A DFT study of electron-phonon interactions for theC2CNandVNNBdefects in hexagonal boron nitride: investigating the role of the transition dipole direction.

Quantum emitters in two-dimensional hexagonal boron nitride (h-BN) have generated significant interest due to observations of ultra-bright emission made at room temperature. The expectation that solid-state emitters exhibit broad zero-phonon lines at elevated temperatures has been put in question by recent observations of Fourier transform (FT) limited photons emitted from h-BN flakes at room temperature. All decoupled emitters produce photons that are directed in-plane, suggesting that the dipoles are perpendicular to the h-BN plane. Motivated by the promise of an efficient and scalable source of indistinguishable photons that can operate at room temperature, we have developed an approach using density functional theory (DFT) to determine the electron-phonon coupling for defects that have in- and out-of-plane transition dipole moments. Our DFT calculations reveal that the transition dipole for theC2CNdefect is parallel to the h-BN plane, and for theVNNBdefect is perpendicular to the plane. We calculate both the phonon density of states and the electron-phonon matrix elements associated with the h-BN defective structures. We find no indication that an out-of-plane transition dipole by itself will result in the low electron-phonon coupling that is expected to produce FT-limited photons at room temperature. Our work provides direction to future DFT software developments and adds to the growing list of calculations relevant to researchers in the field of solid-state quantum information processing.

Experimental Analysis of Energy Transfers between a Quantum Emitter and Light Fields.

Energy can be transferred between two quantum systems in two forms: unitary energy-that can be used to drive another system-and correlation energy-that reflects past correlations. We propose and implement experimental protocols to access these energy transfers in interactions between a quantum emitter and light fields. Upon spontaneous emission, we measure the unitary energy transfer from the emitter to the light field and show that it never exceeds half the total energy transfer and is reduced when introducing decoherence. We then study the interference of the emitted field and a coherent laser field at a beam splitter and show that the nature of the energy transfer quantitatively depends on the quantum purity of the emitted field.

Forecasting brain activity based on models of spatiotemporal brain dynamics: A comparison of graph neural network architectures.

Comprehending the interplay between spatial and temporal characteristics of neural dynamics can contribute to our understanding of information processing in the human brain. Graph neural networks (GNNs) provide a new possibility to interpret graph-structured signals like those observed in complex brain networks. In our study we compare different spatiotemporal GNN architectures and study their ability to model neural activity distributions obtained in functional MRI (fMRI) studies. We evaluate the performance of the GNN models on a variety of scenarios in MRI studies and also compare it to a VAR model, which is currently often used for directed functional connectivity analysis. We show that by learning localized functional interactions on the anatomical substrate, GNN-based approaches are able to robustly scale to large network studies, even when available data are scarce. By including anatomical connectivity as the physical substrate for information propagation, such GNNs also provide a multimodal perspective on directed connectivity analysis, offering a novel possibility to investigate the spatiotemporal dynamics in brain networks.

Bright Polarized Single-Photon Source Based on a Linear Dipole.

Semiconductor quantum dots in cavities are promising single-photon sources. Here, we present a path to deterministic operation, by harnessing the intrinsic linear dipole in a neutral quantum dot via phonon-assisted excitation. This enables emission of fully polarized single photons, with a measured degree of linear polarization up to 0.994±0.007, and high population inversion-85% as high as resonant excitation. We demonstrate a single-photon source with a polarized first lens brightness of 0.50±0.01, a single-photon purity of 0.954±0.001, and single-photon indistinguishability of 0.909±0.004.

A graph neural network framework for causal inference in brain networks.

