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The 9.4T scanner in Maastricht is a whole-body magnet with head gradients and parallel RF transmit capability. At the time of the design, it was conceptualized to be one of the best fMRI scanners in the world, but it has also been used for anatomical and diffusion imaging. 9.4T offers increases in sensitivity and contrast, but the technical ultra-high field (UHF) challenges, such as field inhomogeneities and constraints set by RF power deposition, are exacerbated compared to 7T. This article reviews some of the 9.4T work done in Maastricht. Functional imaging experiments included blood oxygenation level-dependent (BOLD) and blood-volume weighted (VASO) fMRI using different readouts. BOLD benefits from shorter T2* at 9.4T while VASO from longer T1. We show examples of both ex vivo and in vivo anatomical imaging. For many applications, pTx and optimized coils are essential to harness the full potential of 9.4T. Our experience shows that, while considerable effort was required compared to our 7T scanner, we could obtain high-quality anatomical and functional data, which illustrates the potential of MR acquisitions at even higher field strengths. The practical challenges of working with a relatively unique system are also discussed.

Background: breast cancer has a significant heritable basis, of which ∼60% remains unexplained. Testing for BRCA1/BRCA2 offers useful discrimination of breast cancer risk within families, and identification of additional breast cancer susceptibility genes could offer clinical utility. Patients and methods: we included 2135 invasive breast cancer cases recruited via the Breast and Ovarian Cancer Susceptibility study, a retrospective UK study of familial breast cancer. Eligibility criteria: female, BRCA-negative, white European ethnicity, and one of: (i) breast cancer family history, (ii) bilateral disease, (iii) young age of onset (Results: 159/2135 (7.4%) cases had a qualifying variant in an established breast cancer susceptibility gene, with minimal evidence of signal in other cancer susceptibility genes. Known breast cancer susceptibility genes PALB2, CHEK2, and ATM were the only genes to retain statistical significance after correcting for multiple testing. Due to the enrichment of hereditary cases in the series, we had good power (>80%) to detect a gene of BRCA1-like risk [odds ratio (OR) = 10.6] down to a population minor allele frequency of 4.6 × 10 −5 (1 in 10 799, less than one-tenth that of BRCA1)and of PALB2-like risk (OR = 5.0) down to a population minor allele frequency of 2.8 × 10 −4 (1 in 1779, less than half that of PALB2). Power was lower for identification of novel moderate penetrance genes (OR = 2-3) like CHEK2 and ATM. Conclusions: this is the largest case-control whole-exome analysis of enriched breast cancer published to date. Whilst additional breast cancer susceptibility genes likely exist, those of high penetrance are likely to be of very low mutational frequency. Contention exists regarding the clinical utility of such genes.

We conducted a preregistered multilaboratory project ( k = 36; N = 3,531) to assess the size and robustness of ego-depletion effects using a novel replication method, termed the paradigmatic replication approach. Each laboratory implemented one of two procedures that was intended to manipulate self-control and tested performance on a subsequent measure of self-control. Confirmatory tests found a nonsignificant result ( d = 0.06). Confirmatory Bayesian meta-analyses using an informed-prior hypothesis (δ = 0.30, SD = 0.15) found that the data were 4 times more likely under the null than the alternative hypothesis. Hence, preregistered analyses did not find evidence for a depletion effect. Exploratory analyses on the full sample (i.e., ignoring exclusion criteria) found a statistically significant effect ( d = 0.08); Bayesian analyses showed that the data were about equally likely under the null and informed-prior hypotheses. Exploratory moderator tests suggested that the depletion effect was larger for participants who reported more fatigue but was not moderated by trait self-control, willpower beliefs, or action orientation.

Plant chromatin dynamics are generally recognized as playing a role in the genomic response to environmental stress. Although stress‐induced transcriptional activities of LTR‐retrotransposons have been reported, whether the stress response can be detected at the level of chromatin structure for LTR‐retrotransposons is largely unknown. Using differential nuclease sensitivity profiling, we identified that two out of 29 maize LTR‐retrotransposon families change their chromatin structure in response to drought stress in leaf tissue. The two LTR‐retrotransposon families, uloh and vegu, are classified as nonautonomous LTR‐retrotransposons. Differently from other families, the chromatin structure of these two families shifted from more open in normal conditions to more closed following drought stress. Although uloh and vegu lack sequence similarity, most of them shared an intriguing feature of having a new and uncharacterized insertion of a DNA sequence near one side of an LTR. In the uloh family, nine members with a strong drought response also exhibited a drought‐induced reduction of published H3K4me3 histone modification in the inserted DNA region, implicating this modification in the chromatin structural changes. Our results provide new insight into how LTR‐retrotransposons can alter their chromatin structure following stress response in plants.

