Space-time clustering of childhood cancer around the residence at birth.
Previously, we identified space-time clustering in certain childhood cancers around diagnosis residence. These findings provided support for the involvement of environmental agents in etiological processes occurring close to diagnosis. We have reanalyzed the same British population-based dataset. The aim of the study was to determine whether there was space-time clustering around the residence at birth in relation to time of birth and separately from time of diagnosis. A total of 29,553 cases, diagnosed during the period 1969-1993, were examined by a second-order procedure based on K-functions. Locations were birth addresses, but separately, both dates of birth and diagnosis were analyzed. There was statistically significant space-time clustering for Hodgkin lymphoma (HL) and central nervous system (CNS) tumors (p=0.047 and 0.01, respectively, based on birth date) and for total leukemia at ages 1-4 years only, Non-Hodgkin lymphoma (NHL) and Wilms tumor (p=0.01, 0.02 and 0.006, respectively, based on diagnosis date). These results, interpreted together with other epidemiological evidence, suggest an etiological role for environmental factors focused around birth address for certain childhood cancers. For HL and CNS tumors, findings suggest that etiological exposures occurred at similar ages or in utero. For leukemia, NHL and Wilms tumor there is support for exposures occurring at similar times before diagnosis. For leukemia, HL, NHL and CNS tumors, but not Wilms tumor, the findings are consistent with infectious hypotheses.


Computer algorithms for three-dimensional measurement of humeral anatomy: analysis of 140 paired humeri.
In the presence of severe osteoarthritis, osteonecrosis, or proximal humeral fracture, the contralateral humerus may serve as a template for the 3-dimensional (3D) preoperative planning of reconstructive surgery. The purpose of this study was to develop algorithms for performing 3D measurements of the humeral anatomy and further to assess side-to-side (bilateral) differences in humeral head retrotorsion, humeral head inclination, humeral length, and humeral head radius and height. The 3D models of 140 paired humeri (70 cadavers) were extracted from computed tomographic data. Geometric characteristics quantifying the humeral anatomy in 3D were determined in a semiautomatic fashion using the developed computer algorithms. The results between the sides were compared for evaluating bilateral differences. The mean bilateral difference of the humeral retrotorsion angle was 6.7° (standard deviation [SD], 5.7°; range, -15.1° to 24.0°; P = .063); the mean side difference of the humeral head inclination angle was 2.3° (SD, 1.8°; range, -5.1° to 8.4°; P = .12). The side difference in humeral length (mean, 2.9 mm; SD, 2.5 mm; range, -8.7 mm to 10.1 mm; P = .04) was significant. The mean side difference in the head sphere radius was 0.5 mm (SD, 0.6 mm; range, -3.2 mm to 2.2 mm; P = .76), and the mean side difference in humeral head height was 0.8 mm (SD, 0.6 mm; range, -2.4 mm to 2.4 mm; P = .44). The contralateral anatomy may serve as a reliable reconstruction template for humeral length, humeral head radius, and humeral head height if it is analyzed with 3D algorithms. In contrast, determining humeral head retrotorsion and humeral head inclination from the contralateral anatomy may be more prone to error.


Revisiting [PtCl₂(cis-1,4-DACH)]: an underestimated antitumor drug with potential application to the treatment of oxaliplatin-refractory colorectal cancer.
Although the encouraging antitumor activity of [PtCl(2)(cis-1,4-DACH)] (1; DACH = diaminocyclohexane) was shown in early studies almost 20 years ago, the compound has remained nearly neglected. In contrast, oxaliplatin, containing the isomeric 1(R),2(R)-DACH carrier ligand, enjoys worldwide clinic application as a most important therapeutic agent in the treatment of colorectal cancer. By extending the investigation to human chemotherapy-resistant cancer cells, we have demonstrated the real effectiveness of 1 in circumventing cisplatin and oxaliplatin resistance in LoVo colon cancer cells. The uptake of compound 1 by the latter cells was similar to that of sensitive LoVo cells. This is not the case for all other compounds considered in this investigation. Interaction with double-stranded DNA, investigated by a biosensor assay and by quantum mechanical/molecular mechanical geometry optimization of the 1,2-GG intrastrand cross-link, does not show significant differences between 1 and oxaliplatin. However, the DNA adducts of 1 are removed from repair systems with lower efficiency and are more effective in inhibiting DNA and RNA polymerase.


Coronary β2-adrenoreceptors mediate endothelium-dependent vasoreactivity in humans: novel insights from an in vivo intravascular ultrasound study.
The interaction between coronary β(2)-adrenoreceptors and segmental plaque burden is complex and poorly understood in humans. We aimed to validate intracoronary (IC) salbutamol as a novel endothelium-dependent vasodilator utilizing intravascular ultrasound (IVUS), and thus assess relationships between coronary β(2)-adrenoreceptors, regional plaque burden and segmental endothelial function. In 29 patients with near-normal coronary angiograms, IVUS-upon-Doppler Flowire imaging protocols were performed. Protocol 1: incremental IC salbutamol (0.15, 0.30, 0.60 μg/min) infusions (15 patients, 103 segments); protocol 2: salbutamol (0.30 μg/min) infusion before and after IC administration of N(G)-monomethyl-L-arginine (L-NMMA) (10 patients, 82 segments). Vehicle infusions (IC dextrose) were performed in 4 patients (21 segments). Macrovascular response [% change segmental lumen volume (ΔSLV)] and plaque burden [per cent atheroma volume (PAV)] were studied in 5-mm coronary segments. Microvascular response [per cent change in coronary blood flow (ΔCBF)] was calculated following each infusion. Intracoronary salbutamol demonstrated significant dose-response ΔSLV and ΔCBF from baseline, respectively (0.15 μg/min: 3.5 ± 1.3%, 28 ± 14%, P = 0.04, P = NS; 0.30 μg/min: 5.5 ± 1.4%, 54 ± 17%, P = 0.001, P < 0.0001; 0.60 μg/min: 4.8 ± 1.6%, 66 ± 15%, P = 0.02, P < 0.0001), with ΔSLV responses further exemplified in low vs. high plaque burden groups. Salbutamol vasomotor responses were suppressed by l-NMMA, supporting nitric oxide-dependent mechanisms. Vehicle infusions resulted in no significant ΔSLV or ΔCBF. Multivariate analysis including conventional cardiovascular risk factors, PAV, segmental remodelling and plaque eccentricity indices identified PAV as the only significant predictor of a ΔSLV to IC salbutamol (coefficient -0.18, 95% CI -0.32 to -0.044, P = 0.015). Conclusions Intracoronary salbutamol is a novel endothelium-dependent epicardial and microvascular coronary vasodilator. Intravascular ultrasound-derived regional plaque burden is a major determinant of segmental coronary endothelial function.


Childhood forecasting of a small segment of the population with large economic burden.
Policy-makers are interested in early-years interventions to ameliorate childhood risks. They hope for improved adult outcomes in the long run, bringing return on investment. How much return can be expected depends, partly, on how strongly childhood risks forecast adult outcomes. But there is disagreement about whether childhood determines adulthood. We integrated multiple nationwide administrative databases and electronic medical records with the four-decade Dunedin birth-cohort study to test child-to-adult prediction in a different way, by using a population-segmentation approach. A segment comprising one-fifth of the cohort accounted for 36% of the cohort's injury insurance-claims; 40% of excess obese-kilograms; 54% of cigarettes smoked; 57% of hospital nights; 66% of welfare benefits; 77% of fatherless childrearing; 78% of prescription fills; and 81% of criminal convictions. Childhood risks, including poor age-three brain health, predicted this segment with large effect sizes. Early-years interventions effective with this population segment could yield very large returns on investment.


Identification and structure characterization of a Cdk inhibitory peptide derived from neuronal-specific Cdk5 activator.
The activation of cyclin-dependent kinase 5 (Cdk5) depends on the binding of its neuronal specific activator Nck5a. The minimal activation domain of Nck5a is located in the region of amino acid residues 150 to 291 (Tang, D., Chun, A. C. S., Zhang, M., and Wang, J. H. (1997) J. Biol. Chem. 272, 12318-12327). In this work we show that a 29-residue peptide, denoted as the alphaN peptide, encompassing amino acid residues Gln145 to Asp173 of Nck5a is capable of binding Cdk5 to result in kinase inhibition. This peptide also inhibits an active phospho-Cdk2-cyclin A complex, with a similar potency. Direct competition experiments have shown that this inhibitory peptide does not compete with Nck5a or cyclin A for Cdk5 or Cdk2, respectively. Steady state kinetic analysis has indicated that the alphaN peptide acts as a non-competitive inhibitor of Cdk5. Nck5a complex with respect to the peptide substrate. To understand the molecular basis of kinase inhibition by the peptide, we determined the structure of the peptide in solution by circular dichroism and two-dimensional 1H NMR spectroscopy. The peptide adopts an amphipathic alpha-helical structure from residues Ser149 to Arg162 which can be further stabilized by the helix-stabilizing solvent trifluoroethanol. The hydrophobic face of the helix is likely to be the kinase binding surface.


Heart rate variability in patients with fibromyalgia and patients with chronic fatigue syndrome: a systematic review.
The goal of this systematic literature review is to determine whether there are differences and similarities in heart rate variability (HRV) between adult patients with fibromyalgia (FM), chronic fatigue syndrome (CFS), and healthy pain-free control subjects. To obtain relevant articles, PubMed and Web of Knowledge were searched for case-control studies. Selection of the literature was based on selection criteria ascertaining studies with adult human patient groups comparing HRV. Risk of bias and levels of evidence were determined. Sixteen case-control studies were included, 10 comparing FM patients to controls and 6 comparing CFS patients to controls. Methodological quality was moderate to good. Both time domain and frequency domain measurements were used. The majority of the researchers observed lower HRV in FM patients compared to healthy control persons, as well as increased sympathetic activity and a blunted autonomic response to stressors. Resistance training improved HRV in FM patients. In CFS patients HRV was only reduced during sleep. FM patients show more HRV aberrances and indices of increased sympathetic activity. Increased sympathetic activity is only present in CFS patients at night. Since direct comparisons are lacking and some confounders have to be taken into account, further research is warranted. The role of pain and causality can be subject of further research, as well as therapy studies directed to reduced HRV.