A central question in neuroscience is how self-organizing dynamic interactions in the brain emerge on their relatively static structural backbone. Due to the complexity of spatial and temporal dependencies between different brain areas, fully comprehending the interplay between structure and function is still challenging and an area of intense research. In this paper we present a graph neural network (GNN) framework, to describe functional interactions based on the structural anatomical layout. A GNN allows us to process graph-structured spatio-temporal signals, providing a possibility to combine structural information derived from diffusion tensor imaging (DTI) with temporal neural activity profiles, like that observed in functional magnetic resonance imaging (fMRI). Moreover, dynamic interactions between different brain regions discovered by this data-driven approach can provide a multi-modal measure of causal connectivity strength. We assess the proposed model's accuracy by evaluating its capabilities to replicate empirically observed neural activation profiles, and compare the performance to those of a vector auto regression (VAR), like that typically used in Granger causality. We show that GNNs are able to capture long-term dependencies in data and also computationally scale up to the analysis of large-scale networks. Finally we confirm that features learned by a GNN can generalize across MRI scanner types and acquisition protocols, by demonstrating that the performance on small datasets can be improved by pre-training the GNN on data from an earlier study. We conclude that the proposed multi-modal GNN framework can provide a novel perspective on the structure-function relationship in the brain. Accordingly this approach appears to be promising for the characterization of the information flow in brain networks.

Hong-Ou-Mandel Interference with Imperfect Single Photon Sources.

Hong-Ou-Mandel interference is a cornerstone of optical quantum technologies. We explore both theoretically and experimentally how unwanted multiphoton components of single-photon sources affect the interference visibility, and find that the overlap between the single photons and the noise photons significantly impacts the interference. We apply our approach to quantum dot single-photon sources to access the mean wave packet overlap of the single-photon component. This study provides a consistent platform with which to diagnose the limitations of current single-photon sources on the route towards the ideal device.

Hybridizing EMD with cICA for fMRI Analysis of Patient Groups.

Independent component analysis (ICA), as a data driven method, has shown to be a powerful tool for functional magnetic resonance imaging (fMRI) data analysis. One drawback of this multivariate approach is, that it is naturally not convenient for analysis of group studies. Therefore various techniques have been proposed in order to overcome this limitation of ICA. In this paper a novel ICA based work-flow for extracting resting state networks from fMRI group studies is proposed. An empirical mode decomposition (EMD) is used to generate reference signals in a data driven manner, which can be incorporated into a constrained version of ICA (cICA), what helps to overcome the inherent ambiguities. The results of the proposed workflow are then compared to those obtained by a widely used group ICA approach. It is demonstrated that intrinsic modes, extracted by EMD, are suitable to serve as references for cICA to obtain typical resting state patterns, which are consistent over subjects. This novel processing pipeline makes it transparent for the user, how comparable activity patterns across subjects emerge, and also the trade-off between similarity across subjects and preserving individual features can be well adjusted and adapted for different requirements in the new work-flow.

Ruminal degradation of quercetin and its influence on fermentation in ruminants.

The aim of the present study was to investigate the ruminal degradation of the flavonol quercetin and to determine its potential antimicrobial effects on ruminal fermentation in cows. Ruminal degradation of quercetin (0 or 100µmol/L, respectively) as well as its influence on ruminal gas production (0, 50, or 100µmol of quercetin equivalents/L, respectively, either applied as aglycone or as its glucorhamnoside rutin) using concentrate, grass hay, and straw as substrates were investigated in vitro using the Hohenheim gas test. Additionally, the influence of quercetin on ruminal concentrations of volatile fatty acids and their molar ratio in rumen-fistulated, nonlactating cows (n=5) after intraruminal application of quercetin as aglycone or as rutin (0, 10, or 50mg of quercetin equivalents/kg of BW, respectively) was evaluated. Quercetin was rapidly and extensively degraded, whereby the disappearance of quercetin was accompanied by the simultaneous appearance of 2metabolites 3,4-dihydroxyphenylacetic acid and 4-methylcatechol. In vitro total gas and methane production were not reduced by the addition of quercetin aglycone or rutin, respectively, using concentrate, grass hay, and straw as substrates. As expected, however, effects of the substrates used were detected on total gas and methane production. Highest gas production was found with concentrate, whereas values obtained with grass hay and straw were lower. Relative methane production was highest with grass hay compared with concentrate and straw (27.1 vs. 25.0 and 25.5%). After intraruminal application of the quercetin aglycone or rutin, respectively, neither total concentration nor the molar ratio of volatile fatty acids in the rumen fluid were influenced. Results of the present study show that quercetin underlies rapid ruminal degradation, whereby 3,4-dihydroxyphenylacetic acid and 4-methylcatechol are the main metabolites, whereas the latter one most likely is formed by dehydroxylation from 3,4-dihydroxyphenylacetic acid. Regarding antimicrobial effects of quercetin, results obtained indicate that fermentation processes in the forestomachs are not substantially influenced by quercetin or rutin, respectively. With regard to potential health-promoting effects of quercetin, its application in cows, especially in the form of the better available rutin, might not be accompanied by negative effects on ruminal fermentation.