Background and purpose: In neuro-oncology, high spatial accuracy is needed for clinically acceptable high-precision radiation treatment planning (RTP). In this study, the clinical applicability of anatomically optimised 7-Tesla (7T) MR images for reliable RTP is assessed with respect to standard clinical imaging modalities. Materials and methods: System- and phantom-related geometrical distortion (GD) were quantified on clinically-relevant MR sequences at 7T and 3T, and on CT images using a dedicated anthropomorphic head phantom incorporating a 3D grid-structure, creating 436 points-of-interest. Global GD was assessed by mean absolute deviation (MADGlobal). Local GD relative to the magnetic isocentre was assessed by MADLocal. Using 3D displacement vectors of individual points-of-interest, GD maps were created. For clinically acceptable radiotherapy, 7T images need to meet the criteria for accurate dose delivery (GD

Background In the past decade, the zebrafish community has widely embraced targeted mutagenesis technologies, resulting in an abundance of mutant lines. While many lines have proven to be useful for investigating gene function, many have also shown no apparent phenotype, or phenotypes not of interest to the originating lab. In order for labs to document and share information about these lines, we have created ZebraShare as a new resource offered within ZFIN. Methods ZebraShare involves a form-based submission process generated by ZFIN. The ZebraShare interface (https://zfin.org/action/zebrashare) can be accessed on ZFIN under “Submit Data”. Users download the Submission Workbook and complete the required fields, then submit the completed workbook with associated images and captions, generating a new ZFIN publication record. ZFIN curators add the submitted phenotype and mutant information to the ZFIN database, provide mapping information about mutations, and cross reference this information across the appropriate ZFIN databases. We present here examples of ZebraShare submissions, including phf21aa, kdm1a, ctnnd1, snu13a, and snu13b mutant lines. Results Users can find ZebraShare submissions by searching ZFIN for specific alleles or line designations, just as for alleles submitted through the normal process. We present several potential examples of submission types to ZebraShare including a phenotypic mutants, mildly phenotypic, and early lethal mutants. Mutants for kdm1a show no apparent skeletal phenotype, and phf21aa mutants show only a mild skeletal phenotype, yet these genes have specific human disease relevance and therefore may be useful for further studies. The p120-catenin encoding gene, ctnnd1, was knocked out to investigate a potential role in brain development or function. The homozygous ctnnd1 mutant disintegrates during early somitogenesis and the heterozygote has localized defects, revealing vital roles in early development. Two snu13 genes were knocked out to investigate a role in muscle formation. The snu13a;snu13b double mutant has an early embryonic lethal phenotype, potentially related to a proposed role in the core splicing complex. In each example, the mutants submitted to ZebraShare display phenotypes that are not ideally suited to their originating lab’s project directions but may be of great relevance to other researchers. Conclusion ZebraShare provides an opportunity for researchers to directly share information about mutant lines within ZFIN, which is widely used by the community as a central database of information about zebrafish lines. Submissions of alleles with a phenotypic or unexpected phenotypes is encouraged to promote collaborations, disseminate lines, reduce redundancy of effort and to promote efficient use of time and resources. We anticipate that as submissions to ZebraShare increase, they will help build an ultimately more complete picture of zebrafish genetics and development.

Development of novel anti-tuberculosis combination regimens that increase efficacy and reduce treatment timelines will improve patient compliance, limit side-effects, reduce costs, and enhance cure rates. Such advancements would significantly improve the global TB burden and reduce drug resistance acquisition. Bioenergetics has received considerable attention in recent years as a fertile area for anti-tuberculosis drug discovery. Targeting the electron transport chain (ETC) and oxidative phosphorylation machinery promises not only to kill growing cells but also metabolically dormant bacilli that are inherently more drug tolerant. Over the last two decades, a broad array of drugs targeting various ETC components have been developed. Here, we provide a focused review of the current state of art of bioenergetic inhibitors of Mtb with an in-depth analysis of the metabolic and bioenergetic disruptions caused by specific target inhibition as well as their synergistic and antagonistic interactions with other drugs. This foundation is then used to explore the reigning theories on the mechanisms of antibiotic-induced cell death and we discuss how bioenergetic inhibitors in particular fail to be adequately described by these models. These discussions lead us to develop a clear roadmap for new lines of investigation to better understand the mechanisms of action of these drugs with complex mechanisms as well as how to leverage that knowledge for the development of novel, rationally-designed combination therapies to cure TB.

Immune checkpoint inhibitor (ICI) therapies activate the immune system to unmask cancer cells that the body might otherwise not detect. These cancer therapies alter the immune system at different "checkpoint" proteins such as PD-1, PD-L1, or CTLA-4 to better target tumor cells, but also have the potential to affect normal tissues. In patients receiving ICI therapy, cutaneous reactions have been frequently documented, ranging from mild urticarial rashes to widespread cutaneous necrosis. Proper identification and management of ICI therapy side effects is essential to the care of these patients. Here, we present an unusual granulomatous cutaneous reaction in a patient receiving anti-CTLA-4 therapy for chronic myelomonocytic leukemia.