Hollow fiber surface plasmon resonance sensor for the detection of liquid with high refractive index.
A new kind of surface plasmon resonance (SPR) sensor based on silver-coated hollow fiber (HF) structure for the detection of liquids with high refractive index (RI) is presented. Liquid sensed medium with high RI is filled in the hollow core of the HF and its RI can be detected by measuring the transmission spectra of the HF SPR sensor. The designed sensors with different silver thicknesses are fabricated and the transmission spectra for filled liquids with different RI are measured to investigate the performances of the sensors. Theoretical analysis is also carried out to evaluate the performance. The simulation results agree well with the experimental results. Factors that might affect sensitivity and detection accuracy of the sensor are discussed. The highest sensitivity achieved is 6,607 nm/RIU, which is comparable to the sensitivities of the other reported fiber SPR sensors.


Assessing fuel spill risks in polar waters: Temporal dynamics and behaviour of hydrocarbons from Antarctic diesel, marine gas oil and residual fuel oil.
As part of risk assessment of fuel oil spills in Antarctic and subantarctic waters, this study describes partitioning of hydrocarbons from three fuels (Special Antarctic Blend diesel, SAB; marine gas oil, MGO; and intermediate grade fuel oil, IFO 180) into seawater at 0 and 5°C and subsequent depletion over 7days. Initial total hydrocarbon content (THC) of water accommodated fraction (WAF) in seawater was highest for SAB. Rates of THC loss and proportions in equivalent carbon number fractions differed between fuels and over time. THC was most persistent in IFO 180 WAFs and most rapidly depleted in MGO WAF, with depletion for SAB WAF strongly affected by temperature. Concentration and composition remained proportionate in dilution series over time. This study significantly enhances our understanding of fuel behaviour in Antarctic and subantarctic waters, enabling improved predictions for estimates of sensitivities of marine organisms to toxic contaminants from fuels in the region.


Data Sharing in the Context of Health-Related Citizen Science.
As citizen science expands, questions arise regarding the applicability of norms and policies created in the context of conventional science. This article focuses on data sharing in the conduct of health-related citizen science, asking whether citizen scientists have obligations to share data and publish findings on par with the obligations of professional scientists. We conclude that there are good reasons for supporting citizen scientists in sharing data and publishing findings, and we applaud recent efforts to facilitate data sharing. At the same time, we believe it is problematic to treat data sharing and publication as ethical requirements for citizen scientists, especially where there is the potential for burden and harm without compensating benefit.


Factors predicting entry of injecting drug users into substance abuse treatment.
A prospective study of 823 injecting drug users (IDUs) was made to identify baseline variables differentiating those who entered treatment during the study from those who did not enter. Variables independently associated with entering treatment in a multiple logistic regression model included (a) expressed desire for treatment, (b) being eligible for methadone maintenance, (c) two or more previous treatment admissions, (d) frequency of injection, (e) heroin use in the past 30 days, (e) being human immunodeficiency virus (HIV) positive, (f) giving money or drugs for sex, and (g) level of injection-related risk for HIV infection.


Treatment for lexical retrieval in progressive aphasia.
BACKGROUND: Treatment for lexical retrieval impairment has been shown to yield positive outcomes in individuals with aphasia due to focal lesions, but there has been little research regarding the treatment of such impairments in individuals with progressive aphasia. AIMS: The purpose of this study was to examine the therapeutic effects of a semantic treatment for anomia in progressive aphasia relative to the outcome in an individual with stroke-induced aphasia. METHODS #ENTITYSTARTX00026; PROCEDURES: Two individuals with progressive aphasia and one with aphasia resulting from stroke participated in the study. Each participant presented with fluent, anomic aphasia; however, one of the patients with progressive aphasia demonstrated characteristics indicating a likely progression towards non-fluency. Each participant received a brief, intensive treatment intended to improve lexical retrieval in the context of generative naming for selected semantic categories. Treatment tasks included guided lexical retrieval prompted by the identification and elaboration of items within semantic subcategories, as well as other semantic tasks. Treatment outcomes were quantified using standard effects sizes as well as nonparametric tests comparing pre- versus post-treatment performance. OUTCOMES #ENTITYSTARTX00026; RESULTS: One of the individuals with progressive aphasia showed large treatment effects for lexical retrieval of items from targeted semantic categories. The other progressive aphasia patient showed very small effects overall for treated categories. The individual with the focal lesion due to stroke showed medium-sized effects for trained categories as well as significant improvement on a standardised measure of naming. CONCLUSIONS: Findings indicate that intensive, semantically based treatment for lexical retrieval can result in positive outcomes in individuals with progressive as well as stroke-induced aphasia. Examination of individual differences suggests that the status of semantic and episodic memory may provide predictive information regarding responsiveness to treatment.


Expert in nursing care but sometimes disrespected-Telenurses' reflections on their work environment and nursing care.
To describe telenurses' reflections on their work environment and how it impacts on their nursing care. Telenursing is one of the largest healthcare settings in Sweden today; approximately 5.5 million care-seekers call the designated number-1177-each year. Telenursing is regarded as highly qualified nursing care, and providing care over the telephone is considered a complex form of nursing. Within other fields of nursing, the work environment has been shown to affect the outcome of care, patient safety, nurse job satisfaction and burnout. The study used a descriptive design and followed the COREQ checklist. Twenty-four interviews were performed and analysed using qualitative content analysis. The main theme concerned "feeling like a nursing care expert but sometimes being disrespected." The telenurses reported that their work environment supported their work as nursing care experts via the telephone in some respects, but also hindered them. Appreciation and respect they received from the vast majority of callers positively impacted the work environment and contributed to work satisfaction. However, they also felt disrespected by both their employers and healthcare staff; they sometimes felt like a dumping ground. Receiving support from colleagues seemed invaluable in helping them feel like and be a nursing care expert. Work was perceived as cognitively demanding and sometimes exhausting, but appreciation from care-seekers and the feeling of being able to provide qualified nursing care made working as a telenurse worthwhile. If telenurses are to perform good nursing care over the telephone, managers must provide them with resources, for example, support, education and opportunities for recovery during shifts. It seems that the role of the 1177 service has not been properly implemented and accepted within the healthcare system, and politicians need to anchor its mission within the healthcare organisation.


Automated solid-phase extraction coupled online with HPLC-FLD for the quantification of zearalenone in edible oil.
Established maximum levels for the mycotoxin zearalenone (ZEN) in edible oil require monitoring by reliable analytical methods. Therefore, an automated SPE-HPLC online system based on dynamic covalent hydrazine chemistry has been developed. The SPE step comprises a reversible hydrazone formation by ZEN and a hydrazine moiety covalently attached to a solid phase. Seven hydrazine materials with different properties regarding the resin backbone, pore size, particle size, specific surface area, and loading have been evaluated. As a result, a hydrazine-functionalized silica gel was chosen. The final automated online method was validated and applied to the analysis of three maize germ oil samples including a provisionally certified reference material. Important performance criteria for the recovery (70-120 %) and precision (RSDr <25 %) as set by the Commission Regulation EC 401/2006 were fulfilled: The mean recovery was 78 % and RSDr did not exceed 8 %. The results of the SPE-HPLC online method were further compared to results obtained by liquid-liquid extraction with stable isotope dilution analysis LC-MS/MS and found to be in good agreement. The developed SPE-HPLC online system with fluorescence detection allows a reliable, accurate, and sensitive quantification (limit of quantification, 30 μg/kg) of ZEN in edible oils while significantly reducing the workload. To our knowledge, this is the first report on an automated SPE-HPLC method based on a covalent SPE approach.


Registration of images with N -fold dihedral blur.
In this paper, we extend our recent registration method designed specifically for registering blurred images. The original method works for unknown blurs, assuming the blurring point-spread function (PSF) exhibits an N -fold rotational symmetry. Here, we also generalize the theory to the case of dihedrally symmetric blurs, which are produced by the PSFs having both rotational and axial symmetries. Such kind of blurs are often found in unfocused images acquired by digital cameras, as in out-of-focus shots the PSF typically mimics the shape of the shutter aperture. This makes our registration algorithm particularly well-suited in applications where blurred image registration must be used as a preprocess step of an image fusion algorithm, and where common registration methods fail, due to the amount of blur. We demonstrate that the proposed method leads to an improvement of the registration performance, and we show its applicability to real images by providing successful examples of blurred image registration followed by depth-of-field extension and multichannel blind deconvolution.


Variations in jump height explain the between-sex difference in patellar tendon loading during landing.
Patellar tendinopathy is the most common overuse knee injury in volleyball, with men reporting more than twice the injury prevalence than women. Although high patellar tendon loading is thought to be a causative factor of patellar tendinopathy, it is unknown whether between-sex variations in landing technique account for differences in patellar tendon loading. It was hypothesized that male volleyball players would display differences in landing technique and would generate higher patellar tendon loading than their female counterparts. The landing technique and patellar tendon loading of 20 male and 20 female volleyball players performing a lateral stop-jump block movement were collected. Independent t-tests were used to identify any between-sex differences in landing technique with the data grouped to account for differences in jump height and in anthropometry. Male volleyball players were taller and heavier, landed from a higher height, displayed differences in landing kinematics, generated a significantly greater knee extensor moment, and experienced higher patellar tendon loading than female players when all 40 participants were compared. However, when participants were matched on jump height, they generated similar patellar tendon loading, irrespective of their sex. These results imply that jump height is a more important determinant of patellar tendon loading than sex.