Bioavailability of the flavonol quercetin in cows after intraruminal application of quercetin aglycone and rutin.

The bioavailability of quercetin has been intensively investigated in monogastric species, but knowledge about its bioavailability in ruminants does not exist. Thus, the aim of the present study was to determine the bioavailability of quercetin in nonlactating cows equipped with indwelling catheters placed in one jugular vein after intraruminal and additionally after i.v. application, respectively. Quercetin was administered intraruminally in equimolar amounts, either in the aglycone form or as its glucorhamnoside rutin, each at 2 dosages [10 and 50 mg of quercetin/kg of body weight (BW)]. In a second trial, 0.8 mg of quercetin aglycone/kg of BW was applied i.v. Blood samples were drawn 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 h after intraruminal application and every 5 min (first hour), every 10 min(second hour), and at 3 and 6h after i.v. bolus application, respectively. Quercetin and quercetin metabolites with an intact flavonol structure (isorhamnetin, tamarixetin, and kaempferol) in plasma samples were analyzed by HPLC with fluorescence detection. After intraruminal application of quercetin and rutin, respectively, quercetin and its methylated (isorhamnetin, tamarixetin) and dehydroxylated (kaempferol) derivatives were present in plasma mainly as conjugated forms, whereas free quercetin and its derivatives were scarcely detected. For rutin, the relative bioavailability of total flavonols (sum of conjugated and nonconjugated quercetin and its conjugated and nonconjugated derivatives after intake of 50 mg/kg of BW) was 767.3% compared with quercetin aglycone (100%). Absolute bioavailability of total flavonols was only 0.1 and 0.5% after quercetin aglycone and rutin applications, respectively. Our data demonstrate that bioavailability of quercetin from rutin is substantially higher compared with that from quercetin aglycone in cows after intraruminal (or oral) application, unlike in monogastric species.

Transport and pharmacodynamics of albitiazolium, an antimalarial drug candidate.

BACKGROUND AND PURPOSE: Choline analogues, a new type of antimalarials, exert potent in vitro and in vivo antimalarial activity. This has given rise to albitiazolium, which is currently in phase II clinical trials to cure severe malaria. Here we dissected its mechanism of action step by step from choline entry into the infected erythrocyte to its effect on phosphatidylcholine (PC) biosynthesis. EXPERIMENTAL APPROACH: We biochemically unravelled the transport and enzymatic steps that mediate de novo synthesis of PC and elucidated how albitiazolium enters the intracellular parasites and affects the PC biosynthesis. KEY RESULTS: Choline entry into Plasmodium falciparum-infected erythrocytes is achieved both by the remnant erythrocyte choline carrier and by parasite-induced new permeability pathways (NPP), while parasite entry involves a poly-specific cation transporter. Albitiazolium specifically prevented choline incorporation into its end-product PC, and its antimalarial activity was strongly antagonized by choline. Albitiazolium entered the infected erythrocyte mainly via a furosemide-sensitive NPP and was transported into the parasite by a poly-specific cation carrier. Albitiazolium competitively inhibited choline entry via the parasite-derived cation transporter and also, at a much higher concentration, affected each of the three enzymes conducting de novo synthesis of PC. CONCLUSIONS AND IMPLICATIONS: Inhibition of choline entry into the parasite appears to be the primary mechanism by which albitiazolium exerts its potent antimalarial effect. However, the pharmacological response to albitiazolium involves molecular interactions with different steps of the de novo PC biosynthesis pathway, which would help to delay the development of resistance to this drug.