Cancer immunotherapy has impacted the treatment of numerous tumor types, including skin, lung, and colon cancers. Immune checkpoint inhibitors (ICI) activate the immune system to attack cancer cells, but this mechanism can also impact healthy cells. Dermatomyositis, an autoimmune syndrome affecting multiple organ systems, is often associated with cancer as a paraneoplastic syndrome, but this syndrome can also be induced by ICI. Here, we describe a case of dermatomyositis in a patient receiving pembrolizumab for treatment of squamous cell carcinoma of the lung and discuss the importance of recognizing complications of ICI.

Adverse medication side effects are not uncommon in the inpatient setting, where polypharmacy is the norm. Linear IgA bullous dermatosis (LABD) can be a cutaneous side effect of commonly used inpatient medications, such as vancomycin. Symptoms of LABD can be severe, and proper recognition of this drug-induced disease is important to ensuring proper treatment, including the removal of the inciting agent. This report describes a case of vancomycin-associated LABD in a 66-year-old man and the proper management of drug-induced LABD.

As aberrant Notch signaling has been linked to cancerous growth, Notch inhibitors represent a novel category of targeted oncological therapy. Notch pathways in tumor cells may contribute to proliferation or limit apoptosis and differentiation. Healthy skin differentiation and homeostasis are reliant on normal Notch expression, and disruption of this signaling has been implicated in dermatological conditions such as hidradenitis suppurativa, psoriasis, atopic dermatitis, and lichen planus. Here, we describe two cases of patients with cutaneous side effects from Notch inhibitor treatment for adenoid cyst carcinoma (ACC) and review the role of Notch signaling in skin disease. By illuminating connections between medication side effects and disease pathogenesis, our goal is to increase awareness of the cutaneous side effects of Notch inhibitor treatment.

A concerted action on the part of international agencies and national governments has resulted in the near-eradication of poliomyelitis. However, both the oral polio vaccine (OPV) and the inactivated polio vaccine (IPV) have deficiencies which make them suboptimal for use after global eradication. OPV is composed of attenuated Sabin strains and stimulates robust immunity, but may revert to neurovirulent forms in the intestine which can be shed and infect susceptible contacts. The majority of IPV products are manufactured using pathogenic strains inactivated with formalin. Upon eradication, the production of large quantities of pathogenic virus will present an increased biosecurity hazard. A logical ideal endgame vaccine would be an inactivated form of an attenuated strain that could afford protective immunity while safely producing larger numbers of doses per unit of virus stock than current vaccines. We report here the development of an ionizing radiation (IR)-inactivated Sabin-based vaccine using a reconstituted Mn-decapeptide (MDP) antioxidant complex derived from the radioresistant bacterium Deinococcus radiodurans. In bacteria, Mn2+-peptide antioxidants protect proteins from oxidative damage caused by extreme radiation exposure. Here we show for the first time, that MDP can protect immunogenic neutralizing epitopes in picornaviruses. MDP protects epitopes in Polio Virus 1 and 2 Sabin strains (PV1-S and PV2-S, respectively), but viral genomic RNA is not protected during supralethal irradiation. IR-inactivated Sabin viruses stimulated equivalent or improved neutralizing antibody responses in Wistar rats compared to the commercially used IPV products. Our approach reduces the biosecurity risk of the current PV vaccine production method by utilizing the Sabin strains instead of the wild type neurovirulent strains. Additionally, the IR-inactivation approach could provide a simpler, faster and less costly process for producing a more immunogenic IPV. Gamma-irradiation is a well-known method of virus inactivation and this vaccine approach could be adapted to any pathogen of interest.

Risen and Gilovich (2008) found that subjects believed that “tempting fate” would be punished with ironic bad outcomes (a main effect), and that this effect was magnified when subjects were under cognitive load (an interaction). A previous replication study (Frank & Mathur, 2016) that used an online implementation of the protocol on Amazon Mechanical Turk failed to replicate both the main effect and the interaction. Before this replication was run, the authors of the original study expressed concern that the cognitive-load manipulation may be less effective when implemented online than when implemented in the lab and that subjects recruited online may also respond differently to the specific experimental scenario chosen for the replication. A later, large replication project, Many Labs 2 (Klein et al. 2018), replicated the main effect (though the effect size was smaller than in the original study), but the interaction was not assessed. Attempting to replicate the interaction while addressing the original authors’ concerns regarding the protocol for the first replication study, we developed a new protocol in collaboration with the original authors. We used four university sites ( N = 754) chosen for similarity to the site of the original study to conduct a high-powered, preregistered replication focused primarily on the interaction effect. Results from these sites did not support the interaction or the main effect and were comparable to results obtained at six additional universities that were less similar to the original site. Post hoc analyses did not provide strong evidence for statistical inconsistency between the original study’s estimates and our estimates; that is, the original study’s results would not have been extremely unlikely in the estimated distribution of population effects in our sites. We also collected data from a new Mechanical Turk sample under the first replication study’s protocol, and results were not meaningfully different from those obtained with the new protocol at universities similar to the original site. Secondary analyses failed to support proposed substantive mechanisms for the failure to replicate.