Association between physical activity and sub-types of cardiovascular disease death causes in a general population cohort.
Physical activity is thought to be cardioprotective, but associations with different subtypes of cardiovascular disease (CVD) are poorly understood. We examined associations between physical activity and seven major CVD death causes. The sample comprised 65,093 adults (aged 58 ± 12 years, 45.4% men) followed up over mean [SD] 9.4 ± 4.5 years, recruited from The Health Survey for England and the Scottish Health Surveys. A CVD diagnosis was reported in 9.2% of the sample at baseline. Physical activity was self-reported. Outcomes were subtypes of CVD death; acute myocardial infarction; chronic ischaemic heart disease; pulmonary heart disease; a composite of cardiac arrest, arrhythmias, and sudden cardiac death; heart failure; cerebrovascular; composite of aortic aneurysm and other peripheral vascular diseases. There were 3050 CVD deaths (30.8% of all deaths). In Cox proportional hazards models adjusted for confounders, physical activity was associated with reduced relative risk of all CVD outcomes; compared with the lowest, the highest physical activity quintile was associated with reduced risk of acute myocardial infarction (Hazard ratio 0.66: 95% CI 0.50, 0.89), chronic ischaemic heart disease (0.49: 0.38, 0.64), pulmonary heart disease (0.48: 0.22, 1.07), arrhythmias (0.18: 0.04, 0.76); heart failure (0.35: 0.20, 0.63), cerebrovascular events (0.53: 0.38, 0.75); aneurysm and peripheral vascular diseases (0.54: 0.34, 0.93). Results were largely consistent across participants with and without existing CVD at baseline. Physical activity was associated with reduced risk of seven major CVD death causes. Protective benefits were apparent even at levels of activity below the current recommendations.


Induction of tissue factor on monocytes by adhesion to endothelial cells.
Activated monocytes express tissue factor (TF), a protein that is important in the pathogenesis of thrombotic disorders. We sought to characterize an adhesion-dependent pathway for monocyte activation. In this study, we showed that adhesion of monocytes to cytokine-activated endothelial cells (EC) increased (approximately 5- to 10-fold) monocyte procoagulant activity (PCA). The PCA was attributed to TF because it was dependent on the coagulation factors VII and X, but not VIII, and was completely blocked by an anti-TF mAb. Direct cell-cell contact between monocytes and EC was required. The induction of TF was rapid, peaked at 30 min, and persisted for 4 h. Northern analysis revealed a rapid (approximately 30 min) increase in TF mRNA following adhesion, distinct from that induced by LPS (approximately 2-4 h). Four-hour TNF-treated EC supported TF expression, but 0.5- and 24-h TNF-treated EC had no effect. An anti-E-selectin mAb (H18/7) exerted partial inhibition, whereas anti-VCAM-1, ICAM-1, and CD11/CD18 mAbs had no inhibition. Synthetic Lewis X (Le(x)) oligosaccharide partially blocked TF induction, whereas sialyl-Le(x) (sLex) oligosaccharide had no effect. Cross-linking Le(x) on monocytes, but not sLex, significantly increased (approximately 10-fold) the TF expression. Le(x) cross-linking induced TF in 30 min and lasted for 4 h. All seventeen anti-Le(x) mAbs induced significant amount of TF generation, and epitope mapping revealed a single binding epitope on Le(x). These findings indicate that adhesion of monocytes to activated EC induces TF generation, and also suggest that Le(x) may represent an important signaling molecule on monocytes.


A community-based study to examine the effect of a youth HIV prevention intervention on young people aged 15-24 in South Africa: results of the baseline survey.
To determine whether South African youths living in communities that had either of two youth human immunodeficiency virus (HIV) prevention interventions [(a) loveLife Youth Centre or (b) loveLife National Adolescent Friendly Clinic Initiative] would have a lower prevalence of HIV, sexually transmitted infections (STIs), and high risk sexual behaviours than communities without either of these interventions. In 2002 the baseline survey of a quasi-experimental, community-based study was conducted in South Africa. In total 33 communities were included in three study arms (11 communities per study arm). The final sample included 8735 youths aged 15-24 years. All participants took part in a behavioural interview and were tested for HIV, gonorrhoea (Neisseria gonorrhoeae) and Chlamydia (Chlamydia trachomatis). HIV prevalence was 20.0% among females and 7.5% among males (OR 3.93 95% CI 2.51-6.15). There were no significant differences between study arms for HIV, NG or CT prevalence at baseline. In multiple regression analyses, HIV was significantly associated with NG infection (OR 1.96 95% CI 1.24-3.12) but not with CT infection. Youths who reported >1 lifetime partner were also significantly more likely to be infected with HIV (OR 1.98 95% CI 1.55-2.52), as were those who reported ever having engaged in transactional sex (OR 1.86 P = 0.02) or having had genital ulcers in the past 12 months (OR 1.71 P < or = 0.001). HIV prevention programmes must ensure that gender inequities that place young women at greater risk for HIV infection are urgently addressed and they must continue to emphasize the importance of reducing the number of sexual partners and STI treatment.


Dissolution of Interlayers from Intergradient Soil Clays after Preheating at 400{degrees}C.
Dehydroxylated interlayers have been removed from chlorite-vermiculite-montmorillonite intergrades by boiling the preheated sample in 0.5N NaOH for 2.5 minutes. Elements extracted can be conveniently analyzed spectrophotometrically. A convenient method of estimating the amount of elements present in interlayer positions and preparing the sample for analysis for expanding and nonexpanding mineral components is thus provided.


The medical student as a patient: attitudes towards involvement in the quality and safety of health care.
In recent years, factors that affect patients' willingness and ability to participate in safety-relevant behaviours have been investigated. However, how trained healthcare professionals or medical students would feel participating in safety-relevant behaviours as a patient in hospital remains largely unexplored. To investigate medical students' willingness to participate in behaviours related to the quality and safety of their health care. A cross-sectional exploratory study using a survey that addressed willingness to participate in different behaviours recommended by current patient safety initiatives. Three types of interactional behaviours (asking factual or challenging questions, notifying doctors or nurses of errors/problems) and three non-interactional behaviours (choosing a hospital based on the safety record, bringing medicines and a list of allergies into hospital, and reporting an error to a national reporting system) were assessed. One hundred and seventy-nine medical students from an inner city London teaching hospital participated in the study. Students' willingness to participate was affected (P < 0.05) by the action required by the patient and (for interactional behaviours) whether the patient was engaging in the specific action with a doctor or nurse. Students were least willing to ask 'challenging' questions to doctors and nurses and to report errors to a national reporting system. Doctors' and nurses' encouragement appeared to increase self-reported willingness to participate in behaviours where baseline willingness was low. Similar to research on lay patient populations; medical students do not view involvement in safety-related behaviours equally. Interventions should be tailored at encouraging students to participate in behaviours they are less inclined to take on an active role in. Future research is required to examine students' motivations for participation in this important but heavily under-researched area.


Thrombolysis by ultrasound.
1. A new method of destroying thrombi in blood vessels by ultrasound and simultaneously removing them is reported. 2. Experiments were performed in twenty dogs with artificial thrombi in the iliac and femoral arteries and veins. The length of the thrombi ranged from 4 to 5 cm and the age from 12 h to 10 days. The unit used consisted of a generator, a frequency counter, an ultrasonic transducer with the hollow waveguide and a vacuum pump. For protection of the vessel wall the guide is surrounded by a plastic tube. The ultrasonic frequency is 26-5 kHz, the amplitude 25-30 micronm. The time needed to destroy the thrombus by ultrasound and suck out the thrombotic material ranged from 2-5 to 5 min. 3. To check side effects, experiments were performed in forty-four dogs. No significant changes were seen in the fibrinolytic system or microscopic structure of the vessel wall after ultrasound.


Fumarase activity: an in vivo and in vitro biomarker for acute kidney injury.
Renal ischemia/reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI), and at present, there is a lack of reliable biomarkers that can diagnose AKI and measure early progression because the commonly used methods cannot evaluate single-kidney IRI. Hyperpolarized [1,4-13C2]fumarate conversion to [1,4-13C2]malate by fumarase has been proposed as a measure of necrosis in rat tumor models and in chemically induced AKI rats. Here we show that the degradation of cell membranes in connection with necrosis leads to elevated fumarase activity in plasma and urine and secondly that hyperpolarized [1,4-13C2]malate production 24 h after reperfusion correlates with renal necrosis in a 40-min unilateral ischemic rat model. Fumarase activity screening on bio-fluids can detect injury severity, in bilateral as well as unilateral AKI models, differentiating moderate and severe AKI as well as short- and long-term AKI. Furthermore after verification of renal injury by bio-fluid analysis the precise injury location can be monitored by in vivo measurements of the fumarase activity non-invasively by hyperpolarized [1,4-13C]fumarate MR imaging. The combined in vitro and in vivo biomarker of AKI responds to the essential requirements for a new reliable biomarker of AKI.


Best practice for motor imagery: a systematic literature review on motor imagery training elements in five different disciplines.
The literature suggests a beneficial effect of motor imagery (MI) if combined with physical practice, but detailed descriptions of MI training session (MITS) elements and temporal parameters are lacking. The aim of this review was to identify the characteristics of a successful MITS and compare these for different disciplines, MI session types, task focus, age, gender and MI modification during intervention. An extended systematic literature search using 24 databases was performed for five disciplines: Education, Medicine, Music, Psychology and Sports. References that described an MI intervention that focused on motor skills, performance or strength improvement were included. Information describing 17 MITS elements was extracted based on the PETTLEP (physical, environment, timing, task, learning, emotion, perspective) approach. Seven elements describing the MITS temporal parameters were calculated: study duration, intervention duration, MITS duration, total MITS count, MITS per week, MI trials per MITS and total MI training time. Both independent reviewers found 96% congruity, which was tested on a random sample of 20% of all references. After selection, 133 studies reporting 141 MI interventions were included. The locations of the MITS and position of the participants during MI were task-specific. Participants received acoustic detailed MI instructions, which were mostly standardised and live. During MI practice, participants kept their eyes closed. MI training was performed from an internal perspective with a kinaesthetic mode. Changes in MI content, duration and dosage were reported in 31 MI interventions. Familiarisation sessions before the start of the MI intervention were mentioned in 17 reports. MI interventions focused with decreasing relevance on motor-, cognitive- and strength-focused tasks. Average study intervention lasted 34 days, with participants practicing MI on average three times per week for 17 minutes, with 34 MI trials. Average total MI time was 178 minutes including 13 MITS. Reporting rate varied between 25.5% and 95.5%. MITS elements of successful interventions were individual, supervised and non-directed sessions, added after physical practice. Successful design characteristics were dominant in the Psychology literature, in interventions focusing on motor and strength-related tasks, in interventions with participants aged 20 to 29 years old, and in MI interventions including participants of both genders. Systematic searching of the MI literature was constrained by the lack of a defined MeSH term.


