Interface-Generated Spin Currents.

Transport calculations based on ab initio band structures reveal large interface-generated spin currents at Co/Pt, Co/Cu, and Pt/Cu interfaces. These spin currents are driven by in-plane electric fields but flow out of plane and can have similar strengths to spin currents generated by the spin Hall effect in bulk Pt. Each interface generates spin currents with polarization along z[over ^]×E, where z[over ^] is the interface normal and E denotes the electric field. The Co/Cu and Co/Pt interfaces additionally generate spin currents with polarization along m[over ^]×(z[over ^]×E), where m[over ^] gives the magnetization direction of Co. The latter spin polarization is controlled by-but not aligned with-the magnetization, providing a novel mechanism for generating spin torques in magnetic trilayers.

Anti-TNF therapy is not associated with an increased risk of post-colectomy complications, a population-based study.

AIM: Previous studies have raised concerns that the use of anti-tumour necrosis factor (anti-TNF) therapy in patients with ulcerative colitis (UC) undergoing surgery may increase the risk of postoperative complications. We have taken a population-based approach to investigate whether there is an association between anti-TNF therapy and postoperative complications in UC patients undergoing subtotal colectomy. METHOD: Hospital Episode Statistics (HES) data and procedural coding were used to identify all patients in England between April 2006 and March 2015 undergoing subtotal colectomy for UC. Patients were grouped into those who received anti-TNF therapy within 12 or 4 weeks of surgery and those who did not. The incidence of postoperative complications was evaluated by HES coding and compared between groups. RESULTS: In all, 6225 UC patients underwent subtotal colectomy. 753 patients received anti-TNF therapy within 12 weeks prior to surgery (418 within 4 weeks). There was no difference in postoperative complications between groups although groups were not comparable for age and comorbidities. Logistic regression with complications as the outcome variable did not show any significant association between anti-TNF therapy and complications. Colectomy performed during an unplanned admission (vs planned admission) and smoking were associated with complications. CONCLUSION: This large population-based study does not demonstrate any association between preoperative anti-TNF therapy and postoperative complications in UC patients undergoing subtotal colectomy. The only variables associated with complications were colectomy performed during an unplanned admission and smoking.

Effects of dopamine receptor antagonist antipsychotic therapy on blood pressure.

WHAT IS KNOWN AND OBJECTIVE: Hypertension, a major risk factor for adverse cardiovascular events, such as stroke and myocardial infarction, affects 80 million American adults. The aetiology of hypertension is multifaceted and difficult to identify. Dopamine receptors, especially those in the kidneys, play a role in blood pressure regulation, and alterations in their function can cause hypertension. The objective of this review was to investigate the association between the use of dopamine antagonists with hypertension focusing especially on second-generation antipsychotics, like clozapine that is D4 receptor antagonist. METHODS: A literature review was conducted using MEDLINE, Ovid, Science Direct, Web of Science and Cochrane Database of Systematic Reviews databases with keywords:hypertension, hypotension, renin-angiotensin-aldosterone system, dopaminergic receptors, blood pressure, antipsychotics. Inclusion criteria were human or animal studies, systematic reviews, meta-analyses, randomized controlled trials, case report/series, published in selected for inclusion. RESULTS AND DISCUSSION: All 5 dopamine receptor subtypes (ie D1, D2, D3, D4 and D5) regulate sodium excretion and BP. The D1, D3 and D4 receptors interact directly with the renin-angiotensin-aldosterone system, whereas D2 and D5 receptors directly interact with the sympathetic nervous system to regulate BP. Use of dopaminergic agonists or antagonists could therefore disturb the regulation of BP by dopamine receptors. WHAT IS NEW AND CONCLUSION: Based upon this review, individuals on antipsychotic agents, particularly clozapine, should be routinely monitored for hypertension, and addition of antihypertensive agents such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) is indicated if hypertension occurs.

Evaluation of FLT-PET-CT as an imaging biomarker of proliferation in primary breast cancer.

