High-Statistics Measurement of Neutrino Quasielasticlike Scattering at 6 GeV on a Hydrocarbon Target.

We measure neutrino charged-current quasielasticlike scattering on hydrocarbon at high statistics using the wideband Neutrinos at the Main Injector beam with neutrino energy peaked at 6 GeV. The double-differential cross section is reported in terms of muon longitudinal (p_{∥}) and transverse (p_{⊥}) momentum. Cross section contours versus lepton momentum components are approximately described by a conventional generator-based simulation, however, discrepancies are observed for transverse momenta above 0.5 GeV/c for longitudinal momentum ranges 3-5 and 9-20 GeV/c. The single differential cross section versus momentum transfer squared (dσ/dQ_{QE}^{2}) is measured over a four-decade range of Q^{2} that extends to 10 GeV^{2}. The cross section turnover and falloff in the Q^{2} range 0.3-10 GeV^{2} is not fully reproduced by generator predictions that rely on dipole form factors. Our measurement probes the axial-vector content of the hadronic current and complements the electromagnetic form factor data obtained using electron-nucleon elastic scattering. These results help oscillation experiments because they probe the importance of various correlations and final-state interaction effects within the nucleus, which have different effects on the visible energy in detectors.

Tailoring the properties of (catalytically)-active inclusion bodies.

BACKGROUND: Immobilization is an appropriate tool to ease the handling and recycling of enzymes in biocatalytic processes and to increase their stability. Most of the established immobilization methods require case-to-case optimization, which is laborious and time-consuming. Often, (chromatographic) enzyme purification is required and stable immobilization usually includes additional cross-linking or adsorption steps. We have previously shown in a few case studies that the molecular biological fusion of an aggregation-inducing tag to a target protein induces the intracellular formation of protein aggregates, so called inclusion bodies (IBs), which to a certain degree retain their (catalytic) function. This enables the combination of protein production and immobilization in one step. Hence, those biologically-produced immobilizates were named catalytically-active inclusion bodies (CatIBs) or, in case of proteins without catalytic activity, functional IBs (FIBs). While this strategy has been proven successful, the efficiency, the potential for optimization and important CatIB/FIB properties like yield, activity and morphology have not been investigated systematically. RESULTS: We here evaluated a CatIB/FIB toolbox of different enzymes and proteins. Different optimization strategies, like linker deletion, C- versus N-terminal fusion and the fusion of alternative aggregation-inducing tags were evaluated. The obtained CatIBs/FIBs varied with respect to formation efficiency, yield, composition and residual activity, which could be correlated to differences in their morphology; as revealed by (electron) microscopy. Last but not least, we demonstrate that the CatIB/FIB formation efficiency appears to be correlated to the solvent-accessible hydrophobic surface area of the target protein, providing a structure-based rationale for our strategy and opening up the possibility to predict its efficiency for any given target protein. CONCLUSION: We here provide evidence for the general applicability, predictability and flexibility of the CatIB/FIB immobilization strategy, highlighting the application potential of CatIB-based enzyme immobilizates for synthetic chemistry, biocatalysis and industry.

Genetic variation in the shape of cold-survival curves in a single fly population suggests potential for selection from climate variability.

Temperature variation is one of the primary challenges facing ectotherms, and the ability to tolerate a range of thermal environments is critical for setting current and future species distributions. Low temperature is particularly challenging for ectotherms because winter conditions have strong latitudinal and temporal variation. Lower lethal temperature (LLT) is a common metric of cold tolerance used in studies of local adaptation and plasticity. Comparisons of LLT across groups typically assume parallel S-shaped survival curves, but genetic variation in the shape of survival vs. temperature curves has not been assessed. Here, we measured the ability of 36 lines of the Drosophila Genetic Reference Panel (DGRP) to survive a 1-h cold shock at seven ecologically relevant low temperatures (-1 to -7 °C) to create a high-resolution response curve for each genotype. We observed surprising variation both in the magnitude of survival and in the shapes of the response curves, with the curves clustering into four distinct shapes. To encompass variation in the shapes of these survival curves, we developed a new cold tolerance metric, cumulative cold tolerance (CCT). By comparing our survival data with climatological data, we propose that variation in the shapes of cold-survival curves arose from weak selection pressure to survive intermediate subzero temperatures in this mid-latitude population of flies. Using publicly available genome sequence and transcript expression data for these lines, we identified several candidate genes associated with CCT, and using transgenic RNAi, we confirmed a functional role for many of these genes.