Dietary flavonoids do not affect vitamin E status in growing rats.

This study aimed at investigating potential effects of the flavonoids genistein, quercetin and catechin and the role of co-ingested dietary fat on vitamin E concentrations in rats. In experiment 1, genistein, quercetin and catechin were fed to rats, incorporated into semisynthetic diets at concentrations of 2 g/kg, either as individual compounds or in combination to investigate their individual and possible synergistic actions towards alpha-tocopherol in plasma and selected tissues. For experiments 2 and 3, quercetin was selected as a representative model flavonoid to study the effects of the quantity (5% vs. 10%) and type of dietary fat (coconut fat plus corn oil vs. rapeseed oil; experiment 2) and the role of cholesterol (experiment 3) on potential flavonoid-vitamin E interactions. The concentrations of alpha-tocopherol and gamma-tocopherol in the plasma, liver, lung and cortex of flavonoid-fed rats were not significantly different from the concentrations measured in control rats in all three experiments. However, increasing the amount of coconut fat plus corn oil from 5 to 10% resulted in lower alpha-tocopherol concentrations in plasma and tissue. The alpha-tocopherol concentrations in the rats fed rapeseed oil were significantly higher than in rats fed coconut fat plus corn oil. The addition of 0.2% cholesterol to the diet did not influence the tocopherol concentrations in plasma and tissue in both quercetin-supplemented and control rats. Additionally, the mRNA levels of alpha-TTP, CYP3A4, CYP4F and Mdr2, which are integral proteins involved in vitamin E homeostasis were measured. Only genistein reduced the Mdr2 mRNA level, but none of the other transcripts. All other flavonoids were without effect. In conclusion, co-ingested dietary fat appears to influence vitamin E concentrations in rats, but does not seem to be an important determinant of flavonoid-vitamin E interactions.

Quantitative analysis of a bis-thiazolium antimalarial compound, SAR97276, in mouse plasma and red blood cell samples, using liquid chromatography mass spectrometry.

A sensitive and selective liquid chromatography-mass spectrometry (LC-MS) method has been developed for the determination of a new antimalarial bisthiazolium salt, SAR97276, in mouse plasma and red blood cells (RBCs). A drug of the same chemical series as the test drug, T2, was used as internal standard. The method involved solid phase extraction of the compound and the internal standard from the two matrices using Oasis HLB columns. LC separation was performed on a Zorbax eclipse XDB C8 column (5 microm) with a mobile phase of acetonitrile containing trimethylamine (130 microl/l, solvent A) and 2 mM ammonium formate buffer (solvent B). MS data were acquired in single ion monitoring mode at m/z 227 for SAR97276 and m/z 326 for T2. The matrix had no influence on the detection of either SAR97276 or T2. The drug/internal standard peak area ratios were linked via quadratic relationships to plasma (1.65-1322 ng/ml) and RBC concentrations (3.31-2644 ng/ml). Precision was below 14% and accuracy was 91.4-104%. Dilution of the samples had no influence on the performance of the method. Extraction recoveries of SAR97276 were > or =90% in plasma and > or =60% in RBCs. The lower limits of quantitation were 1.65 ng/ml in plasma and 3.31 ng/ml in RBCs. Stability tests under various conditions were also investigated. The method was successfully used to determine the pharmacokinetic profile of SAR97276 in healthy mouse.