BACKGROUND: [(18)F]fluorothymidine (FLT) has been proposed as a positron emission tomography (PET)-imaging biomarker of proliferation for breast cancer. The aim of this prospective study was to assess the feasibility of FLT-PET-CT as a technique for predicting the response to neoadjuvant chemotherapy (NAC) in primary breast cancer and to compare baseline FLT with Ki-67. METHODS: Twenty women with primary breast cancer had a baseline FLT-PET-CT scan that was repeated before the second cycle of chemotherapy. Expression of Ki-67 in the diagnostic biopsy was quantified. From the FLT-PET-CT scans lesion maximum and mean standardised uptake values (SUVmax, SUVmean) were calculated. RESULTS: Mean baseline SUVmax was 7.3, and 4.62 post one cycle of NAC, representing a drop of 2.68 (36.3%). There was no significant association between baseline, post chemotherapy, or change in SUVmax and pathological response to NAC. There was a significant correlation between pre-chemotherapy Ki-67 and SUVmax of 0.604 (P=0.006). CONCLUSIONS: Baseline SUVmax measurements of FLT-PET-CT were significantly related to Ki-67 suggesting that it is a proliferation biomarker. However, in this series neither the baseline value nor the change in SUVmax after one cycle of NAC were able to predict response as most patients had a sizeable SUVmax reduction.

Allelic imbalance in Drosophila hybrid heads: exons, isoforms, and evolution.

Unraveling how regulatory divergence contributes to species differences and adaptation requires identifying functional variants from among millions of genetic differences. Analysis of allelic imbalance (AI) reveals functional genetic differences in cis regulation and has demonstrated differences in cis regulation within and between species. Regulatory mechanisms are often highly conserved, yet differences between species in gene expression are extensive. What evolutionary forces explain widespread divergence in cis regulation? AI was assessed in Drosophila melanogaster-Drosophila simulans hybrid female heads using RNA-seq technology. Mapping bias was virtually eliminated by using genotype-specific references. Allele representation in DNA sequencing was used as a prior in a novel Bayesian model for the estimation of AI in RNA. Cis regulatory divergence was common in the organs and tissues of the head with 41% of genes analyzed showing significant AI. Using existing population genomic data, the relationship between AI and patterns of sequence evolution was examined. Evidence of positive selection was found in 30% of cis regulatory divergent genes. Genes involved in defense, RNAi/RISC complex genes, and those that are sex regulated are enriched among adaptively evolving cis regulatory divergent genes. For genes in these groups, adaptive evolution may play a role in regulatory divergence between species. However, there is no evidence that adaptive evolution drives most of the cis regulatory divergence that is observed. The majority of genes showed patterns consistent with stabilizing selection and neutral evolutionary processes.

Experimental demonstration of scanned spin-precession microscopy.

We present a new tool for imaging spin properties. We show that a spatially averaged spin signal, measured as a function of a scanned magnetic probe's position, contains information about the local spin properties. In this first demonstration we map the injected spin density in GaAs by measuring spin photoluminescence with a resolution of 1.2 µm. The ultimate limit of the technique is set by the gradient of the probe's field, allowing for a resolution beyond the optical diffraction limit. Such probes can also be integrated with other detection methods. This generality allows the technique to be extended to buried interfaces and optically inactive materials.

Detection of electrically modulated inverse spin hall effect in an Fe/GaAs microdevice.

We report the detection of the inverse spin Hall effect (ISHE) in n-gallium arsenide (n-GaAs) combined with electrical injection and modulation of the spin current. We use epitaxial ultrathin-Fe/GaAs injection contacts with strong in-plane magnetic anisotropy. This allows us to simultaneously perform Hanle spin-precession measurements on an Fe detection electrode and ISHE measurements in an applied in-plane hard-axis magnetic field. In this geometry, we can experimentally separate the ordinary from the spin-Hall signals. Electrical spin injection and detection are combined in our microdevice with an applied electrical drift current to modulate the spin distribution and spin current in the channel. The magnitudes and external field dependencies of the signals are quantitatively modeled by solving drift-diffusion and Hall-cross response equations.

A case of VIPoma.