Maternal androgens in avian brood parasites and their hosts: Responses to parasitism and competition?

In the coevolutionary dynamic of avian brood parasites and their hosts, maternal (or transgenerational) effects have rarely been investigated. We examined the potential role of elevated yolk testosterone in eggs of the principal brood parasite in North America, the brown-headed cowbird, and three of its frequent host species. Elevated maternal androgens in eggs are a common maternal effect observed in many avian species when breeding conditions are unfavorable. These steroids accelerate embryo development, shorten incubation period, increase nestling growth rate, and enhance begging vigor, all traits that can increase the survival of offspring. We hypothesized that elevated maternal androgens in host eggs are a defense against brood parasitism. Our second hypothesis was that elevated maternal androgens in cowbird eggs are a defense against intra-specific competition. For host species, we found that elevated yolk testosterone was correlated with parasitized nests of small species, those whose nest success is most reduced by cowbird parasitism. For cowbirds, we found that elevated yolk testosterone was correlated with eggs in multiply-parasitized nests, which indicate intra-specific competition for nests due to high cowbird density. We propose experimental work to further examine the use of maternal effects by cowbirds and their hosts.

Neuromuscular performance of maximal voluntary explosive concentric contractions is influenced by angular acceleration.

Torque production during maximal voluntary explosive contractions is considered to be a functionally more relevant neuromuscular measure than steady-state torque, but little is known about accelerated concentric contractions. This study investigated torque, muscle activity, and fascicle behavior during isometric and fast concentric contractions of quadriceps femoris. Ten participants performed maximal voluntary explosive isometric, isovelocity, and additional concentric knee extensions at angular accelerations ranging from 700 to 4000° s-2 that resulted in an angular velocity of 300° s-1 at 40° knee flexion. Concentric torque at 40° knee flexion was corrected for inertia, and the corresponding isometric torque was matched to the time when the target knee angle of 40° was reached during concentric contractions. Electromyography of quadriceps femoris and hamstrings and ultrasound of vastus lateralis were measured to determine muscle activity, fascicle length, and fascicle velocity (FV). The faster the acceleration, the more torque was produced during concentric contractions at 40° knee flexion, which was accompanied by a reduction in FV. In comparison with isometric conditions, concentric quadriceps muscle activity was increased and torque during accelerations ≥3000° s-2 equaled the time-matched isometric torque. Our results provide novel evidence that acceleration influences torque production during maximal voluntary explosive concentric contractions. This is suggested to be due to series elasticity and reduced force depression.

[Knowledge of Human Papillomavirus Infection and the Possibilities for Prevention among 13- to 21-Year-Old Students from Fulda, Hessen]. / Kenntnisstand zu Infektionen mit humanen Papillomaviren und deren Präventionsmöglichkeiten von 13- bis 21-jährigen Schülerinnen und Schülern aus Fulda, Hessen.

Study Aim: The aim of this investigation was to assess awareness and knowledge of HPV and HPV vaccination in a sample of female and male students from Fulda. Further vaccination uptake was investigated. Methods: In 2011 a regional cross-sectional survey of 13- to 21-year-old students (n=1 515) was conducted by using a standardised questionnaire. Results: Overall, the awareness and knowledge of human papillomavirus (HPV) was poor. 29% of the sample had heard of HPV. Multivariate analyses demonstrate that females as well as Christians knew HPV better than males and Muslims. Mean HPV knowledge score was 7.8 of 21 (SD=3.3). None of the tested sociodemographic variables was a predictor for better HPV knowledge. 77% of the sample was aware of the HPV vaccination. Females, persons without migration background as well as persons with middle or higher education knew HPV vaccination better than males, persons with migration background and lower educational level. Mean HPV vaccination knowledge score of the female students was 2.9 of 5 (SD=1.3). Older female students had a better level of knowledge than younger ones. 30% of the females had received at least one dose. Higher age, no migration background and middle or higher education status were tested as significant predictors of vaccine uptake. Conclusion: School lessons and consultations would be appropriate places to transfer knowledge in order to prevent health inequalities caused by social determinants.