Srull and Wyer (1979) demonstrated that exposing participants to more hostility-related stimuli caused them subsequently to interpret ambiguous behaviors as more hostile. In their Experiment 1, participants descrambled sets of words to form sentences. In one condition, 80% of the descrambled sentences described hostile behaviors, and in another condition, 20% described hostile behaviors. Following the descrambling task, all participants read a vignette about a man named Donald who behaved in an ambiguously hostile manner and then rated him on a set of personality traits. Next, participants rated the hostility of various ambiguously hostile behaviors (all ratings on scales from 0 to 10). Participants who descrambled mostly hostile sentences rated Donald and the ambiguous behaviors as approximately 3 scale points more hostile than did those who descrambled mostly neutral sentences. This Registered Replication Report describes the results of 26 independent replications ( N = 7,373 in the total sample; k = 22 labs and N = 5,610 in the primary analyses) of Srull and Wyer’s Experiment 1, each of which followed a preregistered and vetted protocol. A random-effects meta-analysis showed that the protagonist was seen as 0.08 scale points more hostile when participants were primed with 80% hostile sentences than when they were primed with 20% hostile sentences (95% confidence interval, CI = [0.004, 0.16]). The ambiguously hostile behaviors were seen as 0.08 points less hostile when participants were primed with 80% hostile sentences than when they were primed with 20% hostile sentences (95% CI = [−0.18, 0.01]). Although the confidence interval for one outcome excluded zero and the observed effect was in the predicted direction, these results suggest that the currently used methods do not produce an assimilative priming effect that is practically and routinely detectable.

Functional mapping of cerebral blood volume (CBV) changes has the potential to reveal brain activity with high localization specificity at the level of cortical layers and columns. Non-invasive CBV imaging using Vascular Space Occupancy (VASO) at ultra-high magnetic field strengths promises high spatial specificity but poses unique challenges in human applications. As such, 9.4 T B1+ and B0 inhomogeneities limit efficient blood tagging, while the specific absorption rate (SAR) constraints limit the application of VASO-specific RF pulses. Moreover, short T2* values at 9.4 T require short readout duration, and long T1 values at 9.4 T can cause blood-inflow contaminations. In this study, we investigated the applicability of layer-dependent CBV-fMRI at 9.4 T in humans. We addressed the aforementioned challenges by combining multiple technical advancements: temporally alternating pTx B1+ shimming parameters, advanced adiabatic RF-pulses, 3D-EPI signal readout, optimized GRAPPA acquisition and reconstruction, and stability-optimized RF channel combination. We found that a combination of suitable advanced methodology alleviates the challenges and potential artifacts, and that VASO fMRI provides reliable measures of CBV change across cortical layers in humans at 9.4 T. The localization specificity of CBV-fMRI, combined with the high sensitivity of 9.4 T, makes this method an important tool for future studies investigating cortical micro-circuitry in humans.

Background Histone deacetylases (HDACs) are epigenetic factors that function to repress gene transcription by removing acetyl groups from the N-terminal of histone lysines. Histone deacetylase 4 (HDAC4), a class IIa HDAC, has previously been shown to regulate the process of endochondral ossification in mice via repression of Myocyte enhancer factor 2c (MEF2C), a transcriptional activator of Runx2, which in turn promotes chondrocyte maturation and production of bone by osteoblasts. Methods & Materials In this study, we generated two zebrafish lines with mutations in hdac4 using CRISPR/Cas9 and analyzed mutants for skeletal phenotypes and expression of genes known to be affected by Hdac4 expression. Results Lines have insertions causing a frameshift in a proximal exon of hdac4 and a premature stop codon. Mutations are predicted to result in aberrant protein sequence and a truncated protein, eliminating the Mef2c binding domain and Hdac domain. Zygotic mutants from two separate lines show a significant increase in ossification of pharyngeal ceratohyal cartilages at 7 days post fertilization (dpf) (p p runx2a and runx2b in the ceratohyal cartilage (p p in situ hybridizations from zygotic stages to 75–90% epiboly indicates that hdac4 is highly expressed in early embryos, but diminishes by late epiboly, becoming expressed again in larval stages. Discussion Loss of function of hdac4 in zebrafish is associated with increased expression of runx2a and runx2b targets indicating that a role for hdac4 in zebrafish is to repress activation of ossification of cartilage. These findings are consistent with observations of precocious cartilage ossification in Hdac4 mutant mice, demonstrating that the function of Hdac4 in skeletal development is conserved among vertebrates. Expression of hdac4 mRNA in embryos younger than 256–512 cells indicates that there is a maternal contribution of hdac4 to the early embryo. The increase in ossification and profound loss of first pharyngeal arch elements and anterior neurocranium in a subset of maternal-zygotic mutant and heterozygote larvae suggests that maternal hdac4 functions in cartilage ossification and development of cranial neural crest-derived structures.