This case report addresses the management of a pregnant woman in the peripartum period with a VIPoma. This rare and highly malignant neuroendocrine tumour secretes vasoactive intestinal peptide (VIP), a substance that may cause potentially life-threatening disruption to physiology. A 36-year-old woman presented for induction of labour with a three-year history of chronic diarrhoea, hypophosphataemia, palpitations and skin flushing. Raised VIP levels indicated presence of a VIPoma, however despite extensive investigation prior to pregnancy by neuroendocrine specialists, the tumour location remained unidentified. The patient delivered a healthy boy with the aid of forceps in theatre following an epidural top-up. Key features of management were a multidisciplinary approach, avoidance of triggers for VIP secretion, strict management of electrolytes and avoidance of severe changes in sympathetic tone during labour with epidural analgesia.

Interfacial spin-orbit torques.

Spin-orbit torques offer a promising mechanism for electrically controlling magnetization dynamics in nanoscale heterostructures. While spin-orbit torques occur predominately at interfaces, the physical mechanisms underlying these torques can originate in both the bulk layers and at interfaces. Classifying spin-orbit torques based on the region that they originate in provides clues as to how to optimize the effect. While most bulk spin-orbit torque contributions are well studied, many of the interfacial contributions allowed by symmetry have yet to be fully explored theoretically and experimentally. To facilitate progress, we review interfacial spin-orbit torques from a semiclassical viewpoint and relate these contributions to recent experimental results. Within the same model, we show the relationship between different interface transport parameters. For charges and spins flowing perpendicular to the interface, interfacial spin-orbit coupling both modifies the mixing conductance of magnetoelectronic circuit theory and gives rise to spin memory loss. For in-plane electric fields, interfacial spin-orbit coupling gives rise to torques described by spin-orbit filtering, spin swapping and precession. In addition, these same interfacial processes generate spin currents that flow into the non-magnetic layer. For in-plane electric fields in trilayer structures, the spin currents generated at the interface between one ferromagnetic layer and the non-magnetic spacer layer can propagate through the non-magnetic layer to produce novel torques on the other ferromagnetic layer.

Size-fractionated heparins have differential effects on human neutrophil function in vitro.

BACKGROUND AND PURPOSE: Heparin is known to possess a range of activities, other than effects on blood coagulation, many of which are anti-inflammatory. Effects with potential anti-inflammatory applications include the inhibition of elastase release from neutrophils, as well as the adhesion of these cells to vascular endothelium. In the present study we aimed to investigate whether fractionation of heparin may yield molecules with enhanced or specific effects on human neutrophil function. EXPERIMENTAL APPROACH: Fractions of defined molecular size were obtained from heparin by different methods and assessed for their effects on elastase release induced by formyl Met-Leu-Phe (fMLP), from neutrophils, in some cases following the priming of these cells with tumour necrosis factor-alpha (TNF-alpha). Effects of the fractions on neutrophil adhesion to interleukin-1beta (IL-beta)-stimulated human umbilical vein endothelial cells (HUVECs) were also examined. KEY RESULTS: Elastase release was inhibited by very low molecular weight fractions of heparin, with an apparent minimum chain length of 10 saccharides required for full effect. In contrast, neutrophil-endothelial adhesion was unaffected by these fractionated heparins, suggesting that certain non-anticoagulant actions of heparin may be lost by such an approach. CONCLUSIONS AND IMPLICATIONS: These data suggest that an optimum chain length of heparin possibly exists for certain non-anticoagulant actions of heparin, which may prove to be useful in the design of novel drugs with specific anti-inflammatory actions.

Over-expression of heat shock protein 70 protects neuronal cells against both thermal and ischaemic stress but with different efficiencies.

Primary cultures of dorsal root ganglia (DRG) sensory neurons can be protected against subsequent severe thermal or ischaemic stress by prior exposure to a mild thermal or ischaemic insult. The degree of protection correlates with the amount of 70 kDa heat shock protein (hsp70) induced by the mild stress. We show directly that over-expression of hsp70 alone is sufficient to protect DRG neurons against thermal or ischaemic stress with a given level of hsp70 over-expression providing greater protection against thermal stress. In contrast over-expression of the 90 kDa heat shock protein (hsp90) has little or no protective effect against either stress. These results are discussed in terms of the role of individual hsps in protecting neuronal cells against different stresses.