A novel mutation in BCS1L associated with deafness, tubulopathy, growth retardation and microcephaly.

UNLABELLED: We report a novel homozygous missense mutation in the ubiquinol-cytochrome c reductase synthesis-like (BCS1L) gene in two consanguineous Turkish families associated with deafness, Fanconi syndrome (tubulopathy), microcephaly, mental and growth retardation. All three patients presented with transitory metabolic acidosis in the neonatal period and development of persistent renal de Toni-Debré-Fanconi-type tubulopathy, with subsequent rachitis, short stature, microcephaly, sensorineural hearing impairment, mild mental retardation and liver dysfunction. The novel missense mutation c.142A>G (p.M48V) in BCS1L is located at a highly conserved region associated with sorting to the mitochondria. Biochemical analysis revealed an isolated complex III deficiency in skeletal muscle not detected in fibroblasts. Native polyacrylamide gel electrophoresis (PAGE) revealed normal super complex formation, but a shift in mobility of complex III most likely caused by the absence of the BCS1L-mediated insertion of Rieske Fe/S protein into complex III. These findings expand the phenotypic spectrum of BCS1L mutations, highlight the importance of biochemical analysis of different primary affected tissue and underline that neonatal lactic acidosis with multi-organ involvement may resolve after the newborn period with a relatively spared neurological outcome and survival into adulthood. CONCLUSION: Mutation screening for BCS1L should be considered in the differential diagnosis of severe (proximal) tubulopathy in the newborn period. WHAT IS KNOWN: • Mutations in BCS1L cause mitochondrial complex III deficiencies. • Phenotypic presentations of defective BCS1L range from Bjornstad to neonatal GRACILE syndrome. What is New: • Description of a novel homozygous mutation in BCS1L with transient neonatal acidosis and persistent de Toni-Debré-Fanconi-type tubulopathy. • The long survival of patients with phenotypic presentation of severe complex III deficiency is uncommon.

Mid-term Functional Outcome and Return to Sports after Proximal Hamstring Tendon Repair.

Proximal hamstring tendon ruptures are commonly associated with a significant loss of function, and operative treatment is recommended in active patients. The objective was to evaluate objective/subjective functional results and return to sports following proximal hamstring tendon repair in the mid-term follow-up. 16 repairs of proximal hamstring ruptures were performed in 15 patients (9 males, 6 females). The average age at the time of injury was 47 years (range, 21-66). All patients were clinically examined at a mean follow-up of 56 months (range, 24-112 months). Validated patient-oriented assessment scores focussing on sports activity including the Lysholm Score, Tegner Activity Score, UCLA Activity Score, adapted WOMAC Score, and the VAS were evaluated as well as the return to sports. Isokinetic strength of both legs was tested using a rotational dynamometer. The Lysholm, Tegner, UCLA Activity Score and the adapted WOMAC demonstrated predominantly a return to a preinjury activity level at follow-up. Functional measurements of the operated leg showed similar results to the uninjured leg in knee extension and flexion strength (p>0.094). In return to sports, no signficant (p>0.05) differences concerning types or frequency were noted. The surgical repair of proximal hamstring tendon ruptures leads to constantly good functional results in the mid-term follow-up, where patients demonstrate similar isokinetic results in the healthy leg.

Routine assessment of psychosocial problems after cancer genetic counseling: results from a randomized controlled trial.