Microbiological quality and presence of foodborne pathogens in raw milk cheeses and raw meat products marketed at farm level in Switzerland.
This study investigated the microbiological quality and presence of bacterial foodborne pathogens in 51 raw milk cheeses (mainly semihard and hard cheese) and 53 raw meat products (cured meat products and sausages) marketed at farm level. With regard to Enterobacteriaceae, Escherichia (E.) coli, and coagulase-positive staphylococci (CPS), the examined products were generally of a good microbiological quality. Enterobacteriaceae were found in seven cheeses (1.0×102 - 8.8×104 CFU/g) and one sausage (2.0×102 CFU/g). Three of these cheeses were also positive for E. coli. CPS results were comparable for cheeses (5.9%; 1.0-6.0×102 CFU/g) and meat products (3.8%; 1.0-2.0×102 CFU/g). On the other hand, such raw products may harbor potential health hazards as Listeria (L.) monocytogenes, Shiga toxin-producing E. coli (STEC), and staphylococcal enterotoxin (SE)-producing Staphylococcus (S.) aureus. L. monocytogenes were found in one sausage and the isolate belonged to the serotype 1/2c. The two STEC isolates harbored stx1a (cheese) or stx2e (sausage), but both lacked eae and did not belong to the top five-serogroups. Of the five S. aureus isolates, the three cheese isolates belonged to the clonal complex (CC) 8, CC22, and CC705, the two sausage isolates belonged to CC7, and all isolates harbored genes for SEs. Thus, to avoid contaminations and to prevent foodborne pathogens from entering the food chain, strict compliance with good hygiene practices during milk and cheese production or meat production is of central importance.


Unraveling the interactions between cold atmospheric plasma and skin-components with vibrational microspectroscopy.
Using infrared and Raman microspectroscopy, the authors examined the interaction of cold atmospheric plasma with the skin's built-in protective cushion, the outermost skin layer stratum corneum. Following a spectroscopic analysis, the authors could identify four prominent chemical alterations caused by plasma treatment: (1) oxidation of disulfide bonds in keratin leading to a generation of cysteic acid; (2) formation of organic nitrates as well as (3) of new carbonyl groups like ketones, aldehydes and acids; and (4) reduction of double bonds in the lipid matter lanolin, which resembles human sebum. The authors suggest that these generated acidic and NO-containing functional groups are the source of an antibacterial and regenerative environment at the treatment location of the stratum corneum. Based upon the author's results, the authors propose a mechanistic view of how cold atmospheric plasmas could modulate the skin chemistry to produce positive long-term effects on wound healing: briefly, cold atmospheric plasmas have the potential to transform the skin itself into a therapeutic resource.


Failure of CD4 T Cell-Deficient Hosts To Control Chronic Nontyphoidal Salmonella Infection Leads to Exacerbated Inflammation, Chronic Anemia, and Altered Myelopoiesis.
Immunocompromised patients are more susceptible to recurrent nontyphoidal Salmonella (NTS) bacteremia. A key manifestation of HIV infection is the loss of CD4 T cells, which are crucial for immunity to Salmonella infection. We characterized the consequences of CD4 T cell depletion in mice where virulent Salmonella establish chronic infection, similar to chronic NTS disease in humans. Salmonella-infected, CD4-depleted 129X1/SvJ mice remained chronically colonized for at least 5 weeks, displaying increased splenomegaly and more severe splenitis than infected mice with CD4 T cells. Mature erythrocytes, immature erythroid cells, and phagocytes accounted for the largest increase in splenic cellularity. Anemia, which is associated with increased mortality in Salmonella-infected humans, was exacerbated by CD4 depletion in infected mice and was accompanied by increased splenic sequestration of erythrocytes and fewer erythropoietic elements in the bone marrow, despite significantly elevated levels of circulating erythropoietin. Splenic sequestration of red blood cells, the appearance of circulating poikilocytes, and elevated proinflammatory cytokines suggest inflammation-induced damage to erythrocytes contributes to anemia and splenic retention of damaged cells in infected animals. Depleting CD4 T cells led to increased myeloid cells in peripheral blood, spleen, and bone marrow, as well as expansion of CD8 T cells, which has been observed in CD4-depleted humans. This work describes a mouse model of Salmonella infection that recapitulates several aspects of human disease and will allow us to investigate the interplay of innate and adaptive immune functions with chronic inflammation, anemia, and susceptibility to Salmonella infection.


Melatonin secretion profile after experimental pineal gland compression in rats.
Pineal gland hormone, melatonin, is a current issue of interest for accumulating data concerning its diverse physiological functions. The disturbances in melatonin secretion are observed in different pathological conditions involving pineal regions, but it is not ascertained if those disturbances present any clinical implications. The aim of this work was to examine whether pineal gland compression changes melatonin secretion. The experiment was carried out on adult rats, divided into four equal groups: (i) control (no surgery was performed), (ii) sham-operated, (iii) with sham pineal gland compression and (iv) with pineal gland compression performed by cotton piece application. The profile of melatonin secretion was assessed in blood samples collected five times daily, every second day, starting from 8 to 14 day following surgery. We found that surgery itself significantly increased night melatonin secretion in comparison to controls. By contrast, in pineal-gland compressed rats, melatonin secretion was lower than in control group, suggesting that the influence of pineal compression overcame that induced by operation stress. In conclusion, we presume that pineal gland compression (like in case of some tumors) results in decrease of the concentration of blood melatonin, that may possibly result in decreased protective action of the indoleamine.


Nutrition and disease progression pre-highly active antiretroviral therapy (HAART) and post-HAART: can good nutrition delay time to HAART and affect response to HAART?
Several studies have investigated a variety of nutritional supplementation interventions in adults with HIV. In this narrative review, we summarize the evidence from 31 clinical trials that explore clinical benefits of macronutrient and micronutrient supplementation in this population while attempting to answer the question of whether good nutrition can delay the time to highly active antiretroviral therapy (HAART) initiation and response. We focused on trials published in English between 1990 and 2010 that reported on CD4 count, viral load, and disease progression or survival. Among 9 macronutrient and 22 micronutrient trials, we found that evidence for improved CD4 count and HIV viral load with nutritional supplementation was limited; only 11.1% and 36.8% of macronutrient and micronutrient supplementation trials, respectively, reported improved CD4 count; and 33.3% and 12.5% of macronutrient and micronutrient trials, respectively, reported decreased viral load. Given their utility as surrogate markers of HIV disease progression, this suggests limited evidence for nutritional interventions having an impact on delaying HAART initiation or on improving HAART response. However, there are challenges in evaluating the effects of nutritional supplementation on clinical disease in that comparisons are difficult due to heterogeneity in study design, patient population, nutrient doses and combinations, baseline levels of deficiency, and study endpoints, including lack of clarity in defining and reporting HAART status. Future studies need to adopt a more rigorous standard design with adequate power and follow-up and require a consensus on composition and dose of nutrient interventions to be tested to more specifically answer the question on the impact of nutritional interventions on HIV disease progression and HAART response.


Fetal aortic blood flow and echocardiographic findings in human pregnancy.
Relationships between human fetal aortic blood flow parameters and the corresponding echocardiographic findings were investigated in 51 normal, 26 hypertensive and 18 diabetic late pregnancies. In the normal pregnancies the time-averaged mean and peak velocities and the waveform indexes of the flow in the fetal aorta were not dependent on the cardiac size nor on the fractional shortening of the myocardium. Total blood flow in the aorta correlated well with heart size and left ventricular output. Hypertensive cases had, as a group, lower aortic velocities and higher waveform indexes than normal and diabetic pregnancies, and the difference from normal was particularly great if the fetus was growth-retarded. Myocardial contractility in these fetuses remained good in spite of these peripheric hemodynamic alterations, but the relative size of the right ventricle was increased. The diabetic cases had smaller blood flow volume in fetal aorta than in the normal cases. In contrast with normal pregnancies the myocardial fractional shortening of these fetuses decreased if the pulsatility of the aortic blood flow increased or the total blood flow in the aorta was high. These findings point to a decreased functional capacity of the fetal heart in a diabetic pregnancy, in particular in the late weeks of gestation.


LIGHT ADAPTATION KINETICS: THE INFLUENCE OF SPATIAL FACTORS.
Reducing the target diameter of an adapting (conditioning) flash of light results in a progressive rise in the conventional light adaptation curve, as measured with a small superimposed test flash presented at the end of adapting flashes of variable duration. When both targets are the same size, an abrupt and marked rise in threshold is obtained, resulting from a unique effect that occurs near the termination of the adapting flash. This effect can be demonstrated by means of a variable delay procedure, and it indicates that neural as well as photo-chemical processes limit the time course of light adaptation.


Variation in deliberate self-harm around Christmas and New Year.
Seasonal and temporal variations in suicide by patient and demographic groups, though important, have been investigated infrequently. This study examined patterns of non-fatal deliberate self-harm (DSH) during Christmas and New Year (from December 16th to January 6th) by specific patient and demographic group. The sample comprised 19,346 people who presented with 31,369 episodes of DSH to a general hospital Emergency Department in Oxford, UK. Autoregression analysis of all episodes from 1976 to 2003 (controlling for day of the week, month and year) revealed significant reductions (-30% to -40%) in the occurrence of DSH compared with expected numbers on each day from December 19th to 26th (except the 23rd), though no significant increase was found on any of the subsequent 11 days. When analysed separately, young people aged under 25 years showed decreases (-60%) in the occurrence of DSH on several days throughout Christmas (p<0.001) and New Year (p<0.01). Patients with partner relationship problems showed a decrease 3 days before Christmas Day (-80%, p<0.001) and an increase on New Year's Day (+100%, p<0.01). Patients with family relationship problems showed decreases before Christmas and after New Year (-60%, p<0.01). Patients with social isolation problems, or a previous history of DSH showed decreases (-60%, p<0.01) before Christmas only. Patients who used alcohol at the time of DSH or in the 6h beforehand, but did not chronically misuse alcohol, showed an increase (+250%, p<0.01) on New Year's Day. There was no significant variation in the occurrence of DSH for patient groups with either low/medium or high suicide intent. The findings elucidate how social and individual factors may interact in contributing to DSH. They are of theoretical interest, and have important clinical implications regarding identification of patient groups especially susceptible to DSH at New Year.