Concerted action of leptin in regulation of fatty acid oxidation in skeletal muscle and liver.

Central action of leptin on food intake and energy expenditure is integrated with leptin's peripheral action modulating the fatty acid and glucose metabolism and preventing the accumulation of lipids in nonadipose tissues. However, exact mechanism(s) of the leptin's action in the peripheral tissues has not yet been fully elucidated. Therefore, we investigated the effect of a single intravenous injection of leptin on palmitoyl-CoA and palmitoyl-carnitine oxidation rate in liver and skeletal muscle followed by measurements of the carnitine-palmitoyl transferase 1 (CPT1) activity and activities of ss-oxidation enzymes in mitochondria (acyl-CoA dehydrogenase) and in peroxisomes (acyl-CoA oxidase) of rats. Animals were euthanized and tissues and serum harvested 15 min, 1 hour, 3 hours and 6 hours after leptin administration. Intravenous leptin injection increased mitochondrial palmitoyl-CoA oxidation rate in both liver (95%; P<0.025) and skeletal muscle (2.7-fold; P<0.05). This was paralleled by lowering hepatic (-156%; P<0.001) and skeletal muscle (-191%; P<0.001) triglyceride content. Leptin-induced elevation of palmitoyl-CoA oxidation rate in liver was paralleled by increased CPT1 activity (52%; P<0.05) and ss-oxidation capacity (52%; P<0.05). Lack of the leptin's effect on the CPT1-activity in muscle (20%; p=0.09) suggests the existence of an alternative pathway for increasing the palmitoyl-CoA-oxidation rate bypassing the CPT1 regulatory step. Interestingly, leptin stimulated the overall ss-oxidation capacity in muscle by 69% (P=0.027). This may indicate to an involvement of mitochondrial acyl-CoA dehydrogenases as well as of peroxisomal fat catabolism. Taken together, we showed that leptin acutely increases palmitoyl-CoA oxidation rate in liver and in skeletal muscle, which was associated with tissue specific effect on the CPT1 activity as well as on the downstream enzymes of fatty acid oxidation pathways in rat mitochondria and peroxisomes. Tangible evidence for the leptin-induced increase of fatty acid catabolism was provided by a lowered skeletal muscle and hepatic lipid deposition.

Rapid screening for depression--validation of the Brief Case-Find for Depression (BCD) in medical oncology and palliative care patients.

Depression in oncology patients is under-recognised and associated with poor outcomes. Screening can increase case recognition. The Brief Case-Find for Depression (BCD) is a four-question, interviewer-administered instrument that has been previously validated in a general medical setting. The primary aim of this study was to validate the BCD in a medical oncology/palliative care setting, primarily by comparing its association with physical illness measures and with the Primary Care Evaluation of Mental Disorders (PRIME-MD), the Beck Depression Inventory (BDI) and the Hospital Anxiety and Depression Scale (HADS). Eligible adult oncology patients gave informed consent and completed the above measures and a pain scale. Agreement between the BCD and other instruments was assessed. Construct validity was determined by comparing depressed/nondepressed patients with respect to performance status, symptoms, pain score and functional impairment. A total of 100 patients had a median age of 58 (range 21-90) and ECOG performance status (PS) 2 (0-4). In all, 60% had metastatic disease. The therapeutic goal was curative/adjuvant in 39% and palliative in 61%. Prevalence of depression according to the various measures was: BCD 34%, PRIME-MD 12%, BDI 19% and HADS 14%. In total, 45% of patients responded positively to a single-item screening question. The BCD showed fair agreement with the PRIME-MD (kappa=0.21), moderate agreement with the BDI (kappa=0.43) and fair agreement with the HADS (kappa=0.27). Against the PRIME-MD diagnosis of depression, the BCD had greater sensitivity, but lesser specificity and overall agreement, compared with the BDI and depression scale of the HADS. Patients with probable depression (according to BCD) had inferior PS (P=0.0064), increased pain (P=0.045) and greater impairment of functioning (PRIME-MD: P=0.0003). There was no association with gender, age, disease status or therapeutic goal. Depression is common in oncology patients. The BCD is a quick, easy-to-administer screen for depression, which has reasonable psychometric properties in this population.