Item does not contain fulltext OBJECTIVES: The use of 7 Tesla (T) magnetic resonance imaging (MRI) has recently shown great potential for high-resolution soft-tissue neuroimaging and visualization of microvascularization in glioblastoma (GBM). We have designed a clinical trial to explore the value of 7 T MRI in radiation treatment of GBM. For this aim we performed a preparatory study to investigate the technical feasibility of incorporating 7 T MR images into the neurosurgical navigation and radiotherapy treatment planning (RTP) systems via qualitative and quantitative assessment of the image quality. MATERIALS AND METHODS: The MR images were acquired with a Siemens Magnetom 7 T whole-body scanner and a Nova Medical 32-channel head coil. The 7 T MRI pulse sequences included magnetization-prepared two rapid acquisition gradient echoes (MP2RAGE), T2-SPACE, SPACE-FLAIR and gradient echo sequences (GRE). A pilot study with three healthy volunteers and an anthropomorphic 3D phantom was used to assess image quality and geometrical image accuracy. RESULTS: The MRI scans were well tolerated by the volunteers. Susceptibility artefacts were observed in both the cortex and subcortical white matter at close proximity to air-tissue interfaces. Regional loss of signal and contrast could be minimized by the use of dielectric pads. Image transfer and processing did not degrade image quality. The system-related spatial uncertainty of geometrical distortion-corrected MP2RAGE pulse sequences was

Objective: A fine structure of the corpus callosum (CC), consisting of radial lines, is seen in historical anatomical atlases as far back as that of Vicq d'Azyr (1786). This study examines a similar pattern observed in vivo using high-resolution MR images at 7 T. Methods: 8 healthy subjects were examined with 7.0-T MRI. Anatomical images were collected with a gradient echo scan with 0.5-mm isotropic resolution, which were rated for visibility of the radial pattern. In addition, the second eigenvector of the diffusion tensor images was examined. Results: The fine radial lines are detected not only in the sagittal view but also in the axial view of the in vivo MR images. From this, it is likely that these structures are two-dimensional ribbons. Interestingly, and confirming the structural nature of these stripes, the second eigenvector of the diffusion tensor imaging data shows an extremely similar pattern of oriented foliate structure. A similar modular structure involving transient septa has been observed previously in histological sections of human fetal CC. Conclusion: The separate sets of data—the atlas of Klingler, anatomical images and second eigenvector images—all indicate a ribbon-like arrangement of the fibres in the CC. As such, they closely match the structures shown in the drawn atlases of as old as 1786. Advances in knowledge: This ribbon arrangement of fibres in the CC, previously unseen in CT or lower field MRI, can now be observed in vivo. This appears to match over two centuries of ex vivo observations.

Thousand cankers disease (TCD) is an insect-mediated disease of walnut trees (Juglans spp.) involving walnut twig beetle (Pityophthorus juglandis) and a fungal pathogen (Geosmithia morbida). Although first documented on walnut species in the western U.S., TCD is now found on black walnut (J. nigra) in five states in the eastern U.S. Most collections of P. juglandis or G. morbida are from trees in agriculturally- or residentially-developed landscapes. In 2013, 16 pheromone-baited funnel traps were deployed in or near black walnuts in forested conditions to assess the risk of infestation of forested trees by P. juglandis. Four of the 16 funnel traps collected adult P. juglandis from three forested areas (one in North Carolina and two in Tennessee). These collections, while in forested settings, may still be strongly influenced by human activities. The greatest number of P. juglandis (n = 338) was collected from a forested location in an urbanized area near a known TCD-positive tree. The other two forested locations where P. juglandis (n = 3) was collected were in areas where camping is common, and infested firewood may have introduced P. juglandis unintentionally into the area. Future studies to assess P. juglandis on more isolated forested walnuts are planned.

Thousand Cankers Disease (TCD) is a disease complex wherein the fungus (Geosmithia morbida) is vectored by the walnut twig beetle (WTB, Pityophthorus juglandis). The disease causes mortality primarily of eastern black walnut (Juglans nigra), although other walnut and wingnut (Pterocarya) species are also susceptible. Black walnut is native to the Eastern and Midwestern U.S. but is widely planted in western states. Total standing volume in both urban and forested settings is approximately 96 million cubic meters, and is valued at $539 billion. Although native to the Southwestern U.S., the range of WTB has expanded considerably. The spread of G. morbida coincides with that of WTB. TCD was introduced into Tennessee in 2010, and has spread to seven eastern states. Trees infected with TCD exhibit drought-like symptoms, making field detection difficult without molecular and/or morphological methods. The recently sequenced G. morbida genome will provide valuable research tools focused on understanding gene interactions between organisms involved in TCD and mechanisms of pathogenicity. With no chemical treatments available, quarantine and sanitation are preeminent options for slowing the spread of TCD, although biological control agents have been discovered. High levels of black walnut mortality due to TCD will have far-reaching implications for both eastern and western states.