Communicating psychosocial well-being in motor neurone disease to staff: results from a World Café approach.
Little to no research has evaluated staff training and its effects on the well-being of people with MND. The aim of this study was to assess how educating multi-disciplinary staff about psychosocial well-being in MND can change approaches to working with people with MND. Multi-disciplinary staff attended a half-day workshop to receive training on psychosocial well-being in people with MND and to discuss QoL issues using the World Café approach. Prior to the workshop and 2 weeks post-workshop, staff completed a questionnaire on their knowledge of this topic. A selection of staff completed a follow-up interview 2 months later to assess changes in their practice. 19 staff, including dieticians and occupational therapists, attended the workshop and completed the pre-workshop questionnaire. Ten filled in the post-workshop questionnaire and were interviewed. Clinicians identified six strategies/barriers of improving communication amongst MND staff, suggesting the need for better collaborative working, raising awareness of psychological and emotional issues in MND and barriers to service access due to health inequalities, amongst others. This workshop raised staff awareness on communicating QoL in MND. Future work needs to look into implementing this training in clinical practice and evaluate their impact on QoL in MND.


Melanopsin and rod-cone photoreceptive systems account for all major accessory visual functions in mice.
In the mammalian retina, besides the conventional rod-cone system, a melanopsin-associated photoreceptive system exists that conveys photic information for accessory visual functions such as pupillary light reflex and circadian photo-entrainment. On ablation of the melanopsin gene, retinal ganglion cells that normally express melanopsin are no longer intrinsically photosensitive. Furthermore, pupil reflex, light-induced phase delays of the circadian clock and period lengthening of the circadian rhythm in constant light are all partially impaired. Here, we investigated whether additional photoreceptive systems participate in these responses. Using mice lacking rods and cones, we measured the action spectrum for phase-shifting the circadian rhythm of locomotor behaviour. This spectrum matches that for the pupillary light reflex in mice of the same genotype, and that for the intrinsic photosensitivity of the melanopsin-expressing retinal ganglion cells. We have also generated mice lacking melanopsin coupled with disabled rod and cone phototransduction mechanisms. These animals have an intact retina but fail to show any significant pupil reflex, to entrain to light/dark cycles, and to show any masking response to light. Thus, the rod-cone and melanopsin systems together seem to provide all of the photic input for these accessory visual functions.


Psychometric properties of the Caregiving Burden Scale for Family Caregivers with Relatives in Nursing Homes: scale development.
Most family caregivers continue their caregiving for frail relatives after admitting them to long-term care facilities. The characteristics of this caregiving differ from those related to caregiving in home-care settings. Thus, a new tool to evaluate the burden of family caregivers in institutional settings is needed. The aim of this study was to develop a new scale, the Caregiving Burden Scale for Family Caregivers with Relatives in Nursing Homes, and to confirm its validity and reliability. We conducted two cross-sectional questionnaire surveys. The participants were a convenience sample of family members of residents in seven nursing homes for the validation study and in three nursing homes for the test-retest study in Japan. Statistical analyses examined exploratory/confirmatory factor analyses, internal consistency, concurrent/discriminate validity, and test-retest reliability. A four-factor solution with 16 items was selected as the most interpretable questionnaire. In the confirmatory factor analysis, the indices of fitness highly supported these results. The Cronbach's alpha coefficient for the total score was 0.86 and varied between 0.77 and 0.87 in the four domains. The scale showed moderate correlation with the Nursing Home Hassles Scale, suggesting its concurrent validity. The four domains had only a medium correlation with each other, indicating discriminate validity. The developed scale has acceptable validity and reliability for measuring the caregiving burden of family members with relatives in Japanese nursing homes. Future studies using the scale might lead to the improvement of care for family members with relatives in a long-term care setting.


Horse liver alcohol dehydrogenase. A study of the essential lysine residue.
1. The inactivation of horse liver alcohol dehydrogenase by pyridoxal 5'-phosphate in phosphate buffer, pH8, at 10 degrees C was investigated. Activity declines to a minimum value determined by the pyridoxal 5'-phosphate concentration. The maximum inactivation in a single treatment is 75%. This limit appears to be set by the ratio of the first-order rate constants for interconversion of inactive covalently modified enzyme and a readily dissociable non-covalent enzyme-modifier complex. 2. Reactivation was virtually complete on 150-fold dilution: first-order analysis yielded an estimate of the rate constant (0.164min-1), which was then used in the kinetic analysis of the forward inactivation reaction. This provided estimates for the rate constant for conversion of non-covalent complex into inactive enzyme (0.465 min-1) and the dissociation constant of the non-covalent complex (2.8 mM). From the two first-order constants, the minimum attainable activity in a single cycle of treatment may be calculated as 24.5%, very close to the observed value. 3. Successive cycles of modification followed by reduction with NaBH4 each decreased activity by the same fraction, so that three cycles with 3.6 mM-pyridoxal 5'-phosphate decreased specific activity to about 1% of the original value. The absorption spectrum of the enzyme thus treated indicated incorporation of 2-3 mol of pyridoxal 5'-phosphate per mol of subunit, covalently bonded to lysine residues. 4. NAD+ and NADH protected the enzyme completely against inactivation by pyridoxal 5'-phosphate, but ethanol and acetaldehyde were without effect. 5. Pyridoxal 5'-phosphate used as an inhibitor in steady-state experiments, rather than as an inactivator, was non-competitive with respect to both NADH and acetaldehyde. 6. The partially modified enzyme (74% inactive) showed unaltered apparent Km values for NAD+ and ethanol, indicating that modified enzyme is completely inactive, and that the residual activity is due to enzyme that has not been covalently modified. 7. Activation by methylation with formaldehyde was confirmed, but this treatment does not prevent subsequent inactivation with pyridoxal 5'-phosphate. Presumably different lysine residues are involved. 8. It is likely that the essential lysine residue modified by pyridoxal 5'-phosphate is involved either in binding the coenzymes or in the catalytic step. 9. Less detailed studies of yeast alcohol dehydrogenase suggest that this enzyme also possesses an essential lysine residue.


Record of mid-Archaean subduction from metamorphism in the Barberton terrain, South Africa.
Although plate tectonics is the central geological process of the modern Earth, its form and existence during the Archaean era (4.0-2.5 Gyr ago) are disputed. The existence of subduction during this time is particularly controversial because characteristic subduction-related mineral assemblages, typically documenting apparent geothermal gradients of 15 degrees C km(-1) or less, have not yet been recorded from in situ Archaean rocks (the lowest recorded apparent geothermal gradients are greater than 25 degrees C km(-1)). Despite this absence from the rock record, low Archaean geothermal gradients are suggested by eclogitic nodules in kimberlites and circumstantial evidence for subduction processes, including possible accretion-related structures, has been reported in Archaean terrains. The lack of spatially and temporally well-constrained high-pressure, low-temperature metamorphism continues, however, to cast doubt on the relevance of subduction-driven tectonics during the first 1.5 Gyr of the Earth's history. Here we report garnet-albite-bearing mineral assemblages that record pressures of 1.2-1.5 GPa at temperatures of 600-650 degrees C from supracrustal amphibolites from the mid-Archaean Barberton granitoid-greenstone terrain. These conditions point to apparent geothermal gradients of 12-15 degrees C-similar to those found in recent subduction zones-that coincided with the main phase of terrane accretion in the structurally overlying Barberton greenstone belt. These high-pressure, low-temperature conditions represent metamorphic evidence for cold and strong lithosphere, as well as subduction-driven tectonic processes, during the evolution of the early Earth.


Local VE-cadherin mechanotransduction triggers long-ranged remodeling of endothelial monolayers.
In this study, we present results demonstrating that mechanotransduction by vascular endothelial cadherin (VE-cadherin, also known as CDH5) complexes in endothelial cells triggers local cytoskeletal remodeling, and also activates global signals that alter peripheral intercellular junctions and disrupt cell-cell contacts far from the site of force application. Prior studies have documented the impact of actomyosin contractile forces on adherens junction remodeling, but the role of VE-cadherin in force sensation and its ability to influence endothelial cell and tissue mechanics globally have not been demonstrated. Using mechanical manipulation of VE-cadherin bonds and confocal imaging, we demonstrate VE-cadherin-based mechanotransduction. We then demonstrate that it requires homophilic VE-cadherin ligation, an intact actomyosin cytoskeleton, Rho-associated protein kinase 1 (ROCK1) and phosphoinositide 3-kinase. VE-cadherin-mediated mechanotransduction triggered local actin and vinculin recruitment, as well as global signals that altered focal adhesions and disrupted peripheral intercellular junctions. Confocal imaging revealed that VE-cadherin-specific changes appear to propagate across cell junctions to disrupt distant inter-endothelial junctions. These results demonstrate the central role of VE-cadherin adhesions and the actomyosin cytoskeleton within an integrated, mechanosensitive network that both induces local cytoskeletal remodeling at the site of force application and regulates the global integrity of endothelial tissues.


ASAS-NANP SYMPOSIUM: RUMINANT/NONRUMINANT FEED COMPOSITION: Challenges and opportunities associated with creating large feed composition tables.
Traditional feed composition tables have been a useful tool in the field of animal nutrition throughout the last 70 yr. The objective of this paper is to discuss the challenges and opportunities associated with creating large feed ingredient composition tables. This manuscript will focus on three topics discussed during the National Animal Nutrition Program (NANP) Symposium in ruminant and nonruminant nutrition carried out at the American Society of Animal Science Annual Meeting in Austin, TX, on July 11, 2019, namely: 1) Using large datasets in feed composition tables and the importance of standard deviation in nutrient composition as well as different methods to obtain accurate standard deviation values, 2) Discussing the importance of fiber in animal nutrition and the evaluation of different methods to estimate fiber content of feeds, and 3) Description of novel feed sources, such as insects, algae, and single-cell protein, and challenges associated with the inclusion of such feeds in feed composition tables. Development of feed composition tables presents important challenges. For instance, large datasets provided by different sources tend to have errors and misclassifications. In addition, data are in different file formats, data structures, and feed classifications. Managing such large databases requires computers with high processing power and software that are also able to run automated procedures to consolidate files, to screen out outlying observations, and to detect misclassified records. Complex algorithms are necessary to identify misclassified samples and outliers aimed to obtain accurate nutrient composition values. Fiber is an important nutrient for both monogastrics and ruminants. Currently, there are several methods available to estimate the fiber content of feeds. However, many of them do not estimate fiber accurately. Total dietary fiber should be used as the standard method to estimate fiber concentrations in feeds. Finally, novel feed sources are a viable option to replace traditional feed sources from a nutritional perspective, but the large variation in nutrient composition among batches makes it difficult to provide reliable nutrient information to be tabulated. Further communication and cooperation among different stakeholders in the animal industry are required to produce reliable data on the nutrient composition to be published in feed composition tables.