Approximately 70% of counselees undergoing cancer genetic counseling and testing (CGCT) experience some degree of CGCT-related psychosocial problems. We evaluated the efficacy of an intervention designed to increase detection and management of problems 4 weeks after completion of CGCT. In this randomized, controlled trial, 118 participants completed a CGCT-related problem questionnaire prior to an - audiotaped - telephone session with their counselor 1 month after DNA-test disclosure. For those randomized to the intervention group (n = 63), a summary of the questionnaire results was provided to the counselor prior to the telephone session. Primary outcomes were discussion of the problems, counselors' awareness of problems, and problem management. Secondary outcomes included self-reported distress, cancer worries, CGCT-related problems, and satisfaction. Counselors who received a summary of the questionnaire were more aware of counselees' problems in only one psychosocial domain (practical issues). No significant differences in the number of problems discussed, in problem management, or on any of the secondary outcomes were observed. The prevalence of problems was generally low. The telephone session, combined with feedback on psychosocial problems, has minimal impact. The low prevalence of psychosocial problems 1 month post-CGCT recommends against its use as a routine extension of the CGCT procedure.

Cerebral Venous Thromboses in a Child with Nephrotic Syndrome.

Nephrotic syndrome is associated with several complications among which are thrombo embolic phenomena. These are uncommon in children. This report describes an 8 year old male child with relapse of steroid resistant minimal change nephrotic syndrome who developed cerebral sagittal and transverse sinus thromboses. He presented with headaches, vomiting and photophobia; and developed VI cranial nerve palsy during the course of the illness. Diagnosis was made by Computed Tomographic Scan and Magnetic Resonance Angiography of the brain. He was treated with low molecular weight heparin initially and then, oral warfarin with close monitoring of the INR and anti-Factor Xa. He recovered without neurological deficits from the venous thromboses, and with marked improvements in his radiological features.

Impact of rapid genetic counselling and testing on the decision to undergo immediate or delayed prophylactic mastectomy in newly diagnosed breast cancer patients: findings from a randomised controlled trial.

BACKGROUND: Female breast cancer patients with a BRCA1/2 mutation have an increased risk of contralateral breast cancer. We investigated the effect of rapid genetic counselling and testing (RGCT) on choice of surgery. METHODS: Newly diagnosed breast cancer patients with at least a 10% risk of a BRCA1/2 mutation were randomised to an intervention group (offer of RGCT) or a control group (usual care; ratio 2 : 1). Primary study outcomes were uptake of direct bilateral mastectomy (BLM) and delayed contralateral prophylactic mastectomy (CPM). RESULTS: Between 2008 and 2010, we recruited 265 women. On the basis of intention-to-treat analyses, no significant group differences were observed in percentage of patients opting for a direct BLM (14.6% for the RGCT group vs 9.2% for the control group; odds ratio (OR) 2.31; confidence interval (CI) 0.92-5.81; P=0.08) or for a delayed CPM (4.5% for the RGCT group vs 5.7% for the control group; OR 0.89; CI 0.27-2.90; P=0.84). Per-protocol analysis indicated that patients who received DNA test results before surgery (59 out of 178 women in the RGCT group) opted for direct BLM significantly more often than patients who received usual care (22% vs 9.2%; OR 3.09, CI 1.15-8.31, P=0.03). INTERPRETATION: Although the large majority of patients in the intervention group underwent rapid genetic counselling, only a minority received DNA test results before surgery. This may explain why offering RGCT yielded only marginally significant differences in uptake of BLM. As patients who received DNA test results before surgery were more likely to undergo BLM, we hypothesise that when DNA test results are made routinely available pre-surgery, they will have a more significant role in surgical treatment decisions.

Psychosocial aspects of hereditary cancer (PAHC) questionnaire: development and testing of a screening questionnaire for use in clinical cancer genetics.

BACKGROUND: Up to three-quarters of individuals who undergo cancer genetic counseling and testing report psychosocial problems specifically related to that setting. The objectives of this study were to develop and evaluate the screening properties of a questionnaire designed to assess specific psychosocial problems related to cancer genetic counseling. METHODS: We adopted the European Organisation for Research and Treatment of Cancer Quality of Life Group guidelines to develop the Psychosocial Aspects of Hereditary Cancer (PAHC) questionnaire, a 26-item questionnaire organized into six problem domains: genetics, practical issues, family, living with cancer, emotions, and children. The Distress Thermometer and a question per domain on the perceived need for extra psychosocial services were included as well. We administered the questionnaire and the Hospital Anxiety and Depression Scale to 127 counselees at the time of genetic counseling and 3 weeks after DNA test disclosure. As a gold standard to evaluate the screening properties of the questionnaire, participants underwent a semi-structured interview with an experienced social worker who assessed the presence and severity of problems per domain. RESULTS: A cutoff score representing responses of 'quite a bit' or 'very much' to one or more items within a given problem domain yielded moderate to high sensitivity across domains. A cutoff of 4 on the Distress Thermometer yielded high sensitivity. The questions regarding the perceived need for extra psychosocial services yielded high specificity and negative predictive values. CONCLUSION: The Psychosocial Aspects of Hereditary Cancer questionnaire in combination with the Distress Thermometer can be used as a first-line screener for psychosocial problems within the cancer genetic counseling setting.