OBJECTIVES: To overcome the challenges of B0 and RF excitation inhomogeneity at ultra-high field MRI, a workflow for volumetric B0 and flip-angle homogenisation was implemented on a human 9.4 T scanner.MATERIALS AND METHODS: Imaging was performed with a 9.4 T human MR scanner (Siemens Medical Solutions, Erlangen, Germany) using a 16-channel parallel transmission system. B0- and B1-mapping were done using a dual-echo GRE and transmit phase-encoded DREAM, respectively. B0 shims and a small-tip-angle-approximation kT-points pulse were calculated with an off-line routine and applied to acquire T1- and T 2 (*) -weighted images with MPRAGE and 3D EPI, respectively.RESULTS: Over six in vivo acquisitions, the B0-distribution in a region-of-interest defined by a brain mask was reduced down to a full-width-half-maximum of 0.10 ± 0.01 ppm (39 ± 2 Hz). Utilising the kT-points pulses, the normalised RMSE of the excitation was decreased from CP-mode's 30.5 ± 0.9 to 9.2 ± 0.7 % with all B 1 (+) voids eliminated. The SNR inhomogeneities and contrast variations in the T1- and T 2 (*) -weighted volumetric images were greatly reduced which led to successful tissue segmentation of the T1-weighted image.CONCLUSION: A 15-minute B0- and flip-angle homogenisation workflow, including the B0- and B1-map acquisitions, was successfully implemented and enabled us to reduce intensity and contrast variations as well as echo-planar image distortions in 9.4 T images.

In 2010, thousand cankers disease (TCD) was documented in Tennessee, representing the first confirmation of this disease in the native range of black walnut and the first known incidence of TCD east of Colorado. Tennessee Department of Agriculture personnel conducted surveys to determine the extent of TCD in counties in eastern Tennessee. Samples of symptomatic black walnuts were sent to the University of Tennessee for processing. The causative agents, walnut twig beetle, Pityophthorus juglandis, and the fungal pathogen Geosmithia morbida, were documented on the same trees in four counties. Tree mortality was observed in two counties, and tree decline was observed in at least 10 counties although it may be attributed to previous droughts or to TCD. In 2010, four confirmed counties were quarantined by TDA, and 10 buffer counties were also regulated. Research is underway to further assess the incidence and impact of TCD on black walnut in Tennessee.

Using next-generation sequencing, 18 microsatellite loci were developed and characterized for walnut twig beetle, Pityophthorus juglandis, a vector of thousand cankers disease (TCD) affecting Juglans spp. Although all Juglans species are susceptible to TCD infection, native populations of J. nigra and J. cinerea, which is endangered in Canada, are most susceptible and threatened by habitat loss. Novel primers amplified di-, tri-, and tetra nucleotide repeats and detected 4–14 alleles per locus. Averaged observed and expected heterozygosity was 0.22 and 0.67, respectively. Our results indicate that P. juglandis microsatellite loci can be used to investigate genetic diversity and population structure of this vector across a widespread geography. These markers will be useful tools for evaluating genetic structure of P. juglandis population outbreaks and developing appropriate conservation strategies. Microsatellite loci obtained in this study can also be utilized to determine relationships of P. juglandis to other closely related Pityophthorus spp.

♦Background The impact of climatic variations on peritoneal dialysis (PD)–related peritonitis has not been studied in detail. The aim of the current study was to determine whether various climatic zones influenced the probability of occurrence or the clinical outcomes of peritonitis. ♦Methods Using ANZDATA registry data, the study in cluded all Australian patients receiving PD between 1 October 2003 and 31 December 2008. Climatic regions were defined according to the Köppen classification. ♦Results The overall peritonitis rate was 0.59 episodes per patient–year. Most of the patients lived in Temperate regions (65%), with others residing in Subtropical (26%), Tropical (6%), and Other climatic regions (Desert, 0.6%; Grassland, 2.3%). Compared with patients in Temperate regions, those in Tropical regions demonstrated significantly higher overall peritonitis rates and a shorter time to a first peritonitis episode [adjusted hazard ratio: 1.15; 95% confidence interval (CI): 1.01 to 1.31]. Culture-negative peritonitis was significantly less likely in Tropical regions [adjusted odds ratio (OR): 0.42; 95% CI: 0.25 to 0.73]; its occurrence in Subtropical and Other regions was comparable to that in Temperate regions. Fungal peritonitis was independently associated with Tropical regions (OR: 2.18; 95% CI: 1.22 to 3.90) and Other regions (OR: 3.46; 95% CI: 1.73 to 6.91), where rates of antifungal prophylaxis were also lower. Outcomes after first peritonitis episodes were comparable in all groups. ♦Conclusions Tropical regions were associated with a higher overall peritonitis rate (including fungal peritonitis) and a shorter time to a first peritonitis episode. Augmented peritonitis prophylactic measures such as antifungal therapy and exit-site care should be considered in PD patients residing in Tropical climates.