The degree of protection provided to neuronal cells by a pre-conditioning stress correlates with the amount of heat shock protein 70 it induces and not with the similarity of the subsequent stress.

A mild thermal stress protects primary cultures of dorsal root ganglion (DRG) neurons against a subsequent lethal heat stress as well as to a lesser extent against a subsequent lethal ischaemia. In contrast, a mild ischaemic stress protects DRG neurons only against a subsequent severe thermal stress and not against severe ischaemia. A greater induction of heat shock protein (hsp) synthesis was observed in these cells following mild temperature stress compared to mild ischaemia. This suggests that the protective effect observed is dependent on hsp synthesis resulting in the observed cross-protective effect and does not involve a particular pre-stress specifically protecting against a subsequent, more severe application of the same stress. Moreover, a particular level of hsp induction produces a better protective effect against lethal heat stress than against lethal ischaemia.

Glandular kallikrein in plasma and urine: evaluation of a direct RIA for its determination.

To determine whether there is glandular kallikrein in plasma, untreated as well as acetone-treated and heated-acidified rat plasmas together with rabbit anti-rat urinary kallikrein were used in counterimmunoelectrophoresis. Precipitation bands were observed with untreated and acetone-treated plasma, suggesting that glandular kallikrein is present in plasma. This enzyme, however, cannot be quantified in the untreated plasma by a new direct RIA since kallikrein inhibitors present in plasma appear to interfere with this assay. Destroying the inhibitors by acetone treatment or by heat and acidification of the plasma partially solves this problem. In the second part of the study, this RIA as well as a kininogenase and an esterase assay were used to measure urinary kallikrein in DOCA-salt treated rats and in control rats. There is a significant correlation between urinary kallikrein measured by the direct RIA and by a kininogenase method (r = 0.75, p less than 0.001) in both DOCA-salt treated and in the control rats. Although the results obtained by the direct RIA and an esterase method significantly correlate in the control rats (r = -0.048, p greater than 0.1). This suggests that part of the urinary esterase activity in the Doca-salt rats is due to urinary enzymes other than kallikrein and that the esterase assay is not reliable for the determination of urinary kallikrein in pathological situations. However, the direct RIA and the kininogenase assay are suitable for this purpose.

Repeatability of ultrasound-predicted percentage of intramuscular fat in feedlot cattle.

We used data from 144 bulls, heifers, and steers to determine the repeatability of ultrasound-predicted percentage of intramuscular fat and to study the effect of repeated measurements on the standard error of prediction. Animals were scanned at an average age of 433 d by a certified technician. Individual bulls, heifers, and steers were scanned five to six times each with two Aloka 500-V machines, and the percentage of intramuscular fat was predicted from two regions of interest within an image. Variance components and repeatability values were computed for the overall data and by machine, region of interest, and sex. Animals were broadly divided into two groups based on mean ultrasound-predicted percentage of intramuscular fat. Variance components and repeatability values were then estimated within each group. The overall repeatability of ultrasound-predicted percentage of intramuscular fat was .63 +/- .03. Differences in the repeatability values between machines and between regions of interest were not different from zero (P > .05). Bulls showed a lower within-animal SD of .82% as compared to .97 and 1.02% for steers and heifers, respectively. However, steer ultrasound-predicted percentage of intramuscular fat measures were more repeatable (P < .05) than those of bulls and heifers. The difference in repeatability between bull and heifer measures was not important (P > .05). Animals with mean ultrasound-predicted percentage of intramuscular fat less than 4.79% showed less repeatable measures (P < .05) than those with means above 4.79%. The image variance contributed to nearly 70% of the total variance of observations within an animal. Standard error of animal mean measures showed a 50% reduction when the number of images per animal increased to four. Therefore, we concluded that increasing the number of images per animal plays a more significant role in reducing the standard error of prediction than taking multiple measurements within a single image.

Predicting percentage of intramuscular fat using two types of real-time ultrasound equipment.