Deletions affecting hemolytic and toxin activities of Bordetella pertussis adenylate cyclase.
The Bordetella pertussis cyaA gene encodes a virulence factor which is a bifunctional protein exhibiting calmodulin-sensitive adenylate cyclase and hemolytic activities (P. Glaser, H. Sakamoto, J. Bellahov, A. Ullmann, and A. Danchin, EMBO J. 7:3997-4004, 1988). We characterized the hemolytic and toxin activities of the 200-kilodalton (kDa) bifunctional (CyaA) protein and showed that, whether cell associated or secreted, the 200-kDa CyaA protein carries hemolytic and toxin functions. The catalytically active 45-kDa form of adenylate cyclase released by proteolytic digestion of the 200-kDa CyaA protein displayed neither hemolytic nor toxin activities. We constructed in-phase deletions in the 3' region of the cyaA gene, which presumably carries the hemolytic determinant, and showed that the resulting proteins exhibited wild-type adenylate cyclase activity and were secreted without processing into culture supernatants. The hemolytic activities of these mutant CyaA proteins were severely reduced, and their toxin activities were abolished. These results suggest that the structural integrity of the 200-kDa CyaA protein is necessary for toxin activity and that distinct structural determinants within the CyaA protein are involved in secretion, pore formation, and entry into target cells.


Bystander cricothyrotomy with ballpoint pen: a fresh cadaveric feasibility study.
In motion pictures and anecdotal reports, ballpoint pens have been used for life-saving cricothyroidotomies. The objective of this study was to examine the widespread belief that ballpoint pens can perforate the skin and cricothyroid ligament and could be used as substitute tracheostomy sets in an emergency setting. Three different ballpoint pens were examined regarding their inner diameter, their demountability to form a cannula and their airflow properties. Ten medical laypersons were asked to try to puncture the trachea through the skin and the cricothyroid ligament in 10 fresh cadavers just using the ballpoint pens. Two of three pens had inner diameters of >3 mm and were both suitable as cannulas in a tracheotomy. All participants could perforate the skin with both ballpoint pens. However, almost no one could penetrate through the cricothyroid ligament or the ventral wall of the trachea, except for one participant. He performed the tracheostomy after three attempts in >5 min with a lot of patience and force. A cricothyroidotomy just with a ballpoint pen is virtually impossible. First, the airflow resistance in commercially available ballpoint pens is too high to produce effective ventilation. Second, the cricothyroid ligament is too strong to be penetrated by ballpoint pens.


Neutrophils sequestered in the liver suppress the proinflammatory response of Kupffer cells to systemic bacterial infection.
The liver plays a major role in clearing bacteria from the bloodstream. Rapid clearance is primarily the function of fixed tissue macrophages (Kupffer cells) that line the hepatic sinusoids. Although Kupffer cells play a critical role in blood clearance, the actual elimination of the bulk of bacteria taken up by the liver depends upon the accumulation of bactericidal neutrophils. Subsequent experiments demonstrating neutrophils inside Kupffer cells derived from infected animals prompted our speculation that neutrophils modulate the proinflammatory response of Kupffer cells to bacteria cleared from the bloodstream. Indeed, we report here that neutrophils accumulated in the liver sinusoids suppress cytokine and chemokine mRNA expression and protein production by Kupffer cells. Using listeriosis in mice as an experimental model, we found that IL-1beta, IL-6, IL-10, IL-12, TNF-alpha, MIP-1alpha, keratinocyte-derived chemokine, and MCP-1 mRNA levels were >or=10-fold more in the livers of Listeria-infected, relative to noninfected control, mice at 0.5-2 h after i.v. infection. Most message levels were sharply diminished thereafter, correlating inversely with increased neutrophil sequestration. Relative to intact animals, mice rendered neutrophil deficient exhibited marked increases in cytokine/chemokine mRNA expression and protein production in the liver subsequent to infection. Moreover, purified Kupffer cells derived from infected, neutrophil-depleted mice produced significantly more IL-6, IL-10, IL-12, TNF-alpha, keratinocyte-derived chemokine, and MCP-1 in culture. These findings document the critical role of neutrophils in moderating the proinflammatory response of Kupffer cells to bacteria taken up by the liver.


An EEG Study on Emotional Intelligence and Advertising Message Effectiveness.
Some electroencephalography (EEG) studies have investigated emotional intelligence (EI), but none have examined the relationships between EI and commercial advertising messages and related consumer behaviors. This study combines brain (EEG) techniques with an EI psychometric to explore the brain responses associated with a range of advertisements. A group of 45 participants (23 females, 22 males) had their EEG recorded while watching a series of advertisements selected from various marketing categories such as community interests, celebrities, food/drink, and social issues. Participants were also categorized as high or low in emotional intelligence (n = 34). The EEG data analysis was centered on rating decision-making in order to measure brain responses associated with advertising information processing for both groups. The findings suggest that participants with high and low emotional intelligence (EI) were attentive to different types of advertising messages. The two EI groups demonstrated preferences for "people" or "object," related advertising information. This suggests that differences in consumer perception and emotions may suggest why certain advertising material or marketing strategies are effective or not.


Femtosecond damage resistance of femtosecond multilayer and hybrid mirrors.
Improving the laser-induced damage threshold of optical components is a basic endeavor in femtosecond technology. By testing more than 30 different femtosecond mirrors with 42 fs laser pulses at 1 kHz repetition rate, we found that a combination of high-bandgap dielectric materials and improved design and coating techniques enable femtosecond multilayer damage thresholds exceeding 2 J/cm2 in some cases. A significant ×2.5 improvement in damage resistance can also be achieved for hybrid Ag-multilayer mirrors exhibiting more than 1 J/cm2 threshold with a clear anticorrelation between damage resistance and peak field strength in the stack. Slight dependence on femtosecond pulse length and substantial decrease for high (megahertz) repetition rates are also observed.


Evaluation of the protective effect of quercetin against cisplatin-induced renal and testis tissue damage and sperm parameters in rats.
The protective effect of quercetin on cisplatin-induced renal and testicular tissue damage was investigated using biochemical, histopathological and histological approaches. A total of 40 male rats were divided into 5 groups as follows: control; cisplatin alone; quercetin alone; cisplatin + quercetin; and quercetin + cisplatin. Cisplatin was administered to rats at a single dose of 7 mg kg(-1) intraperitoneal. Quercetin was administered by gavage daily for 10 days at dosage 50 mg kg(-1) . At the end of the study serum, total antioxidant capacity (TAC) levels and total oxidant status (TOS) were determined. Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and xanthine oxidase (XO) were studied separately in serum, renal tissue and testicular tissue. Renal and testicular morphological alterations were assessed, histopathologically. Epididymal sperm concentration, motility and morphology were investigated. Testicular and renal TAC and TOS values did not alter significantly. Renal CAT levels were increased by cisplatin and cisplatin plus quercetin groups that is reversed by administration of quercetin before cisplatin. MDA, CAT, SOD ve XO levels of testicular tissue did not differ significantly. Cisplatin and cisplatin plus quercetin groups had decreased sperm motility ratio and increased abnormal spermatozoa. Quercetin partially reverses some of the cisplatin-related pathological effects on kidney and testis.


Calcium-calmodulin does not alter the anion permeability of the mouse TMEM16A calcium-activated chloride channel.
The transmembrane protein TMEM16A forms a Ca(2+)-activated Cl(-) channel that is permeable to many anions, including SCN(-), I(-), Br(-), Cl(-), and HCO3 (-), and has been implicated in various physiological functions. Indeed, controlling anion permeation through the TMEM16A channel pore may be critical in regulating the pH of exocrine fluids such as the pancreatic juice. The anion permeability of the TMEM16A channel pore has recently been reported to be modulated by Ca(2+)-calmodulin (CaCaM), such that the pore of the CaCaM-bound channel shows a reduced ability to discriminate between anions as measured by a shift of the reversal potential under bi-ionic conditions. Here, using a mouse TMEM16A clone that contains the two previously identified putative CaM-binding motifs, we were unable to demonstrate such CaCaM-dependent changes in the bi-ionic potential. We confirmed the activity of CaCaM used in our study by showing CaCaM modulation of the olfactory cyclic nucleotide-gated channel. We suspect that the different bi-ionic potentials that were obtained previously from whole-cell recordings in low and high intracellular [Ca(2+)] may result from different degrees of bi-ionic potential shift secondary to a series resistance problem, an ion accumulation effect, or both.


6-thioguanine selectively kills BRCA2-defective tumors and overcomes PARP inhibitor resistance.
Familial breast and ovarian cancers are often defective in homologous recombination (HR) due to mutations in the BRCA1 or BRCA2 genes. Cisplatin chemotherapy or poly(ADP-ribose) polymerase (PARP) inhibitors were tested for these tumors in clinical trials. In a screen for novel drugs that selectively kill BRCA2-defective cells, we identified 6-thioguanine (6TG), which induces DNA double-strand breaks (DSB) that are repaired by HR. Furthermore, we show that 6TG is as efficient as a PARP inhibitor in selectively killing BRCA2-defective tumors in a xenograft model. Spontaneous BRCA1-defective mammary tumors gain resistance to PARP inhibitors through increased P-glycoprotein expression. Here, we show that 6TG efficiently kills such BRCA1-defective PARP inhibitor-resistant tumors. We also show that 6TG could kill cells and tumors that have gained resistance to PARP inhibitors or cisplatin through genetic reversion of the BRCA2 gene. Although HR is reactivated in PARP inhibitor-resistant BRCA2-defective cells, it is not fully restored for the repair of 6TG-induced lesions. This is likely to be due to several recombinogenic lesions being formed after 6TG. We show that BRCA2 is also required for survival from mismatch repair-independent lesions formed by 6TG, which do not include DSBs. This suggests that HR is involved in the repair of 6TG-induced DSBs as well as mismatch repair-independent 6TG-induced DNA lesion. Altogether, our data show that 6TG efficiently kills BRCA2-defective tumors and suggest that 6TG may be effective in the treatment of advanced tumors that have developed resistance to PARP inhibitors or platinum-based chemotherapy.