Peritoneal dialysis (PD) is a preferred home dialysis modality and has a number of added advantages including improved initial patient survival and cost effectiveness over haemodialysis. Despite these benefits, uptake of PD remains relatively low, especially in developed countries. Wider implementation of PD is compromised by higher technique failure from infections (e.g., PD peritonitis) and ultrafiltration failure. These are inevitable consequences of peritoneal injury, which is thought to result primarily from continuous exposure to PD fluids that are characterised by their “unphysiologic” composition. In order to overcome these barriers, a number of more biocompatible PD fluids, with neutral pH, low glucose degradation product content, and bicarbonate buffer have been manufactured over the past two decades. Several preclinical studies have demonstrated their benefit in terms of improvement in host cell defence, peritoneal membrane integrity, and cytokine profile. This paper aims to review randomised controlled trials assessing the use of biocompatible PD fluids and their effect on clinical outcomes.

Objective Management of peritoneal dialysis (PD)–associated peritonitis requires timely intervention by experienced staff, which may not be uniformly available throughout the week. The aim of the present study was to examine the effects of weekend compared with weekday presentation on peritonitis outcomes. Methods The study, which used data from the Australia and New Zealand Dialysis and Transplant Registry, included all Australian patients receiving PD between 1 October 2003 and 31 December 2008. The independent predictors of weekend presentation and subsequent peritonitis outcomes were assessed by multivariate logistic regression. Results Peritonitis presentation rates were significantly lower on Saturdays [0.46 episodes per year; 95% confidence interval (CI): 0.42 to 0.49 episodes per year] and on Sundays (0.43 episodes per year; 95% CI: 0.40 to 0.47 episodes per year) than all other weekdays; they peaked on Mondays (0.76 episodes per year; 95% CI: 0.72 to 0.81 episodes per year). Weekend presentation with a first episode of peritonitis was independently associated with lower body mass index and residence less than 100 km away from the nearest PD unit. Patients presenting with peritonitis on the weekend were significantly more likely to be hospitalized [adjusted odds ratio (OR): 2.32; 95% CI: 1.85 to 2.90], although microbial profiles and empiric antimicrobial treatments were comparable between the weekend and weekday groups. Antimicrobial cure rates were also comparable (79% vs 79%, p = 0.9), with the exception of cure rates for culture-negative peritonitis, which were lower on the weekend (80% vs 88%, p = 0.047). Antifungal prophylaxis was less likely to be co-prescribed for first peritonitis episodes presenting on weekdays (OR: 0.68; 95% CI: 0.05 to 0.89). Conclusions Patients on PD are less likely to present with peritonitis on the weekend. Nevertheless, the microbiology, treatment, and outcomes of weekend and weekday PD peritonitis presentations are remarkably similar. Exceptions include the associations of weekend presentation with a higher hospitalization rate and a lower cure rate in culture-negative infection.

A 64-yr-old male with a longstanding history of psoriatic arthritis presented with a 6-week history of dry cough without other respiratory symptoms. His other past medical history showed hypertension and type II diabetes mellitus. He took methotrexate 12.5 mg weekly (commenced 9 yrs previously), folic acid, aspirin, nortriptyline, metformin, valsartan and insulin. The patient was an ex-smoker of 5 pack-yrs, having stopped smoking 32 yrs earlier. He kept no pets and there was no significant occupational exposure or travel history. On examination his chest was clear. There was no lymphadenopathy or clubbing. A chest radiograph (fig. 1⇓) showed multiple pulmonary nodules. C-reactive protein was 6 mg·L−1, erythrocyte sedimentation rate was 17 mm·h−1 and white blood cell count was 13×109 cells·L−1 …

Pseudomonas peritonitis is a serious complication of peritoneal dialysis. To date, there as been no comprehensive, multicenter study of this condition.The predictors, treatment, and clinical outcomes of Pseudomonas peritonitis were examined by binary logistic regression and multilevel, multivariate Poisson regression in all Australian PD patients in 66 centers between 2003 and 2006.A total of 191 episodes of Pseudomonas peritonitis (5.3% of all peritonitis episodes) occurred in 171 individuals. Its occurrence was independently predicted by Maori/Pacific Islander race, Aboriginal/Torres Strait Islander race, and absence of baseline peritoneal equilibration test data. Compared with other organisms, Pseudomonas peritonitis was associated with greater frequencies of hospitalization (96 versus 79%; P = 0.006), catheter removal (44 versus 20%; P0.001), and permanent hemodialysis transfer (35 versus 17%; P0.001) but comparable death rates (3 versus 2%; P = 0.4). Initial empiric antibiotic choice did not influence outcomes, but subsequent use of dual anti-pseudomonal therapy was associated with a lower risk for permanent hemodialysis transfer (10 versus 38%, respectively; P = 0.03). Catheter removal was associated with a lower risk for death than treatment with antibiotics alone (0 versus 6%; P0.05).Pseudomonas peritonitis is associated with high rates of catheter removal and permanent hemodialysis transfer. Prompt catheter removal and use of two anti-pseudomonal antibiotics are associated with better outcomes.