In the present study, 500 steers were used to develop models for predicting the percentage of intramuscular fat (PIMF) in live beef cattle. Before slaughter, steers were scanned across the 11th and 13th ribs using Aloka 500V (AL-500) and Classic Scanner 200 (CS-200) machines. Four to five images were collected per individual steer using each machine. After slaughter, a cross-sectional slice of the longissimus muscle from the 12th rib facing was used for chemical extraction to determine actual carcass percentage of intramuscular fat (CPIMF). Texture analysis software was used by two interpreters to select a region for determination of image parameters, which included Fourier, gradient, histogram, and co-occurrence parameters. Four prediction models were developed separately for each of AL-500 and CS-200 based on images captured by the respective machines. These included models developed without transformation of CPIMF (Model I), models based on logarithmic transformation of CPIMF (Model II), ridge regression procedure (Model III), and principal component regression procedure (Model IV). Model R2 and root mean square error of AL-500 Models I, II, III, and IV were 0.72, 0.84%; 0.72, 0.85%; 0.69, 0.91%; and 0.71, 0.86%; respectively. The corresponding R2 and root mean square error values of CS-200 Models I, II, III, and IV were 0.68, 0.87%; 0.70, 0.85%; 0.64, 0.94%; and 0.65, 0.91%; respectively. Initially, AL-500 and CS-200 prediction models were validated separately on an independent data set from 71 feedlot steers. The overall mean bias, standard error of prediction, and rank correlation coefficient across the four AL-500 models were 0.42%, 0.84%, and 0.88, respectively. For the four CS-200 models, the corresponding overall mean values were 0.67%, 0.81%, and 0.91, respectively. In a second validation test, only Model II of AL-500 and CS-200 was evaluated separately based on data from 24 feedlot steers. The overall mean bias, absolute difference, and standard error of prediction of AL-500 Model II were 0.71, 0.92, and 0.98%. For CS-200 Model II, the corresponding values were 0.59, 0.97, and 1.03%. Both AL-500 and CS-200 equipment can be used to accurately predict PIMF in live cattle. Further improvement in the accuracy of prediction equations could be achieved through increasing the development data set and the variation in PIMF of cattle used.

Clinical profile of cholera in young children--a hospital based report.

Clinical profile of cholera was studied in children attending Diarrhea Training and Treatment Unit from January-December 1993. Out of a total 8714 cases of acute watery diarrhea, 64 children (0.7%) were suspected to have cholera on the basis of acute onset loose water/rice watery stools, high purge rate with or without excessive vomiting and/or severe dehydration. Stool culture was positive for cholera in 33 cases (51.6%). All the isolates were V. cholerae 01 biotype El Tor serotype Ogawa. Sixty four per cent of stool culture positive cases were below 5 years of age. The results assume importance because out of 28 children < 2 years with clinical suspicion of cholera, 11 cases (39.3%) were culture positive for V. cholerae, youngest child being 3 months old. Comparison of various parameters revealed that presence of vomiting > 4 episodes/ day (p < 0.005), frequency of stools >12/24 hours (p <0.002), rice watery stools (p < 0.01) and presence of severe dehydration (p < 0.01) were significant parameters associated with positive stool culture. Beside examination of stool sample by hanging drop method was an excellent diagnostic tool (p < 0.001) with a sensitivity of 51.5%, specificity 100% and positive predictive value of 100%. The isolates of V. cholerae were susceptible to furazolidone, cephelexin, nalidixic acid, norfloxacin and gentamicin. Our observations indicate that cholera is not uncommon in infants and young children. Like children in the older age group, acute onset diarrhea with watery/rice watery stools and high purge rate with or without excessive vomiting and/or rapid development of severe dehydration should arouse suspicion of cholera in younger children also. They should be investigated for cholera even in non-endemic areas and in the absence of cholera outbreaks.

[Anti-leukotoxin antibodies against Actinobacillus actinomycetemcomitans in serum and saliva samples from patients with localized juvenile periodontitis]. / Anticorpos antileucotoxina contra Actinobacillus actinomycetemcomitans em amostras de soro e saliva de pacientes com periodontite juvenil localizada.

