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Purpose Use of stereotactic ablative radiation therapy (SABR) for subcentimeter lung tumors is controversial. We report our outcomes for tumors with diameter ≤1 cm and their visibility on cone beam computed tomography (CBCT) scans and retrospectively evaluate the planned dose using a deterministic dose calculation algorithm (Acuros XB [AXB]). Methods and Materials We identified subcentimeter tumors from our institutional SABR database. Tumor size was remeasured on an artifact-free phase of the planning 4-dimensional (4D)-CT. Clinical plan doses were generated using either a pencil beam convolution or an anisotropic analytic algorithm (AAA). All AAA plans were recalculated using AXB, and differences among D95 and mean dose for internal target volume (ITV) and planning target volume (PTV) on the average intensity CT dataset, as well as for gross tumor volume (GTV) on the end respiratory phases were reported. For all AAA patients, CBCT scans acquired during each treatment fraction were evaluated for target visibility. Progression-free and overall survival rates were calculated using the Kaplan-Meier method. Results Thirty-five patients with 37 subcentimeter tumors were eligible for analysis. For the 22 AAA plans recalculated using AXB, Mean D95 ± SD values were 2.2 ± 4.4% (ITV) and 2.5 ± 4.8% (PTV) lower using AXB; whereas mean doses were 2.9 ± 4.9% (ITV) and 3.7 ± 5.1% (PTV) lower. Calculated AXB doses were significantly lower in one patient (difference in mean ITV and PTV doses, as well as in mean ITV and PTV D95 ranged from 22%-24%). However, the end respiratory phase GTV received at least 95% of the prescription dose. Review of 92 CBCT scans from all AAA patients revealed that the tumor was visualized in 82 images, and its position could be inferred in other images. The 2-year local progression-free survival was 100%. Conclusions Patients with subcentimeter lung tumors are good candidates for SABR, given the dosimetry, ability to localize tumors with image guidance, and excellent local control.

A study was conducted in sheep on Canadian farms to describe the relationship between packed cell volume (PCV) or fecal egg counts (FEC) and subjective clinical parameters that may indicate the severity of parasitic gastroenteritis. Twenty-one farms in Ontario (ON) and 8 farms in Quebec (QC) were purposively selected and visited during April–May (spring) and August (summer) 2007. At each farm visit, blood and fecal samples were collected from 10 ewes and 10 female lambs; body condition score (BCS), dag score (DS), fecal consistency score (FCS) and FAMACHA score were recorded for all sampled sheep. Packed cell volume was determined for all blood samples, and FEC were performed for all fecal samples. Summary statistics and simple correlations were performed for the parameters recorded. Two mixed models with random effects at the farm level were developed; one using PCV as the response variable and another using the natural log of eggs per gram of feces (lnEPG). Finally, the residuals from both models were correlated to the covariates in the models. The mean PCV values during the spring were 29.7% and 36.7% for lambs, and 28.8% and 31.1% for ewes, in ON and QC, respectively. During the summer, the mean PCV was 32.0% and 32.8% for lambs, and 30.1% and 29.9% for ewes, in ON and QC, respectively. The arithmetic mean FEC per gram of feces (EPG) during the spring was 3 and 2 for lambs, and 1266 and 789 for ewes, in ON and QC, respectively, whereas during summer the arithmetic mean EPG was 907 and 237 for lambs, and 458 and 246 for ewes, in ON and QC, respectively. Results from simple correlations indicated that PCV was negatively correlated with lnEPG (r = −0.255; r2 = 6.5%) and FAMACHA (r = −0.312; r2 = 9.7%), and positively correlated with BCS (r = 0.317; r2 = 10%). LnEPG was negatively correlated with BCS (r = −0.232; r2 = 5.4%) and PCV (r = −0.255; r2 = 6.5%), but positively correlated with FAMACHA (r = 0.178; r2 = 3.2%) and DS (r = 0.086; r2 = 0.7%). Results from the models indicated that PCV and lnEPG residuals were negatively correlated with FAMACHA, FCS and almost all categories of BCS and DS, although the correlations were very low. The main results from this study suggested that none of the subjective clinical parameters evaluated were highly correlated with PCV or lnEPG and therefore were not good predictors of lnEPG or PCV on the studied farms in Ontario and Quebec. Fil: Mederos, A.. Instituto Nacional de Investigación Agropecuaria; Uruguay Fil: Kelton, D.. University of Guelph; Canadá Fil: Peregrine, A. S.. University of Guelph; Canadá Fil: VanLeeuwen, J.. University Of Prince Edward Island; Canadá Fil: Fernández, Alicia Silvina. University of Guelph; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: LeBoeuf, A.. Ministère de l’Agriculture, des Pêcheries et de l’Alimentation du Québec; Canadá Fil: Menzies, P.. University of Guelph; Canadá Fil: Martin, R.. Nova Scotia Agricultural College; Canadá