Successful survival in a competitive world requires the employment of efficient procedures for selecting new in preference to old information. Recent behavioral studies have shown that efficient selection is dependent not only on properties of new stimuli but also on an intentional bias that we can introduce against old stimuli. Event-related analysis of functional magnetic resonance imaging data from a task involving visual search across time as well as space indicates that the superior parietal lobule is specifically involved in processes leading to the efficient segmentation of old from new items, whereas the temporoparietal junction area and the ascending limb of the right intraparietal sulcus are involved in the detection of salient new items and in response preparation. The study provides evidence for the functional segregration of brain regions within the posterior parietal lobe.

We would like to provide the following additional material to Appendix 3 “Sources of information and help available for patients and carers” which appeared on 263–4 of the BTS statement on malignant mesothelioma in the UK published recently in Thorax . …

This study examines the value of spin-echo-based fMRI for cognitive studies at the main magnetic field strength of 3 T using a spin-echo EPI (SE-EPI) sequence and a Stroop color-word matching task. SE-EPI has the potential advantage over conventional gradient-echo EPI (GE-EPI) that signal losses caused by dephasing through the slice are not present, and hence although image distortion will be the same as for an equivalent GE-EPI sequence, signal voids will be eliminated. The functional contrast in SE-EPI will be lower than for GE-EPI, as static dephasing effects do not contribute. As an auxiliary experiment interleaved diffusion-weighted and non-diffusion-weighted SE-EPI was performed in the visual cortex to further elucidate the mechanims of functional contrast. In the Stroop experiment activation was detected in all areas previously found using GE-EPI. Additional frontopolar and ventral frontomedian activations were also found, which could not be detected using GE-EPI. The experiments from visual cortex indicated that at 3 T the BOLD signal change has contributions from the extravascular space and larger blood vessels in roughly equal amounts. In comparison with GE-EPI the absence of static dephasing effects would seem to result in a superior intrinsic spatial resolution. In conclusion the sensitivity of SE-EPI at 3 T is sufficient to make it the method of choice for fMR studies that require a high degree of spatial localization or where the requirement is to detect activation in regions affected by strong susceptibility gradients.

The magneto-impedance (MI) of glass-coated Fe-Ni-Cu microwires was investigated for longitudinal radio-frequency (RF) currents up to a frequency of 200 MHz using an RF lock-in amplifier method. The MI, defined as DZ/Z = [Z(H)-Z(H=0.3T)]/Z(H=0.3T), displays a peak structure (negative MI) at zero field for RF currents with frequencies less than 20MHz and this crosses over to a sharp dip (positive MI) at higher frequencies. This crossover behavior is ascribed to the skin-depth-limited response primarily governed by the field-dependence of the permeability. Large saturation fields (300 to 600 Oe) and other anomalies indicate the possible influence of giant magneto-resistance (GMR) on the MI., 3 pages, 2-column, 3 figures. To be published in J. Appl. Phys. 2000 (44th MMM conference proceedings)

A resonant method based on a tunnel-diode oscillator (TDO) for precision measurements of relative impedance changes in materials, is described. The system consists of an effective self-resonant LC-tank circuit driven by a forward-biased tunnel diode operating in its negative resistance region. Samples under investigation are placed in the core of an inductive coil and impedance changes are determined directly from the measured shift in resonance frequency. A customized low temperature insert is used to integrate this experiment with a commercial Model 6000 Physical Property Measurement System (Quantum Design). Test measurements on a manganese-based perovskite sample exhibiting colossal magneto-resistance (CMR) indicate that this method is well suited to study the magneto-impedance in these materials., Rev. Sci. Instrum. (in press), PDF file, 6 pages, 2-column, embedded figures

A 74 year old woman presented with a two month history of recurrent small hemoptyses and died after a subsequent massive haemoptysis. At postmortem examination the source of bleeding was found to be a leaking saccular, atheromatous abdominal aortic aneurysm, which had ruptured through the diaphragm into the lower lobe of the right lung.

High levels of distress in medical students have been reported in several studies and have been attributed to the stresses of medical training. In order to compare the severity of distress in medical students to that of other students, we administered the Hopkins Symptom Checklist and the Symptom Questionnaire to 60 medical students (30 first-year and 30 third-year) and to matched law students. Law students reported significantly more depression and anger-hostility and less contentment and feelings of friendliness. Third-year students rated themselves as significantly more distressed than first-year students and females more distressed than males. Distress levels in medical students may be lower than those of other graduate students.