The leukotoxin produced by Actinobacillus actinomycetemcomitans is considered the major virulence factor with potential to cause damage to the host defenses. The present work analyzed the serumal and salivary levels of antibodies against the leukotoxin produced by A. Actinomycetemcomitans, in patients with Localized Juvenile Periodontitis (LJP) and in healthy controls. Additionally, analysis of the immune complex (IC) was carried out in saliva samples. The classic ELISA method, with leukotoxin obtained through Sephadex G-200 gel filtration, and the capture ELISA method, using rabbit anti-A. Actinomycetemcomitans (leukotoxic, FDC Y4, IgG) adsorbed with a non-leukotoxic strain of A. actinomycetemcomitans, were used. The results obtained demonstrated significantly higher serumal levels of IgG in patients with LJP, when they were compared with the healthy controls, both for the classic and capture ELISA methods (p < 0.05). However, no significant differences were observed between the salivary levels of IgG, SIgA and IC in the examined individuals. These results suggest that even though A. actinomycetemcomitans presents virulence factors that affect the immune response, there is immune response to leukotoxin in LJP patients. This increase of IgG in the blood stream might contribute to host defense, limiting the lesion to the periodontal regions already colonized by A. actinomycetemcomitans.

Potential femoral head osteonecrosis model induced by high-intensity focused ultrasound.

Osteonecrosis of the femoral head is a common disease that can result in complex hip replacement. To evaluate potential treatments, a model that consistently creates osteonecrosis is needed. We studied and demonstrated the possibility of developing an osteonecrosis model using high-intensity focused ultrasound (HIFU) on canine femora in vitro. To achieve these goals, the temperature in the medullary cavity of the femoral head was measured. A phenomenological model was developed to fit the measured temperature variations with the HIFU parameters for similar HIFU experiments on femoral heads. The average temperature discrepancy between model and measured values was less than 0.83°C. Histology confirmed that the temperature in the medullary cavity can be elevated to a level at which an acute thermal injury is created. HIFU has the potential to be used in a non-invasive model of osteonecrosis.

Intensity-modulated proton therapy further reduces normal tissue exposure during definitive therapy for locally advanced distal esophageal tumors: a dosimetric study.

PURPOSE: We have previously found that ≤ 75% of treatment failures after chemoradiotherapy for unresectable esophageal cancer appear within the gross tumor volume and that intensity-modulated (photon) radiotherapy (IMRT) might allow dose escalation to the tumor without increasing normal tissue toxicity. Proton therapy might allow additional dose escalation, with even lower normal tissue toxicity. In the present study, we compared the dosimetric parameters for photon IMRT with that for intensity-modulated proton therapy (IMPT) for unresectable, locally advanced, distal esophageal cancer. PATIENTS AND METHODS: Four plans were created for each of 10 patients. IMPT was delivered using anteroposterior (AP)/posteroanterior beams, left posterior oblique/right posterior oblique (LPO/RPO) beams, or AP/LPO/RPO beams. IMRT was delivered with a concomitant boost to the gross tumor volume. The dose was 65.8 Gy to the gross tumor volume and 50.4 Gy to the planning target volume in 28 fractions. RESULTS: Relative to IMRT, the IMPT (AP/posteroanterior) plan led to considerable reductions in the mean lung dose (3.18 vs. 8.27 Gy, p<.0001) and the percentage of lung volume receiving 5, 10, and 20 Gy (p≤.0006) but did not reduce the cardiac dose. The IMPT LPO/RPO plan also reduced the mean lung dose (4.9 Gy vs. 8.2 Gy, p<.001), the heart dose (mean cardiac dose and percentage of the cardiac volume receiving 10, 20, and 30 Gy, p≤.02), and the liver dose (mean hepatic dose 5 Gy vs. 14.9 Gy, p<.0001). The IMPT AP/LPO/RPO plan led to considerable reductions in the dose to the lung (p≤.005), heart (p≤.003), and liver (p≤.04). CONCLUSIONS: Compared with IMRT, IMPT for distal esophageal cancer lowered the dose to the heart, lung, and liver. The AP/LPO/RPO beam arrangement was optimal for sparing all three organs. The dosimetric benefits of protons will need to be tailored to each patient according to their specific cardiac and pulmonary risks. IMPT for esophageal cancer will soon be investigated further in a prospective trial at our institution.