One phase of the dormancy developmental pathway is critical for the evolution of insect seasonality.

Evolutionary change in the timing of dormancy enables animals and plants to adapt to changing seasonal environments and can result in ecological speciation. Despite its clear biological importance, the mechanisms underlying the evolution of dormancy timing in animals remain poorly understood because of a lack of anatomical landmarks to discern which phase of dormancy an individual is experiencing. Taking advantage of the nearly universal characteristic of metabolic suppression during insect dormancy (diapause), we use patterns of respiratory metabolism to document physiological landmarks of dormancy and test which of the distinct phases of the dormancy developmental pathway contribute to a month-long shift in diapause timing between a pair of incipient moth species. Here, we show that divergence in life cycle between the earlier-emerging E-strain and the later-emerging Z-strain of European corn borer (ECB) is clearly explained by a delay in the timing of the developmental transition from the diapause maintenance phase to the termination phase. Along with recent findings indicating that life-cycle differences between ECB strains stem from allelic variation at a single sex-linked locus, our results demonstrate how dramatic shifts in animal seasonality can result from simple developmental and genetic changes. Although characterizing the multiple phases of the diapause developmental programme in other locally adapted populations and species will undoubtedly yield surprises about the nature of animal dormancy, results in the ECB moth suggest that focusing on genetic variation in the timing of the dormancy termination phase may help explain how (or whether) organisms rapidly respond to global climate change, expand their ranges after accidental or managed introductions, undergo seasonal adaptation, or evolve into distinct species through allochronic isolation.

Enhanced innate immune responses in a brood parasitic cowbird species: Degranulation and oxidative burst.

We examined the relative effectiveness of two innate immune responses in two species of New World blackbirds (Passeriformes, Icteridae) that differ in resistance to West Nile virus (WNV). We measured degranulation and oxidative burst, two fundamental components of phagocytosis, and we predicted that the functional effectiveness of these innate immune responses would correspond to the species' relative resistance to WNV. The brown-headed cowbird (Molothrus ater), an obligate brood parasite, had previously shown greater resistance to infection with WNV, lower viremia and faster recovery when infected, and lower subsequent antibody titers than the red-winged blackbird (Agelaius phoeniceus), a close relative that is not a brood parasite. We found that cowbird leukocytes were significantly more functionally efficient than those of the blackbird leukocytes and 50% more effective at killing the challenge bacteria. These results suggest that further examination of innate immunity in the cowbird may provide insight into adaptations that underlie its greater resistance to WNV. These results support an eco-immunological interpretation that species like the cowbird, which inhabit ecological niches with heightened exposure to parasites, experience evolutionary selection for more effective immune responses.

Precomputed Radiative Heat Transport for Efficient Thermal Simulation.

Architectural design and urban planning are complex design tasks. Predicting the thermal impact of design choices at interactive rates enhances the ability of designers to improve energy efficiency and avoid problematic heat islands while maintaining design quality. We show how to use and adapt methods from computer graphics to efficiently simulate heat transfer via thermal radiation, thereby improving user guidance in the early design phase of large-scale construction projects and helping to increase energy efficiency and outdoor comfort. Our method combines a hardware-accelerated photon tracing approach with a carefully selected finite element discretization, inspired by precomputed radiance transfer. This combination allows us to precompute a radiative transport operator, which we then use to rapidly solve either steady-state or transient heat transport throughout the entire scene. Our formulation integrates time-dependent solar irradiation data without requiring changes in the transport operator, allowing us to quickly analyze many different scenarios such as common weather patterns, monthly or yearly averages, or transient simulations spanning multiple days or weeks. We show how our approach can be used for interactive design workflows such as city planning via fast feedback in the early design phase.