Objective To investigate the association between sustained postoperative anaemia and outcome after coronary artery bypass graft (CABG) surgery.Design Retrospective analysis of the IMAGINE trial, which tested the effect of the ACE inhibitor quinapril on cardiovascular events after CABG.Setting Thoracic surgery clinic/outpatient department.Patients 2553 stable patients with left ventricular ejection fraction >40% 2-7 days after scheduled CABG.Interventions Randomisation to quinapril or placebo.Main outcome measures Cox regression analysis for the association between postoperative anaemia and cardiovascular events and the effect of quinapril on the incidence of anaemia.Results Postoperative anaemia was sustained for >50 days in 44% of patients. Sustained postoperative anaemia was associated with an increased incidence of cardiovascular events during the first 3 months (adjusted HR (adjHR) 1.77, 95% CI 1.10 to 2.85, p=0.012) and during the maximum follow-up of 43 months (adjHR 1.37, 95% CI 1.14 to 1.65, p=0.008). When haemoglobin (Hb) was considered as a continuous variable, every 1 mg/dl decrease in Hb was associated with a 13% increase in cardiovascular events (adjHR 0.87, 95% CI 0.81 to 0.95, p=0.003) and a 22% increase in all-cause mortality (adjHR 0.78, 95% CI 0.60 to 0.99, p=0.034). Quinapril was associated with a slower postoperative recovery of Hb levels and a higher incidence of cardiovascular events in patients with anaemia (adjHR 1.60, 95% CI 1.1 to 2.4, p=0.024).Conclusions Postoperative anaemia is common, frequently persists for months after CABG surgery and is associated with an impaired outcome. In patients with anaemia, ACE inhibitors slowed recovery from postoperative anaemia and increased the incidence of cardiovascular events after CABG.

Conceptual density-functional theory (DFT) provides a mathematical framework for using changes of the electron density to understand chemical reactions and chemical reactivity. The key idea is that by studying the response of a molecule or materials to perturbations, one can decipher its reactivity preferences. If a system reacts favorably to a perturbation, then this indicates that the system will react favorably with a certain class of reagents. Differentials of the energy may thus be interpreted as reactivity indicators. Because of the key role of energy differentials, the mathematical framework of conceptual DFT is similar to classical thermodynamics, with state functions, variational principles, and Legendre transforms. In this chapter we use this thermodynamic simile to present the mathematical underpinnings of conceptual DFT. Applications to systems of interest to organic, inorganic, and biological chemists are used to demonstrate how these abstract concepts may be applied to concrete chemical problems.

AbstractPolar bears (Ursus maritimus) are exposed to high concentrations of mercury because they are apex predators in the Arctic ecosystem. Although mercury is a potent neurotoxic heavy metal, it is not known whether current exposures are of neurotoxicological concern to polar bears. We tested the hypotheses that polar bears accumulate levels of mercury in their brains that exceed the estimated lowest observable adverse effect level (20 μg/g dry wt) for mammalian wildlife and that such exposures are associated with subtle neurological damage, as determined by measuring neurochemical biomarkers previously shown to be disrupted by mercury in other high‐trophic wildlife. Brain stem (medulla oblongata) tissues from 82 polar bears subsistence hunted in East Greenland were studied. Despite surprisingly low levels of mercury in the brain stem region (total mercury = 0.36 ±0.12 μg/g dry wt), a significant negative correlation was measured between N‐methyl‐D‐aspartate (NMDA) receptor levels and both total mercury (r = —0.34, p < 0.01) and methylmercury (r = —0.89, p < 0.05). No relationships were observed among mercury, selenium, and several other neurochemical biomarkers (dopamine‐2, gamma‐aminobutyric acid type A, muscarinic cholinergic, and nicotinic cholinergic receptors; cholinesterase and monoamine oxidase enzymes). These data show that East Greenland polar bears do not accumulate high levels of mercury in their brain stems. However, decreased levels of NMDA receptors could be one of the most sensitive indicators of mercury's subclinical and early effects.

