinentia Pigmenti or Bloch Sulzberger disease is a multisystemic neuroectodermal disorder that affects mostly women, which includes as initial manifestation cutaneous lesions

that evolve by outbreaks. Occasionally, it is associated with neurologic, ophthalmologic, and dental compromise. This must be considered as a differential diagnosis when a neonate presents vesiculobullous lesions.”
“A partial resistance to maize mosaic virus (MMV) and maize stripe virus (MStV) was mapped in a RILs population derived from a cross between AZD9291 inhibitor lines MP705 (resistant) and B73 (susceptible). A genetic map constructed from 131 SSR markers spanned 1399cM with an average distance of 9.6cM. A total of 10 QTL were detected for resistance to MMV and MStV, using composite interval mapping. A major QTL explaining 34-41% of the phenotypic variance for early resistance to MMV was detected on chromosome 1. Another major QTL explaining up to 30% of the phenotypic variation for all traits of resistance to MStV was detected in the centromeric region of chromosome 3 (3.05 bin). After adding supplementary SSR markers, this region was found to correspond well to the one where Selleckchem IWR-1-endo a QTL of resistance to MStV already was located in a previous mapping

study using an F-2 population derived from a cross between Rev81 and B73. These results suggested that these QTL of resistance to MStV detected on chromosome 3 could be allelic in maize genome.”
“This study was carried out in three geographically contrasting countries of the Mediterranean region. It aims to understand the impact of climate change, particularly the temperature increases, on phenological stage of three taxonomically different species (early and late-spring-flowering species). Three species, namely olive (Olea europaea), apple (Malus domestica Borkh.) and almond (Prunus dulcis (Mill.)) were investigated to highlight the phenological behavior of one species at different locations and different species at one location. Climatic and phenological data were collected from Morocco, France and Italy over the last 40 years.

A carer accompanied 77 % of patients. Among carers, 36.6 % required time off from work, and 77.6 % had to interrupt daily activities. Median distance traveled was 36 km. The average cost of travel was 10 euros with 25 % of patients spending more than 30 euros.\n\nData from patients enrolled in the TARIFF registry confirm that there are social and economic www.selleckchem.com/products/nu7441.html impacts to patients attending routine device checks in hospital which can be significantly reduced by using a remote monitoring strategy.”
“Visual prosthetics is an expanding

subfield of functional electrical stimulation which has gained increased interest recently in light of new advances in treatments and technology. These treatments and technology represent a major improvement over prior art, but are still subject to a host of limitations which are dependent on the manner in GDC-0941 solubility dmso which one approaches the topic of visual prosthetics. These limitations pose new research challenges whose solutions are directly applicable to the well-being of blind individuals everywhere. In this review, we will outline and critically compare major current approaches to visual prosthetics, and in particular

retinal prosthetics. Then, we will engage in an in-depth discussion of the limitations imposed by current technology, physics, and the underlying biology of the retina to highlight several of the challenges currently facing researchers.”
“The syntheses of optically active compounds (whether of pharmaceutical or synthetic importance, or as promising candidates as chiral ligands and auxiliaries in asymmetric syntheses) result in the formation of a mixture of products with one enantiomer predominating. Usually, the practice is to use standard open-column chromatography for

the first purification step in an enantioselective synthesis; the workup of the reaction product by crystallization or achiral chromatography would mask the real efficiency of the enantioselective methodology, since GSK2879552 in vivo enantiomeric ratio (er) of the product may change by any of these methods. Most of the synthetic organic chemists are aware of the influence of crystallization on the er value. Majority of synthetic organic chemists are, however, not aware, while employing standard chromatography, that there may be an increase or decrease of er value. In other words, an undesired change in er goes unnoticed when such a mixture of enantiomers is isolated by chromatography on an achiral-phase because of the prevalent concept of basic stereochemistry. Such unnoticed errors in enantioselective reactions may lead to misinterpretations of the enantioselective outcome of the synthesis. The scientific issue is, what is the difference between a racemic and nonracemic mixture in achiral environment (e.g.