Mammalian CAP interacts with CAP, CAP2, and actin.
We previously identified human CAP, a homolog of the yeast adenylyl cyclase-associated protein. Previous studies suggest that the N-terminal and C-terminal domains of CAP have distinct functions. We have explored the interactions of human CAP with various proteins. First, by performing yeast two-hybrid screens, we have identified peptides from several proteins that interact with the C-terminal and/or the N-terminal domains of human CAP. These peptides include regions derived from CAP and BAT3, a protein with unknown function. We have further shown that MBP fusions with these peptides can associate in vitro with the N-terminal or C-terminal domains of CAP fused to GST. Our observations indicate that CAP contains regions in both the N-terminal and C-terminal domains that are capable of interacting with each other or with themselves. Furthermore, we found that myc-epitope-tagged CAP coimmunoprecipitates with HA-epitope-tagged CAP from either yeast or mammalian cell extracts. Similar results demonstrate that human CAP can also interact with human CAP2. We also show that human CAP interacts with actin, both by the yeast two-hybrid test and by coimmunoprecipitation of epitope-tagged CAP from yeast or mammalian cell extracts. This interaction requires the C-terminal domain of CAP, but not the N-terminal domain. Thus CAP appears to be capable of interacting in vivo with other CAP molecules, CAP2, and actin. We also show that actin co-immunoprecipitates with HA-CAP2 from mammalian cell extracts.


Tonic 5nM DA stabilizes neuronal output by enabling bidirectional activity-dependent regulation of the hyperpolarization activated current via PKA and calcineurin.
Volume transmission results in phasic and tonic modulatory signals. The actions of tonic dopamine (DA) at type 1 DA receptors (D1Rs) are largely undefined. Here we show that tonic 5nM DA acts at D1Rs to stabilize neuronal output over minutes by enabling activity-dependent regulation of the hyperpolarization activated current (I h). In the presence but not absence of 5nM DA, I h maximal conductance (G max) was adjusted according to changes in slow wave activity in order to maintain spike timing. Our study on the lateral pyloric neuron (LP), which undergoes rhythmic oscillations in membrane potential with depolarized plateaus, demonstrated that incremental, bi-directional changes in plateau duration produced corresponding alterations in LP I hG max when preparations were superfused with saline containing 5nM DA. However, when preparations were superfused with saline alone there was no linear correlation between LP I hGmax and duty cycle. Thus, tonic nM DA modulated the capacity for activity to modulate LP I h G max; this exemplifies metamodulation (modulation of modulation). Pretreatment with the Ca2+-chelator, BAPTA, or the specific PKA inhibitor, PKI, prevented all changes in LP I h in 5nM DA. Calcineurin inhibitors blocked activity-dependent changes enabled by DA and revealed a PKA-mediated, activity-independent enhancement of LP I hG max. These data suggested that tonic 5nM DA produced two simultaneous, PKA-dependent effects: a direct increase in LP I h G max and a priming event that permitted calcineurin regulation of LP I h. The latter produced graded reductions in LP I hG max with increasing duty cycles. We also demonstrated that this metamodulation preserved the timing of LP's first spike when network output was perturbed with bath-applied 4AP. In sum, 5nM DA permits slow wave activity to provide feedback that maintains spike timing, suggesting that one function of low-level, tonic modulation is to stabilize specific features of a dynamic output.


Might migraine damage the brain?
Recent debate concerning the interpretation of studies of regional cerebral blood flow in migraine has re-emphasized that cerebral ischaemia may occur during attacks of migraine with aura. In this article we suggest that the presence of ischaemia during attacks makes it possible that migraine with aura causes neuronal damage in the long term. We argue that damage is likely to occur in the primary visual cortex, given that a recent high-resolution rCBF study has found flow reductions confined to this area. Furthermore, we hypothesize that the extent to which rCBF is reduced in migraine with aura is sufficient to cause damage only to GABA-ergic inhibitory interneurons in layer IV of this cortex. In animal models, similar cells are known to be selectively vulnerable to damage as a result of hypoxic conditions. Evidence consistent with our hypothesis is provided by recent studies of visual function in migraine. Some clinical and pathophysiological implications of this hypothesis are discussed.


C-reactive protein point of care testing and physician communication skills training for lower respiratory tract infections in general practice: economic evaluation of a cluster randomized trial.
An economic evaluation of general practitioner (GP) use of C-reactive protein (CRP) point of care test, GP communication skills training, and both GP use of CRP and communication skills training on antibiotic use for lower respiratory tract infections (LRTIs) in general practice. Cost-effectiveness analysis with a time horizon of 28 days alongside a factorial, cluster randomized trial in 431 patients with LRTIs recruited by 40 GPs. usual care (control group), GP use of CRP point of care test, GP communication skills training, and both CRP use and communication skills training. health care costs. Cost-effectiveness, using the primary outcome measure antibiotic prescribing at index consultation, was assessed by incremental cost-effectiveness ratios (ICER). To adjust for skewed data and clustering, we used non-parametric bootstrapping re-sampling to derive percentile intervals for the mean difference in total costs and the mean difference in effectiveness between the groups. Various implementation scenarios according to GP preference were modelled with corresponding net monetary benefit (NMB) curves based on a given willingness-to-pay (λ) for a 1% lower antibiotic prescribing rate. The total mean cost per patient in the usual care group was €35.96 with antibiotic prescribing of 68%, €37.58 per patient managed by GPs using CRP tests (antibiotic prescribing 39%, ICER €5.79), €25.61 per patient managed by GPs trained in enhanced communication skills (antibiotic prescribing 33%, dominant) and €37.78 per patient managed by GPs using both interventions (antibiotic prescribing 23%, ICER €4.15). The interventions are cost-effective in any combination (yielding NMB at no willingness-to-pay), taking into account GPs' preferences where at least 15% of GPs chose to implement the communication skills training. The two strategies, both singly and combined, are cost-effective interventions to reduce antibiotic prescribing for LRTI, at no, or low willingness-to-pay. Taking GP preferences into account will optimize investment in strategies to reduce antibiotic prescribing for LRTI.


Facilitating patient acceptance of a psychiatric referral.
There are five common ways in which a patient may object to a physician's suggestion of a psychiatric referral. The patient may reject the referral because of the social stigma of being a psychiatric patient; because the referral damages his or her self-esteem; because the patient does not understand the role of emotions in physical discomfort; because the patient feels rejected by the referring physician; or because of the effects of psychiatric illness. Following a thorough medical workup, the physician can best discharge his or her responsibility to the patient by paying attention to these possible misunderstandings. The physician can discuss the role of social stigma, offset the blows to the patient's self-esteem, educate the patient about the psychosomatic model of disease, and assure the patient of the physician's continuing interest and involvement.


Life problems in children and adolescents who self-harm: findings from the multicentre study of self-harm in England.
Self-harm, a significant and increasing global problem in children and adolescents, is often repeated and is associated with risk of future suicide. To identify potential interventions, we need to understand the life problems faced by children and adolescents, and by sub-groups of younger people who self-harm. Our aims were to include the following: (a) investigate the type and frequency of life problems in a large sample of children and adolescents who self-harmed. (b) Examine whether problems differ between those who repeat self-harm and those who do not. We analysed data for 2000 to 2013 (follow up until 2014) from the Multicentre Study of Self-harm in England on individuals aged 11 to 18 years who presented to one of the five study hospitals following self-harm and received a psychosocial assessment including questions about problems, which precipitated self-harm. In 5648 patients (12,261 self-harm episodes), (75.5% female, mean age 16.1 years) the most frequently reported problems at first episode of self-harm were family problems. Problems around study/employment/study and relationships with friends also featured prominently. The types of problems that precede self-harm differed between late childhood/early adolescence. Abuse, mental health problems and legal problems significantly predicted repeat self-harm for females. The most common problems reported by both genders were social/interpersonal in nature, indicating the need for relevant services embedded in the community (e.g. in schools/colleges). Self-harm assessment and treatment choices for children and adolescents must take age and gender into account. To prevent future self-harm, individualised supports and services are particularly needed for abuse, mental health and legal problems.


Vitalistic thinking in adults.
Vitalistic thinking has traditionally been associated with reasoning about biological phenomena. The current research aimed to investigate a broader range of vitalistic thinking than previously studied. Esoteric notions of 'energy' are frequently used by individuals when making causal attributions for strange occurrences, and previous literature has linked such thinking with paranormal, magical, and superstitious beliefs. Two experiments are described that aim to investigate whether adults are vitalistic when asked to make causal judgments, and whether this can be predicted by thinking styles and prior paranormal belief. Experiment 1 asked participants to rate three causal options (one of which was vitalistic) for six vignettes. Scores on one dimension of paranormal belief (New Age Philosophy) and analytical thinking significantly predicted vitalism, but scores on intuitive thinking and Traditional Paranormal Beliefs did not. Experiment 2 extended the findings by asking participants to generate their own causal responses. Again, paranormal belief was found to be the best predictor of vitalism, but this time Traditional Paranormal Beliefs were associated with vitalistic responses whilst both intuitive and analytical thinking were unable to significantly predict classification. Results challenge previous findings, suggesting that vitalistic thinking may operate differently when applied to everyday causal reasoning.


The NIH BD2K center for big data in translational genomics.
The world's genomics data will never be stored in a single repository - rather, it will be distributed among many sites in many countries. No one site will have enough data to explain genotype to phenotype relationships in rare diseases; therefore, sites must share data. To accomplish this, the genetics community must forge common standards and protocols to make sharing and computing data among many sites a seamless activity. Through the Global Alliance for Genomics and Health, we are pioneering the development of shared application programming interfaces (APIs) to connect the world's genome repositories. In parallel, we are developing an open source software stack (ADAM) that uses these APIs. This combination will create a cohesive genome informatics ecosystem. Using containers, we are facilitating the deployment of this software in a diverse array of environments. Through benchmarking efforts and big data driver projects, we are ensuring ADAM's performance and utility.