Comparison of the extrapancreatic action of gamma-linolenic acid and n-3 PUFAs in the high fat diet-induced insulin resistance [corrected].

OBJECTIVE: The effect of dietary borage oil (rich in the gamma-linolenic acid [GLA]) on insulin sensitivity and lipid metabolism was compared with that of fish oil (rich in n-3 polyunsaturated fatty acids [PUFAs]) in high fat (HF) diet-induced insulin resistance (IR) of rats. METHODS: Male Wistar rats were fed ad libitum for 3 weeks a standard laboratory chow (Controls) or high fat diet consisting of 70-cal % fat. In addition, a group of rats was fed high fat (HF) diet where a part of saturated fat was replaced with fish oil as a source of n-3 PUFAs (HF+FO), or borage oil as a source of GLA (HF+GLA). In vivo insulin action was assessed by the euglycemic hyperinsulinemic clamp. Glucose, insulin, free fatty acids (FFA), triglycerides (Tg) and glycerol levels in blood and tissue depots were also measured. RESULTS: Increased levels of Tg, FFA and glycerol in circulation after HF diet were accompanied by their raised accumulation in insulin sensitive tissues. FO feeding lowered the concentration of all lipids in serum and prevented their accumulation in both tissues. On the other hand GLA supplementation into the high fat diet did not suppress increased levels of Tg, FFA and glycerol in circulation and tissue depots as well. FO feeding significantly reduced HF diet-induced in vivo IR, while GLA supplementation did not improve the in vivo insulin sensitivity in HF diet induced insulin resistance. CONCLUSIONS: 1. Substitution of FO into the high fat diet led to an improvement of in vivo insulin action; 2. this insulin sensitizing effect of FO was accompanied by a decrease of circulating Tg, FFA and glycerol levels in the postprandial state and by a lower lipid content in liver and skeletal muscle. 3. on the opposite, GLA treatment failed to improve in vivo insulin action; and 4. was associated with an adverse effect on lipid levels both in circulation and tissue depots.

Reality and fugues in physicians facing death: confrontation, coping, and adaptation at the bedside.

This paper addresses the psychological effects and fears of physicians in their private and professional lives. It specifically looks at their experiences, perceptions, behavior, and vulnerability, especially when confronted with death and dying. The concepts of empathy, fears of oncologists, the mechanisms used for adaptation and coping, recommendations and interventions are presented. The success of a physician can be measured by the empathic yet objective relationship he/she establishes with the patient, while simultaneously building clear emotional and professional boundaries.

Cancer patient expectations of and communication with oncologists and oncology nurses: the experience of an integrated oncology and palliative care service.

The purpose of this study was to evaluate ambulatory cancer patients' knowledge of their diagnosis and stage, their expectations of medical and nursing staff, and issues related to communication with the professional staff. A structured interview was conducted with each of 103 consecutive cancer patients attending the Oncology Day Hospital of the Shaare Zedek Medical Center. There were 77 women and 26 men, and their median age was 56 (18-86) years. Their religious status was elicited: 48% described themselves as religious, 25% as traditional, and 27% as secular. According to their physicians, 41 were in remission, 11 had stable disease, 47 had progressive disease and in 4 the disease status was unknown. Patients tended to underestimate the status of their disease: among those with progressive disease, 36% stated that their disease was stable or in remission. Overwhelmingly, patients expected that their oncologists should be patient and skilled in diagnostic procedures (98%), tactful, considerate and therapeutically skilled (90-95%), and skilled in the management of pain and the psychosocial consequences of cancer (75-85%). When there is bad news to be transmitted, 92% of patients indicated that they would want disclosure, while 6% indicated that they would want the news withheld from them but passed on to their family members. Most patients were very satisfied with the clarity of the information they received about their disease (85%) and the sensitivity with which it was transmitted (90%). Although 88% of patients reported that they relied on their oncologist for therapeutic decision making, 45% indicated that they had sought a second opinion and 32% reported seeking the opinion of a rabbinical medical broker. Almost all, 97%, of patients indicated that they felt comfortable seeking advice from their oncologist, and the oncologist was the staff member most often sought out for both information (69%) and support (66%). The data indicate high patient expectations of nursing and medical oncology staff members' skills and behaviors. Despite expressing a high level of satisfaction, a substantial percentage of patients had an inaccurate understanding of their disease status.