Abstract S -Nitrosoglutathione (GSNO) reacts with the organic mercurial probe, p -hydroxymercury benzoate (PHMB, HO–Hg–(C 6 H 4 )–COO − Na + ) giving the complex GS–Hg(C 6 H 4 )COOH (GS–PHMB). This reaction has been studied by UV measurements at 334 nm also in the presence of ascorbic acid and the product of reaction, the GS–PHMB complex, characterized by Electrospray Ionization Mass Spectrometry (ESI-MS) and by Reversed Phase Chromatography (RPLC) coupled on-line and sequentially with a UV–visible diode array detector (DAD) followed by a cold vapor generation atomic fluorescence spectrometer (CVGAFS). The simultaneous presence of PHMB and ascorbate produced a synergistic effect on GSNO decomposition rate that can be observed only above a given concentration threshold of ascorbate (ascorbate/GSNO molar ratio ≥ 180). The results indicated that the formation of GS–PHMB, both in the presence and the absence of ascorbic acid, does not involve the formation of free thiolic species but it takes place through a more complex mechanism. The PHMB derivatives of GSH and GSNO obtained by the present method were found to be identical by ESI-MS. GSSG did not interfere because it was not reduced and derivatized to GS–PHMB. Once complexed by the alkylating agent N -ethylmaleimide (NEM), GSH did not interfere with the derivatization reaction. This ensured a good selectivity of the developed PHMB derivatization system for RSNO determination. Thus, we have optimized the operating conditions for the selective reaction of PHMB with GSNO and other nitrosothiols (RSNOs) in order to determinate RSNOs in human plasma. LODc for RSNOs in plasma ultrafiltrate was 30 nM (injected concentration, 50 μL loop), the DLR ranged between 0.08 and 50 μM and the CV% was 6.5% at 300 nM concentration level. Reduced and oxidized thiols spiked to plasma did not interfere with the measurement of RSNOs. We found that the sampling procedure was critical for the recovery of endogenous and spiked RSNOs. The ultrafiltrate samples of plasma of 8 healthy humans contained 1460 ± 310 CysNO, 1000 ± 330 nM HCysNO and 320 ± 60 nM GSNO if blood was sampled in a mixture NEM/ethylendiaminotetracetic acid (EDTA)/serine–borate complex (SBC), where serine–borate complex is a potent inhibitor of γ-glutamyltransferase, an enzyme involved in the conversion of GSNO into CysGlyNO. In the absence of SBC during the sampling of blood GSNO concentration found in the ultrafiltrate was lower (at level of the determination limit in plasma ultrafiltrate, i.e. 75 nM) and the peak of CysGlyNO appeared, which corresponded to a concentration of 200 ± 60 nM ( N = 4 blood samples).

In Photosystem I, the backbone nitrogen of Leu722 PsaA forms a hydrogen bond with the C 4 carbonyl oxygen of phylloquinone in the A 1A site. A previous low-temperature EPR study indicated that substitution of Leu722 PsaA with a bulky Trp residue results in a weakened H-bond. Here, we employ room temperature, time-resolved optical spectroscopy and variable temperature, transient EPR spectroscopy to probe the effect of the altered H-bond on the energetics and kinetics of electron transfer. Relative to the wild type, we find that the rate of electron transfer from A 1A - to F x in the L722W PsaA variant is faster by a factor of 3. This change is attributed to a lowered midpoint potential of A 1A /A 1A - , resulting in a larger Gibbs free energy change between A 1A /A 1A - andF x /F x - . An activation energy of 180 ± 10 meV is determined for the A 1A - -to-F x forward electron transfer step in the L722W PsaA variant compared with 220 ± 10 meV in the wild type. The Arrhenius plot shows a break at ~200 K, below which the rate becomes nearly independent of temperature. This behavior is described using a quantum mechanical treatment that takes the zero-point energy into account as well as an alternative model that invokes a dynamical transition in the protein at ~200 K.

STUDY QUESTION: How can we predict chances of natural conception at various time points in couples diagnosed with unexplained subfertility?SUMMARY ANSWER: We developed a dynamic prediction model that can make repeated predictions over time for couples with unexplained subfertility that underwent a fertility workup at a fertility clinic.WHAT IS KNOWN ALREADY: The most frequently used prediction model for natural conception (the 'Hunault model') estimates the probability of natural conception only once per couple, that is, after completion of the fertility workup. This model cannot be used for a second or third time for couples who wish to know their renewed chances after a certain period of expectant management.STUDY DESIGN, SIZE, DURATION: A prospective cohort studying the long-term follow-up of subfertile couples included in 38 centres in the Netherlands between January 2002 and February 2004. Couples with bilateral tubal occlusion, anovulation or a total motile sperm count <1 × 106 were excluded.PARTICIPANTS/MATERIALS, SETTING, METHODS: The primary endpoint was time to natural conception, leading to an ongoing pregnancy. Follow-up time was censored at the start of treatment or at the last date of contact. In developing the new dynamic prediction model, we used the same predictors as the Hunault model, i.e. female age, duration of subfertility, female subfertility being primary or secondary, sperm motility and referral status. The performance of the model was evaluated in terms of calibration and discrimination. Additionally, we assessed the utility of the model in terms of the variability of the calculated predictions.MAIN RESULTS AND THE ROLE OF CHANCE: Of the 4999 couples in the cohort, 1053 (21%) women reached a natural conception leading to an ongoing pregnancy within a mean follow-up of 8 months (5th and 95th percentile: 1-21). Our newly developed dynamic prediction model estimated the median probability of conceiving in the first year after the completion of the fertility workup at 27%. For couples not yet pregnant after half a year, after one year and after one and a half years of expectant management, the median probability of conceiving over the next year was estimated at 20, 15 and 13%, respectively. The model performed fair in an internal validation. The prediction ranges were sufficiently broad to aid in counselling couples for at least two years after their fertility workup.LIMITATIONS, REASONS FOR CAUTION: The dynamic prediction model needs to be validated in an external population.WIDER IMPLICATIONS OF THE FINDINGS: This dynamic prediction model allows reassessment of natural conception chances after various periods of unsuccessful expectant management. This gives valuable information to counsel couples with unexplained subfertility that are seen for a fertility workup.STUDY FUNDING/COMPETING INTERESTS: This study was facilitated by grant 945/12/002 from ZonMW, The Netherlands Organization for Health Research and Development, The Hague, The Netherlands. No competing interests.