Anterior peri-insular quadrantotomy: a cadaveric white matter dissection study.
Anterior quadrant disconnection represents a safe surgical option in well-selected pediatric patients with a large frontal lobe lesion anterior to the motor cortex. The understanding of the anatomy of the white matter tracts connecting the frontal lobe with the rest of the cerebrum forms the basis of a safe and successful disconnective surgery. The authors explored and illustrated the relevant white matter tracts sectioned during each surgical step using fiber dissection techniques. Five human cadaveric hemispheres were dissected to illustrate the frontal connections in the 3 planes. The dissections were performed from lateral to medial, medial to lateral, and ventral to dorsal to describe the various tracts sectioned during the 4 steps of this surgery, namely the anterior suprainsular window, intrafrontal disconnection, anterior callosotomy, and frontobasal disconnection. At the beginning of each surgical step, the U fibers were cut. During the anterior suprainsular window, the superior longitudinal fasciculus (SLF), the uncinate fasciculus, and the inferior fronto-occipital fasciculus (IFOF) were visualized and sectioned, followed by sectioning of the anterior limb of the internal capsule. During the intrafrontal disconnection, the SLF was cut, along with the corona radiata. At the medial surface the cingulum was sectioned. The anterior callosotomy disconnected the anterior third of the body of the callosum, the genu, and the rostrum. The frontobasal disconnection addressed the last remaining fibers connecting the frontal lobe with the rest of the hemisphere, namely the anterior limb of the anterior commissure. The anterior peri-insular quadrantotomy aims at effectively treating children with large lesions of the frontal lobe anterior to the motor cortex. A precise understanding of the gyral anatomy of this lobe along with the several white matter connections is crucial to avoid motor complications and to ensure complete disconnection.


Comparative genetic architectures of schizophrenia in East Asian and European populations.
Schizophrenia is a debilitating psychiatric disorder with approximately 1% lifetime risk globally. Large-scale schizophrenia genetic studies have reported primarily on European ancestry samples, potentially missing important biological insights. Here, we report the largest study to date of East Asian participants (22,778 schizophrenia cases and 35,362 controls), identifying 21 genome-wide-significant associations in 19 genetic loci. Common genetic variants that confer risk for schizophrenia have highly similar effects between East Asian and European ancestries (genetic correlation = 0.98 ± 0.03), indicating that the genetic basis of schizophrenia and its biology are broadly shared across populations. A fixed-effect meta-analysis including individuals from East Asian and European ancestries identified 208 significant associations in 176 genetic loci (53 novel). Trans-ancestry fine-mapping reduced the sets of candidate causal variants in 44 loci. Polygenic risk scores had reduced performance when transferred across ancestries, highlighting the importance of including sufficient samples of major ancestral groups to ensure their generalizability across populations.


Safety and efficacy of Avizyme® 1505 (endo-1,4-beta-xylanase, subtilisin and alpha-amylase) for all poultry species.
Avizyme® 1505 is based on three enzyme activities produced by three genetically modified microorganisms: xylanase, subtilisin and amylase produced by Trichoderma reesei, Bacillus subtilis and Bacillus amyloliquefaciens, respectively. It is authorised for use in chickens and turkeys for fattening, ducks and laying hens. This scientific opinion concerns the request for the renewal of the authorisation of the additive for the species/categories for which there is an authorisation, a reduction of the minimum recommended level in turkeys for fattening and the extension of use to all avian species for laying, for fattening, reared for breeding and reared for laying (except for ducks). Based on recent data, uncertainty remains in the characterisation of the production strains and the possible presence in the final product of viable production strains and their DNA. Therefore, the EFSA Panel on Additives and products or Substances used in Animal Feed (FEEDAP) could not confirm the conclusions previously drawn regarding the safety of Avizyme® 1505 for the target species, consumers, users and environment. This conclusion applies also to the new target species for which a request for an extension of use is made. There was no need for assessing the efficacy of the additive in the context of the renewal of the authorisation for chickens for fattening, ducks and laying hens. The efficacy data previously evaluated allowed the Panel to conclude that the additive has the potential to be efficacious at 187.5 U xylanase, 2,500 U subtilisin and 250 U amylase/kg complete feed for all avian species for fattening (including turkeys), reared for breeding and reared for laying and 300 U xylanase, 4,000 U subtilisin and 400 U amylase/kg complete feed in all avian species for laying.


Nanoparticle-Mediated Photothermal Therapy Limitation in Clinical Applications Regarding Pain Management.
The development of new effective cancer treatment methods has attracted much attention, mainly due to the limited efficacy and considerable side effects of currently used cancer treatment methods such as radiation therapy and chemotherapy. Photothermal therapy based on the use of plasmonically resonant metallic nanoparticles has emerged as a promising technique to eradicate cancer cells selectively. In this method, plasmonic nanoparticles are first preferentially uptaken by a tumor and then selectively heated by exposure to laser radiation with a specific plasmonic resonant wavelength, to destroy the tumor whilst minimizing damage to adjacent normal tissue. However, several parameters can limit the effectiveness of photothermal therapy, resulting in insufficient heating and potentially leading to cancer recurrence. One of these parameters is the patient's pain sensation during the treatment, if this is performed without use of anesthetic. Pain can restrict the level of applicable laser radiation, cause an interruption to the treatment course and, as such, affect its efficacy, as well as leading to a negative patient experience and consequential general population hesitancy to this type of therapy. Since having a comfortable and painless procedure is one of the important treatment goals in the clinic, along with its high effectiveness, and due to the relatively low number of studies devoted to this specific topic, we have compiled this review. Moreover, non-invasive and painless methods for temperature measurement during photothermal therapy (PTT), such as Raman spectroscopy and nanothermometry, will be discussed in the following. Here, we firstly outline the physical phenomena underlying the photothermal therapy, and then discuss studies devoted to photothermal cancer treatment concerning pain management and pathways for improved efficiency of photothermal therapy whilst minimizing pain experienced by the patient.


Low-energy He/Ne laser in the prevention of radiation-induced mucositis. A multicenter phase III randomized study in patients with head and neck cancer.
Use of the low-energy helium-neon laser (LEL) appears to be a simple atraumatic technique for the prevention and treatment of mucositis of various origins. Preliminary findings, and significant results obtained for chemotherapy-induced mucositis in a previous phase III study, prompted a randomized multicenter double-blind trial to evaluate LEL in the prevention of acute radiation-induced stomatitis. Irradiation by LEL corresponds to local application of a high-photon-density monochromatic light source. Activation of epithelial healing for LEL-treated surfaces, the most commonly recognized effect, has been confirmed by numerous in vitro studies. The mechanism of action at a molecular and enzymatic level is presently being studied. From September 1994 to March 1998, 30 patients were randomized. Technical specification: 60 mW (25 mW at Reims, 1 patient), He-Ne, wavelength 632.8 nm. The trial was open to patients with carcinoma of the oropharynx, hypopharynx and oral cavity, treated by radiotherapy alone (65 Gy at a rate of 2 Gy/fraction, 5 fractions per week) without prior surgery or concomitant chemotherapy. The malignant tumor had to be located outside the tested laser application areas (9 points): posterior third of the internal surfaces of the cheeks, soft palate and anterior tonsillar pillars. Patients were randomized to LEL or placebo light treatment, starting on the first day of radiotherapy and before each session. The treatment time (t) for each application point was given by the equation : t(s)= energy (J/cm2) x surface (cm2)/Power (W). Objective assessment of the degree of mucositis was recorded weekly by a physician blinded to the type of treatment, using the WHO scale for grading of mucositis and a segmented visual analogue scale for pain evaluation. Protocol feasibility and compliance were excellent. Grade 3 mucositis occured with a frequency of 35.2% without LEL and of 7.6% with LEL (P<0.01). The frequency of "severe pain" (grade 3) was 23.8% without LEL, falling to 1.9% with LEL (P<0.05). Pain relief was significantly reduced throughout the treatment period (weeks 2-7). LEL therapy is capable of reducing the severity and duration of oral mucositis associated with radiation therapy. In addition, there is a tremendous potential for using LEL in combined treatment protocols utilizing concomitant chemotherapy and radiotherapy.


Quantitative modeling of the accuracy in registering preoperative patient-specific anatomic models into left atrial cardiac ablation procedures.
In cardiac ablation therapy, accurate anatomic guidance is necessary to create effective tissue lesions for elimination of left atrial fibrillation. While fluoroscopy, ultrasound, and electroanatomic maps are important guidance tools, they lack information regarding detailed patient anatomy which can be obtained from high resolution imaging techniques. For this reason, there has been significant effort in incorporating detailed, patient-specific models generated from preoperative imaging datasets into the procedure. Both clinical and animal studies have investigated registration and targeting accuracy when using preoperative models; however, the effect of various error sources on registration accuracy has not been quantitatively evaluated. Data from phantom, canine, and patient studies are used to model and evaluate registration accuracy. In the phantom studies, data are collected using a magnetically tracked catheter on a static phantom model. Monte Carlo simulation studies were run to evaluate both baseline errors as well as the effect of different sources of error that would be present in a dynamic in vivo setting. Error is simulated by varying the variance parameters on the landmark fiducial, physical target, and surface point locations in the phantom simulation studies. In vivo validation studies were undertaken in six canines in which metal clips were placed in the left atrium to serve as ground truth points. A small clinical evaluation was completed in three patients. Landmark-based and combined landmark and surface-based registration algorithms were evaluated in all studies. In the phantom and canine studies, both target registration error and point-to-surface error are used to assess accuracy. In the patient studies, no ground truth is available and registration accuracy is quantified using point-to-surface error only. The phantom simulation studies demonstrated that combined landmark and surface-based registration improved landmark-only registration provided the noise in the surface points is not excessively high. Increased variability on the landmark fiducials resulted in increased registration errors; however, refinement of the initial landmark registration by the surface-based algorithm can compensate for small initial misalignments. The surface-based registration algorithm is quite robust to noise on the surface points and continues to improve landmark registration even at high levels of noise on the surface points. Both the canine and patient studies also demonstrate that combined landmark and surface registration has lower errors than landmark registration alone. In this work, we describe a model for evaluating the impact of noise variability on the input parameters of a registration algorithm in the context of cardiac ablation therapy. The model can be used to predict both registration error as well as assess which inputs have the largest effect on registration accuracy.