Cancer, unproven therapies, and magic.

Commonly used by cancer patients, unproven therapies are treatments that the practitioner claims can alter the disease process although there is no proof to support the claim. The reasons for the popularity of unproven therapies fall into two categories--practical considerations and fundamental mechanisms. Research has implicated the following practical factors: a pragmatic search for relief of symptoms, expression of a philosophical view, a need to reestablish a sense of control in life, and dissatisfaction with conventional medicine. Fundamental mechanisms include traditional magic, the heroic individual, and a delusional pattern of thinking. Underpinning and generating these factors is the fear of death. Particularly in patients with cancer, this is not only a fear of nonexistence, but of loneliness, the unknown, pain, loss of control, and emptiness. The popularity of unproven therapies poses a challenge to the medical system at large, and oncologists, psycho-oncologists, and palliative-care physicians, in particular. The essence of the challenge is to understand the reasons for the use of unproven therapies, to analyze our own behavior, and conclude what if anything our response should be. Unproven therapies (as with magic, a sense of heroism, and delusional thinking) fulfill the function of resolving the inexplicable and the psychologically painful--i.e., relieving the anxiety associated with cancer.

Sedation in the imminently dying patient.

Sedation is a clinically important therapeutic intervention in the imminently dying patient. As the patient with an advanced, irreversible illness nears the end of life, symptoms accumulate that are progressively more difficult to manage and that may become refractory to standard medical interventions. The most common of these intractable symptoms are pain, agitated delirium, dyspnea, and existential or psychological distress. Various therapeutic options available for relieving these symptoms include physician-assisted suicide, euthanasia, acceptance of unrelieved suffering, and terminal sedation. Some commentators have voiced concerns that sedating the imminently dying patient inevitably hastens death, and that this practice, in fact, is a surrogate form of physician-assisted suicide or euthanasia. Ethical arguments invoked to support the use of terminal sedation include the principle of double effect, which draws a moral distinction between the intention of an act (in this case, to relieve suffering) and its foreseen but unintended consequence (premature death). This author views sedation as a necessary, although risk-laden, procedure that, if practiced by trained, dedicated clinicians, maintains the physician's twin obligations to benefit patients and to "do no harm."

Phenobarbital induces cytochrome P4501A2 hnRNA, mRNA and protein in the liver of C57BL/6J wild type and aryl hydrocarbon receptor knock-out mice.

The aryl hydrocarbon receptor mediates the transcriptional response to a variety of hydrocarbons of members of the aryl hydrocarbon gene battery. Phenobarbital does not bind the aryl hydrocarbon receptor with high affinity but induces, in liver cells, expression of cytochrome P4501A. Using both wild type and aryl hydrocarbon receptor knock out C57BL/6J mice, we demonstrate that phenobarbital induced hnRNA, mRNA and protein for the cytochrome P-4501A2 gene in the presence or absence of the aryl hydrocarbon receptor. Using the DNA binding site for the aryl hydrocarbon receptor as a probe, gel retardation analyses showed that phenobarbital treatment induced protein binding, regardless of the presence of the aryl hydrocarbon receptor.