Quantitative myocardial perfusion imaging with a MR cold pressor test.

The response of myocardial blood flow to sympathetic stimulation with cold is modulated by endothelium-related factors. As endothelial dysfunction is an early step in patients with coronary artery disease, the aim of this study was to establish a cold pressor test (CPT) setting for quantitative analysis of myocardial perfusion in a MR scanner. First pass perfusion studies were performed in 10 healthy volunteers using a 1.5 T MR scanner with a multislice steady state free precession perfusion trueFISP sequence in prebolus technique (1 cc/4 cc gadobenate dimeglumine). MR-CPT was established using an over head ice-water bath of the left hand. First pass perfusion imaging was started after 1 min to assure an adequate stimulus followed by a second series after 15 min to evaluate the rest perfusion. After motion correction images were segmented with an adapted, automated tool, myocardial contours were determined. Perfusion was quantitatively evaluated after contamination and baseline correction by deconvolution with the arterial input function using an exponential function model as residuum. All data could be evaluated. Mean myocardial perfusion rose from 0.61 ± 0.22 cc/g/min at rest to 1.15 ± 0.34 cc/g/min under CPT. MR myocardial perfusion values show a comparable increase under CPT as published positron emission tomography data. Consequently, CPT for the presence of endothelial dysfunction is feasible in the MR environment.

Complications after percutaneous placement of totally implantable venous access ports in the forearm.

This article focuses on radiological imaging of complications after interventional percutaneous insertion of totally implantable venous access ports (TIVAPs) which were placed in the forearm. Thus far most reviews have dealt with pectorally-placed TIVAPs. Compared with the pectoral approach, implantation in the forearm has been associated with certain complications owing to a longer route of the port catheter within a smaller vein, and owing to the route across the elbow joint, resulting in higher rates of catheter-associated thrombosis and possible mechanical complications. The purpose of this review is to describe the complications after implantation of TIVAPs in the forearm, and to make radiologists familiar with the key findings of the complications during radiological imaging, including colour-coded and compression Duplex ultrasound, computed tomography, and digital subtraction venography.

[Splenomegaly with multiple unclear parenchymal lesions. Splenomegaly]. / Splenomegalie mit multiplen unklaren Parenchymläsionen. Littoralzellangiom.

A 53-year-old female patient presented with splenomegaly, uncertain lesions of the spleen, pancytopenia and suspected aortitis. Reduced strength and muscular pain but no B symptoms were also present. Alterations of the spleen had been known for a long time. Blood examination, laboratory tests and magnetic resonance imaging (MRI) confirmed an aortitis. Concerning the splenic changes neither ultrasound nor MRI could provide conclusive or even pathognomonic findings. Because of an existing pancytopenia and diagnostic obscurity, the patient underwent splenectomy. The histological diagnosis was finally concluded as multifocal littoral cell angioma.

Patterns of maternal yolk hormones in eastern screech owl eggs (Megascops asio).

Owl clutches typically hatch asynchronously, and brood size hierarchies develop. In this study, we describe intra-clutch variation of testosterone, androstenedione, estradiol, and corticosterone in Eastern screech owl egg yolks. In order to assess whether these hormones may have originated in the follicle, we also characterize variation of testosterone, androstenedione, and corticosterone within the exterior, intermediate, and interior regions of the yolk. Concentrations of testosterone and androstenedione were distributed relatively evenly across egg lay order with the exception of first-laid eggs that had significantly lower concentrations of both androgens than eggs later in the laying sequence. Corticosterone and estradiol did not vary with laying order. Our results suggest that when food is abundant, yolk hormones are deposited in patterns that minimize sibling differences except to reduce dominance by the first-hatching chick. Testosterone and androstenedione concentrations varied throughout the yolk, while corticosterone was evenly distributed throughout the yolk. This supports a follicular origin for both yolk androgens, and an adrenal origin for yolk corticosterone.